pregnancy

pregnancy
/preg"neuhn see/, n., pl. pregnancies.
the state, condition, or quality of being pregnant.
[1520-30; PREGN(ANT) + -ANCY]

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Process of human gestation that takes place in the female's body as a fetus develops, from fertilization to birth (see parturition).

It begins when a viable sperm from the male and egg from the ovary merge in the fallopian tube (see fertility; fertilization). The fertilized egg (zygote) grows by cell division as it moves toward the uterus, where it implants in the lining and grows into an embryo and then a fetus. A placenta and umbilical cord develop for nutrient and waste exchange between the circulations of mother and fetus. A protective fluid-filled amniotic sac encloses and cushions the fetus. Early in pregnancy, higher estrogen and progesterone levels halt menstruation, cause nausea, often with vomiting (morning sickness), and enlarge the breasts and prepare them for lactation. As the fetus grows, so does the uterus, displacing other organs. Normal weight gain in pregnancy is 20–25 lbs (9–11.5 kg). The fetus's nutritional needs require the mother to take in more calories and especially protein, water, calcium, and iron. Folic-acid supplements are recommended during early pregnancy to prevent neural tube defects. Smoking, alcohol, and many legal and illegal drugs can cause congenital disorders and should be avoided during pregnancy. Ultrasound imaging is often used to monitor structural and functional progress of the growing fetus. The due date is estimated as 280 days from the time of last menstruation; 90% of babies are born within two weeks of the estimated date. See also amniocentesis; preeclampsia and eclampsia; premature birth.

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Introduction

      process and series of changes that take place in a woman's organs and tissues as a result of a developing fetus. The entire process from fertilization to birth takes an average of 266–70 days, or about nine months. (For pregnancies other than those in humans, see gestation.)

The normal events of pregnancy

Initiation of pregnancy
 A new individual is created when the elements of a potent sperm merge with those of a fertile ovum, or egg. Before this union both the spermatozoon (sperm) and the ovum have migrated for considerable distances in order to achieve their union. A number of actively motile spermatozoa are deposited in the vagina, pass through the uterus, and invade the uterine (fallopian) tube, where they surround the ovum. The ovum has arrived there after extrusion from its follicle, or capsule, in the ovary. After it enters the tube, the ovum loses its outer layer of cells as a result of action by substances in the spermatozoa and from the lining of the tubal wall. Loss of the outer layer of the ovum allows a number of spermatozoa to penetrate the egg's surface. Only one spermatozoon, however, normally becomes the fertilizing (fertilization) organism. Once it has entered the substance of the ovum, the nuclear head of this spermatozoon separates from its tail. The tail gradually disappears, but the head with its nucleus survives. As it travels toward the nucleus of the ovum (at this stage called the female pronucleus), the head enlarges and becomes the male pronucleus. The two pronuclei meet in the centre of the ovum, where their threadlike chromatin material organizes into chromosomes (chromosome).

      Originally the female nucleus has 44 autosomes (chromosomes other than sex chromosomes) and two (X, X) sex chromosomes. Before fertilization a type of cell division called a reduction division (meiosis) brings the number of chromosomes in the female pronucleus down to 23, including one X-chromosome. The male gamete, or sex cell, also has 44 autosomes and two (X, Y) sex chromosomes. As a result of a reducing division occurring before fertilization, it, too, has 23 chromosomes, including either an X or a Y sex chromosome at the time that it merges with the female pronucleus.

      After the chromosomes merge and divide in a process termed mitosis, the fertilized ovum, or zygote, as it is now called, divides into two equal-sized daughter cells. The mitotic division gives each daughter cell 44 autosomes, half of which are of maternal and half of paternal origin. Each daughter cell also has either two X-chromosomes, making the new individual a female, or an X- and a Y-chromosome, making it a male. The sex of the daughter cells is determined, therefore, by the sex chromosome from the male parent.

      Fertilization occurs in the uterine tube. How long the zygote remains in the tube is unknown, but it probably reaches the uterine cavity about 72 hours after fertilization. It is nourished during its passage by the secretions from the mucous membrane lining the tube. By the time it reaches the uterus, it has become a mulberry-like solid mass called a morula. A morula is composed of 60 or more cells. As the number of cells in a morula increases, the zygote forms a hollow bubblelike structure, the blastocyst. The blastocyst, nurtured by the uterine secretions, floats free in the uterine cavity for a short time and then is implanted in the uterine lining. Normally, the implantation of the blastocyst occurs in the upper portion of the uterine lining. (The mechanism of implantation is described below.)

diagnosis of pregnancy
Symptoms and signs; biological tests
      Outward early indications of pregnancy are missed menstrual periods, morning nausea, and fullness and tenderness of the breasts; but the positive and certain signs of gestation are the sounds of the fetal heartbeat, which are audible with a stethoscope between the 16th and the 20th week of pregnancy; ultrasound images of the growing fetus, which can be observed throughout pregnancy; and fetal movements, which usually occur by the 18th to the 20th week of pregnancy.

      Persons who note their body temperature upon awakening, as many women do who wish to know when they are ovulating, may observe continued elevation of the temperature curve well beyond the time of the missed period; this is strongly suggestive of pregnancy. During the early months of pregnancy, women may notice that they urinate frequently, because of pressure of the enlarging uterus on the bladder; feel tired and drowsy; dislike foods that were previously palatable; have a sense of pelvic heaviness; and are subject to vomiting (which can be severe) and to pulling pains in the sides of the abdomen, as the growing uterus stretches the round ligaments that help support it, singly or together. Most of these symptoms subside as pregnancy progresses. The signs and symptoms of pregnancy are so definite by the 12th week that the diagnosis is seldom a problem.

      Biological tests for pregnancy depend upon the production by the placenta (the temporary organ that develops in the womb for the nourishing of the embryo and the elimination of its wastes) of chorionic gonadotropin, an ovary-stimulating hormone (sex hormone). In practice, the tests have an accuracy of about 95 percent, although false-negative tests may run as high as 20 percent in a series of cases. False-negative reports are frequently obtained during late pregnancy when the secretion of chorionic gonadotropin normally decreases. The possibility not only of false-negative but also of false-positive tests makes the tests, at best, probable rather than absolute evidence of the presence or absence of pregnancy. Chorionic gonadotropin in a woman's blood or urine indicates only that she is harbouring living placental tissue. It does not tell anything about the condition of the fetus. In fact, the greatest production of chorionic gonadotropin occurs in certain placental abnormalities and disorders that can develop in the absence of a fetus.

      Tests using immature mice (mouse) (the Aschheim-Zondek test) and immature rats have been found to be extremely accurate. Tests using rabbits (rabbit) (the Friedman test) have been largely replaced by the more rapid and less expensive frog and toad tests.

      The use of the female South African claw-toed tree toad, Xenopus (clawed frog) laevis, is based on the discovery that this animal will ovulate and extrude visible eggs within a few hours after it has received an injection of a few millilitres of urine from a pregnant woman. The male common frog, Rana pipiens (leopard frog), will extrude spermatozoa when treated in the same way. Both of these tests are considered somewhat unsatisfactory because false-positive reactions are not uncommon.

      Several immunological reaction tests in common use are based upon the inhibition of hemagglutination (clotting (coagulation) of red cells). A positive test is obtained when human chorionic gonadotropin (HCG) in the woman's urine or blood is added to human chorionic gonadotropin antiserum (rabbit blood serum containing antibodies to HCG) in the presence of particles (or red blood cells) coated with human chorionic gonadotropin. The hormone from the woman will inhibit the combination of coated particles and antibody, and agglutination does not occur. If there is no chorionic gonadotropin in her urine, agglutination will occur and the test is negative.

      Several “signs” noted by the physician during an examination will suggest that a patient may be in the early months of pregnancy. Darkening of the areola of the breast (the small, coloured ring around the nipple) and prominence of the sebaceous glands around the nipple (Montgomery's glands); purplish-red discoloration of the vulvar, vaginal, and cervical tissues; softening of the cervix and of the lower part of the uterus and, of course, enlargement and softening of the uterus itself are suggestive but not necessarily proof of pregnancy.

Conditions that may be mistaken for pregnancy
      Other conditions may confuse the diagnosis of pregnancy. Absence of menstruation can be caused by chronic illness, by emotional or endocrine disturbances, by fear of pregnancy, or by a desire to be pregnant. Nausea and vomiting may be of gastrointestinal or psychic origin. Tenderness of the breasts can be due to a hormonal disturbance.

      Any condition that causes pelvic congestion, such as a pelvic tumour, may cause duskiness of the genital tissues. At times a soft tumour of the uterus may simulate a pregnancy. The question of pregnancy may be raised if the woman does not menstruate regularly; the absence of other symptoms and signs of gestation indicates that she is not pregnant. There are rare ovarian and uterine tumours that produce false-positive pregnancy tests. It may be difficult for the physician to exclude pregnancy on the basis of an examination if the uterus is tipped back and difficult to feel, or if it is enlarged by a tumour within it. If other signs of pregnancy are absent, however, and the tests for pregnancy are negative, pregnancy can most likely be ruled out.

      Childless women who greatly desire a baby sometimes suffer from false or spurious pregnancy (pseudocyesis (false pregnancy)). They stop menstruating, have morning nausea, “feel life,” and have abdominal enlargement caused by fat and intestinal gas. At “term” they may have “labour pains.” Signs of pregnancy are absent. Treatment is by psychotherapy.

      Menopausal women often fear pregnancy when their periods stop; information that they show no signs of pregnancy usually reassures them. Retained uterine secretions of bloody or watery fluid, caught above a blocked mouth of the uterus (cervix), prevent menstruation, cause softening and enlargement of the uterus, and may cause the patient to wonder whether she is pregnant. There are no other signs of pregnancy, and the hard cervix, closed by scar tissue, explains the problem.

Duration of pregnancy
      There are, as a rule, 266 to 270 days between ovulation and childbirth, with extremes of 250 and 285 days. Physicians usually determine the date of the estimated time for delivery by adding seven days to the first day of the last menstrual period and counting forward nine calendar months; i.e., if the last period began on January 10, the date of delivery is October 17. Courts of law, in determining the legitimacy (illegitimacy) of a child, may accept much shorter or much longer periods of gestation as being within the periods of possible duration of a pregnancy. One court in the state of New York has accepted a pregnancy of 355 days as legitimate. British courts have recognized 331 and 346 days as legitimate with the approval of medical consultants. Fully developed infants have been born as early as 221 days after the first day of the mother's last menstrual period.

      Because the exact date of ovulation is usually not known, it is seldom possible to make an accurate estimate of the date of delivery. There is a 5 percent chance that a baby will be born on the exact date estimated from the above rule. There is a 25 percent chance that it will be born within four days before or after the estimated date. There is a 50 percent chance that delivery will occur on the estimated date plus or minus seven days. There is a 95 percent chance that the baby will be born within plus or minus 14 days of the estimated date of delivery.

Anatomic and physiologic changes of normal pregnancy
Changes in organs and tissues directly associated with childbearing

Ovaries (ovary)
      The ovaries of a nonpregnant young woman who is in good health go through cyclic changes each month. These changes centre about a follicle, or “egg sac.” A new follicle develops after each menstrual period, casts off an egg (ovulation), and, after ovulation, forms a new structure (the corpus luteum).

      If the egg is fertilized, it is sustained for a short time by the hormones produced by the corpus luteum. progesterone and estrogen, secreted by the corpus luteum, are essential for the preservation of the pregnancy during its early months. If pregnancy does not occur, the egg disintegrates and the corpus luteum shrinks. As it shrinks, the stimulating effect of its hormones, progesterone and estrogen, is withdrawn from the endometrium (the lining of the uterus), and menstruation occurs. The cycle then begins again.

      Pregnancy, if it occurs, maintains the corpus luteum by means of the hormones produced by the young placenta. The corpus luteum is not essential in human pregnancy after the first few weeks because of the takeover of its functions by the placenta. In fact, human pregnancies have gone on undisturbed when the corpus luteum has been removed as early as the 41st day after conception. Gradually the placenta, or afterbirth, begins to elaborate progesterone and estrogen itself. By the 70th day of pregnancy the placenta is unquestionably able to replace the corpus luteum without endangering the pregnancy during the transfer of function. At the end of pregnancy the corpus luteum has usually regressed until it is no longer a prominent feature of the ovary.

      During the first few months of pregnancy the ovary that contains the functioning corpus luteum is considerably larger than the other ovary. During pregnancy, both ovaries usually are studded with fluid-filled egg sacs as a result of chorionic gonadotropin stimulation; by the end of pregnancy, most of these follicles have gradually regressed and disappeared.

      The blood supply to both ovaries is increased during pregnancy. Both glands frequently reveal plaques of bright red fleshy material on their surfaces, which, if examined microscopically, demonstrate the typical cellular change of pregnancy, called a decidual reaction. In this reaction, cells develop that look like the cells in the lining of the pregnant uterus. They result from the high hormone levels that occur during pregnancy and disappear after the pregnancy terminates.

The uterus and the development of the placenta
      The uterus is a thick-walled, pear-shaped organ measuring seven centimetres (about 2.75 inches) in length and weighing 30 grams (about one ounce) in an unpregnant woman in her later teens. It has a buttonlike lower end, the cervix (uterine cervix), that merges with the bulbous larger portion, called the corpus. The corpus comprises approximately three-fourths of the uterus. There is a flat, triangular-shaped cavity within the uterus. At term, the uterus is a large, thin-walled, hollow, elastic, fluid-filled cylinder measuring approximately 30 centimetres (about 12 inches) in length, weighing approximately 1,200 grams (2.6 pounds), and having a capacity of 4,000 to 5,000 millilitres (4.2 to 5.3 quarts).

      The greater size of the uterus as a result of pregnancy is due to a marked increase in the number of muscle fibres, blood vessels, nerves, and lymphatic vessels in the uterine wall. There is also a five- to tenfold increase in the size of the individual muscle fibre and marked enlargement in the diameters of the blood and lymph vessels.

      During the first few weeks of pregnancy, the shape of the uterus is unchanged, but the organ becomes gradually softer. By the 14th week it forms a flattened or oblate spheroid. The fibrous cervix becomes remarkably softer and acquires a protective mucus plug within its cavity, but otherwise it changes little before labour. The lower part of the corpus, the isthmus, first becomes elongated and then, as the uterine contents demand more space, stretches and unfolds to form a bowl-shaped formation called the lower uterine segment. The fibrous nature of the cervix causes it to resist this unfolding action.

      The uterine wall is stretched and thinned during pregnancy by the growing conceptus, as the whole product of conception is called, and by the fluid that surrounds it. By term, this process converts the uterus into an elastic, fluid-filled cylinder. It is only late in pregnancy that the cervix gradually thins out and softens; during labour it dilates for passage of the infant.

      As pregnancy progresses, the uterus rises out of the pelvis and fills the abdominal cavity. It is top-heavy near term so that it falls forward and, because of the large bowel on the left side, rotates to the right. It presses on the diaphragm and pushes the other organs aside. The uterus may sink downward in the pelvis (pelvic girdle) several weeks before term in a process that is known as lightening or dropping. This occurs as the fetal head descends into the pelvis. In some women, particularly those who have borne children, lightening does not occur until the onset of labour. Lightening may be impossible in women who have an abnormally small pelvis, an oversized fetus, or a fetus lying in an abnormal position.

      For a short time after fertilization, the conceptus, a minute bubblelike structure called a blastocyst, lies unattached in the uterine cavity. The cells that will become the embryo (the embryonic disk) form a thickened layer on one side of the bubble. Elsewhere, the walls of the bubble consist of a single layer of cells; these cells are the trophoblast, which has a special ability to attach to and invade the uterine wall. The trophoblast plays an important role later in the development of the placenta or afterbirth. The conceptus makes contact (implantation) with the uterine lining about the fifth or sixth day after conception. After contact the blastocyst collapses to form a rounded disk with the embryonic mass on the surface and the trophoblast against the endometrium (uterine lining). The part of the trophoblast that is in contact with the endometrium grows into and invades the maternal tissue. Concomitant disintegration of the endometrium allows the conceptus to sink into the uterine lining.

      Soon the entire blastocyst is buried in the endometrium. Proliferation of the trophoblast over the part of the collapsed bubble that is opposite the embryo is part of the implantation procedure that helps to cover the blastocyst. After a few days, a cavity forms that bears the same relation to the embryonic disk that the blastocyst cavity did before; this cavity will become the fluid-filled chorionic cavity containing the embryo. Ultimately it will contain the amniotic fluid that surrounds the fetus, the fetus itself, and the umbilical cord.

      The body stalk, which will become the umbilical cord, then begins to separate the embryo from the syncytiotrophoblast, the outer layer of the trophoblast lying against the endometrium; the inner lining of the trophoblast is called cytotrophoblast. As the syncytiotrophoblast advances into the endometrium, it surrounds minute branches of the uterine arteries that contain maternal blood (blood vessel). Erosion of the endometrium about these blood sinuses allows them to open into the small cavities in the trophoblast. The cytotrophoblast, which lines the cavity, forms fingers of proliferating cells extending into the syncytiotrophoblast. After the placenta is developed, these fingers will be the cores of the root-like placental villi, structures that will draw nutrients and oxygen from the maternal blood that bathes them. This is the first step in uteroplacental circulation, which supplies the fetus with all of the sustenance necessary for life and growth and removes waste products from it. During the third week of pregnancy, the syncytiotrophoblast forms a single layer of cells covering the growing villi and lining the syncytial lacunae or small cavities between the villi. The conceptus is buried in the endometrium, and its whole surface is covered at this time by developing villi. The greater part of the chorionic wall is now cytotrophoblast. Fingers of cytotrophoblast in the form of cell masses extend into the syncytial layer. Soon thereafter, a layer of connective tissue, or mesoderm, grows into the villi, which now form branches as they spread out into the blood-filled spaces in the endometrium adjacent to the conceptus.

      By the end of the third week, the chorionic villi that form the outer surface of the chorionic sac are covered by a thick layer of cytotrophoblast and have a connective tissue core within which embryonic blood vessels are beginning to develop. The vessels, which arise from the yolk sac, connect with the primitive vascular system in the embryo. As growth progresses the layer of cytotrophoblast begins to regress. It disappears by the fifth month of pregnancy.

      The layer of endometrium closest to the encroaching conceptus forms, with remnants of the invading syncytio-trophoblast, a thin plate of cells known as the decidua basalis, the maternal component of the mature placenta; it is cast off when the placenta is expelled. The fetal part of the placenta—the villi and their contained blood vessels—is separated from the decidua basalis by a lakelike body of fluid blood. This pool was created by coalescence of the intervillous spaces. The intervillous spaces in turn were formed from the syncytial lacunae in the young conceptus. Maternal blood enters this blood mass from the branches of the uterine arteries. The pool is drained by the uterine veins. It is so choked by intermingling villi and their branches that its continuity is lost on gross inspection.

      The chorionic cavity contains the fluid in which the embryo floats. As its shell or outer surface becomes larger, the decidua capsularis, which is that part of the endometrium that has grown over the side of the conceptus away from the embryo (i.e., the abembryonic side) after implantation, becomes thinner. After 12 weeks or so, the villi on this side, which is the side directed toward the uterine cavity, disappear, leaving the smooth chorion, now called the chorion laeve. The chorion frondosum is that part of the conceptus that forms as the villi grow larger on the side of the chorionic shell next to the uterine wall. The discus-shaped placenta develops from the chorion frondosum and the decidua basalis.

      At term, the normal placenta is a disk-shaped structure approximately 16 to 20 centimetres (about six to seven inches) in diameter, three or four centimetres (about 1.2–1.6 inches) in thickness at its thickest part, and weighing between 500 and 1,000 grams (1.1 and 2.2 pounds). It is thinner at its margins, where it is joined to the membrane-like chorion which spreads out over the whole inner surface of the uterus and contains the fetus and the amniotic fluid. The amnion, a thinner membrane, is adherent to and covers the inner surface of the chorion. The inner or fetal surface of the placenta is shiny, smooth, and traversed by a number of branching fetal blood vessels that come together at the point—usually the centre of the placenta—where the umbilical cord attaches. The maternal or uterine side of the placenta, covered by the thin, flaky decidua basalis, a cast-off part of the uterine lining, is rough and purplish-red, and has a raw appearance. When the placenta is cut across, its interior is seen to be made of a soft, crepelike or spongy matrix from which semisolid or clotted blood, caught when it is separated from the uterine wall to which it was attached, can be squeezed. Detailed examination shows that the villi and their branches form an arborescent (treelike) mass within the huge blood lake of the intervillous space. Anchoring villi extend outward from the fetal side and fuse with the decidua basalis to hold the organ's shape. Others, algae-like, float freely in the blood lake. Dividing partitions, formed from the trophoblast shell, project into the intervillous space from the decidual side. They divide the placenta into 15 or 20 compartments, which are called cotyledons.

      Maternal blood flows from the uterine vessels into the trophoblast-lined intervillous blood lake. Within each villus is a blood vessel network that is part of the fetal circulatory system. Blood within the villous vessel is circulated by the fetal heart. The blood vessel wall, the connective tissue of the villous core, and the syncytiotrophoblast covering the villus lie between the fetal and the maternal bloodstreams. This is known as the placental barrier. As pregnancy progresses, the fetal blood vessels become larger, the connective tissue stretches over them, and the syncytiotrophoblastic layer becomes fragmentary. As a result, the placental barrier becomes much thinner. Normally, blood cells and bacteria do not pass through it, but nutrients, water, salt, viruses, hormones, and many other substances, including many drugs, can filter across it.

Uterine tubes (fallopian tube)
      One of the two uterine tubes is the pathway down which the ripe ovum travels on its way to the uterus or womb. The spermatozoa from the male migrate up the tube, and it is there that they meet the ovum and fertilization occurs. During the first few days after fertilization the zygote, or fertilized egg, moves downward in the tube toward the uterus. While it is lying free in the tubal canal, the young conceptus is nourished by secretions from the tube. After the fertilized egg (or conceptus) passes into the uterus, the tube ceases to play any part in the pregnancy; in fact, the only function the tube has is carried out during those few days before, during, and after conception. As pregnancy goes on, the tube gradually enlarges, however, and contains more blood, as do all the pelvic organs; some of its cells may show a reaction, called a decidual reaction, to the hormones of pregnancy. As the uterus increases in size, the tubes stretch upward with it until they become two greatly enlarged elongated strands, one on each side of the uterus.

      The pinkish tan colour of the lining of the vagina gradually takes on a bluish cast during the early months of pregnancy as a result of the dilation of the blood vessels in the vaginal wall; later the vaginal wall tends to become a purplish red colour as the blood vessels become further engorged. The cells of the vaginal mucosa increase in size. Added numbers of these cells peel off the surface of the mucosa and mix with the increased vaginal fluid. This produces a profuse vaginal secretion. Thickening, softening, and relaxation of the loosely folded, succulent lining of the vagina and the sodden tissues beneath it greatly increase distensibility and capacity of the vaginal cavity; this is a process that partially prepares the birth canal for the passage through it of the large fetal mass.

External genital structures
      Changes in the external genitalia (reproductive system, human) are similar to those in the vagina. The tissues become first softened and more succulent and later extremely fragile, as an increasing amount of blood and fluid collects in them. They take on a purplish red colour because of increased blood supply. Darkening of the vulvar skin, frequently seen during pregnancy, is particularly common among women of Mediterranean ethnic groups.

Other pelvic tissues
      The pelvic blood vessels and lymph channels become larger and longer. They develop new branches adequate to transport the greatly increased amounts of blood and tissue fluid that accumulate in the uterus and the other pelvic organs during pregnancy. Congestion and engorgement of blood in the pelvis, both within and without the uterus, are characteristic of pregnancy.

      Changes in the muscles, ligaments, and other supporting tissues of the pelvis (pelvic girdle) begin early in pregnancy and become progressively more pronounced as pregnancy continues. These changes are induced by the greatly increased hormonal levels in the mother's blood that characterize pregnancy. Before labour starts, the pelvic supporting tissues must have sufficient elasticity and strength to permit the uterus to grow out of the pelvis and yet support it. The muscles must be soft and elastic enough during delivery so that they can stretch apart and not obstruct the baby's birth. Softening and greater elasticity is brought about not only by the growth of new tissue but also by congestion and retained fluid within the tissues themselves.

      The bones forming the mother's pelvis show relatively few changes during pregnancy. Loosening of the joint between the pubic bones in front and of the joints between the sacrum and the pelvis in back occurs as a response to the hormone called relaxin, which is produced by the ovary. Although relaxin, which causes marked separation of the pelvic joints in some animals, usually has too slight an effect in human beings to be noticed, softening of the attachments between the bones may be sufficient to cause a few women considerable distress. The strain on the joint between the sacrum and the spine becomes greater near term when the woman tilts her pelvis forward and bends the upper part of her body backward to compensate for the weight of the heavy uterus. When relaxation is excessive, the woman suffers from backache and difficulty in walking. If it is extreme, she may have a waddling gait. Relaxation of the pelvic joints does not disappear quickly after delivery; it accounts for much of the backache that women with new babies experience.

      The mother's bones (bone) show no structural change if her calcium reserve and intake are normal. If her reserve and intake are not adequate, the fetus may draw so much calcium from her bones that the bones become soft and deformed. This condition is rarely seen, except in areas of the world where extreme poverty and serious calcium deficiency are major problems.

Breasts (mammary gland)
      The earliest changes in the breasts during pregnancy are an exaggeration of the frequently experienced premenstrual discomfort and fullness. The sensation is so specific for pregnancy that many women who have been pregnant before are made aware of their condition by the feeling that they have in their breasts. As pregnancy progresses the breasts become larger, the lightly pigmented area (areola) around each nipple becomes first florid or dusky in colour and then appreciably darker; during the later months the areola takes on a hue that is deep bronze or brownish black, depending on the woman's natural pigmentation. The veins beneath the skin over the breast become enlarged and more prominent. The small oily or sebaceous glands (glands of Montgomery) about the nipple become prominent.

      These changes are due to the greatly increased levels of estrogen and progesterone in the woman's blood. These ovarian hormones also prepare the breast tissue for the action of the lactogenic (lactation) (milk-causing) hormone, prolactin, produced by the pituitary gland. During the later part of pregnancy a milky fluid, colostrum, exudes from the ducts or can be expressed from them.

      After delivery the decrease in estrogen and progesterone levels presumably permits the pituitary gland to release prolactin, which causes the breast to secrete milk. It is thought that the high hormonal levels inhibit the action or secretion of prolactin before delivery. Prolactin continues to be produced, and lactation usually continues, as long as the mother feeds her baby at the breast.

Anatomic and physiologic changes in other organs and tissues

      During pregnancy the increasing needs of the growing fetus and of her own tissues throw an added burden on the mother's heart. The work that the heart does is measured by the amount of blood it expels per minute (the cardiac output). Rapid increase in the cardiac output occurs between the 9th and the 14th week of gestation. During the period from the 28th to the 30th week, when the load is heaviest, the heart of a pregnant woman is doing 25 to 30 percent more work than it was doing before pregnancy. As the time of delivery approaches, the heart's workload diminishes to some extent; when the baby is born, the load is approximately equal to what it was when the mother was in the nonpregnant state. This decrease in cardiac output and cardiac work, which occurs in spite of the continued needs of the fetus and of the maternal tissues for blood-borne oxygen and nutriments, is explained by the more efficient way that the tissues draw on the mother's blood for oxygen and nourishment during the terminal weeks of pregnancy.

      The position of the heart is changed to a greater or lesser degree during pregnancy. As the uterus enlarges, it elevates the diaphragm. This in turn pushes the heart upward, to the left, and somewhat forward, so that it is nearer the chest wall beneath the breast. Near the end of gestation the large uterus may raise the heart until the latter lies almost at a right angle to the long axis of the woman's body. These changes, which also bring some rotation of the heart, vary considerably in different individuals. When present to a marked degree, they may give an examining physician the erroneous impression that a normal heart is considerably enlarged. Actually, in spite of its greater workload, a healthy heart enlarges little or not at all even during the midportion of pregnancy, when the load is greatest.

      Changes in the position of the heart, the greater workload, the increased volume of blood that the heart expels per beat, the decreased viscosity of the blood, and the larger amount of blood in the woman's blood vessels (discussed below) will, in many women, cause some distortion of the sounds that the physician hears when listening to a patient's heart with a stethoscope. Such distorted sounds, called “functional” murmurs (as distinguished from “organic” murmurs, which may be present when the heart is diseased), do not indicate that anything is amiss, although they may be sufficiently atypical to cause the obstetrician to refer the patient to a cardiologist for evaluation. Pregnancy sometimes produces minor changes in the electrocardiogram, but these changes are within normal limits.

      Such is the ability of the heart to respond to an increased workload that even the pregnant woman with serious heart disease, given proper care and without an unexpected complication, will usually go through her pregnancy and delivery without a catastrophe. She may, however, encounter difficulty when she tries to cope with the stress of caring for her family after the baby is born.

      Normal pregnancy does not increase the mother's blood pressure. Indeed, a slight lowering of the blood pressure is commonly noted during the course of the pregnancy. Any notable rise in a pregnant woman's blood pressure is reason for alertness on the part of her physician, and, if it continues to rise, for concern; it usually foretells the onset of preeclampsia (see below).

      The pulse rate is a trifle more rapid during pregnancy, reflecting the more rapid heartbeat that is necessary in order to move the larger volume of blood present. The rate at which blood flows through the myriad of small blood vessels in the skin (the peripheral circulation) is accelerated during pregnancy, leading to the elevated skin temperature, the tendency to perspire, and, in part, to the redness of the palms and the tiny dilated blood vessels in some women as their pregnancies progress.

      The most notable change in the circulatory system during pregnancy, other than those described in the heart, is a slowing of the blood flow in the lower extremities. With this decrease in the rate of flow there is an increase in the pressure within the veins and some stasis—stagnation—of the blood in the legs. These changes, which are believed to be caused primarily by the pressure of the uterus on the large blood vessels in the pelvis, are progressive during pregnancy and disappear after delivery. They also are thought to be caused in part by the marked increase in the amounts of the hormones estrogen and progesterone in the circulating blood. Increased venous pressure, slowing of the rate of venous flow, and partial stasis of the blood in the veins (vein) are major factors in causing the swelling of the legs and the varicose (varicose vein) (abnormally dilated) veins of the lower legs that are commonly present near the end of pregnancy.

      The lymphatic (lymphatic system) vessels of the pregnant woman's pelvis become enlarged in response to the increased amount of tissue fluid (edema) in the engorged pelvic organs. As the uterus grows in size, it presses on these channels, causing impairment of the lymphatic drainage from the woman's legs, with resultant swelling and distention of her feet and legs.

      Although some fluid almost invariably collects in the feet, ankles, and legs near the time of delivery, sudden swelling of the feet and legs or a notable increase in swelling may be an early signal of impending preeclampsia, a serious disorder of pregnancy that is discussed below. Generalized swelling—i.e., swelling of the hands, face, and other parts of the body—is a cause for serious concern.

      One would expect that, as the uterus grows larger and pushes the diaphragm up, it would interfere with breathing, but the lungs actually work as efficiently as they do in the nonpregnant state. This is due to a change in the shape of the chest cavity during pregnancy; the chest diameter increases as its height decreases, so that there is actually a slight increase in the space that the lungs occupy.

      The amount of air drawn in and expelled per minute by the lungs increases progressively during pregnancy. Immediately before delivery the number of breaths per minute is approximately twice what it is after the baby is born. This, like so many of the other changes in the mother's body, is an adaptation of one of her vital functions that is necessary to supply her tissues and those of the growing fetus with increasing amounts of oxygen.

      A number of alterations, often causing more or less distress, occur in the physical condition and functions of the gastrointestinal tract during pregnancy.

      Disturbances of the sensations of taste and smell, relatively common during early months of gestation, are often accompanied by a dislike of odours and a distaste of foods formerly found to be agreeable. The inflammation of the mouth and gums that some pregnant women complain of is more often caused by poor oral hygiene, by vitamin deficiencies, or by anemia than by the pregnancy itself.

       hydrochloric acid and pepsin, adequate amounts of which are necessary for satisfactory digestion, are produced by the stomach in decreased amounts during pregnancy. This decrease in the amount of acid in the stomach may explain some of the otherwise inexplicable anemias that occasionally occur during the course of an otherwise seemingly normal pregnancy.

      During pregnancy the stomach muscles lose some of their tone and become more flabby, and the contractility of the stomach is reduced. As a result, the time it takes for the stomach to empty its contents into the intestinal tract is prolonged. As pregnancy progresses, the stomach is pushed upward; near term it lies like a flabby pouch across the top of the uterus instead of hanging downward, as it normally does, in a semivertical position. The loss of tone of the stomach muscles, the decrease in stomach acidity, and the change in position of the stomach are conducive to the flow of intestinal contents back into the stomach.

      These disturbances in gastric function are responsible, in part at least, for the intolerance for fatty foods, the indigestion, the discomfort felt in the upper part of the abdomen, and the heartburn experienced by most pregnant women at some time during their pregnancies.

      The musculature not only of the stomach but also of the entire intestinal tract loses much of its tonicity. As a result, peristalsis, the series of wavelike movements of the intestines, is slowed, the length of time it takes food to pass through the intestinal tract is prolonged, and there is more or less stagnation of the intestinal contents.

       constipation and hemorrhoids (hemorrhoid) that cause rectal pain and bleeding are common complaints during pregnancy. The constipation is caused by lack of tone of the intestinal (intestine) tract and stagnation of the bowel contents. Pregnant women may also lose the urge to defecate because of the pressure of the uterus on the lower bowel and inhibition of a reflex stimulus, known as the gastrocolic reflex, from the stomach to the rectum. The latter mechanism, which depends on normal stomach function, is responsible for the increased activity of the lower bowel that follows increased stomach activity, such as that induced by eating. It is this reflex that causes many persons to feel a desire to defecate within an hour or so after eating a full meal. Hemorrhoids—greatly enlarged or varicose veins in the lower rectum—that appear during pregnancy are due to constipation, to stasis of blood in the pelvic veins, and to pressure by the enlarging uterus on the blood vessels in the pelvis.

      The liver, which plays an essential role in many of the vital processes—processes as diverse as participating in the metabolism of nutriments and vitamins and the elimination of the waste products of metabolism—changes anatomically and functionally during pregnancy to meet the added load placed on it by the maternal organism, the enlarging uterus, and, to a lesser extent, the growing fetus.

      The liver's ability to synthesize proteins and to supply minerals and nutriments is augmented in response to the increased requirements of the mother's tissue and the fetus. The liver adjusts to the greatly augmented amounts of hormones circulating in the mother's blood during pregnancy. It helps to dispose of or detoxify the larger amounts of waste material produced by the metabolic processes in the growing fetus, the enlarging uterus, and the mother's tissues. Furthermore, the blood vessels in the liver enlarge to accommodate the larger amount of blood in the mother's blood vessels. At the same time, the liver must compensate for the larger number of circulating red blood cells.

      In response to these demands, the liver increases in size and weight, and its blood vessels become larger, but otherwise its anatomic structure changes relatively little during pregnancy.

      The hormones produced by the placenta and the metabolic changes in the maternal organism, rather than the fetus, are the factors responsible not only for the increased work the liver does but also for many of the physical and functional alterations that appear during gestation.

Urinary tract (renal system)
      Changes that take place in the bladder (urinary bladder) and the urethra during pregnancy are attributable to relaxation of the muscles supporting these structures, to change in position, and to pressure.

      The uterus lies over the bladder and presses upon it during early pregnancy. Later the uterus rises out of the pelvis. As the uterus grows larger and moves upward, the bladder is pushed forward and pulled upward. The urethra, the tube through which urine is discharged from the bladder, is stretched and distorted. As these distortions take place, the wall of the bladder becomes thickened, the blood vessels become enlarged, and fluid collects in the tissues forming the wall of the bladder. The results are swelling, stasis of blood in the blood vessels, and some mechanical inflammation of the bladder wall.

      The woman is likely to urinate (urination) frequently during the early months of pregnancy when the heavy uterus presses on the bladder. Frequent urination is less common during midpregnancy, but it recurs after the baby descends into the pelvis near the time of delivery. As the bladder and urethra are pulled upward and distorted by the growing uterus, the stretched muscles that control urination are less efficient, and the woman may lose some urine involuntarily when she coughs, sneezes, or laughs; this is known as stress incontinence.

      The swelling, mechanical inflammation, and stasis of blood in the blood vessels of the bladder near the end of pregnancy are conducive to bladder infection, a symptom of which is pain on urination. A microscopic examination of the urine is necessary to differentiate between the effect of pregnancy on bladder function and the symptoms caused by a bladder infection. An untreated bladder infection may lead to serious urinary tract troubles later.

      Changes in the structure and function of the ureters (ureter), the two rubbery, spaghetti-like tubes that carry urine from the kidneys to the bladder, are present in 80 percent of all pregnancies. As pregnancy progresses, each ureter becomes larger, so that it lies in multiple broad curves rather than forming an almost straight line downward from the kidney. In addition, both ureters, but particularly the right one, become greatly dilated, so that the urine flows very slowly or collects in them.

      The funnellike part of the kidney, called the kidney pelvis, also becomes dilated. With this dilation of the kidney pelvis and the ureters there is also a loss of tonicity or contractility in the pelvis of the kidney and the ureters. This loss of tonicity during pregnancy is similar to that mentioned in the description of the changes in the intestinal tract. Since it is the contractility of peristalsis within the ureter that propels urine downward from the kidney into the bladder, stasis of urine in the ureter is accentuated during the pregnancy. In the nonpregnant state the hydrostatic pressure in the kidney is greater than that in the bladder; during pregnancy the situation is reversed. This change of pressure further increases the stasis of urine in the ureter and kidney pelvis. As a result, bladder infections are more serious during pregnancy, because they are more likely to involve the kidney.

      After delivery the ureters rapidly return to their normal condition.

      The kidney of a healthy person selectively filters and secretes water, sodium, potassium, chlorides, protein, and other substances from the blood. It then reabsorbs water and essential elements in amounts that are needed to maintain the fluid, electrolytic, and other chemical balances in the body. It also filters waste products of metabolism from the blood and excretes them in the urine. During pregnancy the kidney continues to carry on these functions. The workload placed on it, however, is greater because of the increase in the amount of water and blood and in the rate of metabolism during gestation.

      In early pregnancy, secretion of large amounts of dilute urine of decreased acidity, together with pressure of the uterus on the bladder, causes frequency of urination and nocturnal voiding. Less urine is excreted toward the end of pregnancy. The storage of large amounts of nitrogen, as part of the metabolism of proteins (protein), causes a decrease in the urinary excretion of urea and of total nitrogen during gestation.

      Although many healthy pregnant women occasionally show a trace of protein ( albumin) in their urine, the detection of even small amounts of protein in the urine is a cause for alertness on the part of a physician, because anything more than an extremely small amount may be the first signal of impending preeclampsia or kidney disease, both of which are serious complications.

      The kidney's ability to reabsorb sugar ( glucose) is lower during pregnancy, and for this reason many pregnant women have transient periods during which their urine contains small amounts of glucose; such women have unimpaired ability to metabolize carbohydrates and have normal sugar levels in the blood. Glucose in the urine also may be the first sign that a person has diabetes mellitus, however; consequently, a pregnant woman whose urine contains traces of glucose is tested to make sure that she can metabolize sugar normally.

      The preceding discussion of kidney function illustrates the need for a pregnant woman to be under a health-care provider's care, an essential part of which is periodic examination of her urine for protein, sugar, pus, bacteria, and other abnormal constituents.

      The total amount of blood in a pregnant woman's body has increased by approximately 25 percent by the time of delivery. The increase is accounted for by the augmented volume of blood plasma (the liquid part of the blood), which is caused by fluid retention, plus an increase in the total number of red blood cells. Additional blood is needed to fill the large vessels of the uterus. Also, more blood is required to carry the oxygen and nutriments needed by the fetus and the maternal tissues and to carry away waste products. Furthermore, it is a protective reserve in case of hemorrhage during delivery.

      During pregnancy the blood-forming organs, such as the bone marrow, make more erythrocytes (erythrocyte), or red blood cells, which carry iron and oxygen. Despite this, there is usually a decrease in a pregnant woman's blood cell count—the number of red cells per cubic millimetre of blood—because the amount of blood plasma increases approximately 30 percent, while the total number of red blood cells increases by only about 20 percent. This results in apparent anemia. With these changes, the viscosity of the blood decreases and the hematocrit, which measures the relative amounts of liquid and solid constituents in the blood, is lower. Usually there is a moderate increase in the number of white blood cells per cubic millimetre during early pregnancy; this increase disappears during the latter part of pregnancy.

      If a pregnant woman is otherwise healthy and receives adequate available iron for the production of hemoglobin, her red blood cell count does not ordinarily fall below 3,750,000 cells per cubic millimetre, her hemoglobin below 13.5 grams per 100 cubic millimetres of blood, and her hematocrit below 35. (Normal values for nonpregnant women are 4,200,000–5,400,000 cells, 13.8–14.2 grams hemoglobin, and 37–47 hematocrit.) Physicians usually make blood counts for their pregnant patients every two months because of the need for repeated evaluation.

      Most of the endocrine glands become larger, and some display alterations in function, during pregnancy; they all revert to a normal state after delivery.

      The anterior lobe of the pituitary gland increases in size during pregnancy, but the production of pituitary gonadotropins, the gonad-stimulating hormones, ceases soon after the placenta begins to produce chorionic gonadotropins. The pituitary continues to secrete the hormones that stimulate the other endocrine glands. Near term, as the mother's estrogen level drops, a milk-stimulating hormone, prolactin, is produced by the pituitary. The posterior lobe of the pituitary gland does not change in size or weight during pregnancy.

      The thyroid gland enlarges moderately, but there is no true increase in thyroid function during gestation. The parathyroid glands also increase in size during pregnancy but presumably are not otherwise affected by it.

      The part of the pancreas that secretes insulin, the islets of Langerhans (Langerhans, islets of), becomes larger. Whatever increase in function is displayed may be assumed to be a balanced response to the body's demand for the products of carbohydrate metabolism. The level of plasma insulin or of insulin-like substances in the plasma is higher during pregnancy, and the destruction of insulin is also more rapid.

      The blood and urinary levels of 17-hydroxycorticosteroids, hormones (sex hormone) that affect protein, fat, and carbohydrate metabolism and that are produced by the adrenal glands, rise during pregnancy; but there is no increased effect from the hormones, because their higher level is more than offset by the increased levels of transcortin, a protein that inactivates them.

      As gestation progresses, there is an elevation in the secretion of aldosterone, an adrenal hormone that plays a role in the retention of salt and water in the body. It has been suggested that this is a protective mechanism to counterbalance the tendency for progesterone to cause the excretion of sodium ions in the urine.

      Pregnancy usually causes an increase in the secretion of the oil and sweat glands in the skin. Body odours may become more pronounced. Many women notice that their hair becomes thinner and drier and their nails more brittle. Others may develop an increased amount of facial and body hair. The “mask of pregnancy” seen particularly in brunettes is a deposit of brownish pigment in the skin of the forehead, the cheeks, and the nose. Puffiness and thickening of her skin may cause the pregnant woman's face to appear coarse and almost masculine. Increased pigmentation, particularly of the smooth skin about the nipples (the areolas of the breasts) and the vulva, is almost universal.

      Bright red discoloration of the palms of the hands and tiny spiderweb-like red blood vessels in the skin of the arms or face are not unusual during pregnancy. Many of these changes are thought to be associated with the greatly increased levels of estrogen in the mother's bloodstream. Most of the changes disappear after delivery.

      “Stretch marks,” which appear on the breasts and abdomen during pregnancy, are due to the tearing of the elastic tissues in the skin that accompanies enlargement of the breasts, distention of the abdomen, and the deposition of subcutaneous fat. They are pink or purplish red lines during pregnancy. The lines become permanent scarlike marks after delivery. Some women never develop stretch marks despite bearing several children; others lose most of the tone in their skin after one pregnancy. Stretch marks cannot be considered evidence that a woman has borne a child, however, because they sometimes are seen in women who have not been pregnant.

Metabolic changes
      Metabolic changes during pregnancy are among the many adjustments that the mother's organs make to meet the requirements created by the increase in her own breast and genital tissues and the growth of the conceptus (the fetus and afterbirth). In addition, reserves must be established to meet the demands that will be put on her body during pregnancy, delivery, and the postdelivery period.

      The amount of oxygen consumed is an index of the pregnant woman's metabolism when she is at rest—her basal metabolism. The rate begins to rise during the third month of pregnancy and may double the normal rate (+10 percent) by the time of delivery. The rate rises in specific proportion to the size of the fetus and represents the effects of the mother's activities plus those of the fetus and the uterine structures. An elevation of the basal metabolic rate (BMR) to 20 or 25 percent during pregnancy is not an indication of an overly active thyroid gland.

      The early part of pregnancy usually is accompanied by moderate weight loss caused by the woman's lack of appetite and in some cases nausea and vomiting. Between the third and the ninth month of pregnancy most women gain about 9 kilograms (20 pounds) or more. Ideally, during pregnancy, body weight is gained at the rate of about 0.5 kilogram (1 pound) per week for a total of not more than 9 to 11.5 kilograms (20 to 25 pounds). In an average pregnancy the infant, the afterbirth, and the fluid in the uterus weigh about 4.5 kilograms (10 pounds). The uterus and the breasts together weigh approximately 2.25 kilograms (5 pounds). The remaining 2.25 kilograms consist of stored fluids and fat. Weight gain exceeding 11.5 kilograms usually represents fat and fluids that are in excess of the reserve requirements for a normal pregnancy. A woman loses approximately 7 kilograms (15 pounds) at delivery, and another 2.25 kilograms of stored fluid are eliminated as the uterus shrinks. She does not lose many additional kilograms during the weeks following the delivery of the baby unless she limits her caloric intake. Fat stored during pregnancy is lost more slowly than stored fluids, proteins, and carbohydrates.

      Excessive weight gain during pregnancy is a matter of concern for both the patient and the doctor. Although it may be only the result of overeating, it may be caused by a disturbance in metabolism and by an abnormal retention of fluids and salts. In the latter instance it may be the first sign of preeclampsia.

      During pregnancy, nitrogen, derived from the metabolism of ingested protein, is needed for growth of the fetus, the placenta, the uterus, and the mother's breasts and other tissues. A considerable amount of nitrogen also is required for the increase in the mother's red cell volume and blood plasma. The fetus's demand for nitrogen is slight at first, but during the last month of pregnancy it acquires almost half of its total protein. In the process of accumulating this store and of building a reserve for the period after delivery, the woman who is on an adequate diet retains between two and three grams of nitrogen daily during her pregnancy; by term she and the fetus will have acquired approximately 500 grams (about 1.1 pounds) of nitrogen.

Carbohydrates (carbohydrate)
      During pregnancy greater quantities of blood are being processed through the kidneys, but the kidneys are incapable of reabsorbing increased amounts of sugar. Consequently, a lower level of sugar in the blood is tolerated, and slight amounts of sugar are excreted in the urine. During pregnancy the level of sugar in the blood after fasting is slightly lower, probably because there is less usable insulin in the blood to regulate the sugar metabolism. Oral glucose-tolerance tests show a prolonged elevation of blood sugar after ingestion of glucose; this may be an indication that carbohydrate use is less rapid or that the absorption of glucose from the gastrointestinal tract is slower. Glucose-tolerance tests that depend on injection of the sugar solution into the veins show no difference between nonpregnant and pregnant nondiabetic women. A few women demonstrate diabetes for the first time when they are pregnant, a condition referred to as gestational diabetes. This occurs because pregnancy taxes insulin productivity in women with a marginal pancreatic islet reserve, so that diabetes may first become evident during gestation.

      The total blood lipids (lipid) average 600 to 700 milligrams per hundred millilitres of blood in the nonpregnant woman. They increase to approximately 900 to 1,000 milligrams per hundred millilitres of blood during the latter part of pregnancy. This increase, which involves all the lipid fractions, has not been explained, but it is worthy of notice that the gain in fat reaches its acme during the period that the fetus acquires most of its adipose (fatty) tissue.

      Pregnancy is characterized by increases in the amount of body water and in the total volume of body fluid. During pregnancy between 3,500 and 4,000 millilitres of fluid (about 3.2 to 3.6 quarts) will be added to that already present in the tissues of a healthy woman. The uterus, the placenta, the amniotic fluid, and the fetus each account for approximately equal amounts. In addition to the water that increases blood volume, there is also added fluid in the mother's muscles, her pelvic soft tissues, her breasts, and her other tissues.

      Toward the end of pregnancy a considerable amount of retained fluid accumulates in the woman's lower extremities. It is this fluid that produces the pitting and swelling of the legs that many normally pregnant women display during the month or two before delivery.

      Retention of large amounts of electrolytes, particularly sodium, accompanies the increase in the amount of body fluids. Approximately 12 grams of sodium are retained monthly. In addition to a positive sodium balance, there is a positive chloride and potassium balance during pregnancy. As a result, additional water is required to maintain the balance of the solution of sodium, chloride, and potassium in the blood, in the fluid of the spaces between the tissue cells, and within the cells themselves. Not all of the sodium, however, goes into fluid. Some of it is stored, and some replaces potassium in the cells.

      A number of factors contribute to a positive sodium balance, which in turn leads to retention of fluid; these include alterations in the kidneys' excretion of sodium and water; increased retention of water in the pregnant woman's legs; the large amounts of hormones, particularly estrogen, that the placenta secretes; and the secretion of adrenal hormones, especially aldosterone. The latter, in particular, reduces the kidneys' secretion of sodium. Because sodium and water interact with each other, whatever contributes to the retention of one leads to the retention of the other. Generalized swelling appears when the accumulation of sodium and water becomes too great.

Minerals
      The pregnant woman's reserves and intake of iron and calcium must be enough not only for her own needs but also for those of the fetus. An increase in serum copper levels occurs during pregnancy. The mother has some phosphorus reserve but must acquire enough from her diet to supply her own tissues and those of the fetus. The use of phosphorus and that of calcium are interdependent, so that the use of phosphorus depends on the calcium intake.

John W. Huffman

Prenatal care and testing
      An adequate maternal diet is necessary to ensure proper fetal development as well as to maintain the health of the mother. As discussed above, the physiological adjustments of a pregnant woman's body are significant, and nutritional requirements increase as a result. In addition to an awareness of the substances that are of benefit during pregnancy, a knowledge of which substances are harmful and should be avoided is equally important. alcohol has been found to be teratogenic (causing developmental malformations in the fetus). Intake of large to moderate quantities of alcohol during pregnancy is responsible for fetal alcohol syndrome, which is characterized by impaired growth and development, facial abnormalities, cardiac defects, and skeletal and joint malformations. The effects of limited intake of alcohol are not as well known, but avoidance of any amount of alcohol throughout pregnancy is recommended. smoking of tobacco during pregnancy is believed to lower the birth weight of the fetus and is also associated with placenta praevia, abruptio placentae, and elevated maternal blood pressure. Sudden infant death syndrome, delayed mental development in childhood, and spontaneous abortion also have been linked to smoking. Limiting the use of caffeine also is encouraged. While not believed to have teratogenic effects, excessive caffeine intake may account for low birth weight in infants. Over-the-counter medications as well as prescription drugs can adversely affect fetal development and should not be taken unless a health-care provider is consulted.

      The use of high-frequency sound waves to produce a graphic image of the growing fetus—ultrasonography—is becoming a ubiquitous tool in prenatal medicine, furnishing information on the morphological and functional status of the fetus. It is commonly used to estimate the gestational age of the fetus, identify fetal number, assess growth, determine fetal heart activity, and provide a general survey of fetal anatomy. The presentation of the fetus and placenta and the volume of amniotic fluid also can be determined using ultrasound. In most European countries an ultrasound scan is routinely included in obstetric examinations, but, although it is widely used in the United States and Canada, its inclusion in standard prenatal evaluations has not been recommended. This reluctance is based on the lack of clear evidence that this procedure has no negative effects. Theoretical risks are involved because of the invasive nature of this technique (i.e., sound waves are reflected off tissues). Studies to date, however, have revealed no evidence of tissue damage when diagnostic ultrasound is used, and the benefits of this procedure seem to outweigh the risks.

      In the procedure of amniocentesis, amniotic fluid is aspirated (withdrawn) from the uterus by a needle inserted through a woman's abdomen, using ultrasound to circumnavigate the fetus and placenta. Spinal cord defects and a host of genetic abnormalities such as Down syndrome and autosomal recessive diseases such as Tay-Sachs disease and cystic fibrosis can be screened for by amniocentesis. It can also be used to determine the sex of the fetus and identify sex-linked diseases. Not all birth defects, however, can be detected by this procedure. This test is generally performed about the 16th week of pregnancy, and results take several weeks to obtain. Of the potential risks associated with this procedure, the most significant one is that of fetal loss, which may result from disruption of the placenta.

Chorionic villi sampling
      The technique of retrieving a sample of villi from the chorion (outer embryonic membrane) within the uterus is similar to amniocentesis but can be carried out much earlier in pregnancy, between the 8th and 12th week of gestation. The test can be performed through either the abdomen or the vagina and cervix. The latter technique is carried out using ultrasonic visualization, and a thin catheter is inserted through the vagina into the uterus; a sample of villi from the chorion is then extracted and examined. If unfavourable results are received, termination of the pregnancy can be accomplished at an earlier stage than would be possible with amniocentesis. This procedure does carry a slightly higher risk of fetal loss than does amniocentesis, possibly because it is carried out at an earlier stage in fetal development. With this technique there is also concern that fetal limb reduction or malformation may result, but reports are inconclusive.

Alpha-fetoprotein screening
      Shed by the yolk sac and fetal liver, alpha-fetoprotein can be used to screen for neural tube defects such as anencephaly and spina bifida (developmental abnormality in which spinal cord is not fully enclosed). The measurement of elevated levels of alpha-fetoprotein in a woman's blood between the 16th and 18th weeks of pregnancy are associated with this abnormality. Because other circumstances such as multiple pregnancies, underestimation of gestational age, and fetal death are associated with high levels of alpha-fetoprotein, ultrasound should be used to help rule out these different causes. Abnormally low levels of alpha-fetoprotein have been linked to a significant incidence of Down syndrome. A high rate of false-positive results is associated with this test, and so it is not recommended routinely. This procedure has been reserved primarily for those women with a family history of neural tube defects.

Ed.

Abnormal changes in pregnancy

      An ectopic pregnancy is one in which the conceptus (the products of conception—i.e., the placenta, the membranes, and the embryo) implants or attaches itself in a place other than the normal location in the lining of the upper uterine cavity. The site of implantation may be either at an abnormal location within the uterus itself or in an area outside the uterus. Ectopic pregnancies outside the uterine cavity occur about once in every 300 pregnancies. They are one of the major causes of maternal deaths.

      Normally an ovum or egg passes from the ovary into the tube, is fertilized in the tube, and moves downward into the uterus. It buries itself in the lining of the upper part of the uterine cavity. It may pass farther down and attach itself to the lining of the mouth of the uterus (the cervix), creating a cervical pregnancy. These are rare and cause severe vaginal bleeding; the conceptus is expelled or discovered within a few months after implantation.

      If a conceptus attaches itself to the lower part of the uterine cavity, it is a low implantation. When a low implantation occurs, the placenta grows over the cervical opening, in a formation called a placenta praevia. This causes the woman to bleed, often profusely, through the vagina, because the placenta tears as the cervix begins to open during the latter part of pregnancy.

      When the fertilized egg implants in the narrow space or angle of the uterine cavity near the connection of the uterus with the fallopian tube, it is called an angular pregnancy; many angular pregnancies terminate in abortions; others go to term but are complicated because the placenta does not separate properly from the uterine wall after the birth of the baby. An angular pregnancy differs from a cornual pregnancy, which develops in the side of a bilobed or bicornate uterus.

      Implantation in the narrow part of the fallopian, or uterine, tube, which lies within the uterine wall, produces what is called an interstitial pregnancy. This occurs in approximately 4 percent of ectopic pregnancies. An interstitial pregnancy gradually stretches the wall of the uterus until—usually between the 8th and 16th week of gestation—the wall ruptures in an explosive manner and there is profuse bleeding into the abdomen.

      Most persons associate ectopic pregnancies with tubal pregnancies, because most ectopic pregnancies occur in the uterine tubes. The tube beyond the uterus has three parts: the isthmus, a narrow section near the uterus; the ampulla, which is wider and more dilatable; and the infundibulum, the flaring, trumpetlike portion of the tube nearest the ovary. A tubal ectopic pregnancy is designated by the area of the tube in which it is implanted. An isthmic pregnancy differs from one in the ampulla or infundibulum because the narrow tube cannot expand. Rupture of the affected tube with profuse intra-abdominal hemorrhage occurs early, usually within eight weeks after conception.

      Ampullar pregnancies, which are by far the most common, usually terminate either in a tubal abortion, in which the embryo and the developing afterbirth are expelled through the open end of the tube into the abdomen; by a tubal rupture; or, less commonly, by absorption of the conceptus.

      Sometimes the tube ruptures into the tissues attaching it to the wall of the pelvis, producing an intraligamentous pregnancy. Rarely, the embryo is expelled into the abdomen and the afterbirth remains attached to the tube; the embryo lives and grows. Such a condition is referred to as a secondary abdominal pregnancy. Primary abdominal pregnancies, in which the fertilized egg attaches to an abdominal organ, and ovarian pregnancies are rarer still.

      It is generally believed, but not proved, that most tubal pregnancies are caused by scars, pockets, kinks, or adhesions in the tubal lining resulting from tubal infections. The infection may have been gonorrhea; it may have occurred after an abortion, after the delivery of a baby, or after a pelvic surgical operation; or it may have been caused by appendicitis. Kinking, scarring, and partial adhesions of the outside of the tube may be the result of inflammation following a pelvic operation or of an abdominal inflammation. Tubes, defective from birth, may be too small for the passage of the conceptus or may be pocketed or doubled with one tubal half forming a blind pocket. There may be areas in the tubal lining that behave like the lining of the uterus (they show a decidual reaction that is conducive to implantation) so that they offer a favourable spot for the fertilized egg to implant. Pelvic tumours may distort the tube and obstruct it so that the conceptus cannot move downward. Theoretically, endocrine disturbances may delay tubal motility.

      Whatever the cause, when a tubal implantation occurs, it may be assumed that either migration of the fertilized egg within the tube was delayed by an extrinsic factor so that the egg grew to the point where it should implant or that the mechanism for implantation within the egg itself was prematurely activated in the tube. One or the other of these causative factors can sometimes be seen when a woman is operated upon for an ectopic pregnancy. In a great number of cases, however, no tube abnormality can be found. There is no satisfactory explanation for most abnormal implantations in the uterus, although defective uterine structure has been noted in some cases.

      Primary abdominal and ovarian pregnancies can best be explained by a mechanism in which the fertilized ovum is swept out of the tube by a reverse peristalsis of the tube, but it is quite possible that, in rare instances, the ovum and spermatozoa meet and fertilization and implantation take place within the abdomen.

      Ectopic pregnancy is frequently mistaken for other disorders. Typically, but not invariably, the woman who has an ectopic pregnancy in the ampullar part of the tube will have missed one or two menstrual periods. She need not have other symptoms of pregnancy. She has felt enough discomfort in the lower part of her abdomen to lead her to consult a physician. She has had recurrent episodes of rather light, irregular bleeding from the vagina. She has felt weak or faint at times. The signs of pregnancy are not likely to be present, and results of a pregnancy test are more often negative than positive. The physician, on pelvic examination, feels a tender, soft mass in one side of the pelvis. At this stage the differentiation must be made between an ectopic pregnancy and an intrauterine pregnancy with abortion, acute appendicitis, intestinal colic, inflammation of a fallopian tube, and a twisted ovarian tumour. Unless the diagnosis can be made, the patient continues to complain for several more days and then has a sudden severe pain and collapses from brisk bleeding within the abdomen.

      Sudden and acute abdominal pain and collapse due to severe hemorrhage are only rarely the first signs that something is amiss. If this does happen, it is usually because implantation has occurred in the isthmic portion of the tube and hemorrhage and tubal rupture occur simultaneously. More frequently, a woman has missed one menstrual period, has a sensation of pelvic pressure, feels that she must urinate, and collapses in the bathroom. She may be unconscious and pulseless from loss of blood when she arrives at the hospital.

      Interstitial pregnancies are often mistaken for intrauterine ones, but the patient has pain and may have intermittent vaginal bleeding. After several months she has sudden, severe pain, collapses from a massive intra-abdominal hemorrhage, and may die before surgical help can reach her. Most of the women who die from ectopic pregnancies do so from interstitial ones.

      Combined pregnancies, in which there is an ectopic pregnancy and a normal one in the uterus, or a fetus in each tube, have occurred and have compounded the difficulty in making a diagnosis. In a number of instances, the ectopic conceptus has been removed without complications, and the uterine fetus has progressed to term.

      Not all ectopic pregnancies end with a catastrophic hemorrhage and collapse. In a few instances tubal, abdominal, and broad ligament pregnancies have gone on until a living baby was obtained at the time of operation. In other cases the fetus died and, if very young, was resorbed; in others, when the fetus was larger, death was followed by absorption of the fluid in the sac, and the fetus was gradually converted into a more or less mummified mass. Some ectopic pregnancies of this type have caused no symptoms and have been carried by women for years. Undoubtedly many ectopic pregnancies that are in an early stage when they are expelled emerge through the open end of the uterine tube, are resorbed, and are never recognized.

      Once diagnosed, the treatment of ectopic pregnancies outside the uterine cavity is almost always a matter of prompt surgical intervention with proper attention to replacement of blood and fluid.

      Abortion is the termination of a pregnancy before the infant can survive outside the uterus. The age at which a fetus is considered viable has not been completely agreed upon. Many obstetricians use either 21 weeks or 400–500 grams (0.9–1.1 pounds) birth weight as the baseline between abortion and premature delivery, because few infants have survived when they weighed less than 500 grams at birth or when the pregnancy was of less than 21 weeks' duration. Generally speaking, the fetus has almost no chance of living if it weighs less than 1,000 grams (2.2 pounds) and if the pregnancy is of less than 24 weeks' duration. In one effort to resolve the matter, the American College of Obstetricians and Gynecologists has defined abortion as the expulsion or extraction of all (complete) or any part (incomplete) of the placenta or membranes, with or without an abortus, before the 20th week (before 134 days) of gestation. Early abortion is an abortion that occurs before the 12th completed week of gestation (84 days); late abortion is an abortion that occurs after the 12th completed week but before the beginning of the 20th week of gestation (85–134 days).

      In the past the word abortion usually meant to nonmedical persons the elective interruption of a pregnancy, whereas “ miscarriage” indicated a spontaneous expulsion of the uterine contents. The term miscarriage is seldom used medically.

      Spontaneous abortion is the expulsion of the products of conception before the 20th week of gestation without deliberate interference. As a general rule, natural causes are responsible for loss of the pregnancy. An induced abortion is the deliberate interruption of a pregnancy by any means before the 20th week of gestation. In medical terminology an abortion may be therapeutic or elective (voluntary). A therapeutic abortion is the interruption of a pregnancy before the 20th week of gestation because it endangers the mother's life or health or because the baby presumably would not be normal. An elective abortion is the interruption of a pregnancy before the 20th week of gestation at the woman's request for reasons other than maternal health or fetal disease. Most abortions in the United States are performed for this reason.

      A spontaneous abortion usually passes through several progressive stages. The first stage is a threatened abortion in which a woman, known to be less than 20 weeks pregnant, notices a small amount of bloody discharge from her vagina and, perhaps, a few cramping pains in her uterus. By pelvic examination it is determined that her cervix has not started to open or dilate. Either the symptoms subside or the matter progresses to an inevitable abortion, in which there is increased bleeding, the uterine cramps become more severe, and the cervix, or mouth of the uterus, opens for the expulsion of the uterine contents. An inevitable abortion terminates either as a complete or an incomplete abortion, depending on whether or not all the products of gestation are expelled. The process may start abruptly with pain and profuse bleeding and be over in a few hours, or it may go on for days with only a modest loss of blood. Spontaneous abortions early in pregnancy tend to be complete. When the pregnancy is further advanced, it is more likely to be incomplete. Usually the physician removes the retained tissue in the uterus surgically when there is an incomplete abortion.

      If the fetus dies and is retained in the uterus for eight weeks or longer, the condition is referred to as a missed abortion. Women who lose three or more consecutive pregnancies of less than 20 weeks' duration are said to suffer from recurrent abortion. An infected abortion is an abortion associated with infection of the genital organs.

      Approximately 15 percent of all clinically evident pregnancies terminate in spontaneous abortion. A much higher rate of early pregnancy loss—more than 40 percent—is believed to occur. Some are lost so early that the woman and her physician are not sure whether she aborted or had a menstrual period that was slightly delayed, particularly heavy, and more painful than usual. The majority occur between the 6th and the 12th week after conception. Modifications in the abortion laws in several countries, including the United States, have greatly increased the number of requested abortions; it is believed that in some areas the number of abortions exceeds that of babies delivered alive.

      At least half of all spontaneous first-trimester abortions have been found by karyotyping (examination of chromosome characteristics) to have a chromosomal abnormality. Some of these genetic mistakes are caused by abnormal characteristics carried in the egg or sperm or by the failure of normal rearrangement of the chromosomes to occur after the egg and sperm unite. It has been shown in animals that disturbances in the transportation of the fertilized egg to the uterus may cause premature or delayed implantation of the conceptus; fertilized eggs that are too young or too old tend to abort. Inadequate secretion of the ovarian hormones estrogen and progesterone, needed for the development of the newly fertilized egg, may cause failure of the lining of the uterus and its secretions to sustain the young embryo. Later, failure of the placenta to take over the hormone-producing function of the ovary may adversely affect the growth of the uterus and its contractility. X rays in large doses, radium, and certain drugs may cause abortion because they damage embryonic tissues. Abnormal development of the mother's uterus may make it impossible for it to retain the pregnancy.

      Late abortion is sometimes caused by the weakness of the cervix or by fetal death following knotting of the umbilical cord. Uterine tumours may cause abortion because they increase uterine irritability or create an unfavourable environment for embryonic growth. In most instances in which psychological factors allegedly caused an abortion, examination of the baby and of the afterbirth have shown defects in one or both that had occurred before the mother had suffered her emotional disturbance. Physical injury to the mother is a causative factor in only one in a thousand abortions. Abortions thought to be caused by automobile accidents, falls, kicks, and so forth are often the result of deleterious changes in the fetus and sac that occurred before the injury. Systemic diseases may play a role in causing an abortion. This is particularly true of acute infectious diseases with high fever and bacteria in the bloodstream, or of diseases such as pneumonia, in which there is a marked reduction in the supply of oxygen to the fetus. Heart disease, kidney disease, diabetes, high blood pressure, and other chronic diseases may be associated with premature birth and fetal death after the 21st week but do not ordinarily cause abortions.

      Perhaps 3 percent of threatened abortions are prevented by rest and hormonal therapy. Most abortions are inevitable because the fertilized egg is abnormal; these cannot be controlled medically. Many women who suffer from recurrent abortion respond well to treatment; in some of these cases corrective surgery is necessary. An early spontaneous abortion without infection is rarely followed by ill health when the affected person receives proper medical treatment. Infected abortions, many the result of elective interruptions of pregnancy, have caused chronic pelvic distress and, in some cases, sterility.

Systemic diseases and pregnancy
heart disease
      Heart disease occurs in approximately 1 percent of pregnant women. It is first as a cause of maternal deaths among the disorders incidental to pregnancy and fourth, after hemorrhage, preeclampsia, and infection, as a cause of all maternal deaths. Rheumatic heart disease is the most prevalent type. Congenital heart disease accounts for approximately one-fourth of the cases.

      A number of factors, including her response to physical activity, a history of heart failure, the type of heart disease that she has, and her age, are used in estimating how a particular woman will fare during pregnancy and labour. A person whose heart disease causes no limitation of normal physical activity will usually go through a normal pregnancy and delivery without notable difficulty, provided that she avoids undue physical activity, has sufficient rest, avoids infections, and is under the care of an obstetrician and a cardiologist who are on the alert for signs of early heart failure. Such a person will not face an appreciably increased risk, and her heart disease will not be affected by the pregnancy.

      The woman whose physical activity is limited to some extent because it causes undue fatigue, shortness of breath, heart palpitation, or heart pain, but who has never experienced heart failure, will seldom suffer heart failure if she follows a strict regimen outlined by her physicians throughout the pregnancy, the labour, and the puerperium (the period immediately after childbirth) and if she does not experience a complication of pregnancy or of her heart disease. A diseased heart, although able to carry the load put on it by pregnancy, may not be able to stand up under an additional burden. This is particularly true if the pregnant woman gains an excessive amount of weight; if she develops preeclampsia, kidney disease, pulmonary disease, or an infection; or if she overworks physically, is subjected to sudden severe emotional stress, or becomes anemic. The possibility that a woman with serious heart disease will have heart failure is greater if she is over 35 years of age.

      More than half of the women who have suffered from heart failure before they became pregnant do so again during pregnancy, usually between the fifth and the ninth month, when pregnancy throws the greatest workload on the heart. Because so many women with a history of previous heart failure have difficulties during pregnancy, many obstetricians and cardiologists restrict the physical activity of such women and try to keep them in the hospital and under close medical surveillance. Some women with serious heart disease are kept in bed in the hospital throughout the course of the pregnancy and thus avoid heart failure. Cardiac surgery during the first few months of pregnancy, although a hazardous procedure, has lessened the necessity for prolonged bed rest in some cases and materially improved the prognosis in others.

      Women with serious heart disease often deliver prematurely, and their labours are often short and their deliveries easy. There is an increase in fetal mortality because many pregnancies are interrupted and because many of the babies of women with heart disease are born prematurely. Babies who are not born prematurely are not notably different from those of normal mothers.

      Before insulin was available, most diabetic women were sterile, or, if they became pregnant, aborted. Half of the babies and one-fourth of the mothers died if they went to term. Today, if they are adequately supervised, less than 1 percent of pregnant diabetic women die of diabetes during pregnancy or the puerperium. Diabetic women do suffer from an increased incidence of preeclampsia, infections, and hydramnios (excessive amniotic fluid). Abnormalities of labour are increased because the babies tend to be unusually large, and congenital abnormalities of the fetus are more common, as is hydramnios; hydramnios is a problem in 25 percent or more of diabetic women.

      Untreated diabetes is associated with a high incidence of fetal defects, abortion, stillbirths, premature labour, and excessively large babies. Even with diet and insulin, more than 50 percent of the babies delivered by diabetic women weigh over eight pounds at birth. Even though they appear healthy at birth, many of them are not as strong as smaller babies whose mothers are not diabetic. Fetal loss is greater if the mother became diabetic in childhood, if she has been diabetic for a long time, or if she has vascular or kidney disease.

      Pregnancy frequently has an adverse effect on diabetes, and diabetes may first become evident during pregnancy. There is a tendency for the carbohydrate metabolism of the diabetic patient to be upset. Most diabetics need more insulin during gestation; a few, for reasons not understood, need less. The changing condition from day to day makes some diabetics, who have no problem maintaining a balance when they are not pregnant, difficult to treat. Even so, adequate medical supervision can bring most diabetics and their babies safely through pregnancy.

      Simple goitres that are not associated with a change in the amount of thyroid hormone in the mother's blood do not affect pregnancy, nor does pregnancy affect the thyroid in such a case. An inactive or too active thyroid gland, if not adequately treated during pregnancy, may be associated with an increased incidence of abortion. In the few cases in which persons with untreated myxedema, a severe form of hypothyroidism (deficiency of thyroid hormone), have conceived and gone to term, there has been an increased incidence of congenital anomalies of the fetus. Pregnancy and hyperthyroidism (overabundance of thyroid hormone) seem to have no adverse effects on each other.

Pituitary disorders
      Most persons with pituitary hypofunction fail to ovulate because their pituitary glands (pituitary gland) do not produce the gonadotropic hormones necessary for stimulation of the ovaries. Most of these persons also suffer from a lack of hormones from their other endocrine glands because these, too, lack stimulation by the pituitary. A few persons with hypopituitarism have, nevertheless, become pregnant. Their condition is better when they are pregnant because their placentas produce many of the hormones that their endocrine glands, lacking pituitary stimulation, do not ordinarily secrete.

Adrenal glands (adrenal gland)
      Women suffering from adrenal gland insufficiency are not likely to become pregnant. If they do so, they have a greater tendency to suffer from circulatory disturbances and carbohydrate, electrolyte, and fluid imbalances because of the important role the adrenal glands play in the metabolism of water, sodium, potassium, chlorides, and glucose. Such patients and their babies do well if they receive hormonal therapy during gestation.

      The increased secretion of adrenal hormones that occurs with hyperplasia of the adrenal cortex (enlargement of the outer layer of the adrenal gland, also called Cushing's syndrome (Cushing syndrome)) usually inhibits ovulation. A number of women with this disorder, after treatment with cortisone, have conceived, gone to term, and delivered normal children. Cushing's syndrome complicated by pregnancy is rare; the few cases reported have been associated with a high incidence of severe high blood pressure.

      The maternal death rate is approximately 50 percent, and the death rate of the child immediately before or after birth is approximately 40 percent when pheochromocytoma (a type of adrenal tumour associated with, among other things, high blood pressure) complicates pregnancy.

Urinary tract (renal system disease) diseases
      Infections of the urinary tract are more frequent during pregnancy, and women who have acute infections of the bladder and kidneys while pregnant have a higher incidence of premature labour. This is in accord with the fact that pregnant women with any type of acute infection tend to deliver prematurely. Many women with pyelonephritis (infection of the kidney) in one pregnancy will enter a second pregnancy with bacteria already in the urinary tract, although they are asymptomatic. These women have a greatly increased chance of developing acute urinary tract infections during their prepartum course and have some risk of eventually developing serious kidney disease. Glomerulonephritis (Bright disease), a kidney disease that affects the clusters of capillaries in the nephrons, the functioning kidney units, usually is preceded by infection with streptococcus organisms. The incidence of abortion and of premature delivery is increased among women in whom the condition develops during pregnancy. If the glomerulonephritis has become chronic, the fetus may not survive and the mother's life may be endangered by kidney failure.

      Healed tuberculosis of the kidney is not a contraindication to pregnancy if the disease has been quiescent for three years or longer and kidney function is normal. If tuberculosis of the kidneys is present but without symptoms, pregnancy may cause it to become active. If this happens, and if the infection is limited to one kidney, there is an increased danger that the opposite kidney will become infected in some way. The interference with the flow of urine that is characteristic of pregnancy is an important factor in the development of such infections. The accepted treatment when tuberculosis was present in one kidney during pregnancy formerly was therapeutic abortion followed by removal of the tuberculous kidney. This procedure is now avoided in some instances because of the effectiveness of the antituberculotic drugs that have been developed.

      It is sometimes necessary to remove a person's kidney because of an infection, a stone, a tumour, or tuberculosis. The remaining normal kidney has a reserve that is greatly in excess of the demands that will be made by gestation, provided that it does not become infected. Infections, impaired kidney function, congenital defects, and preeclampsia, however, are more serious for a woman with a solitary kidney than they are for the patient with a normal urinary tract.

Pulmonary disease (respiratory disease)
      Pulmonary disorders have an adverse effect on pregnancy if they seriously decrease the amount of oxygen supplied to the fetus, if they make the mother desperately sick, or if they create a blood infection that is transmitted to the placenta.

      An infection of the upper respiratory tract—the nose and throat—does not ordinarily disturb the course of gestation. It may be serious when it occurs in late pregnancy because of the danger that the mother will transmit disease-causing bacteria to her own genitalia or will carry virulent bacteria from her own nose and throat into the labour room and develop a blood infection after the delivery.

      Epidemic influenza is associated with an increased incidence of maternal deaths. Many women who suffer from it abort or deliver prematurely. The infection may pass through the placenta and cause infection in the fetus. Pregnant women who acquire epidemic influenza are more likely to develop pneumonia than are persons who are not pregnant.

      Pregnancy may increase or decrease the severity of asthma or may fail to affect it. A severe attack of asthma may be followed by abortion, but otherwise asthma does not affect pregnancy.

       pneumonia occurring during pregnancy is associated with a high rate of maternal and fetal death unless the pulmonary infection is susceptible to antibiotics or chemotherapy. The mother's cardiovascular system, already carrying the load placed on it by pregnancy, cannot sustain the added stress produced by pneumonia. The fetus often dies from oxygen starvation or from intrauterine infection.

      Severe bronchitis and bronchiectasis—abnormal dilation of bronchi with some destruction of bronchial walls—may so interfere with the mother's respiration that the extra strain put on her cardiorespiratory system by pregnancy may put her life in jeopardy. If the disorders are severe enough to cause impaired pulmonary ventilation, the fetus may suffer from a lack of oxygen and may be either stillborn or delivered prematurely. Pregnancy does not adversely affect the course of these pulmonary diseases.

      Pulmonary tuberculosis is not, as a rule, affected by pregnancy. This is particularly true if the patient's infection has been quiescent for several years before she becomes pregnant. Even women with active tuberculosis, if given adequate care, usually go through pregnancy without any deterioration in their pulmonary condition. This is not universally true, however, because there is a small group with active disease whose disease becomes worse during pregnancy. For that reason individual evaluation of each person is necessary.

      Although there have been a few cases of infection transmitted to the fetus prenatally, the great majority of babies born of tuberculous mothers are healthy at birth.

      Pregnant women who have had portions of their lungs (lung) removed for tuberculosis, tumours, or other reasons do well provided that, before becoming pregnant, they are not short of breath with ordinary exertion. The added load of an additional pulmonary infection may not leave such persons with enough pulmonary reserve for the added burden of pregnancy; they may therefore experience difficulties if they contract pneumonia, severe influenza, or acute bronchitis during pregnancy.

Gastrointestinal diseases
      Women may already suffer from a gastrointestinal (digestive system, human) disease such as gastric or peptic ulcer, gallbladder disease, or ulcerative colitis when they become pregnant; or they may develop some type of gastrointestinal disturbance during the course of the pregnancy. In either event, pregnancy complicates their problems because the gastrointestinal disturbances that often accompany pregnancy may confuse the diagnosis in an individual case.

      Gastrointestinal diseases have little or no effect on pregnancy. Pregnancy, on the other hand, tends to aggravate gastrointestinal disorders; the exception is gastric ulcer, which often improves because the concentration of acid in the stomach is decreased with pregnancy. Women with chronic ulcerative colitis are generally advised to avoid pregnancy until their bowel disease has been quiescent for two years; actually, since the woman's psychological reaction to pregnancy is what affects the bowel, the colitis may be made either better or worse by gestation.

      Acute appendicitis, occurring during pregnancy, is often confused with other gastrointestinal complaints, and many patients' lives have been jeopardized either because they ignored the symptoms or because the diagnosis was confused by pregnancy. A diagnosis of acute appendicitis calls for immediate surgery regardless of the duration of the pregnancy or the hazard to the fetus.

      Neurological disorders and pregnancy most often are coincidental and have no effect on each other, but there are a few neurological diseases that develop during pregnancy, have a deleterious effect on it, or are adversely affected by it.

       epilepsy of unknown cause does not affect the course of pregnancy but may occur for the first time during gestation. An epileptic person may find her condition improved, aggravated, or unchanged by pregnancy; the effect of gestation cannot be foretold. There is some evidence that excessive fluid and salt retention induces epileptic seizures.

      Pregnant women are more susceptible to poliomyelitis (polio) (infantile paralysis), but pregnancy does not affect the severity or the course of the disease, nor does poliomyelitis affect the course of pregnancy. If the muscles of respiration are paralyzed, the patient will have difficulty during the latter part of pregnancy, when the uterus presses upward on the diaphragm. There have been a few instances in which babies have acquired infections from the mother before birth.

      Polyneuritis, a disorder of the nerves usually resulting from vitamin B (vitamin B complex) deficiency, may complicate pregnancy; this is particularly likely if the patient has suffered from severe and prolonged vomiting. Polyneuritis does not affect the gestation.

       neuralgia (pain that radiates along the nerve) occurs frequently near term. It affects especially the sciatic nerve, which is compressed between the pelvic wall and the head of the fetus.

       brain injury, including hemorrhage into the substance of the brain, sometimes occurs as part of the clinical picture of severe preeclampsia or eclampsia. Some types of brain tumours appear to be adversely affected by pregnancy, but, for the most part, brain tumours are not altered by pregnancy and do not disturb gestation.

      Latent psychiatric disorders (mental disorder) in unstable persons may be aggravated by pregnancy, but major psychiatric problems seldom appear for the first time during the period before delivery. There are a number of mild emotional disturbances, such as increased anxiety, emotional irritability, and fear of labour or for the normality of the fetus, that are likely to be most intense during the early months of gestation. Such disturbances seem to be most prevalent in women who did not anticipate becoming pregnant or who are unduly worried about the baby. Psychiatric disorders rarely influence pregnancy. Emotional disturbances have been said to be a factor in some spontaneous abortions, but satisfactory proof of the relationship is lacking.

John W. Huffman

Diseases of pregnancy
Hypertensive disorders of pregnancy
      The increase of blood pressure ( hypertension) during pregnancy, which is often accompanied by accumulation of fluid in the tissues that causes swelling (edema) and proteinuria (protein in the urine), poses a serious threat to both the woman and the fetus. The maternal hazards include seizures, organ disturbances, and death; the fetal risks, premature delivery and death.

      For many years, hypertensive disorders of pregnancy were referred to as toxemias of pregnancy. The basis for this terminology was the belief that circulatory toxins were responsible for the symptoms. These toxins were never discovered, and this terminology has been generally abandoned; however, in its wake, many different terms have been used to describe hypertensive disorders of pregnancy. To help clarify this situation, the Committee on Terminology of the American College of Obstetricians and Gynecologists prepared the following classification system, which has been recommended by the National Institutes of Health Working Group on High Blood Pressure in Pregnancy: (1) chronic hypertension, (2) preeclampsia and eclampsia, (3) preeclampsia superimposed on chronic hypertension, (4) transient hypertension, and (5) unclassified.

      Chronic hypertension is defined as a systolic blood pressure of 140 millimetres of mercury (mm Hg) or higher and a diastolic blood pressure of 90 mm Hg or higher, which antedate pregnancy. (The systolic is the highest blood pressure after the heart has contracted; the diastolic, the lowest after the heart has expanded.) An elevated blood pressure that first develops during pregnancy and persists beyond the 42nd day postpartum also is classified as chronic hypertension.

      Preeclampsia (preeclampsia and eclampsia) is diagnosed after 20 weeks' gestation and is categorized as either mild or severe, although both forms must be considered dangerous to the mother and fetus. Mild preeclampsia is typically characterized by the following symptoms: a rise in blood pressure from that prior to 20 weeks' gestation of at least 30 mm Hg systolic or 15 mm Hg diastolic (or, if the earlier blood pressure is unknown, a level of 140/90 mm Hg after 20 weeks' gestation) on two occasions at least six hours apart; excretion of 0.3 gram (0.01 ounce) of protein or more in the urine during a 24-hour period; and evident swelling or rapid weight gain resulting from fluid retention. Coagulation and disturbances of liver functions are less common but are extremely serious.

      Severe preeclampsia is defined by any of the following symptoms occurring after the 20th week of pregnancy: a systolic blood pressure of 160 mm Hg or higher or a diastolic pressure of 110 mm Hg or higher on two or more occasions at least six hours apart, excretion of five grams or more of protein in the urine during a 24-hour period, a reduction in the amount of urine normally excreted (500 millilitres or less in 24 hours), cerebral or visual disturbances, epigastric pain, and pulmonary edema or cyanosis (bluish or purplish colour of the skin).

      A patient with preeclampsia is always in danger of rapidly developing eclampsia, which is distinguished by convulsions that may lead to coma. Headache, epigastric pain, and facial twitching usually precede these seizures, although occasionally eclampsia can arise with no warning, sometimes developing in a woman who has only mild hypertension. Another type of preeclampsia that includes small variations in blood pressure, minor decreases in blood platelet count, and small elevations in liver enzymes can progress quickly from a benign state to a syndrome of life-threatening proportions. This condition is known as the HELLP syndrome and is denoted by hemolysis, elevated liver enzymes, and low platelet count. In this situation, delivery of the fetus must be induced, or pregnancy must be immediately terminated.

      Preeclampsia can occur in women who have had hypertension prior to becoming pregnant, in which case the prognosis is much more serious for the mother and fetus than when either preeclampsia or chronic hypertension occurs alone. The diagnosis of preeclampsia superimposed on chronic hypertension is made based on increases of blood pressure of 30 mm Hg systolic and 15 mm Hg diastolic that are accompanied by the appearance of proteinuria or edema. A rise in blood pressure either during pregnancy or 24 hours postpartum, unaccompanied by other symptoms of preeclampsia or eclampsia, is categorized as transient hypertension.

      Approximately 7 percent of women whose pregnancies progress beyond the first trimester will develop preeclampsia. It is most common in women who are pregnant for the first time. A higher incidence of this condition occurs in family members of women who have a history of preeclampsia, which provides evidence for involvement of a single maternal gene. Medical disorders such as diabetes mellitus can predispose women to preeclampsia, and conditions such as twin pregnancies increase the risk of preeclampsia. A hydatidiform mole (an abnormal pregnancy caused by an abnormal ovum) is often responsible for a preeclamptic condition that develops before 24 weeks' gestation.

      Although hypertension is an important diagnostic sign of preeclampsia, the disease is actually one of poor perfusion to the tissues, including the fetal-placental unit. This inadequate delivery of fluids to virtually all organs is attributed to the profound vasospasm (constriction of blood vessels that reduces calibre and blood flow) characteristic of preeclampsia that is also responsible for the associated blood-pressure elevation.

      Certain organ systems are characteristically involved in preeclampsia, and their resultant abnormalities—alterations in renal function, endothelial cell injury, and cardiovascular changes—have provided insight into the mechanism of this complex disease. The normal immunologic changes that occur as a result of fetal-maternal interactions also have been postulated as having a pathogenetic role in the development of preeclampsia. The cause of the underlying vasoconstriction, however, still remains undefined.

      Various approaches have been attempted to prevent preeclampsia in women at high risk for developing the condition. Dietary and sodium restrictions have been unsuccessful, but there is interest in the use of low-dose aspirin therapy and calcium supplementation as preventive measures. These methods are still under investigation.

      Treatment of preeclampsia involves slowing the condition's progression to a more severe form to allow fetal growth to continue as long as possible. Bed rest is recommended in cases of mild preeclampsia, but, when more serious symptoms are involved, hospitalization is best. In cases of severe preeclampsia in which the fetus is beyond 30 weeks' gestation, delivery of the infant is thought to be the best course. Antihypertensive drugs are not used, because they mask the clinical signs by which worsening of the condition is recognized.

      In the United States, magnesium sulfate is the drug of choice for preventing and treating eclamptic convulsions. European treatment differs—a variety of narcotics, barbiturates, and benzodiazepine derivatives are used. Because the preeclamptic process often accelerates during labour and the postpartum period, magnesium therapy is used during this time as well.

Gestational diabetes
      Diabetes mellitus that has been diagnosed for the first time during pregnancy and resolves immediately after delivery is referred to as gestational diabetes. It occurs in between 1 and 4 percent of the total pregnant population, usually in the second or third trimester. Approximately 50 percent of women who develop gestational diabetes will, over the course of their lifetime, develop adult onset (type II) diabetes.

      Effects that gestational diabetes can have on the fetus include high birth weight for gestational age, neonatal hypoglycemia, premature delivery with respiratory distress syndrome, difficult delivery, and a higher incidence of fetal-neonatal mortality.

      Previously only women with recognizable risk factors for gestational diabetes were screened for glucose (glucose tolerance test) intolerance; these included obese women, women who had a family history of diabetes, and those older than 35 years. Because a significant proportion of cases of gestational diabetes—up to 50 percent—were missed in this way, it is now recommended that all women between the 24th and 28th week of gestation be screened for glucose intolerance; those at high risk should be screened during their first prenatal visit. Controversy exists concerning the best glucose-tolerance screening procedure to use.

      Treatment of gestational diabetes varies according to the individual case. Controlling diet is the first, conservative approach; insulin therapy is instituted when glucose levels cannot be managed in this way. Fetal monitoring of growth development is necessary to measure the effectiveness of treatment and to anticipate and prevent complications. An early delivery by cesarean section (incision through the abdominal and uterine walls for fetal delivery) was frequently recommended in the past. Today the procedure, which has its own risks, is selected less often, as long as the disease has been well controlled and fetal development is normal.

Ed.

Diseases of the placenta

      Implantation takes place in the lower half of the uterus in approximately 1 in 500 pregnant patients. The condition is known as placenta praevia when the placenta lies over all or a portion of the internal opening of the cervix. A total placenta praevia is present when the cervical opening is completely covered. When there is a low implantation of the placenta, the latter lies close to but not over any part of the cervical opening.

      Recurrent painless bleeding from the vagina without other symptoms after the sixth month of pregnancy is the typical manifestation of placenta praevia. It is caused by disruption of the placenta as the cervix and lower uterine segment are pulled upward. Each bleeding episode tends to become heavier. Without proper treatment, the baby is likely to die and the mother may do so as well. Unremitting watchfulness of the woman with placenta praevia until the fetus has a chance of survival, with preparation for immediate delivery if hemorrhage becomes brisk, a practice accepted in many clinics, has resulted in a decreased infant mortality without an increase in maternal deaths.

Abruptio placentae (placentae abruptio)
      Abruptio placentae is separation, during the latter half of pregnancy, of the normally implanted placenta from its attachment to the uterus before birth of the baby. It also is correctly referred to as “premature separation of the normally implanted placenta” and is called “accidental hemorrhage” in Great Britain. It occurs in approximately 1 in 100 pregnancies. The cause is unknown. It is more common in women who have borne several children.

      When a small portion of the placenta separates from the uterus, a condition called partial abruptio placentae, blood either collects in a pool between the uterus and the placenta (concealed hemorrhage) or seeps out of the uterus into the vagina (external hemorrhage). When the entire placenta separates from the uterus, there is massive hemorrhage into the uterine cavity and sometimes into the wall of the uterus. Massive hemorrhage is associated with uterine tenderness, abdominal pain, shock, and loss of fetal movement and fetal heart tones. The baby usually dies. If hemorrhage is severe, the mother's life is in danger. Defective blood clotting occurs in at least 35 percent of patients with abruptio placentae. Kidney failure develops in approximately 1 percent of the cases; it is seen most often in those instances in which treatment has been delayed. Blood replacement, the treatment of shock, the administration of fibrinogen if the patient's clotting mechanism is defective, the administration of oxytocics, and early delivery are the basic essentials of the treatment of abruptio placentae. Delivery is usually by cesarean section.

      Infarction is degeneration and death of a tissue and its replacement with scar tissue. Small yellowish-white deposits of fibrin (a fibrous protein), caused by interference with the maternal circulation, occur normally in the placenta as pregnancy progresses. The fetus usually is not affected by infarction of the placenta unless the process is extensive.

      Placenta accreta is an abnormal adherence of the placenta to the uterine wall. The chorionic villi attach themselves directly to the uterine muscle in areas where the decidua is poorly developed or absent. All or part of the placenta may be affected. As a result of this abnormality of implantation, the placenta does not separate normally at the time of delivery. Attempts to remove it manually by the physician are frequently followed by severe hemorrhage. Removal of the uterus may be required to save the mother's life.

Placental cysts (cyst) and benign tumours (tumour)
      Placental cysts and benign tumours are relatively rare. Chorionic cysts of small size are disk-shaped, grayish white structures filled with a yellowish fluid and located on the fetal side of the placenta. Decidual cysts are smoothly lined small cavities in the centre of the placenta; they are the result of decidual degeneration and are not true tumours. Angiomas, hemangiomas, fibromas, myxofibromas, and the like are benign growths arising from the placental blood vessels and connective tissue. Solid or semisolid tumours, usually creating small nodular elevations on the fetal side of the placenta, are rarely of clinical significance.

Inflammation of the placenta
      Inflammation of the placenta is usually secondary to infection (infectious disease) of the membranes. Most often such infections follow the introduction of pus-forming bacteria into the uterus by instrumentation through the vagina; they are the aftermath of prolonged labour or of prolonged rupture of the membranes. If labour is prolonged, bacteria penetrate the fetal side of the placenta, enter the fetal circulation, and often cause death of the infant after delivery.

      The placenta may become infected from organisms in the maternal blood. Maternal syphilis, toxoplasmosis, tuberculosis, and malaria may affect the placenta. The viruses of chickenpox and smallpox may cause placental lesions. A number of pathogenic bacteria and viruses cross the placenta and sometimes kill the fetus without causing any specific changes that have been noted in the placenta.

Placental anomalies
      Abnormalities in the structure of the placenta are relatively common. It may be partially divided into two or more lobes; there may be extra lobes; or the placenta may be divided into two or more separate structures. Abnormal placentas result from shallow and from deep implantation. The former type, called placenta circumvallata, is associated with several maternal and fetal complications; the latter type, called placenta membranacea, may cause problems at delivery—e.g., bleeding, failure of the membrane to separate.

Anomalies of the umbilical cord
      “False knots,” which are simply enlarged blood vessels in the cord, are not significant. Actual knots in the cord may become tightened and kill the fetus by cutting off the blood to it. Twisting of the cord also may kill the fetus in the same manner. Spontaneous rupture of the cord interferes with the fetal blood supply and causes fetal death. Extreme shortness of the umbilical cord may interfere with delivery, cause premature separation of the placenta, or tear and cause fetal death from hemorrhage. Another abnormality, called velamentous insertion of the cord, in which multiple blood vessels spread out over the membranes and cervix rather than forming one single cord, is dangerous for the baby because the vessels may tear or be compressed during labour and delivery.

Abnormalities of the amniotic fluid

      Hydramnios, sometimes called polyhydramnios, is the presence of an excessive amount of amniotic fluid. Normally the uterus contains approximately 1,000 millilitres (slightly more than one quart) of amniotic fluid; anything over 2,000 millilitres is abnormal. Accumulations of more than 3,000 millilitres occur in approximately one pregnancy in a thousand. Lesser degrees of hydramnios probably occur in about 1 in 150 deliveries. The appearance of large amounts of fluid within the space of a few days is rare; such a condition is met with in fewer than 1 in 4,000.

      Hydramnios occurs most often in association with fetal abnormalities, particularly those of the nervous, digestive, and renal systems; when the fetus has erythroblastosis (erythroblastosis fetalis), a disease resulting from incompatibility between the infant's and the mother's blood; when there is more than one fetus; or when the mother has diabetes or preeclampsia. Almost all pregnancies in which the fetus suffers from obstruction of the esophagus and half of those in which there are severe brain anomalies are accompanied by excessive amniotic fluid.

      Acute hydramnios causes rapid overdistention and enlargement of the uterus. The woman experiences abdominal pain, nausea and vomiting, and difficulty in breathing. Her heart and blood vessels are put under severe stress; she may show signs of heart failure. Swelling of the feet and legs develops. These manifestations are all caused by the pressure of the rapidly enlarging uterus upon the other viscera.

      Chronic hydramnios usually causes enough pressure from the abnormally enlarged uterus to make the affected person uncomfortable.

      The cause of hydramnios is unknown. The most tenable theory is that there is a reduction in the amount of fluid that passes from the fetus to the mother and an increase in the amount that passes from the fetus to the amniotic sac. This would explain the relationship between fetal anomalies and hydramnios.

      Many pregnancies complicated by an abnormal amount of amniotic fluid terminate prematurely. The fetus has a greatly increased chance of suffering from congenital anomalies. Roughly half of the babies in this group have been lost in the series of cases that have been reported. The greater the amount of fluid, the higher the fetal mortality. Women with hydramnios also are faced with a somewhat higher risk. Premature separation of the placenta and postpartum hemorrhage are the two most significant maternal complications associated with it.

      Minor degrees of hydramnios require no treatment. Removal of the excess fluid is the only effective management if symptoms from uterine distention become too distressing. This may be done either by perforating the membranes through the cervix or, preferably, by inserting a needle through the abdominal wall and the wall of the uterus; care is taken to avoid injury to the woman's bowel or the placenta. Either procedure is likely to start labour.

Oligohydramnios
      True oligohydramnios, a deficiency in amniotic fluid, is a rare condition of unknown cause. It is seen more often in pregnancies that have extended beyond the projected time of delivery. If it occurs early in pregnancy, there are usually firm adhesions between the membranes and the embryo, with distortion of the fetus. A decrease in the amount of fluid later in pregnancy allows the membranes and uterine wall to press on the baby. The baby's position is distorted, and as a result it may be born with a clubfoot or wryneck (torticollis). Its skin is dry and thickened. Defective development of the kidneys is common with oligohydramnios. As a rule, the condition causes the mother no distress, but the infant has a greatly increased chance of being born with major anomalies.

Trophoblastic disease

      A hydatidiform mole is an abnormality of the conceptus in which changes that began early in embryonic life convert the placental villi (villus) into a mass of thin-walled, grapelike, translucent vesicles, or blisters, filled with a gelatinous or watery fluid. In a typical case, the uterus is distended by a spongy mass of these vesicles. The primary cause of molar changes is unknown; however, it has been correctly described as a “temporary missed abortion of a blighted ovum.” The embryo is either absent or dead. The immediate condition that causes hydatidiform swelling is disappearance of the blood vessels in the villi, with continued growth and often overgrowth of the trophoblast. Distention of the villi by fluid is due to continued activity of the trophoblast in the absence of a functioning villous circulation.

      In the ova (ovum) there are many degrees of hydatidiform change; many of the changes, usually in younger specimens, are not marked enough to warrant being called hydatidiform moles. True moles—characterized by hyperplasia, or overgrowth, of the trophoblast, edema of the villous connective tissue framework, and defective growth of the villous blood vessels—occur perhaps once in 2,000 pregnancies. They are not tumours and are not the aftermath of a former pregnancy. They are themselves an abnormality of a current pregnancy. Occasionally in a twin pregnancy one fetus is normal and the other a mole. Eighty percent of the moles are expelled about the 20th week of pregnancy and bring the patient no more trouble. Approximately 16 percent of hydatidiform moles invade the uterine muscle, causing bleeding. This type of mole, referred to as an invasive mole or chorioadenoma destruens, may in rare instances perforate the uterus and cause death from hemorrhage. Molar villi rarely are carried to the lung or brain. When they are, the patient may suffer from hemorrhage into the lung or die from hemorrhage within the brain.

      The woman who develops a hydatidiform mole has the symptoms of pregnancy; her uterus usually enlarges more rapidly than it should, she is more likely to suffer from preeclampsia, and she begins to bleed vaginally, usually by the 20th week of gestation. The molar pregnancy is expelled vaginally, or, if hemorrhage is severe, the obstetrician may remove it by surgery.

      In approximately 2.5 percent of patients, hydatidiform moles change into choriocarcinoma, a highly malignant tumour of the trophoblast. For that reason, patients who have hydatidiform moles are observed carefully. Continued bleeding or a rising quantity of chorionic gonadotropin in her urine or blood after passage of a mole suggests that a patient has either an invasive mole or a choriocarcinoma. Chemotherapy has been effective treatment for many cases of this type. Removal of the uterus may be necessary. The complexities of diagnosis and the differences in situations require that therapy be keyed to the individual.

      Choriocarcinoma is a rare, extremely malignant type of tumour arising from the trophoblast. The reasons that normal chorionic cells undergo cancerous change, with exaggeration of their natural and potent tendency to invade the uterine muscle and break down blood vessels, are unknown. Choriocarcinoma occurs approximately once in 160,000 normal pregnancies. In approximately 50 percent of the cases the tumour develops from a hydatidiform mole, in another 25 percent after an abortion, and in 25 percent after a normal pregnancy. Occasionally it appears after a tubal pregnancy. It has been known to coexist with pregnancy. It is, for some unknown reason, more common in Asia. Choriocarcinoma developing as a teratoid tumour of the ovary (a tumour made up of a number of different tissues) is a rare entity not related to pregnancy and is not to be confused with the tumour being discussed here.

      As a rule, in the development of a choriocarcinoma there has been a normal pregnancy, an abortion, or the delivery of a mole, and the uterus has not returned to its normal size. The woman begins to bleed from the vagina. Blood loss may be modest or excessive in amount. Tissues obtained by a curettage (scraping) may be, but are not always, indicative of choriocarcinoma.

      The tumour begins in the uterus, where it forms a spongy, bleeding mass of easily torn tissue or a shaggy ulcer. When examined microscopically, it is found to consist of both cytotrophoblast and syncytiotrophoblast. The cells spread rapidly by way of the bloodstream, producing secondary tumours in the lung, the brain, the liver, or elsewhere.

      Choriocarcinoma formerly was almost invariably fatal. Today an impressive (two out of three in some case series) number of patients have survived for many months after the administration of chemotherapeutic (chemotherapy) agents. Most workers in this field at this time are using methotrexate. The rapidly growing embryonic cells of the trophoblast need nucleic acids (nucleic acid) for growth and division; for the synthesis of nucleic acids, folinic acid is essential, and methotrexate, by preventing the conversion of folic acid to folinic acid, cuts off the supply of the latter. A number of other cytotoxic drugs (drugs destructive to cells) also are being used in the treatment of choriocarcinoma, and other chemotherapeutic agents are being tested for effect on this type of tumour; actinomycin D has been used successfully. Removal of the uterus is frequently, but not always, a part of the treatment of choriocarcinoma.

John W. Huffman

Additional Reading
General texts include Human Embryology, 4th ed. by W.J. Hamilton and H.W. Mossman (1972); and Williams Obstetrics, 19th ed. by F. Gary Cunningham et al. (1993), a standard textbook in the field. Additional information may be found in the following specialized texts: Irwin R. Merkatz and Joyce E. Thompson (eds.), New Perspectives on Prenatal Care (1990); Robert K. Creasy and Robert Resnik (eds.), Maternal-Fetal Medicine: Principles and Practice, 3rd ed. (1994); Burwell and Metcalfe's Heart Disease and Pregnancy, 2nd ed. by James Metcalfe, John H. McAnulty, and Kent Ueland (1986); and Richard S. Abrams, Handbook of Medical Problems During Pregnancy (1989). John W. Huffman Ed.

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Universalium. 2010.

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