Prenatal stress (or prenatal maternal stress) is exposure of an expectant mother to stress, which can be caused by stressful life events or by environmental hardships. The resulting changes to the mother's hormonal and immune system may harm the fetus's (and after birth, the infant's) immune function and brain development.

Prenatal stress is shown to have several affects in fetal brain development. In the hippocampus of adult male rats, prenatal stress has shown to decrease the rate of proliferation and cell death in the hypothalamus-pituitary axis. Prenatal stressed animals have prolonged corticosterone response. Removing the adrenal glands of the mother eliminates the effect of the pup's corticosterone response. Supplementing the adrenalectamized mother with corticosterone, rescued the hypothalamic-pituitary-axis response to maternal stress for prenatally stressed offspring. Prenatal stress caused high glucocorticoids, which in turn affects the hypothalamic-pituitary-axis negative feedback.

A study by García-Cáceres et al. showed that prenatal stress decreases cell turnover and proliferation in the hypothalamus of adult rats, which reduces structural plasticity and reduces the response to stress in adulthood. This study also showed that when prenatally stressed rats were stressed in adulthood the females showed an increase in corticotropin-releasing hormone suggesting it to be an up-regulation in the hypothalamic-pituitary adrenal axis. Males showed no elevation of corticosterone levels. Increase in adrenocorticotropic hormone with no effect of adult stress and a decrease in the corticotropin-releasing hormone mRNA in the hypothalamus showed a down-regulation. The author concludes that this makes prenatally stressed females less reactive to later life stressors than males.

Antenatal depression, also known as Prenatal depression, is a form of clinical depression that can affect a woman during pregnancy, and can be a precursor to postpartum depression if not properly treated. It is estimated that 7% to 20% percent of pregnant women are affected by this condition. Any form of prenatal stress felt by the mother can have negative effects on various aspects of fetal development, which can cause harm to the mother and child. Antenatal depression is often caused by the stress and worry that pregnancy can bring, only at a more severe level. Other risk factors include unplanned pregnancy, difficulty becoming pregnant, history of abuse, and economic or family situations.

Commonly, symptoms involve how the patient views herself, how she feels about going through such a life changing event, the restrictions on the mother's lifestyle that motherhood will place, or how the partner or family feel about the baby. Pregnancy places significant strain on a woman's body, so some stress, mood swings, sadness, irritability, pain, and memory changes are to be expected. Antenatal depression can be extremely dangerous for the health of the mother, and the baby, if not properly treated.

Antenatal depression is classified based on a woman's symptoms. During pregnancy, a lot of changes to mood, memory, eating habits, and sleep is common. When these common traits become severe, and begin to alter one's day-to-day life, that is when it is considered to be antenatal depression. Symptoms of Antenatal depression are:

- Inability to concentrate.

- Difficulty remembering.

- Feeling emotionally numb.

- Extreme irritability.

- Sleeping too much or not enough, or restless sleep.

- Extreme or unending fatigue.

- Desire to over eat, or not eat at all.

- Weight loss/gain unrelated to pregnancy.

- Loss of interest in sex.

- A sense of dread about everything, including the pregnancy.

- Feelings of failure, or guilt.

- Persistent sadness.

- Thoughts of suicide, or death.

Other symptoms can include the inability to get excited about the pregnancy, and/or baby, a feeling of disconnection with the baby, and an inability to form/feel a bond with the developing baby. This can drastically affect the relationship between the mother and the baby, and can drastically affect the mother's capacity for self care. Such inadequacies can lead to even greater risk factors for the mother. Antenatal depression can be triggered by various causes, including relationship problems, family or personal history of depression, infertility, previous pregnancy loss, complications in pregnancy, and a history of abuse or trauma.

Drug use during pregnancy can have temporary or permanent effects on the fetus. Any drug that acts during embryonic or fetal development to produce a permanent alteration of form or function is known as a teratogen. Drugs may refer to both pharmaceutical drug and recreational drugs.

Slowed growth is well documented in fetuses, but it is not as clear whether older children remain smaller or catch up to their peers. Some studies show that growth remains slowed for as many as ten years. PCE may also interfere with the way the motor system matures. Motor effects that have been documented include poorer reflexes and quality of movement in infants. PCE may have an effect on the neuroendocrine system, but more study is needed to determine whether it does and what the effects are.

A review of the literature reported that cocaine use causes congenital defects between 15 and 20% of the time; however another large-scale study found no difference in rates of birth anomalies in PCE and non-PCE infants. It has been suggested that some birth defects could be due to cocaine's disruption of blood vessel growth.

Most PCE-related congenital defects are found in the brain, heart, genitourinary tract, arms and legs.

Cocaine use by pregnant mothers may directly or indirectly contribute to defects in the formation of the circulatory system and is associated with abnormalities in development of the aorta. Heart malformations can include a missing ventricle and defects with the septum of the heart, and can result in potentially deadly congestive heart failure. Genital malformations occur at a higher-than-normal rate with PCE.

The liver and lungs are also at higher risk for abnormalities. Cloverleaf skull, a congenital malformation in which the skull has three lobes, the brain is deformed, and hydrocephalus occurs, is also associated with PCE. Like birth defects, small head size, and stroke are risks in PCE.

Signs of a miscarriage include vaginal spotting, abdominal pain or cramping, and fluid or tissue passing from the vagina. Bleeding can be a symptom of miscarriage, but many women also have bleeding in early pregnancy and don't miscarry. Bleeding during pregnancy may be referred to as a threatened miscarriage. Of those who seek clinical treatment for bleeding during pregnancy, about half will miscarry. Miscarriage may be detected during an ultrasound exam, or through serial human chorionic gonadotropin (HCG) testing.

Prenatal cocaine exposure (PCE), theorized in the 1970s, occurs when a pregnant woman uses cocaine and thereby exposes her fetus to the drug. "Crack baby" was a term coined to describe children who were exposed to crack (freebase cocaine in smokable form) as fetuses; the concept of the crack baby emerged in the US during the 1980s and 1990s in the midst of a crack epidemic. Other terms are "cocaine baby" and "crack kid". Early studies reported that people who had been exposed to crack in utero would be severely emotionally, mentally, and physically disabled; this belief became common in the scientific and lay communities. Fears were widespread that a generation of crack babies were going to put severe strain on society and social services as they grew up. Later studies failed to substantiate the findings of earlier ones that PCE has severe disabling consequences; these earlier studies had been methodologically flawed (e.g. with small sample sizes and confounding factors). Scientists have come to understand that the findings of the early studies were vastly overstated and that most people who were exposed to cocaine "in utero" do not have disabilities.

No specific disorders or conditions have been found to result for people whose mothers used cocaine while pregnant. Studies focusing on children of six years and younger have not shown any direct, long-term effects of PCE on language, growth, or development as measured by test scores. PCE also appears to have little effect on infant growth.

However, PCE is associated with premature birth, birth defects, attention deficit hyperactivity disorder, and other conditions. The effects of cocaine on a fetus are thought to be similar to those of tobacco and less severe than those of alcohol. No scientific evidence has shown a difference in harm to a fetus between crack and powder cocaine.

PCE is very difficult to study because it very rarely occurs in isolation: usually it coexists with a variety of other factors, which may confound a study's results. Thus, studies have failed to clearly show that PCE has negative cognitive effects, partly because such effects may be due to concurrent factors. Pregnant mothers who use cocaine often use other drugs in addition, or they may be malnourished and lacking in medical care. Children in households where cocaine is abused are at risk of violence and neglect, and those in foster care may experience problems due to unstable family situations. Factors such as poverty that are frequently associated with PCE have a much stronger influence on children's intellectual and academic abilities than does exposure to cocaine in isolation. Thus researchers have had difficulty in determining which effects result from PCE and which result from other factors in the children's histories.

In terms of FASD, growth deficiency is defined as significantly below average height, weight or both due to prenatal alcohol exposure, and can be assessed at any point in the lifespan. Growth measurements must be adjusted for parental height, gestational age (for a premature infant), and other postnatal insults (e.g., poor nutrition), although birth height and weight are the preferred measurements. Deficiencies are documented when height or weight falls at or below the 10th percentile of standardized growth charts appropriate to the population.

Criteria for FASD are least specific in the IOM diagnostic system ("low birth weight..., decelerating weight not due to nutrition..., [or] disproportional low weight to height" p. 4 of executive summary), while the CDC and Canadian guidelines use the 10th percentile as a cut-off to determine growth deficiency. The "4-Digit Diagnostic Code" allows for mid-range gradations in growth deficiency (between the 3rd and 10th percentiles) and severe growth deficiency at or below the 3rd percentile. Growth deficiency (at severe, moderate, or mild levels) contributes to diagnoses of FAS and pFAS, but not ARND or static encephalopathy.

Growth deficiency is ranked as follows by the "4-Digit Diagnostic Code":

- Severe: Height and weight at or below the 3rd percentile.

- Moderate: Either height or weight at or below the 3rd percentile, but not both.

- Mild: Either height or weight or both between the 3rd and 10th percentiles.

- None: Height and weight both above the 10th percentile.

In the initial studies that discovered FAS, growth deficiency was a requirement for inclusion in the studies; thus, all the original people with FAS had growth deficiency as an artifact of sampling characteristics used to establish criteria for the syndrome. That is, growth deficiency is a key feature of FASD because growth deficiency was a criterion for inclusion in the study that defined FAS. This suggests growth deficiency may be less critical for understanding the disabilities of FASD than the neurobehavioral sequelae to the brain damage.

A longitudinal study done on prenatal stress and gender roles showed that prenatal stress only plays a small part in the gender roles the offspring takes on and mentions it has more to do with older siblings, maternal use of alcohol and/or tobacco, maternal education, and the observance or teaching of “traditional sex roles” from the parents.

Several characteristic craniofacial abnormalities are often visible in individuals with FAS. The presence of FAS facial features indicates brain damage, although brain damage may also exist in their absence. FAS facial features (and most other visible, but non-diagnostic, deformities) are believed to be caused mainly during the 10th and 20th week of gestation.

Refinements in diagnostic criteria since 1975 have yielded three distinctive and diagnostically significant facial features known to result from prenatal alcohol exposure and distinguishes FAS from other disorders with partially overlapping characteristics. The three FAS facial features are:

- A smooth philtrum: The divot or groove between the nose and upper lip flattens with increased prenatal alcohol exposure.

- Thin vermilion: The upper lip thins with increased prenatal alcohol exposure.

- Small palpebral fissures: Eye width decreases with increased prenatal alcohol exposure.

Measurement of FAS facial features uses criteria developed by the University of Washington. The lip and philtrum are measured by a trained physician with the Lip-Philtrum Guide, a five-point Likert Scale with representative photographs of lip and philtrum combinations ranging from normal (ranked 1) to severe (ranked 5). Palpebral fissure length (PFL) is measured in millimeters with either calipers or a clear ruler and then compared to a PFL growth chart, also developed by the University of Washington.

Ranking FAS facial features is complicated because the three separate facial features can be affected independently by prenatal alcohol. A summary of the criteria follows:

- Severe: All three facial features ranked independently as severe (lip ranked at 4 or 5, philtrum ranked at 4 or 5, and PFL two or more standard deviations below average).

- Moderate: Two facial features ranked as severe and one feature ranked as moderate (lip "or" philtrum ranked at 3, "or" PFL between one and two standard deviations below average).

- Mild: A mild ranking of FAS facial features covers a broad range of facial feature combinations:

- Two facial features ranked severe and one ranked within normal limits,

- One facial feature ranked severe and two ranked moderate, or

- One facial feature ranked severe, one ranked moderate and one ranked within normal limits.

- None: All three facial features ranked within normal limits.

There are 2 major categories of IUGR: symmetrical and asymmetrical. Some conditions are associated with both symmetrical and asymmetrical growth restriction.

Confined placental mosaicism (CPM) represents a discrepancy between the chromosomal makeup of the cells in the placenta and the cells in the baby. CPM was first described by Kalousek and Dill in 1983. CPM is diagnosed when some trisomic cells are detected on chorionic villus sampling and only normal cells are found on a subsequent prenatal test, such as amniocentesis or fetal blood sampling. In theory, CPM is when the trisomic cells are found only in the placenta. CPM is detected in approximately 1-2% of ongoing pregnancies that are studied by chorionic villus sampling (CVS) at 10 to 12 weeks of pregnancy. Chorionic villus sampling is a prenatal procedure which involves a placental biopsy. Most commonly when CPM is found it represents a trisomic cell line in the placenta and a normal diploid chromosome complement in the baby. However, the fetus is involved in about 10% of cases.

Cannabis consumption in pregnancy might be associated with restrictions in growth of the fetus, miscarriage, and cognitive deficits. The American Congress of Obstetricians and Gynecologists recommended that cannabis use be stopped before and during pregnancy, Cannabis is the most commonly used illicit substance

among pregnant women.

Although it is difficult to draw firm conclusions, there is some evidence that prenatal exposure to marijuana may be associated with deficits in language, attention, cognitive performance, and delinquent behaviors. THC exposure in rats during the prenatal developmental phase may cause epigenetic changes in gene expression, but there is limited knowledge about the risk for psychiatric disorders because of ethical barriers to studying the developing human brain. While animal studies cannot take into account factors that could influence the effects of cannabis on human maternal exposure, such as environmental and social factors, a 2011 review of rodent studies by Campolongo "et al." said there was "... increasing evidence from animal studies showing that cannabinoid drugs ... induce enduring neurobehavioral abnormalities in the exposed offspring ..." Campolongo "et al." added that "clinical studies report hyperactivity, cognitive impairments and altered emotionality in humans exposed in utero to cannabis". Martin "et al." investigated recent trends in substance abuse treatment admissions for cannabis use in pregnancy in the US, based on Treatment Episodes Data Set (TEDS) from 1992 to 2012, and discovered that, while the proportion of treatment admissions for pregnant women was stable (about 4%), the admissions for women who were pregnant and reported any marijuana use grew from 29% to 43%. A 2015 review found that cannabis use by pregnant mothers impaired brain maturation in their children, and that it also predisposed their children to neurodevelopmental disorders.

Miscarriage, also known as spontaneous abortion and pregnancy loss, is the natural death of an embryo or fetus before it is able to survive independently. Some use the cutoff of 20 weeks of gestation, after which fetal death is known as a stillbirth. The most common symptom of a miscarriage is vaginal bleeding with or without pain. Sadness, anxiety and guilt often occur afterwards. Tissue and clot-like material may leave the uterus and pass through and out of the vagina. When a woman keeps having miscarriages, infertility is present.

Risk factors for miscarriage include an older parent, previous miscarriage, exposure to tobacco smoke, obesity, diabetes, thyroid problems, and drug or alcohol use. About 80% of miscarriages occur in the first 12 weeks of pregnancy (the first trimester). The underlying cause in about half of cases involves chromosomal abnormalities. Diagnosis of a miscarriage may involve checking to see if the cervix is open or closed, testing blood levels of human chorionic gonadotropin (hCG), and an ultrasound. Other conditions that can produce similar symptoms include an ectopic pregnancy and implantation bleeding.

Prevention is occasionally possible with good prenatal care. Avoiding drugs, alcohol, infectious diseases, and radiation may prevent miscarriage. No specific treatment is usually needed during the first 7 to 14 days. Most miscarriages will complete without additional interventions. Occasionally the medication misoprostol or a procedure such as vacuum aspiration is used to remove the remaining tissue. Women who have a blood type of rhesus negative (Rh negative) may require Rho(D) immune globulin. Pain medication may be beneficial. Emotional support may help with negative emotions.

Miscarriage is the most common complication of early pregnancy. Among women who know they are pregnant, the miscarriage rate is roughly 10% to 20%, while rates among all fertilisation is around 30% to 50%. In those under the age of 35 the risk is about 10% while it is about 45% in those over the age of 40. Risk begins to increase around the age of 30. About 5% of women have two miscarriages in a row. Some recommend not using the term "abortion" in discussions with those experiencing a miscarriage in an effort to decrease distress.

Developmental toxicity is any structural or functional alteration, reversible or irreversible, which interferes with homeostasis, normal growth, differentiation, development or behavior, and which is caused by environmental insult (including drugs, lifestyle factors such as alcohol, diet, and environmental toxic chemicals or physical factors). It is the study of adverse effects on the development of the organism resulting from exposure to toxic agents before conception (either parent), during prenatal development, or post-natally until puberty. The substance that causes developmental toxicity from embryonic stage to birth is called teratogens. The effect of the developmental toxicants depends on the type of substance, dose and duration and time of exposure.

Certain Pathogens are also included since the toxins they secrete are known to cause adverse effects on the development of the organism when the mother or fetus is infected. Developmental toxicology is a science studying adverse developmental outcomes. This term has widely replaced the early term for the study of primarily structural congenital abnormalities, teratology, to enable inclusion of a more diverse spectrum of congenital disorders. Typical factors causing developmental toxicity are radiation, infections (e.g. rubella), maternal metabolic imbalances (e.g. alcoholism, diabetes, folic acid deficiency), drugs (e.g. anticancer drugs, tetracyclines, many hormones, thalidomide), and environmental chemicals (e.g. mercury, lead, dioxins, PBDEs, HBCD, tobacco smoke). The first-trimester exposure is considered the most potential for developmental toxicity.

Once fertilization has taken place, the toxicants in the environment can pass through the mother to the developing embryo or fetus across the placental barrier. The fetus is at greatest risk during the first 14th to 60th day of the pregnancy when the major organs are being formed. However, depending on the type of toxicant and amount of exposure, a fetus can be exposed toxicant at any time during pregnancy. For example, exposure to a particular toxicant at one time in the pregnancy may result in organ damage and at another time in the pregnancy could cause death of the fetus and miscarriage. There are a number of chemicals, biological agents (such as bacteria and viruses), and physical agents (such as radiation) used in a variety of workplaces that are known to cause developmental disorders. Developmental disorders can include a wide range of physical abnormalities, such as bone or organ deformities, or behavioral and learning problems, such as a mental retardation. Exposures to some chemicals during pregnancy can lead to the development of cancer later in the life of the child and are called transgenerational carcinogens. Exposure to toxicants during the second and the third trimester of a pregnancy can lead to slow fetal grown and result in low birth weight.

Intrauterine growth restriction (IUGR) refers to poor growth of a fetus while in the mother's womb during pregnancy. The causes can be many, but most often involve poor maternal nutrition or lack of adequate oxygen supply to the fetus.

At least 60% of the 4 million neonatal deaths that occur worldwide every year are associated with low birth weight (LBW), caused by intrauterine growth restriction (IUGR), preterm delivery, and genetic/chromosomal abnormalities, demonstrating that under-nutrition is already a leading health problem at birth.

Intrauterine growth restriction can result in a baby being Small for Gestational Age (SGA), which is most commonly defined as a weight below the 10th percentile for the gestational age. At the end of pregnancy, it can result in a low birth weight.

Hyperemesis gravidarum is the presence of severe and persistent vomiting, causing dehydration and weight loss. It is more severe than the more common morning sickness and is estimated to affect 0.5–2.0% of pregnant women.

Anorchia (or anorchism) is an XY disorder of sex development in which individuals have both testes absent at birth. Within a few weeks of fertilization, the embryo develops rudimentary gonads (testes), which produce hormones responsible for the development of the reproductive system. If the testes fail to develop within eight weeks, the baby will develop female genitalia (see Swyer syndrome). If the testes begin to develop but are lost or cease to function between eight and 10 weeks, the baby will have ambiguous genitalia when it is born. However, if the testes are lost after 14 weeks, the baby will have partial male genitalia with the notable absence of gonads.

Tests include observable lack of testes, low testosterone levels (typical female levels), elevated follicle stimulating hormone and luteinizing hormone levels, XY karyotype, ultrasound or magnetic resonance imaging showing absent gonadal tissue, low bone density, low anti-Müllerian hormone levels, and surgical exploration for evidence of male gonadal tissue.

Complications of pregnancy are health problems that are caused by pregnancy. In the immediate postpartum period, 87% to 94% of women report at least one health problem. Long term health problems (persisting after 6 months postpartum) are reported by 31% of women. Severe complications of pregnancy are present in 1.6% of mothers in the US and in 1.5% of mothers in Canada. The relationship between age and complications of pregnancy are now being researched with greater impetus.

In 2013, complications of pregnancy resulted globally in 293,000 deaths, down from 377,000 deaths in 1990. The most common causes of maternal mortality are maternal bleeding, maternal sepsis and other infections, hypertensive diseases of pregnancy, obstructed labor, and , which includes miscarriage, ectopic pregnancy, and elective abortion.

There is no clear distinction between complications of pregnancy and symptoms and discomforts of pregnancy. However, the latter do not significantly interfere with activities of daily living or pose any significant threat to the health of the mother or baby. Still, in some cases the same basic feature can manifest as either a discomfort or a complication depending on the severity. For example, mild nausea may merely be a discomfort (morning sickness), but if severe and with vomiting causing water-electrolyte imbalance it can be classified as a pregnancy complication (hyperemesis gravidarum).

Low birth weight (LBW) is defined by the World Health Organization as a birth weight of a

infant of 2,499 g or less, regardless of gestational age. Subcategories include very low birth weight (VLBW), which is less than 1500 g (3 pounds 5 ounces), and extremely low birth weight (ELBW), which is less than 1000 g (2 pounds 3 ounces). Normal weight at term delivery is 2500–4200 g (5 pounds 8 ounces – 9 pounds 4 ounces).

Postpartum blues, commonly known as "baby blues," is a transient postpartum mood disorder characterized by milder depressive symptoms than postpartum depression. This type of depression can occur in up to 80% of all mothers following delivery. Symptoms typically resolve within two weeks. Symptoms lasting longer than two weeks are a sign of a more serious type of depression. Women who experience "baby blues" may have a higher risk of experiencing a more serious episode of depression later on.

Postpartum psychosis is not a formal diagnosis, but is widely used to describe a psychiatric emergency that appears to occur in about 1 in a 1000 pregnancies, in which symptoms of high mood and racing thoughts (mania), depression, severe confusion, loss of inhibition, paranoia, hallucinations and delusions begin suddenly in the first two weeks after delivery; the symptoms vary and can change quickly. It is different from postpartum depression and from maternity blues. It may be a form of bipolar disorder. It is important not to confuse psychosis with other symptoms that may occur after delivery, such as delirium. Delirium typically includes a loss of awareness or inability to pay attention.

About half of women who experience postpartum psychosis have no risk factors; but a prior history of mental illness, especially bipolar disorder, a history of prior episodes of postpartum psychosis, or a family history put some at a higher risk.

Postpartum psychosis often requires hospitalization, where treatment is antipsychotic medications, mood stabilizers, and in cases of strong risk for suicide, electroconvulsive therapy.

The most severe symptoms last from 2 to 12 weeks, and recovery takes 6 months to a year. Women who have been hospitalized for a psychiatric condition immediately after delivery are at a much higher risk of suicide during the first year after delivery.

Virilization of genetically female (XX) infants usually produces obvious genital ambiguity. Inside the pelvis, the ovaries are normal and since they have not been exposed to testicular antimullerian hormone (MIF), the uterus, fallopian tubes, upper vagina, and other mullerian structures are normally formed as well. However, the high levels of testosterone in the blood can enlarge the phallus, partially or completely close the vaginal opening, enclose the urethral groove so that it opens at the base of the phallus, on the shaft or even at the tip like a boy. Testosterone can cause the labial skin to become as thin and rugated as a scrotum, but cannot produce palpable gonads (i.e., testes) in the folds.

Thus, depending on the severity of hyperandrogenism, a female infant can be mildly affected, obviously ambiguous, or so severely virilized as to appear to be a male. Andrea Prader devised the following Prader scale as a way of describing the degree of virilization.

- An infant at stage 1 has a mildly large clitoris and slightly reduced vaginal opening size. This degree may go unnoticed or may be simply assumed to be within normal variation.

- Stages 2 and 3 represent progressively more severe degrees of virilization. The genitalia are obviously abnormal to the eye, with a phallus intermediate in size and a small vaginal opening.

- Stage 4 looks more male than female, with an empty scrotum and a phallus the size of a normal penis, but not quite free enough of the perineum to be pulled onto the abdomen toward the umbilicus (i.e., what is termed a chordee in a male). The single small urethral/vaginal opening at the base or on the shaft of the phallus would be considered a hypospadias in a male. X-rays taken after dye injection into this opening reveal the internal connection with the upper vagina and uterus. This common opening can predispose to urinary obstruction and infection.

- Stage 5 denotes complete male virilization, with a normally formed penis with the urethral opening at or near the tip. The scrotum is normally formed but empty. The internal pelvic organs include normal ovaries and uterus, and the vagina connects internally with the urethra as in Stage 4. These infants are not visibly ambiguous, and are usually assumed to be ordinary boys with undescended testes. In most cases, the diagnosis of CAH is not suspected until signs of salt-wasting develop a week later.

When the genitalia are determined to be ambiguous at birth, CAH is one of the leading diagnostic possibilities. Evaluation reveals the presence of a uterus, extreme elevation of 17OHP, levels of testosterone approaching or exceeding the male range but low AMH levels. The karyotype is that of an ordinary female: 46,XX. With this information, the diagnosis of CAH is readily made and female sex confirmed.

Evaluation of ambiguous genitalia is described in detail elsewhere. In most cases it is possible to confirm and assign female sex within 12–36 hours of birth. The exception are the rare, completely virilized genetic females (Prader stage 5), who present the most challenging assignment and surgery dilemmas, discussed below.

When the degree of ambiguity is obvious, corrective surgery is usually offered and performed. As reconstructive surgery on infant genitalia has become a focus of controversy, the issues are described in more detail below.

The excessive amounts of adrenal testosterone produce little effect on the genitalia of male infants with severe CAH. If a male infant with CAH is not detected by newborn screening, he will appear healthy and normal and be quickly discharged home to his family.

However, the lack of aldosterone results in a high rate of sodium loss in the urine. Urinary sodium concentrations may exceed 50 mEq/L. With this rate of salt loss, the infant cannot maintain blood volume, and hyponatremic dehydration begins to develop by the end of the first week of life. Potassium and acid excretion are also impaired when mineralocorticoid activity is deficient, and hyperkalemia and metabolic acidosis gradually develop. Ability to maintain circulation is further limited by the effect of cortisol deficiency. The early symptoms are spitting and poor weight gain, but most infants with severe CAH develop vomiting, severe dehydration, and circulatory collapse (shock) by the second or third week of life.

When brought to a hospital, the 1-3 week old infant will be both underweight and dehydrated by appearance. Blood pressure may be low. Basic chemistries will reveal hyponatremia, with a serum Na typically between 105 and 125 mEq/L. Hyperkalemia in these infants can be extreme—levels of K above 10 mEq/L are not unusual—as can the degree of metabolic acidosis. Hypoglycemia may be present. This is termed a salt-wasting crisis and rapidly causes death if not treated.

As ill as these infants can be, they respond rapidly to treatment with hydrocortisone and intravenous saline and dextrose quickly restores blood volume, blood pressure, and body sodium content, and reverses the hyperkalemia. With appropriate treatment, most infants are out of danger within 24 hours.

Trisomy 16 is a chromosomal abnormality in which there are 3 copies of chromosome 16 rather than two. It is the most common trisomy leading to miscarriage and the second most common chromosomal cause of it, closely following X-chromosome monosomy. About 6% of miscarriages have trisomy 16. Those mostly occur between 8 to 15 weeks after the last menstrual period.

It is not possible for a child to be born alive with an extra copy of this chromosome present in all cells (full trisomy 16). It is possible, however, for a child to be born alive with the mosaic form.