thyroid‐stimulating hormone (TSH) in AF may reveal fetal hypothyroidism. A fetal goiter was found on ultrasound examination and confirmed by thyroid function assays on AF; levothyroxine sodium therapy was administered in utero, and the authors reported the birth of a euthyroid infant456 (see also Chapters 3 and 31). In pregnancies at high risk for fetal hypothyroidism, it may be advisable to consider prenatal investigation in view of available in utero fetal therapy. Fetuses with primary pituitary dysgenesis have low levels of prolactin during the second trimester of pregnancy.457
Buscher et al.458 found significantly elevated erythropoietin levels in AF in pregnancies complicated by maternal hypertension and low‐birthweight children. Elevated erythropoietin levels in AF is a marker of fetal hypoxia and growth restriction.459–461
Elevated levels of leptin in both AF and maternal serum of patients with a fetus affected with an NTD was thought due to leakage from the cerebrospinal fluid.462
Other components measured in AF include about 30 organic acids,305 somatomedin,463 surface‐active material,338 and β‐endorphin.464 The concentrations of β‐endorphin in AF at term correlated with the degree of fetal distress. Green or brown AF in midtrimester AF usually reflects episodes of bleeding and transudation (see also Chapter 10), and most pregnancies progress to term normally. It is necessary to distinguish these cases from those with meconium‐stained fluid, which may arise later from fetal distress with a higher risk of neonatal morbidity.465
Drugs/toxicants
Some drugs, such as meperidine, cross the placenta and accumulate in AF, but the direct action of the drug on the fetus is not well understood. The amount of free methadone is 4–5 times that in the maternal plasma, but the active metabolite normeperidine is absent.466 There is evidence of an increased risk of certain heart defects when the fetus is exposed to opioid analgesics early in pregnancy.467 It is exceedingly difficult to tease apart the causation of relatively small effects such as poor school performance when drug abuse, other prenatal exposures, lack of adequate parenting, and exposure to violence coexist.
Blocking factors in the fetus might alter the action of antibodies to acetylcholine receptor at the neuromuscular junction, thus preventing transient or neonatal myasthenia gravis until after birth.197 Fetal hydantoin syndrome is observed in infants of epileptic mothers receiving certain anticonvulsant drugs during pregnancy. Although the exact risk of fetal demise is unknown, it is believed that these mothers have a two‐ to threefold increased risk of giving birth to an infant with mental retardation, cleft lip and/or palate, heart defect, and minor skeletal anomalies. Anticonvulsants are metabolized by a variety of enzymatic reactions, the cytochrome P450 superfamily almost certainly having a key role in determining fast and slow catabolizers.468
An accumulation of nicotine and its metabolites was reported303 in midtrimester AF samples of self‐reported smokers and in fetal arterial blood samples obtained at delivery. Cotinine accumulation in the fetus was noted as early as 7 weeks of gestation in both active and passive smokers.469 Milunsky et al. documented a tobacco‐specific carcinogen in midtrimester AF of smoking mothers (Table 3.5).498 Tobacco smoke is considered the most extreme example of a systemic human mutagen.499
Table 3.5 Examples of environmental drugs and chemicals in the fetal environment
| Chemical class | Chemical | Matrix measured | Selected references |
|---|---|---|---|
| Pharmaceuticals | Anesthetics | Meconium | 471, 472 |
| Analgesics | Meconium | 471, 472 | |
| Antihistamines | Meconium | 471, 472 | |
| Adrenergics | Meconium | 471, 472 | |
| Expectorants | Meconium | 471, 472 | |
| Antidepressants | Meconium | 471, 472 | |
| Anticonvulsants | Meconium | 471, 472 | |
| Herbicides | – | AF | 473 |
| Illicit drugs | Cocaine | Meconium | 471, 472 |
| Opiates | Meconium | 472 | |
| Cannabinoid | Meconium | 472 | |
| Morphine | Meconium | 472 | |
| Methadone | Meconium | 472 | |
| Stimulants | Meconium | 472 | |
| Alcohol | Fatty acid ethyl esters | Meconium | 474 |
| Tobacco | Cotinine/nicotine | Meconium | 475 |
| Trace elements/metals | Arsenic | Meconium | 476 |
| Bromine | Cord blood | 477 | |
| Cadmium | Meconium/cord blood | 476, 478 | |
| Cesium | Cord blood | 479 | |
| Copper | Cord blood/meconium | 480, 481 | |
| Iron | Cord blood | 480, 481 | |
| Lead | Meconium | 476, 478 | |
| Manganese | Cord blood | 482 | |
| Magnesium | Cord blood | 483 | |
| Mercury | Meconium |