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Hormones
ОглавлениеHormones and related metabolites have various origins and are present in measurable quantities in AF during the second trimester. Coelomic fluid contains high concentrations of progesterone, 17β‐estradiol, and 17α‐hydroxyprogesterone, which may be synthesized locally.423 Steroids other than progesterone are found in higher concentrations in coelomic fluid or maternal serum than in AF. Free diffusion of steroids across the amnion is limited, which may protect the embryo from unwanted exposure to biologically active steroids. Abnormal findings may be related to placental dysfunction, renal or adrenal anomalies or insufficiency, or specific endocrine disorders of the reproductive organs. Hormonal changes may also be linked to lipolysis or gluconeogenesis or to thyroid, parathyroid or pancreas malfunction. A list of the major hormone constituents is given in Table 3.4. Fetal and maternal tissues produce hormones that have effects on enzyme synthesis, membrane transport systems, and, not least, cyclic AMP. Measurement of steroid AF levels can be of some value in the evaluation of some pathologies, such as congenital adrenal hyperplasia and molar degeneration of the placenta.445, 446 Steroid concentrations from fetuses with Klinefelter syndrome were found to be normal.447, 448 Testosterone is elevated in the AF of male fetuses, although there is no significant increase of dihydrotestosterone.449, 450 Testosterone glucuronide used in conjunction with unconjugated testosterone was a good indicator for fetal sexing in AF451 but has been replaced by other methods (see Chapter 12).
Table 3.4 Hormones measured in amniotic fluid during the second or third trimesters
| Hormone | Approximate time of gestation (weeks) | Selected references |
|---|---|---|
| Aldosterone | 27 | 424 |
| Androstenedione | 14–22 | 425 |
| Annexin A5 | 15–24 | 380 |
| Apolipoprotein A | 16 | 214 |
| Apolipoprotein A‐I | Second trimester | 213 |
| Apolipoprotein A‐II | Second trimester | 213 |
| Apolipoprotein B | Second trimester | 213 |
| Apolipoprotein E | Second trimester | 213 |
| Cortisol | 13–24, 37, 38 | 426 |
| Dopamine | Second trimester | 323 |
| β‐Endorphin | 16–24 | 427 |
| Epinephrine | Second trimester | 234 |
| Erythropoietin | Second and third trimesters | 428 |
| Estradiol | 14–22 | 429 |
| Estrone | 14–22 | 430 |
| Estriol‐16‐glucuronide | 16 | 430 |
| Follicle‐stimulating hormone | 14–22 | 425 |
| Galanin | 38‐40 | 431 |
| β1‐Glycoprotein | 14–20 | 432 |
| Gonadotropin hCG | 15–20 | 432 |
| Gonadotropin LH | 16–20 | 433 |
| Growth | 17 | 426 |
| 17α‐Hydroxypregnenolone | 14–20 | 382, 434 |
| Insulin | 12–24 | 434 |
| Insulin‐like growth factor 2 and 3 | 12–20 | 435, 436 |
| Leptin | 14–18 | 437, 438 |
| β‐Lipoprotein | 16–21 | 439 |
| Progesterone | 14–22 | 429 |
| Prolactin | 15–20 | 440 |
| Prostaglandin | 15–40 | 441 |
| Relaxin | 9–40 | 355 |
| Renin | 16–20 | 330 |
| Testosterone | 10–22 | 442 |
| Thyroxine | 17–22 | 443 |
| Transthyretin | Third trimester | 444 |
| Triiodothyronine (T3) | 17–22 | 443 |
Levels of hepatocyte growth factor (HGF) are greater between 20 and 29 weeks of gestation than after 30 weeks. HGF was 300‐ to 400‐fold higher in amnion during the second trimester than at term. Placenta and amnion produce and secrete HGF, which plays a role in fetal growth as well as the growth and differentiation of the placenta.262
Elevated insulin‐like growth factor binding protein‐1 level in the second trimester is an early sign of intrauterine growth restriction, and in the third trimester 55 percent of infants small for gestational age were identified.452 The peptide hormone insulin‐like factor 3, made by the fetal testis, is only detectable in AF from male fetuses, with highest concentrations between 15 and 17 weeks gestation.453 This hormone was associated with subsequent preeclampsia and advanced maternal age.453
Congenital adrenal hyperplasia can be diagnosed as early as 11 weeks of pregnancy by the determination of 17‐hydroxyprogesterone in AF. This diagnosis is more precisely made by molecular studies using chorionic villi or cell‐free DNA in maternal plasma (see Chapter 7). Cortisol levels during the second trimester can be lowered by the administration of a synthetic glucocorticoid that crosses the placenta.454
The highest concentration of reverse triiodothyronine in AF occurs between 15 and 20 weeks of gestation.455 Fetal thyroid function can be evaluated via amniocentesis, especially in families at risk. Assay of 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
