1983343 (see also Dawson et al. 1999228).
a Concentration mg/mL.
b Arithmetic mean.
Mean gestational age, 17.1 weeks. All concentrations are ng/mL except where noted.
Copper, zinc, bromine, lead, and rubidium assays show no significant differences among groups of normal, hypotrophic, and trisomic fetuses.288 Bussière et al.230 stressed that the wide dispersion of reported metal concentration values in AF may be secondary to sample variability, lack of technical uniformity, and the presence of contaminants. Nevertheless, results obtained for those trace elements are of the same order of magnitude as in previously published reports.343, 361 Both AF vitamin A and zinc levels were elevated in the presence of a fetal NTD.362, 363
Tamura and co‐workers364 studied the relationships between AF and maternal blood nutrient concentrations. Folate, zinc, copper, and iron concentrations in AF were significantly lower than plasma levels; this relationship was reversed for vitamin B12. No correlation was found between AF and blood nutrient concentrations and pregnancy outcome. Vitamin B12 concentrations are lower in AF in the presence of fetal NTDs compared with unaffected fetuses.365, 366
Luglie and co‐workers367 studied the total concentration of mercury (Hg) in AF and found no direct relationship with the number of occlusal extension of fillings using dental amalgam. Mercury is one of the components of dental amalgam that can pass into the organs and biologic fluids. A study of pregnancies to mothers in a region of Poland with high levels of mercury pollution confirmed high levels of Hg in most of the newborn cord blood samples, but no statistically significant correlation was identified between Hg levels and delivery week, APGAR score, or placenta or newborn weight.368
Milnerowicz et al.369 suggested that smoking may have an impact on uterine blood vessels and may cause placental vascular insufficiency and changes in fetal membranes. In this study, the concentration of Zn and Cd were half the value and Pb 10 times lower in AF from a small number of women as compared with a normal pregnancy. Cotinine and Cd were much higher in women with oligohydramnios who were also heavy smokers.
Creatinine/cystatin C
In early pregnancy, the creatinine level in the AF is similar to that found in maternal serum, rising to reach values twice those of maternal serumat term. In early gestation, it seems that creatinine moves from maternal to fetal serum and then to fetal urine and AF.370 In late pregnancy, AF creatinine may originate from fetal muscle as well.
Creatinine is one of many indices that was used to assess fetal maturity.371 Many workers tried to improve maturity assessments by combining the results of creatinine estimations, the percentage of lipid‐positive cells,372 and the L/S ratio. The simultaneous assessment of the three parameters correlates well with fetal maturity in normal pregnancy. However, in the very cases of abnormal pregnancy states (including diabetes, Rh isoimmunization, hypertensive disorders, intrauterine growth restriction, and hydramnios) in which guidance would be invaluable, these estimations, both singly and together, remain insufficient (see earlier).
As suggested by Muller et al.,373 prognosis on fetal outcome can rely only on sonography in cases of severe or mild uropathies, the most frequent being the obstructive anomalies. Serum creatinine cannot be used as a marker of glomerular filtration (GFR) because it crosses the placenta and is cleared by the mother. Cystatin C has been shown to be an accurate marker of GFR in adults and infants, and can be considered as a marker of fetal renal tubular damage rather than a marker of GFR.
Mussap et al.241 compared the diagnostic accuracy of cystatin C with that of creatinine in discriminating renal function in fetuses without ultrasonographic evidence of renal malformations from those with obstructive uropathies, and concluded that cystatin C is a sensitive biomarker for early identification of obstructive uropathies.
Blood group substances
The Lewis and soluble blood group substances A, B, and H, are present in AF as early as 9–24 weeks of gestation.225, 257 The best evidence suggests that the AF Lewis substances and secretor types are of fetal origin. Because of their molecular weights (about 300,000), the soluble blood group substrates do not easily cross fetal membranes. Because the fetal ABH secretor and Lewis types can be determined from AF in early gestation, they were useful for their linkage relationships to genetic disease. Examples include the linkage relationships of the ABO locus to the nail–patella syndrome374 now detectable by analysis of the LMX1b gene375 and the linkage of the secretor and myotonic dystrophy loci.376 Milunsky et al.377 reported the prenatal diagnosis of six cases and stressed the risk of neurologic impairment when the mother herself is affected. Myotonic dystrophy is now accurately diagnosed by trinucleotide repeat analysis (see Chapter 14).378
The development of fetoscopy facilitated the measurement of factor VIII coagulant antigen and factor VIII‐related antigen. The ratio of factor VIII coagulant antigen to factor VIII‐related antigen has a fairly constant value, and in three affected fetuses, a very low ratio was pathognomonic of classic hemophilia. This immunologic test does not apply to all families at risk, and has been replaced by molecular analysis (see Chapter 14).
Cell‐free HLA‐A and ‐B maternal and paternal antigens have been detected in AF obtained between 16 and 18 weeks of gestation. HLA antigens can be detected in fetal tissues as early as the sixth week of pregnancy, and defective synthesis is seen in severe combined immunodeficiency syndrome.379 Kleinbauer et al.206 studied blood coagulation and fibrinolytic factor activities in the AF. Prothrombin rose during the last trimester, while factor X activity decreased. Plasminogen, α1‐antitrypsin, α2‐antiplasmin, antithrombin III, and α2‐macroglobulin levels did not change significantly during gestation.
Immunoglobulins
Immunoglobulins (IgA, IgA1, IgA2, and IgG) are measurable in AF samples between 11 and 40 weeks of gestation. Whereas IgG, IgD, and IgA levels increase from 11 to 25 weeks and then decrease until term, IgM levels tend to remain constant until 35 weeks and then increase until term.380 Davis et al.381 found similar IgG levels in AF from the second trimester. Their study, however, dealt especially with antibodies to herpes simplex virus (HSV) type 1, which was found in 78 percent of AF samples tested. Antibodies to cytomegalovirus (CMV) were found in 84 percent of the same AF samples tested. No viruses, bacteria, mycoplasma, or chlamydiae were isolated from the samples. Isolation of CMV has been successful in AF from two fetuses showing severe growth restriction and classic CMV infection382 (see Chapter 34).
The immunologic activity of AF remains poorly understood and much remains to be learned about mechanisms involved in neonatal immune disease in babies born to mothers affected with systemic lupus erythematosus, idiopathic thrombocytopenic purpura, Graves disease, and myasthenia gravis. Auger et al.383 studied the antibody response to Candida albicans during the second trimester. Specific IgG was detected in 94.7 percent of the samples and specific IgA in 98 percent. There was a predominance of IgA activity in the AF. There was no correlation between the IgG and IgA titers, suggesting a fetal origin for IgA, which would offer a functional advantage over maternally transmitted IgG. Immunoglobulin C declines as pregnancy progresses toward term.384
