The recurrence risk for neural tube defects in the United States: a collaborative study.

To determine the recurrence risk for patients with one prior pregnancy affected with neural tube defects (NTD), the authors have pooled data from eight testing centers. In 831 pregnancies studied because one sib was affected with an NTD, the recurrence rate was 3.0%, with 95% confidence limits of 2.0-4.3%, and 99% confidence limits of 1.8-4.8%. The recurrent lesion, whether spina bifida or anencephaly, tended to be concordant with the first to a significant degree. Only 12.2% of recurrent NTD were different from the first, with 95% confidence limits of 4.1-26.2%, and 99% confidence limits of 1.7-30.9%. Both an accurate recurrence risk and the information that a recurrent NTD lesions tends to be concordant with that in the first affected child are useful in the genetic counseling of patients in the United States and in the selection of appropriate prenatal diagnostic studies.

Unexplained elevated maternal serum alpha-fetoprotein levels and pregnancy outcome in twins.

OBJECTIVE: To evaluate whether elevated maternal serum alpha-fetoprotein (MSAFP) levels in uncomplicated twin gestations are associated with an increased risk for pregnancy complications and adverse outcomes. METHODS: A retrospective data-base analysis was conducted of 267 women with twin pregnancies delivered between January 1988 and October 1994, of whom 42 had elevated MSAFP levels and 225 had normal levels. We evaluated rates of preterm delivery (defined as gestational age less than 34 weeks at delivery), birth weight less than 1500 g, twin-to-twin birth weight discordance, small for gestational age (SGA) infants (defined as birth weight below the tenth percentile for gestational age), and fetal malformations. Also assessed were potentially confounding variables such as obstetric and medical histories as well as sociodemographic factors. RESULTS: Among nulliparous women, an unexplained elevation in MSAFP levels was associated with a statistically significant increased risk for preterm delivery. Among multiparous women, this association is suggested by the data, but not significantly so. An unexplained elevation in MSAFP level was also associated with a significantly increased risk for birth weight less than 1500 g, but this was related to the increased rate of preterm births. No appreciably increased risk was apparent for SGA infants, fetal malformations (other than neural tube defects and abdominal wall defects), or twin-to-twin birth weight discordance. CONCLUSION: In twin pregnancies, an unexplained elevation in MSAFP level may increase the risk for preterm delivery but not other adverse pregnancy outcomes.

Letter: Routine alpha-fetoprotein studies in amniotic fluid.

PIP: Alpha fetoprotein (AFP) assay of 500 amniotic fluid (AF) specimens was performed by rocket antigen-antibody electrophoresis, and the results were related to the WHO reference serum 72/225. Results obtained in 272 second trimester pregnancies known to have resulted in a normal infant are given tabularly; beyond 34 weeks, all pregnancies resulting in a normal infant had levels below 250 nanounits/ml, and abnormal results were obtained in 9 cases. These are briefly described. In all cases in which there was an abnormal AF AFP there was a severe fetal abnormality, although not necessarily a neural tube defect. In 1 case, the absence of AFP was associated with the absence of fetus. In another, the elevated AFP may have been associated with impending fetal death, rather than the abdominal wall defect found. In yet another case, the elevated third trimester AFP seemed obviously associated with impairment of fetal clearance of AF. As yet, no false positive results have been found, though not all the women studied have given birth. All AF samples should be assayed for AFP.^ieng

Maternal serum levels of alpha-fetoprotein and fetal fibronectin as markers of labor in the third trimester.

Unexplained elevations of maternal serum alpha-fetoprotein (MSAFP) in the second trimester have been found to be associated with a two- to fourfold increase in the rate of preterm delivery, but the sensitivity is low. Therefore, we reasoned that MSAFP levels in the third trimester could prove to be a more useful biochemical marker to predict labor. The presence of placental and membrane-derived fetal fibronectin (FFN) in cervicovaginal secretions has recently been shown to predict preterm delivery with a sensitivity of 81.7% and specificity of 82.5%. We postulated that damage to membranes and microscopic breakdown of fetomaternal blood barrier during labor might result in release of AFP or FFN into maternal serum. Maternal serum alpha fetoprotein and fetal fibronectin levels were measured prospectively in 29 patients in active labor at term and in 25 controls undergoing elective cesarean section. Neither MSAFP nor serum FFN levels were associated with labor at term. We did, however, note significantly higher MSAFP levels in mothers bearing male fetuses versus female fetuses (p < 0.01). Since the current literature supports a sex difference in the MSAFP levels in the second trimester, this does not appear to change as gestation advances. Further studies are needed to determine if, in addition to maternal weight and race, MSAFP levels should be also adjusted for fetal sex diagnosed on sonography.

A paper chromatoelectrophoresis method for the determination of bilirubin binding to serum protein.

A technique is described in which paper chromatoelectrophoresis is used to measure the bilirubin binding capacity of albumin in serum. It is equivalent to the Sephadex G-25 method and its results are highly reproducible. From a single pool of serum, multiple determinations indicated the mean bilirubin binding capacity to be 23.7 +/- 0.76 (SD) mg/dl and the greatest difference between any two values was 2 mg/dl. This new technique can determine the bilirubin binding capacity of a serum sample in 15 min. Highly skilled technicians are not needed and very small quantities of serum are required, which gives it a definite advantage over the Sephadex G-25 method.

Congenital nephrosis in low-risk pregnancies.

Congenital nephrosis is an autosomal recessive disorder requiring neonatal renal transplant for survival. The postnatal diagnosis rests upon the electron microscopic evaluation of the epithelial foot processes and basal membrane of the glomeruli. The prenatal diagnosis can be suspected in the presence of a positive family history with an amniotic fluid (AF) alpha-fetoprotein level greater than 5 standard deviations (SD) above the population mean accompanied by a negative AF acetylcholinesterase, absent haemoglobin F, and an unremarkable fetal sonographic examination. We reviewed our series of seven cases of congenital nephrosis fulfilling the above criteria; four cases had negative family histories, and in two cases the diagnosis of congenital nephrosis was further supported by the presence of elevated AF albumin concentrations. We conclude that (1) the prenatal diagnosis of congenital nephrosis is feasible in a low-risk population, and (2) an elevated AF albumin concentration may represent an additional marker for the diagnosis of congenital nephrosis, even though false-negative results have been reported.