Maternal serum alpha-fetoprotein and altitude.

Maternal serum alpha-fetoprotein (MS-alphaFP) testing is widely used to screen for fetal defects. MS-alphaFP concentrations are affected by a number of variables such as gestational age, maternal weight, number of fetuses, race, and insulin-dependent diabetes. Undefined geographic factors may also influence MS-alphaFP. We have examined the effect of altitude in a sample of 1063 MS-alphaFP results selected to span a range of altitudes. The study sample was subjected to linear regression with and without a term for altitude, and multiple-of-the-median (MoM) values were calculated before and after adjusting for altitude. The median MS-alphaFP was found to decrease an average of 1 ng/mL for every 1100 ft increase in altitude, a change approximately equivalent to that seen with an increase in maternal weight of 6 lb. Adjusting for altitude resulted in the reclassification of 36 of 1063 patient results (3.4%), although the clinical utility of this adjustment remains unexamined.

Mild pyelectasis ascertained with prenatal ultrasonography is pediatrically significant.

Isolated 'mild renal collecting system dilatation' (mild pyelectasis) is a common prenatal sonographic finding. An association between mild pyelectasis and fetal aneuploidy has been established, but in the absence of a concomitant anomaly, mild pyelectasis is usually regarded as benign and of no clinical consequence, and follow-up is often not obtained after the initial ascertainment. To test this, we investigated the relationship between mild pyelectasis and (1) progression to hydronephrosis; (2) postnatal vesicoureteral reflux (VUR); and (3) postnatal surgery. Between 1 January 1992 and 1 January 1995, we performed 453 prenatal sonographic examinations of 306 patients with mild fetal pyelectasis and no other anomalies. During the course of a routine sonographic examination, we performed a detailed evaluation of the fetal genitourinary tract, Mild pyelectasis was defined as a pelvocalyceal fluid-filled space with the smallest of two transverse perpendicular sonographic measurements of > or = 4 mm and < 10 mm. Hydronephrosis was defined similarly, but with a measurement of > or = 10 mm. Postnatal urological assessment was obtained with routine renal ultrasonography, and voiding cystourethrography (VCUG), measurement of 99mTc-labelled diethylenetriamine pentaacetic acid (DPTA) mercaptacetyltriglycerine (MAG3), and intravenous pyelogram, as necessary. After exclusion criteria were applied, 294 (96%) patients with isolated fetal pyelectasis were considered. A total of 251 (82%) of these were followed with ultrasonography prenatally and during the postnatal period. Two or more prenatal examinations were carried out in 129 patients (51%) and in 35 (27%) of these cases the biometry progressed to frank hydronephrosis (> 10 mm). In only six (5%) of the cases followed prenatally did the measurement diminish to < 4 mm. We found a greater variability in prenatal renal biometry throughout gestation in infants found to have VUR, when compared with those who had no VUR. On postnatal follow-up, 84 patients had VCUG. Sixteen of these patients (6% of all patients [16/251] and 19% [16/84] of those who had the test) were found to have an abnormal finding. Whereas the prenatal appearance of mild pyelectasis improved in only a small number of cases, we found that it progressed to hydronephrosis in 27% of cases. Postnatal evaluation found VUR to be common in apparent uncomplicated mild prenatal pyelectasis. Although postnatal surgery was necessary in only a small number of cases, surgical intervention was necessary in 33% (four of 12) of those with VUR.

Practice variations in biochemical screening for Down syndrome.

The American College of Obstetricians and Gynecologists has recommended that when using biochemical screening for Down syndrome, the cut-off selected for counseling the patient should be consistent with the Down syndrome risk at which the obstetrician routinely offers prenatal cytogenetic diagnosis on the basis of maternal age alone. They also state that multiple marker testing in women over the age of 35 years cannot be recommended for routine Down syndrome screening as an equivalent alternative to offering prenatal cytogenetic diagnosis. The American College of Medical Genetics has issued similar statements. We wanted to determine current practices in regard to these suggestions. A questionnaire was mailed to members of the Society of Perinatal Obstetricians asking: (1) At what maternal age do they offer counseling/amniocentesis? (2) Do they adhere to the Colleges' recommendations with regard to counseling/amniocentesis? (3) Do they change the risk for women age 35 years or over based on serum screening? Results showed that (1) Most members currently identify attaining the age of 35 years as a separate risk factor. (2) There were wide variations in the risk quoted for women 35 years old. (3) Many members used a different risk for their biochemical screening cut-off. (4) 74% of the members would increase the age-related risk for women over 35 years based on serum screening and 49% would decrease this risk based on serum screening. Among members, there were wide variations in the risks quoted; the biochemical screening cut-off used; and the use of serum screening in women over the age of 35 years.

Failure of amniotic-fluid-cell growth: is it related to fetal aneuploidy?

We investigated outcome in patients whose amniotic-fluid-cell samples showed unexplained growth failure in culture. 32 of 7872 amniocentesis samples were classified as unexplained growth failures. 10 women did not have repeat cytogenetic testing, but among their pregnancies there were 4 abnormal outcomes (1 fetal bladder-outlet obstruction, 2 stillbirths, and 1 acardiac twin). Of the 22 patients who had repeat karyotypic analysis, 18 had normal fetal karyotypes. However, 4 fetuses were aneuploid (2 trisomy 21, 1 trisomy 13, and 1 Pallister-Killian syndrome).

In vitro bacterial contamination of amniotic fluid: effects on fluorescence polarization lung maturity testing.

OBJECTIVE: We sought to determine the effect of bacteria on fluorescence polarization (FPOL) testing of amniotic fluid. METHODS: Fusobacterium necrophorum and Escherichia coli were inoculated at concentrations of 10(3) and 10(6)/ml in amniotic-fluid specimens from 4 patients with no clinical or laboratory evidence of infection. The FPOL results were obtained at inoculation and again at 24 h of incubation. The results were compared using analysis of variance (ANOVA). RESULTS: The FPOL results from inoculated specimens were all within 2% of the uninoculated controls. The specimens incubated with bacteria showed a < 1-19% variation when compared with the time-zero uninoculated controls. However, uninoculated controls incubated for 24 h exhibited a 2-12% variation when compared with the time-zero controls, suggesting that the variation present was not secondary to the bacterial co-incubation. CONCLUSIONS: In vitro, neither bacterial inoculation nor prolonged co-incubation influences FPOL results beyond the effect of incubation alone. FPOL appears to be an appropriate test to assess fetal lung maturity in patients in whom intraamniotic infection is a concern.

Transverse umbilical arterial diameter: technique for the prenatal diagnosis of single umbilical artery.

We investigated the relationship between the transverse umbilical arterial diameter and the presence of a single umbilical artery. Further, we speculated that fetal physiologic and hemodynamic limitations in pregnancies complicated by a single umbilical artery would result in larger umbilical arterial diameters than the typical three-vessel cord. The identification of a sufficiently large umbilical artery may be pathognomonic for single umbilical artery. The transverse umbilical arterial diameter was obtained in 100 consecutive, uncomplicated singleton pregnancies between 20 and 38 weeks' gestation. These measurements were compared with the transverse umbilical arterial diameter of 23 pregnancies in which a single umbilical artery was identified with ultrasonography and postnatal examination. Transverse umbilical arterial diameter measurements of the two groups were compared. Before 36 weeks' gestation, all pregnancies with a single umbilical artery had a transverse umbilical arterial diameter measurement > 4 mm and all pregnancies with two umbilical arteries had a transverse umbilical arterial diameter measurement < or = 4 mm. Because oligohydramnios, multiple pregnancy, or suboptimal cord position may obscure the expeditious identification of the number of umbilical cord vessels, measurement of the transverse umbilical arterial diameter may prove useful in the identification of single umbilical artery. On the basis of this preliminary evaluation, we suggest that a transverse umbilical arterial diameter measurement > 4 mm is predictive of single umbilical artery between 20 and 36 weeks' gestation.

Assessment of fetal lung maturity by fluorescence polarization in high-risk pregnancies.

Although the validity of amniotic fluid fluorescence polarization (FPOL) has been documented in normal pregnancies, data are lacking on the predictive value of this method in high-risk pregnancies where biochemical maturation of the fetal lung may be altered. In this study, amniotic fluid was obtained from 86 women with pregnancies complicated by insulin-dependent diabetes (42), twin gestation (22), Rh sensitization (13) and known fetal anomalies (9). In all groups, when FPOL was > .280 (immature), phosphatidylglycerol (PG) was always absent and lecithin and sphingomyelin ratio (L/S) was < 2.5:1. When FPOL values were < .260 (mature), PG was always present and L/S was > 2.5 in 45/50 samples. When FPOL values ranged between .260-.280 (intermediate), L/S and PG values varied and were inconsistent. We conclude that FPOL assessment of fetal lung maturity in pregnancies complicated by diabetes, Rh sensitization, twin gestation and fetal anomalies is as accurate a procedure as is fetal lung maturity testing by L/S and PG. In addition, the testing procedure is quicker, more reproducible and, possibly, more reliable.

Rapid fetal lung maturity testing: commercial versus NBD-phosphatidylcholine assay.

We compared the TDx Fetal Lung Maturity test and the fluorescence polarization method using 1-palmitoyl-2(6-[(7-nitro-2,1,3-benzoxadiazol-4- yl)amino]caproyl)phosphatidylcholine (NBD-phosphatidylcholine). Using 76 paired human amniotic fluid samples, the fluorescence polarization values of the two methods were found to have a strong nonlinear correlation (r2 = 0.946). Both assays can be completed in less than 1 hour, have excellent precision (between-day variation less than 2%), and indicate the amount of surfactant phospholipid relative to albumin. The FLM assay is calibrated with surfactant/albumin standards; therefore, the reported results (in mg/g) correlate inversely with polarization of NBD-phosphatidylcholine. Strong correlations were seen for both assays with the lecithin-sphingomyelin ratio and phosphatidylglycerol. The correlations indicate that the recommended reference range for FLM will have more false predictions of immaturity than the NBD-phosphatidylcholine assay.

Comparison of the accuracy of glucose reflectance meters in pregnant insulin-dependent diabetics.

Home monitoring of blood glucose by reflectance meters has been shown to be accurate in the nonpregnant diabetic and is currently used for outpatient glucose control in the pregnant diabetic as well. Beckman ASTRA glucose results from samples collected into sodium fluoride were used as the standard for this study. Comparisons were then made to four glucose reflectance meters: Accu-Check II, One Touch, DiaScan S, and ExacTech. Although the reflectance meters appeared to be useful for assessing blood glucose trends in the pregnant diabetic, the results obtained from these meters would be unacceptable in the laboratory setting. Unfortunately, because of the erratic combination of proportional and constant bias, correction factors are not easily ascertained. Laboratories and physicians should reconsider the use of these reflectance meters for inpatient evaluation and general population screening of pregnant women.

Prenatal diagnosis of autosomal dominant microcephaly and postnatal evaluation with magnetic resonance imaging.

A case of fetal autosomal dominant microcephaly was prenatally diagnosed with ultrasonography in a woman with previously undiagnosed microcephaly. At the time of initial ultrasonographic assessment, the mother was identified to have a markedly small cranium, consistent with maternal microcephaly. The ultrasonographic examination showed the fetal head size to be four standard deviations below the mean for gestational age. Gestational dating from the other biometric parameters and from the last menstrual period was consistent with 31 weeks' gestation. Neurosonographic evaluation of the fetus revealed no obvious structural abnormalities. Serial ultrasonographic examinations at 35 and 38 weeks' gestation showed no changes in the fetal head size. A 2.64 kg male fetus was delivered at term. Neonatal assessment showed the fetal head circumference to be less than the second percentile for gestational age. Neurologic assessment of the neonate with magnetic resonance imaging showed abnormal development of the brain, with small cerebellar and cerebral hemispheres, and pachygyria. These images are compared with the magnetic resonance images of the mother. Our findings of maternal and fetal microcephaly are consistent with autosomal dominant microcephaly. To our knowledge, this is the first report of the prenatal diagnosis of autosomal dominant microcephaly.

Ultrasonographic assessment of intestinal damage in fetuses with gastroschisis: is it of clinical value?

In cases of gastroschisis detected prenatally it has been proposed that ultrasonographic criteria may play an important role in the decision for early delivery. We evaluated five cases of gastroschisis diagnosed before birth and found a correlation between prenatally detected small bowel dilatation and severe intestinal damage. However, from the limited data available these in utero measurements seem to be ineffective as indicators for delivery intervention (1) because not all fetuses with bowel dilatation have postnatal evidence of intestinal damage, (2) because some infants with intestinal damage and a poor postnatal outcome may show no in utero evidence of bowel dilatation, (3) because initial bowel dilatation may occur before a gestational age when lung maturity is achieved, and (4) because, in those cases in which bowel dilatation did correlate with intestinal damage, the bowel was already beyond the point of salvage and the infant required bowel resection.

Combined intravascular and intraperitoneal transfusions for erythroblastosis fetalis. A report of two cases.

In two cases of erythroblastosis fetalis, combined intravascular and intraperitoneal transfusions were used successfully.

Agnathia malformation complex associated with a cystic distention of the oral cavity and hydranencepahly.

A fetus with a severe variant of the agnathia malformation complex (AMC) was delivered following prenatal diagnostic evaluation with ultrasonography. The constellation of anomalies that accompanied the agnathia included holoprosencephaly, hydranencephaly, situs inversus, and polysplenia. Recently, several authors have reported the association between the agnathia, holoprosencephaly, and situs inversus. We present evidence which suggests that, when hydranencephaly is also present, this may represent the most severe variant of the AMC. Our case is presented, the literature is reviewed, and a hypothesis regarding the embryopathologic mechanism is discussed.