Yuval Yaron

Determinants of parental decisions after the prenatal diagnosis of Down syndrome

We evaluated demographic factors and factors specific to the current pregnancy, and their relationship to the decision to continue or terminate a pregnancy after prenatal diagnosis of Down syndrome. All cases of Down syndrome (DS) managed at a tertiary care center from 1989-1997 were retrospectively analyzed with respect to maternal age, parity, gestational age, sonographic findings, insurance status, and race. Of 145 cases of trisomy 21, 19 (13.1%) of women chose continuation of pregnancy, while 126 (86.9%) chose termination. There were no differences between groups in parity, sonographic findings, insurance status, or race at the time of diagnosis. However, patients who chose termination were significantly older and earlier in gestation than those electing to continue their pregnancy. When Down syndrome is diagnosed prenatally, the choice of termination is related to maternal age and gestational age, but only gestational age is a significant independent predictor of pregnancy termination.

Fetal gender impact on multiple‐marker screening results

Maternal serum alpha-fetoprotein (MSAFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) are used in combination with maternal age to calculate the risk for Down syndrome (DS) in pregnancy. Increased levels of hCG and decreased levels of MSAFP and uE3 are consistent with an increased risk for DS. We retrospectively evaluated second-trimester maternal serum marker levels in a large cohort of patients with known normal outcomes and documented fetal gender. These included 15,428 patients who had MSAFP measurements, 11,428 patients with both MSAFP and hCG, and 6,090 patients with all three markers including uE3. MSAFP levels in patients with female fetuses were consistently lower than those with males. Conversely, hCG was higher in pregnancies with females as compared to males. No gender-related difference was noted for uE3. These results would suggest that the computed DS risk for female fetuses is higher than for males, despite the fact that the incidence of DS is similar in both genders. This information could be useful for calculating gender-specific DS risk; however, this would require ultrasonographic determination of fetal sex.

Differential increases in AFP, hCG, and uE3 in twin pregnancies: Impact on attempts to quantify Down syndrome screening calculations

Since the advent of multiple marker screening (MMS) for Down syndrome (DS) risk calculations, limitations for twins have been apparent. Recent attempts have been made to extrapolate mathematically singleton risks to twins. Here we investigate the pattern of levels among AFP, hCG, and uE3 in twins. MMS screening data from 4,443 twin pregnancies were compared to those from 258,885 singletons from 14-21 weeks of gestational age during a 3-year period (1992-1994) in our laboratory. Medians were determined for singletons and twins, and the ratios of twins to singletons were derived. Median AFP levels for twins are approximately double those of singletons, but median increases for hCG and uE3 are less than double. The data were divided further by ethnic groups (white, African American, Asian, and Hispanic), among which there were significant variations in medians, but not in the ratios of twins to singletons. The increased serum levels of different markers in twins are not consistent across analytes, possibly reflecting independent development of different compartments. Such differences mean that a mere mathematical conversion of singleton DS risks would be imbalanced among the analytes and cannot be applied reasonably to twins. Ethnic-specific databases are as important in twins as they are in singletons.

Prenatal diagnosis of cloacal dysgenesis sequence : Differential diagnosis from other forms of fetal obstructive uropathy

Cloacal dysgenesis sequence (CDS) is a rare cause of fetal obstructive uropathy (FOU). The prenatal differentiation of CDS from other FOU is important because CDS is not amenable to in utero surgical intervention in the form of vesicoamniotic shunts. We evaluated the prenatal characteristics of 8 fetuses with CDS, including a pair of monozygotic twins concordant for CDS, in order to identify features that would enable differentiation from other forms of FOU. Pathologic examination in each of the 8 fetuses confirmed characteristic features of absent anal, genital, and urinary orifices associated with a smooth perineum and abnormal phallic development. Associated abnormalities included dysplastic kidneys in 6, hydroureters in 5, intraluminal colonic calcifications in 2, and hypoplastic lungs in 5. Five of these fetuses initially presented as posterior urethral valve syndrome. Six fetuses had megacystis, and 4 underwent vesicocenteses to evaluate urinary electrolytes, all of which were in the ‘poor-risk’ category. Six fetuses were male and 2 female, contradicting earlier claims that CDS occurs only in females. Evaluation of candidates for in utero surgical intervention should include fetal karyotype, and CDS should be suspected in cases of FOU in whom the karyotype reveals a male fetus and sonographic evaluation demonstrates colonic calcifications or abnormal phallic development. Diagnostic microendoscopy may be of benefit in such cases.

Distribution of Neural Tube Defects as a Function of Maternal Weight:No Apparent Correlation

Objectives: Maternal nutritional deficiency is an important predisposing factor to congenital neural tube defects (NTDs). It was hypothesized that obese women may have an increased risk for NTDs. The aim of the present study was to address this question in a large cohort. Methods: A total of 72,915 consecutive cases of biochemical screening that had documented maternal weights and pregnancy outcomes were identified from the Quest Diagnostic Laboratories database. Patients were divided into five ranges of maternal weights, and the incidence of NTDs was calculated for each group. Based on the different definitions of maternal overweight, the data were also analyzed based on 2 groups only, obese and nonobese, using three cutoff points. Results: Seventy-nine pregnancies were complicated by NTDs (incidence of 1.08 per 1,000 pregnancies). Differences between maternal weights ranges were not found to be statistically significant (χ2 = 5.997, p = 0.19, power = 0.99). Differences between obese and nonobese mothers were not found to be statistically significant for all three analyses as well. Conclusions: Our present results do not support an association between maternal obesity and NTDs.

Maternal Weight Differences Do Not Explain Ethnic Differences in Biochemical Screening

In previous work, we and others have shown that serum levels of α-fetoprotein, human chorionic gonadotropin, and estriol vary among the four commonly defined racial/ethnic groups seen in the United States: white, African-American, Asian, and Hispanic. We have suggested that better sensitivity and specificity could improve screening sensitivity and specificity. However, it has been argued that systematic weight differences among the groups could explain the variation. We evaluated the results from 208,257 patients having screening and found systematic weight differences. However, these differences were not as large as the racial/ethnic differences, showing that weight does not fully explain the discrepancy, and, therefore, four separate data bases give more accurate results.

Effect of adjustment of maternal serum α‐fetoprotein levels in insulin‐dependent diabetes mellitus

Our objective was to determine the effect of the 20% upward adjustment of maternal serum alphafetoprotein (MSAFP) in patients with insulin-dependent diabetes mellitus (IDDM) on the number of patients that would be classified at increased risk for pregnancy complicated by either Down syndrome (DS) or neural tube defect (NTD). We retrospectively evaluated a database containing 63,110 patients who underwent multiple serum marker screening between 14 and 22 weeks gestation; 620 patients with IDDM had measurements of MSAFP of which 479 also had measurements of beta-HCG, allowing calculation of DS risk. Increased NTD risk was defined as MSAFP >2.5 MOM while increased DS risk was defined as a calculated risk > or =1/270. One IDDM patient delivered an infant with a NTD; it was not detected on serum screening. No infants were born with DS. Of the 620 patients with MSAFP determinations, 9 had values >2.5 MOM before adjustment. After upward adjustment, 7 additional patients were identified. Sixteen patients were identified at increased risk for DS before and after adjustment. Our data suggest that the 20% upward adjustment of MSAFP increases by 78%, the number of patients who would require further evaluation for NTDs. Although we were able to identify 620 women with IDDM who underwent serum screening for NTD, the low prevalence of NTDs did not allow us to demonstrate an increased detection rate. The effect of upward adjustment of MSAFP on the number of patients categorized at increased DS risk appears to be minimal.

Concordance for Cloacal Dysgenesis

Monozygotic (MZ) twins concordant for cloacal dysgenesis were diagnosed at 15 weeks gestation on ultrasound exam. The structural alterations result from abnormal morphogenesis of the cloacal membrane and contiguous anlage with resultant secondary changes. These defects are suggestive of teratogen exposure or an endogenous event early in gestation, resulting in MZ twinning and the development of a polytopic field defect.

10 Multifetal pregnancy reduction

Multifetal pregnancy reduction (MFPR) has become a mainstay of infertility therapy as its development has allowed physicians to become more aggressive in treating patients resistant to more conservative therapies. Over the course of the past decade, MFPR has become practised in a limited number of tertiary specialty centres, which have improved its performance and very substantially lowered its risks. The majority of physicians performing MFPR employ a transabdominal needle injection of potassium chloride into the fetal thorax. Risks for pregnancy losses of patients starting with triplets and/or quadruplets reduced to twins have improved over the past decade and are not substantially different from those in patients whose pregnancy began as twins. There have been no substantiated risks of coagulopathies or damage to surviving fetuses.

Differences in Measurements of the Atria of the Lateral Ventricle: Does Gender Matter?

OBJECTIVEnTo evaluate possible differences in measurements of the width of atria of the lateral cerebral ventricles of male and female fetuses.nnnSTUDY DESIGNnA prospectively entered database was reviewed to identify patients undergoing ultrasound examination at > 13 weeks between July 1, 1994 and June 30, 1995. Inclusion criteria included identification of fetal gender, measurement of the atria, and the absence of fetal anomalies.nnnRESULTSnThe atrial width of the lateral ventricles was statistically greater in male than in female fetuses (7.1 vs. 7.0 mm, p < 0.001).nnnCONCLUSIONnAlthough statistically significant, the difference between genders in the measurement of the ventricular atria is too small to be of clinical utility.