The effect of fetal gender on second-trimester maternal serum inhibin-A concentration

Second-trimester serum inhibin-A is increasingly used as a fourth marker in addition to the triple test to screen for Down syndrome. We investigated whether fetal gender had an effect on serum inhibin-A concentration. A retrospective analysis was done on 316 normal pregnancies and 48 Down syndrome pregnancies in which maternal serum inhibin-A assays were performed between 15 and 20 weeks of gestation and in which the fetal sex was known. The median inhibin-A MoM (95% CI) for normal pregnancies in the presence of a male fetus was 0.93 (range 0.88–1.03). This was significantly lower than that in the presence of a female fetus (median MoM=1.04). The gender difference was not observed in the Down syndrome pregnancies. The increased inhibin-A concentration would lead to a 2.3-fold higher false-positive rate in the presence of a female fetus (10.6% vs 4.6%; p<0.05, Chi-square test). Because of the small number of cases studied, the results need to be substantiated by a larger series. If the gender effect is confirmed, adjustment for fetal sex may be necessary when inhibin-A is used as a screening marker. Copyright © 2001 John Wiley & Sons, Ltd.     

Expected,prenatally discovered,and born cases of Down syndrome in Denmark during the period 1980–1998

In order to elucidate the consistency between generally used age-dependent risk values for Down syndrome (DS) and estimates of the probability of miscarriage in Down pregnancies we have compared expected numbers with estimated numbers of births with DS in Denmark had no intervention at all been carried out. The expected numbers were calculated from the distribution of newborn children according to maternal age combined with the age-related risk of DS. The estimated numbers of children that actually would have been born without any intervention were estimated from observed numbers of cases of DS, i.e. the cases born plus – with corrections because of the high probability of miscarriage in DS pregnancies – a proportion of those cases discovered prenatally. The analysis was carried out separately for mothers aged 35 years or older and for younger mothers. We found a high degree of compatibility between expected and estimated numbers, probably with a minor underestimation of the expected values for the older mothers. The performance of DS screening in Denmark in the period under consideration (1980–1998) is discussed in relation to the figures presented. Despite the fact that 11.8% of all pregnancies were subjected to an invasive diagnostic procedure, only about 38% of all births with DS were prevented. This means that in the period 1990–1998, reluctance to accept serological screening has indirectly resulted in the birth of almost 300 cases of DS in Denmark and at the same time the miscarriage of an unreasonable high number of normal fetuses. Copyright © 2001 John Wiley & Sons, Ltd.     

Familial orofaciodigital syndrome type I revealed by ultrasound prenatal diagnosis of porencephaly

Porencephaly is a rare central nervous system (CNS) abnormality that can be caused by an intraparenchymal destructive process or a developmental defect. Here we report on a prenatal ultrasound diagnosis of complex CNS abnormalities including agenesis of the corpus callosum, agenesis of the cerebellar vermis, bilateral hydrocephaly, and bilateral porencephaly in fetus at 33 weeks' gestation. The diagnosis of familial orofaciodigital syndrome type I (OFD I) was raised after fetal autopsy, clinical examination of the family, and the X-linked dominant inheritance pattern. This is the fourth report of porencephaly in association with OFD I. We discuss the difficulties in genetic counselling since OFD I shows variable expressivity of the phenotypic features. Furthermore, we emphasize the importance of a detailed ultrasound examination after a prenatal diagnosis of porencephaly. Copyright © 2001 John Wiley & Sons, Ltd.     

Strategies for prenatal and preimplantation genetic diagnosis in Marfan syndrome (MFS)

Marfan syndrome (MFS) is an autosomal dominant disorder with a prevalence of 2–3 per 10 000 individuals. Symptoms range from skeletal overgrowth, cutaneous striae to ectopia lentis and aortic dilatation leading to dissection. Prenatal diagnosis was until recently mainly performed in familial cases by linkage analysis. However, mutation detection has become available with thorough screening methods. The phenotypic variability observed in MFS makes reproductive options difficult, as molecular diagnosis cannot predict clinical severity of the disease. Data are presented on 15 prenatal and/or preimplantation genetic diagnoses (PGD) in nine families, originating from Belgium, the Netherlands, Spain and France. In four families data from linkage analysis were used, whereas in five other families the causative FBN1 mutation was characterised. Four PGD cycles in two couples led to one ongoing pregnancy. In addition, two amniocenteses and nine chorionic villus (CV) samplings were performed. In five pregnancies an affected fetus was diagnosed. In one of them, the couple chose to continue the pregnancy and an affected child was born, whereas the other four couples decided to terminate the pregnancy. It is expected that the greater availability of mutation testing of the FBN1 gene will increase requests for prenatal diagnosis. PGD appears to be an acceptable alternative for couples facing ethical reproductive dilemmas. Copyright © 2002 John Wiley & Sons, Ltd.