A severe neural tube defect diagnosed in a 191/2-week-old "at risk" fetus on the evidence of a markedly elevated alpha-fetoprotein level in the amniotic fluid, turned out to be an occipital myelocoele.
Neural tube defects are associated with an increase of AFP in amniotic fluid, but, as in normal pregnancies, the values decrease with increasing gestational age.
The increased frequency of hydrocephalus among sibs of probands with a NTD and vice versa suggests that, following the birth of a child with either malformations, subsequent pregnancies should be monitored at mid-gestation by amniotic fluid AFP and serial ultrasound examination.
The risk of an open neural tube defect or other serious fetal abnormality was 60% when alpha-fetoprotein levels measured greater than or equal to +3 and 86% for levels greater than or equal to +5 SD.
These results are consistent with the hypothesis that a locus on the HLA-A side of the HLA-DR locus contributes to some fetal loss and susceptibility to NTD.
To test the hypothesis that a locus in or near the human major histocompatibility complex (HLA) contributes to both involuntary fetal loss and neural tube defects (NTD), we evaluated sharing of antigens of the HLA-A, HLA-B, or HLA-DR loci of couples who had three or more first-trimester spontaneous abortions or who had a child with an NTD (myelomeningocele or anencephaly).
The HLA phenotype compatibility among the probands' and controls' parents was within the same range except for locus C where parents of children with neural tube defects (NTD) less frequently shared common HLA-C antigens.
In an attempt to identify biochemical components of the genetic predisposition to neural tube defects (NTDs), levels of folate, cobalamin, apo-transcobalamins I and II and alpha-fetoprotein were studied in midtrimester amniotic fluid from 24 pregnant women who had previously had a child with NTD.
We detected neural tube defects (0.2%) as expected but were surprised by the efficacy with which low serum alpha-fetoprotein values identified aneuploid fetuses.
Since the variation in apo-transcobalamin II in adults is to a high degree genetically determined, the present results may suggest that the genetic predisposition to NTD is associated with variation in this protein.
In contrast, the level of apo-transcobalamin I was doubled and the level of apo-transcobalamin II tripled in amniotic fluid from women who had had a child with NTD compared with the control group.
Routine maternal serum alpha-fetoprotein screening for neural tube defects, and now also for aneuploidy, is a classic example in which there has been a schism between the clinical expertise to manage such a program within a tertiary level reproductive genetics center and the ability to reach patients in regions that are not routinely accessible to the tertiary center.