Fetal mortality in sibships of cases with neural tube defects

Abstract

It has been suggested that rates of fetal mortality in sibships of probands with a malformation inherited as a multifactorial threshold trait may reflect their liability to the malformation. If so, spontaneous abortion rates should be more frequent in sibships thought to have greater liability. For anencephaly and spina bifida (ASB), then, spontaneous abortion should be higher in the sibships of male probands and in families with more than one affected case (multiplex families). This hypothesis was tested using data on cases from The Montreal Children's Hospital and from the literature. Approximately 5000 pregnancies were analyzed. Rates of abortion did not vary with the sex or diagnosis of the proband. The spontaneous abortion rate was slightly higher in multiplex than in simplex families, but the difference was not statistically significant and most likely reflects the differing reproductive patterns in the two types of families. Thus, if male probands and multiplex sibships do have, on average, more liability for ASB, this liability cannot be detected in spontaneous abortion rates in the sibships available for this analysis.

Fetal mortality in sibships of cases with neural tube defects

“…I, reviewed to exclude those with a known etiology for ASB, such as amniotic band syndrome and the Meckel syndrome. The majority of sibships in Lippman's (1984) study (1433/1632; 87.8%) are from the literature and it is not stated whether or not cases were carefully reviewed to identify those with a known etiology for ASB whereas the present data are based on cases which have had thorough follow-up with respect to family history of ASB, the possible etiology of ASB, and pregnancy outcome within ASB sibships.…”

“…Information on pregnancy outcome in the sibships was obtained on follow-up of the families. We analysed the data using the methodology outlined by Lippman (1984). Yates correction for small sample size was used as appropriate.…”

“…In a recent paper, Lippman (1984) looked at fetal mortality in sibships of probands with neural tube defects. She examined data for 5,000 pregnancies from 1,834 sibships mostly ascertained from the literature where the proband had anencephaly or spina bifida (ASB).…”

“…It has been postulated that excess spontaneous abortions observed in sibships of probands with ASB represent fetuses that are also affected with ASB (Evans 1979, James 1978, Laurence & Roberts 1977, Richards 1973. The expectation based on the assumptions of the multifactorial, two-threshold model (Carter 1976, Niswander et al 1972, Lippman 1984 would be to observe an increased rate for spontaneous abortions in sibships where the proband was a male compared with those where the proband was female (males are the less frequently affected sex in ASB); and to also observe an increased rate of spontaneous abortions in multiplex sibships (with two or more affected) compared with simplex sibships (only the proband is affected). In fact, Lippman (1984) did not find a difference in the spontaneous abortion rate in the sibships by the sex of the proband in either simplex or multiplex families.…”