Maternal reproductive loss and cleft lip with or without cleft palate in human embryos

Recognized spontaneous abortions in previous pregnancies were significantly more frequent in mothers of 87 Japanese embryos with cleft lip with or without cleft palate (CL(P] than in mothers of normal embryos. The number of prior pregnancies was found to be smaller in mothers of CL(P) embryos with additional defects, suggesting that unrecognized abortions might also occur more frequently in these women. The higher incidence of abortions was associated with more severe forms of CL(P), ie, CL(P) with associated anomalies rather than isolated CL(P), and bilateral rather than unilateral CL. These results are compatible with the "multifactorial two-threshold" model with a lower threshold beyond which the malformation occurs and a higher one beyond which the embryo dies. The present results are in contrast with the reduced spontaneous abortion rates in families of CL(P) probands reported previously. The reduced rates may be due to selection of those families in which CL(P) embryos escaped spontaneous abortion and survived to birth, although the effects of compensatory reproduction or maternal recall bias in postnatal data cannot be ruled out completely.