Intra-uterine exposure to dual fetal programming sequences among surviving co-twins

Objective. The dynamics of fetal programming following in utero demise of a co-twin are poorly understood. Methods. The authors examined fetal programming using a unique application of the change-point analysis method, and identified two types of fetal programming that occurred when a viable twin sibling died in utero, while the co-twin survived. Results. In one type, the initial twin fetal programming trajectory was maintained while in a subset of surviving co-twins a "switch" from a twin to a singleton fetal program (dual fetal programming exposure) was observed. The results suggest that the timing in utero of conversion from a twin to a singleton programming pattern occurred slightly earlier among oppositesex than in same-sex surviving co-twins. Conclusion. For the conversion from a twin to a singleton program to happen, the surviving co-twin must have attained a "critical mass" when the twin sibling died. Whereas, for same-sex surviving co-twins the critical mass for conversion was the 80th percentile of gestational-age specific birth weight, opposite-sex surviving co-twins converted at a lower critical mass (70th percentile). These novel findings warrant further study to confirm the new hithertofore unknown phenomenon of dual fetal programming sequence, and to determine the implications in terms of subsequent morbidity or mortality during infancy, childhood and adult life.