Effects of in vitro fertilization and maternal characteristics on perinatal outcomes: A population-based study using siblings

Objective To study birthweight in consecutively born sibling singletons conceived with and without in vitro fertilization (IVF) to disentangle the effects of maternal characteristics from those of the IVF treatment itself. Design Population-based study. Setting Not applicable. Patient(s) Firstborn and secondborn children from a 9-year birth cohort (1999-2007) comprising of 272,551 women who conceived two siblings. Intervention(s) No intervention; children were conceived naturally or through IVF. Main Outcome Measure(s) Birthweight. Result(s) The study included 545,102 children born by natural conception (NC) or IVF with the data set obtained from the population-based Netherlands Perinatal Registry (PRN) containing information on pregnancies, deliveries, and neonatal outcomes. We used two approaches: [1] the intersibling approach and [2] the sibling-ship approach. In the first approach we included children born to four groups of mothers who conceived in the following order (numbers indicate birth order): NC1-NC2 (reference, n = 254,721), IVF1-NC2 (n = 1342), NC1-IVF2 (n = 471), and IVF1-IVF2 (n = 687). Several comparisons were made to interpret the effects of IVF and maternal characteristics separately. In the second approach, perinatal outcomes of IVF children (n = 1,813) were compared with those of their NC siblings (n = 1,813). The intersibling analyses suggested an association between maternal characteristics and a lower birthweight, with estimates of the maternal effect ranging from -7 g (95% CI, -40; 26) to -101 g (95% CI, -170; -32). Neither the intersibling analyses nor the sibling-ship analyses indicated an additional adverse effect of IVF treatment itself. Conclusion(s) Maternal characteristics of subfertile women are associated with a lower birthweight. In vitro fertilization treatment itself does not additionally contribute to a lower birthweight in the offspring.