Twins and neurodevelopmental outcomes: the effect of IVF, fetal growth restriction, and preterm birth.

This invited review aimed at presenting the evidence concerning neurodevelopmental outcomes, particularly cerebral palsy (CP), motor disability, cognitive impairment, mental retardation, any major disability, blindness and deafness in cases of twins, conceived after in vitro fertilization, presenting fetal/intrauterine growth restriction (FGR/IUGR) or being prematurely born. FGR/IUGR, prematurity and zygosity affect neurodevelopmental outcome; CP is higher in term infants, those presenting with FGR/IUGR, as well as in survivors of intrauterine co-twin death; cognitive ability of twins versus singletons mainly relates to confounding factors, as FGR/IUGR and prematurity, while evidence for differences in behavioral and psychiatric disorders between twins and singletons is limited. The impact of IVF per se has not been documented. Nevertheless, available literature, usually of heterogeneous and retrospective nature, diverges in the criteria for neurodevelopmental delay. Furthermore, differences in selection/exclusion criteria and small mixed cohorts, including the full range of complications, make comparison of the existing studies difficult. Future studies should focus in confirming the lack of IVF impact on twins' neurodevelopment and general health, in comparing long-term outcome of naturally conceived twins with those conceived following assisted reproduction techniques and in including evaluation of individual, longitudinal trajectories of growth, and development. In this respect, worldwide population-based registries will enable more precise description of neurodevelopmental outcomes among twins.