The placenta and neurologic and psychiatric outcomes in the child: study design matters.

Much information exists about functions of the human placenta and about potential mechanisms by which the placenta may influence human health or disease, including developmental disorders of brain. Recent studies indicate a high frequency of placental pathology in infants with developmental brain disorders, or with risk factors for such disorders. However, most clinical studies of the association of placental features with adverse neurologic or psychiatric outcome have substantial methodologic limitations. We discuss issues of study design as they relate to studies of the placenta and human brain disorders. In addition to the need for further consensus on procedures and terminology for placental evaluation, there are a number of special features that make clinical studies of the association of placental features with neurologic and psychiatric disorders especially difficult: most such disorders are not diagnosed until months or years after the majority of placentas have been discarded; these disorders are individually uncommon, so that prospective studies - needed to provide denominator data to enable estimation of risks - will require very large sample sizes; the administrative structures required to relate features of the placenta with clinical outcome will be complicated and costly. We offer some suggestions concerning study design in the face of these practical difficulties. Systematic and methodologically rigorous exploration of the role of the placenta in human developmental brain disorders has scarcely begun. A new generation of studies, difficult but potentially enormously rewarding, will be needed for clinical investigations of the placenta and fetal brain development. Published by Elsevier Ltd.