Does the evidence support in utero influences on later health and disease? A systematic review of highly cited Barker studies on developmental origins.

The developmental origins of health and disease hypothesis proposes that early exposure to adverse conditions during fetal development and early life have strong detrimental consequences on long-term health and susceptibility to chronic diseases. We conducted a systematic review to critically appraise Barker's highest cited publications using the risk-of-bias assessment tool (ROBINS-I) and investigate effects of overadjustment by later body weight. Our findings revealed that all included studies displayed high risks of bias, with particular concerns regarding confounding (8/8), selection of reported results (8/8), classification of exposure (7/8), selection of participants (5/8) and high rates of missing data (ranged from 15 to 87%). Later body weight was over-adjusted in most (6/8) of the studies. As all studies displayed high bias risk due to confounding, missing data and overadjustment, evidence is insufficient to support causal relationships between low birthweight and adult disease, warranting caution in clinical application. PROTOCOL REGISTRATION: PROSPERO CRD42023433179.