Groningen Health of children born to subfertile couples

Aim: The aim of this study was to assess the associations between dysmorphic features and neurological, mental, psychomotor, and behavioural development in order to improve our understanding of aetiological pathways leading to minor developmental problems. Method: In our cross-sectional study, 272 generally healthy 2-year-olds (143 males, 129 females; median gestational age 39 weeks (range 30-43)), born after a parental history of subfertility either with or without fertility treatment, were examined. Dysmorphic features were classified as abnormalities (clinically relevant or not), minor anomalies, or common variants according to Merks’ classification system. Hempel’s neurological assessment resulted in a neurological optimality score (NOS) and fluency score. Mental and psychomotor development were assessed with the Dutch version of the Bayley Scales of Infant Development and behavioural development with the Achenbach Child Behaviour Checklist. Results: Of the different types of dysmorphic feature, clinically relevant abnormalities were most strongly associated with a lower NOS (difference: -2.53, 95% confidence interval (CI): -4.23 ; -0.83) and fluency score (difference: -0.62, 95% CI: -1.1 ; -0.15). The presence of one or more abnormalities (clinically relevant or not) or one or more common variant was significantly associated with a lower NOS, and the presence of three or more minor anomalies was associated with lower fluency scores. Dysmorphic features were not associated with mental, psychomotor, or behavioural development. Interpretation: As dysmorphic features originate during the first trimester of pregnancy, the association between dysmorphic features and minor alterations in neurodevelopment may suggest an early ontogenetic origin of subtle neurological deviations.