The study aims to elucidate biological mechanisms in the aetiology of adverse neurodevelopmental outcomes in the offspring of multiple births of very low birth weight. First, risk factors for neonatal white matter damage and transient hypothyroxinemia of prematurity (two neonatal predictors of later severe motor and cognitive disability) will be investigated in a cohort of 443 twins and triplets, weighing less than 1500 grams at birth (155 complete sets of 334 infants). These infants were systematically evaluated for evidence of white matter damage according to standardized cranial ultrasound scan protocols during the neonatal period. Second, a sample of these multiple births (227 surviving children of 116 sets) will be evaluated at 7 years of age for cerebral palsy, cognitive functioning, other severe motor, hearing and vision impairments, and behavioral problems. All children will be examined by a pediatric neurologist and will undergo neuropsychological testing. Their mothers (or primary care-givers) will be asked to assess behavior and functioning. The effects on neurodevelopmental outcomes of pregnancy-specific and child-specific risk factors (including white matter damage and hypothyroxinemia), and the role of zygosity, will be investigated. Since twin-pairs are matched by nature on many maternal, perinatal and environmental variables, the effects of exposures can be investigated with strong control for known and unknown confounders.
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