Abstract
Children born small for gestational age have a higher risk of intellectual disability. We investigated associations of birth weight for gestational age percentile and gestational age with risk of intellectual disability in appropriate-for-gestational-age (AGA) children. We included 828,948 non-malformed term or post-term AGA singleton children (including 429,379 full siblings) born between 1998 and 2009 based on data from the Swedish Medical Birth Register. Diagnosis of intellectual disability after 3 years of age was identified through the Patient Register. Using Cox regression models, we calculated hazard ratios (HRs) with 95% confidence intervals (CIs) of intellectual disability among children with different birth weight percentiles and gestational age in the whole population and in a subpopulation of full siblings. A total of 1688 children were diagnosed with intellectual disability during follow-up. HRs (95% CIs) of intellectual disability for the low birth weight percentile groups (10th–24th and 25th–39th percentiles, respectively) versus the reference group (40th–59th percentiles) were 1.43 (1.22–1.67) and 1.28 (1.10–1.50) in population analysis and 1.52 (1.00–2.31) and 1.44 (1.00–2.09) in sibling comparison analysis. The increased risk for low birth weight percentiles in population analysis was stable irrespective of gestational age. A weak U-shaped association between gestational age and intellectual disability was observed in population analysis, although not in sibling comparison analysis. These findings suggest that among AGA children born at term or post-term, lower birth weight percentiles within the normal range are associated with increased risk of intellectual disability, regardless of gestational age.
Highlights
Intellectual disability refers to a group of disorders characterized by significant cognitive limitations and limitation of adaptive functions that affects between 1 and 3% of the world’s population [1, 2]
Model was adjusted for interaction between gestational age and birth weight for gestational age percentile, maternal age at delivery, parity, educational level, country of birth, smoking during pregnancy, height, Body mass index (BMI) in early pregnancy, maternal diabetic and hypertensive diseases, as well as child’s sex, calendar period of delivery, onset of labor, and mode of delivery a P = 0.048. In this nationwide population-based study of non-malformed, term or post-term, AGA children, we found that children born with lower birth weight percentiles had a higher risk of intellectual disability, both when compared with the general population, and with their siblings
A weak U-shaped association between gestational age and intellectual disability was observed in population analysis, indicating that children born early term or post-term had a higher risk of intellectual disability, such pattern was not observed among siblings
Summary
Intellectual disability refers to a group of disorders characterized by significant cognitive limitations and limitation of adaptive functions that affects between 1 and 3% of the world’s population [1, 2]. Fetal growth restriction may affect brain development and impair brain maturation and cognitive function [3]. Small for gestational age (SGA), defined as birth weight for gestational age below the population’s 10th percentile, has been associated with lower IQ and intellectual disability [4, 5]. SGA is not identical to fetal growth restriction: some SGA infants are constitutionally small and have reached their growth potential, whereas larger infants, e.g., infants with appropriate birth weight for gestational age (AGA, i.e., birth weight for gestational age between 10th and 90th percentiles), may. Low birth weight percentiles within the range of AGA have been associated with higher risk of neonatal neurological morbidity, such as convulsion and hypoxic ischemic encephalopathy, but rarely been investigated for long-term neurological outcomes [5, 9]. The association between birth weight for gestational age percentile (hereinafter called birth weight percentile) and risk of intellectual disability in AGA children has, to the best of our knowledge, not been investigated in a nationwide population-based setting
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