Maternal oxidative stress during pregnancy associated with emotional and behavioural problems in early childhood: implications for foetal programming
Cindy Pham, Sarah Thomson, Sung‐Tong Chin, Peter Vuillermin, Martin O’Hely, David Burgner, Samuel Tanner, Richard Saffery, Toby Mansell, Sze-How Bong, Elaine Holmes, Peter D. Sly, Nicola Gray, Anne‐Louise Ponsonby, Barwon Infant Study Investigator Group, John B. Carlin, Mimi L.K. Tang, Fiona Collier, Amy Loughman, Sarath Ranganathan, Lawrence Gray
Abstract
Abstract Childhood mental disorders, including emotional and behavioural problems (EBP) are increasingly prevalent. Higher maternal oxidative stress (OS) during pregnancy ( mat OS preg ) is linked to offspring mental disorders. Environmental factors contribute to mat OS preg . However, the role of mat OS preg in childhood EBP is unclear. We investigated the associations between (i) mat OS preg and offspring EBP; (ii) social and prenatal environmental factors and mat OS preg ; and (iii) social and prenatal factors and childhood EBP and evaluated whether mat OS preg mediated these associations. Maternal urinary OS biomarkers, 8-hydroxyguanosine (8-OHGua; an oxidative RNA damage marker) and 8-hydroxy-2′-deoxyguanosine (8-OHdG; an oxidative DNA damage marker), at 36 weeks of pregnancy were quantified by liquid chromatography-mass spectrometry in a population-derived birth cohort, Barwon Infant Study ( n = 1074 mother-infant pairs). Social and prenatal environmental factors were collected by mother-reported questionnaires. Offspring total EBP was measured by Child Behavior Checklist Total Problems T-scores at age two ( n = 675) and Strengths and Difficulties Questionnaire Total Difficulties score at age four ( n = 791). Prospective associations were examined by multivariable regression analyses adjusted for covariates. Mediation effects were evaluated using counterfactual-based mediation analysis. Higher maternal urinary 8-OHGua at 36 weeks ( mat 8-OHGua 36w ) was associated with greater offspring total EBP at age four ( β = 0.38, 95% CI (0.07, 0.69), P = 0.02) and age two ( β = 0.62, 95% CI (−0.06, 1.30), P = 0.07). Weaker evidence of association was detected for 8-OHdG. Five early-life factors were associated with both mat 8-OHGua 36w and childhood EBP ( P- range < 0.001–0.05), including lower maternal education, socioeconomic disadvantage and prenatal tobacco smoking. These risk factor-childhood EBP associations were partly mediated by higher mat 8-OHGua 36w ( P- range = 0.01–0.05). Higher mat OS preg , particularly oxidant RNA damage, is associated with later offspring EBP. Effects of some social and prenatal lifestyle factors on childhood EBP were partly mediated by mat OS preg . Future studies are warranted to further elucidate the role of early-life oxidant damage in childhood EBP.