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Prenatal Stress and Cerebral Palsy: A Nationwide Cohort Study in Denmark

From the Department of Epidemiology, Institute of Public Health, Danish Epidemiology Science Centre, University of Aarhus, Denmark (J.L., J.O.); Department of General Practice, Institute of Public Health, University of Aarhus, Denmark (M.V., C.O.); Pediatric Department, Holbaek University Hospital, Region Zealand, Denmark (D.H.P.); Department of Neurology, Aarhus University Hospital, Denmark (J.C.); Department of Obstetrics and Gynecology, Schools of Medicine and Public Health, University of California, Los Angeles, California (M.L.); Department of Community Health Sciences, Schools of Medicine and Public Health, University of California, Los Angeles, California (M.L.); and Department of Epidemiology, School of Public Health, University of California, Los Angeles, California (J.O.).

Address correspondence and reprint requests to Jiong Li, PhD, Department of Epidemiology, Institute of Public Health, The Danish Epidemiology Science Centre, The University of Aarhus, Denmark. E-mail: jl{at}soci.au.dk

Objectives: Exposure to prenatal stress may affect neurodevelopment of the fetus, but whether this exposure increases the risk of cerebral palsy (CP) later in life is unknown. We aimed to examine the association between maternal bereavement during the prenatal time period and CP in childhood.

Methods: We conducted a nationwide cohort study by linking information from nationwide registers. All 1,501,894 singletons born in Denmark from 1979 to 2004 were followed up from birth to the end of 2006. We identified 39,601 children whose mothers lost a close relative (child, spouse, parent, sibling) during pregnancy or up to 1 year before pregnancy and they were classified as the exposed group. The outcome of interest was the diagnosis of CP as registered in the National Hospital Register. We used Cox Regression to estimate the hazard ratios (HRs).

Results: Exposure to maternal bereavement after the loss of a child during the prenatal period was associated with an increased risk of CP among children born preterm without intrauterine growth retardation (HR 2.26, 95% CI, 1.09–3.79) and among children born at term with intrauterine growth retardation (HR 2.01, 95% CI, 1.04–3.89). Prenatal stress after maternal bereavement by loss of other relatives was not associated with an increased risk of CP.

Conclusions: Our data suggest that extremely severe stress in prenatal life could increase the susceptibility for CP among children born preterm or with impaired fetal growth.

Key Words: prenatal stress • bereavement • cerebral palsy • fetal programming • intrauterine growth retardation • preterm

Abbreviations: CP = cerebral palsy; IUGR = intrauterine growth retardation; HR = hazard ratio; CI = confidence interval; ICD = International Classification of Diseases; ACTH = adrenocorticotropic hormone.