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

Li, Jiong; Vestergaard, Mogens; Obel, Carsten; Precht, Dorthe Hansen; Christensen, Jakob; Lu, Michael C.; Olsen, Jørn

doi:10.1097/psy.0b013e3181a56ca1

Cited by 33 publications

(22 citation statements)

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“…Excessive glucocorticoids following stress in pregnant mothers may have such a programming effect on brain development (6)(7)(8)(9). In epidemiological studies, prenatal stress has been linked to congenital malformations (10), cerebral palsy (11), and psychiatric disorders including schizophrenia (12;13). Anxiety during pregnancy has been associated with ADHD phenotypical behavior in the offspring (14;15) but no published studies have evaluated the association between prenatal stress and the risk of ADHD.…”

Section: LImentioning

confidence: 99%

Attention-deficit/hyperactivity disorder in the offspring following prenatal maternal bereavement: a nationwide follow-up study in Denmark

Olsen

Vestergaard

et al. 2010

Eur Child Adolesc Psychiatry

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Severe prenatal stress exposure has been found to increase the risk of neuropsychiatric conditions like schizophrenia. We examined the risk of Attention-deficit/hyperactivity disorder (ADHD) in the offspring following prenatal maternal bereavement, as a potential source of stress exposure. We conducted a nationwide population-based cohort study including all 1 015 912 singletons born in Denmark from 1987 to 2001. A total of 29 094 children were born to women who lost a close relative during pregnancy or up to one year before pregnancy. These children were included in the exposed cohort and other children were in the unexposed cohort. We used Cox regression to estimate hazard ratios for ADHD, defined as the first-time ADHD hospitalization or first-time ADHD medication after 3 years of age. Boys born to mothers who were bereaved by unexpected death of a child or a spouse, had a 72% increased risk of ADHD (Hazard ratio [HR]=1.72, 95% confidence interval [CI]=1.09-2.73). Boys born to mothers who lost a child or a spouse during 0-6 months before pregnancy and during pregnancy had a HR of 1.47 (95%CI=1.00-2.16) and 2.10 (95% CI =1.16-3.80), respectively. Our findings suggest that prenatal maternal exposure to severe stress may increase the risk of ADHD in the offspring.Key words Attention-deficit/hyperactivity Disorder (ADHD); stress; bereavement; fetal programming; child psychiatry.Ms No. ECAP-D-09-00192R2, Prenatal stress and ADHD, 04042010 3, LiAttention deficit hyperactivity disorder (ADHD) is one of the most common childhood psychiatric disorders (1;2). This disease causes a number of adverse academic and vocational conditions in children, and exerts stress to the affected families and economic burden on society (3). The disorder has a substantial genetic component but epidemiological studies suggest that environmental factors operating in early life most likely contribute to the disease risk (3-5). Evidence from animal studies suggests that maternal stress during pregnancy may affect fetal neurodevelopment (6;7). One of the underlying mechanisms is termed as 'fetal programming', which occurs when the normal pattern of fetal development is disrupted by an abnormal stimulus or insult at critical time points (6;8). Excessive glucocorticoids following stress in pregnant mothers may have such a programming effect on brain development (6-9). In epidemiological studies, prenatal stress has been linked to congenital malformations (10), cerebral palsy (11), and psychiatric disorders including schizophrenia(12;13). Anxiety during pregnancy has been associated with ADHD phenotypical behavior in the offspring (14;15) but no published studies have evaluated the association between prenatal stress and the risk of ADHD.We hypothesized that prenatal stress had a programming effect on brain development (16-18) and could increase the risk of ADHD in childhood. We examined this hypothesis in a cohort study based on data from several nationwide registers in Denmark.Bereavement is a severe life event known to induce stress (...

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Section: LImentioning

confidence: 99%

Attention-deficit/hyperactivity disorder in the offspring following prenatal maternal bereavement: a nationwide follow-up study in Denmark

Olsen

Vestergaard

et al. 2010

Eur Child Adolesc Psychiatry

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171

131

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“…Interestingly, in this particular cohort, bereaved parents also had an increased risk for myocardial infarction, 23 epilepsy, 24 cancers, 25 psychiatric hospitalization, 26 hospitalization for type II diabetes, 27 and total mortality, 28 and their later children (born after the death of the index child) had an increased risk of congenital malformations, 29 epilepsy, 30 and cerebral palsy. 31 Although it is possible that the risk of all these conditions is related to severe stress, factors associated with the disease of the child or factors related to the sudden death not taken into account in the analyses may also have contributed.…”

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confidence: 99%

Stress and the risk of multiple sclerosis

Riise¹,

Mohr

Munger

et al. 2011

Neurology

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Objective: Several studies have shown that stressful life events are associated with a subsequent significant increase in risk of multiple sclerosis (MS) exacerbations. We wanted to study prospectively whether stress can increase the risk of developing the disease itself. Methods:We studied 2 cohorts of female nurses: the Nurses' Health Study (NHS) (n ϭ 121,700) followed from 1976 and the Nurses' Health Study II (NHS II) (n ϭ 116,671) followed from 1989. The risk of MS after self-report on general stress at home and at work in the NHS in 1982 was studied prospectively using Cox regression. Logistic regression was used to retrospectively estimate the effects of physical and sexual abuse in childhood and adolescence collected in the NHS II 2001. We identified 77 cases of MS in the NHS by 2005 and 292 in the NHS II by 2004. All analyses were adjusted for age, ethnicity, latitude of birth, body mass index at age 18, and smoking. Results:We found no increased risk of MS associated with severe stress at home in the NHS (hazard ratio 0.85 [95% confidence interval (CI)] 0.32-2.26). No significantly increased risk of MS was found among those who reported severe physical abuse during childhood (odds ratio [OR] 0.68, 95% CI 0.41-1.14) or adolescence (OR 0.77, 95% CI 0.46-1.28) or those having been repeatedly forced into sexual activity in childhood (OR 1.47, 95% CI 0.87-2.48) or adolescence (OR 1.21, 95% CI 0.68-2.17). Conclusions:These results do not support a major role of stress in the development of the disease, but repeated and more focused measures of stress are needed to firmly exclude stress as a potential risk factor for MS. Neurology Multiple sclerosis (MS) is a chronic autoimmune disease affecting the CNS with unknown causes. It appears that the etiology is multifactorial, including both genetic and environmental components.

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“…Maternal reports of daily "hassles" during pregnancy-a means of estimating mothers' exposure to everyday stressors-predicted lower scores on infant motor and mental development in the first year of life (5). More extreme stressors during pregnancy, such as loss of a close relative, are associated with severe neurologic deficits in offspring (6). These findings suggest that transmission of the increased burden of disease among socioeconomically disadvantaged individuals may involve maternal stress-immune-related mechanisms during pregnancy (7).…”

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confidence: 99%

Socioeconomic disadvantage, gestational immune activity, and neurodevelopment in early childhood

Gilman

Hornig

Ghassabian

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Children raised in economically disadvantaged households face increased risks of poor health in adulthood, suggesting that inequalities in health have early origins. From the child's perspective, exposure to economic hardship may begin as early as conception, potentially via maternal neuroendocrine-immune responses to prenatal stressors, which adversely impact neurodevelopment. Here we investigate whether socioeconomic disadvantage is associated with gestational immune activity and whether such activity is associated with abnormalities among offspring during infancy. We analyzed concentrations of five immune markers (IL-1β, IL-6, IL-8, IL-10, and TNF-α) in maternal serum from 1,494 participants in the New England Family Study in relation to the level of maternal socioeconomic disadvantage and their involvement in offspring neurologic abnormalities at 4 mo and 1 y of age. Median concentrations of IL-8 were lower in the most disadvantaged pregnancies [−1.53 log(pg/mL); 95% CI: −1.81, −1.25]. Offspring of these pregnancies had significantly higher risk of neurologic abnormalities at 4 mo [odds ratio (OR) = 4.61; CI = 2.84, 7.48] and 1 y (OR = 2.05; CI = 1.08, 3.90). This higher risk was accounted for in part by fetal exposure to lower maternal IL-8, which also predicted higher risks of neurologic abnormalities at 4 mo (OR = 7.67; CI = 4.05, 14.49) and 1 y (OR = 2.92; CI = 1.46, 5.87). Findings support the role of maternal immune activity in fetal neurodevelopment, exacerbated in part by socioeconomic disadvantage. This finding reveals a potential pathophysiologic pathway involved in the intergenerational transmission of socioeconomic inequalities in health.

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

Abstract: 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.

Cited by 33 publications

References 30 publications

Attention-deficit/hyperactivity disorder in the offspring following prenatal maternal bereavement: a nationwide follow-up study in Denmark

Attention-deficit/hyperactivity disorder in the offspring following prenatal maternal bereavement: a nationwide follow-up study in Denmark

Stress and the risk of multiple sclerosis

Socioeconomic disadvantage, gestational immune activity, and neurodevelopment in early childhood

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