Background

The etiology of type-2 diabetes is only partly known, and a possible role of prenatal stress in programming offspring for insulin resistance has been suggested by animal models. Previously, we found an association between prenatal stress and type-1 diabetes. Here we examine the association between prenatal exposure to maternal bereavement during preconception and pregnancy and development of type-2 diabetes in the off-spring.

Methods

We utilized data from the Danish Civil Registration System to identify singleton births in Denmark born January 1st 1979 through December 31st 2008 (N = 1,878,246), and linked them to their parents, grandparents, and siblings. We categorized children as exposed to bereavement during prenatal life if their mothers lost an elder child, husband or parent during the period from one year before conception to the child’s birth. We identified 45,302 children exposed to maternal bereavement; the remaining children were included in the unexposed cohort. The outcome of interest was diagnosis of type-2 diabetes. We estimated incidence rate ratios (IRRs) from birth using log-linear poisson regression models and used person-years as the offset variable. All models were adjusted for maternal residence, income, education, marital status, sibling order, calendar year, sex, and parents’ history of diabetes at the time of pregnancy.

Results

We found children exposed to bereavement during their prenatal life were more likely to have a type-2 diabetes diagnosis later in life (aIRR: 1.31, 1.01–1.69). These findings were most pronounced when bereavement was caused by death of an elder child (aIRR: 1.51, 0.94–2.44). Results also indicated the second trimester of pregnancy to be the most sensitive period of bereavement exposure (aIRR:2.08, 1.15–3.76).

Conclusions

Our data suggests that fetal exposure to maternal bereavement during preconception and the prenatal period may increase the risk for developing type-2 diabetes in childhood and young adulthood.

Background

To examine whether prenatal exposure to parental type 1 diabetes, type 2 diabetes, or gestational diabetes is associated with an increased risk of malignant neoplasm or diseases of the circulatory system in the offspring.

Methods/Principal Findings

We conducted a population-based cohort study of 1,781,576 singletons born in Denmark from 1977 to 2008. Children were followed for up to 30 years from the day of birth until the onset of the outcomes under study, death, emigration, or December 31, 2009, whichever came first. We used Cox proportional hazards model to estimate hazard ratios (HR) with 95% confidence intervals (95% CI) for the outcomes under study while adjusting for potential confounders. An increased risk of malignant neoplasm was found in children prenatally exposed to maternal type 2 diabetes (HR = 2.2, 95%CI: 1.5–3.2). An increased risk of diseases of the circulatory system was found in children exposed to maternal type 1 diabetes (HR = 2.2, 95%CI: 1.6–3.0), type 2 diabetes (HR = 1.4, 95%CI: 1.1–1.7), and gestational diabetes (HR = 1.3, 95%CI: 1.1–1.6), but results were attenuated after excluding children with congenital malformations. An increased risk of diseases of the circulatory system was also found in children exposed to paternal type 2 diabetes (HR = 1.5, 95%CI: 1.1–2.2) and the elevated risk remained after excluding children with congenital malformations.

Conclusions

This study suggests that susceptibility to malignant neoplasm is modified partly by fetal programming. Diseases of the circulatory system may be modified by genetic factors, other time-stable family factors, or fetal programming.

Background

It has been suggested that prenatal stress contributes to the risk of obesity later in life. In a population–based cohort study, we examined whether prenatal stress related to maternal bereavement during pregnancy was associated with the risk of overweight in offspring during school age.

Methodology/Principal Findings

We followed 65,212 children born in Denmark from 1970–1989 who underwent health examinations from 7 to 13 years of age in public or private schools in Copenhagen. We identified 459 children as exposed to prenatal stress, defined by being born to mothers who were bereaved by death of a close family member from one year before pregnancy until birth of the child. We compared the prevalence of overweight between the exposed and the unexposed. Body mass index (BMI) values and prevalence of overweight were higher in the exposed children, but not significantly so until from 10 years of age and onwards, as compared with the unexposed children. For example, the adjusted odds ratio (OR) for overweight was 1.68 (95% confidence interval [CI] 1.08–2.61) at 12 years of age and 1.63 (95% CI 1.00–2.61) at 13 years of age. The highest ORs were observed when the death occurred in the period from 6 to 0 month before pregnancy (OR 3.31, 95% CI 1.71–6.42 at age 12, and OR 2.31, 95% CI 1.08–4.97 at age 13).

Conclusions/Significance

Our results suggest that severe pre-pregnancy stress is associated with an increased risk of overweight in the offspring in later childhood.

Background

To assess the risk of developing Type-1 diabetes among children who were exposed to maternal bereavement during the prenatal or 1-year preconception period.

Methods

We identified N = 1,548,746 singleton births born in Denmark between January 1st 1979 through December 31st 2004, and their next of kin. Altogether, 39,857 children were exposed to bereavement during their prenatal life. The main outcome of interest was hospitalization for type-1 diabetes (ICD 8: 249; ICD 10: E10).

Results

We found the strongest association for type-1 diabetes among children exposed to traumatic father or sibling deaths (aIRR: 2.03, 1.22–3.38); the association was mainly seen for girls (aIRR: 2.91, 1.61–5.26).

Conclusions

We found evidence to suggest that female fetuses exposed to severe prenatal stress are at increased risk for developing type-1 diabetes.