In this population-based cohort study, children exposed to severe prenatal stress had higher BMI values and a higher prevalence of overweight when they approached the age of 10 years. The association was not significantly modified by gender, birth year, birth weight, gestational age, and maternal factors (age, education, income, and cohabitation status). The association was particularly strong when the exposure happened in the months just before conception.
Observational studies have suggested that the intrauterine life may be a critical period for the development of obesity later in life. 
Children born to women who were exposed to the 1944–45 Dutch famine had an increased risk of obesity later in life.
Although this finding was attributed to lack of energy or nutrition to the fetus during the siege, a programming effect of prenatal stress is a plausible alterative explanation. Fetal growth variables like birth weight were often used to estimate the role of prenatal exposures on the future risk of obesity but results have not been conclusive, 
These growth variables are convenient markers or surrogates for summing the interaction between the fetal environment and genetic influences, and their effects may often be subject to the interaction with other early risk factors, or the selection of different outcomes in childhood.
Prenatal factors like maternal gestational diabetes, 
maternal smoking during pregnancy,
and malnutrition 
have also been associated with obesity in later life. However, the inconsistent associations and variations in the magnitude of these estimates call for more investigations on the upstream causes of obesity during prenatal period.
Findings from experimental studies support the biological plausibility of the link between prenatal stress and obesity later in life. 
These studies suggest that glucocorticoid, one of the stress hormones, has a programming effect on obesity. 
Excess maternal glucocorticoid can enter the fetal circulation, which may cause endocrine dysregulation and influence the development of the hypothalamic-pituitary-adrenal (HPA) axis, as well as the metabolism later in life. 
This programming may consequently affect the individuals metabolism by promoting the conversion of proteins and lipids to usable carbohydrates, increase food-seeking behaviors, and inhibit insulin action on glucose uptake. 
It has also been shown that exogenous glucocorticoids in pregnant rats causes insulin resistance in the offspring, as well as epigenetic changes in the developing brain, 
which may lead to an increased susceptibility to obesity. The excessive maternal glucocorticiods in bereaved mothers 
may have such a direct fetal programming effect on obesity in the offspring, and maybe a plausible explanation for the findings we presented here. Additionally, bereavement often leads to more adverse behaviors like smoking and alcohol consumption in mothers, which may also contribute to the observed associations. 
It is interesting to observe that the risk of overweight did not emerge until the pre-pubertal age. Preliminary evidence, mainly from animal studies, has suggested that environmental pollutants during fetal life may cause the puberty to occur at a younger age.
Some pointed to differential endocrine regulatory mechanisms linked to pubertal development acting in the perinatal and the pre-pubertal period. 
Evidence from epidemiological studies also suggests that the prenatal period may represent an early window of susceptibility to long-term ‘programming’ of puberty development. 
For example, an abnormal prenatal environment of children born SGA, may alter the endocrine status and the sensitivity of the receptors for endocrine and metabolic signaling, which may affect maturation of brain and gonads. 
The biological explanation underlying this time-specific association remains unknown but prenatal stress may affect both the timing or the velocity of the pubertal growth spurt 
and the risk of future obesity,
which may be closely linked. 
One of the important findings was related to the timing of exposure where the months just before conception seem to be the most susceptible period. Previous studies have suggested that women become less sensitive to stress as pregnancy advances. 
The reactivity of the two major components involved in the maternal stress response, the HPA and sympathetic-adrenal-medullary axis, are dampened during pregnancy.
For example, the known decrease in vulnerability to acute stress induced by earthquake may reflect increasing protection of the mother and fetus from stress or other adverse influences during pregnancy. 
The Dutch Famine study found that exposure to maternal malnutrition during mid-pregnancy was associated with childhood obesity. 
Bereavement may lead to a similar pattern of excess stress hormones during the initial phase, as do other acute stressors like earthquake. It also causes long-term interruptions in the hormonal balance, leading to an allostatic load, 
which implies a high level of stress hormones in mothers. Thus the event of bereavement before pregnancy could lead to excessive glucocorticoids during early pregnancy. This may explain the higher ORs associated with pre-pregnancy stress in this study. Unfortunately, our study did not have enough statistical power to further differentiate the effect of the exposure in more narrow time windows around gestation.
The strengths of the study are its population-based longitudinal design, objective measurement of exposure, and the high quality data on endpoints that are recorded independent of the exposure. The study included virtually all school children in the Copenhagen municipality area, and selection bias is unlikely. The CSHRR is a unique data source for obesity research with detailed data on growth with a high validity. 
Information on exposure, death of relatives, is accurately recorded in Danish registers. 
One limitation of the study is the classification of overweight based on BMI values, as they might not be an optimal marker for body fatness in childhood due to the fact that BMI estimates not only the fat tissue, but also fat free mass tissue. 
Other limitations of the study include the relatively small size of the exposed cohort, lack of biomarkers of cortisol exposure, and lack of information about socio-economic status during the period of 1970–1979. Denmark is an affluent society with a comprehensive public health system that provides equal access to health care to all, independent of socio-economic status, and mortality rates are low among children and young adults.We also lacked data on lifestyles. However, bereavement may also lead to more adverse life styles that lie in the pathways between exposure and the outcome, thus these life styles should not necessarily be controlled for in the analyses.
Prenatal stress, like maternal bereavement during pregnancy, is expected to affect the fetus and increase the frequency of adverse birth outcomes. 
These factors may be in the pathways between prenatal stress and overweight and it can be argued that they should not be adjusted for in the analyses. Conversely, these factors also have many other causes that could reflect a lack of comparability at baseline in our study. Nevertheless, our results indicate that preterm birth or low birth weight are not strong intermediates.
In conclusion, our findings suggest that severe pre-pregnancy stress may increase the susceptibility to overweight in childhood. Overweight and obesity in childhood are associated with adult obesity and many other negative health consequences. 
In this study, we have focused upon one of the most severe and rare stress exposure. It is likely that many women with poor coping mechanisms may reach similar hormonal responses at lower levels of stress, which is more prevalent at the population level. 
. This should be taken into consideration for prevention strategies, especially in the light that recent experimental animal research has shown that those aberrant phenotypes induced in utero can be reversed.