Two retrospective studies have found that prenatal exposure to stressful events is associated with increased risk of AD. Ward (1990)
compared data from prenatal records of 59 mothers of AD children to records of a matched sample of 59 mothers of healthy children. He found that the mothers of AD children reported having experienced significantly more family discord during the pregnancies with the AD children: 19 of the mothers of AD children, but only 2 of the control mothers, experienced discord during their pregnancies with their children (p
< 0.05). In a similar study, Beversdorf et al. (2005)
found that 188 mothers of AD children reported having experienced significantly more stressful life events–such as job loss or death of husband–during their pregnancies (44.7 events per 100 responses) than did 202 mothers of typically developing children (25.9 events per 100 responses; p
= 0.0007). The study also included a comparison group of 92 mothers of children with Down syndrome; the average number of stressful events reported by these mothers (26.1) was almost identical to that of control mothers. The authors report that the child’s age at the time the mothers reported on stressful life events they experienced during their pregnancies, which might potentially have affected mothers’ recall accuracy, was not, in fact, significantly correlated with the number of stressful life events reported.
These two studies are noteworthy, but they had important limitations. For example, the higher average number of stressful events that mothers reported having experienced during their pregnancies with AD children (Beversdorf et al., 2005
) could potentially have been due to (a) biased maternal retrospective reports, (b) a general tendency for mothers of AD children to experience more stressful life events, regardless of whether they are pregnant, or (c) a tendency for those mothers to experience more stressful life events in all
of their pregnancies, regardless of whether their children develop AD. Another difficulty with the research design used by Ward (1990)
and Beversdorf et al. (2005)
is that it cannot exclude the possibility that the elevated levels of maternal stress during pregnancy might be correlated with other etiologic factors, such as adverse post
natal environments and/or parental genotypes, which might actually be the important contributors to the development of AD in these children. (For example, mothers who experience more marital or financial problems while pregnant might continue to experience more of these problems after their children are born.) The stressors used in these studies also make it difficult to identify possible critical periods of prenatal development when exposure to stressors might be most likely to increase risk for AD. Many stressful life events do not have a precise time of occurrence, and even those that do, such as divorce or loss of job, may also have been preceded or followed by stressful periods associated with the event. There is a need for new research using designs less subject to these problems.
The most powerful tool for testing whether prenatal stress is a causal factor in a disorder such as AD would be a scientific experiment in which pregnant women were randomly assigned to conditions of high or low exposure to stress. Obviously, this would be neither ethical nor feasible. There is an alternative research strategy, however, that can help to overcome these key limitations of previous research on AD: using natural disasters as “experiments of nature” to investigate these questions in a way that is ethical, feasible and economical. Unlike most stressful events, disasters are likely to be independent of subjects’ genotypes, socioeconomic status, personality, or other confounding characteristics; disasters tend to strike in a manner that resembles the random assignment of subjects in a scientific experiment. Moreover, because the chronology and location of natural disasters are often available in public records, they can provide data on prenatal stressors that are not dependent on retrospective recall. Disasters can also be linked more precisely than most stressful events to specific periods of gestation when exposure to environmental stressors may be most likely to lead to a disorder.
Kinney et al. (2008)
used hurricanes and severe tropical storms as natural experiments to investigate whether AD is associated with exposure to stressful events during sensitive periods of gestation. The most destructive storms affecting Louisiana between 1980 and 1996 were identified using National Weather Service data. To measure the effect of exposure, AD prevalence rates in different cohorts were calculated using anonymous limited datasets on birth dates and birth parishes (counties) of children diagnosed with AD in the Louisiana state mental health system, together with corresponding census data on all live births for the same periods and parishes. The severity of prenatal storm exposure experienced by different cohorts of children was ranked using two storm factors: (a) the intensity of a storm’s impact on a parish, and (b) the vulnerability of the residents of a parish to a storm’s effects. Weather Service maps of storm tracks identified the parishes that were hit by a storm’s center and thus were likely to have experienced the most intense
effects of the storm. Mothers in Orleans Parish (which is geographically identical to New Orleans) were particularly likely to be vulnerable
to storms’ effects because, as seen with Hurricane Katrina in 2005, much of New Orleans is below sea level and subject to severe flooding. Moreover, a relatively high proportion of New Orleans residents is near or below the poverty line, and has fewer resources to cope with storms’ effects.
AD prevalence was found to increase significantly, in a dose-response fashion, with the severity of prenatal storm exposure, from (a) the control cohort that had no exposure to either storm factor (prevalence of 4.49 AD cases per 10,000 births), to (b) the cohort exposed to one or the other storm factor (AD prevalence of 6.06), to (c) the cohort exposed to both storm factors (prevalence of 13.32). The increase in AD risk with storm exposure was particularly large for children who had been exposed to storms in specific periods near the middle and end of gestation. Children who had been exposed to storms during gestation months 5–6 or 9–10 had a 3.83 times greater risk of developing AD than children who had been exposed to the same storms, in the same place, but during other months of gestation (p < 0.001).
These results complement evidence from research described later, which indicate that pregnancy and birth complications are associated with increased risk for AD, particularly if the complications occur either in a period of several weeks near the middle of gestation or during the several weeks just before birth. In the study by Beversdorf et al. (2005)
, mothers of AD children reported having experienced more stressful life events in the last several months of pregnancy than in the first three months. However, all studies to date on prenatal stress and AD had limits to their methods; for example, none obtained data on either the AD children’s siblings or factors that may influence an individual mother’s responses to stressful life events. In the Kinney et al. (2008)
study, it was not possible to ask individual mothers about personal storm-related hardships, their social and financial resources for coping with their hardships, or other possible teratogens such as toxins to which they might have been exposed as a result of the storm. These variables are likely to influence the physiological effects of a storm experience on a mother and her fetus. Moreover, because the study involved children with AD who had been seen in the state health system, children with AD who were treated privately would have been missed. However, any incompleteness in ascertainment of AD cases is unlikely to account for the study’s key findings, which involved comparisons of cohorts of children who were born in the same parishes and ascertained in the same manner.
If prenatal stress contributes to AD, one might expect that risk for AD would be very high in cohorts exposed to catastrophes such as earthquakes and tsunamis, particularly in the developing world, where people typically have less access to social and medical support in coping with such disasters. Unfortunately, there have been few studies on the prevalence of AD in developing countries, and no studies there on the effects of prenatal disaster exposure on risk for AD. Such studies are needed, though the logistics of such studies may prove difficult, particularly in developing countries that lack the mental health treatment and record-keeping systems to aid in ascertaining AD cases and estimating prevalence rates.
In summary, two different types of studies, using complementary research designs, have found significant associations between prenatal stress and increased risk for AD. Both types of studies also found evidence for vulnerable periods of gestation when exposure to maternal stressors was more strongly associated with risk for AD. These studies raise the question of whether an etiologic role for prenatal stress is consistent with what is known from other types of research regarding the effects of prenatal stress on postnatal development.