Serious Life Events and Congenital Malformations
Serious Life Events and Congenital Malformations
abstract & commentary
Synopsis: Severe emotional stress during pregnancy, especially that related to the death of a child, might cause congenital fetal malformations, especially those of the cranial neural crest.
Source: Hansen D, et al. Lancet 2000;356:875-880.
In this study, hansen and colleagues posited that emotional stress during organogenesis could cause congenital malformations. In a previous prospective study, they found that maternal stress during pregnancy was associated with a low head circumference and suboptimal neurological results at birth, indicating an effect on development of the fetal central nervous system. Hansen et al sought to extend these findings by examining the effect of psychosocial stress upon the prevalence of malformations, particularly those of the cranial neural crest (e.g., cleft lip, cleft palate, and congenital heart malformations). They postulated that stress during the period of organogenesis is the most important factor.
To address these hypotheses, they conducted a large case-control study using a registry covering the whole population of Denmark from 1980 to 1992. They selected only severe life events such as death or life-threatening diseases in partners or children as stressors, because "these life events probably cause stress in everybody, regardless of personality, ability to cope, or sense of coherence, social support, and network." Altogether, 3560 exposed and 20,299 control singleton pregnancies comprised the study cohort.
The strongest association was seen for women exposed to the death of an older child during the time of organogenesis. The odds ratio of cranial neural crest malformations during the first trimester was 4.75 (confidence interval [CI] 1.63-13.8) and during the second trimester, 4.26 (CI 0.57-31.9). For all congenital malformations, the odds ratio was 2.61 (CI 1.30-5.23) during the first and 1.60 (CI 0.38-6.73) during the second trimester. However, the unexpected death of a child during the first trimester was associated with an odds ratio for cranial neural crest defects of 8.36 (CI 2.41-29.0) during the first trimester, with an odds ratio of 5.10 (CI 2.24-11.6) for all congenital malformations. Events in partners were not associated with an increased odds ratio for either cranial neural crest or other congenital malformations.
COMMENT by Sarah L. Berga, MD
There is a tendency in modern medicine to underestimate the health consequences of mental states. Do we believe that mood and mind-set have no bodily manifestations? Certainly, we understand that if mood states compromise eating or lead to behaviors such as excessive alcohol intake or smoking, there may be a health price to pay. In these instances, we attribute the damage to the lack of adequate nutrition or the effect of known toxins. We think less about the consequences of psychogenic stress. In fact, many people, including some physicians, contend that there is "no such thing" as stress. Because of this commonly held belief, we routinely fail to develop models of disease processes that account for behavioral factors such as stress. However, since much of my research has focused on understanding the endocrine manifestations or concomitants of psychogenic states, including stress, I take issue with this stance. While the endocrine adaptations elicited by psychosocial stressors are not easy to capture, even with sophisticated modern methodologies, they are there. Stress increases cortisol, reduces thyroidal output, suppresses reproductive drive, and, in short, alters the endocrine pattern of every known hormone to some extent.
Given my interest in this topic, I was drawn to the above article. Even I had not thought that maternal stress could be a cause of congenital malformations. But the data are compelling. First, Hansen et al demonstrate a dose-response relationship between the degree of stress or grief, and the relative risk of cranial neural crest malformations. Second, there is strong biological plausibility. Excess cortisol is teratogenic and even subclinical maternal hypothyroidism has been demonstrated to compromise fetal neural development.
What are the practical implications of the present research finding? Hansen et al studied a worse case scenario, but it is very likely that these findings hold for stress not related to extremely unfortunate and unpredictable events. For instance, these data provide yet another reason to avoid ovulation induction in women whose stress is so extreme that they have developed anovulation. Second, we have to wonder if and worry that lesser amounts of stress have more subtle, but still deleterious, consequences upon fetal development. If so, it would behoove us to identify and actively manage stress in pregnant women, particularly during the first trimester. To date, we have mostly owned the metabolic component of this interaction by emphasizing the role of good nutrition. However, stress comes in at least two basic flavors, that which is externally derived and that which is internally generated. Both forms can be ameliorated, the first via public health measures and the second by buttressing individual mental health. It is vogue these days to address the latter by way of various meditative strategies that allow one to adapt to life’s unavoidable misfortunes. Perhaps we should be more active about incorporating at least some of these strategies into clinical practice. Further, it seems that in America we think very little about societal strategies for reducing social stress. In our monkey model of stress-induced anovulation, social stress was much more powerful than metabolic stress. The argument has been made that all medical treatments should address the psychosocial compartment. It is difficult to disagree. Stress of all flavors cannot be entirely prevented, but it can be actively managed and moderated.
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