Interpretation
Meta-analyses have identified an association between antenatal anxiety and low birth weight (OR=1.80). The mechanism underlying this effect is known as “fetal programming”. Several studies using animal models have proved that maternal distress negatively influences infant outcomes in childhood and adulthood. Evidence suggests that this occurs via effects on the development of the fetal nervous system, and maternal mood disorders have also been shown to activate the maternal hypothalamic-pituitary-adrenal (HPA) axis and program the HPA axis and physiology of the fetus in an adverse way. Maternal anxiety during pregnancy may increase fetal exposure to maternal glucocorticoids, leading to low birth weight and higher glucocorticoid levels in the neonate. Cortisol levels in cord blood are increased in intrauterine growth retardation, implicating endogenous cortisol in fetal growth. Glucocorticoid levels normally rise over pregnancy, and glucocorticoid receptors are highly expressed in the placenta, mediating metabolic and anti-inflammatory effects. While lipophilic steroids easily cross the placenta, fetal glucocorticoid levels are much lower than levels in maternal circulation because of placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2), which converts active glucocorticoids (cortisol and corticosterone) to inert 11-keto forms (cortisone, 11-dehydrocorticosterone) . Studies of 11β-HSD-2 null mice provide evidence for a causal association between 11β-HSD-2, reduced birth weight, and anxiety-like behavior in adulthood . This finding is consistent with findings that antenatal maternal stress affects neurodevelopment .
A second area of knowledge concerns the effects of anxiety on infant birth weight. These studies can be classified according to the type of psychological stressor investigated. Some evidence suggests that major life events consistently predicted lower fetal growth or birth weight, whereas measures of perceived stress had small or negligible effects. However, chronic stressors, such as racial disparities, have been even more reliable predictors of low birth weight. Recent experimental evidence suggests that the nature of stressful life events, as well as the timing of exposure to such events, are important determinants of these type of psychological stressors effects. In the present study, the COVID-19 pandemic lockdown was considered as an important stressful event, where anxiety symptoms were increased in pregnant women. In addition, women with higher rates of trait anxiety were more likely to give birth to babies with a lower birth weight. Our findings are consistent with those of a study that explored the potential association between trait anxiety and low birth weight. However, that study did not assess state anxiety, and for trait anxiety, they used the State-Trait Personality Inventory (STPI) instead of the STAI questionnaire. In our study, although only trait anxiety showed a statistically significant correlation with birth weight percentile, state anxiety showed a certain trend for predicting low birth weight percentile.
The effect of trait anxiety on birth weight may be explained by the fact that trait anxiety is related to more prolonged and widespread symptoms, that may impact various aspects of wellbeing, and therefore can increase levels of glucocorticoids on maternal blood for longer periods, activating the fetal HPA axis for a longer period. However, this hypothesis needs further research to be confirmed.
On the other hand, exposure to psychological stressors can be a predictor of increased birth weight when controlling for gestational age. There is data suggesting that the fetoplacental-maternal unit may regulate fetal growth according to the type of stressful event and even increase fetal growth in response to maternal stress due to major stressful events.
Regarding the effect of anxiety timing on birth weight, our study shows a certain correlation between the timing of anxiety symptoms (gestational age at the beginning of the lockdown) and birth weight percentile, indicating that the earlier the stressful event occurs during pregnancy, the lower the birth weight percentile. However, when analyzing the effect of prenatal anxiety timing in other studies, data were inconsistent. Some studies suggest that psychosocial distress (anxiety and depression symptoms) during late pregnancy (30th week of gestation) is a predictor of low birth weight. On the other hand, gestation lengths and predicted birth weight was lower for participants exposed to a stressful event, such as an ice storm, at an earlier gestational age (during early to mid-pregnancy), as compared to the third trimester. Therefore, it is likely that, in a stressful event, such as a natural disaster or a lockdown due to a pandemic, the earlier the gestational age at which the mother is exposed to such stressful event, the lower the birth weight percentile.
In this sense, we have included in the analyses birth weight percentiles adjusted for gestational age and gender, since the effect on birth weight for preterm neonates may have led to bias in many of the studies already published, and our aim was to focus exclusively on low birth weight.
Antenatal anxiety and depression symptoms may place a greater financial burden on healthcare systems. Consequently, an early identification of pregnant women with anxiety or depression symptoms and access to perinatal mental health services are crucial for reducing the impact of perinatal mental disorders. There are already several screening strategies for depression and anxiety during pregnancy, and there is evidence suggesting that an appropriate and timely intervention may minimize symptoms during pregnancy and the postpartum period. Although improvement of anxiety symptoms also improves neonatal outcomes is not yet clear, some mindfulness-based interventions for stress management have shown a reduction in the percentage of neonates with a birth weight below the 10th percentile.
Since the conditions in this study were very specific, as it was conducted during a lockdown due to a global pandemic, the external validity of our results may be limited. Nevertheless, the results of this study may be extrapolated to a population living with chronic stress and showing a higher prevalence of anxiety.
In conclusion, our results show that anxiety during pregnancy impacts birth weight. More specifically, trait anxiety, which is associated with personality traits, is a predictor for low birth weight. A deeper understanding of the mechanisms underlying a stressful event that may impact neonatal outcomes may help to promote the development of interventions that may reduce the effect of psychosocial stressors during pregnancy, thus improving maternal and neonatal outcomes. Regarding the effect of anxiety timing on birth weight, our data seems to suggest that the earlier the anxiety symptoms appear, the lower the birth weight. However, this hypothesis requires further research to be confirmed.