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.