Interpretation
Several studies have focused on effects of anxiety on low birthweight and premature birth, both of which have been recognized as important markers for later mental health problems.5, 18,19 Mean birthweight was lower for infants born to mothers reporting severe symptoms of anxiety, and the lowest birthweight was found for exposure to anxiety symptoms as reported in the 30thgestational week. During the third trimester in a pregnancy, the fetus grows rapidly and triples its weight, and these findings suggest that severe symptoms of anxiety later in pregnancy increase the chance of a lower birthweight. The findings persisted following control for multiple covariates, such as smoking and alcohol exposure, birth complications, and the socio-economic status of the mother. These findings are also in accordance with a meta-analysis performed by Ding et al.5 which found that maternal anxiety was associated with an increased probability of low birthweight. We also found maternal anxiety in pregnancy to be linked to shortened gestational age in the full cohort, with wider overlapping confidence intervals in the sibling control analyses. After multiple imputations maternal anxiety at week 30 in pregnancy was associated with gestational age, as was found in that earlier meta-analysis5.
There are several hypotheses regarding the influence of maternal anxiety on fetal growth and gestation. One such mechanism involves changes to maternal hypothalamic-pictuary-adrenal (HPA) axis activity.20 That is, it is suggested that maternal anxiety during pregnancy increases the production of stress hormones such as cortisol and catecholamines.21,22 Animal models have found these stress hormones to influence uterine blood flow and immunologic functioning, thus potentially increasing risk of shortened gestational length and lower fetal growth.23Another potential explanation for this link, could be through higher risks of infections due to stress. Studies suggests that high levels of stress may be linked to lower immune funcuion24 , and increased infections during pregnancy that could shorten gestation.25
The second aim was to apply a sibling comparison design to compare siblings that differed in exposure to maternal anxiety. This made it possible to estimate associations without the potential confounding by unmeasured constant family effects. Several studies have found individuals high in stress and anxiety to be at risk of poor health outcomes26,27 and to display higher-risk behaviours.28 Thus, several confounders needed to be taken into consideration, including shared-family confounding.
We found that exposure to maternal anxiety was associated with lower birthweight, also when family effects were controlled in sibling analyses. The association increased after controlling for smoking and alcohol exposure. However, the effect became non-significant after parity, birth complications, child’s sex, and preeclampsia were controlled for. These associations were also examined for gestation age; however unlike the case of birthweight, the different set of adjustments did not change the magnitude of the associations. It is possible that for the sibling analyses, these associations were not significant due to a smaller sample size. In fact, after multiple imputations to account for missing, maternal anxiety at week 30 in pregnancy was significantly associated with shorter gestational age.
Self-reported exposure to maternal anxiety during pregnancy has therefore found to be associated with an increased risk of low birthweight and shorter gestation age. This finding is in accordance with previous studies examining prenatal anxiety and birth outcomes.29,30,31 However, the association for prenatal anxiety and gestation was not significant in the sibling sub-sample, this could reflect the fact that a low-risk sample, in which few children are born preterm, was used and it could also reflect the fact that perinatal care was provided for these women to reduce the risk of preterm birth. However, it should be noted that the findings are conflicting and some studies have found only small associations between prenatal maternal anxiety and preterm birth30 and some have found no such association.31