When providing information to patients regarding the use of medications during pregnancy, one key element of the decision-making process is an appraisal of the risks associated with untreated psychiatric illness in the mother.  While there are risks associated with taking medications during pregnancy, untreated illness in the mother also carries some degree of risk. There is evidence to indicate that mothers with untreated psychiatric illness are more likely to have worse pregnancy outcomes and are at greater risk for certain obstetric complications; however, most studies have focused on women with major depressive disorder and bipolar disorder.  

There is a growing body of literature assessing the impact of maternal anxiety on pregnancy outcomes, which was recently reviewed by Grigoriadis and colleagues in the Journal of Clinical Psychiatry.   Articles reporting perinatal outcomes of women with and without antenatal anxiety (either diagnosed or self-reported using validated instrument) with prospectively collected data were identified.  A total of 306 articles were retrieved, and 29 articles were included in the meta-analysis. The full text of this excellent review is available online.  What follows here is a review of the findings of this meta-analysis.

Risk of Preterm Birth

Analyzing data from 16 pooled studies, antenatal anxiety was associated with increased odds for preterm birth, defined as birth occurring before 37 weeks of gestation (pooled odds ratio [OR] = 1.54; 95% confidence interval [CI], 1.39 to 1.70).  

Antenatal anxiety was associated with increased risk of spontaneous preterm birth (OR = 1.41; 95% CI, 1.13 to 1.75).  (Note: 70% to 80% of preterm births are spontaneous: due to preterm labor or preterm premature rupture of membranes, or less commonly cervical insufficiency.  The remaining preterm births are medically induced due to maternal or fetal issues, such as preeclampsia, abruptio placenta, or fetal growth restriction.)

Risk of Low Birth Weight

Antenatal anxiety (assessed as a continuous variable in 12 studies) was associated with lower infant birth weight (mean difference = ?55.96 g, 95% CI, ?93.62 to ?18.31 g; P = .004).  The infants of mothers with clinically diagnosed anxiety had lower birth weights than those born to mothers whose anxiety was self-reported (mean difference = ?143.47 g, 95% CI, ?240.27 to ?46.67 g versus ?30.42 g, 95% CI ?51.87 to ?8.97). 

When the outcome of low birth weight was defined as < 2,500 g, a pooled analysis of 11 studies, demonstrated increased risk for low birth weight among women with antenatal anxiety (OR = 1.80; 95% CI, 1.48 to 2.18, P < .00001).

Impact on Gestational Age

Antenatal anxiety had a small but statistically significant impact on gestational age (mean difference = ?0.13 wk; 95% CI, ?0.22 to ?0.04 wk).  When the outcome “small for gestational age” (SGA) was assessed, antenatal anxiety was associated with increased risk (7 studies, OR = 1.48; 95% CI, 1.26 to 1.74; P < .0001).

Impact on Head Circumference

Antenatal anxiety was associated with smaller head circumference (mean difference = ?0.25 cm; 95% CI, ?0.45 to ?0.06 cm).

Other Perinatal Outcomes

This meta-analysis found no significant associations between antenatal anxiety and preeclampsia, cesarean delivery, or Apgar scores at 1 or 5 minutes; however, the authors note that these outcomes were assessed based on 5 or fewer studies and they noted significant heterogeneity across the included studies. 

Discussion

This meta-analysis examined the impact of antenatal anxiety on a wide range of perinatal outcomes.  Looking at the individual studies included in the analysis, the vast majority of these studies demonstrated a negative effect of antenatal anxiety on risk of preterm birth, gestational age, birth weight, and head circumference, although some of the original studies were small and did not demonstrate statistical significance. In this pooled analysis, however, these observed associations were consistently significant, with little heterogeneity and few moderating factors affecting the findings. 

The findings of this study reveal a strong and robust association between antenatal anxiety and adverse perinatal outcomes.  In contrast, a similar meta-analysis looking at the effects of depression on perinatal outcomes did not find such consistent or robust evidence of adverse effects (Grigoriadis et al, 2013).  This raises the question of whether anxiety may be a stronger determinant of adverse perinatal outcomes than depression.  In this analysis, however, it was not possible to account for comorbidity. Because in perinatal women, anxiety and depression often occur together, it may be difficult to parse out the individual contributions of depression and anxiety. 

Anxiety disorders are common in pregnant and postpartum women; however, most women with anxiety disorders do not seek treatment during pregnancy.  This study, demonstrating a strong association between antenatal anxiety and adverse pregnancy outcomes, highlights the importance of screening for anxiety, as well as depression, in perinatal women.  Additional research is required to determine whether treatment of antenatal anxiety, either non-pharmacoloic or pharmacologic strategies, decreases the risk of adverse perinatal outcomes

 

Ruta Nonacs, MD PhD

 

Grigoriadis S, Graves L, Peer M, Mamisashvili L, et al.  Maternal Anxiety During Pregnancy and the Association With Adverse Perinatal Outcomes: Systematic Review and Meta-Analysis.  J Clin Psychiatry. 2018 Sep 4;79(5). Free Article

Grigoriadis S, VonderPorten EH, Mamisashvili L, et al. The impact of maternal depression during pregnancy on perinatal outcomes: a systematic review and meta-analysis. J Clin Psychiatry. 2013;74(4):e321–e341.