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Original Investigation | Meta-analysis

Neonatal Outcomes in Women With Untreated Antenatal Depression Compared With Women Without Depression A Systematic Review and Meta-analysis

Alexander Jarde, PhD1; Michelle Morais, MD1; Dawn Kingston, PhD2; Rebecca Giallo, PhD3; Glenda M. MacQueen, MD4; Lucy Giglia, MD5; Joseph Beyene, PhD6; Yi Wang, BHSc1; Sarah D. McDonald, MD1
[+] Author Affiliations
1Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada
2Faculty of Nursing, University of Alberta, Edmonton, Alberta, Canada
3Healthy Mothers Healthy Families Group, Murdoch Childrens Research Institute, Parkville, Victoria, Australia
4Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada
5Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
6Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
JAMA Psychiatry. 2016;73(8):826-837. doi:10.1001/jamapsychiatry.2016.0934.
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Importance  Despite the prevalence of antenatal depression and the fact that only one-third of pregnant women with depression consider it acceptable to take antidepressants, the effect of untreated depression on neonatal outcomes remains to be addressed thoroughly.

Objective  To undertake a systematic review and meta-analysis to understand the effect of untreated depression on neonatal outcomes.

Data Sources  We executed our search strategy, with emphasis on its exhaustiveness, in MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health, Cochrane Central Register of Controlled Trials, and Web of Science. The search was conducted in July, 2015.

Study Selection  We included randomized and nonrandomized studies that examined neonatal outcomes in women with depression receiving neither pharmacological nor nonpharmacological treatment compared with women without depression.

Data Extraction and Synthesis  Two reviewers independently screened titles and abstracts, assessed full-text articles, extracted data, and assessed their quality using a modified version of the Newcastle-Ottawa Scale. We pooled data using random-effects meta-analyses, quantified heterogeneity using the I2 statistic, and explored it with subgroup analyses by type of assessment of depression, severity, reported conflicts of interest, and study quality.

Main Outcomes and Measures  Primary outcomes were preterm birth before 37 weeks and before 32 weeks, small and large for gestational age, low birth weight, and neonatal intensive care unit admission.

Results  Of the 6646 titles initially identified, 23 studies met inclusion criteria, all observational, with a total of 25 663 women. Untreated depression was associated with significantly increased risks of preterm birth (odds ratio [OR], 1.56; 95% CI, 1.25-1.94; 14 studies; I2, 39%) and low birth weight (OR, 1.96; 95% CI, 1.24-3.10; 8 studies; I2, 48%), with a trend toward higher risks for exposure to more severe depression. While the odds of preterm birth more than doubled in studies reporting conflicts of interest (OR, 2.50; 95% CI, 1.70-3.67; 5 studies; I2, 0%), studies not reporting such conflicts showed more moderate results (OR, 1.34; 95% CI, 1.08-1.66; 9 studies; I2, 30%).

Conclusions and Relevance  Our results contrast with what is, to our knowledge, the only previous systematic review that examined the question of untreated depression because we found significant risks of 2 key perinatal outcomes, preterm birth and low birth weight. These are important results for pregnant women and clinicians to take into account in the decision-making process around depression treatment.

Figures in this Article

Figures

Place holder to copy figure label and caption
Figure 1.
Flow Diagram of Study Identification and Selection, Including Reasons for Exclusion in Systematic Review

A study could be excluded for more than 1 reason. CENTRAL indicates Central Register of Controlled Trials; CINHAL, Cumulative Index to Nursing and Allied Health.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Results of Subgroup Analyses for Preterm Birth and Low Birth Weight

OR indicates odds ratio; RR, relative risk.

aAfter removing 3 low-quality studies: OR, 1.34; 95% CI, 1.04-1.72.

bAfter removing 2 low-quality studies: OR, 2.66; 95% CI, 1.50-4.73.

cAfter removing 5 low-quality studies: P = .03.

dAfter removing 3 low-quality studies: OR, 2.18; 95% CI, 1.53-3.11.

eAfter removing 3 low-quality studies: P = .22.

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Untreated Antenatal Depression on Neonatal Outcomes: evidence based on quality effect model
Posted on June 15, 2016
Xu Chang
Zhongnan Hospital of Wuhan University
Conflict of Interest: None Declared

To better understand untreated antenatal depression and risk of neonatal outcomes, Jarde et al. used meta-analysis of 23 observational studies [1]. The study, was wonderfully conducted, informative and valuable, suggested that untreated antenatal depression may increase the risk of preterm birth and low birth weight [1].

They employed classical random-effect (RE) model with inverse variance as a weighting scheme to pool the evidence [2]. Under such a model, large studies are allocated more weight than smaller studies. The results then tend to larger studies [2], without taking into account study quality. And more importantly, RE model may lower the coverage probability [3]. This may lead to overconfident as well as biased results [4]. We would like to re-pool the evidence by a quality effect (QE) model, proposed by Suhail et al. [4], which considering both study scale and quality.

We used the QAT score as quality estimator provide in Table 1. By running the QE model, we finally get similar results with the RE model: Compared to depression-free woman, untreated depression significantly increases the risks of preterm birth (ORQE=1.52; 95% CI: 1.20-1.92) and low birth weight (ORQE=2.28; 95% CI, 1.38-3.75). Undoubtedly, our results strengthened their conclusions and quality of evidence.

Therefore, as Jarde et al. [1] claimed, “These are important results for pregnant women and clinicians to take into account in the decision-making process around depression treatment”.

Reference

1.Jarde A, Morais M, Kingston D, et al. Neonatal Outcomes in Women With Untreated Antenatal Depression Compared With Women Without Depression: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2016; In press. doi: 10.1001/jamapsychiatry.2016.0934.
2.DerSimonian R, Laird N. Meta-analysis in clinical trials. Controlled Clinical Trials. 1986; 7:177–188.
3.Brockwell SE, Gordon IR. A comparison of statistical methods for meta-analysis. Stat Med. 2001; 20(6): 825-840.
4.Doi SA, Barendregt JJ, Khan S, et al. Advances in the meta-analysis of heterogeneous clinical trials II: The quality effects model. Contemp Clin Trials. 2015; 45(Pt A): 123-129.
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