Associations Between Maternal Depression, Antidepressant Use During Pregnancy, and Adverse Pregnancy Outcomes

Vlenterie, Richelle; Gelder, Marleen M.H.J. van; Anderson, Hugh; Andersson, Linda; Broekman, Birit F. P.; Dubnov‐Raz, Gal; Marroun, Hanan El; Ferreira, Ema; Fransson, Emma; Heijden, F.M.M.A. van der; Holzman, Claudia; Kim, J. Jo; Khashan, Ali S.; Kirkwood, Betty; Kuijpers, Harold J. H.; Lahti‐Pulkkinen, Marius; Mason, Dan; Misra, Dawn P.; Niemi, Maria; Nordeng, Hedvig; Peacock, Janet L.; Pickett, Kate E.; Prady, Stephanie L.; Premji, Shahirose; Räikkönen, Katri; Rubertsson, Christine; Sahingoz, Mine; Shaikh, Kiran; Silver, Richard K.; Slaughter-Acey, Jaime C.; Soremekun, Seyi; Stein, Dan J.; Sundström‐Poromaa, Inger; Sutter-Dallay, Anne Laure; Tiemeier, Henning; Uğuz, Faruk; Varela, Pinelopi; Vrijkotte, Tanja G. M.; Winterfeld, Ursula; Zar, Heather J.; Zervas, Iannis M.; Prins, Judith B.; Pop-Purceleanu, Monica; Roeleveld, Nel

doi:10.1097/aog.0000000000004538

Cited by 32 publications

(21 citation statements)

References 67 publications

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“…These findings are included for comparison only. Because general population comparisons do not adjust adequately for confounding, they should not be used as a sole basis for making clinical decisions, see discussion) Study (year) Outcomes N AD type Psychiatric control Sibling control Main findings Kautzky (2022) [ 106 ] PNAS 17 SSRI, SNRI Y N Statistically significant associations with preterm birth (OR = 2.36, 95% CI 1.35–4.15), admission to neonatal intensive care (OR = 2.64, 95% CI 1.58–4.40), respiratory problems (OR = 2.85, 95% CI 1.26–6.43), lower gestational age (MD = −0.36, 95% CI −0.81 to 0.08), and lower 5-minute Apgar score (MD = −0.32, 95% CI −0.54 to −0.11) in untreated maternal depression comparisons Vlenterie (2022) [ 107 ] GA, BW, SGA, Apgar score 215 Any N N In general population comparisons, preterm birth associated with prenatal depression (OR = 1.6, 95% CI 1.2–2.1), untreated prenatal depression (OR = 2.2, 95% CI 1.7–3.0), and prenatal antidepressant use for any indication (OR = 1.4, 95% CI 1.1–1.8) Low (<5) 5-minute Apgar score associated with prenatal depression (OR = 1.5, 95% CI 1.3–1.7), and prenatal antidepressant use for any indication (OR = 1.6, 95% CI 1.1–2.5) but not untreated prenatal depression Preterm birth associated with prenatal SSRI use for depression (OR = 1.6, 95% CI 1.0–2.5) and prenatal SSRI use for any indication (OR = 1.9, 95% CI 1.2–2.8) Low 5-minute Apgar score associated with prenatal SSRI use for any indication (OR = 1.7, 95% CI 1.1–2.8) AD use during pregnancy not associated with low BW or SGA De Vries (2021) [ 108 ] Congenital heart defects a 20 Any N N In general population comparisons, statistically significant association between prenatal AD exposure and congenital heart defects (OR = 1.28, 95% CI 1.17–1.41) Statistically significant associations for SSRIs (OR = 1.25, 95% CI 1.15–1.37), SNRIs (OR = 1.69, 95% CI 1.37–2.10), paroxetine (OR = 1.57, 95% CI 1.20–1.97), fluoxetine (OR = 1.36, 95% CI 1.08–1.72), sertraline (OR = 1.29, 95% CI 1.14–1.45), and bupropion (OR = 1.23, 95% CI 1.01–1.49). TCAs, citalopram, escitalopram, and venlafaxine not associated with an increased risk Leung (2021) [ 109 ...…”

Section: What Types Of Study Are To Be Preferred?mentioning

confidence: 99%

Should Antidepressants be Avoided in Pregnancy?

Besag

Vasey²

2022

Drug Saf

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Many (> 40%) women discontinue antidepressants during pregnancy because of concerns about effects on the foetus, based on information from inadequately-controlled studies. The sibling-control study design provides the best control for confounding factors, notably maternal depression. The purpose of this review was to investigate the evidence from sibling-control analyses for adverse outcomes in offspring associated with antidepressant exposure during pregnancy. Fourteen sibling-control studies were identified through searches of PubMed and Embase. Outcomes included preterm birth, small for gestational age, neonatal size, birth defects, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), behavioural problems, neurodevelopmental deficits, and scholastic attainment. For the majority of these outcomes, no statistically significant associations were found when comparing exposed and unexposed siblings. Single studies reported associations with preterm birth, reduced gestational age, ADHD, anxiety at 36 months, and lower mathematics test scores, which persisted in the sibling-control analyses. However, differences were small and possibly not clinically significant. Moreover, effects of residual confounding could not be excluded. These findings provide evidence that many of the previously reported associations between prenatal antidepressant exposure and adverse outcomes in offspring are no longer statistically significant when exposed offspring are compared with unexposed siblings. The few statistically significant differences in sibling-control analyses were generally small with doubtful clinical significance. Decisions on antidepressant treatment during pregnancy should be made individually, based on evidence from properly controlled studies, not on misleading information based on studies that have not controlled adequately for confounding factors.

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Section: What Types Of Study Are To Be Preferred?mentioning

confidence: 99%

Should Antidepressants be Avoided in Pregnancy?

Besag

Vasey²

2022

Drug Saf

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“…However, newborns born to depressed mothers without antidepressant treatment had comparable odds ratios for low Apgar scores. In another large meta-analysis examining the effects of depression and antidepressant use in pregnancy, low Apgar scores were found particularly with SSRI use (fluoxetine and sertraline) compared to other antidepressant drugs [ 27 ]. In preterm infants, one retrospective study comparing 51 exposed preterm infants from 28 to 36 weeks of gestation with 50 non-exposed matched controls [ 7 ] found that a 1 min Apgar score < 7 was more frequent in the exposed group, and lower Apgar scores were associated with a higher sertraline dose.…”

Section: Discussionmentioning

confidence: 99%

The Effect of SSRI Exposure in Pregnancy on Early Respiratory and Metabolic Adaptation in Infants Born Preterm

et al. 2023

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Selective serotonin reuptake inhibitors (SSRIs) are increasingly used for maternal depression during pregnancy; however, their use has been linked to adverse effects in newborns. Respiratory and feeding problems, jaundice, metabolic and temperature dysregulation and hypoglycemia have been described in term infants. However, scarce data exists on early neonatal adaptation in exposed infants born prematurely. We aimed to assess the effects of SSRI exposure on early neonatal adaptation measures in infants born prematurely. Data from preterm infants exposed to maternal SSRIs during pregnancy and from matched controls were retrospectively collected. Forty-two infants comprised the final cohort: 21 infants with SSRI exposure and 21 matched controls. 1 min Apgar score was significantly lower in the exposed group compared to the non-exposed group (p = 0.043). No differences were found in 5 min Apgar scores, cord pH, need for delivery room resuscitation, rate of hypoglycemia, hyponatremia, hyperbilirubinemia, need for phototherapy, temperature stability and maximal oxygen requirements. No differences were found in the total time of respiratory support, time to reaching full enteral feeds, length of stay and complications of prematurity. Unlike studies in term infants, no significant differences were found in adaptation and short-term outcomes between preterm infants with and without SSRI exposure in pregnancy.

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“…Article alerts and targeted searches of journals to identify major studies published in the interim that may affect the conclusions or understanding of the evidence and the related USPSTF recommendation were used as part of ongoing surveillance. The last surveillance was conducted on November 25, 2022, and 1 existing systematic reviews was added to the review …”

Section: Methodsmentioning

confidence: 99%

Depression and Suicide Risk Screening

O’Connor

Perdue

Coppola

et al. 2023

JAMA

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ImportanceDepression is common and associated with substantial burden. Suicide rates have increased over the past decade, and both suicide attempts and deaths have devastating effects on individuals and families.ObjectiveTo review the benefits and harms of screening and treatment for depression and suicide risk and the accuracy of instruments to detect these conditions among primary care patients.Data SourcesMEDLINE, PsychINFO, Cochrane library through September 7, 2022; references of existing reviews; ongoing surveillance for relevant literature through November 25, 2022.Study SelectionEnglish-language studies of screening or treatment compared with control conditions, or test accuracy of screening instruments (for depression, instruments were selected a priori; for suicide risk, all were included). Existing systematic reviews were used for treatment and test accuracy for depression.Data Extraction and SynthesisOne investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality. Findings were synthesized qualitatively, including reporting of meta-analysis results from existing systematic reviews; meta-analyses were conducted on original research when evidence was sufficient.Main Outcomes and MeasuresDepression outcomes; suicidal ideation, attempts, and deaths; sensitivity and specificity of screening tools.ResultsFor depression, 105 studies were included: 32 original studies (N=385 607) and 73 systematic reviews (including ≈2138 studies [N ≈ 9.8 million]). Depression screening interventions, many of which included additional components beyond screening, were associated with a lower prevalence of depression or clinically important depressive symptomatology after 6 to 12 months (pooled odds ratio, 0.60 [95% CI, 0.50-0.73]; reported in 8 randomized clinical trials [n=10 244]; I2 = 0%). Several instruments demonstrated adequate test accuracy (eg, for the 9-item Patient Health Questionnaire at a cutoff of 10 or greater, the pooled sensitivity was 0.85 [95% CI, 0.79-0.89] and specificity was 0.85 [95% CI, 0.82-0.88]; reported in 47 studies [n = 11 234]). A large body of evidence supported benefits of psychological and pharmacologic treatment of depression. A pooled estimate from trials used for US Food and Drug Administration approval suggested a very small increase in the absolute risk of a suicide attempt with second-generation antidepressants (odds ratio, 1.53 [95% CI, 1.09-2.15]; n = 40 857; 0.7% of antidepressant users had a suicide attempt vs 0.3% of placebo users; median follow-up, 8 weeks). Twenty-seven studies (n = 24 826) addressed suicide risk. One randomized clinical trial (n=443) of a suicide risk screening intervention found no difference in suicidal ideation after 2 weeks between primary care patients who were and were not screened for suicide risk. Three studies of suicide risk test accuracy were included; none included replication of any instrument. The included suicide prevention studies generally did not demonstrate an improvement over usual care, which typically included specialty mental health treatment.Conclusions and RelevanceEvidence supported depression screening in primary care settings, including during pregnancy and postpartum. There are numerous important gaps in the evidence for suicide risk screening in primary care settings.

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Associations Between Maternal Depression, Antidepressant Use During Pregnancy, and Adverse Pregnancy Outcomes

Abstract: Depressive symptoms or a clinical diagnosis of depression during pregnancy are associated with preterm birth and low Apgar scores, even without exposure to antidepressants.

Cited by 32 publications

References 67 publications

Should Antidepressants be Avoided in Pregnancy?

Should Antidepressants be Avoided in Pregnancy?

The Effect of SSRI Exposure in Pregnancy on Early Respiratory and Metabolic Adaptation in Infants Born Preterm

Depression and Suicide Risk Screening

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