We have recently seen an increased interest in the subject of perinatal anxiety.  While we have focused more on depressive symptoms, anxiety symptoms are actually very common during pregnancy and the postpartum period.  According to a recent meta-analysis from Fawcett and colleagues (see below), about one out of every five women has at least one type of anxiety disorder during pregnancy or the postpartum period.  Thus, several professional organizations are now recommending that we screen for anxiety, as well as depression, in pregnant and postpartum women.

Parallel to this interest in perinatal anxiety, we have seen over the last few weeks,  multiple articles on the use of benzodiazepines during pregnancy. The use of benzodiazepines during pregnancy continues to be controversial, and information regarding the use of this class of medications is often misinterpreted.   One of the recent publications is a large meta-analysis from Grigoriadis and colleagues (see below), which indicates that prenatal exposure to benzodiazepines is not associated with an increase in the overall risk of malformations. Hopefully, this information will be reassuring; however, there are some quirky bits of information in the study from Grigoriadis and others which we will discuss further over the next few weeks.

Ruta Nonacs, MD PhD


The Prevalence of Anxiety Disorders During Pregnancy and the Postpartum Period: A Multivariate Bayesian Meta-Analysis.

Fawcett EJ, Fairbrother N, Cox ML, White IR, Fawcett JM.  J Clin Psychiatry. 2019 Jul 23;80(4).

Individual disorder prevalence estimates ranged from 1.1% for posttraumatic stress disorder to 4.8% for specific phobia, with the prevalence of having at least 1 or more anxiety disorder estimated to be 20.7%.


The PRogram In Support of Moms (PRISM): study protocol for a cluster randomized controlled trial of two active interventions addressing perinatal depression in obstetric settings.

Moore Simas TA, Brenckle L, Sankaran P, Masters GA, Person S, Weinreb L, Ko JY, Robbins CL, Allison J, Byatt N.  BMC Pregnancy Childbirth. 2019 Jul 22;19(1):256. Free Article



Benzodiazepine Use During Pregnancy Alone or in Combination With an Antidepressant and Congenital Malformations: Systematic Review and Meta-Analysis.

Grigoriadis S, Graves L, Peer M, Mamisashvili L, Dennis CL, Vigod SN, Steiner M, Brown C, Cheung A, Dawson H, Rector N, Guenette M, Richter M.  J Clin Psychiatry. 2019 Jul 9;80(4). 

Benzodiazepine exposure during pregnancy does not appear to be associated with congenital malformations or with cardiac malformations specifically. There may be an increased risk of congenital malformations when benzodiazepines are used in conjunction with antidepressants.


Use of benzodiazepine medications during pregnancy and potential risk for birth defects, National Birth Defects Prevention Study, 1997-2011.

Tinker SC, Reefhuis J, Bitsko RH, Gilboa SM, Mitchell AA, Tran EL, Werler MM, Broussard CS; National Birth Defects Prevention Study.  Birth Defects Res. 2019 Jun 1;111(10):613-620. 

Benzodiazepine use was more common among mothers who were ? 30?years, non-Hispanic white, had more education, smoked, and took antidepressant medication. We observed significantly elevated risk for several types of malformations; however, the sample sizes were small and the confidence intervals wide.


Impact of prenatal exposure to benzodiazepines and z-hypnotics on behavioral problems at 5 years of age: A study from the Norwegian Mother and Child Cohort Study.

Sundbakk LM, Wood M, Gran JM, Nordeng H.  PLoS One. 2019 Jun 6. Free Article

Prenatal exposure to BZD and/or z-hypnotics increased the risks of internalizing behavioral problems (RR: 1.35, 95% CI: 0.73-2.49) and externalizing behavioral problems (RR: 1.51, 95% CI: 0.86-2.64). However, based on sensitivity analyses, researchers concluded that the risks of displaying externalizing and internalizing problems at 5 years of age did not significantly increase after prenatal exposure to BZDs and/or z-hypnotics. Instead, the sensitivity analyses suggested that residual confounding and selection bias might explain the increased risks observed in the main analyses.



Longitudinal assessment of symptoms of postpartum mood disorder in women with and without a history of depression.

Pataky EA, Ehlert U.  Arch Womens Ment Health. 2019 Jul 26. 

A sample of 687 healthy women with (n?=?192) and without (n?=?495) a history of depression were included in the present analyses. 

Women with a history of depression were twice more likely to show peripartum depressive symptoms than women without a history of depression. A history of symptoms of PMS/PMDD prior to the current pregnancy was associated with increased odds of peripartum depressive symptoms.


Introducing mother-baby interaction therapy for mothers with postpartum depression and their infants.

Horowitz JA, Posmontier B, Chiarello LA, Geller PA.  Arch Psychiatr Nurs. 2019 Jun;33(3):225-231.   

Mother-Baby Interaction (MBI) Therapy is designed to promote infant outcomes by supporting mothers’ sensitive, responsive, and contingent interactions with their infants.


Improving Postpartum Depression Screening and Referral in Pediatric Primary Care.

Russomagno S, Waldrop J.  J Pediatr Health Care. 2019 Jul – Aug;33(4):e19-e27. 

By standardizing PPD screening and implementing a referral algorithm in the ambulatory pediatric setting, more PPD cases can be identified, further evaluated, and, hopefully, treated to improve maternal and infant health outcomes.


Association of the previous history of maternal depression with post-partum depression, anxiety and stress in the Neonatal Intensive Care Unit.

Das A, Gordon-Ocejo G, Kumar M, Kumar N, Needlman R.

J Matern Fetal Neonatal Med. 2019 Jul 21:1-161.

A history of depression, documented in the antepartum medical record, identifies post-partum women who are at higher risk for anxiety and stress.


A systematic review investigating if genetic or epigenetic markers are associated with postnatal depression.

Elwood J, Murray E, Bell A, Sinclair M, Kernohan WG, Stockdale J.  J Affect Disord. 2019 Apr 9;253:51-62.

This review highlights the importance of examining the interaction between epigenetic, genetic, hormonal and environmental factors in order to fully understand the risk factors for postpartum depression.



Trajectories of maternal pre- and postnatal anxiety and depressive symptoms and infant fear: Moderation by infant sex.

Nolvi S, Bridgett DJ, Korja R, Kataja EL, Junttila N, Karlsson H, Karlsson L.  J Affect Disord. 2019 Jul 5;257:589-597. 

Infant girls exposed to prenatal-only maternal distress were higher in observed fear than infant boys exposed to prenatal-only distress. Infant girls exposed to consistently high distress also showed lower observed fear than their counterparts exposed to prenatal-only maternal distress.



The role of sleep difficulties in the vasomotor menopausal symptoms and depressed mood relationships: an international pooled analysis of eight studies in the InterLACE consortium.

Chung HF, Pandeya N, Dobson AJ, Kuh D, Brunner EJ, Crawford SL, Avis NE, Gold EB, Mitchell ES, Woods NF, Bromberger JT, Thurston RC, Joffe H, Yoshizawa T, Anderson D, Mishra GD.  Psychol Med. 2018 Nov;48(15):2550-2561. 

At baseline, the prevalence of VMS (40%, range 13-62%) and depressed mood (26%, 8-41%) varied substantially across studies, and a strong dose-dependent association between VMS and likelihood of depressed mood was found. Difficulty in sleeping largely explained the relationship between VMS and subsequent depressed mood, but it had little impact on the relationship between depressed mood and subsequent VMS.



SAGE-217, A Novel GABAA Receptor Positive Allosteric Modulator: Clinical Pharmacology and Tolerability in Randomized Phase I Dose-Finding Studies.

Hoffmann E, Nomikos GG, Kaul I, Raines S, Wald J, Bullock A, Sankoh AJ, Doherty J, Kanes SJ, Colquhoun H.  Clin Pharmacokinet. 2019 Jul 24.

SAGE-217 was generally well tolerated. Based on this profile, SAGE-217 has been advanced into multiple phase II clinical programs and pivotal studies of major depressive disorder and postpartum depression.



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