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. Author manuscript; available in PMC: 2023 Sep 6.
Published in final edited form as: J Affect Disord. 2021 Sep 1;295:530–540. doi: 10.1016/j.jad.2021.08.079

Prenatal maternal posttraumatic stress disorder as a risk factor for adverse birth weight and gestational age outcomes: A systematic review and meta-analysis

Pilar M Sanjuan a,c,1, Kathryn Fokas a, J Scott Tonigan a, Melissa C Henry a, Korinna Christian a,c, Andrea Rodriguez a, Jessica Larsen b, Nicole Yonke c, Lawrence Leeman c,d
PMCID: PMC10481878  NIHMSID: NIHMS1926089  PMID: 34509068

Abstract

Background:

Although not routinely assessed, prenatal posttraumatic stress disorder (PTSD) is associated with poor maternal mental health and mother-infant bonding. Prenatal PTSD may also be associated with birth weight and gestational age outcomes, but this remains unclear. This systematic review and meta-analysis investigated the association of prenatal PTSD with risk of low birth weight (LBW) or preterm birth (PTB) (dichotomous medically-defined cut-offs) or with birth weight (BW) or gestational age (GA) (continuous variables).

Methods:

A comprehensive literature search was conducted in Web of Science, MedLine, PubMed, and PsychInfo. Data were collected and processed according to Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Study quality was assessed with the Newcastle-Ottowa Quality Assessment Scale. Pooled effect sizes were estimated with random-effects models (correlation for continuous and odds ratios for dichotomous outcomes).

Results:

Sixteen studies with 51,470 participants (prenatal PTSD 8%) were included in 4 meta-analyses. Maternal prenatal PTSD was associated with higher risks of LBW (OR = 1.96; 95% CI, 1.26, 3.03; P = .003), PTB (OR = 1.42 (95% CI, 1.16, 1.73; P = .001), and reduced GA (r = −0.04; 95% CI, −0.06, −0.01; P = .002).

Limitations:

Different designs across studies, variety of PTSD assessment practices, and a small pool of studies were noted.

Conclusions:

Findings suggest prenatal PTSD presents increased risks of LBW, PTB, and reduced GA. Evidence of physical harm to neonates from prenatal PTSD provides a powerful rationale to increase prenatal PTSD screening and identify effective prenatal interventions to improve maternal and child outcomes.

Keywords: posttraumatic stress disorder, PTSD, prenatal, birth weight, preterm, gestational age

1. Introduction

Rates of posttraumatic stress disorder (PTSD) in general samples of pregnant women range widely: from 0.6% in a Nigerian general sample using the Mini International Neuropsychiatric Interview (MINI) (Adewuya et al., 2006; Sheehan et al., 1998) to 16% in a United States general sample using the PTSD Checklist (Morland et al., 2007; Viswasam et al., 2019; Weathers et al., 1993). Among women at high risk of PTSD (defined in the Yildiz et al., 2017 review as those with difficult or traumatic pregnancies or births, severe fears of birth, or histories of sexual/physical violence or child abuse), the range is from 1% in a sample of Turkish women with hyperemesis gravidarum (severe nausea and vomiting during pregnancy) (Annagür et al., 2013) to 40% in a sample of women with hyperemesis gravidarum in the United States (Seng et al., 2013a) with a mean prevalence of 19% across the high-risk samples (Yildiz et al., 2017). Within the prenatal PTSD literature, pregnant women who are considered at particularly high risk for PTSD include African-Americans (Seng et al., 2011a); military veterans (Hugin and Shaw, 2019); inmates (Harner et al., 2015); and those with childhood abuse (Wosu et al., 2015; Yildiz et al., 2017), physical/sexual violence histories (Wosu et al., 2015; Yildiz et al., 2017), substance use disorders (Moylan et al., 2001), severe childbirth fear (Yildiz et al., 2017), or prior pregnancy complications (Yildiz et al., 2017). In 2020, overall rates of PTSD increased concurrent with the novel coronavirus (COVID-19) pandemic (Berthelot et al., 2020).

The American College of Obstetricians and Gynecologists (ACOG) has recommended prenatal screening and referral for depression, domestic violence, and anxiety for several years (American College of Obstetricians and Gynecologists, 2018, 2012a). More recently, researchers called to extend these prenatal mental health screening recommendations to include PTSD (Canfield and Silver, 2020). In April of 2021, ACOG published new recommendations for the care of patients who have experienced trauma (American College of Obstetricians and Gynecologists, 2021a). These recommendations include using a trauma-informed approach, trauma screening, and the provision of educational materials and referrals. Previously, the Association of Women’s Health, Obstetric, and Neonatal Nurses had already recommended universal screening for prenatal PTSD among other perinatal mental health disorders (Association of Women’s Health, Obstetric, and Neonatal Nurses, 2015).

Prenatal PTSD can adversely affect health-risk behaviors and prenatal fetal bonding (Onoye et al., 2009; Radoš et al., 2020; Sanjuan et al., 2020, 2019) and is associated with postpartum PTSD (Onoye et al., 2009), postpartum depression, (Seng et al., 2013b), and disrupted mother-child attachment (Muzik et al., 2012; Seng et al., 2013b; Webb and Ayers, 2015). Multiple studies have suggested that prenatal PTSD may also be associated with more direct risks to the growing fetus, yet, the impact of prenatal PTSD on birth outcomes involving fetal development remains unclear (Cook et al., 2018; Grigoriadis et al., 2018; Murphy et al., 2001). Evidence suggests that PTSD may be associated with lower birth weight and gestational age in a manner similar to prenatal maternal depression (Grigoriadis et al., 2013; Grote et al., 2010). The primary mechanism proposed for this association between prenatal PTSD and birth weight or gestational age is sustained activation of the maternal hypothalamic-pituitary-adrenal (HPA) axis in response to chronic psychological stress. This causes neuroendocrine abnormalities including a suppressed cortisol response in both mother and offspring with changes to the gestational uterine environment (Bowers and Yehuda, 2016; Shapiro et al., 2013). Altered circadian cortisol profiles are associated with general prenatal psychological distress, depression, and anxiety (Van den Heuvel et al., 2018); preterm birth (Gilles et al., 2018); and fetal weight (Diego et al., 2006). Low birth weight (LBW: defined as less than 2500g) and preterm birth (PTB: defined as less than 37 weeks gestation) deliveries are strongly associated with neonatal and long-term morbidity and mortality (Blencowe et al., 2012; Crump et al., 2019; Katz et al., 2013) and also with increased risk for postpartum PTSD and depression (de Paula Eduardo et al., 2019). Thus, the aim of this paper is to determine if PTSD is associated with such adverse birth weight or gestational age outcomes and, if so, to quantify the magnitude of this association to inform maternal psychiatric care.

Two summary studies of related research suggest prenatal PTSD may impact these birth outcomes (sometimes reported as dichotomous measures based on medical definitions of LBW and PTB, and sometimes reported as continuous measures of birth weight (BW) or gestational age (GA)). A qualitative literature review without a meta-analysis (N=11) concluded that prenatal PTSD may be associated with LBW, but the evidence was inconsistent for an association with reduced BW, PTB, or reduced GA (Cook et al., 2018). Also suggesting a link between prenatal PTSD and birth outcomes, a 2018 meta-analysis of anxiety and birth outcomes that included some PTSD studies found associations between prenatal anxiety and LBW, reduced BW, PTB, and reduced GA (Grigoriadis et al., 2018). However, the DSM-5 and ICD-11 Working Groups both concluded that, despite PTSD sharing features of and high comorbidity with both depression and anxiety disorders, the symptom profile and course of PTSD fits poorly with anxiety or depression disorders (American Psychiatric Association, 2013; Barbano et al., 2019; Friedman, 2013; Maercker et al., 2013). Thus, PTSD should be examined in meta-analyses separate from anxiety disorders. Moreover, anxiety alone is associated with an increased risk of LBW and PTB (Ding et al., 2014), so analyzing anxiety data mixed with PTSD data may obscure PTSD effects. Thus, these summary studies, while suggesting a possible relationship, do not fill the critical gap in the literature regarding the consistency and degree of associations specifically between prenatal PTSD and these adverse birth outcomes (Engel et al., 2005; Rogal et al., 2007; Seng et al., 2001; Xiong et al., 2008).

The aim of our meta-analytic study was to focus on PTSD and determine the magnitude of any association of prenatal PTSD with low birth weight (LBW), birth weight (BW), preterm birth (PTB), or gestational age (GA). We hypothesized that prenatal PTSD would be associated with greater risk of LBW, reduced BW, PTB, and reduced GA. We also examined between-study variability to identify potential moderators of the associations.

2. Methods

2.1. Search Strategy

A computerized search was completed by the lead author on July 27, 2020 in the Web of Science, MedLine, PubMed, and PsychInfo databases. MeSH search terms included were: for prenatal period (maternal, prenatal, pregnancy, obstetric), PTSD symptomology (PTSD, posttraumatic stress disorder), and adverse pregnancy outcome (birth weight, preterm birth, gestational age, pregnancy outcome). Searches were limited to English peer-reviewed articles from 1981 to 2020 with a total 1167 articles identified. The Boolean search used in Web of Science was: (((TS=((maternal OR prenatal OR pregnancy OR obstetric) AND (PTSD OR posttraumatic stress disorder) AND (preterm birth OR gestational age OR birth weight OR pregnancy outcome))))). Reference lists of all relevant studies and reviews were examined and forward searches were conducted. To identify any published data novel to the search, lead authors with multiple articles (4 authors considered experts in the field) were contacted, and none were aware of any additional published data sources. Removal of duplicate studies resulted in 803 articles (see Figure 1. PRISMA Flow Diagram (Liberati et al., 2009)). All aspects of the meta-analyses were conducted in accordance with Preferred Reporting Items for Systematic Reviews (PRISMA) (Moher et al., 2009) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines (Stroup, 2000).

Figure 1.

Figure 1.

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PRISMA Flow Diagram

From: Maher D, Liberati A, Tetzlaff J, Altman DG. The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and .Meta-Analyses: The PRISMA Statement. PLOS Med 6(6): e1000097. doi;10.1371/jornal.pmed1000097 For more information, visit www.prisma-statement.org

2.2. Study Selection and Eligibility Criteria

Four reviewers independently double-screened each title and reviewed abstracts for inclusion criteria. Included were cohort, longitudinal, and cross-sectional (retrospective reports of prenatal PTSD) studies that reported quantitative data, participants with at least probable PTSD prenatally, and at least one measure of adverse birth outcome (i.e., LBW, BW, PTB, GA). The lead author (P.M.S.) resolved discrepancies between reviewers by consensus through group review of abstracts and/or full text. Title/abstract screening excluded 777 articles from the 803 unduplicated identified articles for the following reasons prioritized in this order: 1) N = 223 were not peer-reviewed quantitative journal articles in English, 2) N = 352 articles lacked participants with at least probable prenatal PTSD (per PTSD measure/medical records), 3) N = 191 lacked birthweight or gestational age outcomes, and 4) N = 11 lacked data analyses of prenatal PTSD with a birth outcome. Articles meeting more than one exclusion criteria were excluded based on the first one met in the prioritized list. Twenty-six articles underwent full text analysis: 6 articles were excluded for reason #4 (no analyses of prenatal PTSD with birth outcome) and 4 articles were excluded for sample overlap with included articles. This resulted in 16 total articles for meta-analyses. See Figure 1.

2.3. Data Extraction and Quality Assessment

Data were extracted using a coding form developed by co-author J.S.T. for a prior published meta-analysis (Tonigan et al., 2018) and revised for this topic. Four reviewers independently (J.L., K.F., M.C.H., K.C.; trained by P.M.S.) extracted data from articles (with 2 reviewers per article). Discrepancies were resolved with the fifth reviewer (P.M.S.). PTSD and birth outcome variables were verified a final time (by P.M.S. and A. R.) for each included article prior to conducting each meta-analysis. Extracted participant data included age range, socioeconomic status, race/ethnicity, education, employment, geographic location, special population characteristics, and PTSD classification. Extracted design data included sample size, PTSD measure, PTSD period, study funding, sample origin, exclusion/inclusion criteria, recruitment strategy, source of outcome data, prospective/secondary hypothesis testing, and statistical analyses. Outcomes were low birth weight (LBW), birth weight (BW), preterm birth (PTB), and gestational age (GA). LBW and PTB were defined by studies either by ICD codes or as LBW: <2500 grams and PTB: <37 weeks. PTSD was defined as “at least probable PTSD” and included meeting diagnostic criteria, meeting a severity scale cutoff, or a diagnostic code (ICD or DSM) from medical records. Study quality was rated by reviewers using the Newcastle-Ottowa Quality Assessment Scale for Cohort Studies (NOS) (Wells et al., 2013). See Table 1 for study characteristics.

Table 1.

Characteristics of All Studies Included in the Meta-analyses

Source N N PTSD Sample Origin Participant Exclusions Design PTSD Meas. PTSD Var. PTSD Period Birth Outcomes Study Qual.
Engel et al. (2005) 50 4 CT MP L, CR PCL S NR BW, GA 7
Ferri et al. (2007) 795 62 OC MP, MA CS CIDI D 1-year LBW 9
Gelaye et al. (2020) 4408 1519 OC MTP, MP, PS,MA, Language L PCL P 30-day BW, LBW, GA, PTB 7
Harville et al. (2015) 297 27 OC, CO, CT MP, PS, MA, PC L, CR PCL P NR BW, LBW, GA, PTB 8
Kang-Yi et al. (2017) 9930 269 DB Date of delivery CR CR D 1-year PTB 7
Koen et al. (2016) 366 106 OC PS, MA L MINI D Lifetime LBW, GA, PTB 4
Lipkind et al. (2010) 446 61 CO, DB, CT MP, MC, EGA, MA, EBW, Sm CS PCL P 30-day BW, LBW, GA, PTB 8
MacGinty et al. (2020) 959 126 OC PS, MA L MPSS P NR BW 5
Morland et al. (2007) 101 16 OC, CO PS, MA L, CR PCL P, S NR BW, GA 3
Rashid et al. (2020) 450 84 OC MP, MC, PS, EGA L MINI P 30-day LBW 9
Rogal et al. (2007) 1100 31 OC None L, CR MINI D 30-day BW, LBW, GA, PTB 8
Seng et al. (2011b) 405 98 OC MTP, MA, MP, Eng, PC L, CR NWS D 30-day BW, LBW, GA, PTB 9
Shaw et al. (2014) 16334 1921 DB None CR CR D 1 year PTB 8
Shaw et al. (2018) 12877 361 DB None CR CR D 1-year PTB 8
Xiong et al. (2008) 298 13 OC, CT MA, Eng L, CR PCL P NR LBW, PTB 7
Yonkers et al. (2014) 2654 129 OC MP, PS, MA, MC, Eng L MPSS P NR PTB 8
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Abbreviations: N = sample size, Meas. = measure, Var. = variable, PTSD = posttraumatic stress disorder, Study Qual. = quality rated using the Newcastle-Ottawa Quality Assessment Scale for Cohort Studies (Wells et al., 2013), NR = Not Reported, CO = community, DB = database, OC = Obstetrics/Prenatal/Maternity Clinic, CT = Common Trauma Sample, MP = multiple pregnancy, MTP = multiparous, MA = Maternal Age, MC = Medical complications, PS = Stage of Pregnancy, PC = prenatal care, EBW = extreme low or high birth weight, EGA = extreme low or high gestational age, Sm = smoking, Eng = non-English speaking, CS = cross sectional, L = longitudinal, CR = Chart review, PCL = PTSD Checklist (-C, −5, or original), MINI = The Mini International Neuropsychiatric Interview, CITI = Composite International Diagnostic Interview, MPSS = Modified PTSD Symptom Scale, NWS = National Women’s Survey, P = Probable PTSD based on a cut-off score on a screening instrument, D = PTSD Diagnosis from clinical interview or medical records, S = PTSD severity (continuous measure), BW = birth weight, LBW = low birth weight, GA = Gestational Age, PTB = preterm birth

2.4. Effect Size Calculation and Statistical Analyses

Separate meta-analyses were conducted for 4 outcomes: 1) LBW (dichotomous), 2) BW (continuous), 3) PTB (dichotomous), and 4) GA (continuous) using Comprehensive Meta-Analysis version 3.3.070 (CMA) (Borenstein et al., 2014). One-tailed P values of .50 and sample sizes were entered for studies reporting non-significant results without statistical values (Rosenthal, 1995) when contacted authors could not provide values (2 studies). Sensitivity analyses were conducted with these 2 studies removed (from each of the 3 meta-analyses that included them). Pearson’s r was computed for effect sizes with continuous birth outcome measures. Odds ratios were computed for effect sizes with dichotomous birth outcomes (OR: odds for PTSD group over odds for non-PTSD group). The actual number of events/non-events (e.g. LBW/no LBW or PTB/no PTB) and sample sizes for conditions (e.g. PTSD/no PTSD) were entered for dichotomous outcome variables, when available (Chang and Hoaglin, 2017). Data for current-PTSD versus trauma-exposed PTSD-resilient comparison groups were entered when more than 2 PTSD groups (e.g., current PTSD, recovered from PTSD, trauma-exposed PTSD-resilient, no trauma) were reported. Forest plots with 95% confidence intervals (CI) for sensitivity and specificity were created. Random effects models were used for all meta-analyses due to heterogeneity across samples pulled from varied sub-populations of pregnant women (Borenstein et al., 2010). Potential publication bias was evaluated by visual inspection of funnel plots (Sterne et al., 2011) and Eggers Tests (Egger et al., 1997).

2.5. Risk of Bias Across Studies

Cochran’s Q and I2 were computed to determine heterogeneity in pooled effect size and true variation between studies, respectively. When statistically significant heterogeneity was observed, we used mixed-effects models to test for moderating effects of 1) type of PTSD measure: self-administered checklist versus interview, 2) type of exclusion criteria: confounding risks for adverse prenatal outcome (e.g., twins, prior PTB) versus study logistics exclusions (e.g., language spoken, clinic enrollment), and 3) PTSD period: prenatal period (e.g., 30-day, 1-year before birth) versus not clearly limited to prenatal period (e.g., lifetime, undefined).

3. Results

3.1. Study Characteristics

Of the 16 articles included, 11 were longitudinal in design, 9 used chart review, and 2 were cross sectional. Among the studies, 10 reported LBW, 7 reported BW, 11 reported PTB, and 7 reported GA outcomes. See Table 1 for study characteristics. Studies had a total of 51,470 participants, 4,334 (8%) with PTSD diagnoses, probable PTSD (based on severity cut-off), or subclinical PTSD (symptoms present but below criteria scoring threshold: combined with PTSD in 1 study). Sample sizes ranged from 50 to 16,334 (mean = 3,216, SD = 5,137). Samples were from the United States (11 articles), Africa (2 articles), Central/South America (2 articles), and Asia (1 article).

3.2. Risk of Bias Within Studies

The average study quality was high at 7.2, SD = 1.76 with a range of 3–9 (the NOS scale measures a range of 0–9; See Table 1). All studies used clinical diagnoses or standardized scales for PTSD with 50% using more conservative interview methods (i.e., interviews require more resources but are generally more reliable than checklists). Half the studies excluded participants with potentially confounding risks for LBW or PTB (e.g., twins, prior PTB), and 56% of studies limited PTSD assessment to a prenatal timeframe (vs. lifetime PTSD or unspecified timeframe). Higher risk of bias within studies was largely related to imprecision in prenatal PTSD determination and, thus, was most likely to result in Type II errors.

3.3. Results for Birth Weight

3.3.1. Low birth weight (LBW: dichotomous)

Prenatal PTSD versus no PTSD was associated with greater odds of LBW. Ten studies (8666 participants) produced a positive combined effect size: OR = 1.96 [95% CI, 1.26 to 3.03]; P = .003; Q = 40.2 (P < .001, I2 = 77.6%); Figure 2. There were no significant subgroup differences for PTSD measure (Q = 0.2, P = .682), exclusion criteria (Q = 2.7, P = .103), or PTSD period (Q = 1.5, P = .223). The funnel plot was symmetrical, suggesting publication bias was unlikely (Figure 3), and the Eggers test was not significant (P = .233).

Figure 2.

Figure 2.

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Forrest Plot of the Association of Prenatal PTSD with Risk for Low Birth Weight (dichotomous measure)

Figure 3.

Figure 3.

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Publication Bias: Funnel Plot of the Association of Prenatal PTSD with Low Birth Weight (dichotomous)

3.3.2. Birth weight (BW: continuous)

BW was reported by 7 studies (7675 participants). The combined effect size, r, was not significant, indicating no association between PTSD and BW: r = −0.04 [95% CI, −0.09 to 0.01]; P = .096; Q = 16.9 (P = .010, I2 = 64.5%); Figure 4. There were no significant subgroup differences for PTSD measure (Q = 1.0, P = .314), exclusion criteria (Q = 2.1, P = .152), or PTSD period (Q = 1.7, P = .188). The symmetrical funnel plot did not suggest publication bias (Figure 5), and the Eggers test was not significant (P = .512).

Figure 4.

Figure 4.

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Forrest Plot of the Association of Prenatal PTSD with Birth Weight (continuous measure)

Figure 5.

Figure 5.

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Publication Bias: Funnel Plot of the Association of Prenatal PTSD with Birth Weight (continuous)

3.4. Results for Preterm Birth and Gestational Age

3.4.1. Preterm Birth (PTB: dichotomous)

Prenatal PTSD versus no PTSD was associated with greater odds of PTB. Eleven studies (49,115 participants) produced a positive combined effect size: OR = 1.42 [95% CI, 1.16 to 1.73]; P = .001; Q = 18.3 (P = .032; I2 = 50.7%); Figure 6. There were no significant subgroup differences for PTSD measure (Q = 1.3, P = .247), exclusion criteria (Q = 3.2, P = .075), or PTSD period (Q = 0.3, P = .572). A symmetrical funnel plot did not suggest publication bias (Figure 7), and the Eggers test was not significant (P = .141).

Figure 6.

Figure 6.

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Forrest Plot of the Association of Prenatal PTSD with Risk for Preterm Birth (dichotomous measure)

Figure 7.

Figure 7.

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Publication Bias: Funnel Plot of the Association of Prenatal PTSD with Preterm Birth (dichotomous)

3.4.2. Gestational age (GA: continuous)

Prenatal PTSD versus no PTSD was associated with lower GA. Seven studies (7072 participants) produced a negative combined effect size: r = −0.04 [95% CI, −0.06 to −0.01]; P = .002; Q = 5.8 (P = .447; I2 = 0.0%); Figure 8. Subgroup analyses were not conducted because statistically significant heterogeneity was not observed in the analysis. The funnel plot was symmetrical (Figure 9) and the Eggers test was not significant (P = .866), thus there was no suggestion of publication bias.

Figure 8.

Figure 8.

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Forrest Plot of the Association of Prenatal PTSD with Gestational Age (continuous measure)

Figure 9.

Figure 9.

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Publication Bias: Funnel Plot of the Association of Prenatal PTSD with Gestational Age (continuous)

3.5. Sensitivity Analyses

Sensitivity analyses removing the 2 studies reporting non-significant results without statistical values (Rosenthal, 1995) did not substantially change the significance of any meta-analyses results: LBW (OR = 2.42 [95% CI, 1.42 to 4.14]; P = .001); PTB (OR = 1.46 [95% CI, 1.25 to 1.94]; P < .000); and GA (r = −0.04 [95% CI, −0.07 to −0.01]; P = .002).

4. Discussion

This meta-analytic review summarizes results from 16 studies examining associations of prenatal PTSD with birth weight and gestational age outcomes. Prenatal PTSD was found to be associated with increased risk of LBW, PTB, and reduced GA. The higher sensitivity of the continuous BW measure, compared to the more clinically-relevant dichotomous LBW variable, may account for not finding a significant association between prenatal PTSD and BW. However, this non-significant association remained directionally consistent with results of the other 3 meta-analyses.

Our results provide the quantitative summary evidence for adverse impacts of prenatal PTSD on LBW, PTB, and reduced GA that was previously lacking in the literature. A qualitative literature review on this topic suggested a prenatal PTSD and LBW association (Cook et al., 2018). Additionally, a very different but related meta-analysis showed prenatal anxiety (that included some PTSD studies) was associated with adverse birth outcomes including LBW, reduced BW, PTB, and reduced GA (Grigoriadis et al., 2018). Our meta-analyses focused specifically on prenatal PTSD, which is common (Viswasam et al., 2019; Yildiz et al., 2017) and is associated with prenatal health-risk behaviors, disrupted prenatal fetal bonding, postpartum depression, and impaired postpartum mother-infant attachment (Onoye et al., 2009; Radoš et al., 2020; Sanjuan et al., 2020, 2019). Our results show prenatal PTSD is significantly associated with LBW, PTB, and reduced GA. These results provide evidence of potential physical harm to the developing fetus posed by prenatal PTSD. This gives urgency to the calls to include prenatal PTSD as an important clinical consideration in prenatal mental health care and for research to determine the best prenatal PTSD treatments (Canfield and Silver, 2020; Geller and Stasko, 2017; Yildiz et al., 2017).

The American College of Obstetricians and Gynecologists (ACOG) recommends prenatal screening for depression, domestic violence, and anxiety (American College of Obstetricians and Gynecologists, 2018, 2012a). Recently, new guidance from ACOG recommends universal screening for current trauma and history of trauma by obstetricians and gynecologists followed by provision of educational materials and appropriate referrals (American College of Obstetricians and Gynecologists, 2021a). Our results support the recommendation that maternity care providers screen and refer patients for trauma and appropriate PTSD treatment. The results of this meta-analysis also reinforce the need for mental health integrated with maternity care (Cox et al., 2017). ACOG previously recommended screening for trauma and PTSD for specific populations including women in the military (American College of Obstetricians and Gynecologists, 2012b) and survivors of sexual assault (American College of Obstetricians and Gynecologists, 2019), and very recently for incarcerated women (American College of Obstetricians and Gynecologists, 2021b). While our results are of particular relevance in clinical populations with higher PTSD risk (e.g., veterans, people from marginalized populations, those with substance use disorders (Harner et al., 2015; Hugin and Shaw, 2019; Moylan et al., 2001; Seng et al., 2011a)), it is of note that the routine universal trauma screening as newly recommended by ACOG is an improvement that will capture cases missed by an overly-narrow focus on only high-risk patients.

It is important to note that the new ACOG recommendation broadly focuses on psychological trauma and not PTSD specifically. As the conditional risk of developing PTSD following a traumatic experience ranges from 2.5% to 17.6%, most people who have experienced trauma do not develop PTSD, and mental health referrals may be inappropriate in many of cases of reported trauma (Atwoli et al., 2015). Screening for PTSD specifically may better capture the potential risk associated with trauma history in pregnant women.

Similar to prenatal anxiety and depression (Rogers et al., 2020), prenatal PTSD is associated with postpartum PTSD (Onoye et al., 2009), postpartum depression, (Seng et al., 2013b), and disrupted mother-child attachment (Muzik et al., 2012; Seng et al., 2013b; Webb and Ayers, 2015). Thus, routine screening and appropriate referral to treatment of pregnant patients for PTSD can have effects transcending birth outcomes. The 5-item Primary Care PTSD Screen for DSM-5 (PC-PTSD-5) developed by researchers at the National Center for PTSD is one option that could be used for such screening (Prins et al., 2016). An earlier 4-item DSM-IV version was validated with a prenatal sample (Wenz-Gross et al., 2016) and further research is warranted using the updated version.

Fortunately, many PTSD treatments are particularly safe during pregnancy (International Society for Traumatic Stress Studies (ISTSS), 2018), but, as with many mental health treatments, PTSD therapies can take weeks to months for full effects. PTSD is associated with altered circadian cortisol profiles (Bowers and Yehuda, 2016; Yehuda et al., 2010), and this may be a primary mechanism by which prenatal PTSD places women at risk of LBW and PTB (Diego et al., 2006). Similarly, depression and anxiety (disorders with PTSD symptom overlap) are also associated with LBW and PTB (Ding et al., 2014; Gelaye et al., 2020; Grote et al., 2010; Lewis et al., 2016). Moreover, altered circadian cortisol profiles are linked to general prenatal psychological distress, depression, and anxiety (Van den Heuvel et al., 2018); mediate the relationship between broad prenatal psychological distress and PTB (Gilles et al., 2018); and predict fetal weight (Diego et al., 2006). This suggests that reduction of PTSD-related distress leading to improved cortisol profiles earlier in pregnancy may be ideal to improve birth outcomes. Additionally, if rapid physiological stress-reduction is a critical treatment goal, this may indicate a role for complementary interventions (often tailored for pregnancy: e.g., prenatal yoga, doulas, tai chi) provided in conjunction with psychotherapy to enhance treatment effects (Beddoe et al., 2009; Dhillon et al., 2017; Field et al., 2013; Hong Gong et al., 2015; International Society for Traumatic Stress Studies (ISTSS), 2018; Lanning and Klaman, 2019). The recent increase in studies examining prenatal PTSD and birth outcomes mirrors the growing interest among clinical providers to consider prenatal psychological disorders overall, however prenatal PTSD treatment research is still at an early stage (Rowe et al., 2014; Weinreb et al., 2018). It remains unknown whether current PTSD interventions can improve birth weight or gestational age outcomes at all, and if so, whether there might exist critical periods for such intervention. Research in these areas is greatly needed to determine whether PTSD treatment can improve these outcomes and, if so, the most effective prenatal PTSD treatments and critical periods for intervention to reduce risk of LBW, PTB, and reduced GA. Additional research might also examine whether different trauma types (e.g., sexual assault, motor vehicle accidents, combat) are differentially associated with these outcomes.

4.1. Limitations

First, as this is an emerging area of research, the pool of studies was modest, with limited PTSD-positive cases in some studies. More studies with higher numbers of positive cases would increase confidence in aggregated findings. The modest sample size also increased the chances of Type II error for the heterogeneity and Eggers tests, which are prone to low power. Second, heterogeneity across studies was detected in 3 meta-analyses. Despite sufficient information for sub-group analyses with some moderators, variation in participant characteristics reported across studies made it impossible to examine other potential moderators (e.g., race, trauma-type, substance use, poverty). For example, one study found trauma history and race mediated PTSD effects on birth outcomes (Seng et al., 2011b). Yet, we could not evaluate this, because trauma history and race (especially as race is not uniformly defined internationally) were not consistently reported across studies. The included studies also differed in PTSD assessment methods (e.g., interview versus checklist, symptom duration). Although we conducted subgroup analyses for some PTSD assessment differences, we could not account for all differences across studies. Third, we also did not include non-English publications because we lacked adequate translation resources.

The potential public health impact of our results is great, despite modest magnitudes of these associations (Chen et al., 2010), as preterm birth is the leading cause of perinatal morbidity and mortality (Goldenberg et al., 2008). Fetal growth restriction is similarly a major risk factor for still-birth as well as neonatal mortality and morbidity (Resnik, 2002). Our findings should be viewed in context with other risks for these outcomes. Many factors beyond mental health are associated with LBW (Lewis et al., 2016) and PTB (Muglia and Katz, 2010), and our results are similar in magnitude to those found for the associations of prenatal depression (Grote et al., 2010) or anxiety disorders (Ding et al., 2014; Grigoriadis et al., 2018) with LBW and PTB. This is consistent with a dimensional framework of psychopathology where biological mechanisms underlie, or are otherwise associated with, psychiatric diagnoses (Kozak and Cuthbert, 2016). Thus, it may be that any of the broader group of affective disorders alter HPA axis functioning, thereby increasing risks of adverse birth weight and gestational age outcomes.

5. Conclusions

Our meta-analyses found prenatal PTSD was associated with increased risk for low birth weight, preterm birth, and reduced gestational age. Our results suggest that prenatal PTSD screening and referral to evidence-based PTSD interventions (similar to recommended prenatal protocols for depression, domestic violence, and anxiety) could provide an opportunity to improve these birth outcomes. More research is critical to determine physiological mechanisms for this relationship and to identify those mental health interventions that best reduce this risk.

Supplementary Material

1

Highlights.

  • Prenatal posttraumatic stress disorder is associated with risk of low birth weight.

  • Prenatal posttraumatic stress disorder is associated with lower gestational age.

  • Prenatal posttraumatic stress disorder is associated with risk of preterm birth.

  • Prenatal PTSD may adversely affect maternal and child well-being.

  • Prenatal PTSD screening and interventions may improve mother and child outcomes.

Acknowledgements

We thank Carly Poremba who assisted substantially with the initial review of abstracts and titles. We also thank the authors we contacted who supplied us with additional information. Finally, we thank Joseph Guydish and Kevin Delucchi at the University of California, San Francisco and Hortensia Amaro at Florida International University for their critiques of drafts and research design advice.

Funding

This study was supported in part by the National Institutes of Health K23AA025094 (Sanjuan), R21DA048058 (Sanjuan), R21MH118765 (Sanjuan), K24AA021157 (Tonigan), and R25DA035163 (Masson, Sorensen).

Role of the Funder/Sponsor

The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.

Footnotes

Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Conflict of Interest Disclosures

All authors declare they have no conflicts of interest.

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