posttraumatic

Original Research

Posttraumatic Stress Disorder and Risk ofSpontaneous Preterm Birth

Jonathan G. Shaw, MD, MS, Steven M. Asch, MD, MPH, Rachel Kimerling, PhD, Susan M. Frayne, MD, MPH,Kate A. Shaw, MD, MS, and Ciaran S. Phibbs, PhD

OBJECTIVE: To evaluate the association between ante-

natal posttraumatic stress disorder (PTSD) and sponta-

neous preterm delivery.

METHODS: We identified antenatal PTSD status and

spontaneous preterm delivery in a retrospective cohort of

16,334 deliveries covered by the Veterans Health Adminis-

tration from 2000 to 2012. We divided mothers with

PTSD into those with diagnoses present the year before

delivery (active PTSD) and those only with earlier diagnoses

(historical PTSD). We identified spontaneous preterm birth

and potential confounders including age, race, military

deployment, twins, hypertension, substance use, depres-

sion, and results of military sexual trauma screening and

then performed multivariate regression to estimate

adjusted odds ratio (OR) of spontaneous preterm delivery

as a function of PTSD status.

RESULTS: Of 16,334 births, 3,049 (19%) were to mothers

with PTSD diagnoses, of whom 1,921 (12%) had active

PTSD. Spontaneous preterm delivery was higher in those

with active PTSD (9.2%, n5176) than those with historical(8.0%, n590) or no PTSD (7.4%, n5982) before adjustment(P5.02). The association between PTSD and preterm birthpersisted, when adjusting for covariates, only in those with

active PTSD (adjusted OR 1.35, 95% confidence interval

[CI] 1.141.61). Analyses adjusting for comorbid psychiatric

and medical diagnoses revealed the association with active

PTSD to be robust.

CONCLUSION: In this cohort, containing an unprece-

dented number of PTSD-affected pregnancies, mothers with

active PTSD were significantly more likely to suffer sponta-

neous preterm birth with an attributable two excess preterm

births per 100 deliveries (95% CI 14). Posttraumatic stress

disorders health effects may extend, through birth out-

comes, into the next generation.

(Obstet Gynecol 2014;124:11119)

DOI: 10.1097/AOG.0000000000000542

LEVEL OF EVIDENCE: II

Preterm birth is a leading cause of infant morbidityand mortality.1 In the United States 12% of deliver-ies are preterm, and roughly half are spontaneous asopposed to medically indicated.2 Although certain riskfactors for spontaneous preterm birth have been clearlyidentified, including demographic characteristics, sub-stance use, and multiple gestations, the etiology remainspoorly understood; efforts to reduce the preterm birthrate have made little progress over the past two deca-des.14 A growing number of studies suggest a role forpsychosocial factors such as maternal stress57 anddepression.810 However, the effect of posttraumaticstress disorder (PTSD) remains unclear.

Posttraumatic stress disorder is a complex ofdisruptive symptoms arising from a traumatic experi-ence (eg, violence, disaster). Its prevalence variessubstantially between populations based on expo-sure.11 U.S. surveys show women affected at higher

From the Center for Innovation to Implementation, the National Center forPosttraumatic Stress Disorder, the Womens Health Section, and the Health Econom-ics Resource Center, Department of Veterans Affairs, Palo Alto Health Care System,Palo Alto, and the March of Dimes Center for Prematurity Research at Stanford, theCenters for Health Policy/Primary Care & Outcomes Research, the Division of Gen-eral Medical Disciplines, and the Departments of Obstetrics & Gynecology and Pedi-atrics, Stanford University School of Medicine, Stanford, California.

Dr. Shaw was supported in part by the VA Office of Academic Affairs andHealth Services Research & Development funds. Development of the WomensHealth Evaluation Initiative (WHEI) data used in this study was supported byVA Womens Health Services.

The authors thank Laurie Zephyrin, MD, MPH, MBA, of Womens HealthServices in the VA Central Office, and Rita Popat, PhD, of Stanford Universityfor thoughtful review of the manuscript, and VA Palo Alto Staff, LakshmiAnanth, MS, Vidhya Balasubramanian, MS, Eric Berg, MS, Sarah Friedman,MSPH, Fay Saechao, MPH, Meghan Saweikis, MS, JD, and Susan Schmitt,PhD, for invaluable consultation and technical advice.

The findings and conclusions in this report are those of the authors and do notnecessarily represent the official position of the Department of Veterans Affairs.

Corresponding author: Jonathan G. Shaw, MD, MS, 117 Encina Commons,Room 206, Stanford, CA 94305; e-mail: [email protected].

Financial DisclosureThe authors did not report any potential conflicts of interest.

2014 by The American College of Obstetricians and Gynecologists. Publishedby Lippincott Williams & Wilkins.ISSN: 0029-7844/14

VOL. 124, NO. 6, DECEMBER 2014 OBSTETRICS & GYNECOLOGY 1111

rates than men, and estimate lifetime prevalence ofPTSD among females to be 1014%.12,13

Posttraumatic stress disorder could affect pretermdelivery directly through biological pathways orindirectly through risky health behaviors and poorself-care (eg, attendance to medical care, nutrition,and sleep). Previous studies have been limited byinadequate sample size, heterogeneity in diagnosticcriteria, and generalizability concerns.1423

We examined whether PTSD is associated withspontaneous preterm birth by evaluating deliveriescovered by the Veterans Health Administration. Withstandardized mandatory PTSD screening,24 a highPTSD prevalence (1321% in reproductive-agedwomen),25,26 and centralized national data, the Veter-ans Health Administration provides an ideal setting inwhich to examine the association between PTSD andpreterm birth in a cohort of unprecedented size.

MATERIALS AND METHODS

Using data from national clinical and administrativedatabases for Veterans Health Administration-based(nonobstetric) care and outsourced (obstetric) Veter-ans Health Administration care, we conducted a ret-rospective cohort analysis of all Veterans HealthAdministration-reimbursed deliveries in fiscal years20002012 and evaluated associations between ante-partum PTSD and spontaneous preterm delivery:16,477 deliveries were identified using a validatedalgorithm.27 Our main Veterans Health Administra-tion data set is derived from standardized hospitaldischarge abstracts, entered by professional coders,and diagnosis data from such discharge abstracts havepreviously been shown to be reliably coded.28 Weexcluded 102 women without Veterans HealthAdministration encounters before delivery (and thuswithout antecedent Veterans Health AdministrationPTSD screening or clinical data) and 41 additionaldeliveries resulting from irreconcilable data.

Our primary outcome was spontaneous pretermbirth. Spontaneous cases were deemed most relevant toevaluating the direct contribution of PTSD to prematuredelivery. Cases were identified by International Classi-fication of Diseases, 9th Revision, Clinical Modification(ICD-9-CM) diagnosis code 644.2 spontaneous onset ofdelivery before 37 weeks in the delivery claim, which inexternal validation corresponds to a median gestationalage of 35 weeks (see Appendix 1, available online athttp://links.lww.com/AOG/A571, for a description ofvalidation).

The Veterans Health Administration routinelyscreens for PTSD within its primary care system,29

and prior Veterans Health Administration studies

confirm the reliability of ICD-9-CM 309.81 to identifyPTSD.30,31 We used Veterans Health Administrationencounters from 1997 to 2012 (ensuring a minimum3-year look-back for our cohort, which begins withdeliveries in 2000) to identify PTSD in any encounterbefore delivery. For each delivery, we further distin-guished two mutually exclusive categories of PTSDstatus in pregnancy: active PTSD and historicalPTSD. This distinction was invoked based on priorresearch that observed poorer birth outcomes inwomen with current PTSD symptoms during preg-nancy, not past (recovered) PTSD.32 We categorizedas active PTSD those cases in which a PTSD diag-nosis was documented in any encounter(s) within 365days before the day of delivery, presuming these repre-sented pregnancies with clinically relevant PTSD symp-toms in the prenatal period; PTSD cases not meetingthis criterion were labeled historical PTSD. In choos-ing a 1-year window to define active PTSD, we aimed tomaximize overlap with the pregnancy and ensure likeli-hood of a Veterans Health Administration encounter forall participants in that time period. (A more restrictive9-month window was explored in a sensitivity analysis.)By our inclusion criteria, all women had VeteransHealth Administration encounters before delivery, andmore than 99% had an encounter within 1 year beforedelivery and thus the opportunity for active PTSD to bedocumented.

We collected data on two potential trauma expo-sures, military sexual trauma and recent military deploy-ment, both associated with high rates of PTSD within theVeterans Health Administration.25,33 Mandatory one-time screening for military sexual trauma has been inplace since 2002 through a brief validated instrument33

(see Appendix 1, http://links.lww.com/AOG/A571, forscreening questions). We used the Department ofDefense Roster34 to identify veterans with recent deploy-ment in support of operations in Afghanistan or Iraq.

We obtained demographic covariates from Veter-ans Health Administration administrative data, includ-ing maternal age, race, and marital status. We identifiedobstetric risk factors including twins or higher-ordergestations and prior cesarean delivery from obstetrichospitalizations using validated ICD-9-CM codes.35,36

We extracted medical comorbidities from previouslydeveloped Veterans Health Administration chroniccondition data sets.37 Specifically, we recorded thoseconditions that were both prevalent in our cohort(2% or more) and have been suggested as risk factorsfor preterm birth3: hypertension, diabetes, and asthma.

To identify mental health diagnoses other thanPTSD, we used a modified version38 of the Agency forHealthcare Research andQuality Clinical Classifications

1112 Shaw et al PTSD and Risk of Spontaneous Preterm Birth OBSTETRICS & GYNECOLOGY

Softwares categories of mental illness.39 Applying thesame criteria as for PTSD, we created three-level indi-cator variables (active, historical, none) for the mostprevalent disorders. We identified active drug and alco-hol abuse and tobacco dependence in the antenatalperiod by the presence of diagnostic codes in VeteransHealth Administration encounters within 1 year beforedelivery or within reimbursed prenatal encounters(where screening for substances should be standard ofcare) to maximize sensitivity.

Delivery was our unit of analysis and we usedstatistical methods accounting for repeated measuresadjusting effect estimates to take into account a within-person correlation for women with repeat deliveries inour cohort. We performed unadjusted x2 bivariate anal-ysis, then performed adjusted multivariate logisticregression (SAS 9.2) using generalized estimating equa-tions modeling (clustered by individual) to determineadjusted odds ratio (OR) of spontaneous preterm deliv-ery by PTSD status as a three-level predictor comparingactive PTSD and historical PTSD with none.

We performed regressions in an iterative (addi-tive) fashion, exploring demographic and obstetricfactors, and potential trauma (military sexual trauma,deployment) as possible confounders. For parsi-mony, covariates were only retained in subsequentmodels if they altered the b coefficient of the primarypredictor, active PTSD, by 10% or more. All modelswere adjusted for multiple gestations given theirundisputed association with spontaneous pretermbirth. Our resulting primary model adjusted forage, race, multiple gestation, and deployment his-tory. We examined interaction terms for PTSD*mili-tary sexual trauma and PTSD*deployment history.We explored three possible explanatory pathways:preselected chronic comorbidities (hypertension,diabetes, asthma), behavioral risks (drug, alcohol,or tobacco use), and other mental health disordersfrequently codiagnosed with PTSD (those disorderswith prevalence 2% or more in our cohort). We did notinclude these as confounders in our primary analysisbecause they could arguably represent intermediatesteps in the causal pathway (ie, if the pathophysiologyof chronic PTSD predisposes women to the selectedcomorbidities). In evaluating the potential explanatoryrole of codiagnosed mental health conditions, weplaced these variables in regression models, bothalongside PTSD and in place of PTSD. Lastly, wetested our model assumptions in a series of sensitivityanalyses, including models restricted to first deliver-ies or singleton deliveries, models adjusted forobstetric history (eg, prior spontaneous pretermbirth, excluding multiples), and models applying

more restrictive timeframes (see Appendix 2, avail-able online at http://links.lww.com/AOG/A571, fora detailed description).

This research was approved by Stanford Univer-sitys institutional review board as part of the Wom-ens Health Evaluation Initiative.

RESULTS

The cohort included 16,334 deliveries among 14,047women. There were 1,248 (7.6%) spontaneous pre-term deliveries. Of the 16,334 deliveries, 3,049 (19%)were to women who carried an antepartum diagnosisof PTSD, two thirds of whom (1,921 [12%]) had activePTSD. Nearly one third of the deliveries (4,948) wereto women with recent deployment (Afghanistan orIraq); 3,568 (23%) deliveries were to women reportinga history of military sexual trauma.

Table 1 presents descriptive characteristics byPTSD status. Those with active PTSD were signif-icantly more likely to have been deployed (45%)than were those with historical (32%) or no PTSD(28%). Those with active and historical PTSDwere more likely to report military sexual trauma(57% and 46%) than those without PTSD (16%) andcarried a significantly higher burden of activecomorbid mental health, drug-, and alcohol-related diagnoses (P,.001 for all). The unadjustedproportion of spontaneous preterm birth (Table 1)was significantly higher in those with active PTSD(9.2%) than those with historical (8.0%) or no PTSD(7.4%) (P5.02).

In our primary adjusted model (Table 2), activePTSD remained associated with spontaneous pretermdelivery (adjusted OR 1.35 [1.141.61]), whereas his-torical PTSDs association was nonsignificant(adjusted OR 1.06 [0.841.34]).

Although deployment history was associated witha lower risk of spontaneous preterm birth, adjusted OR0.71 (0.610.81)consistent with our expectation thatthe selection process for deployment results in a subpop-ulation of healthier, lower-risk individuals (the healthywarrior effect)40we found no statistical support for oura priori hypothesis that deployment modifies the effectof PTSD (P5.42 for interaction term active PTSD*de-ployment added to our base model). In contrast, militarysexual trauma showed no association with spontaneouspreterm birth (unadjusted OR 1.08 [0.941.24]; adjustedOR 0.99 [0.841.15]; see Appendix 3, available onlineat http://links.lww.com/AOG/A571, Table A1).However, as shown in Table 3, when the interactionof military sexual trauma and PTSD was explored, weobserved that those with both active PTSD and mil-itary sexual trauma carried the greatest, and most

VOL. 124, NO. 6, DECEMBER 2014 Shaw et al PTSD and Risk of Spontaneous Preterm Birth 1113

Table 1. Characteristics of Deliveries Covered by the Veterans Administration (20002012), byPosttraumatic Stress Disorder Status

Characteristic

Deliveries by PTSD Status

P*

Active PTSD Diagnosis(Within 365 Days

Antepartum) (n51,921)

Historical PTSD Diagnosis(More Than 365 DaysAntepartum) (n51,128)

None(n513,285)

Spontaneous preterm birth 176 (9.2) 90 (8.0) 982 (7.4) .02Demographics

Maternal age (y) ,.0011924 273 (14.2) 65 (5.8) 2,290 (17.2)2529 787 (41.0) 429 (38.0) 5,257 (40.0)3034 515 (26.8) 375 (33.2) 3,689 (27.8)3539 269 (14.0) 198 (17.6) 1,614 (12.2)4048 77 (4.0) 61 (5.4) 435 (3.3)

Race ,.001White 1,344 (70.0) 776 (68.8) 8,142 (61.3)African American or black 371 (19.3) 243 (21.5) 3,059 (23.0)Asian 26 (1.4) 11 (1.0) 219 (1.7)Native Hawaiian or other Pacific

Islander36 (1.9) 9 (0.8) 188 (1.4)

American Indian or Alaskan Native 20 (1.0) 8 (0.7) 102 (0.8)Missing or declined to answer 124 (6.5) 81 (7.2) 1,575 (11.9)

Married 824 (43.2) 475 (43.0) 6,187 (47.5) ,.001Potential trauma exposure

Military sexual trauma 1,085 (57.7) 513 (46.2) 1,970 (15.7) ,.001Previously deployed (U.S. Operations

Enduring Freedom, IraqiFreedom, and New Dawn)

863 (44.9) 361 (32.0) 3,760 (28.3) ,.001

Obstetric historyTwins or higher-order gestation 41 (2.1) 31 (2.8) 276 (2.1) .3Prior cesarean delivery 275 (14.3) 195 (17.3) 1,847 (13.9) .007

Parity ,.0011 1,677 (87.3) 863 (76.5) 11,494 (86.5)2 220 (11.5) 223 (19.8) 1,574 (11.9)3 or more (maximum 5) 24 (1.3) 42 (3.7) 217 (1.6)

Prior spontaneous preterm delivery 30 (1.6) 25 (2.2) 132 (1.0) ,.001Chronic medical conditions (within 3 y

antepartum)Hypertension 169 (8.8) 91 (8.1) 835 (6.3) ,.001Diabetes 90 (4.7) 36 (3.2) 414 (3.1) .002Asthma 206 (10.7) 138 (12.2) 990 (7.5) ,.001

Substance abuse or dependence diagnoses(within 1 y antepartum)

Drug 217 (11.3) 50 (4.4) 387 (2.9) ,.001Alcohol 165 (8.6) 26 (2.3) 175 (1.3) ,.001Tobacco 351 (18.3) 143 (12.7) 1,219 (9.2) ,.001

Active mental health comorbidities (within1 y antepartum)

Depressive disorder 1,190 (62.0) 327 (29.0) 2,089 (15.7) ,.001Anxiety disorder (other than PTSD) 552 (28.7) 148 (13.1) 1,019 (7.7) ,.001Adjustment disorder 188 (9.8) 45 (4.0) 553 (4.2) ,.001Bipolar disorder 181 (9.4) 62 (5.5) 342 (2.6) ,.001Personality disorder 172 (9.0) 29 (2.6) 178 (1.3) ,.001

PTSD, posttraumatic stress disorder.Data are n (%) unless otherwise specified.* x2. Missing for 307 (2%). Missing for 814 (5%). Estimate; data unavailable for deliveries before 2000 and nonVeterans Health Administration deliveries.


significant, risk (adjusted OR 1.43 [1.151.77]),although the interaction term was not statistically sig-nificant (P5.25 for interaction term active PTSD*mi-litary sexual trauma).

In analysis of possible explanatory pathways (Table 4;see Appendix 3, http://links.lww.com/AOG/A571,Table A2 for full details), adjusting for comorbidhypertension, diabetes, and asthma, made little differ-encesuggesting that the higher prevalence of thesechronic conditions observed in PTSD-affected womendid not explain the increased risk of spontaneous pre-term birth. Only hypertension was a significant predic-tor of spontaneous preterm birth (adjusted OR 1.75[1.432.13]) and its addition to the model did not sig-nificantly change the effect of active PTSD (fromadjusted OR 1.35 to adjusted OR 1.33 [1.121.59]).Adjusting for drug, alcohol, and tobacco use mildlyattenuated the independent risk estimate for activePTSD (adjusted OR 1.29 [1.081.55]); among the threesubstance categories, only active drug dependence orabuse was itself a significant predictor (adjusted OR1.38 [1.031.85]). Lastly, adjusting for co-occurring psy-chiatric disorders, we found no evidence that an alter-native comorbid mental health condition betterexplained the effect observedno other active mentaldisorder was predictive of spontaneous preterm birth ata statistically significant level and, when all wereincluded in the model, the effect of active PTSD, inde-pendent of co-occurring mental disorders, remained

Table 3. Interaction of Posttraumatic StressDisorder Status and Military SexualTrauma History as Predictors ofSpontaneous Preterm Birth*

Multilevel VariableCombining PTSDand Military Sexual

Trauma Status

n OR 95% CI PPTSD

MilitarySexualTrauma

Active + 1,085 1.43 1.151.77 .001Active 2 797 1.19 0.891.58 .2Historical + 598 0.93 0.661.33 .7Historical 2 513 1.16 0.851.57 .3None + 1,970 0.96 0.791.16 .7None 2 10,557 1 Reference Reference

OR, odds ratio; CI, confidence interval; PTSD, posttraumatic stressdisorder; +, positive screen; 2, negative screen.

* In model adjusted for age, race, twins or higher-order gestations,and deployment history.

Table 2. Association of Posttraumatic Stress Disorder Status and Spontaneous Preterm Birth: Unadjustedand Primary Adjusted Model (N516,334; Preterm Delivery Events51,248)

Parameter n

Unadjusted Model Multivariate Model*

OR 95% CI P aOR 95% CI P

PTSDNone 13,285 1 Reference 1 ReferenceHistorical (more than 365 d antepartum) 1,128 1.09 0.871.36 0.5 1.06 0.841.34 .6Active (within 365 d antepartum) 1,921 1.26 1.071.50 0.006 1.35 1.141.61 ,.001

Maternal age (y)1925 2,628 1 Reference2529 6,473 0.99 0.831.19 .93034 4,579 1.15 0.961.40 .13539 2,081 1.19 0.951.49 .140 or older 573 1.21 0.871.69 .3

RaceWhite 10,262 1 ReferenceBlack or African American 3,673 1.49 1.291.71 ,.001Asian 256 1.27 0.821.96 .3American Indian or Alaskan Native 187 1.99 1.153.45 .01Hawaiian or Pacific Islander 130 1.35 0.852.13 .2Missing or not reported 1,780 1.10 0.901.35 .3

Twins or higher-order gestation 348 7.15 5.669.03 ,.001Deployed (U.S. Operations Enduring Freedom, Iraqi

Freedom, and New Dawn)4,984 0.71 0.610.81 ,.001

OR, odds ratio; CI, confidence interval; aOR, adjusted odds ratio; PTSD, posttraumatic stress disorder.* Generalized estimating equations with logit linkage and clustered by unique individual using exchangeable correlation matrix for repeat

deliveries. Independent variables are those listed. Model fit: C-statistic (in logistic regression model without clustering)50.62 in adjustedmodel as compared with 0.52 in unadjusted model;58,536.6 in the adjusted model as compared with 8,816.0 in the unadjusted model.


similar and significant (adjusted OR 1.30 [1.071.58]).Numerous additional sensitivity analyses of our modelwere exploredincluding adjusting for prior spontaneouspreterm birth, restricting cohort to first deliveries, rein-clusion of dropped demographic covariates, and alterna-tive timeframes and definitions for active PTSDand theeffect size for active PTSD remained robust (Table 5; seeAppendix 3, http://links.lww.com/AOG/A571, TablesA3A5 for full details).

DISCUSSION

We analyzed an unprecedented1423 number of partu-rients with active PTSD (nearly 2,000) within a healthcare system that routinely screens for PTSD and af-firmed it is associated with increased risk of spontane-ous preterm deliverya finding robust to adjustmentfor other known risk factors. The 35% increased oddsof spontaneous preterm delivery in those with activePTSD is clinically relevant (two excess preterm birthsper 100 affected deliveries) and on par with risks suchas advanced maternal age (older than 35 years)41 and,

within our cohort, only slightly smaller than the well-established risk factor of African American race.

Our findings build on suggestive previous studiestoo small to detect this association.1423 We benefit froma design that confirms PTSD temporally preceded thedelivery, adding support for a causal relationship. TheVeterans Health Administration has mandatory PTSDscreening, using a validated instrument24 built intothe electronic medical record,42 and our reliance onclinician-entered encounter diagnoses is supported byprior Veterans Health Administration studies confirm-ing the ICD-9-CM diagnosis reliably predicts PTSD.30,31

Several limitations are noteworthy. First, we wereunable to measure degree of prematurity and do notaccount for medically indicated (eg, induced) pretermbirths; however, the preterm births that we focused onspontaneousdisproportionately account for very pre-term births3 and are most relevant to understanding therole stress plays in early-onset delivery. Second,deployment and military sexual trauma were the onlytwo trauma exposures examined; neither demonstratedsignificant interaction with PTSD, but they are unlikely

Table 5. Key Sensitivity Analyses of the Association of Active Posttraumatic Stress Disorder andSpontaneous Preterm Birth: Robustness Checks of Model Structure

Model Structural Assumptions Modified aOR 95% CI P

5 Model 1 with adjustment for prior spontaneous preterm birth 1.35 1.131.60 ,.0016 Model 1 with cohort restricted to first deliveries (n514,034) 1.37 1.141.65 ,.0017 Model 1 with cohort restricted to singleton deliveries (n515,986) 1.32 1.101.59 .0038 Model 1 with cohort restricted to deliveries after year 2007* (n59,932) 1.36 1.101.69 .004

aOR, adjusted odds ratio; CI, confidence interval.All models use generalized estimating equations with logit linkage, clustered by unique individual for repeat deliveries, except Model 6,

which had no repeat deliveries and thus used standard logistic regression. N516,334 in all models unless otherwise specified.* Year in which an electronic reminder for PTSD screening implemented in the Veterans Health Administration.

Table 4. Key Sensitivity Analyses of the Association of Active Posttraumatic Stress Disorder andSpontaneous Preterm Birth: Exploration of Potential Intermediaries

Model Covariates Included

Active PTSD*: aOR of Preterm Birth(Reference5No PTSD)

aOR 95% CI P

1 (base model) PTSD status*+age+race+twins or higher order+deployed 1.35 1.141.61 ,.0012 Model 1+chronic disease indicators 1.32 1.111.58 .0023 Model 1+substance abuse 1.29 1.081.55 .0054 Model 1+other psychiatric diagnosesk 1.30 1.071.58 .004

PTSD, posttraumatic stress disorder; aOR, adjusted odds ratio; CI, confidence interval.All models use generalized estimating equations with logit linkage, clustered by unique individual for repeat deliveries, except Model 6,

which had no repeat deliveries and thus used standard logistic regression. N516,334 in all models unless otherwise specified.* PTSD status modeled as three-level variable (active, historical, or none), but for simplicity, only active PTSD results shown; see Appendix 3

(http://links.lww.com/AOG/A571) for full results. Previously deployed in service of U.S. Operations Enduring freedom, Iraqi Freedom, or New Dawn. Chronic disease indicators are hypertension, diabetes, and asthma. Substance abuse is drug dependence or abuse, alcohol dependence or abuse, and tobacco use diagnoses in the prenatal period.k Psychiatric diagnoses adjusted for are depressive, anxiety, adjustment, bipolar, and personality disorders.


the only sources of PTSD in our sample, and we cannotcomment on the role of premilitary trauma. Third, thegeneralizability of our findings to non-Veterans HealthAdministration populations is uncertain. However, theassociation is not unique to combat veterans becausethe majority of our cohort was nondeployed. The spon-taneous preterm birthrate in our cohort (7.6%) is similarto the 8.1% observed nationally43; the 12% prevalenceof active PTSD in our veteran cohort is disturbinglyhigh but comparable to the 714% reported in popula-tions receiving maternity care in urban, public-payerclinics.32,44 Military women experience diverse trau-mas, yet their most common antecedent of PTSDremains sexual trauma45the same as for women inthe general population.46

Although we cannot rule out unmeasured orresidual confounding, the robustness of our findingsto adjustments for known risk factors is reassuring.The stark difference observed for active comparedwith historical PTSD suggests we are not confoundedby the shared, unobserved, sociodemographic char-acteristics predisposing these mothers to PTSD. Onepotential confounder is antidepressant use. Althoughprior observation links antidepressants to pretermbirth,47 it remains uncertain whether the effect is fromantidepressants or the underlying depression9; adjust-ing for antidepressant use may introduce additionalconfounding (by indication) rather than resolvingit.48 Given this, and limitations of Veterans HealthAdministration pharmacy data, we did not adjust forpsychiatric medication use. However, post hoc analy-sis confirms that women with active antenatal depres-sion were more likely prescribed antidepressantsthan women with active PTSD. If antidepressant useexplained the increased spontaneous preterm riskassociated with PTSD, we would see equal or greaterincreased risk among the more than 3,500 deliveriesto women with active depression; but, in our cohort,we detected no such signalthus, it is improbable thatantidepressant use is the pathway from PTSD to spon-taneous preterm birth.

Our study adds to the nascent understanding ofthe relationship between stress and preterm labor,suggesting the abnormal stress response imparted byPTSD49 might contribute to premature delivery. Italso identifies PTSD-affected patients as an importantclinical population in which to focus efforts to eluci-date, and hopefully interrupt, the pathway from stressto preterm birth. Plausible biologic mechanisms asso-ciating PTSD with spontaneous preterm birth includeneuroendocrine, inflammatory, and cardiovascularalterationsall of which have been implicated inour incomplete understanding of premature labor.3

Among the indirect mechanisms that we could exam-ine, drug abuse and hypertension only slightly atten-uated the relationship between active PTSD andspontaneous preterm delivery, suggesting direct ef-fects over and above these factors.

Identifying PTSD-affected pregnancies as high riskis clinically important and widely relevant. One in 20U.S. pregnancies is likely in women affected by PTSD12

and one in five among women veterans returning frommilitary duty in Iraq and Afghanistan.26

Regardless of setting or population, obstetric andprimary care providers will inevitably find them-selves caring for women with active PTSD inpregnancy and preconception and need to be awareof it as a risk factor. Brief, effective screening toolsfor PTSD exist24 and could feasibly be included inprenatal care, especially in populations with highprevalence. Our study highlights the importance ofensuring women with PTSD are connected to appro-priate mental health care in the prenatal periodnot only to address stress dysregulation, but alsothe potential maladaptive behaviors that too oftenaccompany untreated PTSD, and raises hope thatappropriate treatment will not only improve maternalwell-being, but may well improve infant outcomes. Iffuture clinical trials determine that PTSD treatmentreduces risk for preterm delivery, we will have a blue-print for how to prevent the invisible wounds oftrauma from extending into the next generation.

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Maintenance of Certication Articles

Maintenance of Certication is a program of the American Board of Obstetrics and Gynecology (ABOG; http://www.abog.org). All articles from the reading lists for the current year will be listed on the Obstetrics & Gynecology web site at the beginning of January, May, and August.

To access the lists, go to www.greenjournal.org and click on the ABOG MOC II tab.

Links to content are provided, as well as an indication of the articles status (ie, available by subscription only or open access).

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