Abstract
Objective:
To evaluate the association between periviable delivery and new onset or exacerbation of existing mental health disorders within 12 months postpartum.
Methods:
Retrospective cohort study of individuals with a liveborn singleton delivery ≥22 weeks’ gestation from 2008–2017 in the MarketScan Commercial Research Database. The exposure was periviable delivery, defined as delivery between 22w0d and 25w6d. The primary outcome was a mental health morbidity composite of one or more of the following: emergency department encounter associated with depression, anxiety, psychosis, posttraumatic stress disorder, adjustment disorder, self-harm or suicide; new psychotropic medication prescription; new behavioral therapy visit; or inpatient psychiatry admission in the 12 months post-delivery. Secondary outcomes included components of the primary composite. Those with and without periviable delivery were compared using multivariable logistic regression adjusted for clinically relevant covariates, with results reported as adjusted incident rate ratios (aIRR). Effect modification by history of mental health diagnoses was assessed. Incidence of the primary outcome by 90-day intervals post-delivery was assessed.
Results:
Of 2,300,244 deliveries included, 16,275 (0.7%) were periviable. Individuals with periviable delivery were more likely to have a chronic health condition (43.9% vs 35.9%, p<0.001), have a cesarean delivery (46.3% vs 34.5%, p<0.001), and experience severe maternal morbidity (4.2% vs 1.2%, p<0.001). Periviable delivery was associated with increased risk of the primary composite, occurring in 13.8% with and 11.0% without periviable delivery (aIRR 1.18, 95% CI 1.12–1.24). Periviable delivery was associated with increased risk of new psychotropic medication (aIRR 1.16, 95% CI 1.09–1.23), new behavioral therapy (aIRR 1.18, 95% CI 1.109–1.27), and inpatient psychiatry services (aIRR 1.57, 95% CI 1.02–2.30). History of mental health diagnosis did not modify the association between periviable delivery and mental health outcomes (interaction p=0.37). The highest risk period for the composite primary outcome was the first 90 days in those with versus without periviable delivery (51.6% vs 42.4%; IRR 1.56, 95% CI 1.47–1.66).
Conclusions:
Periviable delivery was associated with mental health morbidity in the 12 months postpartum. The first 90-days represented the highest risk period for mental health care utilization.
Précis:
New onset or exacerbation of existing mental health disorders was common in the first 12 months following periviable delivery.
Introduction
Pregnancy is a risk factor for new onset, or worsening of pre-existing, mental health disorders.1,2 Unexpected outcomes such as stillbirth and miscarriage, as well as pregnancy complications, are associated with increased risk for postpartum depression.3–5 Preterm delivery less than 37 weeks’ gestation is often an unanticipated and stressful life event and is associated with higher rates of postpartum depression.6,7
Periviable delivery, defined as delivery at 22 to 26 weeks’ gestation when infant survival is possible but not probable, affects <1% of pregnancies but carries additional uncertainties about both immediate and long-term neonatal outcomes, and requires complex parental decision making about perinatal interventions.8,9 Further, periviable deliveries may stress finances, relationships, and maternal physical health.10,11 For neonates surviving beyond the immediate neonatal period, families may face months-long admissions to the neonatal intensive care unit (NICU) and years of potential complex childhood health care needs.
Increased self-reported parental depression following periviable deliveries has been described, especially when parents perceive low decision control.12 The death of a child has been associated with increased risk of parental psychiatric hospitalization.13 In a survey of 188 families following the death of a child in the neonatal or pediatric intensive care unit, 31.8% reported parental hospitalization within the subsequent 13 months; of these, 28% were attributed to mental health diagnoses.14 The association between periviable delivery itself and new onset or exacerbation of existing mental health disorders is less clear. Prior studies have been limited to survey methodology which is at risk for recall bias, and larger studies have not been completed due to the rarity of periviable delivery. The MarketScan Research Database provides data from commercial insurance claims providing a large, nationally representative U.S. sample.15 Using this database, we aimed to evaluate the association between periviable delivery and new onset or exacerbation of existing mental health disorders within the first 12 months postpartum. We hypothesized periviable delivery would be associated with an increased risk of new onset or exacerbation of existing mental health disorders.
Methods
This was a retrospective cohort study of individuals with a liveborn singleton delivery ≥22 weeks’ gestation between 2008 and 2017 in the MarketScan Commercial Research Database. MarketScan contains data from inpatient, outpatient, and pharmacy commercial health insurance claims for all U.S. states.15 This analysis used the commercial health insurance dataset only.
All deliveries in females aged 13 to 50 were identified using a validated algorithm of International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnosis and procedure codes, Diagnosis Related Group (DRG) codes, and Current Procedural Terminology (CPT) codes for delivery.16 The study timespan included the conversion from ICD-9-CM to the updated International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM). Therefore, the utilized codes in the enhanced delivery identification algorithm were cross-walked to ICD-10-CM (Appendix 1).
The gestational age at delivery was derived using adaptation from a hierarchical algorithm previously described.17–21 In brief, for records with linked maternal-neonatal records (2011–2017), gestational age was determined using neonatal diagnosis codes specifying gestational age at delivery. For records without linked maternal-neonatal records (2008–2011), either antepartum procedural codes (e.g., nuchal translucency, gestational diabetes screening, amniocentesis) and delivery date were utilized to assign gestational age, or maternal ICD codes associated with gestational age were used (Appendix 2). Deliveries in the first nine months of the study period in 2008 were excluded to allow a lead-in period for availability of diagnosis codes within MarketScan necessary for delivery identification and gestational age assignment.
Both multifetal gestation and stillbirth are associated with postpartum mental health morbidity and were therefore excluded to focus this analysis on the association between periviable singleton live birth and mental health morbidity.3,4 Only the first delivery for an individual within the database was included. Individuals without at least nine months of insurance enrollment prior to delivery were also excluded.
The primary exposure was periviable delivery, defined as delivery between 22 weeks 0 days and 25 weeks 6 days gestation. Though deliveries >20 weeks 0 days are included in the American College of Obstetricians and Gynecologists (ACOG) guidelines on periviability, this study used a gestational age threshold of ≥22 weeks 0 days consistent with guidelines on availability of interventions (e.g., corticosteroids, resuscitation).9,22 This allowed the analysis to focus on deliveries with a chance of neonatal survival.
The primary outcome was a mental health morbidity composite of emergency department encounters for mental health disorders (depression, anxiety, psychosis, posttraumatic stress disorder, adjustment disorder), self-harm, or suicide; new psychotropic medication; new behavioral therapy visit; or use of inpatient psychiatry services. Secondary outcomes included components of the primary composite. Outcomes were assessed up to 365 days following delivery.
Emergency department encounters for mental health disorders were defined as emergency department encounters with ICD-CM diagnosis codes for psychiatric diagnoses of depression, anxiety, psychosis, posttraumatic stress disorder, adjustment disorder, self-harm, or suicide attempt based on previously established ICD-CM codes in the literature (Appendix 3).4,23,24 New psychotropic prescriptions were identified using pharmacy claims for medications identified by National Drug Codes (NDC) for antidepressants, antipsychotics, anxiolytics, and stimulants.25 New behavioral therapy visits were assessed using insurance claims for therapy. For the purposes of the primary analysis, ‘new’ was defined as a psychotropic medication prescription or behavioral therapy visit with no history of psychotropic medication prescriptions or behavioral therapy visits in the 9 months prior to delivery. Inpatient psychiatry services were assessed using insurance claims for inpatient services through MarketScan. Follow-up was censored at the first of the following: 12 months after index delivery, discontinuation of MarketScan insurance enrollment, or new pregnancy identifier present.
For every delivery, maternal demographics, medical history, and delivery characteristics were recorded. Maternal comorbidities were identified during the pregnancy and delivery hospitalization using ICD-CM codes adapted from the conditions included in the maternal comorbidity index (Appendix 4).26–28 The presence of any maternal comorbidity condition was recorded, as well as specific co-morbid conditions within the index, such as diabetes mellitus and chronic hypertension. Presence of severe maternal morbidity was assessed at delivery admission using the Centers for Disease Control and Prevention maternal morbidity ICD-CM code-based definitions.29 Severe maternal morbidity during delivery admission has been associated with psychiatric illness in the 12 months postpartum and we planned a priori to control for this in multivariable analysis.5 A history of mental health disorder was defined by an ICD code diagnosis for depression, anxiety, psychosis, posttraumatic stress disorder, or adjustment disorder in the 9 months prior to delivery.
Demographic and baseline clinical data were compared between those with and without periviable delivery using Chi-squared tests for categorical variables and Kruskal-Wallis tests for continuous variables. Unadjusted and adjusted logistic regression was performed for the primary and secondary outcomes controlling for clinically relevant covariates. Covariates selected a priori included mode of delivery, maternal age, presence of any component of the severe maternal morbidity definition, presence of any condition within the maternal comorbidity index, and mental health history. The unadjusted and adjusted incidence rate ratios (IRR) are reported for the effect of periviable delivery on outcomes. Individuals with missing data for key covariates were excluded in multivariable regression.
In the primary analysis, individuals with or without a history of mental health disorders were included. To evaluate whether a history of mental health disorder altered the relationship between periviable delivery and outcomes, effect modification was assessed using an interaction term between periviable delivery and the presence or absence of mental health disorder history.
In secondary analysis, the incidence of the primary composite outcome was assessed by 90-day intervals for the first 12 months postpartum. The incidence of the primary composite outcome was compared among individuals with and without periviable delivery within each 90-day interval using logistic regression with the number of days enrolled in MarketScan included as an offset.
To address potential confounding by ongoing insurance enrollment, a sensitivity analysis was performed limited to those individuals with insurance enrollment in MarketScan for the full 365 days postpartum.
A two-sided p<0.05 was considered statistically significant. This analysis is considered exploratory and hypothesis generating with adjustments for multiple comparisons not made to avoid false negatives.30 This study was exempt from Institutional Review Board (IRB) approval given use of deidentified data. All analyses were completed using R version 4.0. The Strengthening the Reporting of Observational Studies in epidemiology (STROBE) reporting guidelines for observational studies were followed.31
Results
Following exclusions, the final cohort included 2,300,244 individuals, of whom 16,275 (0.71%) had periviable deliveries (Figure 1). Demographic and clinical characteristics were compared between those with and without periviable delivery. The median gestational age at delivery was 24 weeks (IQR 23.0–24.5) in the periviable delivery group compared to 38 weeks (IQR 35.4–39.0) in the non-periviable delivery group. Tier 1 of the gestational age algorithm (Appendix 2) resulted in a gestational age assignment for the majority of included deliveries (99.9% non-periviable vs 99.1% periviable). There were marginal increases in gestational age ascertainment with the addition of tiers 2 and 3 (0.1% for non-periviable vs 0.9% for periviable deliveries). Individuals in the periviable delivery group were more likely to have medical comorbidities defined by the maternal comorbidity index (43.9% vs 35.9%, p<0.001), to deliver by cesarean (46.3% vs 34.5%, p<0.001), and to experience severe maternal morbidity (4.2% vs 1.2%, p<0.001) during delivery hospitalization (Table 1).
Figure 1.
Study population.
*A pregnancy may meet more than one exclusion criterion.
Table 1.
Baseline characteristics for the analytic population by periviable or non-periviable delivery
| Characteristic | Full Cohort (N=2,300,244) |
Periviable delivery (n=16,275) |
Non-periviable delivery (n=2,283,969) |
p |
|---|---|---|---|---|
| Age (years) | 31 (25–34) | 30 (25–34) | 31 (27–34) | <0.001 |
| Urban residence | 2,012,929 (87.51) | 13,209 (81.16) | 1,999,720 (87.55) | <0.001 |
| Region | <0.001 | |||
| Northeast | 396,220 (17.23) | 1,854 (11.39) | 394,366 (17.27) | |
| Midwest | 518,373 (22.54) | 3,531 (21.70) | 514,842 (22.54) | |
| South | 903,986 (39.3) | 7,327 (45.02) | 896,659 (39.26) | |
| West | 433,265 (18.84) | 3,163 (19.43) | 430,102 (18.83) | |
| Unknown | 48,400 (2.1) | 400 (2.46) | 48,000 (2.1) | |
| Gestational age (delivery, in weeks) | 37.7 (35.3–39.0) | 24 (23.0–24.5) | 37.7 (35.4–39.0) | <0.001 |
| Mode of delivery | <0.001 | |||
| Cesarean | 794,932 (34.56) | 7,534 (46.29) | 787,398 (34.47) | |
| Spontaneous vaginal delivery | 1,402,309 (60.96) | 8,096 (49.75) | 1,394,213 (61.04) | |
| Operative vaginal delivery | 96,878 (4.21) | 406 (2.49) | 96,472 (4.22) | |
| Unknown | 6,125 (0.27) | 239 (1.47) | 5,886 (0.26) | |
| Severe maternal morbidity* | 27,841 (1.21) | 687 (4.22) | 27,154 (1.19) | <0.001 |
| Maternal Comorbidity Index* | 827,508 (35.97) | 7,140 (43.87) | 820,368 (35.92) | <0.001 |
| Maternal comorbidities | ||||
| Hypertensive disorders of pregnancy | 162,716 (7.07) | 1,929 (11.85) | 1620,787 (7.04) | <0.001 |
| Pre-existing hypertension | 117,156 (5.09) | 1,890 (11.61) | 115,266 (5.06) | <0.001 |
| Gestational diabetes | 312,603 (13.59) | 2,116 (13.0) | 310,487 (13.59) | 0.029 |
| Pre-existing diabetes | 86,538 (3.76) | 994 (6.11) | 85,544 (3.75) | <0.001 |
| Mental health history | ||||
| Depression | 76,568 (3.33) | 698 (4.29) | 75,870 (3.32) | <0.001 |
| Anxiety | 76,177 (3.31) | 638 (3.92) | 75,539 (3.31) | <0.001 |
| Psychosis | 1,481 (0.06) | 22 (0.14) | 1,459 (0.06) | 0.001 |
| Posttraumatic stress disorder | 5,080 (0.22) | 45 (0.28) | 5,035 (0.22) | 0.152 |
| Adjustment disorder | 44,440 (1.93) | 336 (2.06) | 44,104 (1.93) | 0.228 |
| Pregnancy complications | ||||
| Fetal growth restriction | 279,714 (12.16) | 2,736 (16.81) | 276,978 (12.13) | <0.001 |
| Assisted reproductive technology (ART) | 24,269 (1.06) | 276 (1.7) | 23,993 (1.05) | <0.001 |
| Placental abruption | 27,058 (1.18) | 1,114 (6.84) | 25,944 (1.14) | <0.001 |
Presented as n(%) for categorical data or median (interquartile range) for continuous data
Presence of at least 1 component
The primary composite outcome occurred in the first 12 months postpartum following 2,242 periviable deliveries (14%) and 252,038 non-periviable deliveries (11%). In both unadjusted and adjusted models, periviable delivery was associated with increased likelihood of experiencing the composite primary outcome (IRR 1.25, 95% CI 1.10–1.42; aIRR 1.18, 95% CI 1.12–1.24; Table 2). The incidence of emergency department visits for mental health disorder, self-harm or suicide attempt did not differ by periviable (0.8%) versus non-periviable delivery (0.5%; aIRR 1.24, 95% CI 1.00–1.52). Periviable delivery was associated with new psychotropic medication (aIRR 1.16, 95% CI 1.09–1.23) and new behavioral therapy visits (aIRR 1.18, 95% CI 1.09–1.27). Periviable delivery was not associated with inpatient psychiatry services in unadjusted modeling but was associated in adjusted modeling (0.25% after periviable delivery vs 0.12% after non-periviable delivery; IRR 2.03, 95% CI 0.80–4.16; aIRR 1.57, 95% CI 1.02–2.30).
Table 2.
Primary and secondary mental health outcomes in 12 months following delivery among individuals with and without periviable delivery
| Outcome | Periviable delivery (n=16,275) |
Non-periviable delivery (n=2,283,969) |
Unadjusted IRR (95% CI) |
Adjusted IRR (95% CI) |
|---|---|---|---|---|
| Composite primary outcome | 2,242 (13.78) | 252,038 (11.04) | 1.25 (1.10–1.42) | 1.18 (1.12–1.24) |
| ED visit (all) | 131 (0.80) | 11,829 (0.52) | 1.56 (0.75–2.82) | 1.24 (1.00–1.52) |
| Suicide attempt/self-harm | 2 (0.01) | 181 (0.01) | † | † |
| Depression | 65 (0.4) | 6,017 (0.26) | † | † |
| Anxiety | 76 (0.47) | 6,757 (0.3) | † | † |
| PTSD | 4 (0.02) | 168 (0.01) | † | † |
| Psychosis | 7 (0.04) | 392 (0.02) | † | † |
| Adjustment disorder | 11 (0.07) | 657 (0.03) | † | † |
| New psychotropic medication | 1,300 (7.99) | 148,065 (6.48) | 1.24 (1.05–1.44) | 1.16 (1.09–1.23) |
| New behavioral therapy visits | 1,337 (8.22) | 151,159 (6.62) | 1.25 (1.11–1.40) | 1.18 (1.09–1.27) |
| Inpatient psychiatry services | 41 (0.25) | 2,839 (0.12) | 2.03 (0.80–4.16) | 1.57 (1.02–2.30) |
Data as n(%); Unadjusted and adjusted incident rate ratio (IRR)
ED, emergency department; PTSD, posttraumatic stress disorder
Unable to report secondary to low numbers
Adjusted for delivery mode, maternal age, severe maternal morbidity (SMM), maternal comorbidity index (MCI), and mental health history
In testing for effect modification, the association between periviable delivery and the primary composite was not modified by history of mental health disorder (no mental health history: IRR 1.19, 95% CI 1.12–1.26 vs with mental health history: IRR 1.11, 95% CI 1.04–1.17; interaction p-value 0.373). Mental health history did not modify the association between periviable delivery and emergency department visit for mental health, new psychotropic medication, new behavioral therapy visits, or inpatient psychiatry services (Figure 2).
Figure 2.
Adjusted incident rate ratios for primary and secondary outcomes after periviable delivery including interaction with history of mental health diagnosis
Emergency department (ED)
Adjusted for delivery mode, maternal age, severe maternal morbidity (SMM), and maternal comorbidity index (MCI). P-value <0.002 considered statistically significant.
In secondary analysis among all individuals experiencing the primary outcome with or without periviable delivery, the primary composite occurred in 42.5% in the first 90 days postpartum (first quarter) followed by 24.4% in the second, 18.3% in the third, and 14.8% in the fourth quarter. The incidence of the primary composite outcome was higher in the first quarter among those with versus without periviable delivery (51.6% vs 42.4%; IRR 1.56, 95% CI 1.47–1.66). The incidence of the primary composite outcome was lower among those with versus without periviable delivery in the second (22.2% vs 24.4%; IRR 0.88, 95% CI 0.80–0.98), third (14.2% vs 18.4%; IRR 0.74, 95% CI 0.65–0.84) and fourth quarters (12.0% vs 14.8%; IRR 0.81, 95% CI 0.71–0.93) (Figure 3).
Figure 3.
Kaplan-Meier Curve for primary mental health composite outcome in the 12 months following delivery by 90-day intervals by periviable delivery Unadjusted Kaplan-Meier curves for the primary composite outcome by periviable delivery (PVD) and non-periviable delivery (Non-PVD) as time since delivery (Log rank test p<0.001). Shading represent 95% confidence intervals (CIs).
In sensitivity analyses limited to those who retained commercial insurance in MarketScan for a full 365 days postpartum, results were similar (Appendix 5).
Discussion
In this large retrospective cohort study, mental health morbidity, including new-onset or exacerbation of existing mental health disorders, was common in the first 12 months postpartum among those with and without periviable delivery (13.8% and 11.0%, respectively). Periviable delivery was associated with a higher incidence of the primary composite outcome, new psychotropic medication, new behavioral therapy visits, and inpatient psychiatry services but not emergency department visits for mental health. The incidence of new-onset or exacerbation of existing mental health disorders was highest in the first 90 days after periviable delivery.
Our findings are consistent with national data suggesting a 1 in 7 prevalence of perinatal depression with postpartum depression and anxiety affecting 14–20%.2,32,33 Previous studies have demonstrated a further increased risk for perinatal depression following an unexpected pregnancy outcome, including miscarriage, stillbirth, or traumatic birth.3,4,6,7 Similarly, increased mental health morbidity has been found following complicated pregnancies, such as multifetal gestations or those affected by severe maternal morbidity.5,7,8 While the magnitude of association between our outcome and exposure was modest, our findings suggest periviable delivery is another pregnancy outcome resulting in heightened mental health risk.
Prior studies found 28% of parental hospitalizations in the 13 months following death of a child in the NICU were associated with mental health diagnoses.14 We found emergency department utilization for self-harm, suicide, or mental health diagnoses was low in the 12 months postpartum and did not differ by periviable delivery. While rare overall, periviable delivery was associated with higher utilization of inpatient psychiatry services.
ACOG has outlined recommendations for perinatal mental health screening and interventions.33 In particular, efforts have been made to emphasize the “Fourth Trimester” – the 12 weeks following delivery – as a critical period of ongoing maternal, and mental, health needs.34,35 Our findings support these ongoing clinical efforts. While new-onset or exacerbation of mental health disorders were identified most commonly in the first 90 days after delivery, it is worth noting that these outcomes were prevalent throughout the first postpartum year. Continued allocation of resources for screening and treatment are likely valuable beyond the first 90 days of postpartum care.34
Those with periviable delivery had higher rates of pregnancy complications including maternal co-morbid conditions, fetal growth restriction, abruption, and severe maternal morbidity. These concomitant maternal morbidities could influence maternal mental health further. However, models were adjusted for both maternal comorbidity index and severe maternal morbidity, suggesting periviable delivery itself is independently associated with risk for new-onset or exacerbation of existing maternal health disorders.
Our study has strengths. The MarketScan database provided a large sample size representative of the geographic diversity of the United States. Additionally, the large database allowed us to evaluate a rare outcome, periviable singleton births, while excluding stillbirth and multifetal gestation to reduce confounding.3,7 Similarly, we are able to adjust for severe maternal morbidity, a rare event, in analyses.5 The selected ICD-CM codes for delivery outcomes, mental health disorders, and comorbidities have previously been used and validated.16,23,24,26–29,36 We were able to evaluate clinician-diagnosed mental health disorders while prior studies have relied largely on patient self-report. This data source allowed assessment of a rare event.
This study also has limitations. The database reflects commercial insurance-claims, and therefore findings are not generalizable to patients of all insurance types. Use of ICD-CM diagnosis and procedure codes for outcome and covariate identification in a large database risks under-ascertainment and misclassification. Clinical details surrounding indication for delivery, periviable decision making, and long-term neonatal outcomes could not be assessed.37,38 Additional social support through maternal and neonatal health care teams may be offered following periviable delivery; differences in detection rates for outcomes by group attributable to variable health care system contact could not be adjusted for in analyses. While we found an association between periviable delivery and postpartum mental health morbidity, our findings in a retrospective cohort study are modest and cannot demonstrate causality. Use of a claims database requires continuous insurance enrollment to ascertain outcomes. However, in sensitivity analysis excluding individuals without 365 days of postpartum follow-up, results were similar.
The observed association lends support to the concept that pregnancy complications such as periviable delivery compound the mental health risk related to pregnancy and delivery itself. Heightened awareness of periviable delivery as a potential trigger for worsening of mental health disorders may be warranted.
Supplementary Material
Acknowledgements:
We thank the University of Utah Department of Surgery and the Surgical Population Analysis Research Core for its role in facilitating data collection, database management, and analysis.
Funding:
There was no funding for this work.
Financial Disclosure:
Dr. Smid serves as a medical consultant for Gilead Science Incorporated, Organon Inc and American Academy of Addiction Psychiatrist. Dr. Smid also receives funding from National Institute on Drug Abuse and the Centers for Disease Control and Prevention. Outside of the submitted work, Dr. Metz reports personal fees from Pfizer for her role as a medical consultant for a SARS-CoV-2 vaccination in pregnancy study, grants from Pfizer for role as a site PI for SARS-CoV-2 vaccination in pregnancy study, grants from Pfizer for role as a site PI for RSV vaccination in pregnancy study, and grants from Gestvision for role as a site PI for a preeclampsia study. The other authors report no conflict of interest.
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