Faculty Bibliography

OBJECTIVE:The objective of this study was to characterize the risk for severe maternal morbidity and other pregnancy complications by maternal age during delivery hospitalizations. STUDY DESIGN:This retrospective cohort analysis used the Perspective database to characterize the risk for adverse maternal outcomes from 2006 to 2015 based on maternal age. Women were divided into 7 categories based on maternal age: 15-17, 18-24, 25-29, 30-34, 35-39, 40-44, and 45-54 years of age. The primary outcome of this study was severe maternal morbidity as defined by the Centers for Disease Control and Prevention. Secondary outcomes included (1) overall comorbid risk; (2) risk for pregnancy complications such as postpartum hemorrhage, gestational diabetes, preeclampsia, and cesarean delivery; and (3) risk for individual severe morbidity diagnoses such as stroke, embolism, eclampsia, and hysterectomy. Adjusted models were fitted to assess factors associated with severe morbidity with adjusted risk ratios (aRRs) and 95% confidence intervals (CI) as measures of effect. Population weights were applied to create national estimates. RESULTS:Of 36,944,292 deliveries included, 2.5% occurred among women aged 15-17 years (n = 921,236), 29.1% to women aged 18-24 years (n = 10,732,715), 28.6% to women aged 25-29 years (n = 10,564,850), 24.9% to women aged 30-34 years (n = 9,213,227), 12.1% to women aged 35-39 years (n = 4,479,236), 2.6% to women aged 40-44 years (n = 974,289), and 0.2% to women aged 45-54 years (n = 58,739). In unadjusted analyses, severe morbidity was more than 3 times higher (risk ratio [RR], 3.33, 95% confidence interval [CI], 3.03-3.66) for women 45-54 years compared with women 25-29 years. Women aged 40-44, 35-39, and 15-17 years were also at increased risk (RR, 1.83, 95% CI, 1.77-1.89; RR, 1.36, 95% CI, 1.33-1.39; RR, 1.39, 95% CI, 1.34-1.45, respectively). In the adjusted model, the 45-54 year old group was associated with the highest relative risk (aRR, 3.46, 95% CI, 3.15-3.80) followed by the 40-44 year old group (aRR 1.90, 95% CI, 1.84-1.97), the 35-39 year old group (aRR, 1.43, 95% CI, 1.40-1.47), and the 15-17 year old group (aRR, 1.20, 95% CI, 1.15-1.24). Cesarean delivery, preeclampsia, postpartum hemorrhage, and gestational diabetes were most common among women aged 45-54 years, as were thrombosis and hysterectomy. CONCLUSION:While differential risk was noted across maternal age categories, women aged 45 years old and older were at highest risk for a broad range of adverse outcomes during delivery hospitalizations.

OBJECTIVE:To assess trends in use of long-acting opioids during delivery hospitalizations. METHODS:The Perspective database, an administrative inpatient database that includes medication receipt, was analyzed to evaluate patterns of long-acting opioid use during delivery hospitalizations from January 2006 through March 2015. Medications evaluated included methadone, formulations including buprenorphine and extended-release formulations of oxycodone, morphine, fentanyl, and other opioids. Temporal trends in use of these medications were determined. Unadjusted and adjusted models evaluating the role of demographic and hospital factors were created evaluating both use of these medications and risk for severe morbidity. Risk for severe morbidity was determined based on Centers for Disease Control and Prevention criteria. RESULTS:Our analysis included 2,994,630 delivery hospitalizations meeting study criteria. Over the entire study period, use of long-acting opioids increased significantly from 457 to 844 per 100,000 deliveries. Although buprenorphine and methadone use increased, use of other long-acting opioids decreased. In 2006, methadone and buprenorphine accounted for less than one third of all long-acting opioids used during delivery hospitalizations. By 2015, buprenorphine and methadone represented 73.5% of long-acting opioids used. In adjusted and unadjusted models, risk for severe morbidity was significantly lower with buprenorphine or methadone compared with other long-acting opioids. Restricting the cohort to only women with drug abuse or dependence, risk for severe morbidity was lower with methadone and buprenorphine than without any long-acting opioids. CONCLUSION:Increased use of methadone and buprenorphine in this study supports the feasibility of use of these medications during pregnancy and uptake of clinical recommendations for women with opioid use disorder. Use of methadone and buprenorphine is associated with decreased maternal morbidity, although causation cannot be presumed from this study model.

OBJECTIVE:The objective of this study was to characterize risk for and temporal trends in postpartum hemorrhage across hospitals with different delivery volumes. STUDY DESIGN/METHODS:This study used the Nationwide Inpatient Sample (NIS) to characterize risk for postpartum hemorrhage from 1998 to 2011. Hospitals were classified as having either low, moderate or high delivery volume (≤1000, 1001 to 2000, >2000 deliveries per year, respectively). The primary outcomes included postpartum hemorrhage, transfusion, and related severe maternal morbidity. Adjusted models were created to assess factors associated with hemorrhage and transfusion. RESULTS:Of 55,140,088 deliveries included for analysis 1,512,212 (2.7%) had a diagnosis of postpartum hemorrhage and 361,081 (0.7%) received transfusion. Risk for morbidity and transfusion increased over the study period, while the rate of hemorrhage was stable ranging from 2.5 to 2.9%. After adjustment, hospital volume was not a major risk factor for transfusion or hemorrhage. DISCUSSION/CONCLUSIONS:While obstetric volume does not appear to be a major risk factor for either transfusion or hemorrhage, given that transfusion and hemorrhage-related maternal morbidity are increasing across hospital volume categories, there is an urgent need to improve obstetrical care for postpartum hemorrhage. Those risk factors are able to discriminate women at increased risk supports routine use of hemorrhage risk assessment.

Importance/UNASSIGNED:Whether the changing gestational age distribution in the United States since 2005 has affected perinatal mortality remains unknown. Objective/UNASSIGNED:To examine changes in gestational age distribution and gestational age-specific perinatal mortality. Design, Setting, and Participants/UNASSIGNED:This retrospective cohort study examined trends in US perinatal mortality by linking live birth and infant death data among more than 35 million singleton births from January 1, 2007, through December 31, 2015. Exposures/UNASSIGNED:Year of birth and changes in gestational age distribution. Main Outcomes and Measures/UNASSIGNED:Changes in the proportion of births at gestational ages 20 to 27, 28 to 31, 32 to 33, 34 to 36, 37 to 38, 39 to 40, 41, and 42 to 44 weeks; changes in perinatal mortality (stillbirth at ≥20 weeks, and neonatal deaths at <28 days) rates; and contribution of gestational age changes to perinatal mortality. Trends were estimated from log-linear regression models adjusted for confounders. Results/UNASSIGNED:Among the 34 236 577 singleton live births during the study period, the proportion of births at all gestational ages declined, except at 39 to 40 weeks, which increased (54.5% in 2007 to 60.2% in 2015). Overall perinatal mortality declined from 9.0 to 8.6 per 1000 births (P < .001). Stillbirths declined from 5.7 to 5.6 per 1000 births (P < .001), and neonatal mortality declined from 3.3 to 3.0 per 1000 births (P < .001). Although the proportion of births at gestational ages 34 to 36, 37 to 38, and 42 to 44 weeks declined, perinatal mortality rates at these gestational ages showed annual adjusted relative increases of 1.0% (95% CI, 0.6%-1.4%), 2.3% (95% CI, 1.9%-2.8%), and 4.2% (95% CI, 1.5%-7.0%), respectively. Neonatal mortality rates at gestational ages 34 to 36 and 37 to 38 weeks showed a relative adjusted annual increase of 0.9% (95% CI, 0.2%-1.6%) and 3.1% (95% CI, 2.1%-4.1%), respectively. Although the proportion of births at gestational age 39 to 40 weeks increased, perinatal mortality showed an annual relative adjusted decline of -1.3% (95% CI, -1.8% to -0.9%). The decline in neonatal mortality rate was largely attributable to changes in the gestational age distribution than to gestational age-specific mortality. Conclusions and Relevance/UNASSIGNED:Although the proportion of births at gestational age 39 to 40 weeks increased, perinatal mortality at this gestational age declined. This finding may be owing to pregnancies delivered at 39 to 40 weeks that previously would have been unnecessarily delivered earlier, leaving fetuses at higher risk for mortality at other gestational ages.

Importance/UNASSIGNED:Preterm and postterm deliveries have declined since 2005 in the United States, but the association between these changes and neonatal mortality remains unknown. Objective/UNASSIGNED:To estimate changes in the gestational age distribution among spontaneous and clinician-initiated deliveries between 2006 and 2013 and associated changes in neonatal mortality. Design, Setting, and Participants/UNASSIGNED:A retrospective cohort analysis was conducted of 22 million singleton live births without major malformations in the United States from 2006 to 2013. Data analysis was performed from August to October 2017. Main Outcomes and Measures/UNASSIGNED:Changes in gestational age distribution among spontaneous and clinician-initiated deliveries at extremely preterm (20-27 weeks), very preterm (28-31 weeks), moderately preterm (32-33 weeks), late preterm (34-36 weeks), early term (37-38 weeks), term (39-40), late term (41 weeks), and postterm (42-44 weeks) gestations and changes in neonatal mortality rates at less than 28 days between 2006 and 2013. These changes were estimated from log-linear Poisson regression models with robust variance, adjusted for confounders. Results/UNASSIGNED:Among 22 million births, 12 493 531 (56.7%) were spontaneous and 9 557 815 (43.3%) were clinician-initiated deliveries. Among spontaneous deliveries, the proportion of births at 20 to 27, 28 to 31, 32 to 33, 34 to 36, and 37 to 38 weeks declined. Among clinician-initiated deliveries, the proportion of births at 34 to 36 and 37 to 38 weeks declined and the proportion at 39 to 40 weeks increased. Among spontaneous deliveries, overall neonatal mortality rates declined from 1.8 to 1.3 per 1000 live births, mainly at 20 to 27 weeks (adjusted annual decline, 1%; 95% CI, -2% to -1%) and 28 to 31 weeks (adjusted annual decline, 6%; 95% CI, -8% to -5%). Among clinician-initiated deliveries, overall mortality rates remained unchanged (2.1 to 2.2 per 1000 live births). However, mortality rates declined (0.6 to 0.5 per 1000 live births) at 39 to 40 weeks by 1% (95% CI, -3% to -0.4%) annually, adjusted for confounders. Conclusions and Relevance/UNASSIGNED:In the United States, there was a decline in spontaneous deliveries associated with an overall decline in neonatal mortality. Although clinician-initiated deliveries increased at 39 to 40 weeks, neonatal mortality at that gestation declined.

OBJECTIVE:Placental abruption has a profound impact on perinatal mortality, but implications for neurodevelopment during childhood remain unknown. We examined the association between abruption and neurodevelopment at 8 months and 4 and 7 years and evaluated the extent to which these associations were mediated through preterm delivery. DESIGN:Secondary analysis of a multicenter prospective cohort study. SETTING:Multicenter US National Collaborative Perinatal Project (1959-76). POPULATION:Women that delivered singleton live births. METHODS:Analyses of IQ scores were based on marginal structural models (MSM) to account for losses to follow-up. We also carried out a causal mediation analysis to evaluate if the association between abruption and cognitive deficits was mediated through preterm delivery, and performed a sensitivity analysis for unobserved confounding. MAIN OUTCOME MEASURES:We evaluated cognitive development based on the Bayley scale at 8 months (Mental and Motor Scores), and intelligent quotient (IQ) based on the Stanford-Binet scale at 4 years and the Wechsler Intelligence Scale for Children at 7 years. RESULTS:The confounder and selection-bias adjusted risk ratio (RR) of abnormal 8-month Motor and Mental assessments were 2.35 (95%CI 1.39, 3.98) and 2.03 (95%CI 1.13, 3.64), respectively, in relation to abruption. The associations at 4 years were attenuated and resolved at 7 years. The proportion of children with abruption-associated neurological deficits mediated through preterm delivery ranged from 27 to 75%. Following adjustment for unobserved confounding the proportion mediated through preterm delivery was attenuated. CONCLUSION:The effect of abruption on neurodevelopmental outcomes appears restricted to an effect that is largely mediated through preterm delivery. TWEETABLE ABSTRACT:Increased risk of cognitive deficits in relation to abruption appears to be mediated through preterm delivery.