Spencer G. Kuper

The effect of omega-3 supplementation on pregnancy outcomes by smoking status.

BACKGROUND: Smoking during pregnancy is associated with adverse maternal and neonatal outcomes such as preterm delivery, intrauterine growth restriction, stillbirth, and low birth weight. Because smoking causes oxidative stress, some have suggested using antioxidants to counteract the effects of oxidative stress. Smokers have lower serum levels of omega‐3 fatty acids, an important antioxidant, and thus, investigating whether omega‐3 supplementation in smokers reduces adverse maternal and neonatal outcomes represents an important area of research. OBJECTIVE: To investigate whether the antioxidant effect of omega‐3 fatty acid supplementation on the incidence of adverse pregnancy outcomes differs between smokers and nonsmokers. STUDY DESIGN: Secondary analysis of a multicenter randomized controlled trial of omega‐3 supplementation for preterm delivery prevention in women with a singleton pregnancy and a history of a previous singleton spontaneous preterm delivery. Subjects were randomized to begin omega‐3 or placebo before 22 weeks, which was continued until delivery. All women received 17 alpha‐hydroxyprogesterone caproate intramuscularly weekly beginning between 16 and 20 weeks of gestation and continued until 36 weeks of gestation or delivery, whichever occurred first. The primary outcome was spontaneous preterm delivery. Secondary outcomes were indicated preterm delivery, any preterm delivery (spontaneous and indicated), pregnancy‐associated hypertension (gestational hypertension and preeclampsia), a neonatal composite (retinopathy of prematurity, intraventricular hemorrhage grade III or IV, patent ductus arteriosus, necrotizing enterocolitis, sepsis, respiratory morbidity, or perinatal death), low birth weight (<2500 g), small for gestational age (less than the 10th percentile), and neonatal intensive care unit or intermediate nursery admission. The study population was stratified into smokers and nonsmokers, and the incidence of each outcome was compared by omega‐3 supplementation versus placebo in each subgroup. Zelen tests were performed to test for homogeneity of effect in smokers and nonsmokers. RESULTS: Of 851 subjects included in the analysis, 136 (16%) smoked. Baseline characteristics between omega‐3 and placebo groups did not differ in smokers or nonsmokers. Omega‐3 supplementation was associated with a lower risk of spontaneous preterm delivery in smokers (relative risk, 0.56, 95% confidence interval, 0.36–0.87) but not in nonsmokers (relative risk 1.04, 95% confidence interval 0.84–1.29); P value for interaction = 0.013. Low birth weight was also less frequent in smokers receiving omega‐3 supplementation (relative risk 0.57, 95% confidence interval 0.36–0.90) compared with nonsmokers (relative risk 0.93, 95% confidence interval 0.71–1.24); P value for interaction = 0.047. The effect on other secondary outcomes did not differ significantly between smokers and nonsmokers. CONCLUSION: Omega‐3 supplementation in smokers may have a protective effect against recurrent spontaneous preterm delivery and low birth weight.

Predictors of vaginal delivery in medically indicated early preterm induction of labor

Background When delivery is indicated prior to 34 weeks, many providers perform a cesarean delivery rather than induce labor based on perceptions of a high failure rate. Given the morbidity of cesarean delivery, an accurate estimate of the success rate and factors associated with success in preterm induction of labor is important in management decisions. Objective We sought to develop a prediction model for successful induction of labor in preterm patients using factors known at the time the decision is made to deliver. Study Design A retrospective cohort study of all live singletons undergoing an indicated induction of labor between 23 and 34 0/7 weeks from 2011 through 2015. Pregnancies with major fetal anomalies or no intrapartum fetal monitoring were excluded. Successful induction of labor was defined as vaginal delivery. The cohort was randomly split into a training cohort to develop a prediction model for vaginal delivery and a validation cohort to test the model. Factors significantly associated with vaginal delivery were identified using univariate analyses, and candidate factors were used in the multivariate logistic regression model. Only factors known at the start of the induction of labor were used in the model. Receiver‐operating characteristic curves were created to estimate the predictive value of the model. Sensitivity and specificity of the model were assessed. Results Of 331 patients who underwent induction of labor, 208 (62.8%) delivered vaginally and 123 (37.1%) by cesarean delivery. Of the factors significantly associated with cesarean delivery, the final model included gestational age, simplified Bishop score, suspected intrauterine growth retardation, chronic hypertension, and body mass index. In the training cohort, the model correctly classified 72.3% of subjects with a sensitivity (cesarean delivery predicted/cesarean delivery performed) of 56.7% and a specificity (vaginal delivery predicted/vaginal delivery performed) of 84.1%. When applied to the validation cohort, 73.9% of subjects were correctly classified, with a sensitivity of 44.6% and specificity of 89.0%. Receiver‐operating characteristic curves had an area under the curve of 0.75 for the training cohort and 0.77 for the validation cohort. Conclusion More than 60% of women undergoing induction of labor at <34 0/7 weeks deliver vaginally. For women undergoing induction of labor at <34 0/7 weeks, this prediction model rarely classifies individuals who can have a vaginal delivery as needing a cesarean delivery. This model may provide an accurate assessment tool to evaluate which patients will likely deliver vaginally to avoid the morbidity of cesarean delivery while conversely identifying subjects at high risk of cesarean delivery <34 0/7 weeks.

maternal and Neonatal Outcomes in Indicated Preterm Births Based on the Intended Mode of Delivery

OBJECTIVE To compare maternal and neonatal outcomes in women who underwent induction of labor or planned cesarean delivery in indicated preterm births before 34 weeks of gestation. METHODS We conducted a retrospective cohort study of all indicated singleton preterm births (23-34 weeks of gestation) in a tertiary center from 2011 to 2014. The primary maternal outcome was a composite of early postpartum hemorrhage, blood transfusion, operative complications, postpartum complications, and clinical chorioamnionitis. The primary neonatal outcome was a composite of neonatal death, cardiopulmonary resuscitation in the delivery room, grade 3 or 4 intraventricular hemorrhage, necrotizing enterocolitis, culture-proven sepsis, birth trauma, arterial cord gas pH less than 7 or base excess less than -12, and 5-minute Apgar score 3 or less. Outcomes were compared by intended mode of delivery (induction of labor compared with cesarean) and adjusted for confounders. In secondary analyses, maternal and neonatal outcomes based on the intended mode of delivery were stratified by gestational age (23-27 6/7, 28-31 6/7, and 32-33 6/7 weeks of gestation). RESULTS Of 629 patients with indicated early preterm births during the study period, 331 (53%) underwent induction of labor, of whom 208 (63%) delivered vaginally. Induction of labor was not associated with an increased risk of the primary maternal (16.3% compared with 19.5%, adjusted odds ratio [OR] 0.8, 95% CI 0.5-1.3) or neonatal composite outcome (14.5% compared with 35.9%, adjusted OR 0.7, 95% CI 0.4-1.1). Analyses stratified by gestational age were consistent with the overall analysis. CONCLUSION Maternal and neonatal outcomes do not differ based on the intended mode of delivery. Induction of labor should be considered when early preterm birth is indicated.

Baseline Renal Function Tests and Adverse Outcomes in Pregnant Patients With Chronic Hypertension.

OBJECTIVE: To examine the relationship between baseline renal function tests in pregnant patients with chronic hypertension and adverse pregnancy outcomes. METHODS: This was a retrospective cohort study of women with a singleton pregnancy and chronic hypertension with assessment of renal function (urine protein-to-creatinine ratio and serum creatinine) before 20 weeks of gestation. The primary outcome was severe preeclampsia at less than 34 weeks of gestation. Secondary outcomes were severe preeclampsia at any gestational age, any preeclampsia, preterm birth at less than 35 weeks of gestation, composite perinatal outcome (perinatal death, assisted ventilation, cord pH less than 7, 5-minute Apgar score 3 or less, or neonatal seizures), and small for gestational age. The association between baseline renal function and the primary outcome was assessed with receiver operating characteristic (ROC) curves and objective cutoffs determined. Outcomes were compared between those with values above and below the cutoffs using univariable and multivariable analyses. RESULTS: Seven hundred fifty-five pregnant women with chronic hypertension had baseline renal function assessment. The urine protein-to-creatinine ratio and creatinine cutoffs for severe preeclampsia at less than 34 weeks of gestation were 0.12 or greater and 0.75 mg/dL or greater, respectively. The area under the ROC curves for severe preeclampsia at less than 34 weeks of gestation was 0.74 (95% confidence interval [CI] 0.7–0.8) for urine protein-to-creatinine ratio and 0.67 (95% CI 0.6–0.8) for creatinine. A urine protein-to-creatinine ratio 0.12 or greater was associated with an increased risk of developing severe preeclampsia at less than 34 weeks of gestation (16.4% compared with 2.6%, adjusted odds ratio [OR] 7.5, 95% CI 3.9–14.6) as was a creatinine 0.75 mg/dL or greater (15.7% compared with 4.6%, adjusted OR 3.5, 95% CI 1.9–6.3). Severe preeclampsia at less than 34 weeks of gestation occurred in only 1.6% of patients if their baseline tests were below both cutoffs. CONCLUSION: Baseline assessment of renal function can be used as a risk stratification tool in pregnant patients with chronic hypertension.

Outcomes of Medically Indicated Preterm Births Differ by Indication

Objective We aim to examine whether outcomes of preterm birth (PTB) are further modified by the indication for delivery. Study Design We performed a retrospective cohort study of all singletons delivered at 23 to 34 weeks from 2011 to 2014. Women were classified by their primary indication for delivery: maternal (preeclampsia) or fetal/obstetric (growth restriction, nonreassuring fetal status, and vaginal bleeding). The primary neonatal outcome was a composite of neonatal death, cord pH <7 or base excess < − 12, 5‐minute Apgar ≤3, C‐reactive protein during resuscitation, culture‐proven sepsis, intraventricular hemorrhage, and necrotizing enterocolitis. Secondary outcomes included the individual components of the primary outcome. Groups were compared using Students t ‐test and chi‐squared tests. Logistic regression was used to adjust for confounding variables. Results Of 528 women, 395 (74.8%) were delivered for maternal and 133 (25.2%) for fetal/obstetric indications. Compared with those delivered for a maternal indication, those with a fetal/obstetric indication for delivery had an increased risk of the composite neonatal outcome (adjusted odds ratio [AOR]: 1.9, 95% confidence interval [CI]: 1.13‐3.21) and acidemia at birth (AOR: 4.2, 95% CI: 1.89‐9.55). Conclusion Preterm infants delivered for fetal/obstetric indications have worsened outcomes compared with those delivered for maternal indications. Additional research is needed to further tailor counseling specific to the indication for delivery.

Association between antenatal corticosteroids and neonatal hypoglycemia in indicated early preterm births

Abstract Purpose: We sought to determine if administration of antenatal corticosteroids in early preterm births (<34 weeks) is associated with an increased risk of developing neonatal hypoglycemia (<40 mg/dL) within the first 48 h of neonatal life. Materials and methods: Retrospective cohort of all indicated singleton preterm births (23−34 weeks) in a single tertiary center from 2011 to 2014. The primary outcome was neonatal hypoglycemia (<40 mg/dL) within the first 48 h of life. The outcome was compared by antenatal corticosteroids received at any point during the gestation, within 2–7 d of delivery, and whether the patient received a partial, full, or repeat course of antenatal corticosteroids. Logistic regression was used to adjust for confounders. Results: Six hundred thirty-five patients underwent an indicated preterm birth during the study period. Six hundred and four (95%) received antenatal corticosteroids prior to delivery and 31 (5%) did not. The incidence of neonatal hypoglycemia within 48 h of life was not significantly different between those who received any antenatal corticosteroids and those who did not (23.0 versus 16.1%, adjusted odds ratio [OR] 1.3, 95%CI 0.5–3.6). Infants who received a full antenatal corticosteroid course within 2–7 d of delivery had similar incidences of hypoglycemia compared with those who received antenatal corticosteroids more than 7 d before delivery (20.4 versus 25.4%, adjusted OR 1.5, 95% confidence interval(CI) 0.8–2.9). Neonatal hypoglycemia was not increased by the number of antenatal corticosteroid doses (partial, full, or repeat course) administered. There was not a correlation between timing of antenatal corticosteroid administration before delivery, up to 250 h, and the lowest neonatal blood sugar in the first 48 h of life. Conclusion: Our findings suggest antenatal corticosteroid administration in indicated early preterm infants (<34 weeks) may not increase the risk of developing neonatal hypoglycemia within the first 48 h of life. Further studies should validate our findings.

Neonatal Outcomes Based on Duration of Exposure to Antenatal Corticosteroids in Indicated Preterm Deliveries

Objective To evaluate how duration of exposure to antenatal corticosteroids (ACSs) prior to delivery affects neonatal outcomes in indicated preterm deliveries. Study Design This is a retrospective cohort of all indicated singleton preterm deliveries (23‐34 weeks) in a single tertiary center from 2011 to 2014 comparing those who received ACS 2 to 7 days versus >7 days prior to delivery. The primary neonatal outcome was a composite of arterial cord pH < 7 or base excess ≤ 12, 5‐minute Apgar ≤ 3, cardiopulmonary resuscitation, culture‐proven neonatal sepsis, intraventricular hemorrhage grade III/IV, necrotizing enterocolitis, and neonatal death. Analyses were stratified by delivering gestational age (230/7 ‐276/7, 280/7 ‐316/7, and 320/7 ‐336/7 weeks). Multivariate logistic regression refined point estimates and adjusted for confounders. Results In total, 301 women delivered >48 hours after initial ACS dose, 230 delivered within 2 to 7 days, and 71 delivered >7 days. Infants with an interval of >7 days had no significant increase in the unadjusted composite neonatal outcome (p = 0.42), but when adjusted, the composite neonatal outcome (adjusted odds ratio [AOR]: 2.7; 95% confidence interval [CI]: 1.18‐6.31) and neonatal death (AOR: 4.20; 95% CI: 1.39‐12.69) were significantly increased with an ACS interval of >7 day. Conclusion In this cohort, the benefit of ACS diminished >7 days after administration, particularly when delivery occurred at <32 weeks.

Opioid Detoxification in Pregnancy: Systematic Review and Meta-Analysis of Perinatal Outcomes

OBJECTIVE  We sought to compare the efficacy and safety of detoxification from opioids compared with opioid replacement therapy (ORT) during pregnancy. STUDY DESIGN  We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception to June 2017 for English-language randomized-controlled trials or cohort studies that compared detoxification with ORT. We sought studies with outcomes data on maternal abstinence at the time of delivery, neonatal abstinence syndrome (NAS), stillbirth, and preterm birth (PTB). We calculated pooled relative risks (RRs) with a random-effects model, assessed heterogeneity using the chi-square test for heterogeneity, and quantified heterogeneity using the I 2 test. We assessed publication bias using funnel plots and the Harbord test. RESULTS  Three cohort studies met the inclusion criteria; eligible studies included 235 women with opioid use disorder in pregnancy. Maternal detoxification was associated with increased risk of relapse (RR = 1.91; 95% confidence interval [CI] = 1.14-3.21); however, no treatment differences were observed for the rates of NAS (RR = 0.99; 95% CI = 0.38-2.53) or PTB (RR = 0.39; 95% CI = 0.10-1.60). CONCLUSION  Our findings suggest an increased risk of relapse with detoxification treatment compared with ORT; however, detoxification does not alter the risk of PTB or NAS. Further studies should confirm our findings and explore mechanisms to fight the current opioid epidemic.

Does Early Artificial Rupture of Membranes Speed Labor in Preterm Inductions

Objective In full‐term patients, early artificial rupture of membranes (AROMs) decreases time in labor. We assessed the impact of early AROM in preterm patients undergoing indicated induction of labor. Study Design We conducted a retrospective cohort study of all patients undergoing indicated preterm induction (23‐34 weeks) at a single tertiary care center from 2011 to 2014. Early AROM was defined as <4 cm and late AROM was defined as ≥4 cm. The primary outcomes evaluated were cesarean delivery and time in labor. Secondary outcomes were chorioamnionitis and a composite of maternal and neonatal adverse outcomes. Results Of the 149 women included, 65 (43.6%) had early AROM. Early AROM was associated with an increased time from the start of induction to delivery (25.7 ± 13.0 vs. 19.0 ± 10.3 hours, p < 0.01) and with an increase in the risk of cesarean (53.4 vs. 22.6%, adjusted odds ratio: 3.5, 95% confidence interval: 1.60‐7.74). Early AROM was not associated with an increased risk of chorioamnionitis or adverse maternal or fetal outcomes. Conclusion In this observational cohort, early AROM was associated with an increased risk of cesarean. A randomized controlled trial is necessary to determine the optimal timing of AROM in preterm patients requiring delivery.

Impact of Intended Mode of Delivery on Outcomes in Preterm Growth-Restricted Fetuses

Background Scheduled cesarean is frequently performed for fetal growth restriction due to concerns for fetal intolerance of labor. Objective We compared neonatal outcomes in preterm growth‐restricted fetuses by intended mode of delivery. Study Design We performed a retrospective cohort study of indicated preterm births with prenatally diagnosed growth restriction from 2011 to 2014 at a single institution. Patients were classified by intended mode of delivery. The primary outcome was a composite of adverse neonatal outcomes, including perinatal death, cord blood acidemia, chest compressions during neonatal resuscitation, seizures, culture‐proven sepsis, necrotizing enterocolitis, and grade III‐IV intraventricular hemorrhage. Secondary analysis was performed examining the impact of umbilical artery Dopplers. Results Of 101 fetuses with growth restriction, 75 underwent planned cesarean deliveries. Of those induced, 46.2% delivered vaginally. Delivery by scheduled cesarean was not associated with a decreased risk of the composite outcome (adjusted odds ratio [aOR], 1.61; 95% confidence interval [CI], 0.45‐5.78), even when only those with abnormal umbilical artery Dopplers were considered (aOR, 2.8; 95% CI, 0.40‐20.2). Conclusion In this cohort, planned cesarean was not associated with a reduction in neonatal morbidity, even when considering only those with abnormal umbilical artery Dopplers. In otherwise appropriate candidates for vaginal delivery, fetal growth restriction should not be considered a contraindication to trial of labor.