Tranexamic Acid to Prevent Obstetrical Hemorrhage after Cesarean Delivery.

BACKGROUND: Prophylactic use of tranexamic acid at the time of cesarean delivery has been shown to decrease the calculated blood loss, but the effect on the need for blood transfusions is unclear. METHODS: We randomly assigned patients undergoing cesarean delivery at 31 U.S. hospitals to receive either tranexamic acid or placebo after umbilical-cord clamping. The primary outcome was a composite of maternal death or blood transfusion by hospital discharge or 7 days post partum, whichever came first. Key secondary outcomes were estimated intraoperative blood loss of more than 1 liter (prespecified as a major secondary outcome), interventions for bleeding and related complications, the preoperative-to-postoperative change in the hemoglobin level, and postpartum infectious complications. Adverse events were assessed. RESULTS: A total of 11,000 participants underwent randomization (5529 to the tranexamic acid group and 5471 to the placebo group); scheduled cesarean delivery accounted for 50.1% and 49.2% of the deliveries in the respective groups. A primary-outcome event occurred in 201 of 5525 participants (3.6%) in the tranexamic acid group and in 233 of 5470 (4.3%) in the placebo group (adjusted relative risk, 0.89; 95.26% confidence interval [CI], 0.74 to 1.07; P = 0.19). Estimated intraoperative blood loss of more than 1 liter occurred in 7.3% of the participants in the tranexamic acid group and in 8.0% of those in the placebo group (relative risk, 0.91; 95% CI, 0.79 to 1.05). Interventions for bleeding complications occurred in 16.1% of the participants in the tranexamic acid group and in 18.0% of those in the placebo group (relative risk, 0.90; 95% CI, 0.82 to 0.97); the change in the hemoglobin level was -1.8 g per deciliter and -1.9 g per deciliter, respectively (mean difference, -0.1 g per deciliter; 95% CI, -0.2 to -0.1); and postpartum infectious complications occurred in 3.2% and 2.5% of the participants, respectively (relative risk, 1.28; 95% CI, 1.02 to 1.61). The frequencies of thromboembolic events and other adverse events were similar in the two groups. CONCLUSIONS: Prophylactic use of tranexamic acid during cesarean delivery did not lead to a significantly lower risk of a composite outcome of maternal death or blood transfusion than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT03364491.).

A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection.

BACKGROUND: Primary cytomegalovirus (CMV) infection during pregnancy carries a risk of congenital infection and possible severe sequelae. There is no established intervention for preventing congenital CMV infection. METHODS: In this multicenter, double-blind trial, pregnant women with primary CMV infection diagnosed before 24 weeks' gestation were randomly assigned to receive a monthly infusion of CMV hyperimmune globulin (at a dose of 100 mg per kilogram of body weight) or matching placebo until delivery. The primary outcome was a composite of congenital CMV infection or fetal or neonatal death if CMV testing of the fetus or neonate was not performed. RESULTS: From 2012 to 2018, a total of 206,082 pregnant women were screened for primary CMV infection before 23 weeks of gestation; of the 712 participants (0.35%) who tested positive, 399 (56%) underwent randomization. The trial was stopped early for futility. Data on the primary outcome were available for 394 participants; a primary outcome event occurred in the fetus or neonate of 46 of 203 women (22.7%) in the group that received hyperimmune globulin and of 37 of 191 women (19.4%) in the placebo group (relative risk, 1.17; 95% confidence interval [CI] 0.80 to 1.72; P = 0.42). Death occurred in 4.9% of fetuses or neonates in the hyperimmune globulin group and in 2.6% in the placebo group (relative risk, 1.88; 95% CI, 0.66 to 5.41), preterm birth occurred in 12.2% and 8.3%, respectively (relative risk, 1.47; 95% CI, 0.81 to 2.67), and birth weight below the 5th percentile occurred in 10.3% and 5.4% (relative risk, 1.92; 95% CI, 0.92 to 3.99). One participant in the hyperimmune globulin group had a severe allergic reaction to the first infusion. Participants who received hyperimmune globulin had a higher incidence of headaches and shaking chills while receiving infusions than participants who received placebo. CONCLUSIONS: Among pregnant women, administration of CMV hyperimmune globulin starting before 24 weeks' gestation did not result in a lower incidence of a composite of congenital CMV infection or perinatal death than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences; ClinicalTrials.gov number, NCT01376778.).

Optimizing the length of the second stage and management of pushing.

Although the optimal length of the second stage of labor to minimize maternal and neonatal morbidities and optimize spontaneous vaginal delivery is not known, available evidence suggests that increasing length of the second stage is associated with increasing maternal and neonatal morbidity. Thus, evidence-based strategies to safely shorten the second stage, such as initiating pushing when complete dilation is reached among those with neuraxial anesthesia, is prudent. Many aspects of optimal management of the second stage of labor require future study to continue to guide clinical second-stage management.

Optimal misoprostol dosing among patients with a body mass index greater than 30: a randomized controlled trial.

BACKGROUND: Patients with obesity experience an increased duration of labor with an increased risk for perinatal morbidity. When compared with parturients without obesity, they also experience fewer uterine contractions after administration of misoprostol. It is unclear if the same dose of misoprostol should be used for induction of labor in patients with obesity compared to non-obese patients. Therefore, we sought to investigate if a higher dose of misoprostol for patients with obesity is more effective. OBJECTIVE: This study aimed to determine if 50 µg compared with 25 µg of vaginal misoprostol reduced the time from induction start to delivery among patients with obesity. STUDY DESIGN: We performed a double-blinded, pragmatic randomized controlled trial, between June 1, 2022, and July 17, 2023. Patients with a body mass index ≥30 kg/m2 who underwent labor induction at ≥ 36 weeks' gestation, had a singleton gestation, and a cervical dilation ≤3 cm at admission were included. Patients were excluded if they had a contraindication to vaginal delivery or misoprostol administration. Patients were randomized to 25 or 50 µg of vaginal misoprostol, stratified by parity, body mass index <40 kg/m2 or ≥40 kg/m2, and provider intent to use mechanical dilation at the onset of labor induction. Usual labor management was followed at the discretion of the provider. The primary outcome was time from induction to delivery. A priori, we estimated that 90 subjects per group (N=180) were needed for an 85% power to detect a 3-hour difference between groups with a type I error of 5%. Analysis was by intention-to-treat. A 2-sample t test was used for the primary outcome, Cohen's d was used as a measure of effect, and P values were reported. RESULTS: Of the 180 patients randomized, 88 were assigned to the 25 µg group and 92 were assigned to the 50 µg group. Of those, 96.1% of patients received the designated intervention. The baseline characteristics were similar between groups. No difference was found in the primary outcome of time to delivery (21.6 hours vs 18.6 hours; d=.28; 95% confidence interval, -0.02 to 0.57). In a planned subgroup analysis, multiparous patients delivered faster in the 50 µg group (15.2 hours vs 12.0 hours; d=.51; 95% confidence interval, 0.04-0.97). The risk for tachysystole associated with fetal heart tracing changes was rare overall (2.2%) and not significantly different between groups. No differences in maternal or neonatal adverse effects were observed. CONCLUSION: Patients with obesity who underwent cervical ripening with 50 µg of vaginal misoprostol experienced a similar time to delivery when compared with those who received 25 µg of misoprostol. However, multiparous patients had a significantly reduced time to delivery when 50 µg was used. A higher dose of misoprostol may be a promising intervention for reducing time in labor, which warrants further study.

First and Second Stage Risk Factors Associated with Perineal Lacerations.

OBJECTIVE: To determine intrapartum factors associated with perineal laceration at delivery. METHODS: This was a planned secondary analysis of a multicenter randomized clinical trial of delayed versus immediate pushing among term nulliparous women in labor with neuraxial analgesia conducted in the United States. Intrapartum characteristics were extracted from the medical charts. The primary outcome was perineal laceration, defined as second degree or above, characterized at delivery in women participating in longer term pelvic floor assessments post-delivery. Multivariable logistic regression was used to refine risk estimates while adjusting for randomization group, birth weight, and maternal age. RESULTS: Among the 941 women participating in the pelvic floor follow-up, 40.6% experienced a perineal laceration. No first stage labor characteristics were associated with perineal laceration, including type of labor or length of first stage. Receiving an amnioinfusion appeared protective of perineal laceration (adjusted odds ratio, 0.48; 95% confidence interval 0.26-0.91; P = 0.01). Second stage labor characteristics associated with injury were length of stage (2.01 h vs. 1.50 h; adjusted odds ratio, 1.36; 95% confidence interval 1.18-1.57; P < 0.01) and a prolonged second stage (adjusted odds ratio, 1.64; 95% confidence interval 1.06-2.56; P < 0.01). Operative vaginal delivery was strongly associated with perineal laceration (adjusted odds ratio, 3.57; 95% confidence interval 1.85-6.90; P < 0.01). CONCLUSION: Operative vaginal delivery is a modifiable risk factor associated with an increased risk of perineal laceration. Amnioinfusion appeared protective against injury, which could reflect a spurious finding, but may also represent true risk reduction similar to the mechanism of warm perineal compress.

Elective Induction of Labor following Prior Cesarean Delivery.

OBJECTIVE: Following the release of A Randomized Trial of Induction versus Expectant Management (ARRIVE) trial, the induction of labor at 39 weeks has increased in the United States. The risk of uterine rupture and optimal timing of elective induction in those patients with a prior cesarean delivery is not well-described, and they were not included in the original trial. We aimed to determine the risk of uterine rupture in those patients undergoing elective induction of labor with prior cesarean delivery. STUDY DESIGN: This was a retrospective cohort of participants with prior cesarean delivery from 1996 to 2000. Participants were included if they had two or more prior cesareans. Participants were excluded if they had a history of an unknown prior incision, a classical incision, gestational age <39 weeks, any diabetes, chronic hypertension, twin gestation, collagen or vascular disease, or HIV. Those undergoing expectant management were compared with those undergoing elective induction with no medical or obstetrical indications for delivery. Analysis was performed at three gestational age groups: 39 weeks, 40 weeks, and 41 weeks. The primary outcomes were uterine rupture, rates of successful vaginal delivery, and a composite major morbidity risk. Multivariable logistic regression was performed. RESULTS: At 39 weeks, 618 (10.3%) elective inductions were compared with 5,365 (89.7%) undergoing expectant management; uterine rupture occurred more frequently (13 patients [2.1%] vs. 49 patients [0.9%]; adjusted odds ratio [aOR], 2.5; 95% confidence interval, 1.3-4.6) with fewer successful vaginal birth after cesarean [VBAC; 66.8 vs. 75%; aOR, 0.6; 95% confidence interval, 0.5-0.7]. The risk of uterine rupture was similar between groups at 40 weeks (5 patients [0.8%] vs. 21 patients [1.2%]; p = 0.387) and 41 weeks (7 patients [1.4%] vs. 2 patients (0.8%); p = 0.448). CONCLUSION: Patients undergoing elective induction of labor with a prior cesarean scar had an increased risk of uterine rupture when compared with expectant management at 39 weeks, with fewer successful VBAC. KEY POINTS: · TOLAC elective induction at 39 weeks has an increased risk of uterine rupture.. · TOLAC elective induction at 39 weeks has a less successful chance of vaginal delivery.. · Awaiting spontaneous labor in this cohort does not increase the risk of uterine rupture..

Neurodevelopmental Outcomes After Late Preterm Antenatal Corticosteroids: The ALPS Follow-Up Study.

Importance: The Antenatal Late Preterm Steroids (ALPS) trial changed clinical practice in the United States by finding that antenatal betamethasone at 34 to 36 weeks decreased short-term neonatal respiratory morbidity. However, the trial also found increased risk of neonatal hypoglycemia after betamethasone. This follow-up study focused on long-term neurodevelopmental outcomes after late preterm steroids. Objective: To evaluate whether administration of late preterm (34-36 completed weeks) corticosteroids affected childhood neurodevelopmental outcomes. Design, Setting, and Participants: Prospective follow-up study of children aged 6 years or older whose birthing parent had enrolled in the multicenter randomized clinical trial, conducted at 13 centers that participated in the Maternal-Fetal Medicine Units (MFMU) Network cycle from 2011-2016. Follow-up was from 2017-2022. Exposure: Twelve milligrams of intramuscular betamethasone administered twice 24 hours apart. Main Outcome and Measures: The primary outcome of this follow-up study was a General Conceptual Ability score less than 85 (-1 SD) on the Differential Ability Scales, 2nd Edition (DAS-II). Secondary outcomes included the Gross Motor Function Classification System level and Social Responsiveness Scale and Child Behavior Checklist scores. Multivariable analyses adjusted for prespecified variables known to be associated with the primary outcome. Sensitivity analyses used inverse probability weighting and also modeled the outcome for those lost to follow-up. Results: Of 2831 children, 1026 enrolled and 949 (479 betamethasone, 470 placebo) completed the DAS-II at a median age of 7 years (IQR, 6.6-7.6 years). Maternal, neonatal, and childhood characteristics were similar between groups except that neonatal hypoglycemia was more common in the betamethasone group. There were no differences in the primary outcome, a general conceptual ability score less than 85, which occurred in 82 (17.1%) of the betamethasone vs 87 (18.5%) of the placebo group (adjusted relative risk, 0.94; 95% CI, 0.73-1.22). No differences in secondary outcomes were observed. Sensitivity analyses using inverse probability weighting or assigning outcomes to children lost to follow-up also found no differences between groups. Conclusion and Relevance: In this follow-up study of a randomized clinical trial, administration of antenatal corticosteroids to persons at risk of late preterm delivery, originally shown to improve short-term neonatal respiratory outcomes but with an increased rate of hypoglycemia, was not associated with adverse childhood neurodevelopmental outcomes at age 6 years or older.

The "30-minute rule" for expedited delivery: fact or fiction?

Initially developed from hospital feasibility data from the 1980s, the "30-minute rule" has perpetuated the belief that the decision-to-incision time in an emergency cesarean delivery should be <30 minutes to preserve favorable neonatal outcomes. Through a review of the history, available data on delivery timing and associated outcomes, and consideration of feasibility across several hospital systems, the use and applicability of this "rule" are explored, and its reconsideration is called for. Moreover, we have advocated for balanced consideration of maternal safety with rapidity of delivery, encouraged process-based approaches, and proposed standardization of terminology regarding delivery urgency. Furthermore, a standardized 4-tier classification system for delivery urgency, from class I, for a perceived threat to maternal or fetal life, to class IV, a scheduled delivery, and a call for further research with a standardized structure to facilitate comparison have been proposed.

First- or second-trimester SARS-CoV-2 infection and subsequent pregnancy outcomes.

BACKGROUND: SARS-CoV-2 infection during pregnancy is associated with adverse pregnancy outcomes, including fetal death and preterm birth. It is not known whether that risk occurs only during the time of acute infection or whether the risk persists later in pregnancy. OBJECTIVE: This study aimed to evaluate whether the risk of SARS-CoV-2 infection during pregnancy persists after an acute maternal illness. STUDY DESIGN: A retrospective cohort study of pregnant patients with and without SARS-CoV-2 infection delivering at 17 hospitals in the United States between March 2020 and December 2020. Patients experiencing a SARS-CoV-2-positive test at or before 28 weeks of gestation with a subsequent delivery hospitalization were compared with those without a positive SAR-CoV-2 test at the same hospitals with randomly selected delivery days during the same period. Deliveries occurring at <20 weeks of gestation in both groups were excluded. The study outcomes included fetal or neonatal death, preterm birth at <37 weeks of gestation and <34 weeks of gestation, hypertensive disorders of pregnancy (HDP), any major congenital malformation, and size for gestational age of <5th or <10th percentiles at birth based on published standards. HDP that were collected included HDP and preeclampsia with severe features, both overall and with delivery at <37 weeks of gestation. RESULTS: Of 2326 patients who tested positive for SARS-CoV-2 during pregnancy and were at least 20 weeks of gestation at delivery from March 2020 to December 2020, 402 patients (delivering 414 fetuses or neonates) were SARS-CoV-2 positive before 28 weeks of gestation and before their admission for delivery; they were compared with 11,705 patients without a positive SARS-CoV-2 test. In adjusted analyses, those with SARS-CoV-2 before 28 weeks of gestation had a subsequent increased risk of fetal or neonatal death (2.9% vs 1.5%; adjusted relative risk, 1.97; 95% confidence interval, 1.01-3.85), preterm birth at <37 weeks of gestation (19.6% vs 13.8%; adjusted relative risk, 1.29; 95% confidence interval, 1.02-1.63), and HDP with delivery at <37 weeks of gestation (7.2% vs 4.1%; adjusted relative risk, 1.74; 95% confidence interval, 1.19-2.55). There was no difference in the rates of preterm birth at <34 weeks of gestation, any major congenital malformation, and size for gestational age of <5th or <10th percentiles. In addition, there was no significant difference in the rate of gestational hypertension overall or preeclampsia with severe features. CONCLUSION: There was a modest increase in the risk of adverse pregnancy outcomes after SARS-CoV-2 infection.

Cervical Pessary for Prevention of Preterm Birth in Individuals With a Short Cervix: The TOPS Randomized Clinical Trial.

Importance: A short cervix as assessed by transvaginal ultrasound is an established risk factor for preterm birth. Study findings for a cervical pessary to prevent preterm delivery in singleton pregnancies with transvaginal ultrasound evidence of a short cervix have been conflicting. Objective: To determine if cervical pessary placement decreases the risk of preterm birth or fetal death prior to 37 weeks among individuals with a short cervix. Design, Setting, and Participants: We performed a multicenter, randomized, unmasked trial comparing a cervical pessary vs usual care from February 2017 through November 5, 2021, at 12 centers in the US. Study participants were nonlaboring individuals with a singleton pregnancy and a transvaginal ultrasound cervical length of 20 mm or less at gestations of 16 weeks 0 days through 23 weeks 6 days. Individuals with a prior spontaneous preterm birth were excluded. Interventions: Participants were randomized 1:1 to receive either a cervical pessary placed by a trained clinician (n = 280) or usual care (n = 264). Use of vaginal progesterone was at the discretion of treating clinicians. Main Outcome and Measures: The primary outcome was delivery or fetal death prior to 37 weeks. Results: A total of 544 participants (64%) of a planned sample size of 850 were enrolled in the study (mean age, 29.5 years [SD, 6 years]). Following the third interim analysis, study recruitment was stopped due to concern for fetal or neonatal/infant death as well as for futility. Baseline characteristics were balanced between participants randomized to pessary and those randomized to usual care; 98.9% received vaginal progesterone. In an as-randomized analysis, the primary outcome occurred in 127 participants (45.5%) randomized to pessary and 127 (45.6%) randomized to usual care (relative risk, 1.00; 95% CI, 0.83-1.20). Fetal or neonatal/infant death occurred in 13.3% of those randomized to receive a pessary and in 6.8% of those randomized to receive usual care (relative risk, 1.94; 95% CI, 1.13-3.32). Conclusions and Relevance: Cervical pessary in nonlaboring individuals with a singleton gestation and with a cervical length of 20 mm or less did not decrease the risk of preterm birth and was associated with a higher rate of fetal or neonatal/infant mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT02901626.

Genetic and Phenotypic Landscape of Peripartum Cardiomyopathy.

BACKGROUND: Peripartum cardiomyopathy (PPCM) occurs in ≈1:2000 deliveries in the United States and worldwide. The genetic underpinnings of PPCM remain poorly defined. Approximately 10% of women with PPCM harbor truncating variants in TTN (TTNtvs). Whether mutations in other genes can predispose to PPCM is not known. It is also not known if the presence of TTNtvs predicts clinical presentation or outcomes. Nor is it known if the prevalence of TTNtvs differs in women with PPCM and preeclampsia, the strongest risk factor for PPCM. METHODS: Women with PPCM were retrospectively identified from several US and international academic centers, and clinical information and DNA samples were acquired. Next-generation sequencing was performed on 67 genes, including TTN, and evaluated for burden of truncating and missense variants. The impact of TTNtvs on the severity of clinical presentation, and on clinical outcomes, was evaluated. RESULTS: Four hundred sixty-nine women met inclusion criteria. Of the women with PPCM, 10.4% bore TTNtvs (odds ratio=9.4 compared with 1.2% in the reference population; Bonferroni-corrected P [P*]=1.2×10-46). We additionally identified overrepresentation of truncating variants in FLNC (odds ratio=24.8, P*=7.0×10-8), DSP (odds ratio=14.9, P*=1.0×10-8), and BAG3 (odds ratio=53.1, P*=0.02), genes not previously associated with PPCM. This profile is highly similar to that found in nonischemic dilated cardiomyopathy. Women with TTNtvs had lower left ventricular ejection fraction on presentation than did women without TTNtvs (23.5% versus 29%, P=2.5×10-4), but did not differ significantly in timing of presentation after delivery, in prevalence of preeclampsia, or in rates of clinical recovery. CONCLUSIONS: This study provides the first extensive genetic and phenotypic landscape of PPCM and demonstrates that predisposition to heart failure is an important risk factor for PPCM. The work reveals a degree of genetic similarity between PPCM and dilated cardiomyopathy, suggesting that gene-specific therapeutic approaches being developed for dilated cardiomyopathy may also apply to PPCM, and that approaches to genetic testing in PPCM should mirror those taken in dilated cardiomyopathy. Last, the clarification of genotype/phenotype associations has important implications for genetic counseling.

Neonatal morbidity and mortality by mode of delivery in very preterm neonates.

BACKGROUND: The safest mode of delivery to use for very preterm infants is an ongoing topic of debate. There are many reasons to perform a cesarean delivery in cases of extremely preterm and very preterm infants, including indication for labor, fetal distress, maternal indications, and malpresentation. OBJECTIVE: This study aimed to determine whether cesarean delivery is associated with a considerable improvement in neonatal morbidity. STUDY DESIGN: This study is a retrospective cohort study of all singleton pregnancies, delivered from 22 to 29 weeks' gestation between 2010 and 2015, admitted for preterm labor or preterm premature rupture of membranes and excluded neonates with a delivery weight ≤500 g, multiple gestations, cases with intrauterine fetal demise, and induced terminations. The primary outcome for the study was a neonatal morbidity composite (Apgar score of <5 at 5 minutes, prolonged ventilation (>28 days), intraventricular hemorrhage, necrotizing enterocolitis, coagulopathy, discharged on home ventilator support, or discharged with enteric feeding tube). Cesarean deliveries were performed for standard obstetrical indications. Regression models were used and adjusted for nulliparity, delivery year, and presentation at the time of delivery to determine whether cesarean delivery is associated with neonatal morbidity or neonatal death. RESULTS: There were 271 eligible deliveries, which included 128 cesarean deliveries and 143 vaginal deliveries. The cesarean delivery group had fewer nulliparous patients and more fetuses presenting in breech position at the time of delivery. The overall composite neonatal morbidity occurred in 202 of the 271 (74.5%) deliveries and mortality occurred in 26 of the 271 (9.59%) deliveries. When adjusting for nulliparity, delivery year, and fetal presentation at the time of delivery, cesarean delivery was associated with a decreased risk for death in the delivery room or within 24 hours after delivery (adjusted risk ratio, 0.18; 95% confidence interval, 0.05-0.63; P=.03). Cesarean delivery was associated with an increased use of exogenous surfactant (adjusted risk ratio, 1.20; 95% confidence interval, 1.05-1.38; P=.01) and bag mask ventilation (adjusted risk ratio, 1.17; 95% confidence interval, 1.01-1.37; P=.03). In a secondary analysis that included only patients who received a complete course of steroids, there were no differences in the composite morbidity or mortality. CONCLUSION: Cesarean delivery performed for standard obstetrical indications in cases of very preterm neonates is associated with a decreased risk for death in the delivery room or within 24 hours of delivery but is not associated with an improvement in the overall morbidity or mortality.

Pilot Randomized Controlled Trial of Diabetes Group Prenatal Care.

OBJECTIVE: This study aimed to determine the feasibility and effectiveness of Diabetes Group Prenatal Care to increase patient engagement in diabetes self-care activities. STUDY DESIGN: A pilot randomized controlled trial was conducted at two sites. Inclusion criteria were English or Spanish speaking, type 2 or gestational diabetes, 22 to 34 weeks of gestational age at first study visit, ability to attend group care at specified times, and willingness to be randomized. Exclusion criteria included type 1 diabetes, multiple gestation, major fetal anomaly, serious medical comorbidity, and serious psychiatric illness. Women were randomized to Diabetes Group Prenatal Care or individual prenatal care. The primary outcome was completion of diabetes self-care activities, including diet, exercise, blood sugar testing, and medication adherence. Secondary outcomes included antenatal care characteristics, and maternal, neonatal, and diabetes management outcomes. Analysis followed the intention-to-treat principle. RESULTS: Of 159 eligible women, 84 (53%) consented to participate in the study and were randomized to group (n = 42) or individual (n = 42) prenatal care. Demographic characteristics were similar between study arms. Completion of diabetes self-care activities was similar overall, but women in group care ate the recommended amount of fruits and vegetables on more days per week (5.1 days/week ± 2.0 standard deviation [SD] in group care vs. 3.4 days ± 2.6 SD in individual care; p < 0.01) and gained less weight per week during the study period (0.2 lbs/week [interquartile range: 0-0.7] vs. 0.5 lbs/week [interquartile range: 0.2-0.9]; p = 0.03) than women in individual care. Women with gestational diabetes randomized to group care were 3.5 times more likely to have postpartum glucose tolerance testing than those in individual care (70 vs. 21%; relative risk: 3.5; 95% confidence interval: 1.4-8.8). Other maternal, neonatal, and pregnancy outcomes were similar between study arms. CONCLUSION: Diabetes group care is feasible and shows promise for decreasing gestational weight gain, improving diet, and increasing postpartum diabetes testing among women with pregnancies complicated by diabetes. KEY POINTS: · Women with gestational diabetes in group care were 3.5 times more likely to return for postpartum glucose tolerance testing.. · Women with gestational diabetes in group care had less gestational weight gain during the study period.. · Diabetes Group Prenatal Care is a promising intervention to improve outcomes for women with diabetes in pregnancy..

Association of SARS-CoV-2 Infection With Serious Maternal Morbidity and Mortality From Obstetric Complications.

Importance: It remains unknown whether SARS-CoV-2 infection specifically increases the risk of serious obstetric morbidity. Objective: To evaluate the association of SARS-CoV-2 infection with serious maternal morbidity or mortality from common obstetric complications. Design, Setting, and Participants: Retrospective cohort study of 14 104 pregnant and postpartum patients delivered between March 1, 2020, and December 31, 2020 (with final follow-up to February 11, 2021), at 17 US hospitals participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development's Gestational Research Assessments of COVID-19 (GRAVID) Study. All patients with SARS-CoV-2 were included and compared with those without a positive SARS-CoV-2 test result who delivered on randomly selected dates over the same period. Exposures: SARS-CoV-2 infection was based on a positive nucleic acid or antigen test result. Secondary analyses further stratified those with SARS-CoV-2 infection by disease severity. Main Outcomes and Measures: The primary outcome was a composite of maternal death or serious morbidity related to hypertensive disorders of pregnancy, postpartum hemorrhage, or infection other than SARS-CoV-2. The main secondary outcome was cesarean birth. Results: Of the 14 104 included patients (mean age, 29.7 years), 2352 patients had SARS-CoV-2 infection and 11 752 did not have a positive SARS-CoV-2 test result. Compared with those without a positive SARS-CoV-2 test result, SARS-CoV-2 infection was significantly associated with the primary outcome (13.4% vs 9.2%; difference, 4.2% [95% CI, 2.8%-5.6%]; adjusted relative risk [aRR], 1.41 [95% CI, 1.23-1.61]). All 5 maternal deaths were in the SARS-CoV-2 group. SARS-CoV-2 infection was not significantly associated with cesarean birth (34.7% vs 32.4%; aRR, 1.05 [95% CI, 0.99-1.11]). Compared with those without a positive SARS-CoV-2 test result, moderate or higher COVID-19 severity (n = 586) was significantly associated with the primary outcome (26.1% vs 9.2%; difference, 16.9% [95% CI, 13.3%-20.4%]; aRR, 2.06 [95% CI, 1.73-2.46]) and the major secondary outcome of cesarean birth (45.4% vs 32.4%; difference, 12.8% [95% CI, 8.7%-16.8%]; aRR, 1.17 [95% CI, 1.07-1.28]), but mild or asymptomatic infection (n = 1766) was not significantly associated with the primary outcome (9.2% vs 9.2%; difference, 0% [95% CI, -1.4% to 1.4%]; aRR, 1.11 [95% CI, 0.94-1.32]) or cesarean birth (31.2% vs 32.4%; difference, -1.4% [95% CI, -3.6% to 0.8%]; aRR, 1.00 [95% CI, 0.93-1.07]). Conclusions and Relevance: Among pregnant and postpartum individuals at 17 US hospitals, SARS-CoV-2 infection was associated with an increased risk for a composite outcome of maternal mortality or serious morbidity from obstetric complications.

Labor Induction versus Expectant Management in Low-Risk Nulliparous Women.

BACKGROUND: The perinatal and maternal consequences of induction of labor at 39 weeks among low-risk nulliparous women are uncertain. METHODS: In this multicenter trial, we randomly assigned low-risk nulliparous women who were at 38 weeks 0 days to 38 weeks 6 days of gestation to labor induction at 39 weeks 0 days to 39 weeks 4 days or to expectant management. The primary outcome was a composite of perinatal death or severe neonatal complications; the principal secondary outcome was cesarean delivery. RESULTS: A total of 3062 women were assigned to labor induction, and 3044 were assigned to expectant management. The primary outcome occurred in 4.3% of neonates in the induction group and in 5.4% in the expectant-management group (relative risk, 0.80; 95% confidence interval [CI], 0.64 to 1.00). The frequency of cesarean delivery was significantly lower in the induction group than in the expectant-management group (18.6% vs. 22.2%; relative risk, 0.84; 95% CI, 0.76 to 0.93). CONCLUSIONS: Induction of labor at 39 weeks in low-risk nulliparous women did not result in a significantly lower frequency of a composite adverse perinatal outcome, but it did result in a significantly lower frequency of cesarean delivery. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ARRIVE ClinicalTrials.gov number, NCT01990612 .).

Association between delivering live-born twins and acute psychiatric illness within 1 year of delivery.

BACKGROUND: Having twins is associated with more depressive symptoms than having singletons. However, the association between having twins and psychiatric morbidity requiring emergency department visit or inpatient hospitalization is less well known. OBJECTIVE: This study aimed to determine whether women have higher risk of having a psychiatric diagnosis at an emergency department visit or inpatient admission in the year after having twins vs singletons. STUDY DESIGN: This retrospective cohort study used International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis and procedure codes within the Florida State Inpatient Database and State Emergency Department Database, which have an encrypted identifier allowing nearly all inpatient and emergency department encounters statewide to be linked to the medical record. The first delivery of Florida residents at the age of 13 to 55 years from 2005 to 2014 was included, regardless of parity; women with International Classification of Diseases, Ninth Revision, Clinical Modification coding for psychiatric illness or substance misuse during pregnancy or for stillbirth or higher-order gestations were excluded. The exposure was an International Classification of Diseases, Ninth Revision, Clinical Modification code during delivery hospitalization of live-born twins. The primary outcome was an International Classification of Diseases, Ninth Revision, Clinical Modification code during an emergency department encounter or inpatient admission within 1 year of delivery for a psychiatric morbidity composite (suicide attempt, depression, anxiety, posttraumatic stress disorder, psychosis, acute stress reaction, or adjustment disorder). The secondary outcome was drug or alcohol use or dependence within 1 year of delivery. We compared outcomes after delivery of live-born twins with singletons using multivariable logistic regression adjusting for sociodemographic and medical factors. We tested for interactions between independent variables in the primary model and conducted sensitivity analyses stratifying women by insurance type and presence of severe intrapartum morbidity or medical comorbidities. RESULTS: A total of 17,365 women who had live-born twins and 1,058,880 who had singletons were included. Within 1 year of birth, 1.6% of women delivering twins (n=270) and 1.6% of women delivering singletons (n=17,236) had an emergency department encounter or inpatient admission coded for psychiatric morbidity (adjusted odds ratio, 1.00; 95% confidence interval, 0.88-1.14). Coding for drug or alcohol use or dependence in an emergency department encounter or inpatient admission in the year after twin vs singleton delivery was also similar (n=96 [0.6%] vs n=6222 [0.6%]; adjusted odds ratio, 1.11; 95% confidence interval, 0.91-1.36). However, women with public health insurance were more likely to be coded for drug or alcohol use or dependence after twin than singleton delivery (n=75 [1.2%] vs n=4858 [1.0%]; adjusted odds ratio, 1.27; 95% confidence interval, 1.01-1.60). Women with ≥1 medical comorbidity, severe maternal morbidity, or low income also had an increased risk of psychiatric morbidity after twin delivery (comorbidities, n=7438 [42.8%]; adjusted odds ratio, 1.30; 95% confidence interval, 1.25-1.34; severe maternal morbidity, n=940 [5.4%]; adjusted odds ratio, 1.65; 95% confidence interval, 1.49-1.81; lowest income quartile, n=4409 [26.8%]; adjusted odds ratio, 1.31; 95% confidence interval, 1.23-1.40; second-lowest income quartile, n=4770 [29.0%]; adjusted odds ratio, 1.34; 95% confidence interval, 1.26-1.43). CONCLUSION: Overall, diagnostic codes for psychiatric illness or substance misuse in emergency department visits or hospital admissions in the year after twin vs singleton delivery are similar. However, women with who are low income or have public health insurance, comorbidities, or severe maternal morbidity are at an increased risk of postpartum psychiatric morbidity after twin vs singleton delivery.

Obesity, Second Stage Duration, and Labor Outcomes in Nulliparous Women.

OBJECTIVE: This study aimed to estimate second stage duration and its effects on labor outcomes in obese versus nonobese nulliparous women. STUDY DESIGN: This was a secondary analysis of a cohort of nulliparous women who presented for labor at term and reached complete cervical dilation. Adjusted relative risks (aRR) were used to estimate the association between obesity and second stage characteristics, composite neonatal morbidity, and composite maternal morbidity. Effect modification of prolonged second stage on the association between obesity and morbidity was assessed by including an interaction term in the regression model. RESULTS: Compared with nonobese, obese women were more likely to have a prolonged second stage (aRR: 1.48, 95% CI: 1.18-1.85 for ≥3 hours; aRR: 1.65, 95% CI: 1.18-2.30 for ≥4 hours). Obesity was associated with a higher rate of second stage cesarean (aRR: 1.78, 95% CI: 1.34-2.34) and cesarean delivery for fetal distress (aRR: 2.67, 95% CI: 1.18-3.58). Obesity was also associated with increased rates of neonatal (aRR: 1.38, 95% CI: 1.05-1.80), but not maternal morbidity (aRR: 1.06, 95% CI: 0.90-1.25). Neonatal morbidity risk was not modified by prolonged second stage. CONCLUSION: Obesity is associated with increased risk of neonatal morbidity, which is not modified by prolonged second stage of labor.

Mild Neonatal Acidemia is Associated with Neonatal Morbidity at Term.

OBJECTIVE: The aim of this study is to determine the association between mild acidemia (umbilical artery [UA] pH: 7.11-7.19) and neonatal morbidity in neonates at term. STUDY DESIGN: This is a secondary analysis of a prospective cohort of women admitted for labor at ≥37 weeks of gestation within a single institution from 2010 to 2015. Universal umbilical cord blood gas assessment was performed and validated. A composite neonatal morbidity index was created including respiratory distress, mechanical ventilation, meconium aspiration syndrome, suspected or confirmed sepsis, hypoxic-ischemic encephalopathy, need for therapeutic hypothermia, seizures and death. The cohort was stratified by UA pH into normal (≥7.20), mild acidemia (7.11-7.19), acidemia (7.00-7.10), and severe acidemia (≤7.00). A subanalysis was also performed where neonates with UA pH between 7.11 and 7.19 were further stratified into two groups (7.11-7.14 and 7.15-7.19) to determine if mildly acidotic infants at the lower end of the pH range were at increased risk of morbidity. Multivariable logistic regression was used to estimate the association between UA pH and neonatal morbidity. RESULTS: Among 6,341 participants, 614 (9.7%) had mild acidemia. These infants were more likely to experience morbidity compared with those with normal UA pH (adjusted odds ratio [aOR]: 2.14; [1.68-2.73]). Among neonates with mild acidemia, UA pH 7.11 to 7.14 was associated with increased risk of composite neonatal morbidity (aOR: 3.02; [1.89-4.82]), as well as respiratory distress and suspected or confirmed sepsis when compared with UA pH 7.15 to 7.19. CONCLUSION: These data demonstrate that term neonates with mild acidemia at birth are at higher odds for short-term morbidity compared with neonates with normal UA pH. Furthermore, among neonates with mild acidemia, those with lower UA pH had worse neonatal outcomes than those with higher UA pH. This suggests that closer evaluation of neonates with UA pH higher than traditionally used could allow for earlier detection of morbidity and possible intervention. KEY POINTS: · Neonates with mild acidemia (umbilical artery [UA] pH: 7.11-7.19) demonstrated an increased risk of composite morbidity compared with those with normal UA pH (≥7.20).. · Among neonates with mild acidemia, those with lower UA pH (7.11-7.14) had a greater risk of morbidity compared with those with higher UA pH (7.15-7.19), suggesting a progression of risk of morbidity as UA pH decreases.. · The majority of prior research has focused on severe acidemia (UA pH ≤ 7.00) using outcomes of severe neurologic morbidity and mortality. These data suggest that an increased risk of morbidity exists at higher pH values when more proximal and less severe outcomes are included, such as respiratory distress and neonatal sepsis..

The duration of intrapartum supplemental oxygen administration and umbilical cord oxygen content.

BACKGROUND: Maternal oxygen (O2) administration is a commonly performed intrauterine resuscitation technique though to improve fetal oxygenation. However, hyperoxygenation is known to be harmful in both neonates and adults. Currently, there are no formal recommendations on whether a certain dose or duration of O2 may be most helpful in improving umbilical cord gases or neonatal outcomes. OBJECTIVE: We tested the hypothesis that prolonged supplemental O2 exposure during labor is associated with increased umbilical cord O2 concentrations. STUDY DESIGN: This was a planned secondary analysis of a randomized noninferiority trial comparing O2 with room air in laboring patients. Patients were randomized to receive either 10 L/min O2 or room air at any point during active labor when they developed a category II fetal heart tracing that would otherwise require resuscitation. The primary outcome variable for this analysis was partial pressure of O2 in the umbilical vein. The secondary outcome variable was partial pressure of O2 in the umbilical artery. These outcome variables were compared between patients with short durations of O2 exposure and those with long durations of O2 exposure, defined as <75th percentile and ≥75th percentile of duration, respectively. The outcomes were also compared among the groups that received room air, O2 for short durations, and O2 for long durations. RESULTS: Among the 99 patients with paired and validated cord gases who were included in this analysis, the partial pressure of O2 in the umbilical vein was significantly lower in patients who received O2 supplementation for longer durations than in those who received O2 for shorter durations (median interquartile range 25.5 [21.5-33] vs 32.5 [26.5-37.5] mm Hg; P<.03). There was no difference in the partial pressure of O2 in the umbilical artery or other cord gases between the short and long duration O2 supplementation groups. Other methods of intrauterine resuscitation were similar between the short and long duration O2 supplementation groups. There was no difference in the partial pressure of O2 in the umbilical artery or in the umbilical vein when the room air, short duration O2 supplementation, and long duration O2 supplementation groups were compared. CONCLUSION: Longer durations of O2 exposure are not associated with a higher partial pressure of O2 in the umbilical cord. In fact, patients with longer durations of O2 exposure had lower partial pressure of O2 in the umbilical vein, suggesting impaired placental O2 transfer with prolonged O2 exposure.