Risk of Postpartum Hemorrhage in Hypertensive Disorders of Pregnancy: Stratified by Severity.

OBJECTIVE: We aimed to determine the composite maternal hemorrhagic outcome (CMHO) among individuals with and without hypertensive disorders of pregnancy (HDP), stratified by disease severity. Additionally, we investigated the composite neonatal adverse outcome (CNAO) among individuals with HDP who had postpartum hemorrhage (PPH) versus did not have PPH. STUDY DESIGN: Our retrospective cohort study included all singletons who delivered at a Level IV center over two consecutive years. The primary outcome was the rate of CMHO, defined as blood loss ≥1,000 mL, use of uterotonics, mechanical tamponade, surgical techniques for atony, transfusion, venous thromboembolism, intensive care unit admission, hysterectomy, or maternal death. A subgroup analysis was performed to investigate the primary outcome stratified by (1) chronic hypertension, (2) gestational hypertension and preeclampsia without severe features, and (3) preeclampsia with severe features. A multivariable regression analysis was performed to investigate the association of HDP with and without PPH on a CNAO which included APGAR <7 at 5 minutes, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, seizures, neonatal sepsis, meconium aspiration syndrome, ventilation >6 hours, hypoxic-ischemic encephalopathy, or neonatal death. RESULTS: Of 8,357 singletons, 2,827 (34%) had HDP. Preterm delivery <37 weeks, induction of labor, prolonged oxytocin use, and magnesium sulfate usage were more common in those with versus without HDP (p < 0.001). CMHO was higher among individuals with HDP than those without HDP (26 vs. 19%; adjusted relative risk [aRR] 1.11, 95% CI 1.01-1.22). In the subgroup analysis, only individuals with preeclampsia with severe features were associated with higher CMHO (n = 802; aRR 1.52, 95% CI 1.32-1.75). There was a higher likelihood of CNAO in individuals with both HDP and PPH compared to those with HDP without PPH (aRR 1.49, 95% CI 1.06-2.09). CONCLUSION: CMHO was higher among those with HDP. After stratification, only those with preeclampsia with severe features had an increased risk of CMHO. Among individuals with HDP, those who also had a PPH had worse neonatal outcomes than those without hemorrhage. KEY POINTS: · Individuals with HDP had an 11% higher likelihood of CMHO.. · After stratification, increased CMHO was limited to those with preeclampsia with severe features.. · There was a higher likelihood of CNAO in those with both HDP and PPH compared to HDP without PPH..

Equivalence of single and standard doses of antenatal corticosteroids for late preterm neonatal outcomes: insights from a secondary analysis.

BACKGROUND: The recent paradigm shift of treating individuals at risk of late preterm birth with antenatal corticosteroids warrants an assessment of the effect of single dosage. OBJECTIVE: To compare outcomes of neonates born in the late preterm period (34.0-36.6 weeks) after a single dose of antenatal corticosteroids vs placebo. STUDY DESIGN: We performed a secondary analysis of the Antenatal Late Preterm Steroids trial. All individuals enrolled in the parent trial who received only a single dose of either antenatal corticosteroids or placebo and delivered within 24 hours were included. Primary outcome was a composite of respiratory support at 72 hours, including continuous positive airway pressure or high-flow nasal cannula ≥2 hours, oxygen with an inspired fraction of ≥30% for ≥4 hours, or mechanical ventilation. RESULTS: Of the 2831 individuals in the parent trial, 1083 (38.3%) met inclusion criteria; of them, 539 (49.8%) received a single dose of antenatal corticosteroids and 544 (50.2%) a single placebo dose. The placebo and antenatal corticosteroids groups had similar demographic and clinical characteristics. There was no difference in the rate of the primary respiratory outcome (adjusted risk ratio, 1.12; 95% confidence interval, 0.85-1.47) or in the rate of respiratory distress syndrome (adjusted risk ratio, 1.47; 95% confidence interval, 0.95-2.26) between those who received a single antenatal corticosteroids dose and placebo. An exploratory stratification by randomization-to-delivery intervals of 12-hour increments also showed no association with lower primary respiratory outcome rates. CONCLUSION: In individuals with late preterm birth pregnancies who received antenatal corticosteroids and delivered before a second dose, there were no differences in neonatal respiratory morbidities compared with placebo. However, this study is not powered to detect treatment efficacy.

Implementing a Bundle for Evidence-based Cesarean Delivery May Not Be As Beneficial as Expected: A Multi-center, Pre- and Post- Study.

BACKGROUND: Standardization of procedures improves outcomes. Though systematic reviews have summarized the evidence-based steps (EBS) of cesarean delivery (CD), their bundled implementation has not been investigated. OBJECTIVE: In this pre- and post-implementation trial, we sought to ascertain if bundled EBS of CD, compared to surgeon's preference, improves outcomes. STUDY DESIGN: A StaRI (Standards for Reporting Implementation Studies) compliant, multi-center pre- and post-implementation trial at 4 teaching hospitals was conducted. The pre-implementation period consisted of CD done based on the physicians' preferences for 3 months; educational intervention (e.g., didactics, badge cards, posters, video) occurred at the 4th month. CDs in post-implementation period employed the bundled EBS. A pre-planned 10% randomized audit of both groups assessed adherence and uptake of EBS. The primary outcome was a composite maternal morbidity (CMM), which included estimated blood loss > 1,000 mL, blood transfusion, endometritis, post-partum fever, wound complications, sepsis, thrombosis, ICU admission, hysterectomy, or death. The secondary outcome was a composite neonatal morbidity (CNM) and some of its components were 5-min Apgar score < 7, positive pressure oxygen use, hypoglycemia, or sepsis. A priori Bayesian sample size calculation indicated 700 CD in each group was needed to demonstrate 20% relative reduction (from 15% to 12%) of CMM with 75% certainty. Bayesian logistic regression with neutral priors was used to calculate likelihood of net-improvement in adjusted relative risk (aRR) with 95% credible intervals (CrI). RESULTS: A total of 1,425 consecutive CD (721 in pre- and 704 in post-implementation group) were examined. Audited data indicated that the baseline EBS utilization rate during the pre-implementation period was 79%; after the implementation bundled EBS of CD the audited adherence was 89%-an uptake of 10.0% of the EBS. In four aspects, the maternal characteristics differed significantly in the pre- and post-implementation periods: race/ethnicity, hypertensive disorder, and the relative contribution of the 4 centers to the cohorts and the gestational age at delivery, but the indications for CD and whether its duration was < versus > 60 min did not. The rates of CMM in the pre- and post-implementation groups were 26% and 22%, respectively (aRR, 0.88; 95% CrI, 0.73-1.04), with a 94 % Bayesian probability of a reduction in CMM. The CNM occurred in 37% of the pre- and in 41% of the post-implementation group (aRR, 1.12; 95% CrI 0.98-1.39), with a 95% Bayesian probability of worsening in CNM. When CMM were segregated by preterm (<37 wks) and term (> 37 weeks) CD, the improvement in maternal outcomes persisted; when CNM were segregated by gestational age subgroupsthe potential for worsening neonatal outcomes persisted as well. CONCLUSIONS: Standardization of the evidence-based bundled steps of cesarean delivery resulted in a modest reduction of the composite maternal outcome; however, a paradoxical increase in neonatal composite morbidity was noted. Although individual evidence-based steps may be of value, while awaiting additional intervention trials a formal bundling of such steps is currently not recommended.

Indicated versus universal third trimester ultrasound examination in low-risk pregnancies: a pre- and post-intervention study.

BACKGROUND: In low-risk pregnancies, third trimester ultrasound examination is indicated if fundal height measurement and gestational age discrepancy is observed. Despite potential improvement in detection of ultrasound abnormality, prior trials to date on universal third trimester ultrasound examination in low-risk pregnancies, compared to indicated ultrasound examination, have not demonstrated improvement in neonatal or maternal adverse outcomes. OBJECTIVE: The primary objective was to determine if universal third trimester ultrasound examination in low-risk pregnancies could attenuate composite neonatal adverse outcome. The secondary objectives were to compare change in composite maternal adverse outcomes and detection of abnormalities of fetal growth (fetal growth restriction or large for gestational age) or amniotic fluid (oligo- or poly-hydramnios). STUDY DESIGN: Our pre- and post-intervention study at 9 locations included low-risk pregnancies; those without indication for ultrasound examination in the third trimester. Compared to indicated ultrasound in the pre-implementation period, in the post-implementation period all patients were scheduled for ultrasound examination at 36.0 - 37.6 weeks. In both periods clinicians intervened based on abnormalities identified. Composite neonatal adverse outcomes included any of: Apgar score ≤ 5 at 5 min, cord pH < 7.00, birth trauma (bone fracture or brachial plexus palsy), intubation for > 24 hours, hypoxic ischemic encephalopathy, seizure, sepsis (bacteremia proven with blood culture), meconium aspiration syndrome, intraventricular hemorrhage grade III or IV, periventricular leukomalacia, necrotizing enterocolitis, stillbirth after 36 weeks, or neonatal death within 28 days of birth. Composite maternal adverse outcomes included any of: chorioamnionitis, wound infection, estimated blood loss >1000mL, blood transfusion, deep venous thrombus or pulmonary embolism, admission to intensive care unit, or death. Using Bayesian statistics, we calculated a sample size of 600 individuals in each arm to detect >75% probability of any reduction in primary outcome, (80% power; 50% hypothesized risk reduction). RESULTS: During the pre-intervention phase, 747 individuals were identified during the initial ultrasound examination and among them 568 (76.0%) met the inclusion criteria at 36.0 to 37.6 weeks; during the post-intervention period, the corresponding numbers were 770 and 661 (85.8%). The rate of identified abnormalities of fetal growth or of amniotic fluid increased from between pre- and post-intervention period (7.1% versus 22.2%, p< 0.0001; number needed to diagnose, 7; 95% confidence interval, 5-9). The primary outcome occurred in 15 of 568 (2.6%) individuals in the pre- and 12 of 661 (1.8%) in the post-intervention group (83% probability of risk reduction, posterior relative risk, 0.69; 95% credible interval, 0.34-1.42). The composite maternal adverse outcomes occurred in 8.6% in the pre- and 6.5% in post-intervention group (90% probability of risk (posterior relative risk, 0.74; 95% credible interval, 0.49-1.15). The number needed to treat to reduce composite neonatal adverse outcomes was 121 (95% confidence interval, 40-200), to reduce composite maternal adverse outcomes was 46 (95% confidence interval, 19-74), and to prevent cesarean delivery was 18 (95% confidence interval, 9-31). CONCLUSION: Among low-risk pregnancies, compared to routine care with indicated ultrasound examination, implementation of a universal third-trimester ultrasound examination at 36.0-37.6 weeks attenuated composite neonatal and maternal adverse outcomes.

Gestational diabetes mellitus and late preterm birth: outcomes with and without antenatal corticosteroid exposure.

BACKGROUND: Unlike pregestational diabetes mellitus, the American College of Obstetricians and Gynecologists recommends antenatal corticosteroids in those with gestational diabetes mellitus at risk for preterm birth. However, this recommendation is based on limited data, only 10.6% of the Antenatal Late Preterm Steroids study sample had gestational diabetes mellitus. There is a paucity of data on the risk of neonatal respiratory and other morbidity in this population. OBJECTIVE: This study aimed to examine respiratory outcomes in parturients with gestational diabetes mellitus who received antenatal corticosteroids and delivered during the late preterm period vs those who did not. STUDY DESIGN: This population-based cohort study used the US Vital Statistics dataset between 2016 to 2020. The inclusion criteria were singleton, nonanomalous individuals who delivered between 34.0 to 36.6 weeks with gestational diabetes mellitus and known status of antepartum corticosteroid exposure. The primary outcome, a composite neonatal adverse outcome, included Apgar score <5 at 5 minutes, immediate assisted ventilation, assisted ventilation >6 hours, surfactant use, seizure, or neonatal mortality. The secondary outcome was a composite maternal adverse outcome, including maternal blood transfusion, ruptured uterus, unplanned hysterectomy, and admission to the intensive care unit. Multivariable Poisson regression models were used to estimate adjusted relative risks and 95% confidence intervals. Average annual percent change was calculated to assess changes in rates of corticosteroid exposure over the study period. RESULTS: Of 19 million births during the study period, 110,197 (0.6%) met the inclusion criteria, and among them, 23,028 (20.9%) individuals with gestational diabetes mellitus received antenatal corticosteroids. The rate of antenatal steroid exposure remained stable over the 5 years (APC=10.7; 95% confidence interval, -5.4 to 29.4). The composite neonatal adverse outcome was significantly higher among those who received corticosteroids than among those who did not (137.1 vs 216.5 per 1000 live births; adjusted relative risk 1.24; 95% confidence interval, 1.20-1.28). Three components of the composite neonatal adverse outcome-immediate assisted ventilation, intubation >6 hours, and surfactant use-were significantly higher with exposure than without. In addition, the composite maternal adverse outcome was significantly higher among those who received corticosteroids (adjusted relative risk, 1.34; 95% confidence interval, 1.18-1.52). Three components of the composite maternal adverse outcome-admission to intensive care unit, blood transfusion, and unplanned hysterectomy-were significantly higher among the exposed group. Subgroup analysis, among large for gestational age, by gestational age, and race and ethnicity, confirm the trend of increased likelihood of adverse outcomes with exposure to corticosteroid. CONCLUSION: Individuals with gestational diabetes mellitus and antenatal corticosteroid exposure, who delivered in the late preterm, were at higher risk of neonatal and maternal adverse outcomes than those unexposed to corticosteroid.

The association between maternal insurance status on maternal and neonatal outcomes in women with hypertensive disorders of pregnancy.

The objective of this study was to examine the association between maternal insurance status and maternal and neonatal adverse outcomes in women who had hypertensive disorders in pregnancy. A population-based retrospective cohort study was undertaken using the US Vital Statistics dataset on Period Linked Birth-Infant Data from 2016-2020. The study population was restricted to non-anomalous births from women whose pregnancies were complicated by hypertensive disorders. Insurance status was categorized as private, Medicaid, self-pay and other. The primary outcome was a composite of maternal adverse outcomes, which included admission to the intensive care unit, unplanned hysterectomy, maternal blood transfusion or uterine rupture. We examined the role of prenatal care in these relationships using a mediation analysis with Kotelchuck's Adequacy of Prenatal Care Utilization Index. Multivariable logistic regression models were used to estimate the association between maternal insurance status and adverse outcomes (using adjusted odds ratios [aOR] and 99% confidence interval [CI]). Of the 18,999,865 live births in the five-year study, 1,642,654 (8.6%) met the inclusion criteria. The frequency of the composite maternal adverse outcome was 1.3%. The maternal composite occurred more frequently in women with Medicaid (aOR = 1.11, 99% CI: 1.06, 1.16) or self-pay (aOR = 1.40, 99% CI: 1.25, 1.55) when compared to private insurance. Adjusting for prenatal care slightly attenuated this association, but remained significant. Among women with hypertensive disorders in pregnancy, women with Medicaid insurance or self-pay were more likely to experience maternal and neonatal adverse outcomes than women with private insurance.

Ambulation for latency during expectant management of preterm prelabor rupture of membranes: a randomized controlled trial (AMBLE).

BACKGROUND: Individuals hospitalized with preterm prelabor rupture of membranes are often advised to limit their activity or adhere to bed rest. Some evidence suggests that greater activity is associated with longer latency and improved outcomes, but no high-quality evidence from a randomized controlled trial exists. OBJECTIVE: This study aimed to evaluate whether encouragement to ambulate at least 2000 steps daily affects latency among individuals with preterm prelabor rupture of membranes compared with usual care. STUDY DESIGN: This was a multisite unblinded, 2-arm randomized trial of individuals at 23 0/7 to 35 0/7 weeks of gestation undergoing inpatient expectant management of preterm prelabor rupture of membranes with planned delivery at least 7 days away. Each participant wore a Fitbit Inspire that tracked steps. The intervention arm was encouraged (verbal and Fitbit-based reminders) to reach a goal of 2000 steps per day. The usual-care arm was allowed ad libitum activity with no step goal or reminders. The primary outcome was latency (days) from randomization to delivery. Secondary analyses included composite neonatal and maternal clinical outcomes and maternal mental health survey results. Statistical analyses were conducted with an intent-to-treat approach under a Bayesian framework using neutral priors (a priori assumed 50:50 likelihood of longer latency in either arm). A total of 100 participants were required to have 80% power to demonstrate a 4-day difference in latency with 75% certainty (Bayesian probability). RESULTS: Among 163 eligible individuals, 100 (61%) were randomized, and after loss to follow-up, 95 were analyzed. Gestational age at randomization was 29 3/7 weeks (interquartile range, 26 2/7 to 31 5/7) in the intervention arm and 27 4/7 weeks (interquartile range, 25 4/7 to 29 6/7) in the usual-care arm. Median step counts were 1690 per day in the intervention arm (interquartile range, 1031-2641) and 1338 per day in the usual-care arm (interquartile range, 784-1913). Median days of latency were 9 days in the intervention arm (interquartile range, 4-17) and 6 days in the usual-care arm (interquartile range, 2-14). The primary analysis indicated a 65% posterior probability that the intervention increased latency relative to usual care (posterior relative risk, 1.09; 95% credible interval, 0.70-1.71). The relative risk was 0.55 (95% credible interval, 0.32-0.82) for the composite neonatal adverse outcome, with 99% posterior probability of intervention benefit, and was 0.94 (95% credible interval, 0.72-1.20) for the composite maternal adverse outcome, with 70% posterior probability of intervention benefit. There was a 94% posterior probability of the intervention arm having a greater decrease in maternal stress score from baseline to before delivery compared with the usual-care arm (mean arm difference, 3.24 points [95% credible interval, -7.23 to 0.79]). Adjustment for gestational age at randomization had minimal impact on secondary outcome results. CONCLUSION: Individuals with preterm prelabor rupture of membranes randomized to encouragement to ambulate had a longer latency to delivery and improved neonatal and mental health outcomes, with similar maternal clinical outcomes compared with usual care.

Maternal and Neonatal Outcomes of Gunshot Wounds in Pregnancy: A Systematic Review of Case Reports.

A systematic review was performed to compare adverse maternal and neonatal outcomes among pregnant patients with gunshot wounds (GSW) to the abdominopelvic vs other region(s) at > 20 weeks gestation. A search of Medline Ovid, Elsevier Embase, EBSCO CINAHL, and Cochrane Library in July 2022 and reference searches resulted in 1742 studies, which were screened. The 41 included studies reported outcomes for 59 pregnant patients with GSW, of which 31 (52.5%) had an isolated abdominopelvic GSW and 28 (47.5%) had an extremity, thorax, head/neck, back/spine, poly-site, or other/unknown GSW. Stillbirth occurred in 26.7% of abdominopelvic GSW and 26% of non-abdominopelvic GSW. Maternal death occurred in 3.7% of abdominopelvic GSW and 10.7% of non-abdominopelvic GSW. Neonatal death occurred in 9.1% of abdominopelvic GSW and 5.3% of non-abdominopelvic GSW. Further research is needed to standardize the approach for the evaluation and management of patients with GSW in pregnancy.

Validation of Three Models for Prediction of Blood Transfusion during Cesarean Delivery Admission.

OBJECTIVE: Prediction of blood transfusion during delivery admission allows for clinical preparedness and risk mitigation. Although prediction models have been developed and adopted into practice, their external validation is limited. We aimed to evaluate the performance of three blood transfusion prediction models in a U.S. cohort of individuals undergoing cesarean delivery. STUDY DESIGN: This was a secondary analysis of a multicenter randomized trial of tranexamic acid for prevention of hemorrhage at time of cesarean delivery. Three models were considered: a categorical risk tool (California Maternal Quality Care Collaborative [CMQCC]) and two regression models (Ahmadzia et al and Albright et al). The primary outcome was intrapartum or postpartum red blood cell transfusion. The CMQCC algorithm was applied to the cohort with frequency of risk category (low, medium, high) and associated transfusion rates reported. For the regression models, the area under the receiver-operating curve (AUC) was calculated and a calibration curve plotted to evaluate each model's capacity to predict receipt of transfusion. The regression model outputs were statistically compared. RESULTS: Of 10,785 analyzed individuals, 3.9% received a red blood cell transfusion during delivery admission. The CMQCC risk tool categorized 1,970 (18.3%) individuals as low risk, 5,259 (48.8%) as medium risk, and 3,556 (33.0%) as high risk with corresponding transfusion rates of 2.1% (95% confidence interval [CI]: 1.5-2.9%), 2.2% (95% CI: 1.8-2.6%), and 7.5% (95% CI: 6.6-8.4%), respectively. The AUC for prediction of blood transfusion using the Ahmadzia and Albright models was 0.78 (95% CI: 0.76-0.81) and 0.79 (95% CI: 0.77-0.82), respectively (p = 0.38 for difference). Calibration curves demonstrated overall agreement between the predicted probability and observed likelihood of blood transfusion. CONCLUSION: Three models were externally validated for prediction of blood transfusion during cesarean delivery admission in this U.S. COHORT: Overall, performance was moderate; model selection should be based on ease of application until a specific model with superior predictive ability is developed. KEY POINTS: · A total of 3.9% of individuals received a blood transfusion during cesarean delivery admission.. · Three models used in clinical practice are externally valid for blood transfusion prediction.. · Institutional model selection should be based on ease of application until further research identifies the optimal approach..

Spinal Hypotension and Time from Spinal-to-Delivery in Scheduled Cesarean Deliveries: Association with Neonatal Acidosis.

OBJECTIVE: This work aimed to study the effect of sustained hypotension after spinal on neonatal acidosis and adverse outcomes in those undergoing scheduled cesarean delivery (CD) with universal prophylactic vasopressor exposure and to examine differences in spinal-to-delivery time by neonatal acidosis status. STUDY DESIGN: This retrospective cohort study conducted at a quaternary care center from January 2019 to December 2021 included singleton, term, nonanomalous pregnancies, with scheduled CD under spinal anesthesia. Hypotension was defined as a systolic blood pressure (SYS-BP) < 100 mm Hg (SYS-BP100) or a >20% drop from baseline blood pressure (SYS-BP20). Both the occurrence of hypotension and its magnitude and duration were studied; the latter through the development of a hypotension index. The 90th and 95th percentiles of the hypotension index for SYS-BP20 and SYS-BP100, respectively, were used to define sustained hypotension. The primary outcome was neonatal acidosis (umbilical artery pH ≤ 7.1 or base excess ≤ -12 mmol). Secondary outcomes were composites of neonatal (CNAO) and maternal (CMAO) adverse outcomes. Multivariable Poisson regression models with robust error variance analysis was used to estimate adjusted relative risks (aRRs) and 95% confidence intervals (CIs). RESULTS: Our study included 332 individuals who underwent scheduled CD; among them 330 (99.4%) received prophylactic vasopressors. The rate of neonatal acidosis was 4.2%. Sustained hypotension after spinal anesthesia, which occurred in 12.3% of the cohort, was associated with increased risk for neonatal acidosis (aRR 3.96, 95% CI 1.21-12.98), but was not associated with CNAO or CMAO. Time from spinal-to-delivery was not different in those with and without neonatal acidosis. CONCLUSION: Despite universal exposure to prophylactic vasopressors, sustained hypotension after spinal anesthesia was still associated with neonatal acidosis, but no other adverse perinatal outcomes. Our findings may provide additional support for the adoption of prophylactic vasopressors to reduce spinal hypotension and downstream effects on the neonate from intraoperative hemodynamic instability. KEY POINTS: · Despite prophylactic vasopressors during scheduled CD, neonatal acidosis occurred in 4% of subjects.. · Sustained hypotension after spinal anesthesia was associated with neonatal acidosis, but not adverse neonatal outcomes.. · Spinal-to-delivery time was not associated with neonatal acidosis in scheduled CD..

Misoprostol with balloon vs oxytocin with balloon in high-risk pregnancy induction: a randomized controlled trial.

BACKGROUND: Pregnancies at high risk for maternal, fetal, or placental complications often necessitate induction of labor in the late preterm or early term period for delivery. Limited data exist on the safest method of induction to use in this specific patient population. OBJECTIVE: This study aimed to compare the combination of oxytocin plus a Cook balloon vs misoprostol plus a Cook balloon for induction of labor in high-risk pregnancies. STUDY DESIGN: We conducted an open-label, randomized controlled trial at a single institution from July 2020 to May 2022. The study was approved by the institutional review board and registered with ClinicalTrials.gov (NCT04492072). Individuals with a high-risk pregnancy, at least ≥22 weeks' gestation, with a singleton in cephalic presentation, Bishop score ≤6, and intact membranes were offered enrollment. A high-risk pregnancy was defined as a pregnancy with any of the following complications: hypertensive disease of pregnancy, fetal growth restriction, oligohydramnios, suspected placental abruption requiring delivery, uncontrolled pregestational diabetes, or abnormal biophysical profile or nonstress test requiring delivery. The primary outcome was the rate of cesarean delivery. Secondary maternal outcomes included induction to delivery interval, number of vaginal deliveries within 24 hours, rates of uterine tachysystole, intraamniotic infection, operative vaginal delivery, and postpartum hemorrhage. Secondary fetal outcomes included fetal heart rate abnormalities, stillbirth, Apgar scores <7 at 5 minutes, admission to the neonatal intensive care unit, arterial umbilical blood pH <7.1, sepsis, and neonatal death. A subgroup analysis was planned for the primary outcome to assess the different indications for cesarean delivery. An intent-to-treat analysis was performed. RESULTS: During the 22 months of the trial, a total of 150 patients were randomized, and 73 (49%) of those were induced with oxytocin and a Cook balloon and 77 (51%) were induced with misoprostol and a Cook balloon. There was no significant difference in the overall rate of cesarean delivery between the study groups, (21.9% vs 31.1%; relative risk, 0.70; 95% confidence interval, 0.41-1.21), nor among those for which the cesarean delivery was performed for a specific indication. There were no differences in the secondary maternal and fetal or neonatal adverse outcomes. CONCLUSION: In high-risk pregnancies, the rate of cesarean delivery and adverse maternal and fetal outcomes were similar for induction of labor with oxytocin and a Cook balloon and for induction with misoprostol and a Cook balloon.

Desirability of outcome ranking for obstetrical trials: illustration and application to the ARRIVE trial.

BACKGROUND: In randomized trials, 1 primary outcome is typically chosen to evaluate the consequences of an intervention, whereas other important outcomes are relegated to secondary outcomes. This issue is amplified for many obstetrical trials in which an intervention may have consequences for both the pregnant person and the child. In contrast, desirability of outcome ranking, a paradigm shift for the design and analysis of clinical trials based on patient-centric evaluation, allows multiple outcomes-including from >1 individual-to be considered concurrently. OBJECTIVE: This study aimed to describe desirability of outcome ranking methodology tailored to obstetrical trials and to apply the methodology to maternal-perinatal paired (dyadic) outcomes in which both individuals may be affected by an intervention but may experience discordant outcomes (eg, an obstetrical intervention may improve perinatal but worsen maternal outcomes). STUDY DESIGN: This secondary analysis applies the desirability of outcome ranking methodology to data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network ARRIVE trial. The original analysis found no substantial difference in the primary (perinatal composite) outcome, but a decreased risk of the secondary outcome of cesarean delivery with elective induction at 39 weeks. In the present desirability-of-outcome-ranking analysis, dyadic outcomes ranging from spontaneous vaginal delivery without severe neonatal complication (most desirable) to cesarean delivery with perinatal death (least desirable) were classified into 8 categories ranked by overall desirability by experienced investigators. Distributions of the desirability of outcome ranking were compared by estimating the probability of having a more desirable dyadic outcome with elective induction at 39 weeks of gestation than with expectant management. To account for various perspectives on these outcomes, a complementary analysis, called the partial credit strategy, was used to grade outcomes on a 100-point scale and estimate the difference in overall treatment scores between groups using a t test. RESULTS: All 6096 participants from the trial were included. The probability of a better dyadic outcome for a randomly selected patient who was randomized to elective induction was 53% (95% confidence interval, 51-54), implying that elective induction led to a better overall outcome for the dyad when taking multiple outcomes into account concurrently. Furthermore, the desirability-of-outcome-ranking probability of averting cesarean delivery with elective induction was 52% (95% confidence interval, 51-53), which was not at the expense of an operative vaginal delivery or a poorer outcome for the perinate (ie, survival with a severe neonatal complication or perinatal death). Randomization to elective induction was also advantageous in most of the partial credit score scenarios. CONCLUSION: Desirability-of-outcome-ranking methodology is a useful tool for obstetrical trials because it provides a concurrent view of the effect of an intervention on multiple dyadic outcomes, potentially allowing for better translation of data for decision-making and person-centered care.

Time to Completion of Two-Step Screening for Gestational Diabetes and Adverse Outcomes.

OBJECTIVE: This study aimed to ascertain whether the length of time to complete the gestational diabetes mellitus (GDM) screening was associated with adverse neonatal outcomes. STUDY DESIGN: This was a retrospective cohort study of singleton, nonanomalous individuals who were screened for GDM at ≥24 weeks' gestation at an academic hospital system. We compared outcomes among people who were diagnosed with GDM and completed the 3-hour glucose tolerance test (GTT) ≤14 second versus >14 days from the 1-hour glucose challenge test (GCT). The primary outcome was a composite adverse neonatal outcome of the following: large for gestational age, shoulder dystocia, birth injury, respiratory distress, hypoglycemia, or fetal/neonatal death. The secondary outcomes included several individual neonatal and maternal morbidities. Multivariable Poisson's regression models were used to evaluate the association. Adjusted relative risk (aRR) and 95% confidence intervals (CI) were calculated. RESULTS: Among the 313 individuals who completed the two-step screening for GDM and had an 1-hour GCT ≥ 135 mg/dL; of them, 171 (54.6%) completed the 3-hour GTT ≤14 days, 142 (45.4%) completed the 3-hour GTT > 14 days. Overall rate of the primary outcome was 44.1%. After multivariable adjustment, the risk of the primary outcome was similar between people who completed the two-step method in ≤14 versus >14 days (aRR = 1.11, 95% CI = 0.81-1.52). There was no significant difference in all secondary adverse outcomes between the two groups. Subgroup analyses, limited to people diagnosed with GDM (N = 89, 23.4%), also found similar results as the full analyses. CONCLUSION: Among individuals who completed the two-step screening for GDM, completion of the 3-hour GTT within ≤14 versus ≥ 14 days was not associated with an increase rate of the adverse outcomes. KEY POINTS: · Among pregnant people in an academic practice, 50% of people with abnormal 1-hour GTT completed GDM two-step screening in 14 days.. · Longer length of time to completion of diagnostic testing for GDM was not associated with an increased rate of adverse outcomes.. · Pregnant people that were diagnosed with GDM and completed the two-step method in >14 days did not have worse perinatal outcomes..

Association of adverse outcomes with three-tiered risk assessment tool for obstetrical hemorrhage.

BACKGROUND: Guidelines promote stratification for the risk for postpartum hemorrhage among parturients, although the evidence for the associated differential morbidity among the groups remains inconsistent among published reports. OBJECTIVE: Using the California Maternal Quality Care Collaborative schema modified by the American College of Obstetrics and Gynecology, we compared the composite maternal hemorrhagic outcome and the composite neonatal adverse outcome among singletons who were categorized after delivery by the researchers as low-, medium-, or high-risk for postpartum hemorrhage. We hypothesized that the composite outcomes would be significantly different among the individuals in the different 3-tiered categories. STUDY DESIGN: This was a retrospective cohort study of all singleton parturients with a gestational age of at least 14 weeks who delivered at a single site within 1 year. The composite maternal hemorrhagic outcome included any of the following: estimated blood loss ≥1000 mL, use of uterotonics (excluding prophylactic oxytocin) or Bakri balloon, surgical management of postpartum hemorrhage, blood transfusion, hysterectomy, thromboembolism, admission to the intensive care unit, or maternal death. The composite neonatal adverse outcome included Apgar score <7 at 5 minutes, birth injury, bronchopulmonary dysplasia, intraventricular hemorrhage, neonatal seizure, sepsis, ventilation > 6 hrs., brachial plexus palsy, hypoxic-ischemic encephalopathy, or neonatal death. Multivariable Poisson regression models with robust error variance were used to estimate the adjusted relative risks with 95% confidence intervals. RESULTS: Of the 4544 deliveries in the study period, 4404 (96.7%) met the inclusion criteria, and among them, 1745 (39.6%) were categorized as low, 1376 (31.2%) as medium, and 1283 (29.1%) as high risk. Overall, 941 (21.4%) participants experienced the composite maternal hemorrhagic outcome with 285 (16.4%) of those being in the low-risk group, 319 (23.2%) in the medium-risk group, and 337 (26.3%) in the high-risk group. Among all parturients, 95.7% in the low-, 89.4% in the medium-, and 85.3% in the high-risk group neither had an estimated blood loss or a quantified blood loss ≥1000 mL nor were transfused. After multivariable adjustment and when compared with the low-risk group, there was a significantly higher risk for the composite maternal hemorrhagic outcome in the medium-risk group (adjusted relative risk, 1.23; 95% confidence interval, 1.05-1.43) and in the high-risk group (adjusted relative risk, 1.51; 95% confidence interval, 1.31-1.75). Overall, 366 newborns (8.4%) developed the composite neonatal adverse outcome with 76 (4.2%) in of those being in the low-risk group, 153 (11.3%) in the medium-risk group, and 140 (11.1%) in the high-risk group. After multivariable adjustment and when compared with the low-risk group, there were no significant differences in the composite neonatal adverse outcome in the medium- (adjusted relative risk, 1.27; 95% confidence interval, 0.97-1.68) or the high-risk group (adjusted relative risk, 1.29; 95% confidence interval, 0.98-1.68). CONCLUSION: Although 8 of 10 parturients categorized as high risk neither had blood loss ≥1000 mL nor underwent transfusion, the risk stratification provides information regarding the composite maternal hemorrhagic outcome.

Unpublished completed obstetric randomized clinical trials registered at ClinicalTrials.gov: how big is this issue?

BACKGROUND: A portion of obstetrical randomized clinical trials registered on ClinicalTrials.gov are not published in peer-reviewed journals. OBJECTIVE: This study aimed to compare the characteristics of completed published vs unpublished randomized clinical trials in obstetrics registered on ClinicalTrials.gov and to identify barriers to publication. STUDY DESIGN: This cross-sectional study queried ClinicalTrials.gov for all completed obstetrical randomized clinical trials registered between January 1, 2009, and December 31, 2018. For each completed obstetrical randomized clinical trial, we abstracted the following registration fields from ClinicalTrials.gov: ClinicalTrials.gov identifier, recruitment status, trial start and completion dates, study results, type of intervention, study phase, enrollment size, funder type, location, and facilities. Calculated variables included time to completion. In May 2021, we used PubMed and Google Scholar to identify the publication status of completed trials, and we compared the characteristics of published vs unpublished randomized clinical trials. The corresponding authors' e-mail addresses for the unpublished studies were collected from ClinicalTrials.gov and departmental websites. Between September 2021 and March 2022, the authors of these completed but unpublished obstetrical randomized clinical trials were contacted and invited to respond to a survey examining perceptions of barriers to publication, responses of which were collected and presented as counts and percentages. RESULTS: Of the 647 obstetrical randomized clinical trials marked as completed on ClinicalTrials.gov, 378 (58%) were published, and 269 (42%) were unpublished. Unpublished trials were more likely to have an enrollment size of <50 participants (14.5% published vs 25.3% unpublished; P<.001) and less likely to be conducted at multiple sites (25.4% published vs 17.5% unpublished; P<.02). The main barriers to publication reported in the survey by authors whose trials were not published included lack of time (30%), change in employment or completion of training (25%), and results that were not of statistical significance (15%). CONCLUSION: Among the obstetrical randomized clinical trials registered and marked as completed on ClinicalTrials.gov, more than 40% were unpublished. Unpublished trials were more likely to be smaller studies, conducted by researchers who reported experiencing a lack of time as the most common barrier to study publication.

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.