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.).

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.

Permissive Intrapartum Glucose Control: An Equivalence Randomized Control Trial (PERMIT).

BACKGROUND: There is limited high quality data to determine best practices for maternal blood glucose management during labor. OBJECTIVE: We compared permissive care (target maternal blood glucose 70-180 mg/dL) to usual care (blood glucose 70-110 mg/dL) among laboring individuals with diabetes. STUDY DESIGN: This was a two-site equivalence randomized control trial for individuals with diabetes (pregestational or gestational) at ≥ 34 weeks in labor. Individuals were randomly allocated to usual care or permissive care. Maternal blood glucose was evaluated by capillary blood glucose monitoring in latent and active labor every 4 and 2 hours. Insulin drip was initiated if maternal blood glucose exceeded the upper bounds of the allocated target. The primary outcome was first neonatal heel stick glucose within two hours of birth before feeding. We assumed a mean first neonatal blood glucose of 50 ±10 mg/dL. To ensure that the use of permissive care did not increase or decrease the first neonatal blood glucose >10 mg/dL (two-tailed, α= 0.05, ß= 0.1), 96 total participants were required. We calculated adjusted relative risk (aRR) and 95% confidence intervals (CI) in an intention-to-treat analysis. A Bayesian analysis was preplanned to estimate the probability of equivalence with a neutral informative prior. RESULTS: Of 511 deliveries with diabetes assessed for eligibility (10/2022 - 6/2023), 280 (54.8%) met eligibility criteria, and 96 (34.3%) agreed and were randomized. In the usual care group, 17% required an insulin drip compared to none in permissive care. There was equivalence in the primary outcome between usual and permissive care (57.9 vs. 57.1 mg/dL, adjusted mean difference -0.72, 95% CI -8.87,7.43). Bayesian analysis indicated 98% posterior probability of mean difference not being greater than ±10 mg/dL. The rate of neonatal hypoglycemia was 25% in the usual care group and 29% in permissive group (adjusted relative risk 1.14, 95% CI 0.60, 2.17). There was no difference in other neonatal or maternal outcomes. CONCLUSION: In this randomized control trial, while almost 1 in 6 individuals with diabetes required an insulin drip with usual intrapartum maternal blood glucose care, permissive care was associated with equivalent neonatal blood glucose.

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.

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..

Large for Gestational Age and Adverse Outcomes: Stratified By Diabetes Status.

OBJECTIVE: To examine the association of adverse outcomes among parturients with large for gestational age (LGA; birth weight ≥ 90th) newborns, stratified by diabetes status. Additionally, we described the temporal trends of adverse outcomes among LGA neonates. STUDY DESIGN: This retrospective cohort study used the U.S. Vital Statistics dataset between 2014 and 2020. The inclusion criteria were singleton, nonanomalous LGA live births who labored and delivered at 24 to 41 weeks with known diabetes status. The coprimary outcomes were composite neonatal adverse outcomes of the following: Apgar score < 5 at 5 minutes, assisted ventilation > 6 hours, seizure, or neonatal or infant mortality, and maternal adverse outcomes of the following: maternal transfusion, ruptured uterus, unplanned hysterectomy, admission to intensive care unit, or unplanned procedure. Multivariable Poisson regression models were used to estimate adjusted relative risks (aRR) and 95% confidence intervals (CI). Average annual percent change (AAPC) was calculated to assess changes in rates of LGA and morbidity over time. RESULTS: Of 27 million births in 7 years, 1,843,467 (6.8%) met the inclusion criteria. While 1,656,888 (89.9%) did not have diabetes, 186,579 (10.1%) were with diabetes. Composite neonatal adverse outcomes (aRR = 1.48, 95% CI = 1.43, 1.52) and composite maternal adverse outcomes (aRR = 1.37, 95% CI = 1.36, 1.38) were significantly higher among individuals with diabetes, compared with those without diabetes. From 2014 to 2020, the LGA rate was stable among people without diabetes. However, there was a downward trend of LGA in people with diabetes (AAPC = - 2.4, 95% CI = - 3.5, -1.4). CONCLUSION: In pregnancies with LGA newborns, composite neonatal and maternal morbidities were higher in those with diabetes, compared with those without diabetes. KEY POINTS: · Large for gestational age stratified by diabetes status.. · Composite neonatal and maternal adverse outcomes are worse among individuals with diabetes as compared to those without.. · During 2014 to 2020, the trend of LGA in individuals without diabetes increased..

Trends and Outcomes among Pregnancy and Nonpregnancy-Related Hospitalizations with Diabetic Ketoacidosis.

OBJECTIVE: The study's primary objective was to evaluate adverse outcomes among reproductive-age hospitalizations with diabetic ketoacidosis (DKA), comparing those that are pregnancy-related versus nonpregnancy-related and evaluating temporal trends. STUDY DESIGN: We conducted a retrospective cross-sectional study using the National Inpatient Sample to identify hospitalizations with DKA among reproductive-age women (15-49 years) in the United States (2016-2020). DKA in pregnancy hospitalizations was compared with DKA in nonpregnant hospitalizations. Adverse outcomes evaluated included mechanical ventilation, coma, seizures, renal failure, prolonged hospital stay, and in-hospital death. Multivariable Poisson regression models with robust error variance were used to estimate adjusted relative risk (aRR) and 95% confidence interval (CI). Annual percent change (APC) was used to calculate the change in DKA rate over time. RESULTS: Among 35,210,711 hospitalizations of reproductive-age women, 447,600 (1.2%) were hospitalized with DKA, and among them, 13,390 (3%) hospitalizations were pregnancy-related. The rate of nonpregnancy-related DKA hospitalizations increased over time (APC = 3.8%, 95% CI = 1.5-6.1). After multivariable adjustment, compared with pregnancy-related hospitalizations with DKA, the rates of mechanical ventilation (aRR = 1.56, 95% CI = 1.18-2.06), seizures (aRR = 2.26, 95% CI = 1.72-2.97), renal failure (aRR = 2.26, 95% CI = 2.05-2.50), coma (aRR = 2.53, 95% CI = 1.68-3.83), and in-hospital death (aRR = 2.38, 95% CI = 1.06-5.36) were higher among nonpregnancy-related hospitalizations with DKA. CONCLUSION: A nationally representative sample of hospitalizations indicates that over the 5-year period, the rate of nonpregnancy-related DKA hospitalizations increased among reproductive age women, and a higher risk of adverse outcomes was observed when compared with pregnancy-related DKA hospitalizations. KEY POINTS: · Over 5 years, the rate of pregnancy-related DKA hospitalizations was stable.. · Over 5 years, the rate of nonpregnancy-related DKA hospitalizations increased.. · There is a higher risk of adverse outcomes with DKA outside of 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..

Oral combined hydrochlorothiazide and lisinopril vs nifedipine for postpartum hypertension: a comparative-effectiveness pilot randomized controlled trial.

BACKGROUND: Angiotensin-converting enzyme inhibitors and diuretics may be underutilized for postpartum hypertension because of their teratogenicity during pregnancy. OBJECTIVE: We evaluated whether combined oral hydrochlorothiazide and lisinopril therapy produced superior short-term blood pressure control when compared with nifedipine among postpartum individuals with hypertension requiring pharmacologic treatment. STUDY DESIGN: We performed a pilot randomized controlled trial (October 2021 to June 2022) that included individuals with chronic hypertension or hypertensive disorders of pregnancy with 2 systolic blood pressure measurements ≥150 mm Hg and/or diastolic blood pressure measurements ≥100 mm Hg within 72 hours after delivery. Participants were randomized to receive either combined hydrochlorothiazide and lisinopril therapy or nifedipine therapy after stratifying the participants by diagnosis (chronic hypertension vs hypertensive disorders of pregnancy). The primary outcome was stage 2 hypertension (systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg) determined using a home blood pressure monitor on days 7 to 10 after delivery or at readmission to the hospital for blood pressure control. The secondary outcomes included severe maternal morbidity (any of the following: intensive care unit admission; hemolysis, elevated liver enzymes, low platelet count syndrome; eclampsia; stroke; cardiomyopathy; or maternal death), need for intravenous medications after randomization, hospital length of stay, blood pressure during first clinic visit, medication compliance, and adverse events. A pilot trial with 70 individuals was planned given the limited available data on combined hydrochlorothiazide and lisinopril therapy use in postpartum care. We calculated relative risks and 95% credible intervals in an intention-to-treat analysis. Finally, we conducted a preplanned Bayesian analysis to estimate the probability of benefit or harm with a neutral informative prior. RESULTS: Of 111 eligible individuals, 70 (63%) agreed and were randomized (31 in the hydrochlorothiazide and lisinopril group and 36 in the nifedipine group; 3 withdrew consent after randomization), and the characteristics were similar at baseline between the groups. The primary outcome was unavailable for 9 (12.8%) participants. The primary outcome occurred in 27% of participants in the hydrochlorothiazide and lisinopril group and in 43% of the participants in the nifedipine group (posterior adjusted relative risk, 0.74; 95% credible interval, 0.40-1.31). Bayesian analysis indicated an 85% posterior probability of a reduction in the primary outcome with combined hydrochlorothiazide and lisinopril therapy relative to nifedipine treatment. No differences were noted in the secondary outcomes or adverse medication events. CONCLUSION: The results of the pilot trial suggest a high probability that combined hydrochlorothiazide and lisinopril therapy produces superior short-term BP control when compared with nifedipine. These findings should be confirmed in a larger trial.

Continuous glucose monitoring in individuals undergoing gestational diabetes screening.

BACKGROUND: Among guidelines on gestational diabetes mellitus, there is an incongruity about the threshold of maternal hyperglycemia to diagnose gestational diabetes mellitus. OBJECTIVE: This study aimed to ascertain the association between continuous glucose monitoring metrics and adverse outcomes among individuals undergoing gestational diabetes mellitus screening. STUDY DESIGN: This was a prospective study (from June 2020 to January 2022) of individuals who underwent 2-step gestational diabetes mellitus screening at ≤30 weeks of gestation. The participants wore a blinded continuous glucose monitoring device (Dexcom G6 Pro; Dexcom, Inc, San Diego, CA) for 10 days starting when they took the 50-g glucose challenge test. The primary outcome was a composite of adverse neonatal outcomes (large for gestational age, shoulder dystocia or neonatal injury, respiratory distress, need for intravenous glucose treatment for hypoglycemia, or fetal or neonatal death). The secondary neonatal outcomes included preterm birth, neonatal intensive care unit admission, hypoglycemia, mechanical ventilation or continuous positive airway pressure, hyperbilirubinemia, and hospital length of stay. The secondary maternal outcomes included weight gain during pregnancy, hypertensive disorders of pregnancy, induction of labor, cesarean delivery, and postpartum complications. Time within the target range (63-140 mg/dL), time above the target range (>140 mg/dL) expressed as a percentage of all continuous glucose monitoring readings, and mean glucose level were analyzed. The Youden index was used to choose the threshold of ≥10% for the time above the target range and association with adverse outcomes. RESULTS: Of 136 participants recruited, data were available from 92 individuals (67.6%). The 2-step method diagnosed gestational diabetes mellitus in 2 individuals (2.2%). Continuous glucose monitoring indicated that 17 individuals (18.5%) had time above the target range of ≥10%. Individuals with time above the target range of ≥10% had a significantly higher likelihood of composite adverse neonatal outcomes than individuals with time above the target range of <10% (63% vs 18%; P=.001). Furthermore, compared with neonates born to individuals with time above the target range of <10%, neonates born to individuals with time above the target range of ≥10% had an increased likelihood for hypoglycemia (14.5% vs 47%; P=.009) and had a longer length of stay (2 vs 4 days; P=.03). No difference in maternal outcomes was noted between the groups. CONCLUSION: In this prospective study of individuals undergoing gestational diabetes mellitus screening, a cutoff of the time above the target range of ≥10% using continuous glucose monitoring was associated with a higher rate of neonatal adverse outcomes. A randomized trial of continuous glucose monitoring vs 2-step screening for gestational diabetes mellitus to lower the rate of adverse outcomes is underway (identification number: NCT05430204).

Three-tiered fetal heart rate interpretation system and adverse neonatal and maternal outcomes: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the rate of adverse neonatal or maternal outcomes in parturients with fetal heart rate tracings categorized as I, II or, III within the last 30 to 120 minutes of delivery. DATA SOURCES: The MEDLINE Ovid, Scopus, Embase, CINAHL, and Clinicaltrials.gov databases were searched electronically up to May 2022, using combinations of the relevant medical subject heading terms, keywords, and word variants that were considered suitable for the topic. STUDY ELIGIBILITY CRITERIA: Only observational studies of term infants reporting outcomes of interest with category I, II, or III fetal heart rate tracings were included. STUDY APPRAISAL AND SYNTHESIS METHODS: The coprimary outcome was the rate of either Apgar score <7 at 5 minutes or umbilical artery pH <7.00. Secondary outcomes were divided into neonatal and maternal adverse outcomes. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale. Random-effect meta-analyses of proportions were used to estimate the pooled rates of each categorical outcome in fetal heart rate tracing category I, II, and III patterns, and random-effect head-to-head meta-analyses were used to directly compare fetal heart rate tracings category I vs II and fetal heart rate tracing category II vs III, expressing the results as summary odds ratio or as mean differences with relative 95% confidence intervals. RESULTS: Of the 671 articles reviewed, 3 publications met the inclusion criteria. Among them were 47,648 singletons at ≥37 weeks' gestation. Fetal heart rate tracings in the last 30 to 120 minutes before delivery were characterized in the following manner: 27.0% of deliveries had category I tracings, 72.9% had category II tracings, and 0.1% had category III tracings. A single study, which was rated to be of poor quality, contributed 82.1% of the data and it did not provide any data for category III fetal heart rate tracings. When compared with category I fetal heart rate tracings (0.74%), the incidence of an Apgar score <7 at 5 minutes were significantly higher among deliveries with category II fetal heart rate tracings (1.51%) (odds ratio, 1.56; 95% confidence interval, 1.23-1.99) and among those with category III tracings (14.63%) (odds ratio, 14.46; 95% confidence interval, 2.77-75.39). When compared with category II tracings, category III tracings also had a significantly higher likelihood of a low Apgar score at 5 minutes (odds ratio, 14.46; 95% confidence interval, 2.77-75.39). The incidence of an umbilical artery pH <7.00 were similar among those with category I and those with category II tracings (0.08% vs 0.24%; odds ratio, 2.85; 95% confidence interval, 0.41-19.55). When compared with category I tracings, the incidence of an umbilical artery pH <7.00 was significantly more common among those with category III tracings (31.04%; odds ratio, 161.56; 95% confidence interval, 25.18-1036.42); likewise, when compared with those with category II tracings, those with category III tracings had a significantly higher likelihood of having an umbilical artery pH <7.00 (odds ratio, 42.29; 95% confidence interval, 14.29-125.10). Hypoxic-ischemic encephalopathy occurred with similar frequency among those with categories I and those with category II tracings (0 vs 0.81%; odds ratio, 5.86; 95% confidence interval, 0.75-45.89) but was significantly more common among those with category III tracings (0 vs 18.97%; odds ratio, 61.43; 95% confidence interval, 7.49-503.50). Cesarean delivery occurred with similar frequency among those with category I (13.41%) and those with category II tracings (11.92%) (odds ratio, 0.87; 95% confidence interval, 0.72-1.05) but was significantly more common among those with with category III tracings (14.28%) (odds ratio, 3.97; 95% confidence interval, 1.62-9.75). When compared with those with category II tracings, cesarean delivery was more common among those with category III tracings (odds ratio, 4.55; 95% confidence interval, 1.88-11.01). CONCLUSION: Although the incidence of an Apgar score <7 at 5 minutes and umbilical artery pH <7.00 increased significantly with increasing fetal heart rate tracing category, about 98% of newborns with category II tracings do not have these adverse outcomes. The 3-tiered fetal heart rate tracing interpretation system provides an approximate but imprecise measurement of neonatal prognosis.

Susceptible windows of exposure to fine particulate matter and fetal growth trajectories in the Spanish INMA (INfancia y Medio Ambiente) birth cohort.

While prior studies report associations between fine particulate matter (PM2.5) exposure and fetal growth, few have explored temporally refined susceptible windows of exposure. We included 2328 women from the Spanish INMA Project from 2003 to 2008. Longitudinal growth curves were constructed for each fetus using ultrasounds from 12, 20, and 34 gestational weeks. Z-scores representing growth trajectories of biparietal diameter, femur length, abdominal circumference (AC), and estimated fetal weight (EFW) during early (0-12 weeks), mid- (12-20 weeks), and late (20-34 weeks) pregnancy were calculated. A spatio-temporal random forest model with back-extrapolation provided weekly PM2.5 exposure estimates for each woman during her pregnancy. Distributed lag non-linear models were implemented within the Bayesian hierarchical framework to identify susceptible windows of exposure for each outcome and cumulative effects [ßcum, 95% credible interval (CrI)] were aggregated across adjacent weeks. For comparison, general linear models evaluated associations between PM2.5 averaged across multi-week periods (i.e., weeks 1-11, 12-19, and 20-33) and fetal growth, mutually adjusted for exposure during each period. Results are presented as %change in z-scores per 5 µg/m3 in PM2.5, adjusted for covariates. Weeks 1-6 [ßcum = -0.77%, 95%CrI (-1.07%, -0.47%)] were identified as a susceptible window of exposure for reduced late pregnancy EFW while weeks 29-33 were positively associated with this outcome [ßcum = 0.42%, 95%CrI (0.20%, 0.64%)]. A similar pattern was observed for AC in late pregnancy. In linear regression models, PM2.5 exposure averaged across weeks 1-11 was associated with reduced late pregnancy EFW and AC; but, positive associations between PM2.5 and EFW or AC trajectories in late pregnancy were not observed. PM2.5 exposures during specific weeks may affect fetal growth differentially across pregnancy and such associations may be missed by averaging exposure across multi-week periods, highlighting the importance of temporally refined exposure estimates when studying the associations of air pollution with fetal growth.

Factors associated with exclusive formula feeding among individuals with low-risk pregnancies in the United States.

BACKGROUND: Better understanding of the factors associated with formula feeding during the hospital stay can help in identifying potential lactation problems and promote early intervention. Our aim was to ascertain factors associated with exclusive formula feeding in newborns of low-risk pregnancies. METHODS: A population-based, retrospective study using the United States vital statistics datasets (2014-2018) evaluating low-risk pregnancies with a nonanomalous singleton delivery from 37 to 41 weeks. People with hypertensive disorders, or diabetes, were excluded. Primary outcome was newborn feeding (breast vs exclusive formula feeding) during hospital stay. Adjusted relative risks (aRRs) with 95% confidence intervals (CI) were calculated. RESULTS: Of the 19 623 195 live births during the study period, 11 605 242 (59.1%) met inclusion criteria and among them, 1 929 526 (16.6%) were formula fed. Factors associated with formula feeding included: age < 20 years (aRR 1.31 [95% CI 1.31-1.32]), non-Hispanic Black (1.42, 1.41-1.42), high school education (1.69, 1.69-1.70) or less than high school education (1.94, 1.93, 1.95), Medicaid insurance (1.52, 1.51, 1.52), body mass index (BMI) < 18.5 (1.10, 1.09-1.10), BMI 25-29.9 (1.09, 1.09-1.09), BMI 30-34.9 (1.19, 1.19-1.20), BMI 35-39.9 (1.31, 1.30-1.31), BMI ≥ 40 (1.43, 1.42-1.44), multiparity (1.29, 1.29-1.30), lack of prenatal care (1.49, 1.48-1.50), smoking (1.75, 1.74-1.75), and gestational age (ranged from 37 weeks [1.44, 1.43-1.45] to 40 weeks [1.11, 1.11-1.12]). CONCLUSIONS: Using a large cohort of low-risk pregnancies, we identified several modifiable factors associated with newborn feeding (eg, prepregnancy BMI, access to prenatal care, and smoking cessation). Improving the breast feeding initiation rate should be a priority in our current practice to ensure equitable care for all neonates.

Maternal Sepsis: A Review of National and International Guidelines.

Sepsis is a life-threatening syndrome caused by the body's response to infection. The Global Maternal Sepsis Study (GLOSS) suggests sepsis plays a larger role in maternal morbidity and mortality than previously thought. We therefore sought to compare national and international guidelines for maternal sepsis to determine their consistency with each other and the Third International Consensus for Sepsis and Septic Shock (SEPSIS-3). Using Cochrane Database of Systematic Reviews, PubMed, Google Scholar, and organization Web sites, we identified seven guidelines on maternal sepsis in the English language-The American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine, Royal Australian and New Zealand College of Obstetricians and Gynaecologists, Society of Obstetric Medicine of Australia and New Zealand, Royal College of Obstetricians and Gynaecologists, Royal College of Physicians of Ireland Institute of Obstetricians and Gynaecologists, and World Health Organization. Guidelines were reviewed to ascertain the commonality and variation, if any, in definitions of maternal sepsis, tools and criteria utilized for diagnosis, obstetric warning systems used, as well as evaluation and management of maternal sepsis. These variables were also compared with SEPSIS-3. All guidelines provided definitions consistent with a version of the SEPSIS, although the specific version utilized were varied. Clinical variables and tools employed for diagnosis of maternal sepsis were also varied. Evaluation and management of maternal sepsis and septic shock were similar. In conclusion, national and international maternal sepsis guidelines were incongruent with each other and SEPSIS-3 in diagnostic criteria and tools but similar in evaluation and management recommendations. KEY POINTS: · Definitions for maternal sepsis and septic shock are varied.. · Maternal sepsis guidelines differ in proposed criteria and tools.. · Maternal sepsis guidelines have similar management recommendations..

Development of the Sepsis-Associated Adverse Outcomes in Pregnancy Score.

OBJECTIVE: This study aimed to develop and evaluate a scoring system-called the Sepsis-Associated Adverse Outcomes in Pregnancy (SAAP) Score-to identify individuals with maternal infection that have composite maternal adverse outcomes (CMAO). STUDY DESIGN: Using the International Classification of Disease codes, we identified pregnant and postpartum (up to 6 weeks after birth) individuals admitted at our center with a primary diagnosis of infection. The primary outcome was CMAO which included any of the following: maternal intensive care unit admission, surgical intervention, vasopressor use, acute respiratory distress syndrome, pulmonary edema, mechanical ventilation, high-flow nasal cannula, disseminated intravascular coagulation, dialysis, organ failure, venous thromboembolism, or maternal death. Regularized logistic regression was used to identify variables that best discriminate CMAO status. Variables were chosen for inclusion following evaluation of statistical and clinical significance. Model performance was evaluated using area under the curve (AUC) with 95% confidence intervals (CIs), sensitivity, specificity, and predictive values. RESULTS: Of the 23,235 deliveries during the study period, 227 (0.9%) individuals met inclusion criteria and among them CMAO occurred in 39.2% (95% CI: 33.1-45.7%). The SAAP score consisted of six variables (white blood cell count, systolic blood pressure, respiratory rate, heart rate, lactic acid, and abnormal diagnostic imaging) with scores ranging from 0 to 11 and a score of ≥7 being abnormal. An abnormal SAAP score had an AUC of 0.80 (95% CI: 0.74-0.86) for CMAO. The sensitivity and specificity of the SAAP score for CMAO was 0.71 (95% CI: 0.60-0.80) and 0.73 (95% CI: 0.64-0.80), respectively. The positive predictive value was 0.62 (95% CI: 0.52-0.72) and negative predictive value was 0.79 (95% CI: 0.71-0.86). CONCLUSION: Pending external validation, the sixth variable SAAP score may permit early recognition of pregnant and postpartum individuals with infection who are likely to develop adverse maternal outcomes. KEY POINTS: · Sepsis is a leading cause of maternal morbidity and mortality.. · Early recognition improves maternal sepsis outcomes.. · The SAAP score may permit early recognition of maternal adverse outcomes due to infection..

The Role of Cerclage in Subsequent Pregnancy following Previable Prelabor Rupture of Membranes.

OBJECTIVE: This study aimed to ascertain the outcomes associated with a cervical cerclage among individuals with a history of previable prelabor rupture of membranes (PROM). STUDY DESIGN: This study was a retrospective cohort study conducted at a single tertiary center between 2011 and 2021. We included individuals with a history of previable (before 24 weeks) PROM and the subsequent viable pregnancy. Women with multifetal gestation, preterm birth (PTB) or cerclage in previous gestation, or abdominal cerclage after trachelectomy were excluded. Primary outcome was PTB rate (delivery <37 weeks). Recurrence of preterm PROM and adverse composite maternal and neonatal outcomes (CMO and CNO) were evaluated as secondary outcomes. CMO included any of the following: suspected chorioamnionitis, endometritis, red blood cell transfusion, uterine rupture, unplanned hysterectomy, or death. CNO included any of the following: previable PTB (<24 weeks of gestation), bronchopulmonary dysplasia, grade 3 or 4 intraventricular hemorrhage, necrotizing enterocolitis, mechanical ventilation, seizures, hypoxic ischemic encephalopathy, or death. RESULTS: During the study period, 118 individuals had a history of previable PROM and a documented subsequent pregnancy, out of which 74 (62.7%) met inclusion criteria. Nineteen (25.7%) of eligible individuals underwent a cerclage for prior previable PROM and were compared with controls (n = 55, 74.3%). Women who underwent a cerclage had higher rates of PTB < 37 weeks (63.2 vs. 10.9%, p < 0.001; odds ratio [OR]: 14.00, 95% confidence interval [CI]: 3.97-49.35) and < 34 weeks (21.1 vs. 3.6%, p = 0.03; OR: 7.07, 95% CI: 1.18-42.39) compared with those without cerclage. Furthermore, recurrent preterm PROM and previable PTB rates were higher among patients who underwent cerclage. The survival curve further indicated that individuals with cerclage delivered earlier. CMO and CNO rates were similar in those with and without cerclage. CONCLUSION: Cerclage placement in individuals with prior previable PROM was associated with higher rates of recurrent preterm PROM and PTB. KEY POINTS: · The management of individuals in a subsequent pregnancy following previable PROM is a conundrum.. · Cerclage following previable PROM is associated with higher rates of recurrent preterm PROM and PTB.. · Composite maternal and neonatal outcome rates were similar in those with and without cerclage..

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..

Racial and Ethnic Disparities among Pregnancies with Chronic Hypertension and Adverse Outcomes.

OBJECTIVE: We aimed to ascertain whether the risk of adverse pregnancy outcomes in the United States among individuals with chronic hypertension differed by maternal race and ethnicity and to assess the temporal trend. STUDY DESIGN: Population-based retrospective study using the U.S. Vital Statistics datasets evaluated pregnancies with chronic hypertension, singleton live births that delivered at 24 to 41 weeks. The coprimary outcomes were a composite maternal adverse outcome (preeclampsia, primary cesarean delivery, intensive care unit admission, blood transfusion, uterine rupture, or unplanned hysterectomy) and a composite neonatal adverse outcome (preterm birth, small for gestational age, Apgar's score <5 at 5 minutes, assisted ventilation> 6 hours, seizure, or death). Multivariable Poisson regression models were used to estimate adjusted relative risks (aRRs) and 95% confidence intervals (CIs). RESULTS: Between 2014 and 2019, the rate of chronic hypertension in pregnancy increased from 1.6 to 2.2%. After multivariable adjustment, an increased risk for the composite maternal adverse outcome was found in Black (aRR = 1.10, 95% CI = 1.09-1.11), Hispanic (aRR = 1.04, 95% CI = 1.02-1.05), and Asian/Pacific Islander (aRR = 1.07, 95% CI = 1.05-1.10), compared with White individuals. Compared with White individuals, the risk of the composite neonatal adverse outcome was higher in Black (aRR = 1.39, 95% CI = 1.37-1.41), Hispanic (aRR = 1.15, 95% CI = 1.13-1.16), Asian/Pacific Islander (aRR = 1.34, 95% CI = 1.31-1.37), and American Indian (aRR = 1.12, 95% CI = 1.07-1.17). The racial and ethnic disparity remained unchanged during the study period. CONCLUSION: We found a racial and ethnic disparity with maternal and neonatal adverse outcomes in pregnancies with chronic hypertension that remained unchanged throughout the study period. KEY POINTS: · Between 2014 and 2019, the rate of chronic hypertension in pregnancy increased.. · Among people with chronic hypertension, there are racial and ethnic disparities in adverse outcomes.. · Black, Hispanic, and Asian/Pacific Islander have a higher risk of the adverse neonatal outcomes..

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..