Neonatal outcomes in term and preterm infants following adjunctive azithromycin antibiotic prophylaxis for non-elective cesarean delivery.

OBJECTIVE: It is currently unknown whether adjunctive azithromycin prophylaxis at the time of non-elective cesarean has differential effects on neonatal outcomes in the context of prematurity. The objective of this study was to compare whether neonatal outcomes differ in term and preterm infants exposed to adjunctive azithromycin prophylaxis before non-elective cesarean delivery. STUDY DESIGN: A planned secondary analysis of a multi-center randomized controlled trial that enrolled women with singleton pregnancies ≥24 weeks gestation undergoing non-elective cesarean delivery (during labor or ≥4 h after membrane rupture). Women received standard antibiotic prophylaxis and were randomized to either adjunctive azithromycin (500 mg) or placebo. The primary composite outcome was neonatal death, suspected or confirmed neonatal sepsis, and serious neonatal morbidities (NEC, PVL, IVH, BPD). Secondary outcomes included NICU admission, neonatal readmission, culture positive infections and prevalence of resistant organisms. Odds ratios (OR) for the effect of azithromycin versus placebo were compared between gestational age strata (preterm [less than 37 weeks] versus term [37 weeks or greater]). Tests of interaction examined homogeneity of treatment effect with gestational age. RESULTS: The analysis includes 2,013 infants, 226 preterm (11.2%) and 1,787 term. Mean gestational ages were 34 and 39.5 weeks, respectively. Within term and preterm strata, maternal and delivery characteristics were similar between the azithromycin and placebo groups. There was no difference in the odds of composite neonatal outcome between those exposed to azithromycin versus placebo in preterm neonates (OR 0.82, 95% CI 0.48-1.41) and in term neonates (OR 1.06, 95% CI 0.77-1.46), with no difference between gestational age strata (p = 0.42). Analysis of secondary outcomes also revealed no differences in treatment effects within or between gestational age strata. CONCLUSION: Exposure to adjunctive azithromycin antibiotic prophylaxis for non-elective cesarean delivery does not increase neonatal morbidity or mortality in term or preterm infants. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov, NCT01235546.

Well-Child Visits for Early Detection and Management of Maternal Postpartum Hypertensive Disorders.

Importance: Innovative approaches are needed to address the increasing rate of postpartum morbidity and mortality associated with hypertensive disorders. Objective: To determine whether assessing maternal blood pressure (BP) and associated symptoms at time of well-child visits is associated with increased detection of postpartum preeclampsia and need for hospitalization for medical management. Design, Setting, and Participants: This is a pre-post quality improvement (QI) study. Individuals who attended the well-child visits between preimplementation (December 2017 to December 2018) were compared with individuals who enrolled after the implementation of the QI program (March 2019 to December 2019). Individuals were enrolled at an academic pediatric clinic. Eligible participants included birth mothers who delivered at the hospital and brought their newborn for well-child check at 2 days, 2 weeks, and 2 months. A total of 620 individuals were screened in the preintervention cohort and 680 individuals were screened in the QI program. Data was analyzed from March to July 2022. Exposures: BP evaluation and preeclampsia symptoms screening were performed at the time of the well-child visit. A management algorithm-with criteria for routine or early postpartum visits, or prompt referral to the obstetric emergency department-was followed. Main Outcome and Measures: Readmission due to postpartum preeclampsia. Comparisons across groups were performed using a Fisher exact test for categorical variables, and t tests or Mann-Whitney tests for continuous variables. Results: A total of 595 individuals (mean [SD] age, 27.2 [6.1] years) were eligible for analysis in the preintervention cohort and 565 individuals (mean [SD] age, 27.0 [5.8] years) were eligible in the postintervention cohort. Baseline demographic information including age, race and ethnicity, body mass index, nulliparity, and factors associated with increased risk for preeclampsia were not significantly different in the preintervention cohort and postintervention QI program. The rate of readmission for postpartum preeclampsia differed significantly in the preintervention cohort (13 individuals [2.1%]) and the postintervention cohort (29 individuals [5.6%]) (P = .007). In the postintervention QI cohort, there was a significantly earlier time frame of readmission (median [IQR] 10.0 [10.0-11.0] days post partum for preintervention vs 7.0 [6.0-10.5] days post partum for postintervention; P = .001). In both time periods, a total of 42 patients were readmitted due to postpartum preeclampsia, of which 21 (50%) had de novo postpartum preeclampsia. Conclusions and Relevance: This QI program allowed for increased and earlier readmission due to postpartum preeclampsia. Further studies confirming generalizability and mitigating associated adverse outcomes are needed.

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

BACKGROUND: In low-risk pregnancies, a third-trimester ultrasound examination is indicated if fundal height measurement and gestational age discrepancy are observed. Despite potential improvement in the detection of ultrasound abnormality, prior trials to date on universal third-trimester ultrasound examination in low-risk pregnancies, compared with 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 outcomes. The secondary objectives were to compare changes in composite maternal adverse outcomes and detection of abnormalities of fetal growth (fetal growth restriction or large for gestational age) or amniotic fluid (oligohydramnios or polyhydramnios). STUDY DESIGN: Our pre-post intervention study at 9 locations included low-risk pregnancies, those without indication for ultrasound examination in the third trimester. Compared with indicated ultrasound in the preimplementation period, in the postimplementation period, all patients were scheduled for ultrasound examination at 36.0-37.6 weeks. In both periods, clinicians intervened on the basis of abnormalities identified. Composite neonatal adverse outcomes included any of: Apgar score ≤5 at 5 minutes, 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 the following: chorioamnionitis, wound infection, estimated blood loss >1000 mL, 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 preintervention phase, 747 individuals were identified during the initial ultrasound examination, and among them, 568 (76.0%) met the inclusion criteria at 36.0-37.6 weeks; during the postintervention period, the corresponding numbers were 770 and 661 (85.8%). The rate of identified abnormalities of fetal growth or amniotic fluid increased from between the pre-post intervention period (7.1% vs 22.2%; P<.0001; number needed to diagnose, 7; 95% confidence interval, 5-9). The primary outcome occurred in 15 of 568 (2.6%) individuals in the preintervention and 12 of 661 (1.8%) in the postintervention 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 preintervention and 6.5% in the postintervention 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). In addition, the number to reduce composite maternal adverse outcomes was 46 (95% confidence interval, 19-74), whereas the number to prevent cesarean delivery was 18 (95% confidence interval, 9-31). CONCLUSION: Among low-risk pregnancies, compared with 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.

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

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

Mesenchymal Stem Cells Suppress Inflammatory Cytokines in Lipopolysaccharide Exposed Preterm and Term Human Pregnant Myometrial Cells.

Objective The objective of this study was to determine the cytokine response in human pregnant preterm and term myometrial cells exposed to lipopolysaccharide (LPS) and cocultured with mesenchymal stem cells (MSCs). Study Design Myometrium was obtained at cesarean delivery in term and preterm patients. Human myometrial cells were exposed to 5 µg/mL LPS for 4 hours followed by 1 µg/mL LPS for 24 hours and were cocultured with MSCs for 24 hours. Culture supernatants were collected at 24 hours and expression of cytokines, including interleukin-1ß (IL-1ß), IL-6, IL-8, tumor necrosis factor-α (TNF-α), transforming growth factor-ß (TGF-ß), and IL-10, was quantified by enzyme-linked immunosorbent assay. Results There was significantly increased expression of the proinflammatory cytokines IL-1ß, IL-6, IL-8, and TNF-α in preterm myometrial cells treated with LPS compared with untreated preterm myometrial cells. Coculture with MSCs significantly suppressed the proinflammatory cytokine levels in LPS-treated preterm versus treated term myometrial cells. Moreover, MSC cocultured preterm myometrial cells expressed increased levels of the anti-inflammatory cytokines TGF-ß and IL-10 compared with treated term myometrial cells. Conclusion MSCs ameliorate LPS-mediated inflammation in preterm human myometrial cells compared with term myometrial cells. Immunomodulatory effects of MSCs mediated through anti-inflammatory cytokine regulation suggest a potential cell-based therapy for preterm birth.

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.

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 obstetrical factors associated with short cervical length at midtrimester in women with no history of preterm delivery.

AIM: To evaluate associations between maternal characteristics and a short cervix in patients without history of preterm delivery, and to determine if these characteristics can predict the presence of a short cervix. MATERIALS AND METHODS: This is a retrospective cohort study that included 18,592 women with singleton pregnancies without history of previous preterm deliveries who underwent universal transvaginal cervical length (TVCL) screening between 18 + 0 and 23 + 6 weeks/days of gestation. A short cervix was defined as a cervical length (CL) ≤25 mm, ≤20 mm, and ≤15 mm. Associations between maternal age, weight, height, body mass index (BMI), previous term deliveries, and history of previous miscarriages, with a short cervix were evaluated using logistic regression models. RESULTS: The prevalence of a short cervix in our population was: CL ≤25 mm, 2.2% (n = 403); CL ≤20 mm, 1.2% (n = 224); and CL ≤15 mm, 0.9% (n = 161). Women with BMI >30 and/or previous abortions constituted 45.5% of the total population (8463/18,582). Significant associations with short cervix were observed for women with BMI ≥30, and for women with at least one previous abortion (p < .001). Parous women had a significantly lower association with a short cervix than nulliparous women (p < .001). Maternal age or height were not associated with a short cervix. Prediction of short cervix based on presence of any of the following: BMI ≥ 30 or previous abortions showed sensitivities of 55.8% (≤25 mm), 61.6% (≤20 mm), and 63.4% (≤15 mm) with similar specificity (50.1-54.6%) and likelihood ratio positive (1.2-1.5); and prediction based on BMI ≥ 30 and previous abortions showed sensitivities of 11.1% (≤25 mm), 14.7% (≤20 mm), and 16.7% (≤15 mm) with specificity 93%. CONCLUSIONS: Among low risk women for spontaneous preterm delivery, those with a BMI ≥30 and/or previous miscarriages had a significantly increased risk for a short cervix at 18 + 0 and 23 + 6 weeks/days of gestation. Despite these significant associations, screening by maternal risk factors in a low risk population of pregnant women should not be an alternative to mid-trimester universal CL measurement.

In pregnant women evaluated at 18/0 and 23/6 weeks + days of gestation without history of preterm delivery, a 16.7% detection rate for short cervix ≤15 mm can be achieved by risk factors BMI ≥30, and at least one previous miscarriage. Nevertheless, screening for short cervix by risk factors among low risk women might not be an effective alternative to universal cervical length screening.

Hypertensive Disorders of Pregnancy and Long-Term Maternal Cardiovascular and Metabolic Biomarkers.

OBJECTIVE: This study aimed to measure the association between hypertensive disorders of pregnancy (HDP) and long-term maternal metabolic and cardiovascular biomarkers. STUDY DESIGN: Follow-up study of patients who completed glucose tolerance testing 5 to 10 years after enrollment in a mild gestational diabetes mellitus (GDM) treatment trial or concurrent non-GDM cohort. Maternal serum insulin concentrations and cardiovascular markers VCAM-1, VEGF, CD40L, GDF-15, and ST-2 were measured, and insulinogenic index (IGI, pancreatic ß-cell function) and 1/ homeostatic model assessment (insulin resistance) were calculated. Biomarkers were compared by presence of HDP (gestational hypertension or preeclampsia) during pregnancy. Multivariable linear regression estimated the association of HDP with biomarkers, adjusting for GDM, baseline body mass index (BMI), and years since pregnancy. RESULTS: Of 642 patients, 66 (10%) had HDP: 42 with gestational hypertension and 24 with preeclampsia. Patients with HDP had higher baseline and follow-up BMI, higher baseline blood pressure, and more chronic hypertension at follow-up. HDP was not associated with metabolic or cardiovascular biomarkers at follow-up. However, when HDP type was evaluated, patients with preeclampsia had lower GDF-15 levels (oxidative stress/cardiac ischemia), compared with patients without HDP (adjusted mean difference: -0.24, 95% confidence interval: -0.44, -0.03). There were no differences between gestational hypertension and no HDP. CONCLUSION: In this cohort, metabolic and cardiovascular biomarkers 5 to 10 years after pregnancies did not differ by HDP. Patients with preeclampsia may have less oxidative stress/cardiac ischemia postpartum; however, this may have been observed due to chance alone given multiple comparisons. Longitudinal studies are needed to define the impact of HDP during pregnancy and interventions postpartum. KEY POINTS: · Hypertensive disorders of pregnancy were not associated with metabolic dysfunction.. · Cardiovascular dysfunction was not consistently seen after pregnancy hypertension.. · Longitudinal studies with postpartum interventions after preeclampsia are needed..

Outcomes of induction vs prelabor cesarean delivery at <33 weeks for hypertensive disorders of pregnancy.

BACKGROUND: Hypertensive disorders of pregnancy are the leading cause of indicated preterm birth; however, the optimal delivery approach for pregnancies complicated by preterm hypertensive disorders of pregnancy remains uncertain. OBJECTIVE: This study aimed to compare maternal and neonatal morbidity in patients with hypertensive disorders of pregnancy who either went induction of labor or prelabor cesarean delivery at <33 weeks' gestation. In addition, we aimed to quantify the length of induction of labor and rate of vaginal delivery in those who underwent induction of labor. STUDY DESIGN: This is a secondary analysis of an observational study which included 115,502 patients in 25 hospitals in the United States from 2008 to 2011. Patients were included in the secondary analysis if they were delivered for pregnancy associated hypertension (gestational hypertension or preeclampsia) between 230 and <330 weeks' gestation; and were excluded for known fetal anomalies, multiple gestation, fetal malpresentation or demise, or a contraindication to labor. Maternal and neonatal adverse composite outcomes were evaluated by intended mode of delivery. Secondary outcomes were duration of labor induction and rate of cesarean delivery in those who underwent labor induction. RESULTS: A total of 471 patients met inclusion criteria, of whom 271 (58%) underwent induction of labor and 200 (42%) underwent prelabor cesarean delivery. Composite maternal morbidity was 10.2% in the induction group and 21.1% in the cesarean delivery group (unadjusted odds ratio, 0.42 [0.25-0.72]; adjusted odds ratio, 0.44 [0.26-0.76]). Neonatal morbidity in the induction group vs the cesarean delivery was 51.9% and 63.8 %, respectively (unadjusted odds ratio, 0.61 [0.42-0.89]; adjusted odds ratio, 0.71 [0.48-1.06]). The frequency of vaginal delivery in the induction group was 53% (95% confidence interval, 46.8-58.7) and the median duration of labor was 13.9 hours (interquartile range, 8.7-22.2). The frequency of vaginal birth was higher in patients at or beyond 29 weeks (39.9% at 240-286 weeks, 56.3% at 290-<330 weeks; P=.01). CONCLUSION: Among patients delivered for hypertensive disorders of pregnancy <330 weeks, labor induction compared with prelabor cesarean delivery is associated with significantly lower odds of maternal but not neonatal morbidity. More than half of patients induced delivered vaginally, with a median duration of labor induction of 13.9 hours.

Effect of a Multimedia Educational Tool on Contraception Use 1 Year Postpartum.

FUNDING SOURCE: Supported in part by a research grant from Investigator-Initiated Studies program of Organon. The opinions expressed in this paper are those of the authors and do not necessarily represent Organon. CLINICAL TRIAL REGISTRAION: ClinicalTrials.gov , NCT04291040.

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.

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).

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.

Short-term neonatal outcomes of pregnancies complicated by maternal obesity.

BACKGROUND: Maternal obesity complicates a high number of pregnancies. The degree to which neonatal outcomes are adversely affected is unclear. OBJECTIVE: This study aimed to evaluate neonatal outcomes of pregnancies complicated by maternal obesity. STUDY DESIGN: This study was a secondary analysis of a cohort of deliveries occurring on randomly selected days at 25 hospitals from 2008 to 2011. Data were collected by certified abstractors. This analysis included singleton deliveries between 24 and 42 weeks of gestation. Body mass index was calculated on the basis of maternal height and most recent weight before delivery. Normal and overweight (reference group; body mass index, 18.5-29.9 kg/m2), obese (body mass index, 30.0-39.9 kg/m2), morbidly obese (body mass index, 40.0-49.9 kg/m2), and super morbidly obese (body mass index, ≥50 kg/m2) patients were compared. Patients in the reference group were matched in a 1:1 ratio with those in all other groups with obesity using the baseline characteristics of age, race and ethnicity, previous cesarean delivery, preexisting diabetes mellitus, chronic hypertension, parity, cigarette use, and insurance status. The primary outcome was composite neonatal morbidity, including fetal or neonatal death, hypoxic-ischemic encephalopathy, respiratory distress syndrome, intraventricular hemorrhage grade 3 or 4, necrotizing enterocolitis, sepsis, birth injury, seizures, or ventilator use. We used a modified Poisson regression to examine the associations between body mass index and composite neonatal outcome. Preterm delivery at <37 weeks of gestation and the presence of maternal preeclampsia or eclampsia were included in the final model because of their known associations with neonatal outcomes. RESULTS: Overall, 52,162 patients and their neonates were included after propensity score matching. Of these, 21,704 (41.6%) were obese, 3787 (7.3%) were morbidly obese, and 590 (1.1%) were super morbidly obese. A total of 2103 neonates (4.0%) had the composite outcome. Neonates born to pregnant people with morbid obesity had a 33% increased risk of composite neonatal morbidity compared with those in the reference group (adjusted odds ratio, 1.33; 95% confidence interval, 1.17-1.52), but no significant association was observed for persons with obesity (adjusted odds ratio, 1.05; 95% confidence interval, 0.97-1.14) or with super morbid obesity (adjusted odds ratio, 1.18; 95% confidence interval, 0.86-1.64). CONCLUSION: Compared with the reference group, gravidas with morbid obesity were at higher risk of composite neonatal morbidity.

Oral Glucose Tolerance Test in Pregnancy and Subsequent Maternal Hypertension.

OBJECTIVE: The aim of the study is to evaluate whether values and the shape of the glucose curve during the oral glucose tolerance test (OGTT) in pregnancy identify women at risk of developing hypertension (HTN) later in life. STUDY DESIGN: This category includes the secondary analysis of a follow-up from a mild gestational diabetes mellitus (GDM) study that included a treatment trial for mild GDM (n = 458) and an observational cohort of participants with abnormal 1-hour glucose loading test only (normal OGTT, n = 430). Participants were assessed at a median of 7 (IQR 6-8) years after their index pregnancy, and trained staff measured their blood pressure (systolic blood pressure [SBP]; diastolic blood pressure [DBP]). The association between values and the shape of the glucose curve during OGTT in the index pregnancy and the primary outcome defined as elevated BP (SBP ≥120, DBP ≥80 mm Hg, or receiving anti-HTN medications), and secondary outcome defined as stage 1 or higher (SBP ≥130, DBP ≥80 mm Hg, or receiving anti-HTN medications) at follow-up were evaluated using multivariable regression, adjusting for maternal age, body mass index, and pregnancy-associated hypertension during the index pregnancy. RESULTS: There was no association between fasting, 1-hour OGTT, and the outcomes. However, the 2-hour OGTT value was positively associated (adjusted odds ratio [aRR] per 10-unit increase 1.04, 95% CI 1.01-1.08), and the 3-hour was inversely associated (aRR per 10-unit increase 0.96, 95% CI 0.93-0.99) with the primary outcome. When the shape of the OGTT curve was evaluated, a monophasic OGTT response (peak at 1 hour followed by a decline in glucose) was associated with increased risk of elevated BP (41.3vs. 23.5%, aRR 1.66, 95% CI 1.17-2.35) and stage 1 HTN or higher (28.5 vs. 14.7%, aRR 1.83, 95% CI 1.15-2.92), compared with a biphasic OGTT response. CONCLUSION: Among persons with mild GDM or lesser degrees of glucose intolerance, the shape of the OGTT curve during pregnancy may help identify women who are at risk of HTN later in life, with biphasic shape to be associated with lower risk. KEY POINTS: · The shape of the Oral Glucose Tolerance Test curve may help identify patients who are at risk of having elevated BP or HTN 5 to 10 years following pregnancy.. · The 2-hour Oral Glucose Tolerance Test values is positively associated with elevated BP 5 to 10 years following pregnancy.. · This supports the concept of pregnancy as a window to future health and represents a potential novel biomarker for maternal cardiovascular health screening..

Evaluation of Hypoglycemia in Neonates of Women at Risk for Late Preterm Delivery: An Antenatal Late Preterm Steroids Trial Cohort Study.

OBJECTIVE: In the antenatal late preterm steroids (ALPS) trial betamethasone significantly decreased short-term neonatal respiratory morbidity but increased the risk of neonatal hypoglycemia, diagnosed only categorically (<40 mg/dL). We sought to better characterize the nature, duration, and treatment for hypoglycemia. STUDY DESIGN: Secondary analysis of infants from ALPS, a multicenter trial randomizing women at risk for late preterm delivery to betamethasone or placebo. This study was a reabstraction of all available charts from the parent trial, all of which were requested. Unreviewed charts included those lost to follow-up or from sites not participating in the reabstraction. Duration of hypoglycemia (<40 mg/dL), lowest value and treatment, if any, were assessed by group. Measures of association and regression models were used where appropriate. RESULTS: Of 2,831 randomized, 2,609 (92.2%) were included. There were 387 (29.3%) and 223 (17.3%) with hypoglycemia in the betamethasone and placebo groups, respectively (relative risk [RR]: 1.69, 95% confidence interval [CI]: 1.46-1.96). Hypoglycemia generally occurred in the first 24 hours in both groups: 374/385 (97.1%) in the betamethasone group and 214/222 (96.4%) in the placebo group (p = 0.63). Of 387 neonates with hypoglycemia in the betamethasone group, 132 (34.1%) received treatment, while 73/223 (32.7%) received treatment in placebo group (p = 0.73). The lowest recorded blood sugar was similar between groups. Most hypoglycemia resolved by 24 hours in both (93.0 vs. 89.3% in the betamethasone and placebo groups, respectively, p = 0.18). Among infants with hypoglycemia in the first 24 hours, the time to resolution was shorter in the betamethasone group (2.80 [interquartile range: 2.03-7.03) vs. 3.74 (interquartile range: 2.15-15.08) hours; p = 0.002]. Persistence for >72 hours was rare and similar in both groups, nine (2.4%, betamethasone) and four (1.9%, placebo, p = 0.18). CONCLUSION: In this cohort, hypoglycemia was transient and most received no treatment, with a quicker resolution in the betamethasone group. Prolonged hypoglycemia was uncommon irrespective of steroid exposure. KEY POINTS: · Hypoglycemia was transient and approximately two-thirds received no treatment.. · Neonates in the ALPS trial who received betamethasone had a shorter time to resolution than those with hypoglycemia in the placebo group.. · Prolonged hypoglycemia occurred in approximately 2 out of 100 late preterm newborns, irrespective of antenatal steroid exposure..

The Association of Race and Ethnicity with Severe Maternal Morbidity among Individuals Diagnosed with Hypertensive Disorders of Pregnancy.

OBJECTIVE: This study aimed to examine whether there are racial disparities in severe maternal morbidity (SMM) in patients with hypertensive disorders of pregnancy (HDP). STUDY DESIGN: Secondary analysis of an observational study of 115,502 patients who had a live birth at ≥20 weeks in 25 hospitals in the United States from 2008 to 2011. Only patients with HDP were included in this analysis. Race and ethnicity were categorized as non-Hispanic White, non-Hispanic Black (NHB), and Hispanic and were abstracted from the medical charts. Patients of other races and ethnicities were excluded. Associations were estimated between race and ethnicity, and the primary outcome of SMM, defined as any of the following, was estimated by unadjusted logistic and multivariable backward logistic regressions: blood transfusion ≥4 units, unexpected surgical procedure, need for a ventilator ≥12 hours, intensive care unit (ICU) admission, or failure of ≥1 organ system. Multivariable models were run classifying HDP into three levels as follows: (1) gestational hypertension; (2) preeclampsia (mild, severe, or superimposed); and (3) eclampsia or HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. RESULTS: A total of 9,612 individuals with HDP met inclusion criteria. No maternal deaths occurred in this cohort. In univariable analysis, non-Hispanic White patients were more likely to present with gestational hypertension whereas NHB and Hispanic patients were more likely to present with preeclampsia. The frequency of the primary outcome, composite SMM, was higher in NHB patients compared with that in non-Hispanic White or Hispanic patients (11.8 vs. 4.5% in non-Hispanic White and 4.8% in Hispanic, p < 0.001). This difference was driven by a higher frequency of blood transfusions and ICU admissions among NHB individuals. Prior to adjusting the analysis for confounding factors, the odds ratio (OR) of primary composite outcomes in NHB individuals was 2.85 (95% confidence interval [CI]: 2.38, 3.42) compared with non-Hispanic White. After adjusting for sociodemographic and clinical factors, hospital site, and the severity of HDP, the OR of composite SMM did not differ between the groups (adjusted OR [aOR] = 1.26, 95% CI: 0.95, 1.67 for NHB, and aOR = 1.29, 95% CI: 0.94, 1.77 for Hispanic, compared with non-Hispanic White patients). Sensitivity analysis was done to exclude one single site that was an outliner with the highest ICU admissions and demonstrated no difference in ICU admission by maternal race and ethnicity. CONCLUSION: NHB patients with HDP had higher rates of the composite SMM compared with non-Hispanic White patients, driven mainly by a higher frequency of blood transfusions and ICU admissions. However, once severity and other confounding factors were taken into account, the differences did not persist. KEY POINTS: · Black patients with HDP had higher frequency of SMM compared with non-Hispanic White patients.. · The SMM disparities were driven by blood transfusions and ICU admissions.. · After adjustment for confounders, including HDP severity, the significant difference in SMM did not persist..

Long-Term Maternal Metabolic and Cardiovascular Phenotypes after a Pregnancy Complicated by Mild Gestational Diabetes Mellitus or Obesity.

OBJECTIVE: The aim of this study was to evaluate the association of mild gestational diabetes mellitus (GDM) and obesity with metabolic and cardiovascular markers 5 to 10 years after pregnancy. STUDY DESIGN: This was a secondary analysis of 5- to 10-year follow-up study of a mild GDM treatment trial and concurrent observational cohort of participants ineligible for the trial with abnormal 1-hour glucose challenge test only. Participants with 2-hour glucose tolerance test at follow-up were included. The primary exposures were mild GDM and obesity. The outcomes were insulinogenic index (IGI), 1/homeostatic model assessment of insulin resistance (HOMA-IR), and cardiovascular markers vascular endothelial growth factor, (VEGF), vascular cell adhesion molecule 1 (VCAM-1), cluster of differentiation 40 ligand (CD40L), growth differentiation factor 15 (GDF-15), and suppression of tumorgenesis 2 (ST-2). Multivariable linear regression estimated the association of GDM and obesity with biomarkers. RESULTS: Of 951 participants in the parent study, 642 (68%) were included. Lower 1/HOMA-IR were observed in treated and untreated GDM groups, compared with non-GDM (mean differences, -0.24 and -0.15; 95% confidence intervals [CIs], -0.36 to -0.12 and -0.28 to -0.03, respectively). Lower VCAM-1 (angiogenesis) was observed in treated GDM group (mean difference, -0.11; 95% CI, -0.19 to -0.03). GDM was not associated with IGI or other biomarkers. Obesity was associated with lower 1/HOMA-IR (mean difference, -0.42; 95% CI, -0.52 to -0.32), but not other biomarkers. CONCLUSION: Prior GDM and obesity are associated with more insulin resistance but not insulin secretion or consistent cardiovascular dysfunction 5 to 10 years after delivery. KEY POINTS: · Mild GDM increases the risk of insulin resistance 5 to 10 years postpartum but not pancreatic dysfunction.. · Obesity increases the risk of insulin resistance 5 to 10 years postpartum but not pancreatic dysfunction.. · Neither mild GDM nor obesity increased the risk of cardiovascular dysfunction 5 to 10 years postpartum..