Umbilical cord milking in nonvigorous infants: a cluster-randomized crossover trial.

BACKGROUND: Delayed cord clamping and umbilical cord milking provide placental transfusion to vigorous newborns. Delayed cord clamping in nonvigorous newborns may not be provided owing to a perceived need for immediate resuscitation. Umbilical cord milking is an alternative, as it can be performed more quickly than delayed cord clamping and may confer similar benefits. OBJECTIVE: We hypothesized that umbilical cord milking would reduce admission to the neonatal intensive care unit compared with early cord clamping in nonvigorous newborns born between 35 and 42 weeks' gestation. STUDY DESIGN: This was a pragmatic cluster-randomized crossover trial of infants born at 35 to 42 weeks' gestation in 10 medical centers in 3 countries between January 2019 and May 2021. The centers were randomized to umbilical cord milking or early cord clamping for approximately 1 year and then crossed over for an additional year or until the required number of consented subjects was reached. Waiver of consent as obtained in all centers to implement the intervention. Infants were eligible if nonvigorous at birth (poor tone, pale color, or lack of breathing in the first 15 seconds after birth) and were assigned to umbilical cord milking or early cord clamping according to their birth hospital randomization assignment. The baseline characteristics and outcomes were collected following deferred informed consent. The primary outcome was admission to the neonatal intensive care unit for predefined criteria. The main safety outcome was hypoxic-ischemic encephalopathy. Data were analyzed by the intention-to-treat concept. RESULTS: Among 16,234 screened newborns, 1780 were eligible (905 umbilical cord milking, 875 early cord clamping), and 1730 had primary outcome data for analysis (97% of eligible; 872 umbilical cord milking, 858 early cord clamping) either via informed consent (606 umbilical cord milking, 601 early cord clamping) or waiver of informed consent (266 umbilical cord milking, 257 early cord clamping). The difference in the frequency of neonatal intensive care unit admission using predefined criteria between the umbilical cord milking (23%) and early cord clamping (28%) groups did not reach statistical significance (modeled odds ratio, 0.69; 95% confidence interval, 0.41-1.14). Umbilical cord milking was associated with predefined secondary outcomes, including higher hemoglobin (modeled mean difference between umbilical cord milking and early cord clamping groups 0.68 g/dL, 95% confidence interval, 0.31-1.05), lower odds of abnormal 1-minute Apgar scores (Apgar ≤3, 30% vs 34%, crude odds ratio, 0.72; 95% confidence interval, 0.56-0.92); cardiorespiratory support at delivery (61% vs 71%, modeled odds ratio, 0.57; 95% confidence interval, 0.33-0.99), and therapeutic hypothermia (3% vs 4%, crude odds ratio, 0.57; 95% confidence interval, 0.33-0.99). Moderate-to-severe hypoxic-ischemic encephalopathy was significantly less common with umbilical cord milking (1% vs 3%, crude odds ratio, 0.48; 95% confidence interval, 0.24-0.96). No significant differences were observed for normal saline bolus, phototherapy, abnormal 5-minute Apgar scores (Apgar ≤6, 15.7% vs 18.8%, crude odds ratio, 0.81; 95% confidence interval, 0.62-1.06), or a serious adverse event composite of death before discharge. CONCLUSION: Among nonvigorous infants born at 35 to 42 weeks' gestation, umbilical cord milking did not reduce neonatal intensive care unit admission for predefined criteria. However, infants in the umbilical cord milking arm had higher hemoglobin, received less delivery room cardiorespiratory support, had a lower incidence of moderate-to-severe hypoxic-ischemic encephalopathy, and received less therapeutic hypothermia. These data may provide the first randomized controlled trial evidence that umbilical cord milking in nonvigorous infants is feasible, safe and, superior to early cord clamping.

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..

Racial and Ethnic Disparities in Adverse Perinatal Outcomes at Term.

OBJECTIVE: This study aimed to evaluate whether racial and ethnic disparities in adverse perinatal outcomes exist at term. STUDY DESIGN: We performed a secondary analysis of a multicenter observational study of 115,502 pregnant patients and their neonates (2008-2011). Singleton, nonanomalous pregnancies delivered from 37 to 41 weeks were included. Race and ethnicity were abstracted from the medical record and categorized as non-Hispanic White (White; referent), non-Hispanic Black (Black), non-Hispanic Asian (Asian), or Hispanic. The primary outcome was an adverse perinatal composite defined as perinatal death, Apgar score < 4 at 5 minutes, ventilator support, hypoxic-ischemic encephalopathy, subgaleal hemorrhage, skeletal fracture, infant stay greater than maternal stay (by ≥ 3 days), brachial plexus palsy, or facial nerve palsy. RESULTS: Of the 72,117 patients included, 48% were White, 20% Black, 5% Asian, and 26% Hispanic. The unadjusted risk of the primary outcome was highest for neonates of Black patients (3.1%, unadjusted relative risk [uRR] = 1.16, 95% confidence interval [CI]: 1.04-1.30), lowest for neonates of Hispanic patients (2.1%, uRR = 0.80, 95% CI: 0.71-0.89), and no different for neonates of Asian (2.6%), compared with those of White patients (2.7%). In the adjusted model including age, body mass index (BMI), smoking, obstetric history, and high-risk pregnancy, differences in risk for the primary outcome were no longer observed for neonates of Black (adjusted relative risk [aRR] = 1.06, 95% CI: 0.94-1.19) and Hispanic (aRR = 0.92, 95% CI: 0.81-1.04) patients. Adding insurance to the model lowered the risk for both groups (aRR = 0.85, 95% CI: 0.75-0.96 for Black; aRR = 0.68, 95% CI: 0.59-0.78 for Hispanic). CONCLUSION: Although neonates of Black patients have the highest frequency of adverse perinatal outcomes at term, after adjustment for sociodemographic factors, this higher risk is no longer observed, suggesting the importance of developing strategies that address social determinants of health to lessen extant health disparities. KEY POINTS: · Term neonates of Black patients have the highest crude frequency of adverse perinatal outcomes.. · After adjustment for confounders, higher risk for neonates of Black patients is no longer observed.. · Disparities in outcomes are strongly related to insurance status..

Prediction of vaginal birth after cesarean delivery in term gestations: a calculator without race and ethnicity.

BACKGROUND: Investigators have attempted to derive tools that could provide clinicians with an easily obtainable estimate of the chance of vaginal birth after cesarean delivery for those who undertake trial of labor after cesarean delivery. One tool that has been validated externally was derived from data from the Maternal-Fetal Medicine Units Cesarean Registry. However, concern has been raised that this tool includes the socially constructed variables of race and ethnicity. OBJECTIVE: This study aimed to develop an accurate tool to predict vaginal birth after cesarean delivery, using data easily obtainable early in pregnancy, without the inclusion of race and ethnicity. STUDY DESIGN: This was a secondary analysis of the Cesarean Registry of the Maternal-Fetal Medicine Units Network. The approach to the current analysis is similar to that of the analysis in which the previous vaginal birth after cesarean delivery prediction tool was derived. Specifically, individuals were included in this analysis if they were delivered on or after 37 0/7 weeks' gestation with a live singleton cephalic fetus at the time of labor and delivery admission, had a trial of labor after cesarean delivery, and had a history of 1 previous low-transverse cesarean delivery. Information was only considered for inclusion in the model if it was ascertainable at an initial prenatal visit. Model selection and internal validation were performed using a cross-validation procedure, with the dataset randomly and equally divided into a training set and a test set. The training set was used to identify factors associated with vaginal birth after cesarean delivery and build the logistic regression predictive model using stepwise backward elimination. A final model was generated that included all variables found to be significant (P<.05). The accuracy of the model to predict vaginal birth after cesarean delivery was assessed using the concordance index. The independent test set was used to estimate classification errors and validate the model that had been developed from the training set, and calibration was assessed. The final model was then applied to the overall analytical population. RESULTS: Of the 11,687 individuals who met the inclusion criteria for this secondary analysis, 8636 (74%) experienced vaginal birth after cesarean delivery. The backward elimination variable selection yielded a model from the training set that included maternal age, prepregnancy weight, height, indication for previous cesarean delivery, obstetrical history, and chronic hypertension. Vaginal birth after cesarean delivery was significantly more likely for women who were taller and had a previous vaginal birth, particularly if that vaginal birth had occurred after a previous cesarean delivery. Conversely, vaginal birth after cesarean delivery was significantly less likely for women whose age was older, whose weight was heavier, whose indication for previous cesarean delivery was arrest of dilation or descent, and who had a history of medication-treated chronic hypertension. The model had excellent calibration between predicted and empirical probabilities and, when applied to the overall analytical population, an area under the receiver operating characteristic curve of 0.75 (95% confidence interval, 0.74-0.77), which is similar to the area under the receiver operating characteristic curve of the previous model (0.75) that included race and ethnicity. CONCLUSION: We successfully derived an accurate model (available at https://mfmunetwork.bsc.gwu.edu/web/mfmunetwork/vaginal-birth-after-cesarean-calculator), which did not include race or ethnicity, for the estimation of the probability of vaginal birth after cesarean delivery.

Health resource utilization of labor induction versus expectant management.

BACKGROUND: Although induction of labor of low-risk nulliparous women at 39 weeks reduces the risk of cesarean delivery compared with expectant management, concern regarding more frequent use of labor induction remains, given that this intervention historically has been thought to incur greater resource utilization. OBJECTIVE: The objective of the study was to determine whether planned elective labor induction at 39 weeks among low-risk nulliparous women, compared with expectant management, was associated with differences in health care resource utilization from the time of randomization through 8 weeks postpartum. STUDY DESIGN: This is a planned secondary analysis of a multicenter randomized trial in which low-risk nulliparous women were assigned to induction of labor at 39 weeks or expectant management. We assessed resource utilization after randomization in 3 time periods: antepartum, delivery admission, and discharge through 8 weeks postpartum. RESULTS: Of 6096 women with data available, those in the induction of labor group (n = 3059) were significantly less likely in the antepartum period after randomization to have at least 1 ambulatory visit for routine prenatal care (32.4% vs 68.4%), unanticipated care (0.5% vs 2.6%), or urgent care (16.2% vs 44.3%), or at least 1 antepartum hospitalization (0.8% vs 2.2%, P < .001 for all). They also had fewer tests (eg, sonograms, blood tests) and treatments (eg, antibiotics, intravenous hydration) prior to delivery. During the delivery admission, women in the induction of labor group spent a longer time in labor and delivery (median, 0.83 vs 0.57 days), but both women (P = .002) and their neonates (P < .001) had shorter postpartum stays. Women and neonates in both groups had similar frequencies of postpartum urgent care and hospital readmissions (P > .05 for all). CONCLUSION: Women randomized to induction of labor had longer durations in labor and delivery but significantly fewer antepartum visits, tests, and treatments and shorter maternal and neonatal hospital durations after delivery. These results demonstrate that the health outcome advantages associated with induction of labor are gained without incurring uniformly greater health care resource use.

Effect of Treatment of Mild Gestational Diabetes on Long-Term Maternal Outcomes.

OBJECTIVE: The main purpose of this article is to evaluate whether identification and treatment of women with mild gestational diabetes mellitus (GDM) during pregnancy affects subsequent maternal body mass index (BMI), anthropometry, metabolic syndrome, and risk of diabetes. STUDY DESIGN: This is a follow-up study of women who participated in a randomized controlled treatment trial for mild GDM. Women were enrolled between 5 and 10 years after their index pregnancy. Participants underwent blood pressure, height, weight, and anthropometric measurements by trained nursing personnel using a standardized approach. A nurse-assisted questionnaire regarding screening and treatment of diabetes or hypercholesterolemia, diet, and physical activity was completed. Laboratory evaluation included fasting serum glucose, fasting insulin, oral glucose tolerance test, and a lipid panel. Subsequent diabetes, metabolic syndrome, obesity, and adiposity in those diagnosed with mild GDM and randomized to nutritional counseling and medical therapy (treated) were compared with those who underwent routine pregnancy management (untreated). Multivariable analyses were performed adjusting for race/ethnicity and years between randomization and follow-up visit. RESULTS: Four-hundred fifty-seven women with mild GDM during the index pregnancy were included in this analysis (243 treated; 214 untreated) and evaluated at a median 7 years after their index pregnancy. Baseline and follow-up characteristics were similar between treatment groups. Frequency of diabetes (9.2 vs. 8.5%, p =0.80), metabolic syndrome (32.2 vs. 34.3%, p =0.63), as well as adjusted mean values of homeostasis model assessment for insulin resistance (2.5 vs. 2.3, p =0.11) and BMI (29.4 vs. 29.1 kg/m2, p =0.67) were also not different. CONCLUSION: Identification and treatment of women with mild GDM during pregnancy had no discernible impact on subsequent diabetes, metabolic syndrome, or obesity 7 years after delivery.

Incidence of early-onset sepsis in infants born to women with clinical chorioamnionitis.

Objective To determine the frequency of sepsis and other adverse neonatal outcomes in women with a clinical diagnosis of chorioamnionitis. Methods We performed a secondary analysis of a multi-center placebo-controlled trial of vitamins C/E to prevent preeclampsia in low risk nulliparous women. Clinical chorioamnionitis was defined as either the "clinical diagnosis" of chorioamnionitis or antibiotic administration during labor because of an elevated temperature or uterine tenderness in the absence of another cause. Early-onset neonatal sepsis was categorized as "suspected" or "confirmed" based on a clinical diagnosis with negative or positive blood, urine or cerebral spinal fluid cultures, respectively, within 72 h of birth. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. Results Data from 9391 mother-infant pairs were analyzed. The frequency of chorioamnionitis was 10.3%. Overall, 6.6% of the neonates were diagnosed with confirmed (0.2%) or suspected (6.4%) early-onset sepsis. Only 0.7% of infants born in the setting of chorioamnionitis had culture-proven early-onset sepsis versus 0.1% if chorioamnionitis was not present. Clinical chorioamnionitis was associated with both suspected [OR 4.01 (3.16-5.08)] and confirmed [OR 4.93 (1.65-14.74)] early-onset neonatal sepsis, a need for resuscitation within the first 30 min after birth [OR 2.10 (1.70-2.61)], respiratory distress [OR 3.14 (2.16-4.56)], 1 min Apgar score of ≤3 [OR 2.69 (2.01-3.60)] and 4-7 [OR 1.71 (1.43-2.04)] and 5 min Apgar score of 4-7 [OR 1.67 (1.17-2.37)] (vs. 8-10). Conclusion Clinical chorioamnionitis is common and is associated with neonatal morbidities. However, the vast majority of exposed infants (99.3%) do not have confirmed early-onset sepsis.

Evaluation of delivery options for second-stage events.

BACKGROUND: Cesarean delivery in the second stage of labor is common, whereas the frequency of operative vaginal delivery has been declining. However, data comparing outcomes for attempted operative vaginal delivery vs cesarean in the second stage are scant. Previous studies that examine operative vaginal delivery have compared it to a baseline risk of complications from a spontaneous vaginal delivery and cesarean delivery. However, when a woman has a need for intervention in the second stage, spontaneous vaginal delivery is not an option she or the provider can choose. Thus, the appropriate clinical comparison is cesarean vs operative vaginal delivery. OBJECTIVE: Our objective was to compare outcomes by the first attempted operative delivery (vacuum, forceps vs cesarean delivery) in patients needing second-stage assistance at a fetal station of +2 or below. STUDY DESIGN: We conducted secondary analysis of an observational obstetric cohort in 25 academically affiliated US hospitals over a 3-year period. A subset of ≥37 weeks, nonanomalous, vertex, singletons, with no prior vaginal delivery who reached a station of +2 or below and underwent an attempt at an operative delivery were included. Indications included for operative delivery were: failure to descend, nonreassuring fetal status, labor dystocia, or maternal exhaustion. The primary outcomes included a composite neonatal outcome (death, fracture, length of stay ≥3 days beyond mother's, low Apgar, subgaleal hemorrhage, ventilator support, hypoxic encephalopathy, brachial plexus injury, facial nerve palsy) and individual maternal outcomes (postpartum hemorrhage, third- and fourth-degree tears [severe lacerations], and postpartum infection). Outcomes were examined by the 3 attempted modes of delivery. Odds ratios (OR) were calculated for primary outcomes adjusting for confounders. Final mode of delivery was quantified. RESULTS: In all, 2531 women met inclusion criteria. No difference in the neonatal composite outcome was observed between groups. Vacuum attempt was associated with the lowest frequency of maternal complications (postpartum infection 0.2% vs 0.9% forceps vs 5.3% cesarean, postpartum hemorrhage 1.4% vs 2.8% forceps vs 3.8% cesarean), except for severe lacerations (19.1% vs 33.8% forceps vs 0% cesarean). When confounders were taken into account, both forceps (OR, 0.16; 95% confidence interval, 0.05-0.49) and vacuum (OR, 0.04; 95% confidence interval, 0.01-0.17) were associated with a significantly lower odds of postpartum infection. The neonatal composite and postpartum hemorrhage were not significantly different between modes of attempted delivery. Cesarean occurred in 6.4% and 4.4% of attempted vacuum and forceps groups (P = .04). CONCLUSION: In patients needing second-stage delivery assistance with a station of +2 or below, attempted operative vaginal delivery was associated with a lower frequency of postpartum infection, but higher frequency of severe lacerations.

Preterm neonatal morbidity and mortality by gestational age: a contemporary cohort.

BACKGROUND: Although preterm birth <37 weeks' gestation is the leading cause of neonatal morbidity and mortality in the United States, the majority of data regarding preterm neonatal outcomes come from older studies, and many reports have been limited to only very preterm neonates. Delineation of neonatal outcomes by delivery gestational age is needed to further clarify the continuum of mortality and morbidity frequencies among preterm neonates. OBJECTIVE: We sought to describe the contemporary frequencies of neonatal death, neonatal morbidities, and neonatal length of stay across the spectrum of preterm gestational ages. STUDY DESIGN: This was a secondary analysis of an obstetric cohort of 115,502 women and their neonates who were born in 25 hospitals nationwide, 2008 through 2011. All liveborn nonanomalous singleton preterm (23.0-36.9 weeks of gestation) neonates were included in this analysis. The frequency of neonatal death, major neonatal morbidity (intraventricular hemorrhage grade III/IV, seizures, hypoxic-ischemic encephalopathy, necrotizing enterocolitis stage II/III, bronchopulmonary dysplasia, persistent pulmonary hypertension), and minor neonatal morbidity (hypotension requiring treatment, intraventricular hemorrhage grade I/II, necrotizing enterocolitis stage I, respiratory distress syndrome, hyperbilirubinemia requiring treatment) were calculated by delivery gestational age; each neonate was classified once by the worst outcome for which criteria was met. RESULTS: In all, 8334 deliveries met inclusion criteria. There were 119 (1.4%) neonatal deaths. In all, 657 (7.9%) neonates had major morbidity, 3136 (37.6%) had minor morbidity, and 4422 (53.1%) survived without any of the studied morbidities. Deaths declined rapidly with each advancing week of gestation. This decline in death was accompanied by an increase in major neonatal morbidity, which peaked at 54.8% at 25 weeks of gestation. As frequencies of death and major neonatal morbidity fell, minor neonatal morbidity increased, peaking at 81.7% at 31 weeks of gestation. The frequency of all morbidities fell >32 weeks. After 25 weeks, neonatal length of hospital stay decreased significantly with each additional completed week of pregnancy; among babies delivered from 26-32 weeks of gestation, each additional week in utero reduced the subsequent length of neonatal hospitalization by a minimum of 8 days. The median postmenstrual age at discharge nadired around 36 weeks' postmenstrual age for babies born at 31-35 weeks of gestation. CONCLUSION: Our data show that there is a continuum of outcomes, with each additional week of gestation conferring survival benefit while reducing the length of initial hospitalization. These contemporary data can be useful for patient counseling regarding preterm outcomes.

Use and attitudes of obstetricians toward 3 high-risk interventions in MFMU Network hospitals.

OBJECTIVE: We sought to evaluate the frequency of, and factors associated with, the use of 3 evidence-based interventions: antenatal corticosteroids for fetal lung maturity, progesterone for prevention of recurrent preterm birth, and magnesium sulfate for fetal neuroprotection. STUDY DESIGN: A self-administered survey was conducted from January through May 2011 among obstetricians from 21 hospitals that included 30 questions regarding their knowledge, attitudes, and practice of the 3 evidence-based interventions and the 14-item short version of the Team Climate for Innovation survey. Frequency of use of each intervention was ascertained from an obstetrical cohort of women between January 2010 and February 2011. RESULTS: A total of 329 obstetricians (74% response rate) who managed 16,946 deliveries within the obstetrical cohort participated in the survey. More than 90% of obstetricians reported that they incorporated each intervention into routine practice. Actual frequency of administration in women eligible for the treatments was 93% for corticosteroids, 39% for progesterone, and 71% for magnesium sulfate. Provider satisfaction with quality of treatment evidence was 97% for corticosteroids, 82% for progesterone, and 57% for magnesium sulfate. Obstetricians perceived that barriers to treatment were most frequent for progesterone (76%), 30% for magnesium sulfate, and 17% for corticosteroids. Progesterone use was more frequent among patients whose provider reported the quality of the evidence was above average to excellent compared with poor to average (42% vs 25%, respectively; P < .001), and they were satisfied with their knowledge of the intervention (41% vs 28%; P = .02), and was less common among patients whose provider reported barriers to hospital or pharmacy drug delivery (31% vs 42%; P = .01). Corticosteroid administration was more common among patients who delivered at hospitals with 24 hours a day-7 days a week maternal-fetal medicine specialist coverage (93% vs 84%; P = .046), CONCLUSION: Obstetricians in Maternal-Fetal Medicine Units Network hospitals frequently use these evidence-based interventions; however, progesterone use was found to be related to their assessment of evidence quality. Neither progesterone nor the other interventions were associated with overall climate of innovation within a hospital as measured by the Team Climate for Innovation. National Institutes of Health Consensus Conference Statements may also have an impact on use; there is such a statement for antenatal corticosteroids but not for progesterone for preterm prevention or magnesium sulfate for fetal neuroprotection.

Serious maternal complications after early preterm delivery (24-33 weeks' gestation).

OBJECTIVE: We sought to describe the prevalence of serious maternal complications following early preterm birth by gestational age (GA), delivery route, and type of cesarean incision. STUDY DESIGN: Trained personnel abstracted data from maternal and neonatal charts for all deliveries on randomly selected days representing one third of deliveries across 25 US hospitals over 3 years (n = 115,502). All women delivering nonanomalous singletons between 23-33 weeks' gestation were included. Women were excluded for antepartum stillbirth and highly morbid conditions for which route of delivery would not likely impact morbidity including nonreassuring fetal status, cord prolapse, placenta previa, placenta accreta, placental abruption, and severe and unstable maternal conditions (cardiopulmonary collapse, acute respiratory distress syndrome, seizures). Serious maternal complications were defined as: hemorrhage (blood loss ≥1500 mL, blood transfusion, or hysterectomy for hemorrhage), infection (endometritis, wound dehiscence, or wound infection requiring antibiotics, reopening, or unexpected procedure), intensive care unit admission, or death. Delivery route was categorized as classic cesarean delivery (CCD), low transverse cesarean delivery (LTCD), low vertical cesarean delivery (LVCD), and vaginal delivery. Association of delivery route with complications was estimated using multivariable regression models yielding adjusted relative risks (aRR) controlling for maternal age, race, body mass index, hypertension, diabetes, preterm premature rupture of membranes, preterm labor, GA, and hospital of delivery. RESULTS: Of 2659 women who met criteria for inclusion in this analysis, 8.6% of women experienced serious maternal complications. Complications were associated with GA and were highest between 23-27 weeks of gestation. The frequency of complications was associated with delivery route; compared with 3.5% of vaginal delivery, 23.0% of CCD (aRR, 3.54; 95% confidence interval (CI), 2.29-5.48), 12.1% of LTCD (aRR, 2.59; 95% CI, 1.77-3.77), and 10.3% of LVCD (aRR, 2.27; 95% CI, 0.68-7.55) experienced complications. There was no significant difference in complication rates between CCD and LTCD (aRR, 1.37; 95% CI, 0.95-1.97) or between CCD and LVCD (aRR, 1.56; 95% CI, 0.48-5.07). CONCLUSION: The risk of maternal complications after early preterm delivery is substantial, particularly in women who undergo cesarean delivery. Obstetricians need to be prepared to manage potential hemorrhage, infection, and intensive care unit admission for early preterm births requiring cesarean delivery.

Can differences in obstetric outcomes be explained by differences in the care provided? The MFMU Network APEX study.

OBJECTIVE: The purpose of this study was to determine whether hospital differences in the frequency of adverse obstetric outcomes are related to differences in care. STUDY DESIGN: The Assessment of Perinatal EXcellence cohort comprises 115,502 women and their neonates who were born in 25 hospitals in the United States between March 2008 and February 2011. Hierarchical logistic regression was used to quantify the amount of variation in postpartum hemorrhage, peripartum infection, severe perineal laceration, and a composite adverse neonatal outcome among hospitals that is explained by differences in patient characteristics, hospital characteristics, and obstetric care provided. RESULTS: The study included 115,502 women. For most outcomes, 20-40% of hospital differences in outcomes were related to differences in patient populations. After adjusting for patient-, provider-, and hospital-level factors, multiple care processes were associated with the predefined adverse outcomes; however, these care processes did not explain significant variation in the frequency of adverse outcomes among hospitals. Ultimately, 50-100% of the interhospital variation in outcomes was unexplained. CONCLUSION: Hospital differences in the frequency of adverse obstetric outcomes could not be explained by differences in frequency of types of care provided.

Machine Learning Models for Prediction of Maternal Hemorrhage and Transfusion: Model Development Study.

BACKGROUND: Current postpartum hemorrhage (PPH) risk stratification is based on traditional statistical models or expert opinion. Machine learning could optimize PPH prediction by allowing for more complex modeling. OBJECTIVE: We sought to improve PPH prediction and compare machine learning and traditional statistical methods. METHODS: We developed models using the Consortium for Safe Labor data set (2002-2008) from 12 US hospitals. The primary outcome was a transfusion of blood products or PPH (estimated blood loss of ≥1000 mL). The secondary outcome was a transfusion of any blood product. Fifty antepartum and intrapartum characteristics and hospital characteristics were included. Logistic regression, support vector machines, multilayer perceptron, random forest, and gradient boosting (GB) were used to generate prediction models. The area under the receiver operating characteristic curve (ROC-AUC) and area under the precision/recall curve (PR-AUC) were used to compare performance. RESULTS: Among 228,438 births, 5760 (3.1%) women had a postpartum hemorrhage, 5170 (2.8%) had a transfusion, and 10,344 (5.6%) met the criteria for the transfusion-PPH composite. Models predicting the transfusion-PPH composite using antepartum and intrapartum features had the best positive predictive values, with the GB machine learning model performing best overall (ROC-AUC=0.833, 95% CI 0.828-0.838; PR-AUC=0.210, 95% CI 0.201-0.220). The most predictive features in the GB model predicting the transfusion-PPH composite were the mode of delivery, oxytocin incremental dose for labor (mU/minute), intrapartum tocolytic use, presence of anesthesia nurse, and hospital type. CONCLUSIONS: Machine learning offers higher discriminability than logistic regression in predicting PPH. The Consortium for Safe Labor data set may not be optimal for analyzing risk due to strong subgroup effects, which decreases accuracy and limits generalizability.

Two-Year Outcomes of Umbilical Cord Milking in Nonvigorous Infants: A Secondary Analysis of the MINVI Randomized Clinical Trial.

Importance: Compared with early cord clamping (ECC), umbilical cord milking (UCM) reduces delivery room cardiorespiratory support, hypoxic-ischemic encephalopathy, and therapeutic hypothermia in nonvigorous near-term and full-term infants. However, UCM postdischarge outcomes are not known. Objective: To determine the 2-year outcomes of children randomized to UCM or ECC at birth in the Milking in Nonvigorous Infants (MINVI) trial. Design, Setting, and Participants: A secondary analysis to evaluate longer-term outcomes of a cluster-randomized crossover trial was conducted from January 9, 2021, to September 25, 2023. The primary trial took place in 10 medical centers in the US, Canada, and Poland from January 5, 2019, to June 1, 2021, and hypothesized that UCM would reduce admission to the neonatal intensive care unit compared with ECC; follow-up concluded September 26, 2023. The population included near-term and full-term infants aged 35 to 42 weeks' gestation at birth who were nonvigorous; families provided consent to complete developmental screening questionnaires through age 2 years. Intervention: UCM and ECC. Main Outcomes and Measures: Ages and Stages Questionnaire, 3rd Edition (ASQ-3) and Modified Checklist for Autism in Toddlers, Revised/Follow-Up (M-CHAT-R/F) questionnaires at ages 22 to 26 months. Intention-to-treat analysis and per-protocol analyses were used. Results: Among 1730 newborns from the primary trial, long-term outcomes were evaluated in 971 children (81%) who had ASQ-3 scores available at 2 years or died before age 2 years and 927 children (77%) who had M-CHAT-R/F scores or died before age 2 years. Maternal and neonatal characteristics by treatment group were similar, with median birth gestational age of 39 (IQR, 38-40) weeks in both groups; 224 infants (45%) in the UCM group and 201 (43%) in the ECC group were female. The median ASQ-3 total scores were similar (UCM: 255 [IQR, 225-280] vs ECC: 255 [IQR, 230-280]; P = .87), with no significant differences in the ASQ-3 subdomains. Medium- to high-risk M-CHAT-R/F scores were also similar (UCM, 9% [45 of 486] vs ECC, 8% [37 of 441]; P = .86). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial among late near-term and full-term infants who were nonvigorous at birth, ASQ-3 scores at age 2 years were not significantly different between the UCM and ECC groups. Combined with previously reported important short-term benefits, this follow-up study suggests UCM is a feasible, no-cost intervention without longer-term neurodevelopmental risks of cord milking in nonvigorous near-term and term newborns. Trial Registration: ClinicalTrials.gov Identifier: NCT03631940.

Advanced lipoprotein measures and recurrent preterm birth.

OBJECTIVE: Lipoproteins are associated with atherogenic and inflammatory processes, and these processes may be related to adverse pregnancy outcomes. We therefore examined whether variations in lipoprotein particle size and concentration are associated with preterm birth (PTB) <35 weeks' gestation. STUDY DESIGN: This is a case-control ancillary study to a randomized trial of omega-3 fatty acid supplementation to prevent recurrent PTB. We measured standard lipids and used nuclear magnetic resonance (NMR) spectroscopy to characterize 17 lipoprotein particles from plasma collected at the baseline randomization visit (16-21 weeks' gestation) in 128 cases (PTB <35 weeks' gestation) and 132 term controls. Logistic regression models controlled for study center, race/ethnicity, number of prior PTB, smoking, and treatment group, as well as total low-density lipoprotein (LDL), high-density lipoprotein, and triglyceride concentrations when examining LDLNMR, high-density lipoproteinNMR, and very LDL (VLDL)NMR, respectively. RESULTS: Only 1 of the 17 NMR lipoproteins was associated with recurrent PTB. We observed an increased odds of recurrent PTB of 1.04 (95% confidence interval, 1.01-1.08; P = .02) per nanometer increase in VLDLNMR particle size and an odds ratio of 3.00 (confidence interval, 1.40-6.43; P = .005) for the third tertile of VLDLNMR particle size compared with the first tertile. CONCLUSION: In women with prior PTB, variations in midpregnancy lipoproteins were not associated with recurrent PTB overall, however the association observed with VLDLNMR particle size is suggestive that PTB may be amenable to lifestyle, nutritional, or pharmacologic interventions.

Risk-adjusted models for adverse obstetric outcomes and variation in risk-adjusted outcomes across hospitals.

OBJECTIVE: Regulatory bodies and insurers evaluate hospital quality using obstetrical outcomes, however meaningful comparisons should take preexisting patient characteristics into account. Furthermore, if risk-adjusted outcomes are consistent within a hospital, fewer measures and resources would be needed to assess obstetrical quality. Our objective was to establish risk-adjusted models for 5 obstetric outcomes and assess hospital performance across these outcomes. STUDY DESIGN: We studied a cohort of 115,502 women and their neonates born in 25 hospitals in the United States from March 2008 through February 2011. Hospitals were ranked according to their unadjusted and risk-adjusted frequency of venous thromboembolism, postpartum hemorrhage, peripartum infection, severe perineal laceration, and a composite neonatal adverse outcome. Correlations between hospital risk-adjusted outcome frequencies were assessed. RESULTS: Venous thromboembolism occurred too infrequently (0.03%; 95% confidence interval [CI], 0.02-0.04%) for meaningful assessment. Other outcomes occurred frequently enough for assessment (postpartum hemorrhage, 2.29%; 95% CI, 2.20-2.38, peripartum infection, 5.06%; 95% CI, 4.93-5.19, severe perineal laceration at spontaneous vaginal delivery, 2.16%; 95% CI, 2.06-2.27, neonatal composite, 2.73%; 95% CI, 2.63-2.84). Although there was high concordance between unadjusted and adjusted hospital rankings, several individual hospitals had an adjusted rank that was substantially different (as much as 12 rank tiers) than their unadjusted rank. None of the correlations between hospital-adjusted outcome frequencies was significant. For example, the hospital with the lowest adjusted frequency of peripartum infection had the highest adjusted frequency of severe perineal laceration. CONCLUSION: Evaluations based on a single risk-adjusted outcome cannot be generalized to overall hospital obstetric performance.

Factors Associated with the Uptake of Rotavirus and Pneumococcal Conjugate Vaccines among Children in Armenia: Implications for Future New Vaccine Introductions.

Advances in vaccinology have resulted in various new vaccines being introduced into recommended immunization schedules. Armenia introduced the rotavirus vaccine (RV) and the pneumococcal conjugate vaccine (PCV) into its national schedule in 2012 and 2014, respectively. Using data from the Armenia Demographic and Health Survey, the uptake of the RV and the PCV among children aged younger than three years was estimated. Multilevel logistic regression models were used to evaluate individual- and community-level factors associated with uptake. Intra-cluster correlations were estimated to explain variations in uptake between clusters. The uptake proportionof each RV dose were 90.0% and 86.6%, while each PCV dose had values of 83.5%, 79.4%, and 75.5%, respectively. Non-uptake was highest among children less than 6 months old, children with one sibling, children from a wealthy family, or children whose living distance to a health clinic was problematic. Significant variability in non-uptake due to cluster differences was found for both RV doses (30.5% and 22.8%, respectively) and for the second PCV dose (53.9%). When developing strategies for new vaccine implementation, characteristics of the child, such as age, siblingship, and distance to a health clinic or residence, should be considered. Further exploration of cluster differences may provide insights based on the increased uptake of these and other new vaccines.

Maternal and Delivery Characteristics and Self-Reported Perceived Control During Labor.

OBJECTIVE: To evaluate the association between maternal and delivery characteristics and self-reported perceived control during childbirth. METHODS: A secondary analysis of a multicenter randomized trial was conducted to compare labor induction at 39 weeks of gestation with expectant management in low-risk nulliparous people. Six to 96 hours after delivery, participants who experienced labor completed the Labor Agentry Scale, a validated self-administered questionnaire to ascertain perceived control during childbirth. Scores range from 29 to 203, with higher scores indicating a sense of greater control. Multivariable linear regression was used to determine which maternal and delivery characteristics were associated with the Labor Agentry Scale score. Eligible characteristics included age, self-reported race and ethnicity, marital status, employment status, type of insurance, previous pregnancy loss before 20 weeks of gestation, body mass index (BMI), smoking, alcohol use, mode of delivery, labor pain (0-10 points), and a composite of perinatal death or severe neonatal complications. Significant variables ( P <.05) were retained in the final multivariable model, and adjusted mean differences (95% CIs) between groups were estimated. RESULTS: Of 6,106 people enrolled in the trial, 6,038 experienced labor, of whom 5,750 (95.2%) completed the Labor Agentry Scale and were included in this analysis. Mean [95% CI] adjusted Labor Agentry Scale scores were significantly lower among those who identified as Asian (-6.4 [-10.5 to -2.3]) or Hispanic (-3.7 [-5.7 to -1.7]) compared with White, smoked compared with did not smoke (-2.8 [-5.5 to -0.1]), had BMIs of 35 or higher compared with less than 30 (-2.0 [-3.8 to -0.2]), were unemployed (-3.15 [-4.76 to -1.55]), did not have private health insurance (-2.61 [-4.47 to -0.76]), underwent operative vaginal (-5.1 [-7.7 to -2.6]) or cesarean (-14.4 [-16.1 to -12.6]) delivery compared with spontaneous vaginal delivery, and reported greater labor pain score of 8 or higher compared with less than 8 (-11.9 [-13.4 to -10.4]). Mean [95% CI] adjusted Labor Agentry Scale scores were significantly higher among people who were employed compared with unemployed (3.2 [1.6-4.8]) and had private compared with nonprivate insurance (2.6 [0.76-4.5]). CONCLUSION: In nulliparous people at low risk, unemployment, lack of private health insurance, Asian race, Hispanic ethnicity, smoking, operative delivery, and more labor pain were associated with lower perceived control during labor. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT01990612.

A sensitive cardiac troponin T assay in stable coronary artery disease.

BACKGROUND: In most patients with stable coronary artery disease, plasma cardiac troponin T levels are below the limit of detection for the conventional assay. The distribution and determinants of very low circulating troponin T levels, as well as their association with cardiovascular events, in such patients are unknown. METHODS: We used a new, high-sensitivity assay to determine the concentration of cardiac troponin T in plasma samples from 3679 patients with stable coronary artery disease and preserved left ventricular function. Results of the assay were analyzed in relation to the incidence of cardiovascular events during a median follow-up period of 5.2 years. RESULTS: With the highly sensitive assay, concentrations of cardiac troponin T were at or above the limit of detection (0.001 microg per liter) in 3593 patients (97.7%) and at or above the 99th percentile for apparently healthy subjects (0.0133 microg per liter) in 407 patients (11.1%). After adjustment for other independent prognostic indicators, there was a strong and graded increase in the cumulative incidence of cardiovascular death (adjusted hazard ratio per unit increase in the natural logarithm of the troponin T level, 2.09; 95% confidence interval [CI], 1.60 to 2.74; P<0.001) and of heart failure (adjusted hazard ratio, 2.20; 95% CI, 1.66 to 2.90; P<0.001) in this study group. Increased risk associated with higher levels of troponin T was evident well below the limit of detection of conventional cardiac troponin T assays and below the 99th percentile of values in a healthy population. There was no association between troponin T levels as measured with the highly sensitive assay and the incidence of myocardial infarction (adjusted hazard ratio, 1.16; 95% CI, 0.97 to 1.40; P=0.11). CONCLUSIONS: After adjustment for other independent prognostic indicators, cardiac troponin T concentrations as measured with a highly sensitive assay were significantly associated with the incidence of cardiovascular death and heart failure but not with myocardial infarction in patients with stable coronary artery disease.