Prediction of COVID-19 Severity at Delivery after Asymptomatic or Mild COVID-19 during Pregnancy.

OBJECTIVE: This study aimed to develop a prediction model that estimates the probability that a pregnant person who has had asymptomatic or mild coronavirus disease 2019 (COVID-19) prior to delivery admission will progress in severity to moderate, severe, or critical COVID-19. STUDY DESIGN: This was a secondary analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients who delivered from March through December 2020 at hospitals across the United States. Those eligible for this analysis presented for delivery with a current or previous asymptomatic or mild SARS-CoV-2 infection. The primary outcome was moderate, severe, or critical COVID-19 during the delivery admission through 42 days postpartum. The prediction model was developed and internally validated using stratified cross-validation with stepwise backward elimination, incorporating only variables that were known on the day of hospital admission. RESULTS: Of the 2,818 patients included, 26 (0.9%; 95% confidence interval [CI], 0.6-1.3%) developed moderate-severe-critical COVID-19 during the study period. Variables in the prediction model were gestational age at delivery admission (adjusted odds ratio [aOR], 1.15; 95% CI, 1.08-1.22 per 1-week decrease), a hypertensive disorder in a prior pregnancy (aOR 3.05; 95% CI, 1.25-7.46), and systolic blood pressure at admission (aOR, 1.04; 95% CI, 1.02-1.05 per mm Hg increase). This model yielded an area under the receiver operating characteristic curve of 0.82 (95% CI, 0.72-0.91). CONCLUSION: Among individuals presenting for delivery who had asymptomatic-mild COVID-19, gestational age at delivery admission, a hypertensive disorder in a prior pregnancy, and systolic blood pressure at admission were predictive of delivering with moderate, severe, or critical COVID-19. This prediction model may be a useful tool to optimize resources for SARS-CoV-2-infected pregnant individuals admitted for delivery. KEY POINTS: · Three factors were associated with delivery with more severe COVID-19.. · The developed model yielded an area under the receiver operating characteristic curve of 0.82 and model fit was good.. · The model may be useful tool for SARS-CoV-2 infected pregnancies admitted for delivery..

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.

Prediction of metabolic syndrome following a first pregnancy.

BACKGROUND: The prevalence of metabolic syndrome is rapidly increasing in the United States. We hypothesized that prediction models using data obtained during pregnancy can accurately predict the future development of metabolic syndrome. OBJECTIVE: This study aimed to develop machine learning models to predict the development of metabolic syndrome using factors ascertained in nulliparous pregnant individuals. STUDY DESIGN: This was a secondary analysis of a prospective cohort study (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be Heart Health Study [nuMoM2b-HHS]). Data were collected from October 2010 to October 2020, and analyzed from July 2023 to October 2023. Participants had in-person visits 2 to 7 years after their first delivery. The primary outcome was metabolic syndrome, defined by the National Cholesterol Education Program Adult Treatment Panel III criteria, which was measured within 2 to 7 years after delivery. A total of 127 variables that were obtained during pregnancy were evaluated. The data set was randomly split into a training set (70%) and a test set (30%). We developed a random forest model and a lasso regression model using variables obtained during pregnancy. We compared the area under the receiver operating characteristic curve for both models. Using the model with the better area under the receiver operating characteristic curve, we developed models that included fewer variables based on SHAP (SHapley Additive exPlanations) values and compared them with the original model. The final model chosen would have fewer variables and noninferior areas under the receiver operating characteristic curve. RESULTS: A total of 4225 individuals met the inclusion criteria; the mean (standard deviation) age was 27.0 (5.6) years. Of these, 754 (17.8%) developed metabolic syndrome. The area under the receiver operating characteristic curve of the random forest model was 0.878 (95% confidence interval, 0.846-0.909), which was higher than the 0.850 of the lasso model (95% confidence interval, 0.811-0.888; P<.001). Therefore, random forest models using fewer variables were developed. The random forest model with the top 3 variables (high-density lipoprotein, insulin, and high-sensitivity C-reactive protein) was chosen as the final model because it had the area under the receiver operating characteristic curve of 0.867 (95% confidence interval, 0.839-0.895), which was not inferior to the original model (P=.08). The area under the receiver operating characteristic curve of the final model in the test set was 0.847 (95% confidence interval, 0.821-0.873). An online application of the final model was developed (https://kawakita.shinyapps.io/metabolic/). CONCLUSION: We developed a model that can accurately predict the development of metabolic syndrome in 2 to 7 years after delivery.

Applying Tension to the Transcervical Foley Balloon and Delivery Times in Term Nulliparous Women Undergoing Induction of Labor: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effects of applying tension to a transcervical Foley balloon on delivery time in term nulliparous patients undergoing labor induction. METHODS: This cluster randomized clinical trial included 279 term nulliparous women presenting for labor induction with a plan for cervical ripening through transcervical Foley balloon placement. Participants were assigned to either the tension group (n=138) or the no-tension group (n=141) on the basis of randomized, weekly clusters (26 total clusters). The primary outcome measured was the time from initial Foley balloon insertion to delivery. Secondary outcomes included cesarean delivery rates, peripartum infection, and neonatal intensive care unit (NICU) admission. Our prior data suggested that delivery time in the tension group would be about 1,053 minutes. We estimated a sample size of 260 (130 per group, 26 clusters) on the basis of a 25% difference, power of 80%, and two-sided α of 0.05. RESULTS: A total of 279 term nulliparous patients were included in the analysis. The median time from Foley placement to delivery was 1,596 minutes (range 430-3,438 minutes) for the tension group and 1,621 minutes (range 488-3,323 minutes) for the no-tension group ( P =.8); similar results were noted for time to vaginal delivery. No significant differences were observed in the secondary outcomes, including the rates of cesarean delivery (34.1% vs 29.8%, P =.7), peripartum infection, and NICU admission, between the two groups. CONCLUSION: Applying tension to a transcervical Foley balloon in term nulliparous women undergoing labor induction did not significantly reduce delivery time or improve secondary outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT05404776.

Early vs delayed amniotomy following transcervical Foley balloon in the induction of labor: a randomized clinical trial.

BACKGROUND: The optimal timing of amniotomy during labor induction is a topic of ongoing debate due to the potential risks associated with both amniotomy and prolonged labor. As such, individuals in the field of obstetrics and gynecology must carefully evaluate the associated benefits and drawbacks of this procedure. While amniotomy can expedite the labor process, it may also lead to complications such as umbilical cord prolapse, fetal distress, and infection. Therefore, a careful and thorough examination of the risks and benefits of amniotomy during labor induction is essential in making an informed decision regarding the optimal timing of this procedure. OBJECTIVE: This study aimed to determine if an amniotomy within 2 hours after Foley balloon removal reduced the duration of active labor and time taken to achieve vaginal delivery when compared with an amniotomy ≥4 hours after balloon removal among term pregnant women who underwent labor induction. STUDY DESIGN: This was an open-label, randomized controlled trial that was conducted at a single academic center from October 2020 to March 2023. Term participants who were eligible for preinduction cervical ripening with a Foley balloon were randomized into 2 groups, namely the early amniotomy (rupture of membranes within 2 hours after Foley balloon removal) and delayed amniotomy (rupture of membranes performed more than 4 hours after Foley balloon removal) groups. Randomization was stratified by parity. The primary outcome was time from Foley balloon insertion to active phase of labor. Secondary outcomes, including time to delivery, cesarean delivery rates, and maternal and neonatal complications, were analyzed using intention-to-treat and per-protocol analyses. RESULTS: Of the 150 participants who consented and were enrolled, 149 were included in the analysis. In the intention-to-treat population, an early amniotomy did not significantly shorten the time between Foley balloon insertion and active labor when compared with a delayed amniotomy (885 vs 975 minutes; P=.08). An early amniotomy was associated with a significantly shorter time from Foley balloon placement to active labor in nulliparous individuals (1211; 584-2340 vs 1585; 683-2760; P=.02). When evaluating the secondary outcomes, an early amniotomy was associated with a significantly shorter time to active labor onset (312.5 vs 442.5 minutes; P=.02) and delivery (484 vs 587 minutes; P=.03) from Foley balloon removal with a higher rate of delivery within 36 hours (96% vs 85%; P=.03). Individuals in the early amniotomy group reached active labor 1.5 times faster after Foley balloon insertion than those in the delayed group (hazard ratio, 1.5; 95% confidence interval, 1.1-2.2; P=.02). Those with an early amniotomy also reached vaginal delivery 1.5 times faster after Foley balloon removal than those in the delayed group (hazard ratio, 1.5; 95% confidence interval, 1-2.2; P=.03). A delayed amniotomy was associated with a higher rate of postpartum hemorrhage (0% vs 9.5%; P=.01). No significant differences were observed in the cesarean delivery rates, length of hospital stay, maternal infection, or neonatal outcomes. CONCLUSION: Although an early amniotomy does not shorten the time from Foley balloon insertion to active labor, it shortens time from Foley balloon removal to active labor and delivery without increasing complications. The increased postpartum hemorrhage rate in the delayed amniotomy group suggests increased risks with delayed amniotomy.

Postpartum pharmacologic thromboprophylaxis and complications in a US cohort.

BACKGROUND: Venous thromboembolism accounts for approximately 9% of pregnancy-related deaths in the United States. National guidelines recommend postpartum risk stratification and pharmacologic prophylaxis in at-risk individuals. Knowledge on modern rates of postpartum pharmacologic thromboprophylaxis and its associated risks is limited. OBJECTIVE: This study aimed to describe the rate of, and factors associated with, initiation of postpartum pharmacologic prophylaxis for venous thromboembolism, and to assess associated adverse outcomes. STUDY DESIGN: This was a secondary analysis of a multicenter cohort of individuals delivering on randomly selected days at 17 US hospitals (2019-2020). Medical records were reviewed by trained and certified personnel. Those with an antepartum diagnosis of venous thromboembolism, receiving antepartum anticoagulation, or known SARS-CoV-2 infection were excluded. The primary outcome was use of postpartum pharmacologic thromboprophylaxis. Secondary outcomes included bleeding complications, surgical site infection, hospital readmission, and venous thromboembolism through 6 weeks postpartum. The rate of thromboprophylaxis administration was assessed by mode of delivery, institution, and continuance to the outpatient setting. Multivariable regression models were developed using k-fold cross-validation with stepwise backward elimination to evaluate factors associated with thromboprophylaxis administration. Univariable and multivariable logistic models with propensity score covariate adjustment were performed to assess the association between thromboprophylaxis administration and adverse outcomes. RESULTS: Of 21,114 individuals in the analytical cohort, 11.9% (95% confidence interval, 11.4%-12.3%) received postpartum pharmacologic thromboprophylaxis; the frequency of receipt was 29.8% (95% confidence interval, 28.7%-30.9%) following cesarean and 3.5% (95% confidence interval, 3.2%-3.8%) following vaginal delivery. Institutional rates of prophylaxis varied from 0.21% to 34.8%. Most individuals (83.3%) received thromboprophylaxis only as inpatients. In adjusted analysis, cesarean delivery (adjusted odds ratio, 19.17; 95% confidence interval, 16.70-22.00), hysterectomy (adjusted odds ratio, 15.70; 95% confidence interval, 4.35-56.65), and obesity (adjusted odds ratio, 3.45; 95% confidence interval, 3.02-3.95) were the strongest factors associated with thromboprophylaxis administration. Thromboprophylaxis administration was not associated with surgical site infection (0.9% vs 0.6%; odds ratio, 1.48; 95% confidence interval, 0.80-2.74), bleeding complications (0.2% vs 0.1%; odds ratio, 2.60; 95% confidence interval, 0.99-6.80), or postpartum readmission (0.9% vs 0.3%; adjusted odds ratio, 1.38; 95% confidence interval, 0.68-2.81). The overall rate of venous thromboembolism was 0.06% (95% confidence interval, 0.03%-0.10%) and was higher in those receiving prophylaxis (0.2%) compared with those not receiving prophylaxis (0.04%). CONCLUSION: Approximately 1 in 10 patients received postpartum pharmacologic thromboprophylaxis in this US cohort. Rates of prophylaxis varied widely by institution. Cesarean delivery, hysterectomy, and obesity were predominant factors associated with postpartum thromboprophylaxis administration.

Breastfeeding Initiation, Duration, and Associated Factors Among People With Hepatitis C Virus Infection.

OBJECTIVE: To characterize breastfeeding behaviors and identify factors associated with breastfeeding initiation among people with hepatitis C virus (HCV) infection. METHODS: We conducted a secondary analysis of a multicenter observational cohort of pregnant people with singleton gestations and HCV seropositivity. This analysis includes individuals with data on breastfeeding initiation and excludes those with human immunodeficiency virus (HIV) co-infection. The primary outcome was self-reported initiation of breastfeeding or provision of expressed breast milk. Secondary outcomes included duration of breastfeeding. Demographic and obstetric characteristics were compared between those who initiated breastfeeding and those who did not to identify associated factors. Univariable and multivariable analyses were performed. RESULTS: Overall, 579 individuals (75.0% of participants in the parent study) were included. Of those, 362 (62.5%) initiated breastfeeding or provided breast milk to their infants, with a median duration of breastfeeding of 1.4 months (interquartile range 0.5-6.0). People with HCV viremia , defined as a detectable viral load at any point during pregnancy, were less likely to initiate breastfeeding than those who had an undetectable viral load (59.4 vs 71.9%, adjusted odds ratio [aOR] 0.61, 95% CI, 0.41-0.92). People with private insurance were more likely to initiate breastfeeding compared with those with public insurance or no insurance (80.0 vs 60.1%; aOR 2.43, 95% CI, 1.31-4.50). CONCLUSION: Although HCV seropositivity is not a contraindication to breastfeeding regardless of viral load, rates of breastfeeding initiation were lower among people with HCV viremia than among those with an undetectable viral load. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT01959321 .

Immunosuppressant Medications in Pregnancy.

Pregnant patients are often on immunosuppressant medications, most commonly to manage transplantation or autoimmune disorders. Most immunosuppressant agents, including tacrolimus, corticosteroids, azathioprine, and calcineurin inhibitors, are safe during pregnancy and lactation. However, mycophenolic acid is associated with higher risks of birth defects and should be avoided in pregnancy. Tacrolimus, the commonly used drug in transplantation medicine and autoimmune disorders, requires monitoring of serum levels for dose adjustment, particularly during pregnancy. Although no pregnancy-specific therapeutic range exists, the general target range is 5-15 ng/mL, and pregnant patients may require higher doses to achieve therapeutic levels. Adherence to prescribed immunosuppressive regimens is crucial to prevent graft rejection and autoimmune disorder flare-ups. This review aims to provide essential information about the use of immunosuppressant medications in pregnant individuals. With a rising number of pregnant patients undergoing organ transplantations or having autoimmune disorders, it is important to understand the implications of the use of these medications during pregnancy.

Association of Mild Iodine Insufficiency during Pregnancy with Child Neurodevelopment in Patients with Subclinical Hypothyroidism or Hypothyroxinemia.

OBJECTIVE: Our objective was to evaluate whether iodine status in pregnant patients with either subclinical hypothyroidism or hypothyroxinemia in the first half of pregnancy is associated with measures of behavior and neurodevelopment in children through the age of 5 years. STUDY DESIGN: This is a secondary analysis of a multicenter study consisting of two randomized, double-masked, placebo-controlled treatment trials conducted in parallel. Patients with a singleton gestation before 20 weeks' gestation underwent thyroid screening using serum thyrotropin and free thyroxine. Participants with subclinical hypothyroidism or hypothyroxinemia were randomized to levothyroxine replacement or an identical placebo. At randomization, maternal urine was collected and stored for subsequent urinary iodine excretion analysis. Urinary iodine concentrations greater than 150 µg/L were considered iodine sufficient, and concentrations of 150 µg/L or less were considered iodine insufficient. The primary outcome was a full-scale intelligence quotient (IQ) score at the age of 5 years, the general conceptual ability score from the Differential Ability Scales-II at the age of 3 if IQ was not available, or death before 3 years. RESULTS: A total of 677 pregnant participants with subclinical hypothyroidism and 526 with hypothyroxinemia were randomized. The primary outcome was available in 1,133 (94%) of children. Overall, 684 (60%) of mothers were found to have urinary iodine concentrations >150 µg/L. Children of iodine-sufficient participants with subclinical hypothyroidism had similar primary outcome scores when compared to children of iodine-insufficient participants (95 [84-105] vs. 96 [87-109], P adj = 0.73). After adjustment, there was also no difference in IQ scores among children of participants with hypothyroxinemia at 5 to 7 years of age (94 [85 - 102] and 91 [81 - 100], Padj 1/4 0.11). Treatment with levothyroxine was not associated with neurodevelopmental or behavioral outcomes regardless of maternal iodine status (p > 0.05). CONCLUSION: Maternal urinary iodine concentrations ≤150 µg/L were not associated with abnormal cognitive or behavioral outcomes in offspring of participants with either subclinical hypothyroidism or hypothyroxinemia. KEY POINTS: · Most pregnant patients with subclinical thyroid disease are iodine sufficient.. · Mild maternal iodine insufficiency is not associated with lower offspring IQ at 5 years.. · Iodine supplementation in subclinical thyroid disease is unlikely to improve IQ..

Association between stillbirth and severe maternal morbidity.

BACKGROUND: Severe maternal morbidity has been increasing in the past few decades. Few studies have examined the risk of severe maternal morbidity among individuals with stillbirths vs individuals with live-birth deliveries. OBJECTIVE: This study aimed to examine the prevalence and risk of severe maternal morbidity among individuals with stillbirths vs individuals with live-birth deliveries during delivery hospitalization as a primary outcome and during the postpartum period as a secondary outcome. STUDY DESIGN: This was a retrospective cohort study using birth and fetal death certificate data linked to hospital discharge records from California (2008-2018), Michigan (2008-2020), Missouri (2008-2014), Pennsylvania (2008-2014), and South Carolina (2008-2020). Relative risk regression analysis was used to examine the crude and adjusted relative risks of severe maternal morbidity along with 95% confidence intervals among individuals with stillbirths vs individuals with live-birth deliveries, adjusting for birth year, state of residence, maternal sociodemographic characteristics, and the obstetric comorbidity index. RESULTS: Of the 8,694,912 deliveries, 35,012 (0.40%) were stillbirths. Compared with individuals with live-birth deliveries, those with stillbirths were more likely to be non-Hispanic Black (10.8% vs 20.5%); have Medicaid (46.5% vs 52.0%); have pregnancy complications, including preexisting diabetes mellitus (1.1% vs 4.3%), preexisting hypertension (2.3% vs 6.2%), and preeclampsia (4.4% vs 8.4%); have multiple pregnancies (1.6% vs 6.2%); and reside in South Carolina (7.4% vs 11.6%). During delivery hospitalization, the prevalence rates of severe maternal morbidity were 791 cases per 10,000 deliveries for stillbirths and 154 cases per 10,000 deliveries for live-birth deliveries, whereas the prevalence rates for nontransfusion severe maternal morbidity were 502 cases per 10,000 deliveries for stillbirths and 68 cases per 10,000 deliveries for live-birth deliveries. The crude relative risk for severe maternal morbidity was 5.1 (95% confidence interval, 4.9-5.3), whereas the adjusted relative risk was 1.6 (95% confidence interval, 1.5-1.8). For nontransfusion severe maternal morbidity among stillbirths vs live-birth deliveries, the crude relative risk was 7.4 (95% confidence interval, 7.0-7.7), whereas the adjusted relative risk was 2.0 (95% confidence interval, 1.8-2.3). This risk was not only elevated among individuals with stillbirth during the delivery hospitalization but also through 1 year after delivery (severe maternal morbidity adjusted relative risk, 1.3; 95% confidence interval, 1.1-1.4; nontransfusion severe maternal morbidity adjusted relative risk, 1.2; 95% confidence interval, 1.1-1.3). CONCLUSION: Stillbirth was found to be an important contributor to severe maternal morbidity.

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

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

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

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

Cannabis Exposure and Adverse Pregnancy Outcomes Related to Placental Function.

Importance: Cannabis use is increasing among reproductive-age individuals and the risks associated with cannabis exposure during pregnancy remain uncertain. Objective: To evaluate the association between maternal cannabis use and adverse pregnancy outcomes known to be related to placental function. Design, Setting, and Participants: Ancillary analysis of nulliparous individuals treated at 8 US medical centers with stored urine samples and abstracted pregnancy outcome data available. Participants in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort were recruited from 2010 through 2013; the drug assays and analyses for this ancillary project were completed from June 2020 through April 2023. Exposure: Cannabis exposure was ascertained by urine immunoassay for 11-nor-9-carboxy-Δ9-tetrahydrocannabinol using frozen stored urine samples from study visits during the pregnancy gestational age windows of 6 weeks and 0 days to 13 weeks and 6 days (visit 1); 16 weeks and 0 days to 21 weeks and 6 days (visit 2); and 22 weeks and 0 days to 29 weeks and 6 days (visit 3). Positive results were confirmed with liquid chromatography tandem mass spectrometry. The timing of cannabis exposure was defined as only during the first trimester or ongoing exposure beyond the first trimester. Main Outcome and Measure: The dichotomous primary composite outcome included small-for-gestational-age birth, medically indicated preterm birth, stillbirth, or hypertensive disorders of pregnancy ascertained by medical record abstraction by trained perinatal research staff with adjudication of outcomes by site investigators. Results: Of 10 038 participants, 9257 were eligible for this analysis. Of the 610 participants (6.6%) with cannabis use, 32.4% (n = 197) had cannabis exposure only during the first trimester and 67.6% (n = 413) had ongoing exposure beyond the first trimester. Cannabis exposure was associated with the primary composite outcome (25.9% in the cannabis exposure group vs 17.4% in the no exposure group; adjusted relative risk, 1.27 [95% CI, 1.07-1.49]) in the propensity score-weighted analyses after adjustment for sociodemographic characteristics, body mass index, medical comorbidities, and active nicotine use ascertained via urine cotinine assays. In a 3-category cannabis exposure model (no exposure, exposure only during the first trimester, or ongoing exposure), cannabis use during the first trimester only was not associated with the primary composite outcome; however, ongoing cannabis use was associated with the primary composite outcome (adjusted relative risk, 1.32 [95% CI, 1.09-1.60]). Conclusions and Relevance: In this multicenter cohort, maternal cannabis use ascertained by biological sampling was associated with adverse pregnancy outcomes related to placental dysfunction.

Researching COVID to enhance recovery (RECOVER) pregnancy study: Rationale, objectives and design.

IMPORTANCE: Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER-Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads. METHODS: RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators. DISCUSSION: RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

Body Mass Index, Adverse Pregnancy Outcomes, and Cardiovascular Disease Risk.

BACKGROUND: Obesity is a well-established risk factor for both adverse pregnancy outcomes (APOs) and cardiovascular disease (CVD). However, it is not known whether APOs are mediators or markers of the obesity-CVD relationship. This study examined the association between body mass index, APOs, and postpartum CVD risk factors. METHODS: The sample included adults from the nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be) Heart Health Study who were enrolled in their first trimester (6 weeks-13 weeks 6 days gestation) from 8 United States sites. Participants had a follow-up visit at 3.7 years postpartum. APOs, which included hypertensive disorders of pregnancy, preterm birth, small-for-gestational-age birth, and gestational diabetes, were centrally adjudicated. Mediation analyses estimated the association between early pregnancy body mass index and postpartum CVD risk factors (hypertension, hyperlipidemia, and diabetes) and the proportion mediated by each APO adjusted for demographics and baseline health behaviors, psychosocial stressors, and CVD risk factor levels. RESULTS: Among 4216 participants enrolled, mean±SD maternal age was 27±6 years. Early pregnancy prevalence of overweight was 25%, and obesity was 22%. Hypertensive disorders of pregnancy occurred in 15%, preterm birth in 8%, small-for-gestational-age birth in 11%, and gestational diabetes in 4%. Early pregnancy obesity, compared with normal body mass index, was associated with significantly higher incidence of postpartum hypertension (adjusted odds ratio, 1.14 [95% CI, 1.10-1.18]), hyperlipidemia (1.11 [95% CI, 1.08-1.14]), and diabetes (1.03 [95% CI, 1.01-1.04]) even after adjustment for baseline CVD risk factor levels. APOs were associated with higher incidence of postpartum hypertension (1.97 [95% CI, 1.61-2.40]) and hyperlipidemia (1.31 [95% CI, 1.03-1.67]). Hypertensive disorders of pregnancy mediated a small proportion of the association between obesity and incident hypertension (13% [11%-15%]) and did not mediate associations with incident hyperlipidemia or diabetes. There was no significant mediation by preterm birth or small-for-gestational-age birth. CONCLUSIONS: There was heterogeneity across APO subtypes in their association with postpartum CVD risk factors and mediation of the association between early pregnancy obesity and postpartum CVD risk factors. However, only a small or nonsignificant proportion of the association between obesity and CVD risk factors was mediated by any of the APOs, suggesting APOs are a marker of prepregnancy CVD risk and not a predominant cause of postpartum CVD risk.

Perinatal Outcomes Associated With Management of Stage 1 Hypertension.

OBJECTIVE: To evaluate the association between maternal blood pressure (BP) below 130/80 mm Hg compared with 130-139/80-89 mm Hg and pregnancy outcomes. METHODS: We conducted a planned secondary analysis of CHAP (Chronic Hypertension and Pregnancy), an open label, multicenter, randomized controlled trial. Participants with mean BP below 140/90 mm Hg were grouped as below 130/80 mm Hg compared with 130-139/80-89 mm Hg by averaging postrandomization clinic BP throughout pregnancy. The primary composite outcome was preeclampsia with severe features, indicated preterm birth before 35 weeks of gestation, placental abruption, or fetal or neonatal death. The secondary outcome was small for gestational age (SGA). RESULTS: Of 2,408 patients in CHAP, 2,096 met study criteria; 1,328 had mean BP 130-139/80-89 mm Hg and 768 had mean BP below 130/80 mm Hg. Participants with mean BP below 130/80 mm Hg were more likely to be older, on antihypertensive medication, in the active treatment arm, and to have lower BP at enrollment. Mean clinic BP below 130/80 mm Hg was associated with lower frequency of the primary outcome (16.0% vs 35.8%, adjusted relative risk 0.45; 95% CI 0.38-0.54) as well as lower risk of severe preeclampsia and indicated birth before 35 weeks of gestation. There was no association with SGA. CONCLUSION: In pregnant patients with mild chronic hypertension, mean BP below 130/80 mm Hg was associated with improved pregnancy outcomes without increased risk of SGA. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02299414.

Genetic Predisposition to Adverse Neurodevelopmental Outcome of Extremely Low Birth Weight Infants.

OBJECTIVE: This study aimed to evaluate whether there are genetic variants associated with adverse neurodevelopmental outcomes in extremely low birth weight (ELBW) infants. STUDY DESIGN: We conducted a candidate gene association study in two well-defined cohorts of ELBW infants (<1,000 g). One cohort was for discovery and the other for replication. The discovery case-control analysis utilized anonymized DNA samples and evaluated 1,614 single-nucleotide polymorphisms (SNPs) in 145 genes concentrated in inflammation, angiogenesis, brain development, and oxidation pathways. Cases were children who died by age one or who were diagnosed with cerebral palsy (CP) or neurodevelopmental delay (Bayley II mental developmental index [MDI] or psychomotor developmental index [PDI] < 70) by 18 to 22 months. Controls were survivors with normal neurodevelopment. We assessed significant epidemiological variables and SNPs associated with the combined outcome of CP or death, CP, mental delay (MDI < 70) and motor delay (PDI < 70). Multivariable analyses adjusted for gestational age at birth, small for gestational age, sex, antenatal corticosteroids, multiple gestation, racial admixture, and multiple comparisons. SNPs associated with adverse neurodevelopmental outcomes with p < 0.01 were selected for validation in the replication cohort. Successful replication was defined as p < 0.05 in the replication cohort. RESULTS: Of 1,013 infants analyzed (452 cases, 561 controls) in the discovery cohort, 917 were successfully genotyped for >90% of SNPs and passed quality metrics. After adjusting for covariates, 26 SNPs with p < 0.01 for one or more outcomes were selected for replication cohort validation, which included 362 infants (170 cases and 192 controls). A variant in SERPINE1, which encodes plasminogen activator inhibitor (PAI1), was associated with the combined outcome of CP or death in the discovery analysis (p = 4.1 × 10-4) and was significantly associated with CP or death in the replication cohort (adjusted odd ratio: 0.4; 95% confidence interval: 0.2-1.0; p = 0.039). CONCLUSION: A genetic variant in SERPINE1, involved in inflammation and coagulation, is associated with CP or death among ELBW infants. KEY POINTS: · Early preterm and ELBW infants have dramatically increased risks of CP and developmental delay.. · A genetic variant in SERPINE1 is associated with CP or death among ELBW infants.. · The SERPINE1 gene encodes the serine protease inhibitor plasminogen activator inhibitor..