Betamethasone Exposure and Neonatal Respiratory Morbidity Among Late Preterm Births by Planned Mode of Delivery and Gestational Age.

OBJECTIVE: To estimate the effect of late preterm antenatal steroids on the risk of respiratory morbidity among subgroups of patients on the basis of the planned mode of delivery and gestational age at presentation. METHODS: This was a secondary analysis of the ALPS (Antenatal Late Preterm Steroid) Trial, a multicenter trial conducted within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network of individuals with singleton gestations and without preexisting diabetes who were at high risk for late preterm delivery (34-36 weeks of gestation). We fit binomial regression models to estimate the risk of respiratory morbidity, with and without steroid administration, by gestational age and planned mode of delivery at the time of presentation. We assumed a homogeneous effect of steroids on the log-odds scale, as was reported in the ALPS trial. The primary outcome was neonatal respiratory morbidity, as defined in the ALPS Trial. RESULTS: The analysis included 2,825 patients at risk for late preterm birth. The risk of respiratory morbidity varied significantly by planned mode of delivery (adjusted risk ratio [RR] 1.90, 95% CI, 1.55-2.33 for cesarean delivery vs vaginal delivery) and week of gestation at presentation (adjusted RR 0.56, 95% CI, 0.50-0.63). For those planning cesarean delivery and presenting in the 34th week of gestation, the risk of neonatal respiratory morbidity was 39.4% (95% CI, 30.8-47.9%) without steroids and 32.0% (95% CI, 24.6-39.4%) with steroids. In contrast, for patients presenting in the 36th week and planning vaginal delivery, the risk of neonatal respiratory morbidity was 6.9% (95% CI, 5.2-8.6%) without steroids and 5.6% (95% CI, 4.2-7.0%) with steroids. CONCLUSION: The absolute risk difference of neonatal respiratory morbidity between those exposed and those unexposed to late preterm antenatal steroids varies considerably by gestational age at presentation and planned mode of delivery. Because only communicating the relative risk reduction of antenatal steroids for respiratory morbidity may lead to an inaccurate perception of benefit, more patient-specific estimates of risk expected with and without treatment may inform shared decision making.

Unresolved alterations in bile acid composition and dyslipidemia in maternal and cord blood after ursodeoxycholic acid treatment for intrahepatic cholestasis of pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is characterized by elevated plasma bile acid levels. ICP is linked to adverse metabolic outcomes, including a reported increased risk of gestational diabetes. The standard therapeutic approach for managing ICP is treatment with ursodeoxycholic acid (UDCA) and induction of labor prior to 40 weeks of gestation. To investigate bile acid and metabolic parameters after UDCA treatment, we enrolled 12 ICP patients with singleton pregnancies-half with and half without gestational diabetes-and 7 controls. Our study reveals that after UDCA treatment, notwithstanding a reduction in total bile acid and ALT levels, imbalances persist in the cholic acid (CA) to chenodeoxycholic acid (CDCA) ratio in maternal and cord blood plasma. This indicates a continued dysregulation of bile acid metabolism despite therapeutic intervention. Maternal plasma lipid analysis showed a distinct maternal dyslipidemia pattern among ICP patients, marked by elevated cholesterol levels on VLDL particles and heightened triglyceride concentrations on LDL particles, persisting even after UDCA treatment. Cord plasma lipid profiles in ICP patients exhibited elevated triglyceride and free fatty acid levels alongside a tendency toward increased ß-hydroxybutyrate. The changes in lipid metabolism in both maternal and cord blood correlated with the high CA/CDCA ratio, but not total bile acid levels or gestational diabetes status. Understanding the imbalances in maternal and cord bile acid and lipid profiles that persist after standard UDCA therapy provides insights for improving management strategies and mitigating the long-term consequences of ICP. News and Noteworthy: This study uncovers that despite ursodeoxycholic acid treatment, intrahepatic cholestasis of pregnancy (ICP) is associated with increases in the ratio of cholic acid to chenodeoxycholic acid in both maternal and cord blood, suggesting ongoing dysregulation of bile acid metabolism. The high cholic to chenodeoxycholic acid ratio is correlated with maternal dyslipidemia and high cord blood lipids. These findings may inform more targeted approaches to managing ICP.

Association Between Influenza Vaccination and SARS-CoV-2 Infection.

BACKGROUND: Recent data in nonpregnant individuals suggest a protective effect of influenza vaccination against SARS-CoV-2 infection and its severity. OBJECTIVES: Our primary objective was to evaluate whether influenza vaccination was associated with COVID-19 severity and pregnancy and neonatal outcomes among those infected with SARS-CoV-2. The secondary objective was to examine the association between influenza vaccination and SARS-CoV-2 infection. STUDY DESIGN: Secondary analysis of a multicenter retrospective cohort of pregnant people who tested positive for SARS-CoV-2 between March and August 2020, and a cohort of random deliveries during the same time period. The associations between 2019 influenza vaccination and the primary outcome of moderate-to-critical COVID-19 as well as maternal and perinatal outcomes were examined among all people who tested positive for SARS-CoV-2 between March and August 2020. The association between 2019 influenza vaccination and having a positive SARS-CoV-2 test was examined among a cohort of individuals who delivered on randomly selected dates between March and August 2020. Univariable and multivariable analyses were performed. RESULTS: Of 2325 people who tested positive for SARS-CoV-2, 1068 (45.9%) were vaccinated against influenza in 2019. Those who received the influenza vaccine were older, leaner, more likely to have private insurance, and identify as White or Hispanic. They were less likely to smoke tobacco and identify as Black. Overall, 419 (18.0%) had moderate, 193 (8.3%) severe, and 52 (2.2%) critical COVID-19. There was no association between influenza vaccination and moderate-to-critical COVID-19 (29.2% vs. 28.0%, adjusted OR 1.10, 95% CI 0.90-1.34) or adverse maternal and perinatal outcomes among those who tested positive. Of 8152 people who delivered in 2020, 4658 (57.1%) received the influenza vaccine. Prior vaccination was not associated with a difference in the odds of SARS-CoV-2 infection (3.8% vs. 4.2%, adjusted OR 0.94, 95% CI 0.74-1.19). CONCLUSION: Prior influenza vaccination was not associated with decreased severity of COVID-19 or lower odds of SARS-CoV-2 infection in pregnancy.

Diabetic Ketoacidosis and Adverse Outcomes Among Pregnant Individuals With Pregestational Diabetes in the United States, 2010-2020.

OBJECTIVE: To assess the frequency of, risk factors for, and adverse outcomes associated with diabetic ketoacidosis (DKA) at delivery hospitalization among individuals with pregestational diabetes (type 1 and 2 diabetes mellitus) and secondarily to evaluate the frequency of and risk factors for antepartum and postpartum hospitalizations for DKA. METHODS: We conducted a serial, cross-sectional study using the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project Nationwide Readmissions Database from 2010 to 2020 of pregnant individuals with pregestational diabetes hospitalized for delivery. The exposures were 1) sociodemographic and clinical risk factors for DKA and 2) DKA. The outcomes were DKA at delivery hospitalization, maternal morbidity (nontransfusion severe maternal morbidity (SMM), critical care procedures, cardiac complications, acute renal failure, and transfusion), and adverse pregnancy outcomes (preterm birth, hypertensive disorders of pregnancy, and cesarean delivery) and secondarily DKA at antepartum and postpartum hospitalizations. RESULTS: Of 392,796 deliveries in individuals with pregestational diabetes (27.2% type 1 diabetes, 72.8% type 2 diabetes), there were 4,778 cases of DKA at delivery hospitalization (89.1% type 1 diabetes, 10.9% type 2 diabetes). The frequency of DKA at delivery hospitalization was 1.2% (4.0% with type 1 diabetes, 0.2% with type 2 diabetes), and the mean annual percentage change was 10.8% (95% CI, 8.2-13.2%). Diabetic ketoacidosis at delivery hospitalization was significantly more likely among those who had type 1 diabetes compared with those with type 2 diabetes, who were younger in age, who delivered at larger and metropolitan hospitals, and who had Medicaid insurance, lower income, multiple gestations, and prior psychiatric illness. Diabetic ketoacidosis during the delivery hospitalization was associated with an increased risk of nontransfusion SMM (20.8% vs 2.4%, adjusted odds ratio [aOR] 8.18, 95% CI, 7.20-9.29), critical care procedures (7.3% vs 0.4%, aOR 15.83, 95% CI, 12.59-19.90), cardiac complications (7.8% vs 0.8%, aOR 8.87, 95% CI, 7.32-10.76), acute renal failure (12.3% vs 0.7%, aOR 9.78, 95% CI, 8.16-11.72), and transfusion (6.2% vs 2.2%, aOR 2.27, 95% CI, 1.87-2.75), as well as preterm birth (31.9% vs 13.5%, aOR 2.41, 95% CI, 2.17-2.69) and hypertensive disorders of pregnancy (37.4% vs 28.1%, aOR 1.11, 95% CI, 1.00-1.23). In secondary analyses, the overall frequency of antepartum DKA was 3.1%, and the mean annual percentage change was 4.1% (95% CI, 0.3-8.6%); the overall frequency of postpartum DKA was 0.4%, and the mean annual percentage change was 3.5% (95% CI, -1.6% to 9.6%). Of 3,092 antepartum hospitalizations among individuals with DKA, 15.7% (n=485) had a recurrent case of DKA at delivery hospitalization. Of 1,419 postpartum hospitalizations among individuals with DKA, 20.0% (n=285) previously had DKA at delivery hospitalization. The above risk factors for DKA at delivery hospitalization were similar for DKA at antepartum and postpartum hospitalizations. CONCLUSION: The frequency of DKA at delivery hospitalization and antepartum hospitalizations for DKA increased between 2010 and 2020 among deliveries in individuals with pregestational diabetes in the United States. Diabetic ketoacidosis is associated with an increased risk of maternal morbidity and adverse pregnancy outcomes. Risk factors for DKA at delivery were similar to those for DKA during the antepartum and postpartum periods.

Aspirin resistance in pregnancy is associated with reduced interleukin-2 (IL-2) concentrations in maternal serum: Implications for aspirin prophylaxis for preeclampsia.

OBJECTIVES: To evaluate the impact of aspirin resistance on the incidence of preeclampsia and maternal serum biomarker levels in pregnant individuals at high-risk of preeclampsia receiving low dose aspirin (LDA). STUDY DESIGN: We performed a secondary analysis of a randomized, placebo-controlled trial of LDA (60 mg daily) for preeclampsia prevention in high-risk individuals (N = 524) on pregnancy outcomes and concentrations of PLGF, IL-2, IL-6, thromboxane B2 (TXB2), sTNF-R1 and sTNF-R2 from maternal serum. MAIN OUTCOME MEASURES: LDA-resistant individuals were defined as those having a TXB2 concentration >10 ng/ml or <75 % reduction in concentration at 24-28 weeks after LDA administration. Comparisons of outcomes were performed using a Fisher's Exact Test. Mean concentrations of maternal serum biomarkers were compared using a Student's t-test. Pearson correlation was calculated for all pairwise biomarkers. Longitudinal analysis across gestation was performed using linear mixed-effects models accounting for repeated measures and including BMI and maternal age as covariates. RESULTS: We classified 60/271 (22.1 %) individuals as LDA-resistant, 179/271 (66.1 %) as LDA-sensitive, and 32/271 (11.8 %) as non-adherent. The prevalence of preeclampsia was not significantly different between the LDA and placebo groups (OR = 1.43 (0.99-2.28), p-value = 0.12) nor between LDA-sensitive and LDA-resistant individuals (OR = 1.27 (0.61-2.8), p-value = 0.60). Mean maternal serum IL-2 concentrations were significantly lower in LDA-resistant individuals relative to LDA-sensitive individuals (FDR < 0.05). CONCLUSIONS: These results suggest a potential role for IL-2 in the development of preeclampsia modulated by an individuals' response to aspirin, presenting an opportunity to optimize aspirin prophylaxis on an individual level to reduce the incidence of preeclampsia.

Gestational Weight Gain and Neonatal Biometry during the COVID-19 Pandemic: A Multicenter Observational Cohort.

OBJECTIVE: This study aimed to test the hypothesis that being pregnant and delivering during the coronavirus disease 2019 (COVID-19) pandemic was associated with changes in gestational weight gain (GWG) or frequency of small- (SGA) or large-for-gestational-age (LGA) neonates. STUDY DESIGN: Secondary analysis of a multicenter observational cohort comparing pregnant people who delivered during the COVID-19 pandemic (June-December 2020) to people who delivered prior to the pandemic (March-December 2019). Those with multiple gestations, fetuses with major congenital anomalies, implausible GWG values, unavailable body mass index (BMI), or who were severe acute respiratory syndrome coronavirus-2-positive were excluded. The primary outcome was frequency of optimal recommended GWG based on prepregnancy BMI. Neonatal outcomes included birth weight, ponderal index, and frequency of SGA, LGA, and small head circumference for live births. Multivariable regression analysis was used to assess associations between exposure to the pandemic and outcomes. RESULTS: A total of 10,717 pregnant people were included in our analysis. A total of 4,225 pregnant people were exposed to the pandemic and 6,492 pregnant people delivered prior to the COVID-19 pandemic. Pregnant people exposed to the pandemic were older and more likely to have gestational diabetes. The frequency of appropriate GWG was 28.0% during the pandemic and 27.6% before the pandemic (adjusted odds ratio [aOR]: 1.02, 95% confidence interval [CI]: 0.93-1.11). Excessive GWG was more likely (54.9 vs. 53.1%; aOR: 1.08, 95% CI: 1.001-1.17), and inadequate GWG was less likely during the pandemic (17.0 vs. 19.3%; aOR: 0.86, 95% CI: 0.77-0.95). The frequency of SGA was 5.4% during the pandemic and 6.1% before the pandemic (aOR: 0.90, 95% CI: 0.76-1.06), and the frequency of LGA was 16.0% during the pandemic versus 15.0% before the pandemic (aOR: 1.06, 95% CI: 0.95-1.18). Other neonatal outcomes including birth weight percentile (62.1 [35.8-83.2] vs. 60.2 [34.4-82.2]; adjusted mean difference (aMD) = 1.50, 95% CI: -0.28 to 3.29), ponderal index (2.6 g/cm3 [2.4-2.8] in both groups; aMD = 0.01, 95% CI: 0.00-0.02), and small head circumference for livebirths (<10th percentile [8.2 vs. 8.1%; aOR: 1.03, 95% CI: 0.89-1.19], <3rd percentile [3.5 vs. 3.1%; aOR: 1.16, 95% CI: 0.93-1.44]) were similar between groups as well. CONCLUSION: Being pregnant and delivering during the COVID-19 pandemic was associated with a higher likelihood of excessive GWG and a lower likelihood of inadequate GWG. KEY POINTS: · Delivering during the COVID-19 pandemic was associated with higher likelihood of excessive GWG.. · Delivering during the COVID-19 pandemic was associated with lower likelihood of inadequate GWG.. · COVID-19 pandemic was not associated with changes in frequency of SGA or LGA..

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..

Uterus and cervix anatomical changes and cervix stiffness evolution throughout pregnancy.

The coordinated biomechanical performance, such as uterine stretch and cervical barrier function, within maternal reproductive tissues facilitates healthy human pregnancy and birth. Quantifying normal biomechanical function and detecting potentially detrimental biomechanical dysfunction (e.g., cervical insufficiency, uterine overdistention, premature rupture of membranes) is difficult, largely due to minimal data on the shape and size of maternal anatomy and material properties of tissue across gestation. This study quantitates key structural features of human pregnancy to fill this knowledge gap and facilitate three-dimensional modeling for biomechanical pregnancy simulations to deeply explore pregnancy and childbirth. These measurements include the longitudinal assessment of uterine and cervical dimensions, fetal weight, and cervical stiffness in 47 low-risk pregnancies at four time points during gestation (late first, middle second, late second, and middle third trimesters). The uterine and cervical size were measured via 2-dimensional ultrasound, and cervical stiffness was measured via cervical aspiration. Trends in uterine and cervical measurements were assessed as time-course slopes across pregnancy and between gestational time points, accounting for specific participants. Patient-specific computational solid models of the uterus and cervix, generated from the ultrasonic measurements, were used to estimate deformed uterocervical volume. Results show that for this low-risk cohort, the uterus grows fastest in the inferior-superior direction from the late first to middle second trimester and fastest in the anterior-posterior and left-right direction between the middle and late second trimester. Contemporaneously, the cervix softens and shortens. It softens fastest from the late first to the middle second trimester and shortens fastest between the late second and middle third trimester. Alongside the fetal weight estimated from ultrasonic measurements, this work presents holistic maternal and fetal patient-specific biomechanical measurements across gestation.

Lasix for the prevention of de novo postpartum hypertension: a randomized placebo-controlled trial (LAPP Trial).

BACKGROUND: Birthing people with de novo postpartum hypertensive disorders continue to be among the populations at highest risk for severe maternal morbidity. Randomized controlled trials demonstrate a benefit of oral loop diuretics in decreasing postpartum hypertensive morbidity in patients with an antenatal diagnosis of preeclampsia. It is not known whether this same therapy benefits patients at risk for new-onset postpartum hypertension. OBJECTIVE: This study aimed to evaluate whether oral furosemide can reduce the risk for de novo postpartum hypertension among high-risk birthing people by reducing postdelivery blood pressure. STUDY DESIGN: From October 2021 to April 2022, we conducted a randomized triple-masked placebo-controlled clinical trial of individuals at high risk for de novo postpartum hypertension at a single university-based tertiary care medical center. A total of 82 postpartum patients with no antenatal diagnosis of chronic hypertension or a hypertensive disorder of pregnancy who were at high risk for the development of de novo postpartum hypertension based on a prespecified risk factor algorithm were enrolled after childbirth. The participants were randomly assigned in a 1:1 ratio to a 5-day course of 20-mg oral furosemide daily or identical-appearing placebo starting within 8 hours of delivery. Participants were followed for 6 weeks postpartum using Bluetooth-enabled remote blood pressure monitoring and electronic surveys. The primary outcome was mean arterial pressure averaged over the 24 hours before discharge or the 24 hours before antihypertensive therapy initiation. The study was powered to detect a 5 mm Hg difference in average mean arterial pressure (standard deviation, 6.4 mm Hg) with 90% power at an alpha of 0.05, requiring a sample size of 41 per group. Secondary outcomes included the rate of de novo postpartum hypertension, readmission data, other measures of hypertensive and maternal morbidity, breastfeeding data, and drug-related neonatal outcomes. RESULTS: The primary outcome was assessed in 80 of the 82 participants. Baseline characteristics were similar between the groups. There was no significant difference in average mean arterial pressure in the 24 hours before discharge (or antihypertensive initiation) in the furosemide group (88.9±7.4 mm Hg) compared with the placebo group (86.8±7.1 mm Hg; absolute difference, 2.1 mm Hg; 95% confidence interval, -1.2 to 5.3). Of the 79 participants for whom secondary outcomes were assessed, 10% (n=8) developed de novo postpartum hypertension and 9% (n=7) were initiated on antihypertensive therapy. Rates were not significantly different between the groups (P=.71 and P>.99, respectively). CONCLUSION: De novo postpartum hypertension is a common phenomenon among at-risk patients, warranting close monitoring for severe hypertension and other maternal morbidity. There is insufficient evidence to suggest that furosemide reduces average mean arterial pressure in the 24 hours before discharge from the delivery hospitalization (or antihypertensive medication initiation) compared with placebo.

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.

Antenatal Late Preterm Steroids: The Evolution of the ALPS Trial.

The Antenatal Late Preterm Steroids (ALPS) trial was designed to address respiratory morbidity common in infants born late preterm. The study was published in April, 2016 and, shortly thereafter, changed clinical practice in obstetrics in the United States. The following chapter describes the ALPS trial study design in detail, including the background leading to the trial, the study outcomes, and the initial findings of the long-term follow-up study. The ALPS story would not be complete without Elizabeth Thom, PhD, who died before her time. Her brilliance largely contributed to the design of the ALPS trial.

From Mentee to Leader-Thoughts From an Immigrant.

The editors' request to reflect on one's career is a daunting one. There is an inherent implication that some pivotal point has been achieved, and usually, it's the point of retirement. There is also an assumption that the author can be impartial, though some writers will be laudatory and others excessively critical. I tend to fall in the latter group, and I firmly believe that it stems from my experience as an immigrant. What follows will be my thoughts about my experiences as a mentee and eventual mentor framed in the context of my upbringing.

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.

Behavioural disorders after prenatal exposure to anaesthesia for maternal surgery.

BACKGROUND: The association between prenatal exposure to general anaesthesia for maternal surgery during pregnancy and subsequent risk of disruptive or internalising behavioural disorder diagnosis in the child has not been well-defined. METHODS: A nationwide sample of pregnant women linked to their liveborn infants was evaluated using the Medicaid Analytic eXtract (MAX, 1999-2013). Multivariate matching was used to match each child prenatally exposed to general anaesthesia owing to maternal appendectomy or cholecystectomy during pregnancy with five unexposed children. The primary outcome was diagnosis of a disruptive or internalising behavioural disorder in children. Secondary outcomes included diagnoses for a range of other neuropsychiatric disorders. RESULTS: We matched 34,271 prenatally exposed children with 171,355 unexposed children in the database. Prenatally exposed children were more likely than unexposed children to receive a diagnosis of a disruptive or internalising behavioural disorder (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.23-1.40). For secondary outcomes, increased hazards of disruptive (HR, 1.32; 95% CI, 1.24-1.41) and internalising (HR, 1.36; 95% CI, 1.20-1.53) behavioural disorders were identified, and also increased hazards of attention-deficit/hyperactivity disorder (HR, 1.32; 95% CI, 1.22-1.43), behavioural disorders (HR, 1.28; 95% CI, 1.14-1.42), developmental speech or language disorders (HR, 1.16; 95% CI, 1.05-1.28), and autism (HR, 1.31; 95% CI, 1.05-1.64). CONCLUSIONS: Prenatal exposure to general anaesthesia is associated with a 31% increased risk for a subsequent diagnosis of a disruptive or internalising behavioural disorder in children. Caution is advised when making any clinical decisions regarding care of pregnant women, as avoidance of necessary surgery during pregnancy can have detrimental effects on mothers and their children.

Maternal and Neonatal Morbidities by Race in College-Educated Women.

Objective Non-Hispanic black and Hispanic women experience significantly higher adverse maternal and neonatal outcomes compared with non-Hispanic white women. The purpose of this study is to explore whether disparities in obstetric outcomes exist by race among women who are college-educated. Study Design This is a retrospective cohort study from a multicenter observational cohort of women undergoing cesarean delivery. Women were defined as "college-educated" if they reported completion of a 4-year college degree. Race/ethnicity was categorized as non-Hispanic white, non-Hispanic black, Hispanic, Asian, Native American, or unknown. The primary outcome was a composite of maternal morbidity, and a composite of neonatal morbidity was evaluated as a secondary outcome. A multivariable logistic regression model was then utilized to assess associations of race with the primary and secondary outcomes. Results A total of 2,540 women were included in the study. After adjusting for potential confounding variables, maternal morbidity was found to be significantly higher for college-educated non-Hispanic black women compared with non-Hispanic white women (odds ratio [OR] 1.77, 95% confidence interval [CI] 1.12-2.80). The incidence of neonatal morbidity was significantly higher for non-Hispanic black (OR 1.91, 95% CI 1.31-2.79) and Hispanic (OR 3.34, 95% CI 2.23-5.01) women. Conclusion In this cohort, the odds of cesarean-related maternal and neonatal morbidities were significantly higher for college-educated non-Hispanic black women, compared with their non-Hispanic white counterparts. This demonstrates that even among women with higher level education, racial and ethnic disparities persist in obstetric outcomes.

Regional Variation in Antenatal Late Preterm Steroid Use Following the ALPS Trial.

Importance: The publication of the Antenatal Late Preterm Steroids (ALPS) trial in February 2016 demonstrated that antenatal administration of betamethasone in the late preterm period (between 34 to 36 weeks of gestation) for individuals with a high risk of delivery decreased neonatal respiratory morbidity. National estimates have suggested the trial did change obstetric practice, but little is known if the evidence was adopted uniformly or equitably. Objective: To assess regional variation in the use of late preterm steroids after the publication of the Antenatal Late Preterm Steroids (ALPS) Trial and to understand factors associated with a region's pace of adoption. Design, Setting, and Participants: This cross-sectional study used US natality data from February 2015 to October 2017 from hospital referral regions (HRRs) within the US. Inclusion criteria included live-born, nonanomalous, singleton, late preterm (34 to 36 completed weeks of gestation) neonates born to individuals without pregestational diabetes. This study was conducted from November 15, 2022, to January 13, 2023. Main Outcome and Measures: HRRs were categorized as either a slower adopter or faster adopter of antenatal late preterm steroids based on the observed vs expected pace of antenatal steroid adoption in a 1-year period after the trial's dissemination. Patient and regional factors hypothesized a priori to be associated with the uptake of late preterm steroids were compared between faster and slower adopters. Comparisons were made using Student t test or Wilcoxon rank-sum test, as appropriate. A multivariable logistic regression was constructed to identify factors associated with faster adopter status in the postperiod. Results: There were 666 097 late preterm births in 282 HRRs. The mean (SD) maternal age in HRRs was 27.9 (1.2) years. The median (IQR) percentage of births by race categories in HRRs for patients identifying as American Indian or Alaskan Native was 0.5% (0.2%-1.3%); Asian or Pacific Islander, 3.0% (1.7%-5.3%); Black, 12.9% (5.1%-29.1%); and White, 78.6% (66.6%-87.0%). The median percentage of births in HRRs to patients of Hispanic ethnicity was 11.2% (6.3%-27.4%). In this study, 136 HRRs (48.2%) were classified as faster adopters and 146 (51.8%) were classified as slower adopters. Faster adopters increased their steroid use by 12.1 percentage points (from 5.9% to 18.0%) compared with a 5.5 percentage point increase (from 3.7% to 9.2%) among slower adopters (P < .001). Most examined patient and regional factors were not associated with a region's pace of adoption, with the exception of the regional prevalence of prior preterm birth (adjusted odds ratio [aOR], 2.04 [95% CI, 1.48-2.82]) and the percentage of deliveries at 34 to 35 weeks of gestation (aOR, 0.68 [95% CI, 0.47-0.99]) compared with 36 weeks. Conclusions and Relevance: In this cross-sectional study, there was widespread geographic variation in the adoption of antenatal steroid administration for late preterm births that largely remained unexplained by population factors. These findings should prompt further investigations to barriers to timely or equitable access to new evidence-based practices and guide future dissemination strategies with the goal of more uniform adoption.

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..

Low-dose aspirin and racial disparities in spontaneous preterm delivery in low-risk individuals.

BACKGROUND: Preterm birth is a leading cause of perinatal morbidity and mortality. There are significant racial disparities in the rates of preterm delivery in the United States, with Black individuals at disproportionately higher risk than their White counterparts. Although low-dose aspirin is currently under investigation for reducing the rates of preterm delivery, limited data are available on how the use of low-dose aspirin might affect racial and ethnic disparities in the rates of preterm delivery. OBJECTIVE: Our group and others have shown that low-dose aspirin decreases spontaneous preterm delivery in low-risk parturients. This study aimed to examine whether the relationship between low-dose aspirin and the risk of spontaneous preterm delivery is modified by race and ethnicity. STUDY DESIGN: This was a secondary analysis of a randomized clinical trial examining low-dose aspirin for preeclampsia prevention in low-risk nulliparous individuals. The parent trial defined low risk as the absence of preexisting hypertension or other medical comorbidities. Participants received 60-mg aspirin or placebo between 13 and 25 weeks of gestation. Here, multiple pregnancies, fetal anomalies, terminations or abortions at <20 weeks of gestation, and participants with previous miscarriages were excluded. Our exposure, race and ethnicity, was self-reported in the parent trial and categorized as non-Hispanic White, Hispanic, non-Hispanic Black, and other. The primary outcome was spontaneous preterm delivery at <34 weeks of gestation; the secondary outcomes included spontaneous preterm delivery at <37 weeks of gestation and all preterm deliveries at <34 and <37 weeks of gestation. Fit logistic regression models were used to examine how the use of low-dose aspirin modified the relationship between race and ethnicity and preterm delivery, adjusting for confounders. Furthermore, sensitivity analyses were performed to compare the rates of preterm delivery by race and ethnicity. RESULTS: Of note, 2528 of 3171 parent study participants were included in this analysis. Of the participants, 425 (16.8%) were White, 819 (32.4%) were Hispanic, 1265 (50%) were Black, and 19 (0.8%) were other. The baseline characteristics differed among racial and ethnic groups, including maternal age, body mass index, education level, marital status, tobacco and alcohol use, and pregnancy loss. The rate of spontaneous preterm delivery at <34 weeks of gestation was significantly higher in Black participants (2.8%) than in White (1.2%) and Hispanic (1.2%) participants (P=.04). Logistical regression analysis showed that Black race was no longer an independent risk factor for spontaneous preterm delivery at <34 weeks of gestation when controlling for low-dose aspirin (adjusted odds ratio, 1.71; 95% confidence interval, 0.67-4.40). A similar pattern was found for spontaneous preterm delivery at <37 weeks of gestation and preterm delivery at <34 and <37 weeks of gestation. In our sensitivity analyses, spontaneous preterm delivery at <34 weeks of gestation differed by race and ethnicity in the placebo group (P=.01) but did not differ in the low-dose aspirin group (P=.90). CONCLUSION: The use of low-dose aspirin mitigated racial disparities in spontaneous preterm delivery at <34 weeks of gestation. Additional investigation is warranted to assess the reproducibility of our findings.