Hereditary cancer testing in a diverse sample across three breast imaging centers.

PURPOSE: Up to 10% of all breast cancers (BC) are attributed to inherited pathogenic variants (PV) in BC susceptibility genes; however, most carriers of PVs remain unidentified. Here, we sought to determine the yield of hereditary cancer gene PVs among diverse women attending breast imaging centers, who could benefit from enhanced surveillance and/or risk reduction interventions. METHODS: This cross-sectional retrospective cohort study included consecutive women, unselected for personal or family cancer history, who were offered genetic testing for hereditary cancer genes at the time of breast imaging at three centers (November 2020-March 2022). RESULTS: Among 1943 patients (median age: 66 years), self-reported race/ethnicity was White (34.5%), Hispanic (27.7%), African American (17.9%), Asian (4.5%), Ashkenazi Jewish (0.6%), Other (3.5%), and missing (13.0%). Thirty-nine patients (2%) were identified as carriers of a PV in an autosomal dominant clinically actionable hereditary breast and ovarian cancer (HBOC)-related or Lynch syndrome gene, most frequently, BRCA2 (6/39; 15.4%), PALB2 (8/39; 20.5%), CHEK2 (10/39; 25.6%), and PMS2 (5/39; 12.8%). Of the 34 PVs with known race/ethnicity, 47% were detected among non-White patients. Overall, 354/1,943 (18.2%) of patients met NCCN guidelines for HBOC gene testing and only 15/39 (38.5%) patients with an autosomal dominant clinically actionable PV met guidelines. CONCLUSION: This population health approach extended the reach of genetic cancer risk assessment in a diverse population and highlighted the limits of a guideline-based approach. This may help address inequity in access to risk-appropriate screening and cancer prevention.

The Role of cfDNA Biomarkers and Patient Data in the Early Prediction of Preeclampsia: Artificial Intelligence Model.

OBJECTIVE: Accurate individualized assessment of preeclampsia risk enables the identification of patients most likely to benefit from initiation of low-dose aspirin at 12-16 weeks' gestation when there is evidence for its effectiveness, as well as guiding appropriate pregnancy care pathways and surveillance. The primary objective of this study was to evaluate the performance of artificial neural network models for the prediction of preterm preeclampsia (<37 weeks' gestation) using patient characteristics available at the first antenatal visit and data from prenatal cell-free DNA (cfDNA) screening. Secondary outcomes were prediction of early onset preeclampsia (<34 weeks' gestation) and term preeclampsia (≥37 weeks' gestation). METHODS: This secondary analysis of a prospective, multicenter, observational prenatal cfDNA screening study (SMART) included singleton pregnancies with known pregnancy outcomes. Thirteen patient characteristics that are routinely collected at the first prenatal visit and two characteristics of cfDNA, total cfDNA and fetal fraction (FF), were used to develop predictive models for early-onset (<34 weeks), preterm (<37 weeks), and term (≥37 weeks) preeclampsia. For the models, the 'reference' classifier was a shallow logistic regression (LR) model. We also explored several feedforward (non-linear) neural network (NN) architectures with one or more hidden layers and compared their performance with the LR model. We selected a simple NN model built with one hidden layer and made up of 15 units. RESULTS: Of 17,520 participants included in the final analysis, 72 (0.4%) developed early onset, 251 (1.4%) preterm, and 420 (2.4%) term preeclampsia. Median gestational age at cfDNA measurement was 12.6 weeks and 2,155 (12.3%) had their cfDNA measurement at 16 weeks' gestation or greater. Preeclampsia was associated with higher total cfDNA (median 362.3 versus 339.0 copies/ml cfDNA; p<0.001) and lower FF (median 7.5% versus 9.4%; p<0.001). The expected, cross-validated area under the curve (AUC) scores for early onset, preterm, and term preeclampsia were 0.782, 0.801, and 0.712, respectively for the LR model, and 0.797, 0.800, and 0.713, respectively for the NN model. At a screen-positive rate of 15%, sensitivity for preterm preeclampsia was 58.4% (95% CI 0.569, 0.599) for the LR model and 59.3% (95% CI 0.578, 0.608) for the NN model.The contribution of both total cfDNA and FF to the prediction of term and preterm preeclampsia was negligible. For early-onset preeclampsia, removal of the total cfDNA and FF features from the NN model was associated with a 6.9% decrease in sensitivity at a 15% screen positive rate, from 54.9% (95% CI 52.9-56.9) to 48.0% (95% CI 45.0-51.0). CONCLUSION: Routinely available patient characteristics and cfDNA markers can be used to predict preeclampsia with performance comparable to other patient characteristic models for the prediction of preterm preeclampsia. Both LR and NN models showed similar performance.

Expanding midwifery care in the United States: Implications for clinical outcomes and cost.

BACKGROUND: This study compared clinical and financial outcomes for low-risk birthing people between those attended by midwives and those attended by obstetricians during hospital births. METHODS: We conducted a retrospective cohort analysis of births from January 1, 2016 to December 31, 2020 at hospitals participating in a perinatal quality improvement collaborative, Obstetrical Care Outcomes Assessment Program (OB COAP), in the Northwest region of the United States and estimated risk ratios using a multivariate regression approach with a modified Poisson binomial for mode of delivery, labor interventions, and newborn outcomes comparing midwife-led to obstetrician-led care. Using publicly available data on average costs of vaginal and cesarean births, we then extrapolated the cost differences in care between midwives and obstetricians. RESULTS: Births in the midwife group were less likely to be associated with induction (17.6% vs. 20.3% RR 0.74; 95% CI 0.70-0.78), epidural use (58.9% vs. 76.3% RR 0.78; 95% CI 0.77-0.80), and episiotomy (2.2% vs. 3.4% RR 0.68; 95% CI 0.58-0.81). Cesarean birth was also lower in the midwifery group (7.8% vs. 12.3% RR 0.68, 95% CI 0.62-0.73), without a corresponding increase in risk in adverse neonatal outcomes. We estimated that expanding midwifery care to 100% of low-risk births across the United States could save as much as $340 million per year. CONCLUSIONS: Midwifery care is associated with a lower risk of cesarean birth and other interventions versus care provided by obstetricians and is therefore likely lower-cost.

The impact of the Antenatal Late Preterm Steroids trial on the administration of antenatal corticosteroids.

BACKGROUND: In 2016 the Antenatal Late Preterm Steroids study was published, demonstrating that antenatal corticosteroid therapy given to women at risk of late preterm delivery reduces respiratory morbidity in infants. However, the administration of antenatal corticosteroid therapy in late-preterm infants remains controversial. Late-preterm infants do not suffer from the same rates of morbidity as early-preterm infants, and the short-term benefits of antenatal corticosteroid therapy are less pronounced; consequently, the risk of possible harm is more difficult to balance. OBJECTIVE: This study aimed to evaluate the association between the publication of the Antenatal Late Preterm Steroids study or the subsequent changes in guidelines and the rates of antenatal corticosteroid therapy administration in late-preterm infants in the United States. STUDY DESIGN: Data analyzed were publicly available US birth certificate data from January 1, 2016 to December 31, 2018. An interrupted time series design was used to analyze the association between publication of the Antenatal Late Preterm Steroids study and changes in monthly rates of antenatal corticosteroid administration in late preterm gestation (34+0 to 36+6 weeks). Births at 28+0 to 31+6 weeks' gestation were used as a control. Antenatal corticosteroid therapy administration in women with births at 32+0 to 34+6 weeks was explored to analyze whether the intervention influenced antenatal corticosteroid therapy administration in women in the subgroup approaching 34 weeks' gestation. Antenatal corticosteroid therapy administration in women with term births (>37 weeks' gestation) was analyzed to explore if the intervention influenced the number of term babies exposed to antenatal corticosteroid therapy. Our regression model allowed analysis of both step and slope changes. February 2016 was chosen as the intervention period. RESULTS: Our sample size was 18,031,950 total births. Of these, 1,056,047 were births at 34+0 to 36+6 weeks' gestation, 123,788 at 28+0 to 31+6 weeks, 153,708 at 32 to 33 weeks, and 16,602,699 were term births. There were 95,708 births at <28 weeks' gestation. There was a statistically significant increase in antenatal corticosteroid therapy administration rates in late preterm births following the online publication of the Antenatal Late Preterm Steroids study (adjusted incidence rate ratio, 1.48; 95% confidence interval, 1.36-1.61; P=.00). A significant increase in antenatal corticosteroid therapy administration rates was also seen in full-term births following the online publication of the Antenatal Late Preterm Steroids study. No significant changes were seen in antenatal corticosteroid administration rates in gestational age groups of 32+0 to 33+6 weeks or 28+0 to 31+6 weeks. CONCLUSION: Online publication of the Antenatal Late Preterm Steroids study was associated with an immediate and sustained increase in the rates of antenatal corticosteroid therapy administration in late preterm births across the United States, demonstrating a swift and successful implementation of the Antenatal Late Preterm Steroids study guidance into clinical practice. However, there is an unnecessary increase in full-term infants receiving antenatal corticosteroid therapy. Given that the long-term consequences of antenatal corticosteroid therapy are yet to be elucidated, efforts should be made to minimize the number of infants unnecessarily exposed to antenatal corticosteroid therapy.

Antepartum and intrapartum stillbirth rates across gestation: a cross-sectional study using the revised foetal death reporting system in the U.S.

BACKGROUND: There is a renewed call to address preventable foetal deaths in high-income countries, especially where progress has been slow. The Centers for Disease Control and Prevention released publicly, for the first time, the initiating cause and estimated timing of foetal deaths in 2014. The objective of this study is to describe risk and characteristics of antepartum versus intrapartum stillbirths in the U.S., and frequency of pathological examination to determine cause. METHODS: We conducted a cross-sectional study of singleton births (24-43 weeks) using 2014 U.S. Fetal Death and Natality data available from the National Center for Health Statistics. The primary outcome was timing of death (antepartum (n = 6200), intrapartum (n = 453), and unknown (n = 5403)). Risk factors of interest included maternal sociodemographic, behavioural, medical and obstetric factors, along with foetal sex. We estimated gestational week-specific stillbirth hazard, risk factors for intrapartum versus antepartum stillbirth using multivariable log-binomial regression models, conditional probabilities of intrapartum and antepartum stillbirth at each gestational week, and frequency of pathological examination by timing of death. RESULTS: The gestational age-specific stillbirth hazard was approximately 2 per 10,000 foetus-weeks among preterm gestations and > 3 per 10,000 foetus-weeks among term gestations. Both antepartum and intrapartum stillbirth risk increased in late-term and post-term gestations. The risk of intrapartum versus antepartum stillbirth was higher among those without a prior live birth, relative to those with at least one prior live birth (RR 1.32; 95% CI 1.08-1.61) and those with gestational hypertension, relative to those with no report of gestational hypertension (RR 1.47; 95% CI 1.09-1.96), and lower among Black, relative to white, individuals (RR 0.70; 95% CI 0.55-0.89). Pathological examination was not performed/planned in 25% of known antepartum stillbirths and 29% of known intrapartum stillbirths. CONCLUSION: These findings suggest greater stillbirth risk in the late-term and post-term periods. Primiparous mothers had greater risk of intrapartum than antepartum still birth, suggesting the need for intrapartum interventions for primiparous mothers in this phase of pregnancy to prevent some intrapartum foetal deaths. Efforts are needed to improve understanding, prevention and investigation of foetal deaths as well as improve stillbirth data quality and completeness in the United States.

Impact of the COVID-19 pandemic on perinatal care and outcomes in the United States: An interrupted time series analysis.

BACKGROUND: Hospitals quickly adapted perinatal care to mitigate SARS-CoV-2 transmission at the onset of the COVID-19 pandemic. The objective of this study was to estimate the impact of pandemic-related hospital policy changes on perinatal care and outcomes in one region of the United States. METHODS: This interrupted time series analysis used retrospective data from consecutive singleton births at 15 hospitals in the Pacific Northwest from 2017 to 2020. The primary outcomes were those hypothesized to be affected by pandemic-related hospital policies and included labor induction, epidural use, oxytocin augmentation, mode of delivery, and early discharge (<48 hours after cesarean and <24 hours after vaginal births). Secondary outcomes included preterm birth, severe maternal morbidity, low 5-minute Apgar score, neonatal intensive care unit (NICU) admission, and 30-day readmission. Segmented Poisson regression models estimated the outcome level shift changes after the pandemic onset, controlling for underlying trends, seasonality, and stratifying by parity. RESULTS: No statistically significant changes were detected in intrapartum interventions or mode of delivery after onset of the pandemic. Early discharge increased for all births following cesarean and vaginal birth. Newborn readmission rates increased but only among nulliparas (aRR: 1.49, 95%CI: 1.17, 1.91). Among multiparas, decreases were observed in preterm birth (aRR: 0.90, 95%CI: 0.84, 0.96), low 5-minute Apgar score (aRR: 0.75, 95%CI: 0.68, 0.81), and term NICU admission rates (aRR: 0.85, 95%CI: 0.80, 0.91). CONCLUSIONS: Increases in early discharge and newborn readmission rates among nulliparas suggest a need for more postpartum support during the pandemic. Decreases in preterm birth and term NICU admission among multiparas may have implications beyond the pandemic and deserve further study.

A Simple Approach to Adjust for Case-Mix When Comparing Institutional Cesarean Birth Rates.

OBJECTIVE: This study aimed to develop a validated model to predict intrapartum cesarean in nulliparous women and to use it to adjust for case-mix when comparing institutional laboring cesarean birth (CB) rates. STUDY DESIGN: This multicenter retrospective study used chart-abstracted data on nulliparous, singleton, term births over a 7-year period. Prelabor cesareans were excluded. Logistic regression was used to predict the probability of CB for individual pregnancies. Thirty-five potential predictive variables were evaluated including maternal demographics, prepregnancy health, pregnancy characteristics, and newborn weight and gender. Models were trained on 21,017 births during 2011 to 2015 (training cohort), and accuracy assessed by prediction on 15,045 births during 2016 to 2017 (test cohort). RESULTS: Six variables delivered predictive success equivalent to the full set of 35 variables: maternal weight, height, and age, gestation at birth, medically-indicated induction, and birth weight. Internal validation within the training cohort gave a receiver operator curve with area under the curve (ROC-AUC) of 0.722. External validation using the test cohort gave ROC-AUC of 0.722 (0.713-0.731 confidence interval). When comparing observed and predicted CB rates at 16 institutions in the test cohort, five had significantly lower than predicted rates and three had significantly higher than predicted rates. CONCLUSION: Six routine clinical variables used to adjust for case-mix can identify outliers when comparing institutional CB rates.

Maternal and newborn outcomes with elective induction of labor at term.

BACKGROUND: A growing body of evidence supports improved or not worsened birth outcomes with nonmedically indicated induction of labor at 39 weeks gestation compared with expectant management. This evidence includes 2 recent randomized control trials. However, concern has been raised as to whether these studies are applicable to a broader US pregnant population. OBJECTIVE: Our goal was to compare outcomes for electively induced births at ≥39 weeks gestation with those that were not electively induced. STUDY DESIGN: We conducted a retrospective cohort study using chart-abstracted data on births from January 1, 2012, to December 31, 2017, at 21 hospitals in the Northwest United States. The study was restricted to singleton cephalic hospital births at 39+0-42+6 weeks gestation. Exclusions included previous cesarean birth, missing data for delivery type or gestational week at birth, antepartum stillbirth, cesarean birth without any attempt at vaginal birth, fetal anomaly, gestational diabetes mellitus, prepregnancy diabetes mellitus, and prepregnancy hypertension. The rate of cesarean birth for elective inductions at both 39 and 40 weeks gestation was compared with the rate in all other on-going pregnancies in the same gestational week. Maternal outcomes (operative vaginal birth, shoulder dystocia, 3rd- or 4th-degree perineal laceration, pregnancy-related hypertension, and postpartum hemorrhage) and newborn infant outcomes (macrosomia, 5-minute Apgar <7, resuscitation at delivery, intubation, respiratory complications, and neonatal intensive care unit admission) were also compared between elective inductions and on-going pregnancies at 39 and 40 weeks gestation. Logistic regression modeling was used to produce odds ratios for outcomes with adjustment for maternal age and body mass index. Results were stratified by parity and gestational week at birth. Duration of hospital stay (admission to delivery, delivery to discharge, and total stay) were compared between elective inductions and on-going pregnancies. RESULTS: A total of 55,694 births were included in the study cohort: 4002 elective inductions at ≥39+0 weeks gestation and 51,692 births at 39+0-42+6 weeks gestation that were not electively induced. In nulliparous women, elective induction at 39 weeks gestation was associated with a decreased likelihood of cesarean birth (14.7% vs 23.2%; adjusted odds ratio, 0.61; 95% confidence interval, 0.41-0.89) and an increased rate of operative vaginal birth (18.5% vs 10.8%; adjusted odds ratio, 1.8; 95% confidence interval, 1.28-2.54) compared with on-going pregnancies. In multiparous women, cesarean birth rates were similar in the elective inductions and on-going pregnancies. Elective induction at 39 weeks gestation was associated with a decreased likelihood of pregnancy-related hypertension in nulliparous (2.2% vs 7.3%; adjusted odds ratio, 0.28; 95% confidence interval, 0.11-0.68) and multiparous women (0.9% vs 3.5%; adjusted odds ratio, 0.24; 95% confidence interval, 0.15-0.38). Term elective induction was not associated with any statistically significant increase in adverse newborn infant outcomes. Elective induction of labor at 39 weeks gestation was associated with increased time from admission to delivery for both nulliparous (1.3 hours; 95% confidence interval, 0.2-2.3) and multiparous women (3.4 hours; 95% confidence interval, 3.2-3.6). CONCLUSION: Elective induction of labor at 39 weeks gestation is associated with a decrease in cesarean birth in nulliparous women, decreased pregnancy-related hypertension in multiparous and nulliparous women, and increased time in labor and delivery. How to use this information remains the challenge.

Assessing the potential impact of extending antenatal steroids to the late preterm period.

BACKGROUND: In 2016, guidance statements were issued by the Society for Maternal-Fetal Medicine and the American Congress of Obstetricians and Gynecologists about extending antenatal steroid use to selected late preterm singleton pregnancies. OBJECTIVE: We sought to review antenatal steroid use prior to the 2016 guidance statements and assess the potential impact of these. STUDY DESIGN: This cohort study used chart-abstracted data from singleton deliveries from Jan. 1, 2012, through March 31, 2016, at 12 centers participating in the Obstetrics Clinical Outcomes Assessment Program, a quality initiative in Washington State. Pregnancies with missing gestation at delivery, fetal anomalies, or antepartum demise were excluded. Antenatal steroid use prior to the 2016 guidance was evaluated based on the percentage of early preterm deliveries (23+0-33+6 weeks) and the percentage of all pregnancies that received antenatal steroids. Newborn complication rates were calculated for late preterm deliveries (34+0+0-36+6 weeks), grouped by whether they would be potentially eligible or ineligible for antenatal steroids based on the 2016 guidance statements. RESULTS: The opportunity for antenatal steroids was missed in 21.8% (226/1034) of early preterm deliveries and of all those who received antenatal steroids, 32.2% (614/1908) delivered at term. Of preterm deliveries, 74% (n = 2942) were in the late preterm period. In all, 80% (n = 2363) of late preterm deliveries were potentially eligible for antenatal steroids and 60% of these (n = 1411) delivered at 36 weeks. The rate of respiratory complications in newborns delivering at 34 and 35 weeks was higher in the group potentially eligible for late preterm antenatal steroids compared to those in the ineligible group. Of those delivering at 36 weeks, no differences were detected in prevalence of respiratory complications by potential eligibility for antenatal steroids; however, compared with the ineligible group, those potentially eligible had a lower risk of neonatal intensive care unit admission (P < .001). More than two thirds (69%; 171/248) of newborn respiratory complications among late preterm deliveries potentially eligible for antenatal steroids occurred in those delivering at 34-35 weeks. The highest rate of respiratory complications was in those ineligible for antenatal steroids due to prepregnancy diabetes or chorioamnionitis, regardless of gestational age at delivery. CONCLUSION: Careful consideration of which pregnancies should receive late preterm antenatal steroids and how to identify these pregnancies is important to optimize benefits and mitigate potential risks of this intervention.

Reproductive Carrier Screening: Identifying Families at Risk for Familial Hypercholesterolemia in the United States.

BACKGROUND: Familial hypercholesterolemia is a treatable genetic condition but remains underdiagnosed. We reviewed the frequency of pathogenic or likely pathogenic (P/LP) variants in the LDLR gene in female individuals receiving reproductive carrier screening. METHODS: This retrospective observational study included samples from female patients (aged 18-55 years) receiving a 274-gene carrier screening panel from January 2020 to September 2022. LDLR exons and their 10 base pair flanking regions were sequenced. Carrier frequency for P/LP variants was calculated for the entire population and by race/ethnicity. The most common variants and their likely functional effects were evaluated. RESULTS: A total of 91 637 tests were performed on women with race/ethnicity reported as Asian (8.8%), Black (6.1%), Hispanic (8.5%), White (29.0%), multiple or other (15.0%), and missing (33.0%). Median age was 32.8 years with 83 728 (91%) <40 years. P/LP LDLR variants were identified in 283 samples (1 in 324). No patients were identified with >1 P/LP variant. LDLR carrier frequency was higher in Asian (1 in 191 [95% CI, 1 in 142-258]) compared with White (1 in 417 [95% CI, 1 in 326-533]; P<0.001) or Black groups (1 in 508 [95% CI, 1 in 284-910]; P=0.004). The most common variants differed between populations. Of all variants, at least 25.0% were predicted as null variants. CONCLUSIONS: P/LP variants in LDLR are common. Expanding the use of reproductive carrier screening to include genes associated with FH presents another opportunity to identify people predisposed to cardiovascular disease.

Interpretable machine learning predicts postpartum hemorrhage with severe maternal morbidity in a lower-risk laboring obstetric population.

BACKGROUND: Early identification of patients at increased risk for postpartum hemorrhage (PPH) associated with severe maternal morbidity (SMM) is critical for preparation and preventative intervention. However, prediction is challenging in patients without obvious risk factors for postpartum hemorrhage with severe maternal morbidity. Current tools for hemorrhage risk assessment use lists of risk factors rather than predictive models. OBJECTIVE: To develop, validate (internally and externally), and compare a machine learning model for predicting PPH associated with SMM against a standard hemorrhage risk assessment tool in a lower risk laboring obstetric population. STUDY DESIGN: This retrospective cross-sectional study included clinical data from singleton, term births (>=37 weeks' gestation) at 19 US hospitals (2016-2021) using data from 58,023 births at 11 hospitals to train a generalized additive model (GAM) and 27,743 births at 8 held-out hospitals to externally validate the model. The outcome of interest was PPH with severe maternal morbidity (blood transfusion, hysterectomy, vascular embolization, intrauterine balloon tamponade, uterine artery ligation suture, uterine compression suture, or admission to intensive care). Cesarean birth without a trial of vaginal birth and patients with a history of cesarean were excluded. We compared the model performance to that of the California Maternal Quality Care Collaborative (CMQCC) Obstetric Hemorrhage Risk Factor Assessment Screen. RESULTS: The GAM predicted PPH with an area under the receiver-operating characteristic curve (AUROC) of 0.67 (95% CI 0.64-0.68) on external validation, significantly outperforming the CMQCC risk screen AUROC of 0.52 (95% CI 0.50-0.53). Additionally, the GAM had better sensitivity of 36.9% (95% CI 33.01-41.02) than the CMQCC screen sensitivity of 20.30% (95% CI 17.40-22.52) at the CMQCC screen positive rate of 16.8%. The GAM identified in-vitro fertilization as a risk factor (adjusted OR 1.5; 95% CI 1.2-1.8) and nulliparous births as the highest PPH risk factor (adjusted OR 1.5; 95% CI 1.4-1.6). CONCLUSION: Our model identified almost twice as many cases of PPH as the CMQCC rules-based approach for the same screen positive rate and identified in-vitro fertilization and first-time births as risk factors for PPH. Adopting predictive models over traditional screens can enhance PPH prediction.

Interpretable Predictive Models to Understand Risk Factors for Maternal and Fetal Outcomes.

Although most pregnancies result in a good outcome, complications are not uncommon and can be associated with serious implications for mothers and babies. Predictive modeling has the potential to improve outcomes through a better understanding of risk factors, heightened surveillance for high-risk patients, and more timely and appropriate interventions, thereby helping obstetricians deliver better care. We identify and study the most important risk factors for four types of pregnancy complications: (i) severe maternal morbidity, (ii) shoulder dystocia, (iii) preterm preeclampsia, and (iv) antepartum stillbirth. We use an Explainable Boosting Machine (EBM), a high-accuracy glass-box learning method, for the prediction and identification of important risk factors. We undertake external validation and perform an extensive robustness analysis of the EBM models. EBMs match the accuracy of other black-box ML methods, such as deep neural networks and random forests, and outperform logistic regression, while being more interpretable. EBMs prove to be robust. The interpretability of the EBM models reveal surprising insights into the features contributing to risk (e.g., maternal height is the second most important feature for shoulder dystocia) and may have potential for clinical application in the prediction and prevention of serious complications in pregnancy.

Effects of the ARRIVE (A Randomized Trial of Induction Versus Expectant Management) Trial on Elective Induction and Obstetric Outcomes in Term Nulliparous Patients.

OBJECTIVE: To evaluate the effect of publication of the ARRIVE (A Randomized Trial of Induction Versus Expectant Management) trial on perinatal outcomes in singleton, term, nulliparous patients. METHODS: An interrupted time series analysis was performed using clinical data for nulliparous singleton births at 39 weeks of gestation or later at 13 hospitals in the Northwest region of the United States (January 2016-December 2020). A modified Poisson regression was used to model time trends and changes after the ARRIVE trial (August 9, 2018). Outcomes of interest were elective induction, unplanned cesarean births, hypertensive disorders of pregnancy, a composite of perinatal adverse outcomes, and neonatal intensive care unit admissions. RESULTS: The analysis included 28,256 births (15,208 pre-ARRIVE and 13,048 post-ARRIVE). The rate of elective labor induction was 3.6% during the pre-ARRIVE period (January 2016-July 2018) and 10.8% post-ARRIVE (August 2018-December 2020). In the interrupted time series analysis, elective induction increased by 42% (relative risk [RR] 1.42; 95% CI 1.18-1.71) immediately after the ARRIVE trial publication. Thereafter, the trend was unchanged compared with the pre-ARRIVE period. There was no statistically significant change in cesarean birth (RR 0.96; 95% CI 0.89-1.04) or hypertensive disorders of pregnancy (RR 0.91; 95% CI 0.79-1.06) immediately after the trial, and no change in trend. After the ARRIVE trial, there was no immediate change in adverse perinatal outcomes, but a statistically significant increase in trend of adverse perinatal events (1.03; 95% CI 1.01-1.05) when compared with a declining trend observed in the pre-ARRIVE period. CONCLUSION: Publication of the ARRIVE trial was associated with an increase in elective induction, and no change in cesarean birth or hypertensive disorders of pregnancy in singleton nulliparous patients giving birth at 39 weeks or later. There was a flattening of the pre-ARRIVE decreasing trend in perinatal adverse events.

Reproductive Carrier Screening Results With Maternal Health Implications During Pregnancy.

OBJECTIVE: To identify conditions on a reproductive carrier screening panel with the potential for carrier manifestations during pregnancy and review the implications for obstetric care. METHODS: This was a retrospective cross-sectional study of consecutive samples from female patients aged 18-55 years submitted to a commercial laboratory for a 274-gene carrier screening panel (January 2020 to September 2022). A literature review was performed to identify genes on the panel with potential for pregnancy complications in carriers. Carrier expression and published recommendations for clinical management were reviewed. RESULTS: We identified 12 genes with potential for carrier manifestations during pregnancy based on reports in the literature: nine with manifestations irrespective of the fetal genetic status ( ABCB11 , COL4A3 , COL4A4 , COL4A5 , DMD , F9 , F11 , GLA , and OTC ) and three ( CPT1A , CYP19A1 , and HADHA ) with manifestations only if the fetus is affected by the condition. Manifestations included cardiomyopathy, hemorrhage, gestational hypertensive disorders, cholestasis of pregnancy, acute fatty liver, hyperammonemic crisis, and maternal virilization. Published recommendations for carrier management were identified for 11 of the 12 genes. Of 91,637 tests performed during the study period, a pathogenic or likely pathogenic variant was identified in 2,139 (2.3%), giving a carrier frequency for any of the 12 genes of 1 in 43 (95% CI 1/41-45) 1,826 (2.0%) of the study population were identified as carriers for one of the nine genes with the potential for carrier manifestations irrespective of an affected or unaffected fetus. CONCLUSION: Approximately 1 in 40 female patients were identified as carriers for a condition with potential for maternal manifestations in pregnancy, including some serious or even life-threatening complications. Obstetric care professionals should be aware of the possibility of pregnancy complications among carriers and the available recommendations for management. FUNDING SOURCE: This study was funded by Natera, Inc.

Maternal Malignancy After Atypical Findings on Single-Nucleotide Polymorphism-Based Prenatal Cell-Free DNA Screening.

OBJECTIVE: To evaluate the incidence and clinical outcomes of cell-free DNA results suspicious for maternal malignancy on prenatal cell-free DNA screening with single-nucleotide polymorphism (SNP)-based technology. METHODS: This retrospective cohort study included data from SNP-based, noninvasive prenatal screening samples from a commercial laboratory from January 2015 to October 2021. Maternal plasma was screened for trisomy 21, 18, and 13; monosomy X; and triploidy. Cases were considered suspicious for maternal malignancy if retrospective bioinformatics and visual inspection of the SNP plot were suggestive of multiple maternal copy number variants across at least two of the tested chromosomes. Clinical follow-up on patients was obtained by contacting individual referring clinician offices by telephone, facsimile, or email. RESULTS: A total of 2,004,428 noninvasive prenatal screening samples during the study period met criteria for inclusion in the analysis. Of these, 38 samples (0.002% or 1 in 52,748, 95% CI 1:74,539-1:38,430) had SNP-plot results that were suspicious for maternal malignancy. Maternal health outcomes were obtained in 30 of these patients (78.9%); eight were lost to follow-up. Maternal malignancy or suspected malignancy was identified in 66.7% (20/30) of the 30 patients with clinical follow-up provided by the clinic. The most common maternal malignancies were lymphoma (n=10), breast cancer (n=5), and colon cancer (n=3). CONCLUSION: Results suspicious for maternal malignancy are rare with SNP-based noninvasive prenatal screening (1:53,000), but two thirds of patients who had a noninvasive prenatal screening result concerning for malignancy in this study had a cancer diagnosis. Investigation for malignancy should be recommended for all pregnant patients with this type of result. FUNDING SOURCE: This study was funded by Natera, Inc.

Exclusive Breastfeeding in the Northwest: Disparities Related to Race/Ethnicity and Substance Use.

BACKGROUND AND OBJECTIVES: Mothers who are Black, Indigenous, and people of color (BIPOC) are disproportionately impacted by substance use in pregnancy and less likely to breastfeed. Our objectives were to assess relationships between substance use in pregnancy and exclusive breastfeeding at discharge (EBF) and race/ethnicity and EBF, and determine the extent to which substance use influences the relationship between race/ethnicity and EBF. METHODS: This is a retrospective cohort study of term mother-infant dyads using 2016 to 2019 data from a Northwest quality improvement collaborative, Obstetrical Care Outcomes Assessment Program. Stepwise and stratified multivariable logistic regression analyses were conducted to determine associations between independent variables consisting of characteristics, including maternal race/ethnicity and substance use, and the dependent variable, EBF. RESULTS: Our sample consisted of 84,742 dyads, 69.5% of whom had EBF. The adjusted odds of EBF for non-Hispanic Black and Hispanic mothers were half, and for American Indian/Alaska Native mothers two-thirds, that of White mothers (aOR [95% CI]: 0.52 [0.48, 0.57], 0.51 [0.48, 0.54], 0.64 [0.55, 0.76], respectively). Substance use did not mediate the association between race/ethnicity and EBF, but it modified the association. Among those reporting nicotine or marijuana use, Hispanic mothers were half as likely as White mothers were to exclusively breastfeed. Other factors associated with a lower likelihood of EBF included public or no insurance, rural setting, C-section, NICU admission, and LBW. CONCLUSIONS: Disparities in EBF related to race/ethnicity and substance use were pronounced in this study, particularly among Hispanic mothers with nicotine or marijuana use.