Compromised SARS-CoV-2-specific placental antibody transfer.

SARS-CoV-2 infection causes more severe disease in pregnant women compared to age-matched non-pregnant women. Whether maternal infection causes changes in the transfer of immunity to infants remains unclear. Maternal infections have previously been associated with compromised placental antibody transfer, but the mechanism underlying this compromised transfer is not established. Here, we used systems serology to characterize the Fc profile of influenza-, pertussis-, and SARS-CoV-2-specific antibodies transferred across the placenta. Influenza- and pertussis-specific antibodies were actively transferred. However, SARS-CoV-2-specific antibody transfer was significantly reduced compared to influenza- and pertussis-specific antibodies, and cord titers and functional activity were lower than in maternal plasma. This effect was only observed in third-trimester infection. SARS-CoV-2-specific transfer was linked to altered SARS-CoV-2-antibody glycosylation profiles and was partially rescued by infection-induced increases in IgG and increased FCGR3A placental expression. These results point to unexpected compensatory mechanisms to boost immunity in neonates, providing insights for maternal vaccine design.

The simultaneous occurrence of gestational diabetes and hypertensive disorders of pregnancy affects fetal growth and neonatal morbidity.

BACKGROUND: Gestational diabetes is associated with increased risk of hypertensive disorders of pregnancy, but there are limited data on fetal growth and neonatal outcomes when both conditions are present. OBJECTIVE: We evaluated the risk of abnormal fetal growth and neonatal morbidity in pregnancies with co-occurrence of gestational diabetes and hypertensive disorders of pregnancy. STUDY DESIGN: In a retrospective study of 47,093 singleton pregnancies, we compared the incidence of appropriate for gestational age birthweight in pregnancies affected by gestational diabetes alone, hypertensive disorders of pregnancy alone, or both gestational diabetes and hypertensive disorders of pregnancy with that in pregnancies affected by neither disorder using generalized estimating equations (covariates: maternal age, nulliparity, body mass index, insurance type, race, marital status, and prenatal care site). Secondary outcomes were large for gestational age birthweight, small for gestational age birthweight, and a neonatal morbidity composite outcome (stillbirth, hypoglycemia, hyperbilirubinemia, respiratory distress, encephalopathy, preterm delivery, neonatal death, and neonatal intensive care unit admission). RESULTS: The median (interquartile range) birthweight percentile in pregnancies with both gestational diabetes and hypertensive disorders of pregnancy (50 [24.0-78.0]; N=179) was similar to that of unaffected pregnancies (50 [27.0-73.0]; N=35,833). However, the absolute rate of appropriate for gestational age birthweight was lower for gestational diabetes/hypertensive disorders of pregnancy co-occurrence (78.2% vs 84.9% for unaffected pregnancies). Adjusted analyses showed decreased odds of appropriate for gestational age birthweight in pregnancies with both gestational diabetes and hypertensive disorders of pregnancy compared with unaffected pregnancies (adjusted odds ratio, 0.72 [95% confidence interval, 0.52-1.00]; P=.049), and in pregnancies complicated by gestational diabetes alone (adjusted odds ratio, 0.78 [0.68-0.89]; P<.001) or hypertensive disorders of pregnancy alone (adjusted odds ratio, 0.73 [0.66-0.81]; P<.001). The absolute risk of large for gestational age birthweight was greater in pregnancies with both gestational diabetes and hypertensive disorders of pregnancy (14.5%) than in unaffected pregnancies (8.2%), without apparent difference in the risk of small for gestational age birthweight (7.3% vs 6.9%). However, in adjusted models comparing pregnancies with gestational diabetes/hypertensive disorders of pregnancy co-occurrence with unaffected pregnancies, neither an association with large for gestational age birthweight (adjusted odds ratio, 1.33 [0.88-2.00]; P=.171) nor small for gestational age birthweight (adjusted odds ratio, 1.32 [0.80-2.19]; P=.293) reached statistical significance. Gestational diabetes/hypertensive disorders of pregnancy co-occurrence carried an increased risk of neonatal morbidity that was greater than that observed with either condition alone (gestational diabetes/hypertensive disorders of pregnancy: adjusted odds ratio, 3.13 [2.35-4.17]; P<.001; gestational diabetes alone: adjusted odds ratio, 2.01 [1.78-2.27]; P<.001; hypertensive disorders of pregnancy alone: adjusted odds ratio, 1.38 [1.26-1.50]; P<.001). CONCLUSION: Although pregnancies with both gestational diabetes and hypertensive disorders of pregnancy have a similar median birthweight percentile to those affected by neither condition, pregnancies concurrently affected by both conditions have a higher risk of abnormal fetal growth and neonatal morbidity.

Gross and Histologic Placental Abnormalities Associated With Neonatal Hypoxic-Ischemic Encephalopathy.

OBJECTIVE: To elucidate particular placental pathology findings that are associated with hypoxic ischemic encephalopathy (HIE) and determine which patterns are associated with adverse fetal/neonatal outcomes. STUDY DESIGN: Multi-institutional retrospective case-control study of newborns with HIE (2002-2022) and controls. Four perinatal pathologists performed gross and histologic evaluation of placentas of cases and controls. RESULTS: A total of 265 placentas of neonates with HIE and 122 controls were examined. Infants with HIE were more likely to have anatomic umbilical cord abnormalities (19.7% vs 7.4%, P = .003), fetal inflammatory response in the setting of amniotic fluid infection (27.7% vs 13.9%, P = .004), and fetal vascular malperfusion (30.6% vs 9.0%, P = <.001) versus controls. Fetal vascular malperfusion with maternal vascular malperfusion was more common in those who died of disease (P = .01). CONCLUSION: Placental pathology examination of neonates with HIE may improve our understanding of this disorder and its adverse outcomes.

Assisted reproductive technology (ART) patient information-seeking behavior: a qualitative study.

BACKGROUND: Approximately 13% of women in the United States of reproductive age seek infertility services. Assisted reproductive technology (ART), including in vitro fertilization, is used to help patients achieve pregnancy. Many people are not familiar with these treatments prior to becoming patients and possess knowledge gaps about care. METHODS: This study employed qualitative methods to investigate how patients interact with information sources during care. Patients who underwent ART including embryo transfer between January 2017 and April 2022 at a large urban healthcare center were eligible. Semi-structured, in-depth interviews were conducted between August and October 2022. Fifteen females with an average age of 39 years participated. Reflexive thematic analysis was performed. RESULTS: Two main themes emerged. Participants (1) utilized clinic-provided information and then turned to outside sources to fill knowledge gaps; (2) struggled to learn about costs, insurance, and mental health resources to support care. Participants preferred clinic-provided resources and then utilized academic sources, the internet, and social media when they had unfulfilled information needs. Knowledge gaps related to cost, insurance, and mental health support were reported. CONCLUSION: ART clinics can consider providing more information about cost, insurance, and mental health support to patients. TRIAL REGISTRATION: The Massachusetts General Hospital Institutional Review Board approved this study (#2022P000474) and informed consent was obtained from each participant.

Glycated Albumin and Glycemia in Pregnancy and Postpartum: A Pilot Study.

OBJECTIVE: Percent glycated albumin (%GAlb) is a marker of glycemia over the past 2 to 3 weeks in nonpregnant individuals. Longitudinal changes in %GAlb extending throughout pregnancy and postpartum (PP) have not been described. We aimed to describe levels of %GAlb throughout pregnancy and PP and relationships with glycemia. STUDY DESIGN: Fifty women among those in the Study of Pregnancy Regulation of INsulin and Glucose cohort underwent 75-g oral glucose tolerance tests (OGTTs) at a mean of 13 weeks (V1) and 26 weeks (V2) of gestation and 11 weeks' PP. %GAlb was measured on frozen plasma samples. RESULTS: Total albumin decreased from V1 to V2 and increased PP to levels higher than at V1. %GAlb declined between V1 and V2 (ß = - 0.63% 95% CI [-0.8, -0.6] p < 0.001) and remained stable between V2 and PP (ß = - 0.04% [-0.3, 0.2] p = 0.78). Body mass index (BMI) was inversely related to %GAlb in pregnancy (V1: rho = - 0.5, p = 0.0001; V2 rho = - 0.4, p = 0.006), but not PP (rho = - 0.15, p = 0.31). The longitudinal changes in %GAlb persisted after adjusting for BMI. Neither glycemia measurements nor hemoglobin A1c were associated with %GAlb at any time point, and adjustments for BMI did not reveal additional associations. CONCLUSION: %GAlb decreases between early and late gestation and remains decreased PP, despite a PP increase in total albumin above early pregnancy values. Given the lack of correlation with OGTT values or A1c, %GAlb is unlikely to be useful in assessing glycemia in pregnant or PP women. KEY POINTS: · Changes in %GAlb extending to the postpartum period have not been described.. · %GAlb decreases in pregnancy and remains decreased postpartum, despite a postpartum increase in total albumin above early pregnancy values.. · Glycemia measurements nor A1c were associated with %GAlb at any time point, therefore, %GAlb is unlikely to be useful in assessing glycemia in pregnant or postpartum women..

Performance of a Maternal Risk Stratification System for Predicting Low Apgar Scores.

OBJECTIVE: Maternal risk stratification systems are increasingly employed in predicting and preventing obstetric complications. These systems focus primarily on maternal morbidity, and few tools exist to stratify neonatal risk. We sought to determine if a maternal risk stratification score was associated with neonatal morbidity. STUDY DESIGN: Retrospective cohort study of patients with liveborn infants born at ≥24 weeks at four hospitals in one health system between January 1, 2020, and December 31, 2020. The Expanded Obstetric Comorbidity Score (EOCS) is used as the maternal risk score. The primary neonatal outcome was 5-minute Apgar <7. Logistic regression models determined associations between EOCS and neonatal morbidity. Secondary analyses were performed, including stratifying outcomes by gestational age and limiting analysis to "low-risk" term singletons. Model discrimination assessed using the area under the receiver operating characteristic curves (AUC) and calibration via calibration plots. RESULTS: A total of 14,497 maternal-neonatal pairs were included; 236 (1.6%) had 5-minute Apgar <7; EOCS was higher in 5-minute Apgar <7 group (median 41 vs. 11, p < 0.001). AUC for EOCS in predicting Apgar <7 was 0.72 (95% Confidence Interval (CI) 0.68, 0.75), demonstrating relatively good discrimination. Calibration plot revealed that those in the highest EOCS decile had higher risk of neonatal morbidity (7.6 vs. 1.7%, p < 0.001). When stratified by gestational age, discrimination weakened with advancing gestational age: AUC 0.70 for <28 weeks, 0.63 for 28 to 31 weeks, 0.64 for 32 to 36 weeks, and 0.61 for ≥37 weeks. When limited to term low-risk singletons, EOCS had lower discrimination for predicting neonatal morbidity and was not well calibrated. CONCLUSION: A maternal morbidity risk stratification system does not perform well in most patients giving birth, at low risk for neonatal complications. The findings suggest that the association between EOCS and 5-minute Apgar <7 likely reflects a relationship with prematurity. This study cautions against intentional or unintentional extrapolation of maternal morbidity risk for neonatal risk, especially for term deliveries. KEY POINTS: · EOCS had moderate discrimination for Apgar <7.. · Predictive performance declined when limited to low-risk term singletons.. · Relationship between EOCS and Apgar <7 was likely driven by prematurity..

Fentanyl in the labor epidural impacts the results of intrapartum and postpartum maternal and neonatal toxicology tests.

BACKGROUND: A positive urine fentanyl toxicology test may have considerable consequences for peripartum individuals, yet the extent to which fentanyl administration in a labor epidural may lead to such a positive test is poorly characterized. OBJECTIVE: This study aimed to quantify the extent to which neuraxial fentanyl in labor neuraxial analgesia can lead to a positive peripartum maternal or neonatal urine toxicology test. STUDY DESIGN: We performed a prospective cohort study of pregnant participants planning a vaginal delivery with neuraxial analgesia. Participants with a history of substance use disorder, hypertension, or renal or liver disease were excluded. A urine sample was collected before initiation of neuraxial analgesia, each time the bladder was emptied during labor, and up to 4 times postpartum. Neonatal urine was collected once. Urine fentanyl testing was performed using 2 common toxicology testing methods, namely immunoassay and liquid chromatography with tandem mass spectrometric detection. RESULTS: A total of 33 maternal-infant dyads yielded a total of 178 urine specimens. All maternal specimens were negative for fentanyl using liquid chromatography with tandem mass spectrometric analysis and immunoassay before initiation of neuraxial analgesia. Intrapartum, 26 of 30 (76.7%) participants had positive liquid chromatography with tandem mass spectrometry results for fentanyl or its metabolites, and 12 of 30 (40%) participants had positive immunoassay results. Postpartum, 19 of 21 (90.5%) participants had positive liquid chromatograph with tandem mass spectrometric results, and 13 of 21 (61.9%) had a positive immunoassay result. Of the 13 neonatal specimens collected, 10 (76.9%) were positive on liquid chromatography with tandem mass spectrometry analysis, the last of which remained positive 29 hours and 50 minutes after delivery. CONCLUSION: Neuraxial fentanyl for labor analgesia may lead to positive maternal and neonatal toxicology tests at various times after epidural initiation and cessation and at different rates depending on the testing method used. Caution should be used in interpreting toxicology test results of individuals who received neuraxial analgesia to avoid false assumptions about nonprescribed use.

Patterns of spread and genetic alterations of primary endometrioid carcinomas of the ovary.

OBJECTIVE: The primary objective was to characterize the rate of lymph node involvement in a cohort of patients with primary ovarian endometrioid adenocarcinoma. Additionally, we sought to quantify the recurrence rate, genetic alterations, and impact of lymphadenectomy on survival in this group of patients. METHODS: Patients diagnosed with primary endometrioid adenocarcinoma of the ovary without synchronous carcinomas of the female genital tract between 2012 and 2021 were identified. Demographic and disease-related data were collected from pathology reports and clinical records. Kaplan-Meier survival analysis using log rank test and Cox regression was performed. RESULTS: Sixty-three patients met inclusion criteria. Median age was 60 (range 22-90) years. Histologic grade was 1 in 20 (32%), 2 in 27 (43%), and 3 in 16 (25%) tumors. International Federation of Gynecology and Obstetrics (FIGO) stage after surgery included IA/B (n=20, 32%), IC (n=23, 37%), II (n=16, 25%), and III (n=4, 6%). Forty-one (65%) patients had pelvic and 33 (52%) had both pelvic and para-aortic lymphadenectomy. All assessed lymph nodes were negative for metastatic carcinoma. No patients with clinically pelvis-confined disease had tumors upstaged by either lymphadenectomy or omentectomy. Twenty-eight patients (44%) had germline mutational status documented; two had a germline BRCA mutation, confirmed to be pathogenic by molecular studies. Complete staging did not significantly impact progression free or overall survival, after adjusting for age and histologic grade in a Cox proportional hazards model. The recurrence rate was 15% for patients with grade 1 endometrioid carcinoma, 7% for grade 2, and 31% for grade 3, respectively. CONCLUSION: There were no lymph node metastases in patients with comprehensively staged primary endometrioid ovarian carcinoma. Staging did not impact survival and may be omitted, regardless of grade. Germline BRCA mutations are rare in ovarian endometrioid carcinoma compared with reported rates in high-grade serous carcinomas.

Incidence of de novo stress urinary incontinence following minimally invasive sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: The objective was to investigate the incidence and risk factors of postoperative de novo stress urinary incontinence (SUI) in stress-continent women following minimally invasive sacrocolpopexy without an anti-incontinence procedure. METHODS: We completed a multicenter, retrospective cohort study of women undergoing laparoscopic sacrocolpopexy without concurrent anti-incontinence procedures from October 2006 through January 2021. RESULTS: Of the 169 women who underwent minimally invasive sacrocolpopexy, 17.1% (n=30) developed de novo SUI, and 7.1% eventually underwent a midurethral sling placement. On logistic regression, BMI, preoperative urinary urgency, and history of transvaginal mesh repair were found to be significantly associated with and predictive of de novo SUI. When the concordance index (C-index) was calculated with the model published by Jelovsek et al. for women who developed de novo SUI within 12 months of the prolapse surgery, the current de novo SUI calculator was able to discriminate de novo SUI outcome (C-index = 0.71). CONCLUSIONS: The incidence of de novo SUI after minimally invasive sacrocolpopexy without anti-incontinence procedure correlates directly with higher BMI, preoperative urinary urgency, and transvaginal mesh history for POP. Preoperative counseling for minimally invasive sacrocolpopexy should include discussing the risk of de novo SUI and preoperative factors that may increase this risk.

Pregnancy- and birth-related risk factors for the development of childhood celiac disease.

AIM: To evaluate whether pregnancy and birth-related factors are associated with celiac disease (CD) in a large, United States (US)-based mother-child cohort. METHODS: We analysed data gathering from the Massachusetts General Hospital Maternal Child Cohort (MMCC) of children born between 1998 and 2016. Data included the mode of delivery, maternal pregnancy and their offspring characteristics. We searched for CD cases by using diagnosis billing codes. Cox proportional hazard regression models were created to identify variables associated with CD. RESULTS: We identified 44 539 mother-child pairs who had at least one encounter by 5 years old and identified 173 children (0.4%) with CD diagnosis; median age at the diagnosis was 6 years. Overall, the adjusted hazard ratio (aHR) of caesarean delivery for CD was 1.39 (95% CI: 0.99, 1.96, p = 0.06) when compared to children born vaginally. After stratifying for the presence of labour, children born by Caesarean delivery without labour had a higher risk of CD (aHR 1.56; 95%CI: 1.01, 2.41; p = 0.046) while infants born by Caesarean delivery with labour did not (aHR 1.26; 95% CI: 0.83, 1.93; p = 0.28). CONCLUSION: Being born by Caesarean delivery without labour may be associated with an increased risk for CD in the US children.

Evaluation of Menstrual Cycle Tracking Behaviors in the Ovulation and Menstruation Health Pilot Study: Cross-Sectional Study.

BACKGROUND: Menstrual cycle tracking apps (MCTAs) have potential in epidemiological studies of women's health, facilitating real-time tracking of bleeding days and menstrual-associated signs and symptoms. However, information regarding the characteristics of MCTA users versus cycle nontrackers is limited, which may inform generalizability. OBJECTIVE: We compared characteristics among individuals using MCTAs (app users), individuals who do not track their cycles (nontrackers), and those who used other forms of menstrual tracking (other trackers). METHODS: The Ovulation and Menstruation Health Pilot Study tested the feasibility of a digitally enabled evaluation of menstrual health. Recruitment occurred between September 2017 and March 2018. Menstrual cycle tracking behavior, demographic, and general and reproductive health history data were collected from eligible individuals (females aged 18-45 years, comfortable communicating in English). Menstrual cycle tracking behavior was categorized in 3 ways: menstrual cycle tracking via app usage, that via other methods, and nontracking. Demographic factors, health conditions, and menstrual cycle characteristics were compared across the menstrual tracking method (app users vs nontrackers, app users vs other trackers, and other trackers vs nontrackers) were assessed using chi-square or Fisher exact tests. RESULTS: In total, 263 participants met the eligibility criteria and completed the digital survey. Most of the cohort (n=191, 72.6%) was 18-29 years old, predominantly White (n=170, 64.6%), had attained 4 years of college education or higher (n= 209, 79.5%), and had a household income below US $50,000 (n=123, 46.8%). Among all participants, 103 (39%) were MCTA users (app users), 97 (37%) did not engage in any tracking (nontrackers), and 63 (24%) used other forms of tracking (other trackers). Across all groups, no meaningful differences existed in race and ethnicity, household income, and education level. The proportion of ever-use of hormonal contraceptives was lower (n=74, 71.8% vs n=87, 90%, P=.001), lifetime smoking status was lower (n=6, 6% vs n=15, 17%, P=.04), and diagnosis rate of gastrointestinal reflux disease (GERD) was higher (n=25, 24.3% vs n=12, 12.4%, P=.04) in app users than in nontrackers. The proportions of hormonal contraceptives ever used and lifetime smoking status were both lower (n=74, 71.8% vs n=56, 88.9%, P=.01; n=6, 6% vs n=11, 17.5%, P=.02) in app users than in other trackers. Other trackers had lower proportions of ever-use of hormonal contraceptives (n=130, 78.3% vs n=87, 89.7%, P=.02) and higher diagnostic rates of heartburn or GERD (n=39, 23.5% vs n=12, 12.4%, P.03) and anxiety or panic disorder (n=64, 38.6% vs n=25, 25.8%, P=.04) than nontrackers. Menstrual cycle characteristics did not differ across all groups. CONCLUSIONS: Our results suggest that app users, other trackers, and nontrackers are largely comparable in demographic and menstrual cycle characteristics. Future studies should determine reasons for tracking and tracking-related behaviors to further understand whether individuals who use MCTAs are comparable to nontrackers.

The Application of a Standard Risk Threshold for the Stratification of Maternal Morbidity among Population Subgroups.

OBJECTIVE: The aim of this study was to determine if a universally applied risk score threshold for severe maternal morbidity (SMM) resulted in different performance characteristics among subgroups of the population. STUDY DESIGN: This is a retrospective cohort study of deliveries that occurred between July 1, 2016, and June 30, 2020, in a single health system. We examined the performance of a validated comorbidity score to stratify SMM risk in our cohort. We considered the risk score that was associated with the highest decile of predicted risk as a "screen positive" for morbidity. We then used this same threshold to calculate the sensitivity and positive predictive value (PPV) of this "highest risk" designation among subgroups of the overall cohort based on the following characteristics: age, race/ethnicity, parity, gestational age, and planned mode of delivery. RESULTS: In the overall cohort of 53,982 women, the C-statistic was 0.755 (95% confidence interval [CI], 0.741-0.769) and calibration plot demonstrated that the risk score was well calibrated. The model performed less well in the following groups: non-White or Hispanic (C-statistic, 0.734; 95% CI, 0.712-0.755), nulliparas (C-statistic, 0.735; 95% CI, 0.716-0.754), term deliveries (C-statistic, 0.712; 95% CI, 0.694-0.729), and planned vaginal delivery (C-statistic, 0.728; 95% CI, 0.709-0.747). There were differences in the PPVs by gestational age (7.8% term and 29.7% preterm) and by planned mode of delivery (8.7% vaginal and 17.7% cesarean delivery). Sensitivities were lower in women who were <35 years (36.6%), non-White or Hispanic (40.7%), nulliparous (38.9%), and those having a planned vaginal delivery (40.9%) than their counterparts. CONCLUSION: The performance of a risk score for SMM can vary by population subgroups when using standard thresholds derived from the overall cohort. If applied without such considerations, such thresholds may be less likely to identify certain subgroups of the population that may be at increased risk of SMM. KEY POINTS: · Predictive risk models are helpful at condensing complex information into an interpretable output.. · Model performance may vary among different population subgroups.. · Prediction models should be examined for their potential to exacerbate underlying disparities..

Innovating Evaluation and Treatment of Intrapartum Fevers: Where Do We Go from Here?

As intrapartum fevers are not always infectious in origin, determining whether antibiotics are indicated is challenging. We previously sought to create a point-of-care calculator using clinical data available at the time of an intrapartum fever to identify the subset of women who require antibiotic treatment to avoid maternal and neonatal morbidity. Despite the use of a comprehensive dataset from our institutions, we were unable to propose a valid and highly predictive model. In this commentary, we discuss why our model failed, as well as future research directions to identify and treat true intraamniotic infection. Developing a risk-stratification model is paramount to minimizing maternal and neonatal exposure to unnecessary antibiotics while allowing for early identification of women and babies at risk for infectious morbidity. KEY POINTS: · Determining whether antibiotics are indicated in intrapartum fever is challenging.. · Developing a risk-stratification model for febrile laboring women is critical to decreasing harm.. · A point-of-care calculator based on clinical and biomarker data is the necessary approach..

The impact of anti-Müllerian hormone on endometrial thickness in gonadotropin stimulation/intrauterine insemination cycles: is there an effect on pregnancy outcomes?

PURPOSE: To study the association, if any, between anti-Müllerian hormone (AMH) and pre-ovulatory endometrial thickness (ET) in gonadotropin/intrauterine insemination (IUI) cycles. METHODS: This retrospective cohort study included a total of 964 patients undergoing 1926 gonadotropin/IUI cycles at an academic fertility center. Primary outcome measure was the association between serum AMH and measured ET on the day of and the day before human chorionic gonadotropin hormone (hCG) ovulation trigger. The effect of a model combining AMH and ET on early pregnancy outcomes was a secondary measure. RESULTS: In 52.8% of cycles, ET was last assessed and recorded on the day of hCG administration, while in the remaining 47.2% on the day prior to trigger. In unadjusted regression models, AMH was weakly correlated with ET on hCG trigger day [bAMH (95%CI) = 0.032 (- 0.008, 0.070), p = 0.015]. When adjusting for potential confounders, the positive correlation became significant [0.051 (0.006, 0.102), p = 0.047]. Similar findings were observed when assessing the correlation between AMH and ET on the day prior to hCG trigger. ET was non-significantly associated with the odds of clinical pregnancy, when adjusting for potential confounders, except for when restricting the analysis to couples with idiopathic infertility [OR (95%CI), p-value: 0.787 (0.623, 0.993), 0.044]. CONCLUSION: Our findings support an effect of serum AMH on endometrial development in gonadotropin induced cycles, even when adjusting for the diagnosis of PCOS. ET was not associated with the odds of achieving a clinical pregnancy, except for couples with idiopathic infertility.

Longitudinal changes in glucose during pregnancy in women with gestational diabetes risk factors.

AIMS/HYPOTHESIS: Despite recommendations to screen women with diabetes risk factors for hyperglycaemia in the first trimester, criteria for normal glucose values in early pregnancy have not been firmly established. We aimed to compare glucose levels in early pregnancy with those later in gestation and outside of pregnancy in women with diabetes risk factors. METHODS: In pregnant women (N = 123) followed longitudinally through the postpartum period, and a separate cohort of non-pregnant women (N = 65), we performed 75 g oral glucose tolerance tests. All participants had one or more risk factors for diabetes. Using linear regression, we tested for differences in glucose levels between non-pregnant and pregnant women at early (7-15 weeks) and mid-late (24-32 weeks) gestation as well as postpartum, with adjustment for maternal age, parity, marital status and BMI. In a longitudinal analysis using mixed-effects models, we tested for differences in glucose levels across early and mid-late pregnancy compared with postpartum. Differences are expressed as ß (95% CI). RESULTS: Fasting glucose was lower in pregnant compared with non-pregnant women by 0.34 (0.18, 0.51) mmol/l (p < 0.0001) in early pregnancy and by 0.45 (0.29, 0.61) mmol/l (p < 0.0001) in mid-late pregnancy. In longitudinal models, fasting glucose was lower by 0.13 (0.04, 0.21) mmol/l (p = 0.003) in early pregnancy and by 0.16 (0.08, 0.25) mmol/l (p = 0.0003) in mid-late pregnancy compared with the same women postpartum. Early pregnancy post-load glucose levels did not differ from those in non-pregnant women or the same women postpartum. In mid-late pregnancy, compared with non-pregnant women, elevations in 1 h post-load glucose level (0.60 [-0.12, 1.33] mmol/l, p = 0.10) and 2 h post-load glucose (0.49 [-0.21, 1.19] mmol/l, p = 0.17) were not statistically significant. However, in longitudinal analyses, 1 h and 2 h post-load glucose levels were higher in mid-late pregnancy (by 0.78 [0.35, 1.21] mmol/l, p = 0.0004, and 0.67 [0.30, 1.04] mmol/l, p = 0.0005, respectively) when compared with postpartum. CONCLUSIONS/INTERPRETATION: In women with diabetes risk factors, fasting glucose declines in the first trimester. Post-load glucose increases later in pregnancy. These findings may inform criteria for diagnosing hyperglycaemia early in pregnancy.

Natural language processing of admission notes to predict severe maternal morbidity during the delivery encounter.

BACKGROUND: Severe maternal morbidity and mortality remain public health priorities in the United States, given their high rates relative to other high-income countries and the notable racial and ethnic disparities that exist. In general, accurate risk stratification methods are needed to help patients, providers, hospitals, and health systems plan for and potentially avert adverse outcomes. OBJECTIVE: Our objective was to understand if machine learning methods with natural language processing of history and physical notes could identify a group of patients at high risk of maternal morbidity on admission for delivery without relying on any additional patient information (eg, demographics and diagnosis codes). STUDY DESIGN: This was a retrospective study of people admitted for delivery at 2 hospitals (hospitals A and B) in a single healthcare system between July 1, 2016, and June 30, 2020. The primary outcome was severe maternal morbidity, as defined by the Centers for Disease Control and Prevention; furthermore, we examined nontransfusion severe maternal morbidity. Clinician documents designated as history and physical notes were extracted from the electronic health record for processing and analysis. A bag-of-words approach was used for this natural language processing analysis (ie, each history or physical note was converted into a matrix of counts of individual words (or phrases) that occurred within the document). The least absolute shrinkage and selection operator models were used to generate prediction probabilities for severe maternal morbidity and nontransfusion severe maternal morbidity for each note. Model discrimination was assessed via the area under the receiver operating curve. Discrimination was compared between models using the DeLong test. Calibration plots were generated to assess model calibration. Moreover, the natural language processing models with history and physical note texts were compared with validated obstetrical comorbidity risk scores based on diagnosis codes. RESULTS: There were 13,572 delivery encounters with history and physical notes from hospital A, split between training (Atrain, n=10,250) and testing (Atest, n=3,322) datasets for model derivation and internal validation. There were 23,397 delivery encounters with history and physical notes from hospital B (Bvalid) used for external validation. For the outcome of severe maternal morbidity, the natural language processing model had an area under the receiver operating curve of 0.67 (95% confidence interval, 0.63-0.72) and 0.72 (95% confidence interval, 0.70-0.74) in the Atest and Bvalid datasets, respectively. For the outcome of nontransfusion severe maternal morbidity, the area under the receiver operating curve was 0.72 (95% confidence interval, 0.65-0.80) and 0.76 (95% confidence interval, 0.73-0.79) in the Atest and Bvalid datasets, respectively. The calibration plots demonstrated the bag-of-words model's ability to distinguish a group of individuals at a substantially higher risk of severe maternal morbidity and nontransfusion severe maternal morbidity, notably those in the top deciles of predicted risk. Areas under the receiver operating curve in the natural language processing-based models were similar to those generated using a validated, retrospectively derived, diagnosis code-based comorbidity score. CONCLUSION: In this practical application of machine learning, we demonstrated the capabilities of natural language processing for the prediction of severe maternal morbidity based on provider documentation inherently generated at the time of admission. This work should serve as a catalyst for providers, hospitals, and electronic health record systems to explore ways that artificial intelligence can be incorporated into clinical practice and evaluated rigorously for their ability to improve health.

Physiological subtypes of gestational glucose intolerance and risk of adverse pregnancy outcomes.

BACKGROUND: Women with gestational glucose intolerance, defined as an abnormal initial gestational diabetes mellitus screening test, are at risk of adverse pregnancy outcomes even if they do not have gestational diabetes mellitus. Previously, we defined the physiological subtypes of gestational diabetes mellitus based on the primary underlying physiology leading to hyperglycemia and found that women with different subtypes had differential risks of adverse outcomes. Physiological subclassification has not yet been applied to women with gestational glucose intolerance. OBJECTIVE: We defined the physiological subtypes of gestational glucose intolerance based on the presence of insulin resistance, insulin deficiency, or mixed pathophysiology and aimed to determine whether these subtypes are at differential risks of adverse outcomes. We hypothesized that women with the insulin-resistant subtype of gestational glucose intolerance would have the greatest risk of adverse pregnancy outcomes. STUDY DESIGN: In a hospital-based cohort study, we studied women with gestational glucose intolerance (glucose loading test 1-hour glucose, ≥140 mg/dL; n=236) and normal glucose tolerance (glucose loading test 1-hour glucose, <140 mg/dL; n=1472). We applied homeostasis model assessment to fasting glucose and insulin levels at 16 to 20 weeks' gestation to assess insulin resistance and deficiency and used these measures to classify women with gestational glucose intolerance into subtypes. We compared odds of adverse outcomes (large for gestational age birthweight, neonatal intensive care unit admission, pregnancy-related hypertension, and cesarean delivery) in each subtype to odds in women with normal glucose tolerance using logistic regression with adjustment for age, race and ethnicity, marital status, and body mass index. RESULTS: Of women with gestational glucose intolerance (12% with gestational diabetes mellitus), 115 (49%) had the insulin-resistant subtype, 70 (27%) had the insulin-deficient subtype, 40 (17%) had the mixed pathophysiology subtype, and 11 (5%) were uncategorized. We found increased odds of large for gestational age birthweight (primary outcome) in women with the insulin-resistant subtype compared with women with normal glucose tolerance (odds ratio, 2.35; 95% confidence interval, 1.43-3.88; P=.001; adjusted odds ratio, 1.74; 95% confidence interval, 1.02-3.48; P=.04). The odds of large for gestational age birthweight in women with the insulin-deficient subtype were increased only after adjustment for covariates (odds ratio, 1.69; 95% confidence interval, 0.84-3.38; P=.14; adjusted odds ratio, 2.05; 95% confidence interval, 1.01-4.19; P=.048). Among secondary outcomes, there was a trend toward increased odds of neonatal intensive care unit admission in the insulin-resistant subtype in an unadjusted model (odds ratio, 2.09; 95% confidence interval, 0.99-4.40; P=.05); this finding was driven by an increased risk of neonatal intensive care unit admission in women with the insulin-resistant subtype and a body mass index of <25 kg/m2. Infants of women with other subtypes did not have increased odds of neonatal intensive care unit admission. The odds of pregnancy-related hypertension in women with the insulin-resistant subtype were increased (odds ratio, 2.09; 95% confidence interval, 1.31-3.33; P=.002; adjusted odds ratio, 1.77; 95% confidence interval, 1.07-2.92; P=.03) compared with women with normal glucose tolerance; other subtypes did not have increased odds of pregnancy-related hypertension. There was no difference in cesarean delivery rates in nulliparous women across subtypes. CONCLUSION: Insulin-resistant gestational glucose intolerance is a high-risk subtype for adverse pregnancy outcomes. Delineating physiological subtypes may provide opportunities for a more personalized approach to gestational glucose intolerance.

Perceptions and Attitudes toward COVID-19 Vaccination among Pregnant and Postpartum Individuals.

OBJECTIVE: This study aimed to characterize attitudes toward novel coronavirus disease 2019 (COVID-19) vaccination and to evaluate factors associated with vaccine uptake among pregnant individuals. STUDY DESIGN: An anonymous survey was distributed to a convenience sample of pregnant individuals receiving prenatal care at two large urban academic hospitals in a single health care network in Massachusetts. Individual demographic variables were included in the survey along with questions assessing attitudes toward COVID-19 and vaccination in pregnancy. Data were analyzed using parametric or nonparametric tests when appropriate, and associated odds ratios (OR) were calculated via univariable logistic regression. RESULTS: There were 684 surveys distributed, and 477 pregnant and postpartum individuals completed the survey, for a response rate of 69.7%. Overall, 233 (49.3%) had received or were scheduled to receive a COVID-19 vaccine. Age, White race, non-Hispanic or Latinx ethnicity, working from home, and typical receipt of the influenza vaccine were associated with COVID-19 vaccination. Further, 276 respondents (58.4%) reported that their provider recommended the COVID-19 vaccine in pregnancy; these participants were more likely to have received a vaccine (OR = 5.82, 95% confidence interval [CI]: 3.68-9.26, p < 0.005). Vaccinated individuals were less likely to be worried about the effects of the vaccine on themselves (OR = 0.18, 95% CI: 0.12-0.27, p < 0.005) or their developing babies (OR = 0.17, 95% CI: 0.11-0.26, p < 0.005). Unvaccinated individuals were less likely to report that it is easy to schedule a COVID-19 vaccine (OR = 0.56, 95% CI: 0.34-0.93, p = 0.02), to travel to receive a vaccine (OR = 0.19, 95% CI: 0.10-0.36, p < 0.005), and to miss work to receive a vaccine (OR = 0.30, 95% CI: 0.18-0.48, p < 0.005). CONCLUSION: Strategies are needed to improve patient education regarding vaccine side effects and safety in pregnancy. Policy changes should focus on making it feasible for patients to schedule a vaccine and miss work without loss of pay to get vaccinated. KEY POINTS: · There were racial and ethnic disparities in COVID-19 vaccination.. · Unvaccinated respondents were more likely to be concerned about vaccine effects for themselves or their growing babies.. · Unvaccinated respondents cited work and scheduling-related barriers to vaccination, indicating areas for advocacy..

Optimizing pregnancy outcomes in intrauterine insemination cycles by stratifying pre-wash total motile count and patient-specific factors: a patient counseling tool.

PURPOSE: The purpose of this study is to clarify which pre-wash total motile count are associated with improved clinical pregnancy rate (CPR) and live birth rate (LBR) based on maternal age, AMH level, stimulation regimen, and infertility diagnosis. METHODS: This was a retrospective cohort study of first completed IUI cycles at two academic fertility centers from 5/2015 to 9/2019. Cycles were stratified by pre-wash TMC, maternal age, AMH level, stimulation regimen, and infertility diagnosis. The primary outcome was CPR and secondary outcomes were live birth and miscarriage. RESULTS: One thousand one hundred fifty-four cycles were analyzed. Of the 162 cycles that resulted in a CPR (14.0%), most had an insemination TMC > 20 million. Compared to TMC > 20 million, there was no difference in CPR or LBR for lower TMC categories, excluding the TMC < 2 million group, in which there were no pregnancies. When TMC was stratified by deciles, there was also no difference in CPR and LBR, including within the lowest decile (TMC 0.09-8.6 million). Younger age and higher ovarian reserve parameters were associated with higher pregnancy and LBR when stratified by TMC. There was no difference in pregnancy and LBR when considering different stimulation protocols. CONCLUSIONS: Our data suggest that pregnancy and LBR are equivalent above a TMC of 2 million. Data stratified by TMC and patient parameters can be used to counsel patients pursuing ART.

Placental Expression of ACE2 and TMPRSS2 in Maternal Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Are Placental Defenses Mediated by Fetal Sex?

BACKGROUND: Expression of angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2), host molecules required for viral entry, may underlie sex differences in vulnerability to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated whether placental ACE2 and TMPRSS2 expression vary by fetal sex in the presence of maternal SARS-CoV-2 infection. METHODS: Placental ACE2 and TMPRSS2 expression was quantified by quantitative reverse transcription polymerase chain reaction (RT-PCR) and by Western blot in 68 pregnant women (38 SARS-CoV-2 positive, 30 SARS-CoV-2 negative) delivering at Mass General Brigham from April to June 2020. The impact of fetal sex and maternal SARS-CoV-2 exposure on ACE2 and TMPRSS2 was analyzed by 2-way analysis of variance (ANOVA). RESULTS: Maternal SARS-CoV-2 infection impacted placental TMPRSS2 expression in a sexually dimorphic fashion (2-way ANOVA interaction, P = .002). We observed no impact of fetal sex or maternal SARS-CoV-2 status on ACE2. TMPRSS2 expression was significantly correlated with ACE2 expression in males (Spearman ρ = 0.54, P = .02) but not females (ρ = 0.23, P = .34) exposed to maternal SARS-CoV-2. CONCLUSIONS: Sex differences in placental TMPRSS2 but not ACE2 were observed in the setting of maternal SARS-CoV-2 infection, which may have implications for offspring vulnerability to placental infection.