Noninvasive single-cell-based prenatal genetic testing: A proof of concept clinical study.

OBJECTIVE: To clinically assess a cell-based noninvasive prenatal genetic test using sequence-based copy number analysis of single trophoblasts from maternal blood. METHODS: Blood was obtained from 401 (243 + 158) individuals (8-22 weeks) and shipped overnight. Red cells were lysed, and nucleated cells stained for cytokeratin (CK) and CD45 and enriched for positive CK staining. Automated scanning was used to identify and pick single CK+ /CD45- trophoblasts which were subjected to next-generation sequencing. RESULTS: Blood was obtained from 243 pregnancies scheduled for CVS or amniocentesis. Luna results were normal for 160 singletons while 15 cases were abnormal (14 aneuploidy and one monozygotic twin with Williams syndrome deletion). The deletion was confirmed in both fetuses. Placental mosaicism occurred in 7 of 236 (3.0%) Luna cases and in 3 of 188 (1.6%) CVS cases (total 4.6%). No scorable trophoblasts were recovered in 32 of 236 usable samples. Additionally, 158 low-risk pregnancies not undergoing CVS/amniocentesis showed normal results in 133 cases. Seven had aneuploidy results, and there were three likely pathogenic deletions/duplications, including one15q11-q13 deletion. CONCLUSION: Although the sample size is modest and statistically accurate measures of test performance are not possible, the Luna test detected aneuploidy and deletions/duplications based on concordance with CVS/amniocentesis.

Postpartum Hemorrhage after Vaginal Delivery is Associated with a Decrease in Immediate Breastfeeding Success.

OBJECTIVE: This study aimed to identify the impact of postpartum hemorrhage (PPH) after vaginal delivery on immediate breastfeeding success. STUDY DESIGN: This is a retrospective cohort study examining the impact of PPH on breastfeeding for nulliparous patients after term, singleton, vaginal deliveries at a large academic institution from 2017 to 2018. Indicators of successful breastfeeding in the immediate postpartum period were measured by the presence of breastfeeding, the need for formula supplementation, the average number of breastfeeding sessions per day, the average amount of time spent at each breastfeeding session, the average number of newborn stools and wet diapers produced daily, and the neonatal percentage in weight loss over the first 2 to 3 days of life. RESULTS: A total of 1,904 women met inclusion criteria during the study period, 262 (13.8%) of whom experienced PPH, defined as an estimated blood loss of 500 mL or greater after vaginal delivery. Women who had a PPH had significantly fewer breastfeeding sessions on average (ß = -0.06, p-value 0.01) and required more time at each breastfeeding session (ß = 0.08, p-value <0.002). Neonates of women with PPH had a larger percentage in weight loss over the first 2 to 3 days of life compared with those without PPH (ß = 0.06, p = 0.008). CONCLUSION: Women who experience PPH after vaginal delivery have a decreased number of breastfeeding sessions despite spending more time trying to breastfeed, and an increased percentage in neonatal weight loss over the first 2 to 3 days of life. Further work is needed to elicit the mechanism behind this association; however, it is possible that PPH results in decreased secretion of endogenous oxytocin from the hypothalamic-pituitary axis as a result of hypovolemia. These women may therefore require additional breastfeeding support for successful breastfeeding initiation in the immediate postpartum period. KEY POINTS: · Women who experience PPH after vaginal delivery have decreased breastfeeding success.. · Further work is needed to elicit the mechanism behind this association.. · These women may require additional support for successful breastfeeding initiation postpartum..

Timing of birth and adverse pregnancy outcomes in cases of prenatally diagnosed vasa previa: a systematic review and meta-analysis.

OBJECTIVE: The ideal time for birth in pregnancies diagnosed with vasa previa remains unclear. We conducted a systematic review aiming to identify the gestational age at delivery that best balances the risks for prematurity with that of pregnancy prolongation in cases with prenatally diagnosed vasa previa. DATA SOURCES: Ovid MEDLINE, PubMed, CINAHL, Embase, Scopus, and Web of Science were searched from inception to January 2022. STUDY ELIGIBILITY CRITERIA: The intervention analyzed was delivery at various gestational ages in pregnancies prenatally diagnosed with vasa previa. Cohort studies, case series, and case reports were included in the qualitative synthesis. When summary figures could not be obtained directly from the studies for the quantitative synthesis, authors were contacted and asked to provide a breakdown of perinatal outcomes by gestational age at birth. METHODS: Study appraisal was completed using the National Institutes of Health quality assessment tool for the respective study types. Statistical analysis was performed using a random-effects meta-analysis of proportions. RESULTS: The search identified 3435 studies of which 1264 were duplicates. After screening 2171 titles and abstracts, 140 studies proceeded to the full-text screen. A total of 37 studies were included for analysis, 14 of which were included in a quantitative synthesis. Among 490 neonates, there were 2 perinatal deaths (0.4%), both of which were neonatal deaths before 32 weeks' gestation. In general, the rate of neonatal complications decreased steadily from <32 weeks' gestation (4.6% rate of perinatal death, 91.2% respiratory distress, 11.4% 5-minute Apgar score <7, 23.3% neonatal blood transfusion, 100% neonatal intensive care unit admission, and 100% low birthweight) to 36 weeks' gestation (0% perinatal death, 5.3% respiratory distress, 0% 5-minute Apgar score <7, 2.9% neonatal blood transfusion, 29.2% neonatal intensive care unit admission, and 30.9% low birthweight). Complications then increased slightly at 37 weeks' gestation before decreasing again at 38 weeks' gestation. CONCLUSION: Prolonging pregnancies until 36 weeks' gestation seems to be safe and beneficial in otherwise uncomplicated pregnancies with antenatally diagnosed vasa previa.

Late preterm antenatal corticosteroids in singleton and twin gestations: a retrospective cohort study.

BACKGROUND: In 2016, the American College of Obstetricians and Gynecologists recommended antenatal corticosteroids in the late preterm period for women at risk for preterm delivery. Limited real-world evidence exists on neonatal outcomes, particularly for twin gestations, following the guideline change. The study objective is to determine the association of antenatal corticosteroids in late preterm singleton and twin pregnancies with respiratory complications and hypoglycemia in a real-world clinical setting. METHODS: This is a retrospective cohort study comprising late preterm deliveries (4,341 mother-child pairs) within the Mount Sinai Health System, 2012-2018. The exposure of interest is antenatal corticosteroid administration of betamethasone during pregnancy between 34 0/7 and 36 6/7 weeks. Our primary outcomes are neonatal respiratory complications and hypoglycemia. Multivariable logistic regression was used to estimate the association between antenatal corticosteroid exposure and these two outcomes. We stratified the study population by singleton gestations and twins to minimize the potential confounding from different obstetric management between the two groups. RESULTS: Among a total of 4,341 mother-child pairs (3,309 singleton and 1,032 twin mother-child pairs), 745 mothers received betamethasone, of which 40.94% (305/745) received the full course. Relative to no treatment, a full course of betamethasone was associated with reduced odds of respiratory complications (OR = 0.53, 95% CI:[0.31-0.85], p < 0.01) and increased odds of hypoglycemia (OR = 1.86, 95%CI:[1.34-2.56], p < 0.01) in singletons; however, the association with respiratory complications was not significant in twins (OR = 0.42, 95% CI:[0.11-1.23], p = 0.16), but was associated with increased odds of hypoglycemia (OR = 2.18, 95% CI:[1.12-4.10], p = 0.02). A partial course of betamethasone (relative to no treatment) was not significantly associated with any of the outcomes, other than respiratory complications in twins (OR = 0.34, 95% CI:[0.12-0.82], p = 0.02). CONCLUSIONS: Exposure to antenatal corticosteroids in singletons and twins is associated with increased odds of hypoglycemia. Among singletons, exposure to the full dosage (i.e. two doses) was associated with decreased odds of respiratory complications but this was only the case for partial dose among twins. Twin gestations were not studied by the Antenatal Late Preterm Steroids trial. Therefore, our study findings will contribute to the paucity of evidence on the benefit of antenatal corticosteroids in this group. Health systems should systematically monitor guideline implementations to improve patient outcomes.

Stress and the Psychological Impact of the COVID-19 Pandemic on Frontline Obstetrics and Gynecology Providers.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic rapidly overwhelmed global health care systems in 2020, with New York City (NYC) marking the first epicenter in the United States. High levels of stress amongst health care workers have been reported in pandemics, but less is known about stress amongst Obstetrics and Gynecology (OB/GYN) providers. We sought to describe levels of stress, anxiety, depression, and other aspects of mental health among OB/GYN health care workers during the first wave of the COVID-19 pandemic. STUDY DESIGN: We conducted an anonymous cross-sectional electronic survey of a wide range of OB/GYN clinicians in a large NYC hospital system in the spring of 2020. We used both original survey questions and validated screening tools to assess stress, anxiety, depression, and burnout. We calculated median scores for these tools and compared median score between provider types. We also adapted questions on pandemic-related stressors from the MERS and SARS pandemics to fit the context of the COVID-19 pandemic and OB/GYN providers. RESULTS: A total of 464 providers met study inclusion criteria, and 163 providers completed the survey (response rate = 35.1%). Approximately 35% of providers screened positive for anxiety and 21% for depression. Scores for depression, burnout, and fulfillment varied by provider type, with nurses scoring higher than physicians (p <0.05). The majority of respondents reported stress from pandemic and OB-specific stressors, including the possibility of transmitting COVID-19 to friends and family (83.9%, [95% confidence interval or CI 78.0-89.8%]), uncertainty regarding the pandemic's trajectory (91.3% [86.7-95.8%]), and frequent policy changes on labor and delivery (72.7% [65.1-80.3%]). CONCLUSION: OB/GYN providers reported high levels of stress during the COVID-19 pandemic. The stress of caring for laboring patients during a pandemic may disproportionately affect nurses and trainees and highlights the need to provide interventions to ameliorate the negative impact of a pandemic on the mental health of our OB/GYN health care workers. KEY POINTS: · COVID-19 led to stress amongst OB/GYN providers.. · Some stressors were unique to providing obstetric care.. · Nurses and trainees were more affected by this stress..

Comparison of Breastfeeding Success by Mode of Delivery.

OBJECTIVE: This article identifies how mode of delivery and the presence of labor affect the initiation and effectiveness of breastfeeding. STUDY DESIGN: This is a retrospective cohort study of breastfeeding success after vaginal delivery, cesarean section after labor, and scheduled cesarean section in term, singleton deliveries in nulliparous patients at a large academic institution from 2017 to 2018. Exclusion criteria included major postpartum complications requiring admission to the surgical intensive care unit or neonatal intensive care unit, general anesthesia, and major fetal anomalies. Breastfeeding success in the immediate postpartum period, defined as the first 2 to 3 days postpartum prior to hospital discharge, was measured by the presence of breastfeeding, the need for formula supplementation, the average number of breastfeeding sessions per day, the average amount of time spent at each breastfeeding session, the average number of newborn stools and wet diapers produced daily, and the neonatal percentage in weight loss over the first 2 to 3 days of life. Multivariable linear and logistic regression were used to assess the association between mode of delivery and markers of breastfeeding success after adjusting for potential confounders. A Tukey's post hoc analysis with pairwise comparisons was performed to assess differences in breastfeeding outcomes between vaginal delivery, scheduled cesarean section, and cesarean section after labor. RESULTS: A total of 2,966 women met inclusion criteria during the study period, 1,936 (65.3%) of whom underwent spontaneous vaginal delivery, 415 (14.0%) of whom delivered by scheduled cesarean section, and 615 (20.7%) of whom underwent cesarean section after labor. There were significant differences in maternal age, obesity, race/ethnicity, insurance status, gestational age at delivery, birth weight, and 1-minute Apgar's score less than 7 between vaginal delivery, scheduled cesarean section, and cesarean section after labor. There were also significant differences between indication for oxytocin, type of anesthesia, and postpartum hemorrhage between the three groups. After controlling for these factors, women who underwent vaginal delivery were more likely to have infants with decreased need for formula supplementation (adjusted odds ratio [aOR] = 1.71, 95% confidence interval [CI]: 1.52-1.93) and were less likely to switch from breast to formula feeding (aOR = 1.71, 95% CI: 1.04-1.31) in comparison to women who delivered via cesarean section in labor or scheduled cesarean section. The infants of these women also had an increased number of breastfeeding sessions on average (ß = 0.06, p = 0.002), required fewer number of daily formula feedings (ß = 0.14, p < 0.001), and experienced a smaller percentage in neonatal weight loss over the first 2 to 3 days of life (ß = 0.18, p < 0.001) compared to those born after cesarean section and cesarean section after labor. These women comparatively required less time at each breastfeeding session (ß = 0.06, p = 0.005), and produced fewer wet diapers and stools on average (ß = 0.12, p < 0.001 and ß = 0.12, p < 0.001, respectively). On post hoc analysis with pairwise comparisons, and on separate sensitivity analysis of only women who underwent cesarean delivery, there was no difference in breastfeeding outcome measures between scheduled cesarean section and cesarean section in labor. CONCLUSION: Women who deliver by cesarean section, despite the presence or absence of labor, are less likely to maintain exclusive breastfeeding postpartum and are more likely to require formula supplementation. These women may need more support with breastfeeding after surgery in order to experience similar benefits for neonatal growth and weight gain. KEY POINTS: · Women who deliver by cesarean section are less likely to maintain exclusive breastfeeding.. · Women who deliver by cesarean section are more likely to require formula supplementation.. · Women may need more support with breastfeeding after cesarean delivery..

A Survey of Labor and Delivery Practices in New York City during the COVID-19 Pandemic.

Recently, a novel coronavirus, precisely severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), that causes the disease novel coronavirus disease 2019 (COVID-19) has been declared a worldwide pandemic. Over a million cases have been confirmed in the United States. As of May 5, 2020, New York State has had over 300,000 cases and 24,000 deaths with more than half of the cases and deaths occurring in New York City (NYC). Little is known, however, of how this virus impacts pregnancy. Given this lack of data and the risk for severe disease in this relatively immunocompromised population, further understanding of the obstetrical management of COVID-19, as well as hospital level preparation for its control, is crucial. Guidance has come from expert opinion, professional societies and public health agencies, but to date, there is no report on how obstetrical practices have adapted these recommendations to their local situations. We therefore developed an internet-based survey to elucidate the practices put into place to guide the care of obstetrical patients during the COVID-19 pandemic. We surveyed obstetrical leaders in four academic medical centers in NYC who were implementing and testing protocols at the height of the pandemic. We found that all sites made changes to their practices, and that there appeared to be agreement with screening and testing for COVID-19, as well as labor and delivery protocols, for SARS-CoV-2-positive patients. We found less consensus with respect to inpatient antepartum fetal surveillance. We hope that this experience is useful to other centers as they formulate their plans to face this pandemic. KEY POINTS: · Practices changed to accommodate public health needs.. · Most practices are screened for novel COVID-19 on admission.. · Fetal testing in COVID-19 patients varied..

Comparing pregnancy outcomes and loss rates in elective twin pregnancy reduction with ongoing twin gestations in a large contemporary cohort.

BACKGROUND: As compared with singleton gestations, twin pregnancies are associated with a significantly higher risk of preterm birth and maternal complications as well as fetal and neonatal morbidity and mortality. Multifetal pregnancy reduction is a technique developed in the 1980s to reduce the fetal number in higher-order multiple pregnancies to reduce the risk of adverse pregnancy outcomes, most importantly preterm birth. OBJECTIVE: The objective of the study was to compare pregnancy outcomes and loss rates in elective twin pregnancy reduction to ongoing twin gestations in a large contemporary cohort. STUDY DESIGN: This was a retrospective review of dichorionic diamniotic twin gestations that underwent first-trimester ultrasound at our institution from January 2008 to September 2016. Planned elective 2-to-1 multifetal pregnancy reductions at less than 15 weeks' gestation were compared with ongoing dichorionic diamniotic twin gestations. Data were collected via chart review. Demographics between 2-to-1 reduced singletons and ongoing twins were assessed using a Student t test or a Wilcoxon rank-sum test, as appropriate, for continuous variables and χ2 or Fisher exact tests, as appropriate, for categorical variables. Univariable and multivariable logistic regressions were used to compare pregnancy outcomes between ongoing twins and reduced singletons adjusting for maternal age, body mass index, race, in vitro fertilization, use of chorionic villus sampling, prior term birth, and prior preterm birth. RESULTS: Of 1070 dichorionic diamniotic twin pregnancies identified, completed follow-up data were available and analyzed for 855 patients (79.9%). Among those, 250 (29.2%) were 2-to-1 singletons and 605 (70.8%) were ongoing twins. Reduced singleton patients were slightly older, more likely white, and had lower body mass index. They were also more likely to have undergone in vitro fertilization (63.6% vs 48.8%), had chorionic villus sampling (92% vs 37.5%), and had prior term births (54% vs 35.7%). Compared with 2-to-1 singletons, the adjusted odds of having preterm delivery at 37 weeks for ongoing twins were 5.62 times (95% confidence interval, 3.67-8.61; P < .001) and 2.22 times (95% confidence interval, 1.20-4.11; P < .001) at 34 weeks. While intrauterine growth restriction, placental abruption, and gestational diabetes were not significant, ongoing twins were more likely to have a cesarean delivery (odds ratio, 5.53, 95% confidence interval, 3.60-8.49; P < .001) and preeclampsia (odds ratio, 3.33, 95% confidence interval, 1.60-6.96; P < .001) after adjusting for maternal characteristics. There were also significant differences between groups for preterm premature rupture of membranes and low birthweight at less than the fifth and 10th percentiles. Total pregnancy loss (at 24 and 20 weeks) was similar between singleton and ongoing twins (4% vs 2.5%, P = .23, and 3.6% vs 1.7%, P = .09 for respective weeks). There were no significant differences in the rate of unintended pregnancy loss (2.4% vs 2.3%; P = .94) and the rate of intrauterine fetal death greater than 24 weeks (1.2% vs 0.7%; P = .43) in reduced singleton versus ongoing twin group, respectively. CONCLUSION: In our study, patients who elected to reduce to a singleton pregnancy had a higher gestational age of delivery and lower rates of preterm birth and pregnancy complications without an increased risk of pregnancy loss.

Are Women with a History of Low PAPP-A at Risk for Adverse Perinatal Outcomes in a Subsequent Pregnancy?

OBJECTIVE: To determine if patients with a history of low pregnancy-associated plasma protein A (PAPP-A) in an initial pregnancy are at higher risk for adverse obstetric outcomes in a subsequent pregnancy. STUDY DESIGN: This was a retrospective cohort study in patients who underwent first trimester screening for PAPP-A in two consecutive pregnancies. Two groups were examined: patients who had low PAPP-A in the first pregnancy followed by normal PAPP-A in the second pregnancy and patients who had recurrent low PAPP-A. Maternal and neonatal outcomes were compared between the groups, with the primary outcome being intrauterine growth restriction (IUGR) or preeclampsia. RESULTS: A total of 124 patients were included, representing 248 pregnancies. Ninety-two (74.2%) patients had normal PAPP-A in the second pregnancy, and 32 (12.9%) patients had recurrent low PAPP-A. Patients with recurrent low PAPP-A had a higher rate of IUGR or preeclampsia compared with patients with normal PAPP-A in the second pregnancy but this was not significantly different (12.5 vs. 10.9%, p = 0.51). There were no significant differences for all other outcomes. CONCLUSION: Among patients with a history of low PAPP-A, patients with normal PAPP-A in the subsequent pregnancy have a similar risk of adverse neonatal outcomes compared with patients with recurrent low PAPP-A.

Variation in Cervical Length over Time during a Single Transvaginal Ultrasound Examination.

OBJECTIVE: To quantify the degree of change in cervical length (CL) over a 3-minute transvaginal ultrasound. STUDY DESIGN: We conducted a prospective observational study of nulliparous patients who underwent routine transvaginal CL screening at the time of their second-trimester ultrasound. We recorded CL at four time points (0, 1, 2, 3 minutes) and compared these values to determine the minute-to-minute change within a single patient. RESULTS: A total of 771 patients were included. The mean gestational age was 20.8 weeks (±0.84). We used a linear mixed effect model to assess if each minute during the ultrasound is associated with a change in CL. The intraclass correlation coefficient between minute 0 to minute 3 was 0.82 (95% confidence interval: 0.80, 0.84). This indicates that there is a relatively high within-patient correlation in CL during their ultrasound. Additionally, we stratified patients based on their starting CL; the intraclass correlation coefficient remained high for all groups. We additionally compared CL at each minute. Although there is a statistically significant difference between several time points, the actual difference is small and not clinically meaningful. CONCLUSION: The variation in CL over a 3-minute transvaginal ultrasound examination is not clinically significant. It may be reasonable to conduct this examination over a shorter period.

Prenatal sonography of multicentric infantile myofibromatosis: Case report and review of the literature.

Scant literature exists on prenatally diagnosed infantile myofibromatosis (IM). We report a case of multicentric IM, which was first recognized as a soft-tissue paraspinal mass on prenatal sonography and subsequently characterized by MRI with pathological confirmation.

Trends in characteristics of women choosing contraindicated home births.

OBJECTIVE: To characterize the American College of Obstetricians and Gynecologists (ACOG) contraindicated home births and the women who are receiving these births in hopes of identifying venues for intervention. METHODS: The National Center for Health Statistics (NCHS) birth certificate records from 1990 to 2015 were used. "Planned home births" were defined as those births in which birthplace was coded as "residence" and birth attendant was coded as "certified nurse midwife (CNM)" or "other midwife". Contraindicated home births were defined as "planned home births" from 1990 to 2015 that had one or more of the ACOG risk factors for home births, which include vaginal birth after prior cesarean delivery (VBAC), breech presentation and multiple gestations. RESULTS: A review of trends in contraindicated home births from 1990 to 2015 suggests that they are increasing in number (481-1396) and as a percentage of total births (0.01%-0.04%, P<0.001). There has been an increase in the proportion of college-educated women (31%-51%, P<0.001). Most women receive prenatal care (>95%), which is most frequently initiated in the first trimester. The majority of home births were paid out-of-pocket (65%-69%). CONCLUSION: The increasing number of contraindicated home births in the United States requires public health action. Home births are likely a matter of choice rather than a lack of resources. It is unclear if women choose home births while knowing the risk or due to a lack of information. Prenatal education about contraindicated home births is possible, as almost all women receive prenatal care.

A randomized trial of Foley balloon induction of labor trial in nulliparas (FIAT-N).

BACKGROUND: With an increasing rate of induction of labor, it is important to choose induction methods that are safe and efficient in achieving a vaginal delivery. The optimal method for inducing nulliparous women with an unfavorable cervix is not known. OBJECTIVE: We sought to determine if induction of labor with simultaneous use of oxytocin and Foley balloon vs sequential use of Foley balloon followed by oxytocin decreases the time to delivery in nulliparous women. STUDY DESIGN: We conducted a randomized controlled trial of nulliparous women presenting for induction at a single institution from December 2013 through March 2015. After decision for induction was made by their primary provider, women with gestational age ≥24 weeks with a nonanomalous, singleton fetus in vertex presentation with intact membranes were offered participation. Exclusion criteria included history of uterine surgery, unexplained vaginal bleeding, latex allergy, or contraindication to vaginal delivery. Participants were randomized to either simultaneous (oxytocin and Foley balloon) or sequential (oxytocin after expulsion of Foley balloon) induction group. The primary outcome was time from induction to delivery. Secondary outcomes included mode of delivery, estimated blood loss, postpartum hemorrhage, chorioamnionitis, and composite neonatal outcome. Maternal and neonatal outcomes were collected via chart review. Analyses were done on an intention-to-treat basis. RESULTS: A total of 166 patients were enrolled; 82 in the simultaneous and 84 in the sequential group. There were no differences in baseline characteristics in the 2 groups. Patients who received simultaneous oxytocin with insertion of a Foley balloon delivered significantly earlier (15.92 vs 18.87 hours, P = .004) than those in the sequential group. There was no difference in rate of cesarean delivery, estimated blood loss, postpartum hemorrhage, chorioamnionitis, or composite neonatal outcome. CONCLUSION: Simultaneous use of oxytocin and Foley balloon for induction of labor results in a significantly shorter interval to delivery in nulliparas.

Timing of and outcomes after selective termination of anomalous fetuses in dichorionic twin pregnancies.

OBJECTIVE: The objective of this article is to determine if selective termination (ST) of an anomalous dichorionic twin at early gestational age (GA) is associated with a decreased risk of fetal loss and prematurity. METHOD: All patients who had ST for dichorionic twin pregnancies from 2004 through 2010 at Mount Sinai Medical Center were included. Data were collected via chart review and patient interview. Two case-control analyses were carried out: first, cases were nonviable deliveries, and controls were live births; and second, cases were live births <37 weeks' GA, and controls were live births ≥37 weeks' GA. Univariable and then multivariable analyses identified characteristics associated with pregnancy loss and prematurity. RESULTS: Among 80 participants, there were four (5%) fetal losses and 15 (19%) premature births. GA at ST was the only characteristic associated with pregnancy loss in multivariable exact logistic regression [OR = 1.43, 95% CI (1.03, 2.26), P = 0.03]. GA at ST was the only characteristic associated with premature delivery in multivariable exact logistic regression [OR = 1.18, 95% CI (1.02, 1.37), P = 0.03]. CONCLUSION: This study suggests that ST performed earlier in pregnancy is associated with decreased fetal loss and prematurity.

Pathophysiology of Preeclampsia-Induced Vascular Dysfunction and Implications for Subclinical Myocardial Damage and Heart Failure.

Tragically, preeclampsia is a leading cause of pregnancy-related complications and is linked to a heightened risk for morbid and fatal cardiovascular disease (CVD) outcomes. Although the mechanism connecting preeclampsia to CVD risk has yet to be fully elucidated, evidence suggests distinct pathways of early and late preeclampsia with shared CV risk factors but with profound differences in perinatal and postpartum risk to the mother and infant. In early preeclampsia, <34 weeks of gestation, systemic vascular dysfunction contributes to near-term subclinical myocardial damage. Hypertrophy and diastolic abnormalities persist postpartum and contribute to early onset heart failure (HF). This HF risk remains elevated decades later and contributes to premature death. Black women are at the highest risk of preeclampsia and HF. These findings support closer monitoring of women postpartum, especially for those with early and severe preeclampsia to control chronic hypertension and reduce the potentially preventable sequelae of heightened CVD and HF risk.

Improving preeclampsia risk prediction by modeling pregnancy trajectories from routinely collected electronic medical record data.

Preeclampsia is a heterogeneous and complex disease associated with rising morbidity and mortality in pregnant women and newborns in the US. Early recognition of patients at risk is a pressing clinical need to reduce the risk of adverse outcomes. We assessed whether information routinely collected in electronic medical records (EMR) could enhance the prediction of preeclampsia risk beyond what is achieved in standard of care assessments. We developed a digital phenotyping algorithm to curate 108,557 pregnancies from EMRs across the Mount Sinai Health System, accurately reconstructing pregnancy journeys and normalizing these journeys across different hospital EMR systems. We then applied machine learning approaches to a training dataset (N = 60,879) to construct predictive models of preeclampsia across three major pregnancy time periods (ante-, intra-, and postpartum). The resulting models predicted preeclampsia with high accuracy across the different pregnancy periods, with areas under the receiver operating characteristic curves (AUC) of 0.92, 0.82, and 0.89 at 37 gestational weeks, intrapartum and postpartum, respectively. We observed comparable performance in two independent patient cohorts. While our machine learning approach identified known risk factors of preeclampsia (such as blood pressure, weight, and maternal age), it also identified other potential risk factors, such as complete blood count related characteristics for the antepartum period. Our model not only has utility for earlier identification of patients at risk for preeclampsia, but given the prediction accuracy exceeds what is currently achieved in clinical practice, our model provides a path for promoting personalized precision therapeutic strategies for patients at risk.

Pain perception during transabdominal chorionic villus sampling: a randomized trial comparing topical ethyl chloride anesthetic spray and lidocaine injection.

Background: Chorionic villus sampling is an important invasive procedure used for early antenatal genetic testing that can be associated with anxiety and fear of pain. Pain analgesia prior to chorionic villus sampling can be offered with subdermal lidocaine; however, lidocaine injection itself is associated with pain. Our objective was to determine whether administration of topical ethyl chloride anesthetic spray is associated with decreased pain perception during transabdominal chorionic villus sampling compared to 1% lidocaine subdermal injection.Study design: Women undergoing transabdominal chorionic villus sampling from 10 to 13 weeks and 6 days in an outpatient setting were randomized with equal allocation to either 1% lidocaine injection or topical ethyl chloride anesthetic spray prior to the procedure. Women were asked about their pain on a scale of 0-100 prior to, during, and after the procedure. The primary outcome was pain perception during time of transabdominal chorionic villus sampling as measured on a 100-mm visual analog scale. The secondary outcome was pain immediately after procedure.Results: From October 2016 to June 2017, a total of 120 women were enrolled (63 in the lidocaine injection group and 57 in the topical ethyl chloride anesthetic spray group). Baseline demographic characteristics were similar between groups. During the procedure, patients in the topical ethyl chloride arm demonstrated significantly higher pain scores compared to the lidocaine injection group (median score of 50 mm (interquartile range [IQR]: 40-65) versus 50 mm (IQR: 30-60); p = .03). There was no significant difference in pain scores before or after the procedure.Conclusion: During transabdominal chorionic villus sampling procedures, topical ethyl chloride anesthetic spray is associated with a higher distribution of pain scores as compared to 1% lidocaine subdermal injection, which suggests higher levels of pain.Clinical trial registration: This trial is registered with clinicaltrials.gov (NCT03140293). https://clinicaltrials.gov/ct2/show/NCT03140293?term=NCT03140293&rank=1.

Genomic loss of imprinting in first-trimester human placenta.

OBJECTIVE: The purpose of this study was to investigate imprinting patterns in first-trimester human placentas. STUDY DESIGN: Using samples of 17 first-trimester and 14 term placentas from uncomplicated pregnancies, we assessed loss of imprinting (LOI) at the RNA level in a panel of 14 genes that are known to be imprinted in the placenta with the use of a quantitative allele-specific reverse transcriptase polymerase chain reaction analysis of those genes that contained readout single nucleotide polymorphisms in their transcripts. RESULTS: There is significant LOI (ie, biallelic expression) in all 14 genes in first-trimester placentas. LOI was more variable and generally at lower levels at term. Although there is little difference in gene expression, the level of LOI is higher in the first-trimester placentas, compared with term placentas. CONCLUSION: Genomic imprinting appears to be a dynamic maturational process across gestation in human placenta. In contrast with prevailing theories, epigenetic imprints may continue to evolve past 12 weeks of gestation.