Treatment for Mild Chronic Hypertension during Pregnancy.

BACKGROUND: The benefits and safety of the treatment of mild chronic hypertension (blood pressure, <160/100 mm Hg) during pregnancy are uncertain. Data are needed on whether a strategy of targeting a blood pressure of less than 140/90 mm Hg reduces the incidence of adverse pregnancy outcomes without compromising fetal growth. METHODS: In this open-label, multicenter, randomized trial, we assigned pregnant women with mild chronic hypertension and singleton fetuses at a gestational age of less than 23 weeks to receive antihypertensive medications recommended for use in pregnancy (active-treatment group) or to receive no such treatment unless severe hypertension (systolic pressure, ≥160 mm Hg; or diastolic pressure, ≥105 mm Hg) developed (control group). The primary outcome was a composite of preeclampsia with severe features, medically indicated preterm birth at less than 35 weeks' gestation, placental abruption, or fetal or neonatal death. The safety outcome was small-for-gestational-age birth weight below the 10th percentile for gestational age. Secondary outcomes included composites of serious neonatal or maternal complications, preeclampsia, and preterm birth. RESULTS: A total of 2408 women were enrolled in the trial. The incidence of a primary-outcome event was lower in the active-treatment group than in the control group (30.2% vs. 37.0%), for an adjusted risk ratio of 0.82 (95% confidence interval [CI], 0.74 to 0.92; P<0.001). The percentage of small-for-gestational-age birth weights below the 10th percentile was 11.2% in the active-treatment group and 10.4% in the control group (adjusted risk ratio, 1.04; 95% CI, 0.82 to 1.31; P = 0.76). The incidence of serious maternal complications was 2.1% and 2.8%, respectively (risk ratio, 0.75; 95% CI, 0.45 to 1.26), and the incidence of severe neonatal complications was 2.0% and 2.6% (risk ratio, 0.77; 95% CI, 0.45 to 1.30). The incidence of any preeclampsia in the two groups was 24.4% and 31.1%, respectively (risk ratio, 0.79; 95% CI, 0.69 to 0.89), and the incidence of preterm birth was 27.5% and 31.4% (risk ratio, 0.87; 95% CI, 0.77 to 0.99). CONCLUSIONS: In pregnant women with mild chronic hypertension, a strategy of targeting a blood pressure of less than 140/90 mm Hg was associated with better pregnancy outcomes than a strategy of reserving treatment only for severe hypertension, with no increase in the risk of small-for-gestational-age birth weight. (Funded by the National Heart, Lung, and Blood Institute; CHAP ClinicalTrials.gov number, NCT02299414.).

Placental Abruption and Cardiovascular Event Risk (PACER): Design, data linkage, and preliminary findings.

BACKGROUND: Obstetrical complications impact the health of mothers and offspring along the life course, resulting in an increased burden of chronic diseases. One specific complication is abruption, a life-threatening condition with consequences for cardiovascular health that remains poorly studied. OBJECTIVES: To describe the design and data linkage algorithms for the Placental Abruption and Cardiovascular Event Risk (PACER) cohort. POPULATION: All subjects who delivered in New Jersey, USA, between 1993 and 2020. DESIGN: Retrospective, population-based, birth cohort study. METHODS: We linked the vital records data of foetal deaths and live births to delivery and all subsequent hospitalisations along the life course for birthing persons and newborns. The linkage was based on a probabilistic record-matching algorithm. PRELIMINARY RESULTS: Over the 28 years of follow-up, we identified 1,877,824 birthing persons with 3,093,241 deliveries (1.1%, n = 33,058 abruption prevalence). The linkage rates for live births-hospitalisations and foetal deaths-hospitalisations were 92.4% (n = 2,842,012) and 70.7% (n = 13,796), respectively, for the maternal cohort. The corresponding linkage rate for the live births-hospitalisations for the offspring cohort was 70.3% (n = 2,160,736). The median (interquartile range) follow-up for the maternal and offspring cohorts was 15.4 (8.1, 22.4) and 14.4 (7.4, 21.0) years, respectively. We will undertake multiple imputations for missing data and develop inverse probability weights to account for selection bias owing to unlinked records. CONCLUSIONS: Pregnancy offers a unique window to study chronic diseases along the life course and efforts to identify the aetiology of abruption may provide important insights into the causes of future CVD. This project presents an unprecedented opportunity to understand how abruption may predispose women and their offspring to develop CVD complications and chronic conditions later in life.

Metformin Plus Insulin for Preexisting Diabetes or Gestational Diabetes in Early Pregnancy: The MOMPOD Randomized Clinical Trial.

Importance: Insulin is recommended for pregnant persons with preexisting type 2 diabetes or diabetes diagnosed early in pregnancy. The addition of metformin to insulin may improve neonatal outcomes. Objective: To estimate the effect of metformin added to insulin for preexisting type 2 or diabetes diagnosed early in pregnancy on a composite adverse neonatal outcome. Design, Setting, and Participants: This randomized clinical trial in 17 US centers enrolled pregnant adults aged 18 to 45 years with preexisting type 2 diabetes or diabetes diagnosed prior to 23 weeks' gestation between April 2019 and November 2021. Each participant was treated with insulin and was assigned to add either metformin or placebo. Follow-up was completed in May 2022. Intervention: Metformin 1000 mg or placebo orally twice per day from enrollment (11 weeks -<23 weeks) through delivery. Main Outcome and Measures: The primary outcome was a composite of neonatal complications including perinatal death, preterm birth, large or small for gestational age, and hyperbilirubinemia requiring phototherapy. Prespecified secondary outcomes included maternal hypoglycemia and neonatal fat mass at birth, and prespecified subgroup analyses by maternal body mass index less than 30 vs 30 or greater and those with preexisting vs diabetes early in pregnancy. Results: Of the 831 participants randomized, 794 took at least 1 dose of the study agent and were included in the primary analysis (397 in the placebo group and 397 in the metformin group). Participants' mean (SD) age was 32.9 (5.6) years; 234 (29%) were Black, and 412 (52%) were Hispanic. The composite adverse neonatal outcome occurred in 280 (71%) of the metformin group and in 292 (74%) of the placebo group (adjusted odds ratio, 0.86 [95% CI 0.63-1.19]). The most commonly occurring events in the primary outcome in both groups were preterm birth, neonatal hypoglycemia, and delivery of a large-for-gestational-age infant. The study was halted at 75% accrual for futility in detecting a significant difference in the primary outcome. Prespecified secondary outcomes and subgroup analyses were similar between groups. Of individual components of the composite adverse neonatal outcome, metformin-exposed neonates had lower odds to be large for gestational age (adjusted odds ratio, 0.63 [95% CI, 0.46-0.86]) when compared with the placebo group. Conclusions and Relevance: Using metformin plus insulin to treat preexisting type 2 or gestational diabetes diagnosed early in pregnancy did not reduce a composite neonatal adverse outcome. The effect of reduction in odds of a large-for-gestational-age infant observed after adding metformin to insulin warrants further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT02932475.

Super-Utilizers of Inpatient Care in an Obstetrical Population: A Cross-Sectional Study.

OBJECTIVES: The aim of the study is to estimate hospital charges (HC) and length of stay (LOS) for pregnancy and 6 weeks postpartum and to characterize the outliers who utilize a disproportionate share of health care resources. STUDY DESIGN: We performed a cross-sectional study of 500 subjects at a tertiary center between 2012 and 2014. Subjects were included who had inpatient status and an ICD-9 code for pregnancy; those with an ICD-9 code for ectopic pregnancy were excluded. Data were collected 266 days prior to the estimated date of delivery (EDD) and up to 42 days post-delivery. Medical diagnoses, obstetrical details, demographics, HC, and LOS were collected. Super-utilizers (SUs) were selected as patients with total HC exceeding $75,000, those who incurred $75,000 or less were assigned to the typical utilizer (TU) group. RESULTS: HC was positively skewed, with median's (interquartile range) of $151,143 (97,707-198,732) and $28,186 (19,292-38,943) among SUs and TUs, respectively. Despite the low proportion of SU patients (7%, n = 36), they accounted for 30% of charges. Similarly, SUs had longer LOS (16 vs. 3 days, p <0.05). They had earlier deliveries (34.5 vs. 38.5 weeks, p <0.05), higher cesarean section rates (69 vs. 35%, p <0.05), and more hysterectomies (8.3 vs. 0%, p <0.05). The most common complications in SUs were preterm labor (33.3 vs. 5.4%, p <0.05) and preterm premature rupture of membranes (25 vs. 3.9%, p< 0.05). The most common pre-existing condition in SUs was chronic hypertension (11.1 vs. 3%, p< 0.05). CONCLUSION: Although SUs comprise only 7% of the obstetrical population, they account for almost a third of the total HCs; in turn, SUs are at risk of adverse outcomes. Targeting this population can guide efforts to improve maternal health through prevention, research, and personalized care. SUs may have clustering at hospitals with higher levels of care and this topic warrants further investigation with state and national level data. KEY POINTS: · Just 7% of pregnant patients accounted for 30% of hospital charges.. · Super-utilizers had higher rates of preterm delivery, cesarean section, and hysterectomy.. · The most common pre-existing medical condition in super-utilizers was chronic hypertension..

Epidemiology of coronavirus disease 2019 in pregnancy: risk factors and associations with adverse maternal and neonatal outcomes.

BACKGROUND: Coronavirus disease 2019 may be associated with adverse maternal and neonatal outcomes in pregnancy, but there are few controlled data to quantify the magnitude of these risks or to characterize the epidemiology and risk factors. OBJECTIVE: This study aimed to quantify the associations of coronavirus disease 2019 with adverse maternal and neonatal outcomes in pregnancy and to characterize the epidemiology and risk factors. STUDY DESIGN: We performed a matched case-control study of pregnant patients with confirmed coronavirus disease 2019 cases who delivered between 16 and 41 weeks' gestation from March 11 to June 11, 2020. Uninfected pregnant women (controls) were matched to coronavirus disease 2019 cases on a 2:1 ratio based on delivery date. Maternal demographic characteristics, coronavirus disease 2019 symptoms, laboratory evaluations, obstetrical and neonatal outcomes, and clinical management were chart abstracted. The primary outcomes included (1) a composite of adverse maternal outcome, defined as preeclampsia, venous thromboembolism, antepartum admission, maternal intensive care unit admission, need for mechanical ventilation, supplemental oxygen, or maternal death, and (2) a composite of adverse neonatal outcome, defined as respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, 5-minute Apgar score of <5, persistent category 2 fetal heart rate tracing despite intrauterine resuscitation, or neonatal death. To quantify the associations between exposure to mild and severe or critical coronavirus disease 2019 and adverse maternal and neonatal outcomes, unadjusted and adjusted analyses were performed using conditional logistic regression (to account for matching), with matched-pair odds ratio and 95% confidence interval based on 1000 bias-corrected bootstrap resampling as the effect measure. Associations were adjusted for potential confounders. RESULTS: A total of 61 confirmed coronavirus disease 2019 cases were enrolled during the study period (mild disease, n=54 [88.5%]; severe disease, n=6 [9.8%]; critical disease, n=1 [1.6%]). The odds of adverse composite maternal outcome were 3.4 times higher among cases than controls (18.0% vs 8.2%; adjusted odds ratio, 3.4; 95% confidence interval, 1.2-13.4). The odds of adverse composite neonatal outcome were 1.7 times higher in the case group than to the control group (18.0% vs 13.9%; adjusted odds ratio, 1.7; 95% confidence interval, 0.8-4.8). Stratified analyses by disease severity indicated that the morbidity associated with coronavirus disease 2019 in pregnancy was largely driven by the severe or critical disease phenotype. Major risk factors for associated morbidity were black and Hispanic race, advanced maternal age, medical comorbidities, and antepartum admissions related to coronavirus disease 2019. CONCLUSION: Coronavirus disease 2019 during pregnancy is associated with an increased risk of adverse maternal and neonatal outcomes, an association that is primarily driven by morbidity associated with severe or critical coronavirus disease 2019. Black and Hispanic race, obesity, advanced maternal age, medical comorbidities, and antepartum admissions related to coronavirus disease 2019 are risk factors for associated morbidity.

Pharmacologic intervention for the management of retained placenta: a systematic review and meta-analysis of randomized trials.

BACKGROUND: Retained placenta affects 2% to 3.3% of all vaginal deliveries and is one of the leading causes of postpartum hemorrhage worldwide. Despite the prevalence of this condition, there is limited guidance on its management. OBJECTIVE: A systematic review and meta-analysis were performed to evaluate the efficacy of pharmacologic interventions for the management of retained placenta. STUDY DESIGN: PubMed, ClinicalTrials.gov, Cochrane Library, Web of Science, and Scopus were searched for full-text publications in English. Search terms included "retained placenta" AND "treatment" OR "therapy" OR "disease management" OR "Pitocin" OR "misoprostol" OR "Cytotec" OR "dinoprostone" OR "nitroglycerin" OR "carbetocin" OR "ergotamine," with no restriction on publication dates. Only randomized controlled trials were included. The primary outcome was the need for manual extraction of the placenta or dilation and curettage. Reviewers evaluated the quality of included articles using the Cochrane Collaboration's tool for assessing the risk of bias. Pooled risk ratios were estimated based on random- and fixed-effects analyses. Interstudy heterogeneity was considered when I2≥50%. RESULTS: The literature search identified 29 randomized controlled trials that met the inclusion criteria (2682 subjects). The most commonly used agent across the studies was oxytocin administered via umbilical vein injection; there was high heterogeneity among these studies (I2=62%). Oxytocin was inferior to carbetocin (risk ratio, 1.61; 95% confidence interval, 1.03-2.52) and prostaglandins (risk ratio, 2.63; 95% confidence interval, 1.18-5.86) for the primary outcome. For oxytocin, prostaglandin agents, and nitroglycerin, there was a trend toward favoring the study drug for the primary outcome compared with control or placebo. Compared with placebo or control, estimated blood loss was lower if pharmacologic interventions were administered, with a mean difference of 121.5 mL (95% confidence interval, -185.7 to -52.3). There was no difference in postpartum hemorrhage or the need for blood transfusion between pharmacologic interventions and placebo or control. CONCLUSION: Pooled estimates for oxytocin via umbilical vein injection, prostaglandin agents, and nitroglycerin performed favorably compared with placebo or control for the management of retained placenta. Carbetocin and prostaglandin agents were superior to oxytocin in reducing the need for manual extraction or dilation and curettage.

Top-cited articles in the Journal: a bibliometric analysis.

BACKGROUND: The Journal has had a profound influence in nearly 150 years of publishing. A bibliometric analysis, which uses citation analyses to evaluate the impact of articles, can be used to identify the most impactful papers in the Journal's history. OBJECTIVE: The objective was to identify and characterize the top-cited articles published in the Journal since 1920. STUDY DESIGN: We used the Web of Science and Scopus databases to identify the most frequently cited articles of the Journal from 1920 through 2018. The top 100 articles from each database were included in our analysis. Articles were evaluated for several characteristics including year of publication, article type, topic, open access, and country of origin. Using the Scopus data, we performed an unadjusted categorical analysis to characterize the articles and a 2 time point analysis to compare articles before and after 1995, the median year of publication from each database list. RESULTS: The top 100 articles from each database were included in the analysis. This included 120 total articles: 80 articles listed in both and 20 unique in each database. More than half (52%) were observational studies, 9% were RCTs, and 75% were from US authors. When the post-1995 studies were compared with the articles published before 1995, articles were more frequently cited (median 27 vs 13 citations per year, P < .001), more likely to be randomized (14.0% vs 4.8%, P = .009), and more likely to originate from international authors (33.3% vs 17.5%, P = .045). CONCLUSION: Slightly more than half of the top-cited papers in the Journal since 1920 were observational studies and three quarters of all papers were from US authors. Compared with top-cited papers before 1995, the Journal's top-cited papers after 1995 were more likely to be randomized and to originate from international authors.

Term cesarean delivery in the first pregnancy is not associated with an increased risk for preterm delivery in the subsequent pregnancy.

BACKGROUND: Prior studies have reported an increased risk for preterm delivery following a term cesarean delivery. However, these studies did not adjust for high-risk conditions related to the first cesarean delivery and are known to recur. OBJECTIVE: The objective of the study was to determine whether there is an association between term cesarean delivery in the first pregnancy and subsequent spontaneous or indicated preterm delivery. STUDY DESIGN: This was a retrospective cohort study of women with the first 2 consecutive singleton deliveries (2007-2014) identified through a linked pregnancy database at a single institution. Women with a first pregnancy that resulted in cesarean delivery at term were compared with women whose first pregnancy resulted in a vaginal delivery at term. Exclusion criteria were known to recur medical or obstetrical complications during the first pregnancy. A propensity score analysis was performed by matching women who underwent a cesarean delivery with those who underwent a vaginal delivery in the first pregnancy. The association between cesarean delivery in the first pregnancy and preterm delivery in the second pregnancy in this matched set was examined using conditional logistic regression. The primary outcome was overall preterm delivery <37 weeks in the second pregnancy. Secondary outcomes included type of preterm delivery (spontaneous vs indicated), late preterm delivery (34-36 6/7 weeks), early preterm delivery (<34 weeks), and small-for-gestational-age birth. RESULTS: Of a total of 6456 linked pregnancies, 2284 deliveries were matched; 1142 were preceded by cesarean delivery and 1142 were preceded by vaginal delivery. The main indications for cesarean delivery in the first pregnancy were dystocia in 703 (61.5%), nonreassuring fetal status in 222 (19.4%), breech presentation in 100 (8.8%), and other in 84 (7.4%). The mean (SD) gestational ages at delivery for the second pregnancy was 38.8 (1.8) and 38.9 (1.7) weeks, respectively, for prior cesarean delivery and vaginal delivery. The risks of preterm delivery in the second pregnancy among women with a previous cesarean and vaginal delivery were 6.0% and 5.2%, respectively (adjusted odds ratio, 1.46, 95% confidence interval, [CI] 0.77-2.76). In an analysis stratified by the type of preterm delivery in the second pregnancy, no associations were seen between cesarean delivery in the first pregnancy and spontaneous preterm delivery (4.6% vs 3.9%; adjusted odds ratio, 1.40, 95% confidence interval, 0.59-3.32) or indicated preterm delivery (1.6% vs 1.4%; adjusted odds ratio, 1.21, 95% confidence interval, 0.60-2.46). Similarly, no significant differences were found in late preterm delivery (4.6% vs 4.1%; adjusted odds ratio, 1.13, 95% confidence interval, 0.55-2.29), early preterm delivery (1.6% vs 1.2%; adjusted odds ratio, 1.25, 95% confidence interval, 0.59-2.67), or neonates with birthweight less than the fifth percentile for gestational age (3.6% vs 2.2%; adjusted odds ratio, 1.26, 95% confidence interval, 0.52-3.06). CONCLUSION: After robust adjustment for confounders through a propensity score analysis related to the indication for the first cesarean delivery at term, cesarean delivery is not associated with an increase in preterm delivery, spontaneous or indicated, in the subsequent pregnancy.

Anandamide down-regulates placental transporter expression through CB2 receptor-mediated inhibition of cAMP synthesis.

The BCRP/ABCG2 efflux transporter is expressed on the membrane of placental syncytiotrophoblasts and protects the fetus from toxicant exposure. Syncytiotrophoblasts arise from the fusion of cytotrophoblasts, a process negatively regulated by the endocannabinoid, anandamide (AEA). It is unknown whether AEA can influence fetal concentrations of xenobiotics by modulating the expression of transporters in syncytiotrophoblasts. Here, we sought to characterize and identify the mechanism(s) responsible for AEA-mediated down-regulation of the BCRP transporter in human placental explants and BeWo trophoblasts. Treatment of human placental explants with AEA (1 µM, 24 h) reduced hCGα, syncytin-1, and BCRP mRNAs by ˜30%. Similarly, treatment of BeWo trophoblasts with AEA (0-10 µM, 3-24 h) coordinately down-regulated mRNAs for hCGß, syncytin-2, and BCRP. In turn, AEA increased the sensitivity of trophoblasts to the cytotoxicity of mitoxantrone, a known BCRP substrate, and environmental and dietary contaminants including mycoestrogens and perfluorinated chemicals. AEA-treated trophoblasts also demonstrated reduced BCRP transport of the mycoestrogen zearalenone and the diabetes drug glyburide, labeled with BODIPY. The AEA-mediated reduction of BCRP mRNA was abrogated when placental cells were co-treated with AM630, a CB2 receptor inhibitor, or 8-Br-cAMP, a cAMP analog. AEA reduced intracellular cAMP levels in trophoblasts by 75% at 1 h, and completely inhibited forskolin-induced phosphorylation of the cAMP response element binding protein (CREB). AEA also decreased p-CREB binding to the BCRP promoter. Taken together, our data indicate that AEA down-regulates placental transporter expression and activity via CB2-cAMP signaling. This novel mechanism may explain the repression of placental BCRP expression observed during diseases of pregnancy.

Advanced paternal age, infertility, and reproductive risks: A review of the literature.

Advanced paternal age (APA) is associated with infertility and other reproductive risks. Studies looking at APA and outcomes have used different paternal age cut-offs, which has complicated systematic evaluations of reproductive risk associated with paternal aging. This review of the literature suggests that the impact of paternal aging on adverse reproductive outcomes is small, but significant. Studies suggest the incidence of paternal age effect disorders attributed to de novo autosomal dominant mutations is less than 0.5%. Other risks associated with APA include infertility, miscarriage, birth defects, poor neurodevelopmental outcomes, and childhood cancer. Although the increasing prevalence of APA has mirrored the rise in maternal age, this topic has not received similar attention. In this review, we summarize the available literature on the reproductive risks associated with APA to provide a framework for comprehensive genetic counseling and evidence-based management of APA pregnancies.

Trends in invasive prenatal diagnostic testing at a single institution.

OBJECTIVE: As diagnostic methodologies evolve, we sought to determine whether invasive testing rates would decline, whether there would be a shift in indications for invasive testing, and whether the diagnostic yield would increase. METHODS: We conducted a retrospective, observational study from 2006 through 2015. We quantified the number of invasive procedures per year and examined what percentage of these procedures yielded abnormal results. We also examined the indications for testing and determined the trend of these indications during the study period. RESULTS: The number of amniocenteses showed a steady decline (P < .05). The number of CVS procedures has increased and was recently equivalent to amniocentesis. The percentage of abnormal results steadily increased from 11.4% to 27.0% (P < .001). The abnormal aneuploidy screening indication remained constant over time. Advanced maternal age (AMA) as the sole indication substantially declined from 42.3% to 15.52% (P < .001). Testing for a known single gene disorder steadily increased from 3.0% to 9.20% (P = .018). CONCLUSION: Our study showed a significant decline in the number of amniocenteses, a steady increase in the percentage of abnormal results from invasive testing, and a decline in AMA as the sole indication for invasive testing.

Cerclage in twin pregnancy with dilated cervix between 16 to 24 weeks of gestation: retrospective cohort study.

BACKGROUND: Cervical dilation in the second trimester is associated with a greater than 90% rate of spontaneous preterm birth and a poor perinatal prognosis. OBJECTIVE: To compare the perinatal outcomes of twin pregnancies with dilated cervix in women who underwent either cerclage or expectant management. STUDY DESIGN: Retrospective cohort study of asymptomatic twin pregnancies identified with cervical dilation of ≥1 cm at 16-24 weeks (1997-2014) at 7 institutions. Exclusion criteria were genetic or major fetal anomaly, multifetal reduction at >14 weeks, prior cerclage placement, monochorionic-monoamniotic placentation, active vaginal bleeding, labor, chorioamnionitis, elective termination of pregnancy, or medically indicated preterm birth. The primary outcome was incidence of spontaneous preterm birth at <34 weeks. Secondary outcomes were incidence of spontaneous preterm birth at <32 weeks, <28 weeks, and <24 weeks; perinatal mortality; and composite adverse neonatal outcome (respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, and sepsis). RESULTS: A total of 76 women with twin pregnancy with dilated cervix of 1.0-4.5 cm were managed with either cerclage (n = 38) or expectant management (n = 38). Demographic characteristics were not significantly different. Analysis was adjusted for amniocentesis and vaginal progesterone use. In the cerclage group, 29 women (76%) received prophylactic indomethacin and 36 (94%) received prophylactic antibiotics, whereas the expectant management group did not. Interval from time at diagnosis of open cervix to delivery in the cerclage group was 10.46 ± 5.6 weeks vs 3.7 ± 3.2 weeks in the expectant management group, with a mean difference of 6.76 weeks (95% confidence interval [CI], 4.71-8.81). There were significant decreases in spontaneous preterm birth at <34 weeks (52.6% vs 94.7%; adjusted odds ratio [aOR], 0.06; 95% CI, 0.03-0.34), at <32 weeks (44.7% vs 89.4%; aOR, 0.08; 95% CI, 0.03-0.34); at <28 weeks (31.6% vs 89.4%; aOR, 0.05; 95% CI, 0.01-0.2); and at <24 weeks (13.1% vs 47.3%; aOR, 0.17; 95% CI, 0.05-0.54). There were also significant reductions in perinatal mortality (27.6% vs 59.2%; aOR, 0.24; 95% CI, 0.11-0.5), neonatal intensive care unit admission (75.9% vs 97.6%; aOR, 0.07; 95% CI, 0.01-0.66), and composite adverse neonatal outcome (33.9% vs 90.5%; aOR, 0.05; 95% CI, 0.01-0.21). CONCLUSION: Cerclage, indomethacin, and antibiotics in twin pregnancies with dilated cervix ≥1 cm before 24 weeks were associated with significant longer latency period from diagnosis to delivery (6.7 weeks), decreased incidence of spontaneous preterm birth at any given gestational age, and improved perinatal outcome when compared with expectant management.

Maternal Smoking and Risk of Hypertensive Disorders of Pregnancy: Effect Modification by Body Mass Index and Gestational Weight Gain.

BACKGROUND: Although smoking cigarettes has been shown to have a protective effect on preeclampsia, quitting smoking also results in weight gain. Weight gain leading to an obese body mass index is a risk factor for hypertensive disorders of pregnancy (HDP). METHODS: The objective of this study was to explore the relationship between smoking status, body mass index, and gestational weight gain on the risk of HDP. A cross-sectional analysis was performed utilizing US birth certificate data. We examined HDP risks in relation to maternal smoking, body mass index, and gestational weight gain. Associations were expressed as rate ratios with 95% CIs and adjusted for potential confounders. Clinically important outcomes of smoking throughout pregnancy were also evaluated. RESULTS: Of the 22 191 568 women studied, HDP rates among nonsmokers, those who quit smoking, and persistent smokers were 6.8%, 8.6%, and 7.0%, respectively. The rate ratio of HDP was higher for women who quit smoking, especially evident among those with excessive gestational weight gain. Corrections for exposure misclassification and unmeasured confounding strengthened the associations among women who quit smoking. There was an almost 6-fold increase in the rate of stillbirth for persistent smokers (2.3%) compared with those who quit smoking (0.4%) and nonsmokers (0.4%). CONCLUSIONS: Women who quit smoking during pregnancy were more likely to gain excessive weight and develop HDP. Although quitting smoking during pregnancy may be associated with an increase in the risk of HDP, it is also associated with a reduced risk of stillbirth. Pregnant women counseled to quit smoking should also receive counseling on nutrition and exercise to prevent excessive gestational weight gain.

Evaluating the Efficacy of Cervical Tactile Ultrasound Technique as a Predictive Tool for Spontaneous Preterm Birth.

Background: Premature cervical softening and shortening may be considered an early mechanical failure that predispose to preterm birth. Purpose: This study aims to explore the applicability of an innovative cervical tactile ultrasound approach for predicting spontaneous preterm birth (sPTB). Materials and Methods: Eligible participants were women with low-risk singleton pregnancies in their second trimester, enrolled in this prospective observational study. A Cervix Monitor (CM) device was designed with a vaginal probe comprising four tactile sensors and a single ultrasound transducer operating at 5 MHz. The probe enabled the application of controllable pressure to the external cervical surface, facilitating the acquisition of stress-strain data from both anterior and posterior cervical sectors. Gestational age at delivery was recorded and compared against cervical elasticity. Results: CM examination data were analyzed for 127 women at 240/7 - 286/7 gestational weeks. sPTB was observed in 6.3% of the cases. The preterm group exhibited a lower average cervical stress-to-strain ratio (elasticity) of 0.70 ± 0.26 kPa/mm compared to the term group's 1.63 ± 0.65 kPa/mm with a p-value of 1.1 × 10-4. Diagnostic accuracy for predicting spontaneous preterm birth based solely on cervical elasticity data was found to be 95.0% (95% CI, 88.5 - 100.0). Conclusion: These findings suggest that measuring cervical elasticity with the designed tactile ultrasound probe has the potential to predict spontaneous preterm birth in a cost-effective manner.

Pregnancy Outcomes of Nifedipine Compared With Labetalol for Oral Treatment of Mild Chronic Hypertension.

OBJECTIVE: To evaluate maternal and neonatal outcomes by type of antihypertensive used in participants of the CHAP (Chronic Hypertension in Pregnancy) trial. METHODS: We conducted a planned secondary analysis of CHAP, an open-label, multicenter, randomized trial of antihypertensive treatment compared with standard care (no treatment unless severe hypertension developed) in pregnant patients with mild chronic hypertension (blood pressure 140-159/90-104 mm Hg before 20 weeks of gestation) and singleton pregnancies. We performed three comparisons based on medications prescribed at enrollment: labetalol compared with standard care, nifedipine compared with standard care, and labetalol compared with nifedipine. Although active compared with standard care groups were randomized, medication assignment within the active treatment group was not random but based on clinician or patient preference. The primary outcome was the occurrence of superimposed preeclampsia with severe features, preterm birth before 35 weeks of gestation, placental abruption, or fetal or neonatal death. The key secondary outcome was small for gestational age (SGA) neonates. We also compared medication adverse effects between groups. Relative risks (RRs) and 95% CIs were estimated with log binomial regression to adjust for confounding. RESULTS: Of 2,292 participants analyzed, 720 (31.4%) received labetalol, 417 (18.2%) received nifedipine, and 1,155 (50.4%) received no treatment. The mean gestational age at enrollment was 10.5±3.7 weeks; nearly half of participants (47.5%) identified as non-Hispanic Black; and 44.5% used aspirin. The primary outcome occurred in 217 (30.1%), 130 (31.2%), and 427 (37.0%) in the labetalol, nifedipine, and standard care groups, respectively. Risk of the primary outcome was lower among those receiving treatment (labetalol use vs standard adjusted RR 0.82, 95% CI, 0.72-0.94; nifedipine use vs standard adjusted RR 0.84, 95% CI, 0.71-0.99), but there was no significant difference in risk when labetalol was compared with nifedipine (adjusted RR 0.98, 95% CI, 0.82-1.18). There were no significant differences in SGA or serious adverse events between participants receiving labetalol and those receiving nifedipine. CONCLUSION: No significant differences in predetermined maternal or neonatal outcomes were detected on the basis of the use of labetalol or nifedipine for treatment of chronic hypertension in pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02299414.

Mean Arterial Pressure and Neonatal Outcomes in Pregnancies Complicated by Mild Chronic Hypertension.

OBJECTIVE: To estimate the association between mean arterial pressure during pregnancy and neonatal outcomes in participants with chronic hypertension using data from the CHAP (Chronic Hypertension and Pregnancy) trial. METHODS: A secondary analysis of the CHAP trial, an open-label, multicenter randomized trial of antihypertensive treatment in pregnancy, was conducted. The CHAP trial enrolled participants with mild chronic hypertension (blood pressure [BP] 140-159/90-104 mm Hg) and singleton pregnancies less than 23 weeks of gestation, randomizing them to active treatment (maintained on antihypertensive therapy with a goal BP below 140/90 mm Hg) or standard treatment (control; antihypertensives withheld unless BP reached 160 mm Hg systolic BP or higher or 105 mm Hg diastolic BP or higher). We used logistic regression to measure the strength of association between mean arterial pressure (average and highest across study visits) and to select neonatal outcomes. Unadjusted and adjusted odds ratios (per 1-unit increase in millimeters of mercury) of the primary neonatal composite outcome (bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, or intraventricular hemorrhage grade 3 or 4) and individual secondary outcomes (neonatal intensive care unit admission [NICU], low birth weight [LBW] below 2,500 g, and small for gestational age [SGA]) were calculated. RESULTS: A total of 2,284 participants were included: 1,155 active and 1,129 control. Adjusted models controlling for randomization group demonstrated that increasing average mean arterial pressure per millimeter of mercury was associated with an increase in each neonatal outcome examined except NEC, specifically neonatal composite (adjusted odds ratio [aOR] 1.12, 95% CI, 1.09-1.16), NICU admission (aOR 1.07, 95% CI, 1.06-1.08), LBW (aOR 1.12, 95% CI, 1.11-1.14), SGA below the fifth percentile (aOR 1.03, 95% CI, 1.01-1.06), and SGA below the 10th percentile (aOR 1.02, 95% CI, 1.01-1.04). Models using the highest mean arterial pressure as opposed to average mean arterial pressure also demonstrated consistent associations. CONCLUSION: Increasing mean arterial pressure was positively associated with most adverse neonatal outcomes except NEC. Given that the relationship between mean arterial pressure and adverse pregnancy outcomes may not be consistent at all mean arterial pressure levels, future work should attempt to further elucidate whether there is an absolute threshold or relative change in mean arterial pressure at which fetal benefits are optimized along with maternal benefits. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02299414.

Cesarean scar ectopic pregnancy: nuances in diagnosis and treatment.

A cesarean scar ectopic pregnancy (CSEP) occurs when the embryo implants on the scar of a previous cesarean delivery. The number of births delivered by cesarean section has climbed by 50% over the last decade, from a nadir of 20.7% in 1996 to 32.1% in 2021. As a result, the incidence of CSEP has also increased. Because CSEP may cause serious morbidity such as life-threatening hemorrhage, uterine rupture, placental accreta spectrum, hysterectomy, and even mortality, accurate diagnosis and appropriate management of this condition are essential. This review focuses on the etiology, incidence, clinical diagnosis, and management of CSEPs.

Breastfeeding initiation and duration among people with mild chronic hypertension: a secondary analysis of the Chronic Hypertension and Pregnancy trial.

BACKGROUND: Increased duration of breastfeeding improves maternal cardiovascular health and may be especially beneficial in high-risk populations, such as those with chronic hypertension. Others have shown that individuals with hypertension are less likely to breastfeed, and there has been limited research aimed at supporting breastfeeding goals in this population. The impact of perinatal blood pressure control on breastfeeding outcomes among people with chronic hypertension is unknown. OBJECTIVE: This study aimed to evaluate whether breastfeeding initiation and short-term duration assessed at the postpartum clinic visit differed according to perinatal blood pressure treatment strategy (targeting blood pressure <140/90 mm Hg vs reserving antihypertensive treatment for blood pressure ≥160/105 mm Hg). STUDY DESIGN: We performed a secondary analysis of the Chronic Hypertension and Pregnancy trial. This was an open-label, multicenter, randomized trial where pregnant participants with mild chronic hypertension were randomized to receive antihypertensive medications with goal blood pressure <140/90 mm Hg (active treatment) or deferred treatment until blood pressure ≥160/105 mm Hg (control). The primary outcome was initiation and duration of breastfeeding, assessed at the postpartum clinic visit. We performed bivariate analyses and log-binomial and cumulative logit regression models, adjusting models for variables that were unbalanced in bivariate analyses. We performed additional analyses to explore the relationship between breastfeeding duration and blood pressure measurements at the postpartum visit. RESULTS: Of the 2408 participants from the Chronic Hypertension and Pregnancy trial, 1444 (60%) attended the postpartum study visit and provided breastfeeding information. Participants in the active treatment group had different body mass index class distribution and earlier gestational age at enrollment, and (by design) were more often discharged on antihypertensives. Breastfeeding outcomes did not differ significantly by treatment group. In the active and control treatment groups, 563 (77.5%) and 561 (78.1%) initiated breastfeeding, and mean durations of breastfeeding were 6.5±2.3 and 6.3±2.1 weeks, respectively. The probability of ever breastfeeding (adjusted relative risk, 0.99; 95% confidence interval, 0.93-1.05), current breastfeeding at postpartum visit (adjusted relative risk, 1.01; 95% confidence interval, 0.94-1.10), and weeks of breastfeeding (adjusted odds ratio, 0.87; 95% confidence interval, 0.68-1.12) did not differ by treatment group. Increased duration (≥2 vs <2 weeks) of breastfeeding was associated with slightly lower blood pressure measurements at the postpartum visit, but these differences were not significant in adjusted models. CONCLUSION: In a secondary analysis of the cohort of Chronic Hypertension and Pregnancy trial participants who attended the postpartum study visit and provided breastfeeding information (60% of original trial participants), breastfeeding outcomes did not differ significantly by treatment group. This suggests that maintaining goal blood pressure <140/90 mm Hg throughout the perinatal period is associated with neither harm nor benefit for short-term breastfeeding goals. Further study is needed to understand long-term breastfeeding outcomes among individuals with chronic hypertension and how to support this population in achieving their breastfeeding goals.

Perinatal Outcomes Associated With Management of Stage 1 Hypertension.

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

A comparison of pregnancy-specific risk scoring systems for venous thromboembolic pharmacoprophylaxis in hospitalized maternity patients.

OBJECTIVE: Venous thromboembolism (VTE) remains a leading cause of maternal mortality. The American College of Obstetricians and Gynecologists (ACOG) and the Royal College of Obstetricians & Gynecologists (RCOG) have proposed pregnancy-specific risk scoring guidelines for antepartum (AP) and postpartum (PP) thromboprophylaxis. We compared the impact of scoring thresholds and their potential preventative effect. STUDY DESIGN: We conducted a retrospective cohort study of hospitalized maternity patients over a 4-month period. Patients were assigned an AP and PP risk score using each guideline. Hospitalization-associated VTE was accessed over a 6-year period. Comparison was by Fischer's exact and Chi Square tests. RESULTS: 638 women were included. Of AP patients, 20% met pharmacoprophylaxis criteria for baseline characteristics and 100% for length of stay using RCOG, and 12% met phrarmacoprophylaxis criteria using ACOG (p < .001). For PP patients, 53% met criteria for RCOG compared to 24% using ACOG (p < .001). If pharmacoprophylaxis were performed at a threshold 1 point above recommendation, 7% of AP patients and 11% of PP women would meet ACOG criteria. This increased ACOG threshold captured all cases of VTE following hospitalization. CONCLUSION: In our population, using ACOG prophylaxis guidelines at an increased threshold would have potentially prevented all hospitalization related VTE without excessive anti-coagulation.