Aspirin 162 mg vs 81 mg for preeclampsia prophylaxis in high-risk obese individuals: a comparative effectiveness open-label randomized trial (ASPREO).

BACKGROUND: In the United States, leading medical societies recommend 81 mg of aspirin daily for the prevention of preeclampsia in women at risk, whereas the NICE guidelines in the United Kingdom recommend a dose as high as 150 mg of aspirin. Recent data also suggest that in the obese population, inadequate dosing or aspirin resistance may impact the efficacy of aspirin at the currently recommended doses. OBJECTIVE: We evaluated whether daily administration of 162 mg aspirin would be more effective compared with 81 mg in decreasing the rate of preeclampsia with severe features in high-risk obese pregnant individuals. STUDY DESIGN: We performed a randomized trial between May 2019 and November 2022. Individuals at 12-20 weeks of gestational age with a body mass index ≥30 kg/m2 at the time of enrollment and at least 1 of 3 high-risk factors: history of preeclampsia in a prior pregnancy, at least stage I hypertension documented in the index pregnancy, pregestational diabetes or gestational diabetes diagnosed before 20 weeks of gestational age were randomized to either 162 mg or 81 mg of aspirin daily till delivery, participants were not blinded to treatment allocation. Exclusion criteria were multifetal gestation, known major fetal anomalies, seizure disorder, baseline proteinuria, on aspirin because of other indications, or contraindication to aspirin. The primary outcome was preeclampsia with severe features (preeclampsia or superimposed preeclampsia with severe features; eclampsia; or hemolysis, elevated liver enzymes, low platelet count syndrome). Secondary outcomes included rates of preterm birth because of preeclampsia, small for gestational age, postpartum hemorrhage, abruption, and medication side effects. A sample size of 220 was needed using a preplanned Bayesian analysis of the primary outcome to estimate the posterior probability of benefit or harm with a neutral informative prior. RESULTS: Approximately 220/343 (64.1%) individuals were randomized. The primary outcome was available for 209/220 (95%) individuals. Baseline characteristics were similar between groups, with the median gestational age at enrollment being 15.9 weeks in the 162 mg aspirin group and 15.6 weeks in the 81 mg aspirin group. Enrollment before 16 weeks occurred in 55 of 110 of those assigned to 162 mg and 58 of 110 of those assigned to 81 mg of aspirin. The primary outcome occurred in n of d individuals (35%) in the 162 mg aspirin group and n of d individuals (40%) in the 81 mg aspirin group (posterior relative risk, 0.88; 95% credible interval, 0.64-1.22). Bayesian analysis indicated a 78% probability of a reduction in the primary outcome with 162 mg aspirin compared with 81 mg aspirin dose. Rates of indicated preterm birth because of preeclampsia (21% vs 21%), small for gestational age (6.5% vs 2.9%), abruption (2.8% vs 3.0%), and postpartum hemorrhage (10.0% vs 8.8%) were similar between groups. Medication adverse effects were also similar. CONCLUSION: Among high-risk obese individuals, there was a 78% probability of benefit that 162 mg aspirin compared with 81 mg will decrease the rate of preeclampsia with severe features. With the best estimate of a 12% reduction when using 162 mg of aspirin compared with 81 mg of aspirin in this population. This trial supports doing a larger multicenter trial.

Umbilical-portal-systemic venous shunt and intrauterine growth restriction: an inquiry from a prospective study.

BACKGROUND: The investigation of the fetal umbilical-portal venous system is based on the premise that congenital anomalies of this system may be related to adverse perinatal outcomes. Several small retrospective studies have reported an association between umbilical-portal-systemic venous shunts and intrauterine growth restriction. However, the prevalence of portosystemic shunts in the fetal growth restricted population is yet to be determined. OBJECTIVE: The aims of this study were (1) to determine the prevalence of fetal umbilical-portal-systemic venous shunts in pregnancies complicated by intrauterine growth restriction and (2) to compare the perinatal and neonatal outcomes of pregnancies with intrauterine growth restriction with and without umbilical-portal-systemic venous shunts. STUDY DESIGN: This was a prospective, cross-sectional study of pregnancies diagnosed with intrauterine growth restriction, as defined by the Society for Maternal-Fetal Medicine intrauterine growth restriction guidelines. All participants underwent a detailed anomaly scan, supplemented with a targeted scan of the fetal portal system. Venous shunts were diagnosed using color Doppler mode. The perinatal outcomes of pregnancies with intrauterine growth restriction with and without umbilical-portal-systemic venous shunts were compared. RESULTS: A total of 150 cases with intrauterine growth restriction were recruited. The prevalence of umbilical-portal-systemic venous shunts in our cohort was 9.3% (n=14). When compared with the control group (intrauterine growth restriction without umbilical-portal-systemic venous shunts, n=136), the study group had a significantly lower mean gestational age at the time of intrauterine growth restriction diagnosis (29.7±5.6 vs 32.47±4.6 weeks of gestation; P=.036) and an earlier gestational age at delivery (33.50±6.0 vs 36.13±2.8; P=.005). The study group had a higher rate of fetal death (21.4% vs 0.7%; P<.001) and, accordingly, a lower rate of live births (71.4% vs 95.6%; P=.001). Additional associated fetal vascular anomalies were significantly more prevalent in the study group than in the control group (35.7% vs 4.4%; P≤.001). The rate of other associated anomalies was similar. The study group had a significantly lower rate of abnormal uterine artery Doppler indices (0% vs 40.4%; P=.011) and a higher rate of abnormal ductus venosus Doppler indices (64.3% vs 23%; P=.001). There were no cases of hypertensive disorders of pregnancy in the study group, whereas the control group had an incidence of 12.5% (P=.16). Other perinatal and neonatal outcomes were comparable. CONCLUSION: Umbilical-portal-systemic venous shunt is a relatively common finding among fetuses with growth restriction. When compared with pregnancies with intrauterine growth restriction with a normal portal system, these pregnancies complicated by intrauterine growth restriction and an umbilical-portal-systemic venous shunt are associated with a different Doppler flow pattern, an increased risk for fetal death, earlier presentation of intrauterine growth restriction, a lower gestational age at delivery, additional congenital vascular anomalies, and a lower rate of pregnancy-induced hypertensive disorders. Meticulous sonographic evaluation of the portal system should be considered in the prenatal workup of intrauterine growth restriction, as umbilical-portal-systemic venous shunts may affect perinatal outcomes.

Nulliparous with Class III Obesity at Term: Labor Induction or Cesarean Delivery without Labor.

OBJECTIVE: This study aimed to compare maternal and neonatal outcomes between labor induction versus cesarean delivery (CD) without labor among nulliparous individuals with class III obesity (body mass index [BMI] ≥40 kg/m2). STUDY DESIGN: A retrospective cohort study of all nulliparous singleton deliveries at ≥37 weeks with a BMI of ≥40 kg/m2 at delivery between March 2020 and February 2022. We excluded individuals with spontaneous labor, fetal malformations, and stillbirths. The primary outcome was a composite of maternal mortality and morbidity, including infectious and hemorrhagic morbidity. The secondary outcome was a neonatal composite. A subgroup analysis evaluated patients with a BMI of ≥50 kg/m2. Another subgroup analysis compared outcomes between CD without labor and an indicated CD following induction. A multivariable logistic regression was applied. For adjustment, we used possible confounders identified in a univariate analysis. RESULTS: Among 8,623 consecutive deliveries during the study period, 308 (4%) met the inclusion criteria. Among them, 250 (81%) underwent labor induction, and 58 (19%) had a CD without labor. The most common indications for CD without labor were fetal malpresentation (26; 45%), suspected macrosomia (8; 14%), and previous myomectomy (5; 9%). Indicated CD occurred in 140 (56%) of the induced individuals, with the two leading indications being labor arrest (87; 62%) and non-reassuring fetal heart rate tracing (51; 36%). The rates of composite maternal morbidity (adjusted odds ratio [aOR] = 2.14, 95% confidence interval [CI]: 0.64-7.13) and composite neonatal morbidity (aOR = 3.62, 95% CI: 0.42-31.19) did not differ following a CD without labor compared to labor induction. The subgroup analyses did not demonstrate different outcomes between groups. CONCLUSION: Among nulliparous individuals with class III obesity at term who underwent induction, more than 50% had indicated CD; the rate of short-term maternal and neonatal morbidity, however, did not differ between labor induction and CD without labor. KEY POINTS: · The rate of unplanned CD among those who underwent labor induction was relatively high (56.0%).. · Outcomes did not differ between those who underwent CD without labor and those who were induced.. · Outcomes also did not differ between those who underwent CD without labor and those with CD in labor..

Maternal morbidity following caesarean deliveries with barbed suture for uterine closure.

PURPOSE: Information regarding the use of barbed suture in gynecologic surgery is limited. Our aim was to compare maternal morbidity following caesarean deliveries performed with barbed compared with non-barbed suture for uterine closure. METHODS: A historical cohort study from a single tertiary institution. The study group composed of all women that underwent term, uncomplicated singleton caesarean deliveries, where uterine closure was performed with ETHICON's Stratafix®, a polydioxanone barbed suture, compared with caesarean deliveries where uterine closure was performed with ETHICON's VICRYL®, a Polyglactin 910 non-barbed suture. The primary outcomes were the rate of maternal morbidity including the rate of red packed cells transfusion and a composite of infectious morbidity. Operation duration was also evaluated. An analysis restricted to elective caesarean deliveries was performed comparing the suture types. RESULTS: Three thousand and sixty patients were included in the study; 1337 in the study group and 1723 in the control group. There was no significant difference in the rate of the primary outcomes (red packed cells transfusion: 2.5% in the barbed suture vs. 2.1% in the non-barbed suture groups; p = 0.47; composite maternal morbidity: 3.8% vs. 4.8%, respectively; p = 0.18). Barbed suture was associated with reduced risk of postoperative ileus compared with the non-barbed suture (0.3% vs. 1.0%, respectively; p = 0.02) and a longer operation time (31 vs. 29 min, respectively; p < 0.001). In the analysis restricted to elective caesarean deliveries only the duration of operation remained significantly different between the groups. CONCLUSIONS: The rate of short term maternal morbidities among patients undergoing uterine closure with barbed suture during caesarean delivery is similar to the non-barbed suture.

The association between maternal insurance status on maternal and neonatal outcomes in women with hypertensive disorders of pregnancy.

The objective of this study was to examine the association between maternal insurance status and maternal and neonatal adverse outcomes in women who had hypertensive disorders in pregnancy. A population-based retrospective cohort study was undertaken using the US Vital Statistics dataset on Period Linked Birth-Infant Data from 2016-2020. The study population was restricted to non-anomalous births from women whose pregnancies were complicated by hypertensive disorders. Insurance status was categorized as private, Medicaid, self-pay and other. The primary outcome was a composite of maternal adverse outcomes, which included admission to the intensive care unit, unplanned hysterectomy, maternal blood transfusion or uterine rupture. We examined the role of prenatal care in these relationships using a mediation analysis with Kotelchuck's Adequacy of Prenatal Care Utilization Index. Multivariable logistic regression models were used to estimate the association between maternal insurance status and adverse outcomes (using adjusted odds ratios [aOR] and 99% confidence interval [CI]). Of the 18,999,865 live births in the five-year study, 1,642,654 (8.6%) met the inclusion criteria. The frequency of the composite maternal adverse outcome was 1.3%. The maternal composite occurred more frequently in women with Medicaid (aOR = 1.11, 99% CI: 1.06, 1.16) or self-pay (aOR = 1.40, 99% CI: 1.25, 1.55) when compared to private insurance. Adjusting for prenatal care slightly attenuated this association, but remained significant. Among women with hypertensive disorders in pregnancy, women with Medicaid insurance or self-pay were more likely to experience maternal and neonatal adverse outcomes than women with private insurance.

Pregnancy outcomes among patients with stage 1 chronic hypertension.

In recent years, the American College of Cardiology and the American Heart Association have reduced the thresholds for a hypertension diagnosis among nonpregnant adults. This change has led to more individuals with reproductive potential to be labeled as being chronically hypertensive, and some were started on antihypertensive medications. When these individuals become pregnant, the obstetrical care provider will have to decide whether to manage them as individuals with chronic hypertensive when only a few years ago they would have been managed as normotensive individuals and when the evidence regarding treatment of these patients during pregnancy is limited. If implemented widely, the management of patients with stage 1 hypertension similar to the traditional chronic hypertension will likely lead to additional maternal and fetal testing, to an increase in hospital admissions, and potentially to unnecessary interventions, such as preterm birth. Our goal was to compile the existing evidence regarding the pregnancy outcomes among patients with stage 1 hypertension to assist providers in their diagnosis and management of this patient group.

Well-Child Visits for Early Detection and Management of Maternal Postpartum Hypertensive Disorders.

Importance: Innovative approaches are needed to address the increasing rate of postpartum morbidity and mortality associated with hypertensive disorders. Objective: To determine whether assessing maternal blood pressure (BP) and associated symptoms at time of well-child visits is associated with increased detection of postpartum preeclampsia and need for hospitalization for medical management. Design, Setting, and Participants: This is a pre-post quality improvement (QI) study. Individuals who attended the well-child visits between preimplementation (December 2017 to December 2018) were compared with individuals who enrolled after the implementation of the QI program (March 2019 to December 2019). Individuals were enrolled at an academic pediatric clinic. Eligible participants included birth mothers who delivered at the hospital and brought their newborn for well-child check at 2 days, 2 weeks, and 2 months. A total of 620 individuals were screened in the preintervention cohort and 680 individuals were screened in the QI program. Data was analyzed from March to July 2022. Exposures: BP evaluation and preeclampsia symptoms screening were performed at the time of the well-child visit. A management algorithm-with criteria for routine or early postpartum visits, or prompt referral to the obstetric emergency department-was followed. Main Outcome and Measures: Readmission due to postpartum preeclampsia. Comparisons across groups were performed using a Fisher exact test for categorical variables, and t tests or Mann-Whitney tests for continuous variables. Results: A total of 595 individuals (mean [SD] age, 27.2 [6.1] years) were eligible for analysis in the preintervention cohort and 565 individuals (mean [SD] age, 27.0 [5.8] years) were eligible in the postintervention cohort. Baseline demographic information including age, race and ethnicity, body mass index, nulliparity, and factors associated with increased risk for preeclampsia were not significantly different in the preintervention cohort and postintervention QI program. The rate of readmission for postpartum preeclampsia differed significantly in the preintervention cohort (13 individuals [2.1%]) and the postintervention cohort (29 individuals [5.6%]) (P = .007). In the postintervention QI cohort, there was a significantly earlier time frame of readmission (median [IQR] 10.0 [10.0-11.0] days post partum for preintervention vs 7.0 [6.0-10.5] days post partum for postintervention; P = .001). In both time periods, a total of 42 patients were readmitted due to postpartum preeclampsia, of which 21 (50%) had de novo postpartum preeclampsia. Conclusions and Relevance: This QI program allowed for increased and earlier readmission due to postpartum preeclampsia. Further studies confirming generalizability and mitigating associated adverse outcomes are needed.

Fetal malpresentation following mechanical labor induction.

OBJECTIVE: To evaluate whether the risk of fetal malpresentation following mechanical labor induction could be accurately predicted. METHODS: A retrospective study, including all individuals who underwent labor induction at a single tertiary medical center between March 2011 and May 2021. Cohorts of pharmacological (n = 16 480) and mechanical labor induction (n = 6864) were compared, determining malpresentation rate following induction. Individuals with and without fetal malpresentation following balloon placement were compared. RESULTS: Malpresentation following balloon placement occurred in 62 patients (0.9%). Those patients with malpresentation following balloon placement were older, had higher body mass index during labor, higher parity, polyhydramnios, higher fetal station at the start of labor induction, and delivered at an earlier gestational age compared with control patients. The combined presence of at least three of these risk factors was associated with a malpresentation rate of 8% (7/88) and yielded a positive likelihood ratio of 9.48 (95% confidence interval [CI] 4.57-19.7). A prediction model using these variables was not sufficiently accurate to predict the risk of malpresentation following balloon labor induction; a calculated area under the generated receiver operating characteristic curve was 0.78 (95% CI 0.72-0.84). CONCLUSION: Several risk factors were identified for malpresentation following mechanical labor induction, although these were of low predictive value.

Incorporation of randomized controlled trials into organizational guidelines for obstetricians and gynecologists.

BACKGROUND: The American College of Obstetricians and Gynecologists publishes practice bulletins and committee opinions to serve as clinical guidelines for physicians. The objective of this study was to quantify the frequency that randomized controlled trials become incorporated into the American College of Obstetricians and Gynecologists documents (either practice bulletins or committee opinions). METHODS: Original research articles published in The American Journal of Obstetrics and Gynecology, The Journal of the American Medical Association, The New England Journal of Medicine, and Obstetrics and Gynecology between 2009 and 2014 were examined and randomized controlled trials (RCT) in obstetrics and gynecology were identified. Adjusted odds ratio (aOR) with 95% confidence intervals (CI) were calculated to examine the factors associated with a citable RCT being referenced versus not in ACOG documents. RESULTS: Of the 306 randomized controlled trials identified 248 (81.0%) met the inclusion criteria, with 128 (51.6%) of eligible RCT being cited The factors which increased the likelihood of a RCT being referenced, versus not being, were: if device or surgery was the intervention (aOR 3.60; 95% CI 1.85-7.00) and if the sample size of the trial was 500-999 (aOR 3.70 (1.39-9.82). The following factors were not associated with whether the RCT was or was not referenced in the ACOG documents: topic was obstetric or gynecologic, the trial was conducted in the US or abroad, multi- or single center, year of publication and the journal. CONCLUSION: Since about half of the citable randomized controlled trials published in obstetrics and gynecology are incorporated into ACOG practice bulletins and committee opinions a greater transparency is warranted as to why RCTs are or are not referenced.

Obstetrical randomized controlled trials: individuals screened, approached, and enrolled.

BACKGROUND: The use of randomized clinical trials (RCTs) is predicated on the idea that the study group is representative of the overall clinical population; however, recent studies have suggested that this may not be the case in obstetrics.1,2 The generalizability of several seminal obstetrical RCTs, including the A Randomized Trial of Induction Versus Expectant Management trial, has been questioned because of the high ratio of assessed-to-enrolled individuals.3 Although difficulty in recruitment for obstetrical RCTs is known,4 it has been postulated that this high ratio increases the likelihood of the study population not being truly representative. Our primary objective was to analyze the assessed-to-enrolled ratio in contemporary obstetrical RCTs. STUDY DESIGN: During a 4-year period (January 2017 to December 2020), we identified all obstetrical RCTs published in 6 journals (The New England Journal of Medicine, Journal of the American Medical Association, Lancet, American Journal of Obstetrics & Gynecology, British Journal of Obstetrics and Gynaecology, and Obstetrics & Gynecology). The journals were manually reviewed by 2 coauthors to ensure all obstetrical RCTs were identified and abstracted accurately. Reported patient recruitment data, per Consolidated Standards of Reporting Trials recommendations,5 were abstracted from each RCT. Based on the primary outcome of the study, the purpose of the trial was categorized as preventative or treatment. Medians were compared using Wilcoxon rank-sum testing, and P<.05 was considered significant. RESULTS: Of 240 obstetrical RCTs that were identified, 193 (80%) reported data on the number of individuals screened and recruited. The median number of individuals screened per trial was 850 (interquartile range [IQR], 323-2582), of which 348 were eligible (IQR, 201-1347) and 300 (IQR, 133-894) were randomized. There was no difference in trials based internationally or in the United States (P=.26). Compared with preventative RCTs, the trials that had treatment as the primary outcome were significantly more likely to screen a larger number of individuals for eligibility (P<.01) and subsequently randomize (P<.02). There was no difference in the median number of individuals who declined enrollment between trials with prevention or treatment as their objective (P=.12). More individuals were lost to follow-up in trials with prevention as the primary outcome (P<.01), although the median number lost was low at 3 (IQR, 0-21). CONCLUSION: The low assessed-to-enrolled ratio found in this study suggested that researchers are casting a large net for patient recruitment. The relatively high eligible-to-randomized ratio suggested that most individuals are willing to participate in obstetrical RCTs. This finding was at odds with previous critiques of obstetrical RCTs that had called in to question study results secondary to high eligible-to-randomized ratios. Further research into how patients are recruited and counseled is indicated, to explore this variation. The ratio of patients assessed for study eligibility to patients enrolled in preventative vs treatment RCTs was not substantially different. Based on this result, patients seemed to be similarly interested in being enrolled to prevent a complication from pregnancy as in treating one. These results supported the concept that most individuals in the obstetrical RCTs represent the eligible population.