Large Figure Research Articles

Diverse cardiovascular risk of recurrent spontaneous abortion: A prospective cohort study using UK Biobank

Previous studies have reported that history of recurrent spontaneous abortion (RSA) can increase the risk for cardiovascular disease. However, previous studies mainly focused on atherosclerotic cardiovascular disease (ASCVD), such as coronary artery disease or stroke, hence the effect of RSA on non-atherosclerotic cardiovascular diseases (non-ASCVD) remains unknown. In the current study, we examined if women with a history of RSA have an increased risk for long-term cardiovascular outcomes including both ASCVD and non-ASCVD. The UK Biobank is a prospective cohort study that recruited participants 40 to 69 years old with ongoing follow-up. Among women enrolled in UK Biobank, those with at least one pregnancy history and without pre-existing cardiovascular disease were included. The new occurrence of ASCVD and non-ASCVD after enrollment were compared between the women with RSA history and without RSA history. To evaluate the incidence of cardiovascular outcomes, a Cox proportional hazard model was used with adjustment for covariates including age, race, BMI, nulliparity, use of hormones, smoking, early menopause, hysterectomy, prevalent diseases, and medication by Cox proportional hazards regression analysis. In the presence of a history of RSA, the risk of new occurrence of overall cardiovascular disease, was higher (adjusted hazard ratio (aHR), 1.24 (95% CI 1.15-1.35), Figure 1). Specifically, the incidence of coronary artery disease, myocardial infarction, peripheral artery disease, heart failure, mitral regurgitation, atrial fibrillation/flutter were all increased in cases with a history of RSA (Figure 2). The women with history of RSA had an increased long-term risk of not only ASCVD, but also non-ASCVD.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Association of obesity with outcomes of attempted operative vaginal delivery

To assess whether outcomes of attempted operative vaginal delivery (OVD) are associated with obesity among nulliparous individuals. This is a secondary analysis from the prospective cohort Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be study. This analysis included participants with cephalic liveborn non-anomalous singletons who delivered ≥34 weeks of gestation and had attempted OVD. The primary exposure was maternal obesity defined by body mass index (BMI) at delivery (obese: BMI ≥30 kg/m2 vs. non-obese: BMI < 30 kg/m2 [referent]). The primary outcome was failed OVD, defined as a cesarean delivery following attempted OVD, and secondarily maternal and neonatal adverse outcomes. Multivariable logistic regression was used to adjust for covariates, and statistical interaction between BMI and instrument type (forceps or vacuum) was assessed. When the interaction was significant, stratified analyses were performed and presented. Of 10,038 individuals in the parent study, 791 (7.9%) had an attempted OVD and were included in the analysis. 325 (41%) had BMI ≥30 at delivery. The type of instrument used was no different based on obesity status. Failed OVD, which occurred in 6.8% of attempts, was more frequent in those with obesity (10.1 vs 4.2%; p=0.005; aOR 2.23, 1.16-4.28), with no significant interaction by instrument type (Table 1). There was an interaction (p=0.046) between composite neonatal morbidity and instrument type. Stratified analysis revealed that composite neonatal morbidity was more likely following attempted vacuum in infants of people with obesity (32.7 vs 22.3%, aOR 1.61, 1.07-2.43) but not following forceps attempt. Other adverse outcomes were neither different by obesity status nor had significant interactions with instrument type (Table 2). Among nulliparas, attempted OVD was more likely to fail in people with obesity. Neonates of people with obesity who underwent attempted vacuum, but not attempted forceps, had higher composite morbidity than those with BMI < 30.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Cervical funneling is more predictive of preterm birth than cervical length alone in nulliparous women

Universal mid-trimester cervical length (CL) screening is a well-accepted practice for detection of women at risk of spontaneous preterm birth (sPTB). In those identified with a short cervix, progesterone supplementation is recommended. However, current guidelines do not consider a short cervix an indication for cerclage without a history of sPTB as it has poor sensitivity for this outcome. It is currently unclear if other sonographic features such as cervical funneling can identify a higher sPTB risk in a population without prior sPTB. This was a secondary analysis of the nuMom2b study, which enrolled a large prospective observational cohort of pregnant nulliparous women. Patients were stratified based on CL < 25mm or ≥25mm and presence or absence of funneling at the time of cervical length evaluation between 16-22 weeks’ gestation. Logistic regression was used to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for sPTB adjusting for confounders. A Kaplan-Meier survival analysis was performed between groups and gestational age at delivery. 7,648 nulliparous women were included in the analysis. There were 169 (2.2%) women identified with a short CL < 25 mm and 52 (0.7%) with funneling. While a short CL had a higher risk of PTB (Table 1), a short CL was detected in only 24 (7.1%) of women who ultimately had a sPTB. The presence of a funnel was independently associated with higher odds of sPTB (OR 3.4, CI 1.9-8.1) when compared to CL < 25mm (OR 2.7, CI 1.7-4.4). On survival analysis, a short CL with funneling showed the lowest mean gestational age at delivery (Figure 2, p< .001). In a nulliparous population without prior sPTB, transvaginal cervical length alone is a poor predictor of preterm delivery, but presence of funneling significantly increases risk. This may identify a population of women who would benefit from cerclage.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Application of population modeling to characterize the effect of pregnancy on aspirin pharmacokinetics

Low dose aspirin is recommended for preeclampsia prevention in high risk pregnancies. However, there remains uncertainty regarding its optimal dosing due to the lack of pharmacokinetic (PK) based clinical studies in pregnancy. Herein we developed a population PK model for aspirin in preeclampsia using data from a preliminary study to investigate the alterations of aspirin PK through gestation. A population PK model was developed using data from a clinical trial in which aspirin was started in women at risk of preeclampsia (Table 1) at a daily dose of 81 mg in the first trimester (10-14 weeks’) of pregnancy through delivery (N=10). Samples were collected from 0-6h following the first aspirin dose with a similar schedule in the third trimester (28-32 weeks’). Salicylic acid (primary metabolite) was the analyte used in the construction of the PK model. Modeling was done following standard development and qualification procedures. A one-compartment model with zero-order formation and linear elimination best described the PK of salicylic acid (Table 2). A correlation between volume of distribution (V) and clearance (Cl) was added to adjust for the correlation between random effects. The observed drop in Cmax in the third trimester was explained by the inclusion of the gestational age as a covariate on V as follows: V in pregnancy (L) =5.79 * gestational age (weeks)ˆ0.21, i.e., V increases with the gestational age by a factor beta = 0.21. Cl did not change between trimesters as well as the duration of zero order metabolite formation. Gestational age increases V of salicylic acid without altering elimination. This model-based approach can help optimizing aspirin dosing for the prevention of preeclampsia understanding that V is the principal parameter altered through gestation. Clinical data at 162mg dosing would assist in further refining the model, which could then be used to model aspirin dose/response for future trials or clinical use.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Real-world utilization of an intrauterine vacuum-induced hemorrhage-control device

Intrauterine vacuum-induced hemorrhage control device is a new tool in management of postpartum hemorrhage after being FDA-cleared in Aug 2020. The objective of this study was to report on real-world effectiveness and safety of this device. An observational, post-market registry chart review was conducted at 16 US centers selected for ability to readily collect data on device use (NCT04995887). We report baseline characteristics, treatment outcomes overall and by isolated uterine atony, and adverse events/device effects. The primary outcome, treatment success, was defined as device successfully controlling bleeding with no treatment escalation or bleeding recurrence. Data are presented by mode of delivery. From Oct 2020-Apr 2022, 800 individuals were treated with the device; 94.3% had uterine atony. Treatment success was 92.5% for vaginal births and 83.7% for cesarean births. In cases where uterine atony was the sole cause of bleeding (isolated uterine atony; n=307 vaginal, n=220 cesarean), treatment success was 95.8% for vaginal and 88.2% for cesarean births (Table 1). For vaginal births, mean indwelling time (insertion to removal) was 4.6 hours and bleeding recurred after device removal in 2.8% (Table 1). For cesarean births, mean indwelling time was 6.3 hours and 4.1% had bleeding recur (Table 1). Time to bleeding control was available in 49% of cases. In vaginal births (n=241), 73.8% (n=178) achieved bleeding control in ≤ 5 minutes. In cesarean births (n=151), 62.2% (n=94) achieved bleeding control in ≤ 5 minutes. Of the adverse events/device effects reported (Table 2), 3 serious events were deemed possibly related to the device or procedure [2 (0.4%) vaginal, 1 (0.4%) cesarean]. For both vaginal and cesarean births in real-world settings, rapid and effective bleeding control was observed with an FDA-cleared intrauterine vacuum-induced hemorrhage-control device. The adverse event profile was consistent with that observed in the registrational trial (NCT02883673). This device may help to decrease maternal morbidity and improve obstetric hemorrhage outcomes.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Fetal bladder morphology may predict neonatal outcomes in fetal lower urinary tract obstruction (LUTO)

Objectives: To evaluate postnatal survival outcomes of severe LUTO-affected fetuses based on fetal bladder shape. We hypothesize that fetuses with a “floppy” appearing bladder on initial prenatal ultrasound will have worse neonatal outcomes than fetuses with full/rounded bladders. Study Design: We performed a retrospective case review of all cases of LUTO that were evaluated for fetal intervention in a single large fetal center between January 2013 and December 2021. Fetuses were given a “favorable” or “unfavorable” evaluation based on comprehensive ultrasound, renal biochemistry testing, and bladder refill testing. Favorable evaluations were offered fetal intervention with vesicoamniotic shunt placement. Baseline demographics, ultrasound parameters, prenatal renal function testing, and neonatal outcomes were collected. Those with a diagnosis of severe LUTO were included in analysis. Descriptive statistics were used to analyze candidate data. Primary outcome was survival at 6 months of life. Results: Of the 104 LUTO patients evaluated, 24 were included in analysis. Details of prenatal evaluations are shown in Table 1a; six-month survival among groups based on fetal bladder morphology are shown in Table 1b. Postnatal survival at six months in patients with rounded bladders was 60% overall. Fetuses with floppy bladders showed a 0% six-month overall survival, which was significantly lower (p=0.002) as compared with the full/rounded bladder group. Conclusions: We propose that analysis of bladder shape in fetuses with severe LUTO may be an important prognostication factor for predicting neonatal outcomes. This simple, non-invasive assessment may inform clinical decision-making regarding further testing or fetal intervention.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Trends in cesarean among low-risk deliveries in the United States, 2000-2019

Current recommendations for safely preventing cesarean delivery include allowing for longer labor prior to diagnosing labor arrest. The objective of this study was to determine temporal trends in indications for cesarean delivery (CD) among low-risk patients over a 20-year period. This repeated cross-sectional study analyzed delivery hospitalizations among women aged 15-54 years at low risk for cesarean using the National Inpatient Sample from 2000-2019. Deliveries at low risk for CD were identified using SMFM criteria. CD indications were analyzed, and included non-reassuring fetal monitoring and labor dystocia/arrest. Labor arrest was further characterized as occurring during the active phase, the latent phase, or the second stage. Temporal trends in CD indications were analyzed using joinpoint regression to estimate the average annual percent change (AAPC) with 95% confidence intervals (CIs). Of 76 million delivery hospitalizations identified, an estimated 42,670,197 deliveries were determined to be at low risk for CD. Of these deliveries, 12.7% (5,420,406) delivered by cesarean. From 2000-2009, low-risk cesareans increased from 10.1% to 14.5%, plateaued, and then decreased from 13.7% to 11.9% from 2012-2019 (Figure 1). From 2000-2005, the AAPC for CD was 6.5% (95% CI 5.3%, 7.7%), 1.1% from 2005-2009 (95% CI -1.3%, 3.6%) and -2.1% from 2009-2019 (95% CI -2.5%, -1.6%). CD for non-reassuring fetal monitoring increased from 3.2% of all deliveries in 2000, to 5.1% in 2019 (AAPC 2.7%, 95% CI 2.2%, 3.3%). CD for labor arrest increased from 3.6% in 2000 to a peak of 4.6% in 2009 before decreasing to 2.7% in 2019 (Figure 2). CD for arrest during the active phase, latent phase, and second stage all increased during the first half of the study from 2000 to 2009 and then decreased from 2010 to 2019. Low-risk cesarean deliveries decreased over the latter years of the study period with cesarean for labor arrest becoming less common. Cesarean delivery for non-reassuring fetal monitoring has continued to increase. These findings support uptake of clinical recommendations.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Gestational age-related risk of rupture of membranes in the setting of fetoscopy for twins

To describe, in twin pregnancies, the gestational age-related risk of postoperative rupture of membranes (ROM) < 34 weeks when fetoscopic surgery occurs from 16-26 weeks. Retrospective cohort study of twin pregnancies that underwent fetoscopy at a single fetal center from April 2010 to June 2019. Inclusion criteria was any twin pregnancy in which fetoscopic surgery was performed between 16-26 weeks. Exclusion criteria was aneuploidy, major congenital anomalies, higher order multiples. This study received IRB approval. Pregnancies were stratified by the week of fetoscopy. Primary outcome was the risk of ROM < 34 weeks gestation. Given that earlier surgery carries a longer latency between surgery and 34 weeks, to further measure the risk of ROM, Logrank analysis was used to evaluate the probability of having intact fetal membranes in the 8 weeks immediately post-op. For this analysis, surgeries were grouped into 3 gestational age ranges: surgery < 20 weeks, surgery from 20 0/7-22 6/7 weeks, and surgery from 23-25 6/7 weeks. 696 pregnancies met inclusion. 221 (32%) experienced ROM < 34 weeks. 118 (17%) experienced ROM within 8 weeks of fetoscopy. The risk of ROM with each week of gestation, as well as the 95% CI estimates are listed in table 1. There was a statistically significant decrease in ROM prior to 34 weeks when surgery occurred beyond 20 weeks gestation. Evaluating the probability of pregnancies having continued intact membranes in the 8 weeks immediately post-op revealed an intact membrane rate of 78% (95% CI 72-82%) when surgery occurred < 20 weeks, 87% (95% CI 82-90%) when surgery occurred between 20-22 6/7 weeks, and 79% (95% CI 71-85%) when surgery occurred between 23-25 6/7 weeks (p < 0.001), figure 1. The risk of ROM < 34 weeks decreases when fetoscopy occurs after 20 weeks. Compared to < 20 weeks, there is a lower risk of ROM in the subsequent 8 weeks when surgery occurs between 20-22 6/7 weeks. Interestingly, when surgery occurred < 20 weeks compared to 23-25 6/7 weeks, there was no difference in the risk of ROM in the 8 weeks immediately post-op.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Diagnostic yield of weekly laboratory testing in the outpatient management of hypertensive disorders of pregnancy

Weekly laboratory testing in the outpatient management of Hypertensive Disorders of Pregnancy (HDP) has been recommended by ACOG for the last decade with little evidence regarding its utilization. Our objective was to compare the diagnostic yield of weekly laboratory episodes in symptomatic versus asymptomatic patients with HDP. Retrospective cohort study of singleton pregnancies with HDP managed outpatient from 1/2014 to 7/2021. Our primary outcome was the prevalence of a positive laboratory test resulting in delivery or inpatient management in patients that were symptomatic versus asymptomatic at the time of each laboratory episode. A positive test was defined as a laboratory value diagnostic of preeclampsia with severe features. Patients were considered symptomatic if maternal symptoms (headache, scotoma, RUQ pain) or elevated blood pressure were reported. Secondary outcomes included adverse maternal outcomes and a cost analysis performed using Medicare fee schedule costs of each lab test. The prevalence of 1° and 2° outcomes were compared using chi square test. A total of 543 patients were included in the study. In total, 1082 laboratory episodes were performed: 356 (33%) in symptomatic and 726 (67%) in asymptomatic patients. Overall, the rate of abnormal lab results was low (1%), but the percentage of positive tests was higher in symptomatic versus asymptomatic patients (2.8% versus 0.1%, p< 0.01). Only 1 patient (0.2%) had an adverse maternal outcome, intrapartum placental abruption. The overall cost to screen asymptomatic patients was higher than symptomatic patients ($12,363.78 versus $6,062.68), and the cost per abnormal test was lower for symptomatic patients ($1,212 versus $12,363.78). The diagnostic yield of weekly laboratory evaluation for HDP was low overall, however significantly higher in patients that were symptomatic. Eliminating routine weekly laboratory evaluation of asymptomatic patients with HDP would eliminate approximately 67% of laboratory episodes and result in significant cost savings with minimal effect on the overall diagnostic yield.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Provider willingness towards periviable cervical cerclage placement in singleton gestations: a survey of providers nationwide

Cervical cerclage placement up to 24 weeks may prolong pregnancy and reduce preterm birth rates and associated neonatal morbidity. In certain settings, neonatal viability now extends as early as 22 weeks’ gestational age (GA). This periviability overlap leads to great variability among providers’ willingness to perform an ultrasound-indicated (UC) or physical exam-indicated (PEC) cerclage at 22- and 23-weeks GA. We aimed to elucidate current periviable cerclage placement practices among Maternal-Fetal Medicine (MFM) physicians. A survey was available to all MFM members of the Society for Maternal-Fetal Medicine from February-May 2022. Participants were asked about their practice for UC and PEC between 22 0/7 – 22 6/7 weeks (22 weeks) and between 23 0/7 – 23 6/7 weeks (23 weeks). UC and PEC were defined in the instructions. This abstract specifically addresses provider willingness to provide UC and PEC at each GA in singletons. Rates of cerclage placement were calculated. Chi-square analysis and Fisher’s exact test assessed response differences according to physician characteristics (number of years in practice, practice model, and region of practice in the country). Separate logistic regression models were used on adjusted analysis to estimate the association between the odds of offering cerclage and each characteristic above. 406 responses (response rate 18.1%) revealed that at 22 weeks, 92.1% would offer UC and 95.8% would offer PEC. At 23 weeks, 62.6% would offer UC and 66.3% would offer PEC, with differences noted according to the number of years in practice and the region of the country of practice (Table 1). On adjusted analysis these differences remained, with the odds of UC and PEC being significantly lower at 23 weeks for those in practice > 10 years and providers in the South (Table 2). Periviable cerclage management varies greatly, with willingness to perform UC and PEC being significantly different according to region of the country and the number of years in practice. These differences reflect the need for evidence-based guidelines in these scenarios.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Adverse pregnancy outcomes in people with Type 2 diabetes mellitus utilizing continuous glucose monitoring

In recent years, continuous glucose monitoring (CGM) has become available for people with type 2 diabetes (T2DM) or gestational diabetes (GDM) during pregnancy. However, the recommended time in range (TIR, blood glucose 70-140 mg/dL) and correlation of TIR with adverse pregnancy outcomes in people with T2DM or GDM is not well known. Our aim was to compare maternal and neonatal outcomes in pregnant people with T2DM or GDM with average CGM TIR ≥70% vs < 70% during pregnancy. We conducted a retrospective cohort study of all individuals using CGM during pregnancy from January 2017 to June 2022 at a quaternary center. Individuals with Type 1 diabetes, or those with missing CGM or delivery data were excluded. Primary composite neonatal outcome included any of the following: large for gestational age, NICU admission, need for IV glucose, respiratory support or neonatal death. Secondary outcomes included other maternal and neonatal outcomes. Regression models were used to estimate adjusted odds ratio (aOR) and 95% confidence intervals (CI). During the study period, of 141 individuals with diabetes who utilized CGM during pregnancy, 65 (46%) met inclusion criteria. Excluded were Type 1(n= 57) diabetes, missing CGM data (n=5), missing delivery data (n=14). Of the study population, 28 (43%) had TIR < 70% and 37 (57%) had TIR ≥ 70%. Individuals with TIR < 70% had a higher mean glucose reading (151 vs 109, p< 0.001), and were less likely to have GDM (Table 1). The primary composite outcome occurred more frequently in neonates of individuals with TIR < 70% (71.4% vs 37.8%, aOR 4.8, 95% CI 1.6, 15.7). Furthermore, people with TIR< 70% were more likely to have hypertensive disorders (42.9% versus 16.2%, OR 3.9, 95% CI 1.3, 13.0), have a preterm delivery (54% vs 27%, OR 3.1, 95% CI 1.1, 9.1), and have cesarean delivery (96.4% vs 51.4%, OR 4.6, 95% CI 2.2, 15.1; Table 2) compared to those with TIR≥70%. Among people with T2DM or GDM who utilized CGM during pregnancy, 4 out 10 individuals had TIR < 70% and they are at significantly higher risk of adverse neonatal and maternal outcomes.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The association of sodium intake with the development of hypertensive disorders of pregnancy

To assess the association between daily sodium intake and risk of hypertensive disorders of pregnancy. This was a secondary analysis of the prospective Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be study. In this analysis, we included those with non-anomalous, singleton pregnancies who completed food frequency questionnaires in which they recorded their sodium intake in the 3 months prior to pregnancy. Individuals who did not progress beyond 20 weeks’ gestation were excluded. Sodium intake was categorized as low (< 2g per day), medium (2g to < 3g per day), or high (≥ 3g per day). The primary outcome was development of a new-onset hypertensive disorder of pregnancy (HDP), including antenatal gestational hypertension, preeclampsia, HELLP, and superimposed preeclampsia. Other maternal and neonatal outcomes also were assessed. Kruskal-Wallis and Chi square tests were used to compare baseline characteristics. Adjusted incidence risk ratios (aIRR) with 95% confidence intervals (CIs) were estimated using Poisson regression to control for confounders. Among 7927 individuals eligible for this analysis, 2,482 (31%) reported low sodium intake, 2,978 (38%) medium sodium intake, and 2,467 (31%) high sodium intake. Baseline characteristics, including age, BMI, self-reported race and ethnicity, and tobacco use differed significantly between groups (all p< 0.01, Table 1). The risk of developing HDP was similar among groups (medium vs. low aIRR 1.03, 95% CI 0.88-1.22; high vs. low aIRR 1.13, CI 0.96-1.34). There were no differences in other adverse maternal or neonatal outcomes by sodium intake (Table 2). There was no association between sodium intake and risk of HDP. This may reflect a difference in the pathophysiology underlying pregnancy and non-pregnancy related hypertensive disorders.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

AHA stage 1 hypertension and risk of small for gestational infants in nulliparous women

Non-Obstetric guidelines by the American Heart Association (AHA) have redefined hypertension (HTN) into stages with a systolic blood pressure (BP) of 130-139 mmHg and/or diastolic BP of 80-89 mmHg defined as stage 1. It is well known that stage 1 HTN confers a significantly elevated risk of hypertensive disorders of pregnancy, but less is known regarding effects on placental function and subsequent birth weight. This study aims to assess risk of small for gestational age (SGA) birth weight in women stratified by non-Obstetric HTN cut points. This was a secondary analysis of a large prospective observational study investigating birth outcomes in nulliparous women (nuMoM2b). Subjects were excluded from the current analysis for incomplete outcome data, lack of first trimester blood pressure, structural fetal anomaly, and pregestational diabetes. Women were stratified based on documented first trimester blood pressure defined as normotensive (< 120/< 80), elevated (120-129/< 80), stage 1 HTN (130-139/80-89), or stage 2 HTN (either by medical history or BP ≥140/≥90). Logistic regression was used to generate adjusted odds ratio (aOR) and 95% confidence intervals (CI) for SGA birth weight (< 10%) and pregnancy induced HTN ([PIH], gestational HTN or preeclampsia). 7,951 pregnancies were included in the analysis with 601 (7.6%) meeting criteria for stage 1 hypertension based on AHA guidelines and 754 (9.5%) delivered SGA neonates. There were no significant differences in rates of SGA among groups < 10% (p=0.184) or < 3% (p=.920), Figure 1. There were also no differences in SGA after regression analysis (Table 1). Women with stage 1 HTN had the highest risk of PIH (aOR 2.1, CI 1.7-2.6) while stage 2 HTN was not significant after adjustment (aOR 1.3, CI 0.92-1.8). Nulliparous women with stage 1 hypertension by non-obstetric guidelines do not have an elevated risk of SGA despite and increased risk of hypertensive disorders of pregnancy.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Introducing a novel technique to reduce severe perineal injuries during delivery: the “shoulder-up” maneuver

To investigate if introducing a novel technique to assist the delivery of the posterior shoulder (the “shoulder-up” maneuver) in a tertiary referral unit may positively impact on the rate of severe perineal injuries. Single-center retrospective interventional study including all vaginal deliveries between April 1st 2020 and March 31st 2022. On March 1st, 2021, a bundle to raise the awareness on the perineal wounds prevention at the delivery of posterior shoulder had been introduced. The “shoulder-up” maneuver, which consists in a slow, controlled delivery of the posterior shoulder under direct visualization of perineal plane after the disengagement of anterior shoulder (see the attached figure), had been included as a standard of care. All midwives and physicians completed a full theoretical and practical course to learn the maneuver at the moment of the bundle introduction. A propensity score matching analysis was performed to assess the effect of the “shoulder-up” maneuver on the risk of perineal tears adjusting for those variables that resulted to be independently associated to more severe perineal injury (nulliparity, gestational age at delivery, peridural analgesia, vacuum extraction and birthweight > 4Kg at delivery). We matched a total of 3652 patients (1826 per arm); the analysis showed a significant increase in intact perineum rate (59.5% vs 66.4%, p = 0.009) and a significant reduction in the incidence of 2nd (30.7% vs 25.8%, p = 0.006) and 3rd-4th degree perineal wounds (2.8% vs 1.2%, p < .001) after the introduction of the bundle. Episiotomy rate did not significantly change before and after the maneuver adoption (7.0 % vs 6.5%, p = 0.702). Our study showed that after the introduction of the “shoulder-up” maneuver as a standard of care in the assistance to vaginal delivery the rate of severe perineal wounds significantly decreased.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Resolving placenta accreta spectrum biology with spatial transcriptomics

Placental accreta spectrum (PAS) is associated with severe obstetric morbidity. The pathophysiology involves myometrial invasion as a function of signaling between an abnormal decidual environment and uterine scar dehiscence. The cellular heterogeneity at the site of invasion and the function of cell types at the maternal-fetal interface have not been well characterized. Single-cell spatial transcriptomics allows cellular architecture to be maintained while understanding the cellular heterogeneity, serving as a tool for biomarker discover and more so, understanding PAS disease mechanism. We performed spatial transcriptomics and single-cell RNAseq assays to determine local gene expression profiles at the site of accreta invasion (AI) and a non-invasive site from the same placenta (AO), as well as in controls (C). We utilized the GeoMX Digital Spatial Profiler for RNA library preparation and sequencing for next-generational sequencing. We selected 12 regions of interest (ROI) per condition for spatial transcriptomic analysis. ROIs were compared following segmentation and probe QC. Spatial transcriptomics annotation identified distinct gene signature by condition – AI, AO, and C. Clustering analysis identified 99 genes differently regulated between AI versus AO. AI showed a unique gene signature most prominent in the endothelial and stromal cell populations. The highest expression in AI compared to AO and C was seen in the following genes: HGF, LAMA2, DCN, SPARC, COL3A1, EGFL6 and decreased in ANK1, PTX1 and MGARP. Gene set enrichment analysis identified the following key pathways: blood vessel development, regulation of cell adhesion and migration, and the integrin pathway. We present an in-depth transcriptomic characterization of PAS across the site of invasion and sites of non-adherence with relative morphological context. This high-resolution transcriptomic profiles with locality information of PAS helps to understanding disease mechanism and inform diagnostic and therapeutic discoveries, that currently imply loss of boundary limits on a cellular level.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The utility of severity scoring systems to identify obstetric transports at risk for ICU escalation

Prevention of severe maternal morbidity requires prompt identification of the critically-ill patient requiring intensive care (ICU). We aim to describe different severity scores associated with obstetric transports initially admitted to labor and delivery (L&D) but require escalation to the ICU. Specifically we evaluate the SOFA, APACHE-II, Shock (SI) and ROX (ROXi) index scoring systems. This is a retrospective cohort study of obstetric transports to a single tertiary medical center from 01/1/2017-12/31/2021. EMR was used to collect demographics, maternal risk factors, indication for ICU escalation, lab values, and severity scores at arrival and 24 hours after admission. Propensity score 1-to-1 matching using a 0.1 caliper was used to match patients escalated to the ICU with obstetric patients that did not need ICU. Patients were matched by age, antepartum or postpartum on admission and admitting clinical diagnoses. A total of 1,794 obstetric transport patients were directly admitted to L&D with 52 patients requiring escalation to the ICU during their admission. Of these, 34 ICU escalation were matched with 37 that did not require ICU. There were no differences in the demographic data between the two groups, Table 1. SOFA, APACHE-II, and ROXi scores were significantly higher in patient requiring ICU escalation (p=0.001), with no difference in SI. When comparing 24 hours after admission, SOFA and APACHE II scores were higher (p=0.001), with no difference in SI or ROXi. Median time to ICU escalation was 18.7 h and length of stay were longer for patients requiring ICU (12.7d vs 3.7d, p=0.001),Table 2. In obstetric transport patients, SOFA and APACHE-II were consistently higher on admission and 24 hours after admission in patients that were escalated as compared to those not requiring escalation to the ICU. Future research is needed to develop cut-offs or a composite score to determine whether obstetric transports are appropriate for direct admission to L&D versus the ICU.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The effects of social determinants of health on breastfeeding practices in patients with heart disease

Data on the association between social determinants of health (SDOH), breastfeeding (BF) and maternal cardiac disease (MCD) are lacking. We sought to evaluate BF intent, BF rates at discharge, and continued BF at follow-up in patients managed in a comprehensive cardio-obstetrics program stratified by area deprivation index (ADI). Observational cohort of patients managed by the UAB Cardio-Obstetrics Program. Patients were included if they had ≥1 prenatal visit with the Cardio-Obstetrics team, delivered at UAB, and had a street address on file. The primary outcome was BF rate at hospital discharge. Secondary outcomes included BF intent on admission and BF at the postpartum (PP) visit. ADI reports socioeconomic disadvantage at the census tract level; 1 = least deprived, 100 = most deprived. Baseline characteristics and BF rates were compared by ADI tertiles: Low (ADI 1 – 33), Medium (ADI 34 – 66), and High (ADI 67 – 100). 148 patients were included: 14 (10%) Low ADI, 42 (28%) Medium ADI of 34 – 66, and 92 (62%) with an ADI of 67 – 100. Patients with the highest tertile ADI were younger relative to the medium or lower tertile (26 vs 28 vs. 32 years; p< 0.01) and less likely to be married or living with a partner (30.4% vs. 58.5% vs. 71.4%; p< 0.01). Importantly, BMI, race, GA at delivery, medical comorbidities and MCD classification were not different between groups. There was no difference in BF intent between the highest, medium, and lowest ADI tertiles (81.6% vs. 85.4% vs. 85.7%; p=0.38) or BF rates at hospital discharge (85.6% vs. 92.7% vs. 100%, p=0.23). However, there was a significant difference in BF rates at the PP visit (38.6% vs.63.0% vs. 90%; p< 0.01). Specifically, BF rates among patients from the high ADI group dropped from 86% at hospital discharge to 39% at the PP visit. There is a clear association between disadvantaged status, as defined by ADI, and early cessation of breastfeeding in our population of patients with maternal cardiac disease. Interventions to offset the effects of SDOH on BF in patients with MCD may improve maternal and infant health.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Management of postpartum urinary retention: a multi-center randomized controlled trial

To assess the most effective catheterization strategy to resolve overt postpartum urinary retention (PUR). A prospective randomized controlled trial was conducted at 4 university-affiliated medical centers. Women with PUR (bladder volume >150 mL) up to 6 hours following vaginal or cesarean delivery were randomly allocated to one of two protocols: intermittent catheterization every 6 hours (up to 4 times) or an indwelling urinary catheter for 24 hours (continuous catheterization), until full resolution (defined as post-void residual volume < 150 mL, estimated by either catheter or transabdominal ultrasound). If PUR was not resolved after 24 hours an indwelling catheter was inserted for additional 24 hours in both groups. The primary outcome was mean time to PUR resolution. Secondary outcomes included post-catheter urinary tract infection (UTI) rate and the length of hospital stay. We estimated that 73 women/group would have to be included to have 90% power to detect a 13 hours difference in the primary outcome (from 3024 to 1724 hours). From 1/2020 to 6/2022, 182 women were eligible for enrollment, while 147 women were eventually randomized: 73 in the intermittent group and 74 women in the continuous catheterization group. As shown in table 1, baseline and delivery characteristics were not different between the groups, including mode of delivery. Mean post-void residual bladder volume preceding catheterization was similar between the groups (813410 mL vs. 924448 mL, p=0.12) (Table 2(. Mean time to PUR resolution was significantly shorter in the intermittent catheterization group (10.211.8 vs. 26.59.0 hours, p< 0.001), with 75% and 93% resolution rates after one and two catheterizations, respectively. Satisfaction rate was higher in all categories among intermittent catheterization group. No difference was found in UTI rate or hospital stay. An intermittent catheterization for PUR following delivery, compared to an indwelling catheter for 24-hours, is associated with a quicker PUR resolution, and a higher satisfaction rate, without increasing complications rate.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Meta-analysis on the effect of internal-iliac artery balloon occlusion in placenta accreta spectrum and previa

To examine the efficacy of preoperative prophylactic balloon occlusion (PPBO) of the internal iliac arteries (IIA) in women with placenta accrete spectrum (PAS) and placenta previa in reducing operative bleeding. MEDLINE, EMBASE, Web-of-Sciences, Scopus, the Cochrane Library, and ClinicalTrials.gov were searched from inceptions to March 2022 without language restriction. Search terms were as follows:[“Placenta accrete” OR “placenta increta” OR “placenta percreta” OR “placental abnormalities” OR “placenta accreta spectrum” OR “PAS” OR “placental diseases” OR “abnormal placentation” OR “Placenta Previa”] AND [“prophylactic” OR “balloon” OR “catheter” OR “occlusion” OR “endovascular” OR “iliac artery” OR “uterine artery” OR “interventional radiology”] AND [“randomized control study” OR “RCT” OR “controlled clinical trial” OR “Randomized controlled trial”]. Only peer-reviewed trials that compared the use of PPBO of the IIA compared to no use were included. The studies’ quality was assessed by the Cochrane Risk of Bias tool. Primary outcome was number of packed red blood cell (RBC) units transfused. Secondary outcomes included intra- and postoperative complications. The study was conducted according to a prospectively prepared protocol, registered with PROSPERO under CRD42016024244. Of 164 reports identified, 3 randomized trials representing 167 women (83 and 84 in the intervention and control groups, respectively) were eligible. All were judged to be at a low risk of bias. Mean number of packed RBC units transfused was 4.52±1.70 and 3.70±1.88 in the intervention and control groups, respectively (p=0.001), (Figure 1). Total operating time was significantly higher in the intervention group, (p=0.001) as well as the rate of postoperative fever (p=0.02). Transfusion of additional blood products, and other intra- and postpartum outcomes were comparable (Table 1). Use of PPBO of the IIA in PAS and placenta previa was associated with increased number of packed RBC units transfused, operating time and fever. Other pre- and postoperative outcomes were similar to the controls.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Association between maternal pre-pregnancy BMI category and fetal umbilical artery pH

To evaluate the association between maternal pre-pregnancy body mass index (BMI kg/m2) and fetal umbilical arterial pH at the time of delivery in nulliparous women. We performed a secondary analysis of the nuMoM2b study. Subjects in this study were nulliparous with a singleton pregnancy. Subjects with fetal anomalies or missing fetal umbilical artery pH were excluded. Subjects were categorized based on pre-pregnancy BMI (less than 18.5, 18.5-24.9, 25-29.9, 30-34.9, 35-39.9, and 40 or greater). Our primary outcome was an umbilical artery pH at the time of delivery. We also examined base deficit, the rate of fetal acidosis defined as pH < 7.0, and the need for advanced neonatal resuscitation. Analyses were stratified by the route of delivery. Multivariable linear or logistic regression models were used to calculate adjusted P-values or adjusted odds ratios (95% confidence intervals), controlling for confounders. Of 3,015 subjects, 1,870 (62%) had a vaginal delivery, and 1,145 (38%) had a cesarean delivery. There were significant differences in demographics across the BMI categories in both subjects who had a vaginal delivery and cesarean delivery (age, race, chronic hypertension, gestational diabetes, pregestational diabetes, preeclampsia, and gestational hypertension). Among subjects who had a vaginal delivery, there was no difference in fetal umbilical artery pH (p=0.31) across the BMI categories (Table 1). Base deficit of subjects with BMI < 18.5 and BMI 40 or greater was significantly lower than that of subjects with BMI 18.5-24.9 (adjusted p< 0.05). Among subjects who had a cesarean delivery, the fetal umbilical arterial pH of subjects with BMI 30-34.9 and BMI 40 or greater was significantly lower than that of subjects with BMI 18.5-24.9 (adjusted p< 0.05) (Table 2). In nulliparous subjects with a singleton pregnancy, obesity was associated with decreased fetal umbilical arterial pH at the time of cesarean delivery. However, this finding was not observed in subjects who had a vaginal delivery.View Large Image Figure ViewerDownload Hi-res image Download (PPT)