Sonographic Predictors of Antepartum Bleeding in Placenta Previa.

OBJECTIVE: To evaluate the association between sonographic features of placenta previa and vaginal bleeding (VB). STUDY DESIGN: Retrospective cohort study of women with placenta previa identified on ultrasound between 160/7 and 276/7 weeks gestation. Placental distance past the cervical os (DPO), placental thickness, edge angle, and cervical length (CL) were measured. The primary outcome was any VB and the secondary outcome was VB requiring delivery. Median values of the sonographic features were compared for each of the outcomes using the Mann-Whitney U test. Receiver operating characteristic curves were used to compare the predictive value of sonographic variables markers and to determine optimal cut points for each measurement. Logistic regression was used to estimate the association between each measure and the outcomes while controlling for confounders. RESULTS: Of 149 women with placenta previa, 37% had VB and 15% had VB requiring delivery. Women with VB requiring delivery had significantly more episodes of VB than those who did not require delivery for VB (1.5, interquartile range [IQR] [1-3] vs 1.0 [1-5]; p = 0.001). In univariate analysis, women with VB had decreased CL (3.9 vs. 4.2 cm; p < 0.01) compared with those without. Women with VB requiring delivery had increased DPO (2.6 cm IQR [1.7-3.3] vs. 1.5 cm [1.1-2.4], p = 0.01) compared with those without. After adjusting for confounders, only CL < 4 cm remained independently associated with increased risk of VB (adjusted odds ratio: 2.27, 95% confidence interval [1.12-4.58], p = 0.01). None of the measures were predictive of either outcome (area under the curve < 0.65). CONCLUSION: Decreased CL may be associated with risk of VB in placenta previa. KEY POINTS: · Placenta previa is associated with VB.. · Sonographic markers of placenta previa are associated with VB.. · CL is associated with VB in placenta previa, whereas placental DPO is associated with higher rates of bleeding leading to delivery..

The role of statins in the prevention of preeclampsia.

Preeclampsia is a common hypertensive disorder of pregnancy associated with considerable neonatal and maternal morbidities and mortalities. However, the exact cause of preeclampsia remains unknown; it is generally accepted that abnormal placentation resulting in the release of soluble antiangiogenic factors, coupled with increased oxidative stress and inflammation, leads to systemic endothelial dysfunction and the clinical manifestations of the disease. Statins have been found to correct similar pathophysiological pathways that underlie the development of preeclampsia. Pravastatin, specifically, has been reported in various preclinical and clinical studies to reverse the pregnancy-specific angiogenic imbalance associated with preeclampsia, to restore global endothelial health, and to prevent oxidative and inflammatory injury. Human studies have found a favorable safety profile for pravastatin, and more recent evidence does not support the previous teratogenic concerns surrounding statins in pregnancy. With reassuring and positive findings from pilot studies and strong biological plausibility, statins should be investigated in large clinical randomized-controlled trials for the prevention of preeclampsia.

The Importance of Clinical Presentation in Risk and Management of Recurrent Preterm Birth.

OBJECTIVE: This study aimed to compare the risk of recurrent spontaneous preterm birth (sPTB), as well as cerclage efficacy, between groups stratified by phenotype of the index sPTB. STUDY DESIGN: This is a retrospective cohort study of women with a history of sPTB. Included were women with a history of singleton sPTB who received progesterone in a subsequent pregnancy. Multifetal gestations and abdominal cerclage were excluded. Exposure groups were based upon the presenting symptom that preceded their first sPTB and included painless cervical dilation (PCD), preterm premature rupture of membranes (PPROM), and painful dilation (preterm labor [PTL]). Primary outcome was delivery <34 weeks in a subsequent pregnancy. Secondary outcomes included delivery <28 and <37 weeks. Rates were compared using the Chi-square test. Multivariable Poisson regression was used to adjust for confounders. RESULTS: A total of 723 women were included. A total of 114 (16%) presented with PCD, 305 (42%) with PPROM, and 304 (42%) with PTL in their first sPTB. Cerclage in subsequent pregnancy was highest in the PCD group (42%) when compared with the PPROM (16%) and PTL (12%) groups. Rates of sPTB <34 and 37 weeks were similar among the groups. After adjusting for confounders, PCD was found to significantly increase the risk of recurrent sPTB <28 weeks (incidence rate ratio: 3.46 [1.09-11.0]; p = 0.04). Of the 121 women who underwent cerclage, there were no significant differences in rates of sPTB between the clinical presentation groups. CONCLUSION: PCD as a specific phenotype of sPTB impacts recurrence of delivery before 28 weeks, but not at later gestational ages. In contrast, there was no significant association between clinical presentation of index sPTB and gestational latency in women who also underwent cerclage placement in a subsequent pregnancy. Our data suggest that clinical presentation is important with regards to recurrence of early sPTB, but not sPTB at later gestational ages. KEY POINTS: · Phenotype is critical to understanding PTB.. · Phenotype is associated with recurrent PTB.. · Painless dilation is associated with recurrent PTB..

Intrahepatic Cholestasis of Pregnancy.

Intrahepatic cholestasis of pregnancy is a common disorder of pregnancy manifested by pruritus and elevated bile acids. The etiology of cholestasis is poorly understood and management is difficult due to the paucity of data regarding its diagnosis, treatment, and related adverse outcomes. In this article, we review the epidemiology, pathophysiology, risk factors, laboratory findings, complications, treatment, management, and current evidence surrounding intrahepatic cholestasis of pregnancy.

Exclusion of Pregnant Women from Clinical Trials during the Coronavirus Disease 2019 Pandemic: A Review of International Registries.

OBJECTIVE: Pregnant women have been historically excluded from clinical trials for nonobstetric conditions, even during prior epidemics. The objective of this review is to describe the current state of research for pregnant women during the coronavirus disease 2019 (COVID-19) pandemic. STUDY DESIGN: We conducted a search of international trial registries for trials relating to the novel coronavirus. The eligibility criteria for each trial were reviewed for inclusion/exclusion of pregnant women. Relevant data were extracted and descriptive statistics were calculated for individual and combined data. The total number of trials from each registry were compared, as well as the proportions of pregnancy-related trials within each. RESULTS: Among 621,370 trials in the World Health Organization International Clinical Trials Registry, 927 (0.15%) were COVID-19 related. Of those, the majority (52%) explicitly excluded pregnancy or failed to address pregnancy at all (46%) and only 16 (1.7%) were pregnancy specific. When categorized by region, 688 (74.2%) of COVID-19 trials were in Asia, followed by 128 (13.8%) in Europe, and 66 (7.2%) in North America. Of the COVID-19 trials which included pregnant women, only three were randomized-controlled drug trials. CONCLUSION: Approximately 1.7% of current COVID-19 research is pregnancy related and the majority of trials either explicitly exclude or fail to address pregnancy. Only three interventional trials worldwide involved pregnant women. The knowledge gap concerning the safety and efficacy of interventions for COVID-19 created by the exclusion of pregnant women may ultimately harm them. While "ethical" concerns about fetal exposure are often cited, it is in fact unethical to habitually exclude pregnant women from research. KEY POINTS: · Pregnancy was excluded from past pandemic research.. · Pregnancy is being excluded from COVID-19 research.. · Exclusion of pregnant women is potentially harmful..

Obesity and laboratory aspirin resistance in high-risk pregnant women treated with low-dose aspirin.

BACKGROUND: Low-dose aspirin is used for preeclampsia prevention in high-risk women, but the precise mechanism and optimal dose are unknown. Evidence suggests that an imbalance in prostacyclin and thromboxane A2 (TXA2) plays a key role in the pathogenesis of preeclampsia. Aspirin has a dose-dependent effect blocking production of TXA2, a potent stimulator of platelet aggregation and promoter of vasoconstriction. Incomplete inhibition of platelet aggregation, designated aspirin resistance, can be reduced by increasing the aspirin dose. Evidence in the nonobstetric literature suggests that aspirin resistance may be more common among patients with a high body mass index. OBJECTIVE: To investigate the association of obesity on platelet-derived thromboxane inhibition in high-risk women treated with low-dose aspirin. MATERIALS AND METHODS: This was a secondary analysis of a prospective multi-centered study investigating the effect of low-dose aspirin (60-mg) administration in women at high risk for preeclampsia. Maternal serum TXB2 (an indirect measure of TxA2) levels were drawn at 3 time points: randomization (13-26 weeks' gestation), second trimester (at least 2 weeks after randomization and 24-28 weeks' gestation), and third trimester (34-38 weeks' gestation). Patients were included in the analysis if a TXB2 level was recorded at randomization and at least 1 time point thereafter. Patients were stratified by body mass index category and treatment arm. Median TXB2 levels were calculated at each time point, as well as rates of complete TXB2 inhibition (<0.01 ng/mL). A multivariate logistic regression analysis was performed to generate odds ratios (OR) for complete TXB2 inhibition by body mass index category, adjusting for maternal age, race, high-risk group at randomization, nulliparity, and rate of randomization less than 16 weeks' gestation. RESULTS: A total of 1002 patients were included in the analysis, 496 (49.5%) and 506 (50.5%) in the low-dose aspirin and placebo groups respectively. There were substantial decreases in TXB2 levels among low-dose aspirin-treated women in all body mass index categories. In contrast, women assigned to placebo did not show a marked decrease in TXB2 levels after randomization, and obese women had higher median TXB2 levels in both the second (16.5, interquartile range [IQR] 8.0-31.8 vs 14.0, IQR 6.9-26.7, ng/mL; P = .032) and third (15.7, IQR 7.6-28.5 vs 11.9, IQR 4.6-25.9, ng/mL; P = .043) trimesters. When comparing among stratified body mass index low-dose aspirin groups, women with class III obesity had the lowest odds of undetectable TXB2 levels in the second trimester (adjusted odds ratio [aOR], 0.33; 95% confidence interval [CI], 0.15-0.72) and third trimester (aOR, 0.30; 95% CI, 0.11-0.78) as well as at both time points (aOR, 0.09; 95% CI, 0.02-0.41). CONCLUSION: High-risk obese women receiving low-dose aspirin for the prevention of preeclampsia have lower rates of complete inhibition of TXB2. These data suggest that an increase in aspirin dosing or frequency may be necessary in this population.

Cost Analysis of Azithromycin versus Erythromycin in Pregnancies Complicated by Preterm Premature Rupture of Membranes.

OBJECTIVE: To quantify the potential cost savings if azithromycin is substituted for erythromycin in women with preterm premature rupture of membranes (PPROM). STUDY DESIGN: Secondary analysis of a multicentered study investigating magnesium sulfate for the prevention of cerebral palsy in premature infants. All patients with PPROM who received antibiotics for prophylaxis were included in the analysis. The number of expected doses each patient would have received was calculated for erythromycin, multidose azithromycin, and single-dose azithromycin regimens accounting for latency from PPROM to delivery. The wholesale acquisition cost was used to calculate the expected cost of each regimen. RESULTS: There were 981 PPROM patients who received a penicillin class antibiotic and erythromycin. Patients would have received 7,528 intravenous doses and 10,194 oral doses of erythromycin at a combined cost of $357,169. In comparison, patients would have received 6,422 and 3,942 doses at a cost of $15,669 and $9,574 for the multidose and single-dose azithromycin regimens respectively, which represents a more than 95% cost reduction for either regimen compared with erythromycin. CONCLUSION: The use of azithromycin substituted for erythromycin in the standard antibiotic regimen of women with PPROM represents a potential for substantial cost reduction.

Effect of Maternal Age and Fetal Number on the Risk of Hypertensive Disorders of Pregnancy.

OBJECTIVE: Our primary objective was to compare the differential contribution of fetal number and maternal age to the risk of hypertensive disorders of pregnancy (HDP). STUDY DESIGN: This was a secondary analysis of a large study of primary cesarean delivery. Women with singleton, twin, or triplet gestations were included. Women were divided into groups based on fetal number and maternal age. The primary outcome was HDP. A logistic regression model was fit to adjust for confounders. The incidence of HDP was compared with the reference group and within exposure groups. RESULTS: Of the 70,417 women included, HDP occurred in 8,079 (12%) women. The frequency of HDP among the comparison groups ranged from 11 to 38%. Nearly all groups had significantly increased risk of HDP compared with young maternal age singletons. Twin and triplet gestations increased the risk of HDP over singletons irrespective of maternal age after adjusting for baseline disease and race. The risk of HDP did not significantly increase with maternal age when fetal number was similar. CONCLUSION: Fetal number significantly increased the risk of HDP and contributed more to that risk than maternal age. Maternal age became significant in groups with age greater than 40 years.

Risk of cerebral palsy by gestational age among pregnancies at-risk for preterm birth.

Objective: Our objective was to describe cerebral palsy (CP) incidence stratified by gestational age (GA) groups within a group at risk for spontaneous preterm birth (sPTB).Study design: This is a secondary analysis of a large study of magnesium for neuroprotection. Nonanomalous, singleton gestations complicated by preterm premature rupture of membranes (PPROM) or preterm labor (PTL) were included. Infants that developed CP were compared to controls that did not. The incidence of CP was stratified by GA groups. A logistic regression model was fit to adjust for confounders.Results: Of 1747 included pregnancies, 75 (4.3%) were affected by CP. Increasing GA at delivery was associated with lower rates of CP (RR 0.96, 95% CI 0.95-0.97; p<.0001). The most significant risk factor for CP was neonatal sepsis while the most significant protective factors were magnesium and antibiotic exposure. In the adjusted analysis, magnesium exposure (aRR 0.52, 95% CI 0.33-0.84; p = .007) and antibiotic exposure (aRR 0.52, 95% CI 0.28-0.95; p = .034) remained protective.Conclusion: The risk of CP among populations at high risk for sPTB decreases with advancing GA. While the majority of cases of CP occurred in children born <34 weeks, residual risk persisted thereafter. The effect of magnesium exposure is most pronounced before 28 weeks.

Effect of Fasting on Total Bile Acid Levels in Pregnancy.

OBJECTIVE: To evaluate differences between fasting and nonfasting bile acid levels in asymptomatic and symptomatic pregnant women. METHODS: This is a report of two prospective cohort studies describing bile acid levels in the fasting and nonfasting state in pregnancy. The first cohort included asymptomatic women with singleton pregnancies. Women with a diagnosis of cholestasis, symptoms of cholestasis, or intolerance to components of a standardized meal were excluded. Bile acid levels were measured during the second and third trimesters after fasting and again 2 hours after a standardized meal. The second cohort included symptomatic women with singleton pregnancies in whom fasting and nonfasting bile acid levels were measured at the time of symptom evaluation. A cutoff of 10 micromoles/L was used for diagnosis. RESULTS: A total of 27 women were included in the asymptomatic cohort. Median [interquartile range] fasting bile acid levels were significantly lower than nonfasting levels in both the second trimester (4.65 micromoles/L [1.02-29.57] vs 13.62 micromoles/L [2.03-40.26]; P<.001) and third trimester (8.31 micromoles/L [1.14-51.26] vs 17.35 micromoles/L [1.77-62.93]; P<.001). Bile acid levels exceeded 10 micromoles/L in 21% of the fasting samples and in 58% of the nonfasting samples in the third trimester. A total of 26 women were included in the symptomatic cohort. Median [interquartile range] fasting bile acid levels were significantly lower than nonfasting values (11.5 micromoles/L [7-56] vs 13.5 micromoles/L [9-142]; P<.001). Six patients in the symptomatic cohort (23%) had nonfasting bile acid levels greater than 10 micromoles/L that dropped below 10 micromoles/L when fasting. CONCLUSION: Fasting bile acid levels are significantly lower when compared with nonfasting values in both asymptomatic and symptomatic pregnant women. In asymptomatic women, nonfasting bile acid levels often exceeded 10 micromoles/L whereas fasting values did not. In symptomatic women, fasting bile acid levels resulted in 23% fewer diagnoses of cholestasis when compared with nonfasting values. These findings suggest that fasting evaluation of bile acid levels or a higher threshold for diagnosis of cholestasis should be considered.

Buttock Necrosis after Uterine Artery Embolization for Delayed Hysterectomy in Placenta Percreta.

Background. Morbidly adherent placenta (MAP) is increasing in incidence and is commonly associated with maternal hemorrhage and cesarean hysterectomy. Uterine artery embolization (UAE) may be utilized in the conservative management of placenta percreta to potentially reduce blood loss. The incidence of complications from UAE in the conservative management of placenta percreta is poorly described. To our knowledge, we present the first reported case of buttock necrosis in this setting. Case. A 39-year-old gravida nine para two with placenta percreta who underwent conservative management with UAE complicated by right buttock necrosis. Conclusion. While UAE may potentially decrease blood loss, it is not without risk. More studies must be performed in order to quantify those risks and determine the clinical utility of UAE.