COVID-19 is associated with early emergence of preeclampsia: results from a large regional collaborative.

Objective: To investigate the relationship between preeclampsia and SARS-CoV-2 infection during pregnancy. Methods: This was a retrospective cohort study of pregnant women between March and October 2020. Pregnant patients admitted to 14 obstetrical centers in Michigan, USA formed the study population. Of the N = 1458 participants, 369 had SARS-CoV-2 infection (cases). Controls were uninfected pregnancies that were delivered in the same obstetric unit within 30 days of the index case. Robust Poisson regression was used to estimate relative risk (RR) of preterm and term preeclampsia and preeclampsia involving placental lesions. The analysis included adjustment for relevant clinical and demographic risk factors.Results: SARS-CoV-2 infection during pregnancy increased the risk of preeclampsia [adjusted aRR = 1.69 (1.26-2.26)], preeclampsia involving placental lesions [aRR = 1.97(1.14-3.4)] and preterm preeclampsia 2.48(1.48-4.17). Although the highest rate of preeclampsia was observed in patients infected with SARS-CoV-2 who were symptomatic (18.4%), there was increased risk even in asymptomatic SARS-CoV-2 infected patients (14.2%) relative to non-infected controls (8.7%) (p < 0.05). This association with symptomatology was also noted with preterm preeclampsia for which the rate doubled from 2.7% in controls to 5.2% in asymptomatic cases and reached 11.8% among symptomatic cases (p < 0.05). The rate of preterm preeclampsia among cases of pregnant people self-identified as Black reached 10.1% and was almost double the rate of the reminder of the group of infected pregnancies (5.3%), although the rate among uninfected was almost the same (2.7%) for both Black and non-Black groups (interaction p = 0.05).Conclusions: Infection with SARS-CoV-2 increases the risk of preeclampsia even in the absence of symptoms, although symptomatic persons are at even higher risk. Racial disparities in the development of preterm preeclampsia after SARS-CoV-2 infection may explain discrepancies in prematurity between different populations.

Maternal SARS-COV-2 infection and prematurity: the Southern Michigan COVID-19 collaborative.

OBJECTIVE: COVID-19 has been reported to increase the risk of prematurity, however, due to the frequent absence of unaffected controls as well as inadequate accounting for confounders in many studies, the question requires further investigation. We sought to determine the impact of COVID-19 disease on preterm birth (PTB) overall, as well as related subcategories such as early prematurity, spontaneous, medically indicated preterm birth, and preterm labor (PTL). We assessed the impact of confounders such as COVID-19 risk factors, a-priori risk factors for PTB, symptomatology, and disease severity on rates of prematurity. METHODS: This was a retrospective cohort study of pregnant women from March 2020 till October 1st, 2020. The study included patients from 14 obstetric centers in Michigan, USA. Cases were defined as women diagnosed with COVID-19 at any point during their pregnancy. Cases were matched with uninfected women who delivered in the same unit, within 30 d of the delivery of the index case. Outcomes of interest were frequencies of prematurity overall and subcategories of preterm birth (early, spontaneous/medically indicated, preterm labor, and premature preterm rupture of membranes) in cases compared to controls. The impact of modifiers of these outcomes was documented with extensive control for potential confounders. A p value <.05 was used to infer significance. RESULTS: The rate of prematurity was 8.9% in controls, 9.4% in asymptomatic cases, 26.5% in symptomatic COVID-19 cases, and 58.8% among cases admitted to the ICU. Gestational age at delivery was noted to decrease with disease severity. Cases were at an increased risk of prematurity overall [adjusted relative risk (aRR) = 1.62 (1.2-2.18)] and of early prematurity (<34 weeks) [aRR = 1.8 (1.02-3.16)] when compared to controls. Medically indicated prematurity related to preeclampsia [aRR = 2.46 (1.47-4.12)] or other indications [aRR = 2.32 (1.12-4.79)], were the primary drivers of overall prematurity risk. Symptomatic cases were at an increased risk of preterm labor [aRR = 1.74 (1.04-2.8)] and spontaneous preterm birth due to premature preterm rupture of membranes [aRR = 2.2(1.05-4.55)] when compared to controls and asymptomatic cases combined. The gestational age at delivery followed a dose-response relation with disease severity, as more severe cases tended to deliver earlier (Wilcoxon p < .05). CONCLUSIONS: COVID-19 is an independent risk factor for preterm birth. The increased preterm birth rate in COVID-19 was primarily driven by medically indicated delivery, with preeclampsia as the principal risk factor. Symptomatic status and disease severity were significant drivers of preterm birth.

The association of HBB-related significant hemoglobinopathies and low fetal fraction on noninvasive prenatal screening for fetal aneuploidy.

OBJECTIVES: HBB-related significant hemoglobinopathies have been anecdotally associated with low fetal fraction on noninvasive prenatal screening (NIPS). We sought to compare the difference in fetal fraction using NIPS in women with HBB-related significant hemoglobinopathies (HSH) and women with normal hemoglobin. STUDY DESIGN: This is a retrospective case-control study. Cases were women with a diagnosis of HSH using NIPS from a commercial laboratory. The comparison group was women with hemoglobin AA from a tertiary care center database. We tested for differences in median fetal fraction using quantile regression analysis, adjusting for maternal body weight and gestational age. RESULTS: This study includes 35 women with clinically significant HSH and a comparison group of 636 women with hemoglobin AA. Adjusting for gestational age and body weight, the median fetal fraction was 4.1 point lower in the HSH than in the comparison group (ß - 4.1; 95% -5.7 to -2.5, p < .05). The rate of no-calls due to low fetal fraction was significantly higher in the clinically significant HSH group than in the comparison group [HSH: n = 9/35, 25.7% versus comparison: n = 32/636, 5.0% (p < .001)]. CONCLUSION: Women with HSH were more likely to have a lower fetal fraction and ultimately a five-fold higher no-call rate. What's already known about this topic?Low fetal fraction is one of the most common causes of no-call result in noninvasive prenatal screeningHigh maternal weight, early gestational age and fetal aneuploidies are associated with low fetal fraction What does this study add?HBB-related significant hemoglobinopathies are associated with low fetal fractionReduction in fetal fraction due to HBB-related significant hemoglobinopathies may also result in higher no-call rate.

The Impact of the New Hypertension Guidelines to Low-Dose Aspirin Prophylaxis Eligibility for the Prevention of Preeclampsia: A Cost-Benefit Analysis.

OBJECTIVE: American College of Cardiology and American Heart Association (ACC/AHA) published new guidelines which lower the cut-off for hypertension. We sought to evaluate the impact of these guidelines to cost and benefit of various low-dose aspirin prophylaxis approaches. STUDY DESIGN: Decision tree analysis was created using R software to evaluate four approaches to aspirin prophylaxis in the United States: no aspirin, United States Preventive Service Task Force (USPSTF) with Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) hypertension guidelines, USPSTF with ACC/AHA hypertension guidelines, as well as universal aspirin prophylaxis. This model was executed to simulate a hypothetical cohort of 4 million pregnant women in the United States. RESULTS: The new guidelines would expand the aspirin eligibility by 8% (76,953 women) in the USPSTF guidelines. Even with this increased eligibility, the USPSTF guidelines continue to be the approach with the most cost savings ($386.5 million) when compared with universal aspirin and no aspirin prophylaxis. The new hypertension guidelines are projected to increase the cost savings of the USPSTF approach by $9.4 million. CONCLUSION: Despite the small change in aspirin prophylaxis, using ACC/AHA definition of hypertension still results in an annual cost-saving of $9.4 million in the United States when compared with JNC7.

Starting a regional collaborative research group for COVID-19 in pregnancy: the Southern Michigan experience.

The outbreak of the SARS-CoV-2 elicited a surge in publications. Obstetric reports were with few exceptions characterized by small sample sizes with potentially limited generalizability. In this review, evidence suggests increased susceptibility to COVID-19 in pregnancy; common pregnancy comorbidities may help explain worse outcomes. While the risk of death is low, pregnancy may be associated with increased need for ventilation. Prematurity rates seem to be increased but may be accounted for in part by higher cesarean rates, to a large degree accounted for by elective decision to shorten the course of the labor. Though fetal/neonatal complication rates may be higher in the presence of COVID-19 infection, survival rates seem unaffected and vertical transmission is rare. As the outbreak continues in the USA with resurgence in many other western countries that achieved initial success in suppressing the virus, much remains to be learned. For example, the question related to the degree to pregnancy modifying symptomatology remains open. Currently, routine polymerase chain reaction testing remains limited by supply shortages possibly delaying diagnosis until later in the course of the disorder and thus altering the symptom complex at presentation. To add to the knowledge base, we initiated a regional COVID-19 in pregnancy collaborative observational study with a coordinating center, standardized data collection and a shared database. This was facilitated by a longstanding tradition of collaboration among regional obstetric services. Over an anticipated two-year study duration, we expect to study 400 documented and suspected COVID-19 pregnancies with time and site of services controls for cohort effect and high power to detect several adverse maternal/infant outcomes. We include a complete listing of variables in our database, which, along with our experience in setting up our regional collaborative, we hope and believe will be of use in other settings.

Lessons Learned Serving on a Long-Standing Maternal Mortality Review Committee.

The maternal mortality ratio in the United States is increasing; understanding the significance of this change and developing effective responses requires a granular analysis of the contributing factors that a well-informed maternal mortality review committee can provide. Data collection and analysis, clinical factors, preventability, social determinants of health, and racial inequities combine to affect this outcome, and each factor must be considered individually and in combination to recommend a robust response. Obstetrician-gynecologists formed the State of Michigan's Maternal Mortality Review Committee (the Committee) in 1950 to identify gaps in care that needed to be systematically addressed at the time. In the early years, the Committee witnessed a reduction in the number of maternal deaths; over time, prioritization of maternal mortality decreased, yet the Committee witnessed changing patterns of death, varied data collection and evaluation processes, delayed reviews, and unimplemented recommendations. The calculation of the maternal mortality ratio was not informed by the outcomes of Committee reviews. Today, the Committee, with increased support from the Michigan Department of Health & Human Services, can clearly identify and report preventable pregnancy-related mortality along with its causes and is close to achieving a near real-time surveillance system that allows the development of timely clinical and policy recommendations and interventions. The Committee's adaptations in response to the rise in maternal mortality have resulted in several lessons learned that may be helpful for currently operating committees and in the formation of new ones.

Lack of Uptake of Prophylactic Human Papilloma Virus Vaccine Among Women With Systemic Lupus Erythematosus Seen at a Regional Medical Center.

BACKGROUND/OBJECTIVE: Women with systemic lupus erythematosus (SLE) are at increased risk for cervical neoplasia likely due to infection with high-risk human papillomavirus (HR-HPV) and should be considered for HPV vaccination. We sought to determine the frequency of HR-HPV infection and uptake of HPV vaccination in our regional female lupus population. METHODS: For this medical records review study, data were analyzed from our electronic health records EPIC for women with International Classification of Diseases-10 or International Classification of Diseases -9 billing codes for SLE seen June 6, 2007, to May 1, 2017. This study was approved by the Central Michigan University/Covenant Medical Center institutional review board. Statistical analyses consisted of Student t test, χ, and Z test for proportions using SPSS v. 24 software. RESULTS: A total of 1349 women with SLE were identified, mean age of 53 years, 70.8% white, 20.8% African American, with 49% exposed to cigarette smoke. High-risk HPV testing performed in 195 (14.5%; mean age, 50 years) showed 16.9% (33/195) were positive, with those testing positive for HR-HPV being slightly younger (p < 0.05).Comparing our proportion testing positive for HR-HPV (0.169) versus National Health and Nutrition Examination Survey (0.088), we calculated a Z = 3.99 (p < 0.001) indicating HPV infection is significantly higher (2×) in our female SLE cohort. Only 16.0% (38/238) of the 238 women eligible to receive an HPV vaccine were tested for HR-HPV with 9 being positive and only 4.6% (11/238) vaccinated. CONCLUSIONS: Human papillomavirus infection is a serious health issue in women with SLE, but HPV testing and vaccination rates remain low. Efforts should be directed to promote awareness of the importance of HPV vaccination in this high-risk population.

Prenatal Alcohol Screening During Pregnancy by Midwives and Nurses.

BACKGROUND: Alcohol use during pregnancy can have a variety of harmful consequences on the fetus. Lifelong effects include growth restriction, characteristic facial anomalies, and neurobehavioral dysfunction. This range of effects is known as fetal alcohol spectrum disorders (FASD). There is no amount, pattern, or timing of alcohol use during pregnancy proven safe for a developing embryo or fetus. Therefore, it is important to screen patients for alcohol use, inform them about alcohol's potential effects during pregnancy, encourage abstinence, and refer for intervention if necessary. However, how and how often nurses and midwives inquire about alcohol drinking during pregnancy or use recommended screening tools and barriers they perceive to alcohol screening has not been well established. METHODS: This survey was sent to about 6,000 American midwives, nurse practitioners, and nurses who provide prenatal care about their knowledge of the effects of prenatal alcohol exposure, the prevalence of alcohol use during pregnancy, and practices for screening patients' alcohol use. Participants were recruited by e-mail from the entire membership roster of the American College of Nurse-Midwives. RESULTS: There were 578 valid surveys returned (about 9.6%). Analyses showed that 37.7% of the respondents believe drinking alcohol is safe during at least one trimester of pregnancy. Only 35.2% of respondents reported screening to assess patient alcohol use. Only 23.3% reported using a specific screening tool, and few of those were validated screens recommended for use in pregnant women. Respondents who believe alcohol is safe at some point in pregnancy were significantly less likely to screen their patients. CONCLUSIONS: Respondents who reported that pregnancy alcohol use is unsafe felt more prepared to educate and intervene with patients regarding alcohol use during pregnancy and FASD than respondents who reported drinking in pregnancy was safe. Perceived alcohol safety and perceived barriers to screening appeared to influence screening practices. Improving prenatal care provider knowledge about the effects of prenatal alcohol exposure and the availability of valid alcohol screening tools will improve detection of drinking during pregnancy, provide more opportunities for meaningful intervention, and ultimately reduce the incidence of FASD.

Medical genetics and genomics training in obstetrics and gynecology residencies: are we ready for the future?

OBJECTIVE: The primary objective of this study is to evaluate the availability and duration of formal medical genetics and genomics (MGG) education during obstetrics and gynecology (OB/GYN) residency training in the United States compared to other noncore OB/GYN rotations. METHODS: We performed a review of rotation schedules published in all American Council for Graduate Medical Education (ACGME)-accredited OB/GYN residency programs' websites during the month of December 2016. Information regarding availability and duration of MGG rotation and other noncore OB/GYN rotations (ultrasound, breast health, and family planning) were collected. RESULTS: Among 256 ACGME-accredited OB/GYN residency programs, rotation schedule was available for 238 (93%). Only 34 programs (14.3%) had some form of MGG rotations. In the GLM, when compared to other noncore OB/GYN rotations, the mean duration of MGG rotation was significantly less than ultrasound (0.07 versus 0.57 months, p < .05) and family planning (0.07 versus 0.42 months, p < .05). The number of residents was the only variable significantly correlated with the availability of an MGG rotation (OR 1.07, 95%CI 1.02-1.13). CONCLUSIONS: Despite the growing importance of MGG in day-to-day OB/GYN practice, only a limited number of ACGME-accredited OB/GYN residency programs offer an MGG rotation. When compared to other noncore OB/GYN rotations, such as, ultrasound and family planning, any MGG rotation was significantly shorter. With clear evidence that MGG will continue to radically change practice of OB/GYN in the future, it is imperative that steps need to be taken to address this deficiency in training.

A Current Evaluation of the Economic Costs for Fetal Alcohol Spectrum Disorder (FASD): A Comment on the Systematic Review by Greenmeyer et al.

: Fetal alcohol spectrum disorder is common and associated with economic costs greater than comparable other childhood and adult disorders. We need to turn our attention to prevention and mitigation.

The effect of history of abnormal pap smear or preceding HPV infection on the humoral immune response to Quadrivalent Human Papilloma virus (qHPV) vaccine in women with systemic lupus erythematosus.

OBJECTIVE: To determine if natural human papillomavirus (HPV) infection would induce an anamnestic response to quadrivalent (qHPV) vaccine in women with Systemic Lupus Erythematosus (SLE). METHODS: Thirty four women (19-50 years) with mild to moderate and minimally active or inactive SLE received standard qHPV vaccine. Neutralizing antibody titers to HPV 6, 11, 16 and18 were evaluated pre- and post- vaccine using HPV competitive Luminex Immunoassay. For each HPV type, logistic regressions were performed to explore the relationship between a positive titer at baseline with their final geometric mean titer and with the rise in titer. Fisher's Exact Test was used to assess the association of at least one positive HPV antibody test at baseline and history of abnormal pap. RESULTS: History of abnormal pap smear/cervical neoplasia occurred in 52.9%. Baseline anti HPV antibody titers: 21% = negative for all 4 HPV types, 79% = positive for ≥1 of the HPV types. Statistical analysis showed: those with a history of abnormal pap smear/cervical neoplasia were likely to have a positive anti-HPV antibody result pre-vaccine to ≥ 1 of the 4 types, p = 0.035 Fisher's Exact Test. In general, HPV exposed women showed higher post vaccine GMTs than HPV unexposed women with higher point estimates. However, when examining the rise in titers using logistic regression, there was no evidence of an anamnestic response. CONCLUSION: Prior HPV infection and cervical neoplasia in SLE are linked with no anamnestic response to HPV vaccine. This supports not checking HPV-antibodies pre-vaccine. Women with SLE should be vaccinated for HPV.

Maternal side effects & fetal neuroprotection according to body mass index after magnesium sulfate in a multicenter randomized controlled trial.

OBJECTIVE: Evidence supports the need of dose-adjustment of several drugs according to body mass index (BMI) to prevent toxicity in the underweight, and ensure efficacy in obese women. However, for MgSO4 neuroprotection, the effect of BMI on maternal toxicity and fetal neuroprotection is understudied. We analyze the effect of BMI on maternal/infant outcomes after MgSO4. METHODS: Secondary analysis of a clinical trial that studied MgSO4 neuroprotection. Maternal side effects, magnesium cord levels, and offspring cerebral palsy/death were analyzed along BMI strata using ANOVA and chi-square test. Logistic regression was used to calculate adjusted odds ratios according to the treatment and BMI, using nonobese that received placebo as reference. Interaction analyses were performed to validate differential efficacy of BMI. RESULTS: From 2241 women, more side effects and higher magnesium cord levels were seen in underweight women (p = 0.05). MgSO4 neuroprotection was effective in the non-obese (p = 0.02), but not in obese women (p = 1.00). In multivariate analyses, MgSO4 significantly reduced cerebral palsy only in nonobese women. Interaction analyses showed the moderator effect of BMI (p = 0.169). Increasing MgSO4 dose in obese mothers may ensure neuroprotective efficacy without representing increased maternal risks. Considering costs of studying this association, current analysis may form the basis for reasonable practice.

Racial/ethnic disparities in magnesium sulfate neuroprotection: a subgroup analysis of a multicenter randomized controlled trial.

OBJECTIVE: Despite known racial disparities in obstetrics, as well as differences in magnesium pharmacodynamics according to race, the effect of race/ethnicity in magnesium sulfate (MgSO4) use during pregnancy has not been studied. Whether some mothers are at increased risk of side effects, or infants at decreased neuroprotective effects is unknown. We analyze the effect of race/ethnicity in maternal/infant outcomes after MgSO4 neuroprotection. STUDY DESIGN: Subgroup analysis of a multicenter clinical trial (BEAM trial) where pregnant women at risk of preterm birth were randomized to either MgSO4 or placebo. For this study, nonanomalous singleton pregnancies were studied. The effect of race in maternal/neonatal outcomes after MgSO4 was analyzed with Breslow-Day and multifactorial ANOVA. Logistic regression was used to calculate odds ratios (OR) of complications according to race. RESULTS: 922 MgSO4 and 972 placebo cases were included (45.0% African-American, 36.2% Caucasian, 17.8% Hispanics, and 1.0% Asians). Interaction analysis showed a significant effect of race/ethnicity (p = .043). Hispanics presented the highest frequency (88.3%, p < .001), as well as the highest odds of MgSO4 side effects [OR(95%CI) = 6.6 (1.3-33.8)]. CONCLUSION: Hispanics present increased risk of magnesium toxicity compared to other racial/ethnic groups. Whether specific racial/ethnic groups require closer surveillance for early signs of magnesium toxicity needs to be further explored.

Risk of Expectant Management and Optimal Timing of Delivery in Low-Risk Term Pregnancies: A Population-Based Study.

OBJECTIVE: The benefits of the 39-week rule have been questioned and concerns of increased stillbirth after adoption of this rule have been raised. Whether expectant management risks outweigh the benefits of awaiting 39 weeks has not been studied. We analyze the risks of expectant management at term and the optimal timing for delivery. STUDY DESIGN: All U.S. nonanomalous singleton term deliveries in 2013 were selected, excluding diabetes/hypertension, and low birth weight. Maternal/neonatal complications and stillbirth/infant death were compared among expectant management versus deliveries at each term gestational age. Logistic regression was used to calculate adjust odds ratios of complications according to delivery plan at each gestational age. RESULTS: From approximately 3 million deliveries, maternal complications during expectant management were lower at early term, and became higher at 39 weeks, relative risk [RR] (95% confidence interval [CI]) = 1.18 (1.16-1.19). Neonatal complications during expectant management were lower during early term, and became higher at ≥39 weeks, RR (95% CI) = 1.09 (1.08-1.09). The risk of perinatal mortality in the expectant management group was lower during early term, and became higher at ≥39 weeks, 18.93 (17.83-20.10) versus 17.37 (16.61-18.16), p = 0.010. CONCLUSION: Complications during expectant management occurring while awaiting full term do not outweigh the benefits of better outcomes from reaching 39 weeks. However, extending beyond 39 weeks may put these pregnancies at an increased risk.

Utility of Commercial Ethyl Glucuronide (EtG) and Ethyl Sulfate (EtS) Testing for Detection of Lighter Drinking Among Women of Childbearing Years.

OBJECTIVE: Even moderate alcohol consumption during pregnancy can pose risks to the fetus, making reliable and consistent detection of drinking in pregnancy critical. Ethyl glucuronide (EtG) and ethyl sulfate (EtS) have shown some ability to detect lower levels of drinking, but the sensitivity of commercial EtG/EtS testing to lower levels of drinking among women of childbearing age is unknown. This study sought to determine the ability of an EtG/EtS algorithm, as well as EtG alone, to detect alcohol consumption in women of childbearing age using commercial testing and cutoffs. METHOD: Ten women (ages 21-39 years of age) were administered one, two, or three standard drinks in separate sessions. Urinary EtG/EtS was measured at baseline and again at five timed intervals for 72 hours following each session. Samples from the first five participants used a commercial algorithm in which a positive test was EtG > 100 ng/ml and EtS > 25 ng/ml; samples from the next five participants were considered positive if only EtG was >100 ng/ml. RESULTS: All samples were positive at the 12-hour follow-up. By 24 hours, sensitivity for one standard drink was poor for the combined EtG/EtS assay as well as for EtG alone (20% detection) and modest for two standard drinks (40% detection). There were no positive EtG results after 36 hours. CONCLUSIONS: The EtG/EtS cutoffs used in the present study, which are representative of those used by commercial laboratories, were not sensitive enough to reliably detect light to moderate drinking beyond a 12-hour window among women of childbearing age.

Contemporary epidemiology and novel predictors of uterine rupture: a nationwide population-based study.

PURPOSE: In spite of several policies aiming to decrease cesarean rates and related complications such as uterine rupture, data show that uterine rupture and associated morbidity are increasing along the years. Whether previously unidentified risk factors are currently playing an important role on these trends is unknown. We analyze current risks of uterine rupture and main preceding factors from more recent years compared to former data. METHODS: All uterine rupture cases in the US from 2011-2012 were selected, with matched non-uterine rupture cases selected as controls. Variables considered for analysis included demographics, maternal morbidity, and obstetric complications. Likelihood forward selection was used to identify main risk factors of uterine rupture. Medians of main factors identified were used to simulate groups at risk and calculate odds ratios of uterine rupture. RESULTS: From ~8 million births, 1925 presented uterine rupture. In patients with no prior cesarean delivery, multiple gestation, chronic hypertension and chorioamnionitis presented the highest odds of uterine rupture, with the combination of these factors increasing the odds of rupture 59 times (~1%). In women with prior cesarean delivery, induction/augmentation and chorioamnionitis were the most significant predictors, with the combination increasing the odds 33 times (~3%). CONCLUSIONS: Despite policies implemented and changes in clinical practice, uterine rupture remains an important issue. Previously unidentified risk factors are playing now an important role, information that should be considered during patient counseling and clinical practice. Combinations of some of these factors may increase the risk of uterine rupture significantly enough to modify clinical care.

The safety and immunogenicity of Quadrivalent HPV (qHPV) vaccine in systemic lupus erythematosus.

OBJECTIVE: This study evaluated the safety and immunogenicity of qHPV vaccine in SLE. METHODS: Subjects: 34 women ages 19-50years (yrs.) with mild to moderate SLE & minimally active or inactive SLE received qHPV vaccine at the standard dosing schedule. EXCLUSION CRITERIA: active SLE disease (SELENA-SLEDAI>2), history of severe SLE disease, deep venous thrombosis, on >400mg/day of hydroxychloroquine, on >15mg/day of prednisone, or active infections. Patients were monitored for adverse events (AE), SLE flare, generation of thrombogenic antibodies and thrombosis. Antibody (Ab) levels to HPV 6, 11, 16 & 18 were measured by HPV competitive Luminex Immunoassay and Geometric Mean Titers (GMTs) were calculated for each HPV type. Seroconversion was assessed for those seronegative at baseline. RESULTS: The women in the study: African-American (79%), mean age=38.1years, mean age at diagnosis of SLE=28.6years, 35.3% had a history of smoking, 91% had 4 or more sexual partners, 50% had a history of sexually transmitted diseases, and 27.3% used condoms on a regular basis. Vaccine site reactions (VSRs) occurred in 62%, all mild. Ninety-seven percent experienced at least 1 non vaccine adverse event (nvAE) with a total of 493 nvAEs in 33 patients, of which 90% were mild and none were related to vaccine or SLE. There were 9 serious AEs, none were related to vaccine or SLE, all resolved. No patient experienced an SLE flare, thrombosis, or generation of thrombogenic antibodies. Seroconversion rate was 100% with mean GMTs comparable to Gardasil® package insert data. CONCLUSION: In this SLE vaccine study, qHPV vaccine was generally safe, well tolerated, and highly immunogenic. This clinical trial is registered on Clinical Trials.gov under number, NCT01741012 and was conducted under the FDA IND BB14113.

Contemporary analysis of maternal and neonatal morbidity after uterine rupture: A nationwide population-based study.

AIM: Uterine rupture is a rare but feared perinatal event. Despite abundant research and changes to guidelines implemented to reduce this complication, evaluation of whether uterine rupture still engenders significant maternal/neonatal morbidity has not been conducted. We analyzed recent cases of maternal/neonatal morbidity after uterine rupture. METHODS: Deliveries complicated by uterine rupture from 2011 to 2012 in the United States were selected. Comparison cases without uterine rupture were used as controls. Measures of maternal/neonatal complications were compared with χ2 test, and relative risks were calculated. Logistic regression was used to identify the most significant complications. P < 0.05 indicated statistical significance. RESULTS: From 7 922 016 births, 1925 cases of uterine rupture and 3765 controls were identified. Regression models retained four maternal outcomes; blood transfusion was the most common (~15%) and unplanned hysterectomy had the highest odds (~97-fold). For newborns, the model retained three measures of morbidity; neonatal intensive care unit admission was the most common (~35%) and seizures had the highest odds (~20-fold). CONCLUSIONS: Despite efforts to reduce complications, mothers remain at significant risk of unplanned hysterectomy and intensive care unit admission. Neonates are at sizeable risk for neonatal intensive care unit admission and seizures, recognized markers of long-term neurobehavioral abnormality. Uterine rupture remains a major risk for mothers and babies.

Commercial Ethyl Glucuronide (EtG) and Ethyl Sulfate (EtS) Testing is Not Vulnerable to Incidental Alcohol Exposure in Pregnant Women.

BACKGROUND: Ethyl Glucoronide (EtG) and Ethyl Sulfate (EtS) have shown promise as biomarkers for alcohol and may be sensitive enough for use with pregnant women in whom even low-level alcohol use is important. However, there have been reports of over-sensitivity of EtG and EtS to incidental exposure to sources such as alcohol-based hand sanitizer. Further, few studies have evaluated these biomarkers among pregnant women, in whom the dynamics of these metabolites may differ. OBJECTIVES: This study evaluated whether commercial EtG-EtS testing was vulnerable to high levels of environmental exposure to alcohol in pregnant women. METHODS: Two separate samples of five nurses-one pregnant and the other postpartum, all of whom reported high levels of alcohol-based hand sanitizer use-provided urine samples before and 4-8 hours after rinsing with alcohol-based mouthwash and using hand sanitizer. The five pregnant nurses provided urine samples before, during, and after an 8-hour nursing shift, during which they repeatedly cleansed with alcohol-based hand sanitizer (mean 33.8 uses). The five postpartum nurses used hand sanitizer repeatedly between baseline and follow-up urine samples. RESULTS: No urine samples were positive for EtG-EtS at baseline or follow-up, despite use of mouthwash and-in the pregnant sample-heavy use of hand sanitizer (mean of 33.8 uses) throughout the 8-hour shift. CONCLUSIONS/IMPORTANCE: Current, commercially available EtG-EtS testing does not appear vulnerable to even heavy exposure to incidental sources of alcohol among pregnant and postpartum women.