Prenatal methamphetamine use increases risk of adverse maternal and neonatal outcomes.

BACKGROUND: While methamphetamine use has been rising in recent years and occurring within new populations and in broader geographical areas, there is limited research on its use and impact in pregnancy. OBJECTIVE: The objective of this study is to examine the association between prenatal methamphetamine use, and maternal and neonatal outcomes in a large, contemporary birth cohort. STUDY DESIGN: This is a retrospective cohort study using California-linked vital statistics and hospital discharge data from 2008-2019. Methamphetamine use was identified using International Classification of Disease (ICD-9 and ICD-10) codes. Chi-square tests and multivariable Poisson regression models were used to evaluate associations of methamphetamine use with maternal and neonatal outcomes. RESULTS: A total of 4,775,463 pregnancies met inclusion criteria, of which 18,473 (0.39%) had methamphetamine use. Compared to those with no use, individuals with methamphetamine use had an increased risk of non-severe hypertensive disorders (aRR=1.81, 95% CI 1.71, 1.90), preeclampsia with severe features (aRR=3.38; 95% CI: 3.14, 3.63), placental abruption (aRR=3.77; 95% CI: 3.51, 4.05), cardiovascular morbidity (aRR=4.30; 95% CI: 3.79, 4.88), and severe maternal morbidity (aRR=3.53; 95% CI: 3.29, 3.77). Adverse neonatal outcomes were also increased, including preterm birth <37 weeks (aRR=2.85; 95% CI: 2.77, 2.94), neonatal intensive care unit admission (aRR=2.46; 95% CI: 2.39, 2.53), and infant death (aRR=2.73; 95% CI: 2.35, 3.16). CONCLUSION: Methamphetamine use in pregnancy is associated with an increased risk of adverse maternal and neonatal outcomes that persists after adjustment for confounding variables and sociodemographic factors. The results of this study can inform prenatal and postpartum care for this high-risk, socioeconomically vulnerable population.

Third stage of labor: evidence-based practice for prevention of adverse maternal and neonatal outcomes.

The third stage of labor is defined as the time period between delivery of the fetus through delivery of the placenta. During a normal third stage, uterine contractions lead to separation and expulsion of the placenta from the uterus. Postpartum hemorrhage is a relatively common complication of the third stage of labor. Strategies have been studied to mitigate the risk of postpartum hemorrhage, leading to the widespread implementation of active management of the third stage of labor. Initially, active management of the third stage of labor consisted of a bundle of interventions including administration of a uterotonic agent, early cord clamping, controlled cord traction, and external uterine massage. However, the effectiveness of these interventions as a bundle has been questioned, leading to abandonment of some components in recent years. Despite this, upon review of selected international guidelines, we found that the term "active management of the third stage of labor" was still used, but recommendations for and against individual interventions were variable and not necessarily supported by current evidence. In this review, we: (1) examine the physiology of the third stage of labor, (2) present evidence related to interventions that prevent postpartum hemorrhage and promote maternal and neonatal health, (3) review current global guidelines and recommendations for practice, and (4) propose future areas of investigation. The interventions in this review include pharmacologic agents to prevent postpartum hemorrhage, cord clamping, cord milking, cord traction, cord drainage, early skin-to-skin contact, and nipple stimulation. Treatment of complications of the third stage of labor is outside of the scope of this review. We conclude that current evidence supports the use of effective pharmacologic postpartum hemorrhage prophylaxis, delayed cord clamping, early skin-to-skin contact, and controlled cord traction at delivery when feasible. The most effective uterotonic regimens for preventing postpartum hemorrhage after vaginal delivery include oxytocin plus ergometrine; oxytocin plus misoprostol; or carbetocin. After cesarean delivery, carbetocin or oxytocin as a bolus are the most effective regimens. There is inconsistent evidence regarding the use of tranexamic acid in addition to a uterotonic compared with a uterotonic alone for postpartum hemorrhage prevention after all deliveries. Because of differences in patient comorbidities, costs, and availability of resources and staff, decisions to use specific prevention strategies are dependent on patient- and system-level factors. We recommend that the term "active management of the third stage of labor" as a combined intervention no longer be used. Instead, we recommend that "third stage care" be adopted, which promotes the implementation of evidence-based interventions that incorporate practices that are safe and beneficial for both the woman and neonate.

Association between Gestational Age and Perinatal Outcomes in Women with Late Preterm Premature Rupture of Membranes.

OBJECTIVE: The American College of Obstetricians and Gynecologists (ACOG) suggests expectant management until 34 weeks for patients with preterm premature rupture of membranes (PPROM). New data suggest extending to 37 weeks might enhance neonatal outcomes, reducing prematurity-linked issues. This study aims to assess adverse neonatal outcomes across gestational ages in women with PPROM. STUDY DESIGN: A retrospective cohort study was performed using linked vital statistics and the International Classification of Diseases, Ninth Revision data. Gestational age at delivery ranged from 32 to 36 weeks. Outcomes include neonatal intensive care unit (NICU) admission >24 hours, neonatal sepsis, respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, and neonatal death. Multivariate regression analyses and chi-square tests were employed for statistical comparisons. RESULTS: In this cohort of 28,891 deliveries, there was a statistically significant decline in all studied adverse neonatal outcomes with increasing gestational age, without an increase in neonatal sepsis. At 32 weeks, 93% of newborns were in the NICU >24 hours compared with 81% at 34 weeks and 22% at 36 weeks (p < 0.001). At 32 weeks, 20% had neonatal sepsis compared with 11% at 34 weeks and 3% at 36 weeks (p < 0.001). At 32 weeks, 67% had respiratory distress syndrome compared with 44% at 34 weeks and 12% at 36 weeks (p < 0.001). CONCLUSION: In the setting of PPROM, later gestational age at delivery is associated with decreased rates of adverse neonatal outcomes without an increase in neonatal sepsis. KEY POINTS: · The ACOG recommends expectant management until 34 weeks for patients with PPROM.. · However, expectant management to 37 weeks might improve neonatal outcomes.. · Later gestational age at delivery was associated with decreased rates of adverse neonatal outcomes.. · Later gestational age at delivery was not associated with an increase in neonatal sepsis.. · The management of PPROM is complex and should be individualized..

Ultrasonographic evaluation of endometrial stripe thickness is insufficient to rule out uterine serous carcinoma.

PURPOSE: Uterine serous carcinoma (USC) is a rare endometrial cancer representing less than 10% of uterine cancers but contributing to up to 50% of the mortality. Delay in diagnosis with this high-grade histology can have significant clinical impact. USC is known to arise in a background of endometrial atrophy. We investigated endometrial stripe (EMS) thickness in USC to evaluate current guidelines for postmenopausal bleeding in the context of this histology. METHODS: Retrospective chart review was conducted using ICD-9 and ICD-10 codes over an 18-year period. We included 139 patients with USC and compared characteristics of patients with EMS ≤ 4 mm and EMS > 4 mm. Chi-square or Fisher's exact tests were used to compare proportions and two-tailed t-tests to compare means. A p-value of < 0.05 was considered statistically significant. RESULTS: Most patients were white, obese, and multiparous. Thirty-two (23%) had an EMS ≤ 4 mm; 107 (77%) had an EMS > 4 mm. There were no statistically significant differences in age at diagnosis or presenting symptoms between groups, and postmenopausal bleeding was the most common symptom in each group. CONCLUSION: Nearly 25% of patients with USC initially evaluated with transvaginal ultrasound were found to have an EMS ≤ 4 mm. If transvaginal ultrasound is used to triage these patients, one in four women will potentially experience a delay in diagnosis that may impact their prognosis.

Success Rates of Sentinel Lymph Node Mapping for Endometrial Cancer in Patients with Body Mass Index < 45 Compared with Body Mass Index ≥ 45.

STUDY OBJECTIVE: The objective is to evaluate the rate of sentinel lymph node (SLN) mapping in patients with body mass index (BMI [kg/m2]) BMI ≥ 45 compared with < 45. DESIGN: A retrospective chart review. SETTING: Three urban referral-based settings-1 academic and 2 community based. PATIENTS: Patients age ≥ 18 years, with endometrial intraepithelial neoplasia or clinical stage 1 endometrial cancer who underwent robot-assisted total laparoscopic hysterectomy with attempted SLN mapping between January 2015 and December 2021. INTERVENTIONS: Robot-assisted total laparoscopic hysterectomy with attempted SLN mapping. MEASUREMENTS AND MAIN RESULTS: A total of 933 subjects were included: 795 (85.2%) with BMI < 45 and 138 (14.8%) with BMI ≥ 45. Comparing the BMI < 45 with BMI ≥ 45 group, bilateral mapping was successful in 541 (68.1%) vs 63 (45.7%), respectively. Unilateral mapping was successful in 162 (20.4%) vs 33 (23.9%), respectively. Failure to map occurred in 92 (11.6%) vs 42 (30.4%) (p <.001), respectively. Exploratory analysis also suggested an inverse relationship between success rate of bilateral SLN mapping and BMI, with patients with BMI < 20 having bilateral SLN mapping rates of 86.5% and patients with BMI ≥ 61 having rates of 20.0%. The steepest decline in bilateral SLN mapping rates was from BMI group 46 to 50 compared to 51 to 55, at 55.4% to 37.5%, respectively. Adjusted odds ratio (compared with those with BMI < 30) for those in the BMI 30 to 44 group was 0.36 (95% confidence interval 0.21-0.60) and for those in the BMI ≥ 45 group was 0.10 (95% confidence interval 0.06-0.19). CONCLUSION: There is a statistically significant lower rate of SLN mapping in patients with a BMI ≥ 45 than BMI < 45. Understanding the success of SLN mapping in patients with morbid obesity is essential for preoperative counseling, surgical planning, and developing a risk-appropriate postoperative treatment plan.

A Web-Based Total Worker Health Intervention for Those Fighting Wildland Fires: Mixed Methods Development and Effectiveness Trial.

BACKGROUND: Fire seasons are longer, with more and larger wildfires, placing increased demands and risks on those fighting wildland fires. There are multiple agencies involved with fighting wildland fires and unique worksite conditions make meeting these workers' needs a challenge. OBJECTIVE: The aim of the study is to develop and establish the effectiveness of a web-based safety and health program for those fighting wildland fires. METHODS: This mixed methods project had 3 phases. The initial qualitative phase assessed the needs of 150 diverse firefighters through interviews and focus groups across 11 US sites to establish and prioritize program content. Interview transcripts were read for thematic content with iterative readings used to identify, code, and rank health and safety issues. The second phase used that information to build a comprehensive Total Worker Health program for those fighting wildfires. The program content was based on the qualitative interview data and consisted of 6 core and 8 elective 30-minute, web-based modules primarily done individually on a smartphone or computer. The final, third phase evaluated the program with a quantitative prospective proof-of-concept, usability, and effectiveness trial among wildland firefighter participants. Effectiveness was assessed with paired 2-tailed t tests for pre- and post-Likert agreement scale survey items, adjusted for multiple comparisons. In addition to assessing mean and SD at baseline and postsurvey, observed effect sizes were calculated (Cohen d). Usability and reaction to the program among firefighters who responded to postsurvey were also assessed. RESULTS: The qualitative themes and subthemes were used to inform the program's content. For the effectiveness trial, 131 firefighters completed the presurvey, and 50 (38.2%) completed the postsurvey. The majority of the participants were White (n=123, 93.9%), male (n=117, 89.3%), with an average age of 41 (SD 12.9) years. Significant increases in knowledge and desired health and safety behaviors were found for both cancer (P<.001) and cardiovascular risk (P=.01), nutrition behaviors (P=.01), hydration or overheating (P=.001), binge drinking (P=.002), and getting medical checkups (P=.001). More than 80% (n=40) of postsurvey respondents agreed or strongly agreed that the program was easy to use and would recommend it to others. CONCLUSIONS: An innovative web-based safety and health promotion program for those fighting wildland fires was feasible, scalable, and usable. It improved the health and safety of those fighting wildland fires. TRIAL REGISTRATION: ClinicalTrials.gov NCT05753358; https://classic.clinicaltrials.gov/ct2/show/NCT05753358.

Outcomes among Nulliparous Women Undergoing Nonmedically Indicated Induction of Labor at 39 Weeks Compared with Expectant Management Differ by Maternal Age.

OBJECTIVE: Prior studies have demonstrated the potential benefit of nonmedically indicated induction of labor for nulliparous women at 39 weeks of gestation, yet few have studied the impact of this management strategy in different maternal age groups on obstetric outcomes. We sought to assess whether obstetric outcomes among women undergoing nonmedically indicated induction of labor at 39 weeks of gestation as compared with expectant management vary based on maternal age. STUDY DESIGN: This was a retrospective cohort study of singleton, nonanomalous, deliveries between 2007 and 2012 in California. We defined nonmedically indicated induction of labor as induction of labor without a specific medical indication, and women with planned cesarean sections were excluded. We compared induction of labor with expectant management beyond the gestational age of induction and examined this comparison in different maternal age groups. Numerous maternal and neonatal outcomes were examined. Chi-squared and multivariable logistic regression analyses were used for statistical comparisons and a p-value of less than 0.05 was used to indicate statistical significance. RESULTS: A total of 630,485 women-infant dyads met our inclusion criteria and were included in this study. At 39 weeks' gestation, 6% of women underwent nonmedically indicated induction of labor and 94% underwent expectant management. Women 20 to 34 and ≥35 years old had lower odds of cesarean delivery if they underwent induction of labor. Women of all ages undergoing nonmedically indicated induction of labor had higher odds of operative vaginal delivery. Neonatal outcomes were better with nonmedically indicated induction of labor, including lower odds of neonatal intensive care unit admission and neonatal respiratory distress. CONCLUSION: Our study demonstrated that obstetric outcomes vary among women undergoing nonmedically indicated induction of labor compared with expectant management when stratified by maternal age. These findings illustrate the importance of understanding age-related differences in outcomes associated with nonmedically indicated induction of labor. KEY POINTS: · Outcomes are different by age with nonmedically indicated induction of labor (IOL).. · The odds of cesarean delivery with IOL decreases with increasing maternal age compared with expectant management.. · Neonatal outcomes were improved with IOL compared with expectant management..

Adverse Perinatal and Neonatal Outcomes among Adolescent Pregnancies in the United States.

OBJECTIVE: Despite a downward trend in recent years, adolescent pregnancies in the United States remain higher than any other western country. Adolescent pregnancies have been inconsistently associated with adverse perinatal outcomes. The objective of this study is to investigate the association between adolescent pregnancies and adverse perinatal and neonatal outcomes in the United States. STUDY DESIGN: This is a retrospective cohort study of singleton births in the United States from 2014 to 2020 using national vital statistics data. Perinatal outcomes included gestational diabetes, gestational hypertension, preterm delivery <37 weeks (preterm birth [PTB]), cesarean delivery (CD), chorioamnionitis, small for gestational age (SGA), large for gestational age (LGA), and neonatal composite outcome. Chi-square tests were used to compare outcomes among adolescent (13-19 years) versus adult (20-29 years) pregnancies. Multivariable logistic regression models were used to examine association of adolescent pregnancies with perinatal outcomes. For each outcome, we utilized three models: unadjusted logistic regression, adjusted for demographics, and adjusted for demographics and medical comorbidities. Similar analyses were used to compare younger (13-17 years) and older (18-19 years) adolescent pregnancies to adults. RESULTS: In a cohort of 14,014,078 pregnancies, we found that adolescents were at an increased risk of PTB (adjusted odds ratio [aOR]: 1.12, 99% confidence interval (CI): 1.12-1.13) and SGA (aOR: 1.02, 99% CI: 1.01-1.03) compared with adult pregnancies. We also found that multiparous adolescents with a prior history of CD were at an increased risk of CD, compared with adults. For all other outcomes, adult pregnancies were at higher risk for adverse outcomes in the adjusted models. When comparing birth outcomes among adolescents, we found that older adolescents are at an increased risk of PTB, whereas younger adolescents are at an increased risk of both PTB and SGA. CONCLUSION: After adjusting for confounders, our study demonstrates adolescents have an increased risk of PTB and SGA, compared with adults. KEY POINTS: · Adolescents as a whole subgroup have an increased risk of PTB and SGA compared with adults.. · Younger adolescents have a risk of PTB and SGA, whereas older adolescents have a risk of PTB only.. · Adverse birth outcomes in adults are gestational diabetes, chorioamnionitis, LGA, and worse neonatal composite score..

Characterizing persistent urinary incontinence after successful fistula closure: the Uganda experience.

BACKGROUND: Obstetric fistula is a devastating childbirth injury. Despite successful closure of the fistula, 16% to 55% of women suffer from persistent urinary incontinence after surgery. OBJECTIVE: This study assessed the type and severity of persistent incontinence after successful fistula closure and its impact on the quality of life of Ugandan women post-fistula treatment. STUDY DESIGN: This cross-sectional study enrolled women with a history of obstetric fistula repair who continued to have persistent urinary incontinence (cases, N=36) and women without incontinence (controls, N=52) after successful fistula closure. Data were collected in central and eastern Uganda between 2017 and 2019. All the participants completed a semistructured questionnaire. Cases underwent a clinical evaluation and a 2-hour pad test and completed a series of incontinence questionnaires, including two novel tools designed to assess the severity of incontinence in low-literacy populations. RESULTS: Cases were more likely to have acquired a fistula during their first delivery (63% vs 37%, P=.02), were younger when they developed a fistula (20.3±5.8 vs 24.8±7.5 years old, P=.003), and were more likely to have had >2 fistula surgeries (67% vs 2%, P≤.001). Cases reported a much higher rate of planned home birth for their index pregnancy compared to controls (44% vs 11%), though only 14% of cases and 12% of controls actually delivered at home. Cases reported higher rates of pain with intercourse (36% vs 18%, P=.05), but recent sexual activity status (intercourse within the previous six months) was not significantly different between the groups (47% vs 62%, P=.18). Among cases, 67% reported stress incontinence, 47% reported urgency incontinence, and 47% reported mixed incontinence. The cough stress test was successfully done with 92% of the cases, and of these, almost all (97%) had a positive cough stress test. More than half (53%) rated their incontinence as "very severe," which was consistent with objective findings. The 24-hour voiding diary indicated both high urinary frequency (average 14) and very frequent leakage episodes (average 20). Two-hour pad-tests indicated that 86% of cases had >4 g change in pad weight within 2 hours. Women with more severe incontinence reported a more negative impact on their quality of life. The mean score of the International Consultation on Incontinence Questionnaire-Quality of Life was 62.77±12.76 (range, 28-76, median=67), with a higher score indicating a greater impact on the quality of life. There was also a high mental health burden, with both cases and controls reporting high rates of suicidal ideation at any point since developing fistula (36% vs 31%, P=.67). CONCLUSION: Women with obstetric fistulas continue to suffer from severe persistent urinary incontinence even after successful fistula closure. Both stress and urgency incontinence are highly prevalent in this population. Worsening severity of incontinence is associated with a greater negative impact on the quality of life.

Severe maternal morbidity and other perinatal complications among women with physical, sensory, or intellectual and developmental disabilities.

BACKGROUND: Little is known about severe maternal morbidity (SMM) among women with disabilities. OBJECTIVE: We assessed differences in SMM and other perinatal complications by presence and type of disability. We hypothesised that SMM and other complications would be more common in births to women with disabilities than to women without disabilities. METHODS: We conducted a retrospective cohort study of California births from 2000 to 2012, using birth and death certificate data linked with hospital discharge data. We included singleton deliveries with gestational age of 23-42 weeks. We classified women as having any disability or not and identified disability type (physical, hearing, vision, intellectual/developmental disabilities [IDD]). Our primary outcome was a composite indicator of SMM. Secondary outcomes included additional perinatal complications: gestational hypertension, preeclampsia, gestational diabetes, venous thromboembolism, chorioamnionitis, puerperal endometritis and mental health disorders complicating pregnancy, childbirth or the puerperium. We used modified Poisson regression to obtain covariate-adjusted relative risks (RR) and 95% confidence intervals (CI) for the association of disability status and type with SMM and secondary outcomes. RESULTS: Of 5,787,090 deliveries, 33,044 (0.6%) were to women with disabilities. Of these, 311 per 10,000 were complicated by SMM, compared with 84 per 10,000 deliveries to women without disabilities. In multivariable analyses, risk of SMM for births to women with disabilities was nearly three times that for women without disabilities (RR 2.84, 95% CI 2.67, 3.02). Proportion and risk of SMM were greatest for vision disability (793 per 10,000; RR 4.04, 95% CI 3.41, 4.78). Secondary outcomes were also more common among women with disabilities. In particular, more than a third of births to women with IDD (37.4%) were complicated by mental health disorders (versus 2.2% for women without disabilities). CONCLUSION: As hypothesised, SMM and other perinatal complications were more common among women with disabilities than among women without disabilities.

Association of 12-month contraceptive supply policy and months of oral contraception prescribed by obstetrics and gynecology resident physicians: an exploratory cross-sectional study.

OBJECTIVE: This study sought to determine if there was a difference in the months of oral contraception prescribed by resident physicians living in U.S. states with a 12-month supply policy compared to resident physicians in states without a policy. METHODS: We conducted an exploratory descriptive study using a convenience sample of Obstetrics and Gynecology resident physicians (n = 275) in the United States. Standard bivariate analyses were used to compare the difference between groups. RESULTS: Few resident physicians in both groups (3.8% with a policy and 1.4% without a policy) routinely prescribed a 12-month supply of contraception. The mean coverage prescribed by providers in states with and without a policy was 2.81 and 2.07 months (p < 0.05). CONCLUSIONS: The majority of resident physicians were unaware of 12-month contraceptive supply policies and unable to correctly write a prescription for 12-months of contraception, regardless of whether they lived in a state with a 12-month contraceptive supply policy. Physician education may be needed to effectively implement 12-month contraceptive supply policies.

Differences in Perinatal Outcomes among Rural Women by County Composition.

OBJECTIVE: We compared differences in perinatal outcomes among rural and nonrural women, stratified by maternal race/ethnicity. We also examined differences between majority minority rural counties with majority White rural counties. STUDY DESIGN: We conducted a retrospective cohort study with 2015 national vital statistics birth certificate data. Maternal county of residence was identified, and counties with <50,000 people were designated as rural. We compared adverse perinatal outcomes between rural and nonrural residents, stratified by race/ethnicity. Adverse perinatal outcomes included primary term cesarean, preterm birth (PTB) <37 and <32 weeks, neonatal intensive care unit (NICU) admissions, infant death, small for gestational age, and Apgar's scores <7 and <3 at 5minutes. Majority-minority rural counties were defined as counties having <50% White women. We compared perinatal outcomes among this cohort to those of women from majority White rural counties. Bivariate analysis and multivariable logistic regression were performed. RESULTS: Within the entire cohort, rural residents were more likely to be younger (age ≥35 years, 10.1 vs. 16.8%; p<0.001), Medicaid beneficiaries (50.3 vs. 44.1%; p<0.001), and uninsured (6.6 vs. 4.2%; p<0.001), and less likely to be married (57.4 vs. 60.20%; p<0.001). Rural residence was associated with Apgar's score <7 (adjusted odds ratio [aOR]=2.04; 95% confidence interval [CI]: 1.64-2.54) and <3 (aOR=1.90; 95% CI: 1.04-3.48) among Asian women. Rural residence was also associated with PTB <37 weeks among Black (aOR=1.09; 95% CI: 1.06-1.13) and Asian women (aOR=1.16; 95% CI: 1.03-1.31). When compared with majority White rural county of residence, majority-minority rural county of residence was associated with the adverse perinatal outcomes studied. CONCLUSION: We observed increased rates of adverse perinatal outcomes among rural women. These trends persisted in majority-minority rural. Additional study is needed to find actionable targets for improving outcomes for rural women. KEY POINTS: · Rural county of residence was associated with lower socioeconomic markers.. · Perinatal outcomes were worse among women from rural counties.. · Differences in perinatal outcomes exist among rural women by race/ethnicity..

Is Appropriate Administration of Antenatal Corticosteroids Associated with Maternal Race?

OBJECTIVE: Antenatal corticosteroids (ACSs) improve outcomes for premature infants; however, not all pregnant women at risk for preterm delivery receive ACS. Racial minorities are less likely to receive adequate prenatal care and more likely to deliver preterm. The objective of this study was to determine if maternal race is associated with a lower rate of ACS administration in Washington for women at risk of preterm labor (between 23 and 34 weeks). STUDY DESIGN: This was a population-based retrospective cohort study of singleton, nonanomalous, premature deliveries in Washington state between 2007 and 2014. Descriptive data included maternal sociodemographics, pregnancy complications, facility of birth, and neonatal characteristics. The primary outcome was maternal receipt of ACS and the independent variable was maternal race/ethnicity. The secondary outcomes included neonatal need for assisted ventilation, both initially and for more than 6 hours, and administration of surfactant. Data were analyzed using chi-square tests and logistic regression models. RESULTS: A total of 8,530 nonanomalous, singleton neonates were born between 23 and 34 weeks' gestation. Of those, 55.8% of mothers were self-identified as white, 7.5% as black, 21.4% as Hispanic, 10.9% as Asian, and 4.3% as Native American. After adjusting for confounders, black woman-neonate dyads had significantly lower odds of receiving ACS, (adjusted odds ratio [aOR] = 0.62; 95% confidence interval [CI]: 0.51-0.76), assisted ventilation immediately following delivery (aOR = 0.76; 95% CI: 0.61-0.94) and for more than 6 hours (aOR = 0.64; 95% CI: 0.49-0.84) and surfactant therapy (aOR = 0.62; 95% CI: 0.42-0.92) as compared with whites. CONCLUSION: These findings contribute to the current body of literature by describing racial disparities in ACS administration for pregnant women at risk for preterm delivery. To better understand the association between black race and administration of ACS, future studies should focus on differences within and between hospitals (including quality, location, resources), patient health literacy, social determinants of health, and exposure to systemic racism and discrimination. KEY POINTS: · Black women were less likely to receive antenatal steroids.. · Black neonates had lower odds of respiratory support.. · Black neonates had lower odds of receiving surfactant..

Long and short interpregnancy intervals increase severe maternal morbidity.

BACKGROUND: Severe maternal morbidity is a composite variable that includes adverse maternal outcomes during pregnancy that are associated with maternal mortality. Previous literature has shown that interpregnancy interval is associated with preterm birth, fetal growth restriction, and low birthweight, but the association of interpregnancy interval and composite severe maternal morbidity is not well studied. OBJECTIVE: We sought to determine the relationship between interpregnancy interval (stratified as <6, 6-11, 12-17, 18-23, 24-59, and ≥60 months) and severe maternal morbidity, which we considered both with and without blood transfusion. STUDY DESIGN: This was a retrospective cohort study of multiparous women 15 to 54 years old with singleton, nonanomalous births between 23 and 42 weeks gestation in California (2007-2012). We defined severe maternal morbidity as the composite score of a published list of the International Classification of Diseases, ninth Revision, diagnoses and procedure codes, provided by the Centers for Disease Control and Prevention. We used chi-square tests for categorical variables, and multivariable logistic regression models were used to determine the association of interpregnancy interval (independent variable) with severe maternal morbidity (dependent variable), adjusted for maternal race and ethnicity, age, education, body mass index, insurance, prenatal care, smoking status, and maternal comorbidity index score. RESULTS: Here, 1,669,912 women met the inclusion criteria, and of these women, 14,529 (0.87%) had severe maternal morbidity and 4712 (0.28%) had nontransfusion severe maternal morbidity. Multivariable logistic regression models showed that compared with women with 18 to 23 months interpregnancy interval, women with an interpregnancy interval of <6 months (adjusted odds ratio, 1.23; 95% confidence interval, 1.14-1.34) and ≥60 months (adjusted odds ratio, 1.11; 95% confidence interval, 1.04-1.19) had significantly higher adjusted odds of severe maternal morbidity. The odds of nontransfusion severe maternal morbidity is higher in women with long interpregnancy intervals (≥60 months) after controlling for the same potential confounders (adjusted odds ratio, 1.17, 95% confidence interval, 1.04-1.31). In addition, we found significantly higher odds of requiring ventilation (adjusted odds ratio, 1.34; 95% confidence interval, 1.03-1.75) and maternal sepsis (adjusted odds ratio, 2.08; 95% confidence interval, 1.31-3.31) in women with long interpregnancy interval. CONCLUSION: The risk of severe maternal morbidity was higher in women with short interpregnancy interval (<6 months) and long interpregnancy interval (≥60 months) compared with women with normal interpregnancy interval (18-23 months). The risk of nontransfusion severe maternal morbidity was significantly higher in women with long interpregnancy interval (≥60 months). Interpregnancy interval is a modifiable risk factor, and counseling women to have an adequate gap between pregnancies may be an important strategy to decrease the risk of severe maternal morbidity.

Characteristics of persistent urinary incontinence after successful fistula closure in Ethiopian women.

INTRODUCTION AND HYPOTHESIS: Obstetric fistulas have devastating consequences for women. Although surgical repair is largely successful in closing the defect, many women with successful fistula closure report persistent urinary incontinence. Our study is aimed at characterizing incontinence after successful fistula repair and its impact on quality of life. METHODS: This cross-sectional study enrolled women with a history of successful obstetric fistula closure with (n = 51; cases) or without (n = 50; controls) persistent urinary incontinence. Data were collected in Mekelle, Ethiopia, between 2016 and 2018. All cases underwent clinical evaluation and completed questionnaires characterizing the type, severity, and impact of incontinence. RESULTS: Cases were significantly more likely to have acquired their fistula at an earlier age and with their first vaginal delivery compared with controls. Almost all cases reported both stress (98%) and urgency (94%) incontinence, and half reported constant urinary leakage (49%) despite successful fistula closure. Of cases who completed urodynamic evaluation (n = 22), all had genuine stress incontinence and none had detrusor overactivity. All cases reported moderate to severe (80.4%) or very severe (19.6%) incontinence (measured by ICIQ-SF) and this had a moderate to severe negative impact on their quality of life (as measured by ICIQ-QoL). Although history of suicidal ideation was not significantly different between the groups, among those with suicidal ideation, cases were more likely to report having made a plan and/or attempted to commit suicide. CONCLUSIONS: When urinary incontinence persists after successful fistula closure, it tends to be severe and of mixed etiology and has a significant negative impact on quality of life and mental health.

Obstetric outcomes of pregnancy complicated by urolithiasis: a retrospective cohort study.

OBJECTIVES: Evaluate the association between urolithiasis during pregnancy and obstetric outcomes outside the context of urological intervention. METHODS: We conducted a retrospective cohort study of singleton, non-anomalous gestations delivered at 23-42 weeks in California from 2007 to 2011. Maternal outcomes (preterm delivery [early (<32 weeks) and late (<37 weeks)], preeclampsia, gestational diabetes, cesarean deliveries, urinary tract infection [UTI] at delivery, chorioamnionitis, endomyometritis, and maternal sepsis) and newborn outcomes (seizure, respiratory distress syndrome, hypoglycemia, jaundice, and neonatal abstinence syndrome [NAS]) were compared using χ2-tests and multivariable logistic regression. RESULTS: A total of 2,013,767 pregnancies met inclusion criteria, of which 5,734 (0.28%) were complicated by urolithiasis. Stone disease during pregnancy was associated with 30% greater odds of each early (aOR 1.30; 95% CI 1.19-1.43) and late (aOR 1.29; 95% CI 1.18-1.41) preterm delivery. Cesarean delivery, UTI at delivery, gestational hypertension, gestational diabetes, preeclampsia, and sepsis were all significantly positively associated with urolithiasis. Odds of NAS (aOR 2.11; 95% CI 1.27-3.51) and jaundice were significantly greater in the neonates of stone-forming patients (aOR 1.08; 95% CI 1.01-1.16). CONCLUSIONS: Urolithiasis during pregnancy was associated with 30% greater odds of preterm delivery and increased risk of myriad metabolic, hypertensive, and infectious disorders of gestation. Neonates born to stone-forming patients were more than twice as likely to develop neonatal abstinence syndrome but did not have significantly greater odds of complications of prematurity.

Gut Microbiota Promotes Tumor Growth in Mice by Modulating Immune Response.

We studied the effects of gut microbiome depletion by oral antibiotics on tumor growth in subcutaneous and liver metastases models of pancreatic cancer, colon cancer, and melanoma. Gut microbiome depletion significantly reduced tumor burden in all the models tested. However, depletion of gut microbiome did not reduce tumor growth in Rag1-knockout mice, which lack mature T and B cells. Flow cytometry analyses demonstrated that gut microbiome depletion led to significant increase in interferon gamma-producing T cells with corresponding decrease in interleukin 17A and interleukin 10-producing T cells. Our results suggest that gut microbiome modulation could emerge as a novel immunotherapeutic strategy.

NFκB in Pancreatic Stellate Cells Reduces Infiltration of Tumors by Cytotoxic T Cells and Killing of Cancer Cells, via Up-regulation of CXCL12.

BACKGROUND & AIMS: Immunotherapies are ineffective against pancreatic cancer. We investigated whether the activity of nuclear factor (NF)κB in pancreatic stromal cells contributes to an environment that suppresses antitumor immune response. METHODS: Pancreata of C57BL/6 or Rag1-/- mice were given pancreatic injections of a combination of KrasG12D/+; Trp53 R172H/+; Pdx-1cre (KPC) pancreatic cancer cells and pancreatic stellate cells (PSCs) extracted from C57BL/6 (control) or mice with disruption of the gene encoding the NFκB p50 subunit (Nfkb1 or p50-/- mice). Tumor growth was measured as an endpoint. Other mice were given injections of Lewis lung carcinoma (LLC) lung cancer cells or B16-F10 melanoma cells with control or p50-/- fibroblasts. Cytotoxic T cells were depleted from C57BL/6 mice by administration of antibodies against CD8 (anti-CD8), and growth of tumors from KPC cells, with or without control or p50-/- PSCs, was measured. Some mice were given an inhibitor of CXCL12 (AMD3100) and tumor growth was measured. T-cell migration toward cancer cells was measured using the Boyden chamber assay. RESULTS: C57BL/6 mice coinjected with KPC cells (or LLC or B16-F10 cells) and p50-/- PSCs developed smaller tumors than mice given injections of the cancer cells along with control PSCs. Tumors that formed when KPC cells were injected along with p50-/- PSCs had increased infiltration by activated cytotoxic T cells along with decreased levels of CXCL12, compared with tumors grown from KPC cells injected along with control PSCs. KPC cells, when coinjected with control or p50-/- PSCs, developed the same-size tumors when CD8+ T cells were depleted from C57BL/6 mice or in Rag1-/- mice. The CXCL12 inhibitor slowed tumor growth and increased tumor infiltration by cytotoxic T cells. In vitro expression of p50 by PSCs reduced T-cell migration toward and killing of cancer cells. When cultured with cancer cells, control PSCs expressed 10-fold higher levels of CXCL12 than p50-/- PSCs. The CXCL12 inhibitor increased migration of T cells toward KPC cells in culture. CONCLUSIONS: In studies of mice and cell lines, we found that NFκB activity in PSCs promotes tumor growth by increasing expression of CXCL12, which prevents cytotoxic T cells from infiltrating the tumor and killing cancer cells. Strategies to block CXCL12 in pancreatic tumor cells might increase antitumor immunity.

"Heat shock protein 70 in pancreatic diseases: Friend or foe".

The heat shock response in pancreatitis that is activated via HSP70 protects acinar cells through multiple simultaneous mechanisms. It inhibits trypsinogen activation and modulates NF-κB signaling to limit acinar cell injury. On the other hand, HSP70 is overexpressed in pancreatic cancer and is hijacked by the cellular machinery to inhibit apoptosis. Inhibition of HSP70 in pancreatic cancer by a novel compound, Minnelide, has shown considerable clinical promise.