Association Between Influenza Vaccination and SARS-CoV-2 Infection.

BACKGROUND: Recent data in nonpregnant individuals suggest a protective effect of influenza vaccination against SARS-CoV-2 infection and its severity. OBJECTIVES: Our primary objective was to evaluate whether influenza vaccination was associated with COVID-19 severity and pregnancy and neonatal outcomes among those infected with SARS-CoV-2. The secondary objective was to examine the association between influenza vaccination and SARS-CoV-2 infection. STUDY DESIGN: Secondary analysis of a multicenter retrospective cohort of pregnant people who tested positive for SARS-CoV-2 between March and August 2020, and a cohort of random deliveries during the same time period. The associations between 2019 influenza vaccination and the primary outcome of moderate-to-critical COVID-19 as well as maternal and perinatal outcomes were examined among all people who tested positive for SARS-CoV-2 between March and August 2020. The association between 2019 influenza vaccination and having a positive SARS-CoV-2 test was examined among a cohort of individuals who delivered on randomly selected dates between March and August 2020. Univariable and multivariable analyses were performed. RESULTS: Of 2325 people who tested positive for SARS-CoV-2, 1068 (45.9%) were vaccinated against influenza in 2019. Those who received the influenza vaccine were older, leaner, more likely to have private insurance, and identify as White or Hispanic. They were less likely to smoke tobacco and identify as Black. Overall, 419 (18.0%) had moderate, 193 (8.3%) severe, and 52 (2.2%) critical COVID-19. There was no association between influenza vaccination and moderate-to-critical COVID-19 (29.2% vs. 28.0%, adjusted OR 1.10, 95% CI 0.90-1.34) or adverse maternal and perinatal outcomes among those who tested positive. Of 8152 people who delivered in 2020, 4658 (57.1%) received the influenza vaccine. Prior vaccination was not associated with a difference in the odds of SARS-CoV-2 infection (3.8% vs. 4.2%, adjusted OR 0.94, 95% CI 0.74-1.19). CONCLUSION: Prior influenza vaccination was not associated with decreased severity of COVID-19 or lower odds of SARS-CoV-2 infection in pregnancy.

Phthalate and phthalate replacement concentrations in relationship to adiposity in a multi-racial cohort of children.

BACKGROUND/OBJECTIVE: Phthalates and phthalate replacements are used in multiple everyday products, making many of them bioavailable to children. Experimental studies suggest that phthalates and their replacements may be obesogenic, however, epidemiologic studies remain inconsistent. Therefore, our objective was to examine the association between phthalates, phthalate replacements and childhood adiposity/obesity markers in children. SUBJECTS/METHODS: A cross-sectional study was conducted in 630 racial/ethnically diverse children ages 4-8 years. Urinary oxidative metabolites of DINCH and DEHTP, three low molecular weight (LMW) phthalates, and eleven high molecular weight (HMW) phthalates were measured. Weight, height, waist circumference and % body fat were measured. Composite molar sum groups (nmol/ml) were natural log-transformed. Linear regression models adjusted for urine specific gravity, sex, age, race-ethnicity, birthweight, breastfeeding, reported activity level, mother's education and pre-pregnancy BMI. RESULTS: All children had LMW and HMW phthalate metabolites and 88% had DINCH levels above the limit of detection. One unit higher in the log of DINCH was associated with 0.106 units lower BMI z-score [ß = -0.106 (95% CI: -0.181, -0.031)], 0.119 units lower waist circumference z-score [ß = -0.119 (95% CI: -0.189, -0.050)], and 0.012 units lower percent body fat [ß = -0.012 (95% CI: -0.019, -0.005)]. LMW and HMW group values were not associated with adiposity/obesity. CONCLUSIONS: We report an inverse association between child urinary DINCH levels, a non-phthalate plasticizer that has replaced DEHP in several applications, and BMI z-score, waist circumference z-score and % body fat in children. Few prior studies of phthalates and their replacements in children have been conducted in diverse populations. Moreover, DINCH has not received a great deal of attention or regulation, but it is a common exposure. In summary, understanding the ubiquitous nature of these chemical exposures and ultimately their sources will contribute to our understanding of their relationship with obesity.

Maternal and Delivery Characteristics and Self-Reported Perceived Control During Labor.

OBJECTIVE: To evaluate the association between maternal and delivery characteristics and self-reported perceived control during childbirth. METHODS: A secondary analysis of a multicenter randomized trial was conducted to compare labor induction at 39 weeks of gestation with expectant management in low-risk nulliparous people. Six to 96 hours after delivery, participants who experienced labor completed the Labor Agentry Scale, a validated self-administered questionnaire to ascertain perceived control during childbirth. Scores range from 29 to 203, with higher scores indicating a sense of greater control. Multivariable linear regression was used to determine which maternal and delivery characteristics were associated with the Labor Agentry Scale score. Eligible characteristics included age, self-reported race and ethnicity, marital status, employment status, type of insurance, previous pregnancy loss before 20 weeks of gestation, body mass index (BMI), smoking, alcohol use, mode of delivery, labor pain (0-10 points), and a composite of perinatal death or severe neonatal complications. Significant variables ( P <.05) were retained in the final multivariable model, and adjusted mean differences (95% CIs) between groups were estimated. RESULTS: Of 6,106 people enrolled in the trial, 6,038 experienced labor, of whom 5,750 (95.2%) completed the Labor Agentry Scale and were included in this analysis. Mean [95% CI] adjusted Labor Agentry Scale scores were significantly lower among those who identified as Asian (-6.4 [-10.5 to -2.3]) or Hispanic (-3.7 [-5.7 to -1.7]) compared with White, smoked compared with did not smoke (-2.8 [-5.5 to -0.1]), had BMIs of 35 or higher compared with less than 30 (-2.0 [-3.8 to -0.2]), were unemployed (-3.15 [-4.76 to -1.55]), did not have private health insurance (-2.61 [-4.47 to -0.76]), underwent operative vaginal (-5.1 [-7.7 to -2.6]) or cesarean (-14.4 [-16.1 to -12.6]) delivery compared with spontaneous vaginal delivery, and reported greater labor pain score of 8 or higher compared with less than 8 (-11.9 [-13.4 to -10.4]). Mean [95% CI] adjusted Labor Agentry Scale scores were significantly higher among people who were employed compared with unemployed (3.2 [1.6-4.8]) and had private compared with nonprivate insurance (2.6 [0.76-4.5]). CONCLUSION: In nulliparous people at low risk, unemployment, lack of private health insurance, Asian race, Hispanic ethnicity, smoking, operative delivery, and more labor pain were associated with lower perceived control during labor. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT01990612.

Tranexamic Acid to Prevent Obstetrical Hemorrhage after Cesarean Delivery.

BACKGROUND: Prophylactic use of tranexamic acid at the time of cesarean delivery has been shown to decrease the calculated blood loss, but the effect on the need for blood transfusions is unclear. METHODS: We randomly assigned patients undergoing cesarean delivery at 31 U.S. hospitals to receive either tranexamic acid or placebo after umbilical-cord clamping. The primary outcome was a composite of maternal death or blood transfusion by hospital discharge or 7 days post partum, whichever came first. Key secondary outcomes were estimated intraoperative blood loss of more than 1 liter (prespecified as a major secondary outcome), interventions for bleeding and related complications, the preoperative-to-postoperative change in the hemoglobin level, and postpartum infectious complications. Adverse events were assessed. RESULTS: A total of 11,000 participants underwent randomization (5529 to the tranexamic acid group and 5471 to the placebo group); scheduled cesarean delivery accounted for 50.1% and 49.2% of the deliveries in the respective groups. A primary-outcome event occurred in 201 of 5525 participants (3.6%) in the tranexamic acid group and in 233 of 5470 (4.3%) in the placebo group (adjusted relative risk, 0.89; 95.26% confidence interval [CI], 0.74 to 1.07; P = 0.19). Estimated intraoperative blood loss of more than 1 liter occurred in 7.3% of the participants in the tranexamic acid group and in 8.0% of those in the placebo group (relative risk, 0.91; 95% CI, 0.79 to 1.05). Interventions for bleeding complications occurred in 16.1% of the participants in the tranexamic acid group and in 18.0% of those in the placebo group (relative risk, 0.90; 95% CI, 0.82 to 0.97); the change in the hemoglobin level was -1.8 g per deciliter and -1.9 g per deciliter, respectively (mean difference, -0.1 g per deciliter; 95% CI, -0.2 to -0.1); and postpartum infectious complications occurred in 3.2% and 2.5% of the participants, respectively (relative risk, 1.28; 95% CI, 1.02 to 1.61). The frequencies of thromboembolic events and other adverse events were similar in the two groups. CONCLUSIONS: Prophylactic use of tranexamic acid during cesarean delivery did not lead to a significantly lower risk of a composite outcome of maternal death or blood transfusion than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT03364491.).

Short-term neonatal outcomes of pregnancies complicated by maternal obesity.

BACKGROUND: Maternal obesity complicates a high number of pregnancies. The degree to which neonatal outcomes are adversely affected is unclear. OBJECTIVE: This study aimed to evaluate neonatal outcomes of pregnancies complicated by maternal obesity. STUDY DESIGN: This study was a secondary analysis of a cohort of deliveries occurring on randomly selected days at 25 hospitals from 2008 to 2011. Data were collected by certified abstractors. This analysis included singleton deliveries between 24 and 42 weeks of gestation. Body mass index was calculated on the basis of maternal height and most recent weight before delivery. Normal and overweight (reference group; body mass index, 18.5-29.9 kg/m2), obese (body mass index, 30.0-39.9 kg/m2), morbidly obese (body mass index, 40.0-49.9 kg/m2), and super morbidly obese (body mass index, ≥50 kg/m2) patients were compared. Patients in the reference group were matched in a 1:1 ratio with those in all other groups with obesity using the baseline characteristics of age, race and ethnicity, previous cesarean delivery, preexisting diabetes mellitus, chronic hypertension, parity, cigarette use, and insurance status. The primary outcome was composite neonatal morbidity, including fetal or neonatal death, hypoxic-ischemic encephalopathy, respiratory distress syndrome, intraventricular hemorrhage grade 3 or 4, necrotizing enterocolitis, sepsis, birth injury, seizures, or ventilator use. We used a modified Poisson regression to examine the associations between body mass index and composite neonatal outcome. Preterm delivery at <37 weeks of gestation and the presence of maternal preeclampsia or eclampsia were included in the final model because of their known associations with neonatal outcomes. RESULTS: Overall, 52,162 patients and their neonates were included after propensity score matching. Of these, 21,704 (41.6%) were obese, 3787 (7.3%) were morbidly obese, and 590 (1.1%) were super morbidly obese. A total of 2103 neonates (4.0%) had the composite outcome. Neonates born to pregnant people with morbid obesity had a 33% increased risk of composite neonatal morbidity compared with those in the reference group (adjusted odds ratio, 1.33; 95% confidence interval, 1.17-1.52), but no significant association was observed for persons with obesity (adjusted odds ratio, 1.05; 95% confidence interval, 0.97-1.14) or with super morbid obesity (adjusted odds ratio, 1.18; 95% confidence interval, 0.86-1.64). CONCLUSION: Compared with the reference group, gravidas with morbid obesity were at higher risk of composite neonatal morbidity.

Racial and Ethnic Disparities in Adverse Perinatal Outcomes at Term.

OBJECTIVE: This study aimed to evaluate whether racial and ethnic disparities in adverse perinatal outcomes exist at term. STUDY DESIGN: We performed a secondary analysis of a multicenter observational study of 115,502 pregnant patients and their neonates (2008-2011). Singleton, nonanomalous pregnancies delivered from 37 to 41 weeks were included. Race and ethnicity were abstracted from the medical record and categorized as non-Hispanic White (White; referent), non-Hispanic Black (Black), non-Hispanic Asian (Asian), or Hispanic. The primary outcome was an adverse perinatal composite defined as perinatal death, Apgar score < 4 at 5 minutes, ventilator support, hypoxic-ischemic encephalopathy, subgaleal hemorrhage, skeletal fracture, infant stay greater than maternal stay (by ≥ 3 days), brachial plexus palsy, or facial nerve palsy. RESULTS: Of the 72,117 patients included, 48% were White, 20% Black, 5% Asian, and 26% Hispanic. The unadjusted risk of the primary outcome was highest for neonates of Black patients (3.1%, unadjusted relative risk [uRR] = 1.16, 95% confidence interval [CI]: 1.04-1.30), lowest for neonates of Hispanic patients (2.1%, uRR = 0.80, 95% CI: 0.71-0.89), and no different for neonates of Asian (2.6%), compared with those of White patients (2.7%). In the adjusted model including age, body mass index (BMI), smoking, obstetric history, and high-risk pregnancy, differences in risk for the primary outcome were no longer observed for neonates of Black (adjusted relative risk [aRR] = 1.06, 95% CI: 0.94-1.19) and Hispanic (aRR = 0.92, 95% CI: 0.81-1.04) patients. Adding insurance to the model lowered the risk for both groups (aRR = 0.85, 95% CI: 0.75-0.96 for Black; aRR = 0.68, 95% CI: 0.59-0.78 for Hispanic). CONCLUSION: Although neonates of Black patients have the highest frequency of adverse perinatal outcomes at term, after adjustment for sociodemographic factors, this higher risk is no longer observed, suggesting the importance of developing strategies that address social determinants of health to lessen extant health disparities. KEY POINTS: · Term neonates of Black patients have the highest crude frequency of adverse perinatal outcomes.. · After adjustment for confounders, higher risk for neonates of Black patients is no longer observed.. · Disparities in outcomes are strongly related to insurance status..

Geographic disparities in peripartum cardiomyopathy outcomes.

BACKGROUND: Cardiomyopathy causes more than a third of late postpartum pregnancy-related deaths in the United States, and racial disparities in outcomes among pregnant individuals with cardiomyopathy exist. Underlying community factors may contribute to disparities in peripartum cardiomyopathy outcomes. OBJECTIVE: This study aimed to identify the geographic distribution of and disparities in peripartum cardiomyopathy outcomes, hypothesizing that patients living in communities with higher social vulnerability may have worse outcomes. STUDY DESIGN: This was a retrospective cohort study of patients with peripartum cardiomyopathy per the National Heart, Lung, and Blood Institute definition from January 2000 to November 2017 at a single center, excluding those with a post office box address as a post office box address may not reflect the census tract in which a patient resides. Severe peripartum cardiomyopathy (vs less severe peripartum cardiomyopathy) was defined as ejection fraction <30%, death, intensive care unit admission, left ventricular assist device or implantable cardioverter defibrillator placement, or transplant. The US census tract for the patient's address was linked to the Centers for Disease Control and Prevention Social Vulnerability Index, a 0 to 1 scale of a community's vulnerability to external stresses on health, with higher values indicating greater vulnerability. The Social Vulnerability Index includes social factors divided into socioeconomic, household composition, minority status, and housing type and transportation themes. The Social Vulnerability Index and Social Vulnerability Index components were compared among patients by peripartum cardiomyopathy severity. RESULTS: Of 95 patients in the original cohort, 5 were excluded because of the use of a post office box address. Of the remaining 90 patients, 56 met severe peripartum cardiomyopathy criteria. At baseline, individuals with and without severe peripartum cardiomyopathy had similar ages, marital status, payor type, tobacco use, gestational age at delivery, and mode of delivery; however, individuals with severe peripartum cardiomyopathy were more likely to be Black (vs White) (59% vs 29%; P<.007) and less likely to recover ejection fraction (EF) to ≥55% by 12 months (36% vs 62%; P=.02) than individuals with less severe peripartum cardiomyopathy. Patients with severe peripartum cardiomyopathy were more likely to live in areas with a higher Social Vulnerability Index (0.51 vs 0.31; P=.002) and with more residents who were unemployed, impoverished, without a high school diploma, in single-parent households, of minority status, without a vehicle, and in institutionalized group quarters than patients with less severe peripartum cardiomyopathy. The median income was lower in communities of individuals with severe peripartum cardiomyopathy than in communities of individuals with less severe peripartum cardiomyopathy. CONCLUSION: Patients with severe peripartum cardiomyopathy outcomes were more likely to live in communities with greater social vulnerability than patients with less severe peripartum cardiomyopathy outcomes. To reduce disparities and maternal mortality rates, resources may need to be directed to socially vulnerable communities.

Early Gestational Diabetes Screening Based on ACOG Guidelines.

OBJECTIVE: A recent randomized controlled trial suggested that early gestational diabetes mellitus (GDM) screening in patients with obesity (body mass index [BMI] ≥30 kg/m2) does not improve perinatal outcomes. The American College of Obstetrics and Gynecology currently recommends early screening for gestational diabetes in patients who are overweight with one or more additional risk factors. We evaluated the effect of screening based on the number of additional risk factors for development of gestational diabetes. STUDY DESIGN: This was a secondary analysis of a multicenter randomized controlled trial of obese patients with singleton nonanomalous fetuses comparing early (14-20 weeks' gestation) with routine (24-28 weeks' gestation) GDM screening. Exclusion criteria were pregestational diabetes, major medical illnesses, bariatric surgery, chronic steroid use, and prior cesarean. Early versus routine GDM screening groups were compared and stratified by the number of additional risk factors for GDM (0, 1, 2, and ≥3). The primary outcome was an adverse perinatal composite outcome composed of: macrosomia, primary cesarean delivery, hypertensive disorders of pregnancy, shoulder dystocia, neonatal hyperbilirubinemia, and neonatal hypoglycemia. Analyses examined effects of early versus routine screening by the number of additional risk factors and their possible interaction on the incidences of the primary outcome and GDM. RESULTS: Of 913 patients, 5% had 0, 52% had 1, 33% had 2, and 10% had ≥3 additional risk factors. Baseline characteristics, including the number and type of risk factors, were similar between early and routine screening groups. Breslow-Day test for interaction between early versus routine screening and the number of additional risk factors was not significant for either the primary outcome (p = 0.37) or the diagnosis of GDM (p = 0.28). The incidence of GDM and the adverse perinatal composite outcome increased as the number of risk factors increased (p < 0.001). CONCLUSION: In patients with BMI ≥30 kg/m2 and additional risk factors, early GDM screening does not prevent adverse outcomes. KEY POINTS: · The ACOG currently recommends early screening for gestational diabetes if patients have risk factors.. · Even in patients with multiple risk factors, early screening for GDM does not improve outcomes.. · Patients with three or more risk factors may have worse outcomes if they undergo early screening..

Association of Maternal Body Mass Index and Maternal Morbidity And Mortality.

OBJECTIVE: This study aimed to assess the association of maternal body mass index (BMI) with a composite of severe maternal outcomes. STUDY DESIGN: Secondary analysis of a cohort of deliveries on randomly selected days at 25 hospitals from 2008 to 2011. Data on comorbid conditions, intrapartum events, and postpartum course were collected. The reference group (REF, BMI: 18.5-29.9kg/m2), obese (OB; BMI: 30-39.9kg/m2), morbidly obese (MO; BMI: 40-49.9kg/m2), and super morbidly obese (SMO; BMI ≥ 50kg/m2) women were compared. The composite of severe maternal outcomes was defined as death, intensive care unit (ICU) admission, ventilator use, deep venous thrombosis/pulmonary embolus (DVT/PE), sepsis, hemorrhage, disseminated intravascular coagulation (DIC), unplanned operative procedure, or stroke. Patients in the REF group were matched 1:1 with those in all other obesity groups based on propensity score using the baseline characteristics of age, race/ethnicity, previous cesarean, preexisting diabetes, chronic hypertension, parity, cigarette use, and insurance status. Multivariable Poisson's regression was used to estimate adjusted relative risks (aRRs) and 95% confidence intervals (CIs) for the association between BMI and the composite outcome. Because cesarean delivery may be in the causal pathway between obesity and adverse maternal outcomes, models were then adjusted for mode of delivery to evaluate potential mediation. RESULTS: A total of 52,162 pregnant patients are included in the analysis. Risk of composite maternal outcomes was increased for SMO compared with REF but not for OB and MO [OB: aRR=1.06, 95% CI: 0.99-1.14; MO: aRR=1.10, 95% CI: 0.97-1.25; SMO: aRR=1.32, 95% CI: 1.02-1.70]. However, in the mediation analysis, cesarean appears to mediate 46% (95% CI: 31-50%) of the risk of severe morbidity for SMO compared with REF. CONCLUSION: Super morbid obesity is significantly associated with increased serious maternal morbidity and mortality; however, cesarean appears to mediate this association. Obesity and morbid obesity are not associated with maternal morbidity and mortality. KEY POINTS: · Super morbid obesity is associated with increased morbidity.. · Cesarean appears to mediate the association between super morbid obesity and morbidity.. · Obesity and morbid maternal obesity are not associated with morbidity..

Prefusion F Protein-Based Respiratory Syncytial Virus Immunization in Pregnancy.

BACKGROUND: Respiratory syncytial virus (RSV), a major cause of illness and death in infants worldwide, could be prevented by vaccination during pregnancy. The efficacy, immunogenicity, and safety of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine in pregnant women and their infants are uncertain. METHODS: In a phase 2b trial, we randomly assigned pregnant women, at 24 through 36 weeks' gestation, to receive either 120 or 240 µg of RSVpreF vaccine (with or without aluminum hydroxide) or placebo. The trial included safety end points and immunogenicity end points that, in this interim analysis, included 50% titers of RSV A, B, and combined A/B neutralizing antibodies in maternal serum at delivery and in umbilical-cord blood, as well as maternal-to-infant transplacental transfer ratios. RESULTS: This planned interim analysis included 406 women and 403 infants; 327 women (80.5%) received RSVpreF vaccine. Most postvaccination reactions were mild to moderate; the incidence of local reactions was higher among women who received RSVpreF vaccine containing aluminum hydroxide than among those who received RSVpreF vaccine without aluminum hydroxide. The incidences of adverse events in the women and infants were similar in the vaccine and placebo groups; the type and frequency of these events were consistent with the background incidences among pregnant women and infants. The geometric mean ratios of 50% neutralizing titers between the infants of vaccine recipients and those of placebo recipients ranged from 9.7 to 11.7 among those with RSV A neutralizing antibodies and from 13.6 to 16.8 among those with RSV B neutralizing antibodies. Transplacental neutralizing antibody transfer ratios ranged from 1.41 to 2.10 and were higher with nonaluminum formulations than with aluminum formulations. Across the range of assessed gestational ages, infants of women who were immunized had similar titers in umbilical-cord blood and similar transplacental transfer ratios. CONCLUSIONS: RSVpreF vaccine elicited neutralizing antibody responses with efficient transplacental transfer and without evident safety concerns. (Funded by Pfizer; ClinicalTrials.gov number, NCT04032093.).

Effect of misoprostol on type 3 transformation zone of the cervix among Cameroonian women.

Background: Type 3 transformation zone (TZ) of the cervix has been shown to be associated with a four to five-fold increased risk of missed precancerous/cancerous lesions. The aim of this study was to evaluate the effect of intravaginal misoprostol on the TZ among women with Type 3 TZ in Cameroon. Materials and methods: A single dose of vaginal misoprostol (400 mcg or 600 mcg) was administered as part of the plan of care for women with Type 3 TZ during cervical cancer screening. The primary outcome was successful conversion from Type 3 TZ to Types 1 or 2 TZ. Descriptive analysis was performed using chi-square and Fisher's exact tests. Results: Among the 90 of 107 (84.2%) women who returned for re-evaluation of the cervix, 43 (47.8%, 95% CI: 0.36%-0.60%) had conversion of Type 3 TZ to Types 1 or 2. Women who received misoprostol 600 mcg were more likely to have their Type 3 TZs converted to Types 1 or 2 than women receiving 400 mcg (p = 0.037). Conclusion: Misoprostol converted approximately 50% of Type 3 TZ to Types 1 or 2 in Cameroon. Misoprostol is feasible in converting Type 3 TZ to Types 1 or 2 among Cameroonian women.

Prenatal Nicotine or Cannabis Exposure and Offspring Neurobehavioral Outcomes.

OBJECTIVE: To study the association between nicotine or cannabis metabolite presence in maternal urine and child neurodevelopmental outcomes. METHODS: We conducted a secondary analysis of two parallel multicenter randomized controlled trials of treatment for hypothyroxinemia or subclinical hypothyroidism among pregnant individuals enrolled at 8-20 weeks of gestation. All maternal-child dyads with a maternal urine sample at enrollment and child neurodevelopmental testing were included (N=1,197). Exposure was urine samples positive for nicotine (cotinine) or cannabis 11-nor-9-carboxy-delta-9-tetrahydrocannabinol [THC-COOH]) or both metabolites. Primary outcome was child IQ at 60 months. Secondary outcomes included cognitive, motor and language, attention, behavioral and social competency, and differential skills assessments at 12, 24, 36, and 48 months. Quantile regression analysis was performed with confounder adjustment. RESULTS: Of 1,197 pregnant individuals, 99 (8.3%) had positive cotinine samples and 47 (3.9%) had positive THC-COOH samples; 33 (2.8%) were positive for both. Groups differed in self-reported race and ethnicity, education, marital status, insurance, and thyroid status. Median IQ was similar between cotinine-exposed and -unexposed children (90 vs 95, adjusted difference in medians -2.47, 95% CI -6.22 to 1.29) and THC-COOH-exposed and -unexposed children (89 vs 95, adjusted difference in medians -1.35, 95% CI -7.76 to 5.05). In secondary outcome analysis, children with THC-COOH exposure compared with those unexposed had higher attention scores at 48 months of age (57 vs 49, adjusted difference in medians 6.0, 95% CI 1.11-10.89). CONCLUSIONS: Neither prenatal nicotine nor cannabis exposure was associated with a difference in IQ. Cannabis exposure was associated with worse attention scores in early childhood. Longitudinal studies assessing associations between child neurodevelopmental outcomes and prenatal nicotine and cannabis exposure with a focus on timing and quantity of exposure are needed. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00388297.

The Association of Cesarean Skin Incision Length and Postoperative Wound Complications.

OBJECTIVE: This study was aimed to evaluate the relationship between cesarean skin incision length and wound complications. STUDY DESIGN: Planned secondary analysis of a multicenter double-blind randomized trial of adjunctive azithromycin versus placebo (in addition to standard cefazolin) in women ≥24 weeks undergoing cesarean delivery during labor or ≥4 hours after membrane rupture. Skin incision length (cm) was measured just prior to skin closure. The primary outcome was a composite of wound complications (wound infection, separation, seroma, hematoma, or dehiscence) up to 6 weeks of postpartum. Individual components of the composite were examined as secondary outcomes. Outcomes were compared between groups defined by the lowest (≤25th), middle (25-75th) and highest (>75th) incision length quartiles. Logistic regression was used to adjust for potential confounding variables. RESULTS: Of the 2,013 women enrolled in the primary trial, 1,916 had recorded incision lengths and were included in this secondary analysis. The overall rate of composite wound complications was 7.8%. Median incision length was 15.0 cm (interquartile range: 14.0-16.5) with the lowest quartile defined as ≤14, middle as >14 to ≤16.5, and highest as >16.5 cm. Mean BMI, parity, use of staples, and duration of surgery differed significantly between the three incision length groups. In unadjusted analysis, the longest incision lengths were associated with an increased risk of the wound composite and wound infections (odds ratio [OR] = 2.27, 95% confidence interval [CI]: 1.43-3.60 and OR = 2.30, 95% CI: 1.27-4.15, respectively) compared with the shortest incision lengths. However, after multivariable adjustments, these associations were nullified. Additional analyses considering incision length as a continuous variable and using 10th/90th percentile cut-offs still did not suggest any associations with outcomes. CONCLUSION: Increasing skin incision length is not independently associated with an increased risk of postoperative wound complications. KEY POINTS: · After multivariable adjustments, skin incision length was not independently associated with an increased risk of postoperative wound complications.. · A reasonable incision length needed to safely perform the procedure should be used..

A systematic review of biomarkers associated with maternal infection in pregnant and postpartum women.

BACKGROUND: Serum biomarkers are commonly used to support the diagnosis of infection in non-pregnant patients whose clinical presentation suggests infection. The utility of serum biomarkers for infection in pregnant and postpartum women is uncertain. SEARCH STRATEGY: PubMed, CINAHL, EMBASE, ClinicalTrials.gov, Cochrane Library, CINAHL, and SCOPUS were searched from inception to February 2020. SELECTION CRITERIA: Full-text manuscripts in English were included if they reported the measurement of maternal serum biomarkers-and included a control group-to identify infection in pregnant and postpartum women. DATA COLLECTION AND ANALYSIS: two authors independently screened manuscripts, extracted data, and assessed methodologic quality. MAIN RESULTS: Interleukin-6 (IL-6), C-reactive protein, procalcitonin, insulin-like growth factor binding protein 1, tumor necrosis factor-α, calgranulin B, neopterin, and interferon-γ inducible protein 10 reliably indicated infection. Intercellular adhesion molecule 1, monocyte chemotactic and activating factor, soluble IL-6 receptor, and IL-8 were not useful markers in pregnant and postpartum women. CONCLUSIONS: Findings suggest that certain biomarkers have diagnostic value when maternal infection is suspected, but also confirms limitations in this population.

Misoprostol and estradiol to enhance visualization of the transformation zone during cervical cancer screening: An integrative review.

The purpose of this integrative literature review was to appraise studies conducted worldwide using misoprostol and estradiol in converting Type 3 transformation zone (TZ) of the cervix into Types 1 or 2 and to assess which regimen could be more feasible in low-and-middle-income countries (LMICs). We reviewed the English language literature for peer-reviewed studies that evaluated strategies to convert Type 3 TZs to Types 1 or 2 for cervical cancer screening. Web of Science and PubMed searches were performed up to July 2020. Search terms included: "cervical colposcopy," "inadequate colposcopy", "cervical cancer screening", "transformation zone," "estrogen", "estradiol", and "misoprostol." Inclusion criteria were articles published in the English language, original research, and peer reviewed articles. A total of 127 articles were abstracted, 24 articles were reviewed, and 9 articles met all inclusion criteria. We found that intravaginal misoprostol, intravaginal estradiol, and oral estradiol can successfully convert Type 3 TZ to Types 1 or 2. A single dose of vaginal misoprostol had a similar maximum response rate (20-80%) to a multi-dose regimen over several days or weeks of both intravaginal estradiol (64-83%) and oral estradiol (50-70%). Misoprostol administration was associated with more side effects such as abdominal cramping and vaginal bleeding compared to estradiol, although these were generally mild. In conclusion, Oral estradiol, intravaginal estradiol, and intravaginal misoprostol can be used to convert Type 3 TZ to Types 1 or 2. Intravaginal misoprostol is well tolerated and more feasible in LMICs due to availability and shorter treatment schedule compared to oral or intravaginal estradiol.

Outcomes in Twins Compared With Singletons Subsequent to Preterm Prelabor Rupture of Membranes.

OBJECTIVE: To compare maternal and neonatal outcomes after preterm prelabor rupture of membranes (PROM) from 23 to 34 weeks of gestation in twin compared with singleton gestations. METHODS: We conducted a secondary analysis of an obstetric cohort of 115,502 individuals and their singleton or twin neonates born in 25 hospitals nationwide (2008-2011). Those with preterm PROM from 23 0/7 through 33 6/7 weeks of gestation were included; neonates with major fetal anomalies were excluded. The coprimary outcomes for this analysis were composite maternal morbidity (chorioamnionitis, blood transfusion, postpartum endometritis, wound infection, sepsis, venous thromboembolism, intensive care unit admission, or death) and composite major neonatal morbidity (persistent pulmonary hypertension, intraventricular hemorrhage grade III or IV, seizures, hypoxic-ischemic encephalopathy, necrotizing enterocolitis stage II or III, bronchopulmonary dysplasia, stillbirth subsequent to admission, or neonatal death before discharge). Logistic regression was used to estimate unadjusted and adjusted odds ratios (ORs) with 95% CIs for twin compared with singleton gestations. RESULTS: Of 1,531 (1.3%) individuals who met eligibility criteria for this analysis, 218 (14.2%) had twin gestations. The median gestational age at preterm PROM was similar between those with twins and singletons (31.2 weeks [interquartile range 27.4-32.9] vs 30.6 weeks [interquartile range 26.9-32.7], P=.23); however, those with twin gestations had a shorter median latency period (2.0 days [interquartile range 1.0-5.0] vs 3.0 days [interquartile range 2.0-8.0], P<.001). After adjustment for potential confounders, odds of experiencing composite maternal morbidity (17.9% vs 19.3%, adjusted OR 0.97, 95% CI 0.66-1.42) or composite neonatal morbidity (20.4% vs 20.5%, OR 0.97, 95% CI 0.72-1.31) did not differ between groups. CONCLUSION: In a large, diverse cohort, the likelihood of composite maternal or neonatal morbidity per fetus after preterm PROM was similar for twin and singleton gestations.

Pathology findings among women with alterations in uterine bleeding patterns in cameroon.

PURPOSE: Endometrial cancer is on the rise in high-income countries but it has not been adequately studied in low-and-middle income countries especially in sub-Saharan Africa (SSA), likely due to scarce pathology facilities. The purpose of this study was to characterize and quantify the prevalence of endometrial hyperplasia or cancer in a cohort of women with abnormal uterine bleeding (AUB) who underwent endometrial biopsy in Cameroon. METHODS: We designed a cross-sectional study using medical records to characterize women who underwent endometrial biopsy in the Cameroon Baptist Convention Health Services (CBCHS) from 2008 to 2019. Pathologic diagnoses were classified as either endometrial hyperplasia, endometrial cancer, or no endometrial hyperplasia/cancer. We reported the overall prevalence of endometrial hyperplasia or cancer. Bivariate analyses compared patient characteristics between women with endometrial cancer, endometrial hyperplasia, and neither. RESULTS: The average age was 46.2 years and women had an average of 5.1 parity. We found that, 61 [(36.7% of 166 women; 95% CI (27.6-47.0%)] had endometrial hyperplasia or cancer. There were no cases of hyperplasia with atypia and 13 women had endometrial cancer. The remainder were comprised of benign or infectious pathologic findings. In bivariate analysis, mean ages were statistically different among the three groups (hyperplasia, cancer, and no hyperplasia/cancer), p < 0.001, and women with cancer had the highest age. Parity was statistically significantly different among the three groups (p = 0.002) and women with endometrial cancer had higher parity. CONCLUSION: We found that just over 1 in 3 women with AUB who underwent endometrial biopsy at a health system in SSA were found to have pathologic findings of endometrial hyperplasia or cancer, with no cases of hyperplasia with atypia. Women with endometrial cancer had higher mean age and parity.

Intrapartum opioid analgesia and childhood neurodevelopmental outcomes among infants born preterm.

BACKGROUND: There are concerns regarding neurobehavioral changes in infants exposed to parenteral opioids during labor; however, long-term neurodevelopment remains unstudied. OBJECTIVE: We aimed to examine the association between parenteral opioids used as labor analgesia and perinatal outcomes and childhood neurodevelopment until 2 years of age among infants born prematurely. We hypothesized that intrapartum exposure to parenteral opioids is associated with impaired neurodevelopment and adverse perinatal outcomes. STUDY DESIGN: This was a secondary analysis of a multicenter, randomized controlled trial assessing magnesium for the prevention of cerebral palsy in infants at risk for preterm birth. Women delivering a singleton, nonanomalous, live infant before 37 weeks' gestation were considered for inclusion. Women were excluded if they had missing exposure or primary outcome data, were exposed to general anesthesia, or reported use of heroin or unspecified illicit drugs. Women reporting use of nonopioid illicit drugs such as cocaine and marijuana were not excluded. Groups were compared based on exposure or nonexposure to parenteral opioids (intravenous or intramuscular) used as labor analgesia. The primary outcome was any psychomotor or mental developmental delay at 24 months according to the Bayley Scales of Infant Development II. Secondary outcomes were the Bayley Scales of Infant Development II subdomains and adverse perinatal outcomes. Multivariable logistic regression models were performed and adjusted odds ratios with 95% confidence intervals were estimated. RESULTS: Of the 1404 women included, 535 (38%) received parenteral opioids as labor analgesia. Women receiving parenteral opioids were more likely to be younger, Hispanic, and present with cervical dilation ≥4 cm. Parenteral opioid recipients had lower rates of illicit nonopioid drug or tobacco use, a lower rate of cesarean delivery, lower educational level and were less likely to be undergoing induction. Women receiving parenteral opioids who underwent cesarean delivery were less likely to do so because of a nonreassuring fetal status. In the unadjusted and adjusted analyses, there were no significant differences in the primary outcomes of psychomotor or mental developmental delay at 2 years of age (adjusted odds ratio, 0.96; confidence interval, 0.76-1.20). The only significant difference in secondary outcomes was a shorter O2 requirement duration in the parenteral opioid group (2 vs 4 days; P=.002). CONCLUSION: Among a population of preterm infants vulnerable to neurologic impairment, intrapartum exposure to parenteral opioids was not associated with an increased risk for neurodevelopmental delay up to 2 years of age, nor did these infants have worse perinatal outcomes.

Predicting long-term neurodevelopmental outcomes in very preterm neonates by umbilical cord gas parameters.

BACKGROUND: The predictive value of acidemia at birth on long-term neurodevelopmental outcomes remains poorly understood, especially in preterm neonates. OBJECTIVE: This study aimed to assess the relationship between the umbilical artery acid-base status and major neurodevelopmental disability at an age of between 5 and 8 years among children born very prematurely. STUDY DESIGN: We performed a secondary analysis of the data from a follow-up study of a prospective cohort of 457 children aged between 23 weeks and 31 weeks and 6 days from 1996 to 2001. Arterial cord gas parameters that were <10th percentile in the original cohort of 457 neonates (ie, pH of <7.1, base deficit of <-8.6 mEq/L, and a partial pressure of CO2 of >77 mm Hg) were considered abnormal. Sensitivity analyses considered alternative definitions for abnormal cord gases including a pH of <7.0 or base deficit of <-12 mEq/L. The primary outcome was a composite of major neurodevelopmental disability, including an intelligence quotient score of <70, cerebral palsy, blindness, deafness, abnormal balance, impaired cognition, dystonia, and seizure disorder. A logistic regression analysis was used to adjust for race and caregiver intelligence quotient score and, in an additional analysis, for gestational age. RESULTS: A total of 259 of 261 maternal-infant dyads were evaluated at a mean child age of 6.8 years, with complete umbilical cord gas data for 228 of those. Infants with an abnormal pH and a base deficit (defined above) were over 4-fold more likely to have the composite disability and an intelligence quotient score of <70. These increased odds persisted after adjusting for age and caregiver intelligence quotient score, but when considering gestational age as well, none of the umbilical cord gas parameters significantly predicted the presence of the composite disability or an intelligence quotient score of <70. However, when using the stricter umbilical cord gas criteria (ie, pH of <7.0 and a base deficit of <-12 mEq/L), a base deficit of <-12 mEq/L was independently associated with both neurodevelopmental disability and an intelligence quotient score of <70. CONCLUSION: When defined more strictly, abnormal umbilical cord gases, specifically a base deficit of <-12 mEq/L, are associated with an increased risk for major long-term neurodevelopmental disability and an intelligence quotient score of <70 in children born very prematurely.

Chlamydia Prevalence by Age and Correlates of Infection Among Pregnant Women.

BACKGROUND: There is a paucity of population-based data on chlamydia in pregnancy despite rising rates in US women. Our objectives were to assess chlamydia prevalence by age group and to identify factors associated with infection in pregnant women to inform screening guidelines. METHODS: This cross-sectional study included pregnant women tested for chlamydia who delivered at the University of Alabama at Birmingham between November 1, 2012, and December 31, 2017. The primary outcome was chlamydia prevalence, defined as a positive urogenital chlamydia nucleic acid amplification test result documented in the electronic medical record. Multivariable logistic regression was used to identify factors associated with infection. RESULTS: Among 17,796 women who delivered during the study period, 13,657 (77%) had chlamydia testing performed at the University of Alabama at Birmingham. Chlamydia prevalence (95% confidence interval) was 7.4% (7.0%-7.9%). Age-stratified prevalence rates were 14.6%, 4.3%, and 1.7% for women younger than 25 years, 25 to 29 years, and 30 years or older, respectively. Chlamydia in pregnancy remained strongly associated with age (adjusted odds ratio [95% confidence interval], 7.2 [5.6-9.2] for age <25 years, and 2.3 [1.7-3.0] for ages 25-29 years, when compared with >30 years) after adjustment for race, urban residence, and insurance status. CONCLUSIONS: Among pregnant women living in the southeastern United States, chlamydia was detected in 1 of 14 women who were tested. Chlamydia positivity was highest among women younger than 30 years. Study findings support broad screening for chlamydia in pregnancy.