Researching COVID to enhance recovery (RECOVER) pregnancy study: Rationale, objectives and design.

IMPORTANCE: Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER-Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads. METHODS: RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators. DISCUSSION: RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

The association between a single abnormal glucose and fetal c-peptide.

AIM: We aimed to evaluated if fetuses of subjects with one elevated value on the 3-h GTT had a measurable physiologic difference in fetal C-peptide levels as compared to those with no elevated values on the GTT. METHODS: We performed a prospective cohort study to evaluate insulin levels in singleton non-anomalous fetuses of subjects with one elevated value on the GTT as compared to subjects with no elevated values on their GTT. Fetal insulin levels were measured by fetal C-peptide in cord blood. Distribution of data was assessed and outliers representing values > the 99th and < the 1st percentiles were excluded. Data were log transformed to achieve normal distribution and univariable analyses were performed to compare fetal C-peptide levels, baseline maternal characteristics and perinatal outcomes in subjects with one elevated value as compared those with no elevated values. RESULTS: Our analysis included 99 subjects, with 49 subjects in the one elevated value group and 50 subjects in the no elevated values group. Fetal C-peptide levels (picomoles per liters, pmol/L), were significantly higher in the elevated value group as compared to the no elevated value group (mean ± SD; 4.6 ± 0.8 vs. 4.3 ± 0.7, P = 0.046, respectively). In univariable analysis, there was no significant difference in maternal characteristics or adverse composite perinatal outcomes. CONCLUSION: Fetuses of subjects who had one elevated value on their GTT had a measurable physiologic difference in C-peptide levels as compared to fetuses of subjects with no elevated values on the GTT.

Researching COVID to enhance recovery (RECOVER) pregnancy study: Rationale, objectives and design.

Importance: Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER- Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads. Methods: RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators. Discussion: RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero. Registration: NCT05172024.

Low first-trimester fetal fraction is associated with chronic inflammation in the placenta.

BACKGROUND: Some data suggest an association between abnormal fetal fraction on noninvasive prenatal screening and adverse pregnancy outcomes, including low birthweight, preeclampsia, and preterm birth in the absence of aneuploidy. These findings suggest that abnormal fetal fraction may be associated with placental pathologic processes in early gestation. OBJECTIVE: This study aimed to determine the independent association of fetal fraction on genetic noninvasive prenatal screening with histologic placental types. STUDY DESIGN: This was a retrospective cohort study at a single institution in the period between January 2017 and March 2021, including live births at ≥24 weeks for which noninvasive prenatal screening was performed and placental pathology results were available. Results were stratified by trimester of noninvasive prenatal screening. Clinical characteristics were compared by quartile of fetal fraction using chi-square tests. Linear regression was used to model continuous fetal fraction as a function of 3 histologic types representing chronic placental injury-chronic inflammation, maternal vascular malperfusion, and fetal vascular malperfusion. Inverse probability weighting was used to account for selection bias in characteristics of patients with placental pathology examination. RESULTS: A total of 1374 patients had noninvasive prenatal screening in the first trimester and 262 in the second trimester. Preterm birth and hypertensive disorders of pregnancy were most common in the lowest quartile of fetal fraction. Chronic inflammation was associated with a 0.56 percentage point reduction in fetal fraction (95% confidence interval, -0.95 to -0.16), and maternal vascular malperfusion was associated with a 0.48 percentage point reduction in fetal fraction (95% confidence interval, -0.91 to -0.04) in adjusted models. The association with maternal vascular malperfusion was no longer statistically significant after accounting for selection bias in placentas sent for pathologic examination. Second-trimester fetal fraction was not associated with placental pathology. CONCLUSION: Chronic inflammation is associated with lower first-trimester fetal fraction even after accounting for selection bias. Higher fetal fraction in the second trimester was associated with fetal vascular pathology, although this association was no longer statistically significant after inverse probability weighting to account for selection bias. First-trimester fetal fraction may be a biomarker of adverse outcomes associated with chronic inflammation.

Long-Term Maternal Metabolic and Cardiovascular Phenotypes after a Pregnancy Complicated by Mild Gestational Diabetes Mellitus or Obesity.

OBJECTIVE: The aim of this study was to evaluate the association of mild gestational diabetes mellitus (GDM) and obesity with metabolic and cardiovascular markers 5 to 10 years after pregnancy. STUDY DESIGN: This was a secondary analysis of 5- to 10-year follow-up study of a mild GDM treatment trial and concurrent observational cohort of participants ineligible for the trial with abnormal 1-hour glucose challenge test only. Participants with 2-hour glucose tolerance test at follow-up were included. The primary exposures were mild GDM and obesity. The outcomes were insulinogenic index (IGI), 1/homeostatic model assessment of insulin resistance (HOMA-IR), and cardiovascular markers vascular endothelial growth factor, (VEGF), vascular cell adhesion molecule 1 (VCAM-1), cluster of differentiation 40 ligand (CD40L), growth differentiation factor 15 (GDF-15), and suppression of tumorgenesis 2 (ST-2). Multivariable linear regression estimated the association of GDM and obesity with biomarkers. RESULTS: Of 951 participants in the parent study, 642 (68%) were included. Lower 1/HOMA-IR were observed in treated and untreated GDM groups, compared with non-GDM (mean differences, -0.24 and -0.15; 95% confidence intervals [CIs], -0.36 to -0.12 and -0.28 to -0.03, respectively). Lower VCAM-1 (angiogenesis) was observed in treated GDM group (mean difference, -0.11; 95% CI, -0.19 to -0.03). GDM was not associated with IGI or other biomarkers. Obesity was associated with lower 1/HOMA-IR (mean difference, -0.42; 95% CI, -0.52 to -0.32), but not other biomarkers. CONCLUSION: Prior GDM and obesity are associated with more insulin resistance but not insulin secretion or consistent cardiovascular dysfunction 5 to 10 years after delivery. KEY POINTS: · Mild GDM increases the risk of insulin resistance 5 to 10 years postpartum but not pancreatic dysfunction.. · Obesity increases the risk of insulin resistance 5 to 10 years postpartum but not pancreatic dysfunction.. · Neither mild GDM nor obesity increased the risk of cardiovascular dysfunction 5 to 10 years postpartum..

The Association between Maternal Body Mass Index and the Risk of Perinatal Depression.

OBJECTIVE: The aim of this study was to evaluate whether the risk of perinatal depression is associated with body mass index (BMI) category. STUDY DESIGN: We performed a retrospective cohort study of women who completed an Edinburgh Postnatal Depression Scale (EPDS) questionnaire during the antepartum period at an integrated health system from January 2003 to May 2018. Risk of perinatal depression was defined as a score of ≥10 on the EPDS or an affirmative response to thoughts of self-harm. Risk of perinatal depression was compared by first trimester BMI category, defined as underweight (BMI: <18.5 kg/m2), normal weight (BMI: 18.5-24.9 kg/m2), overweight (BMI: 25.0-29.9 kg/m2), or obese (BMI: ≥30.0 kg/m2). Univariable analyses were performed using χ 2, Fisher's exact test, analysis of variance, Kruskal-Wallis, and Wilcoxon rank-sum tests as appropriate to evaluate the association between maternal BMI category, demographic and clinical characteristics, and risk of perinatal depression. Logistic multivariable regression models were performed to adjust for potential confounders identified as variables with p < 0.10 in univariable analysis. RESULTS: Our analysis included 3,420 obese women, 3,839 overweight women, 5,949 normal weight women, and 1,203 underweight women. The overall median gestational age at EPDS administration was 27 weeks (interquartile range: 23-29). Overweight and obese women were more likely to be non-Hispanic Black, Hispanic, multiparous, to have public insurance, prepregnancy diabetes, and chronic hypertension as compared with normal or underweight women (p < 0.001). In univariable analysis, the risk of perinatal depression was not significantly different among underweight (10.8%, odds ratio [OR]: 0.86, 95% confidence interval [CI]: 0.79-1.18) or overweight women (12%, OR: 0.96, 95% CI: 0.79-1.18); however, the risk was higher among obese women (14.7%, 95% CI: 1.21-1.55) compared with normal weight women (11.2%). In multivariable analysis, obesity remained associated with an increased risk of perinatal depression (adjusted OR: 1.19, 95% CI: 1.04-1.35). CONCLUSION: Obesity is associated with an increased risk of perinatal depression as compared with women of normal weight. KEY POINTS: · Maternal obesity is associated with an increased risk of perinatal depression.. · Maternal BMI is associated with increased risk of perinatal depression.. · Maternal obesity is an independent risk factor for perinatal depression..

AWHONN postpartum discharge education: patient knowledge and sustainability.

OBJECTIVE: The objective is to evaluate whether the implementation of the Association of Women's Health, Obstetric and Neonatal Nurses (AWHONN) postpartum discharge educational initiative is associated with improved patient knowledge of warning signs of severe maternal morbidity (SMM) and if the initiative is self-sustaining. DESIGN: A pre-post design was used to evaluate patient knowledge of warning signs of SMM (Plan-Do-Study-Act, PDSA cycle 1) and if the quality improvement initiative was self-sustaining (PDSA cycle 2). Patient understanding of warning signs of SMM prior to initiation of the AWHONN education (Usual Discharge) was compared with understanding of those who were discharged after implementation (POST-BIRTH discharge). The initiative was designed to be self-sustaining. The POST-BIRTH flyer describes nine warning signs of SMM. Eligible participants were English-speaking patients discharged with a live newborn who were able to be contacted within 2 weeks. Participants completed a telephone administered nine-item survey to assess knowledge of SMM. The primary outcome was the percentage of correct answers. To evaluate sustainability, whether the POST-BIRTH fliers and discharge checklist were still being used at 19 months postinitiative was planned. RESULTS: For PDSA cycle 1, in the Usual Discharge group, 347 patients were discharged, 164 (44.7%) were eligible and 151 (92.1%) completed the survey. In the POST-BIRTH discharge group, 268 patients were discharged, 199 (74.3%) were eligible and 183 (92.0%) completed the survey. Compared with the Usual Discharge group, the POST-BIRTH group had significantly more correct responses (30% vs 60%, p<0.001). In PDSA cycle 2, POST-BIRTH flyers were still being used universally on one of the two floors from which postpartum patients are discharged, but not the other. CONCLUSION: The implementation of an educational initiative for postpartum patients is associated with improved knowledge of warning signs of SMM. The use of the education was self-sustaining on one discharge floor but not the other.

Maternal Diabetes and Intrapartum Fetal Electrocardiogram.

OBJECTIVE: Fetal electrocardiogram (ECG) ST changes are associated with fetal cardiac hypoxia. Our objective was to evaluate ST changes by maternal diabetic status and stage of labor. METHODS: This was a secondary analysis of a multicentered randomized-controlled trial in which laboring patients with singleton gestations underwent fetal ECG scalp electrode placement and were randomly assigned to masked or unmasked ST-segment readings. Our primary outcome was the frequency of fetal ECG tracings with ST changes by the stage of labor. ECG tracings were categorized into mutually exclusive groups (ST depression, ST elevation without ST depression, or no ST changes). We compared participants with DM, gestational diabetes mellitus (GDM), and no DM. RESULTS: Of the 5,436 eligible individuals in the first stage of labor (95 with pregestational DM and 370 with GDM), 4,427 progressed to the second stage. ST depression occurred more frequently in the first stage of labor in participants with pregestational DM (15%, adjusted odds ratio [aOR] 2.20, 95% confidence interval [CI] 1.14-4.24) and with GDM (9.5%, aOR 1.51, 95% CI 1.02-2.25) as compared with participants without DM (5.7%). The frequency of ST elevation was similar in participants with pregestational DM (33%, aOR 0.79, 95% CI 0.48-1.30) and GDM (33.2%, aOR 0.91, 95% CI 0.71-1.17) as compared with those without DM (34.2%). In the second stage, ST depression did not occur in participants with pregestational DM (0%) and occurred more frequently in participants with GDM (3.5%, aOR 2.01, 95% CI 1.02-3.98) as compared with those without DM (2.0%). ST elevation occurred more frequently in participants with pregestational DM (30%, aOR 1.81, 95% CI 1.02-3.22) but not with GDM (19.0%, aOR 1.06, 95% CI 0.77-1.47) as compared with those without DM (17.8%). CONCLUSION: ST changes in fetal ECG occur more frequently in fetuses of diabetic mothers during labor. CLINICALTRIALS: gov number, NCT01131260. PRECIS: ST changes in fetal ECG, a marker of fetal cardiac hypoxia, occur more frequently in fetuses of diabetic parturients. KEY POINTS: · Fetal hypertrophic cardiomyopathy (HCM) and cardiac dysfunction occur frequently among fetuses of diabetic patients.. · Fetal ECG changes such as ST elevation and depression reflect cardiac hypoxia.. · Fetuses of diabetic patients demonstrate a higher prevalence of fetal ECG tracings with ST changes..

Discontinuation of Oxytocin in the Second Stage of Labor and its Association with Postpartum Hemorrhage.

OBJECTIVE: The objective of the study was to evaluate whether patients with oxytocin discontinued during the second stage of labor (≥30 minutes prior to delivery) had a lower rate of postpartum hemorrhage (PPH) compared with those with oxytocin continued until delivery or discontinued <30 minutes prior to delivery. STUDY DESIGN: Retrospective cohort study was performed from August 1, 2014 to July 31, 2019. Singleton pregnancies of 24 to 42 weeks gestation were included if they reached the second stage of labor and received oxytocin during labor. Patients on anticoagulants were excluded. Patients with oxytocin discontinued ≥30 minutes prior to delivery represented STOPPED and those with oxytocin continued until delivery or discontinued <30 minutes prior to delivery represented CONTINUED. Patient data were abstracted from the electronic medical record. The primary outcome was PPH (≥1,000 mL blood loss). Univariable analyses were performed to compare groups. Multi-variable logistic regression was performed to adjust for prespecified confounders. Planned sub-group analyses by the route of delivery were performed. RESULTS: Of 10,421 total patients, 1,288 had oxytocin STOPPED and 9,133 had oxytocin CONTINUED. There were no significant differences in age, race, or ethnicity, body mass index, public insurance, gestational diabetes, or pregnancy-induced hypertension between STOPPED and CONTINUED. The PPH rate was 15.2 and 5.7% in STOPPED and CONTINUED, respectively (p < 0.001). After adjusting for confounders, STOPPED remained at higher odds for PPH (adjusted odds ratio 2.859, 95% confidence interval 2.394, 3.414, p < 0.001). Among cesarean deliveries only, there was no significant difference in the rate of PPH between STOPPED and CONTINUED (38.0 vs. 36.4%, respectively, p = 0.730). However, among vaginal deliveries, the rate of PPH was actually lower in STOPPED than CONTINUED (3.4 vs. 5.2%, respectively, p = 0.024). CONCLUSION: The rate of PPH was higher in patients with oxytocin STOPPED compared with CONTINUED. However, among vaginal deliveries, there was a significantly lower rate of PPH in STOPPED. These disparate findings may be explained by the variable impact of second-stage oxytocin on PPH as a function of delivery type. KEY POINTS: · It is unclear if oxytocin use in the second stage of labor may independently increase the risk of hemorrhage.. · Patients with oxytocin discontinued during the second stage of labor had a higher rate of PPH.. · PPH was significantly lower among vaginal deliveries in patients with oxytocin discontinued..

Circulating Angiogenic Factor Levels in Hypertensive Disorders of Pregnancy.

Circulating Angiogenic Factor in Hypertension in PregnancyThis study measured serum soluble fms-like tyrosine kinase 1 to placental growth factor values in pregnant women hospitalized with hypertension. In women with a hypertensive disorder of pregnancy presenting between 23 and 35 weeks' gestation, a soluble fms-like tyrosine kinase 1:placental growth factor ratio ≥40 provided stratification of the risk of progressing to severe preeclampsia within 2 weeks.

The association between persistent maternal hypotension and small for gestational age neonates.

BACKGROUND: The association between maternal hypotension and poor fetal growth has not been well studied. OBJECTIVE: We hypothesized that the presence of persistent maternal hypotension will reflect a chronic reduction of uteroplacental blood flow, leading to placental hypoperfusion and subsequent poor fetal growth. We aimed to evaluate whether persistent hypotension is associated with the risk of having a small for gestational age neonate. A secondary aim was to evaluate whether transient hypotension is associated with the same risk of having a small for gestational age neonate. STUDY DESIGN: We performed a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be data, a large prospective cohort study of nulliparous women. The inclusion criteria included delivery of subjects with singleton pregnancies at ≥24 weeks' gestation who had systolic and diastolic blood pressure data at 3 antenatal visits between 6 0/7 and 29 6/7 weeks' gestation. Univariable analyses were performed to evaluate the association among persistent hypotension (systolic blood pressure of <100 mm Hg and or diastolic blood pressure of <60 mm Hg at 3 antenatal visits), transient hypotension (systolic blood pressure <100 mm Hg and diastolic blood pressure <60 mm Hg at any 1 of 3 aforementioned visits but not all 3), maternal characteristics and small for gestational age neonates. Variables found to be significant (P<.05) were included in multivariable logistic regression. RESULTS: Here, 164 of 7233 participants (2.3%) had persistent hypotension. In univariable analyses, subjects with persistent hypotension compared with those without were significantly more likely to have small for gestational age neonates (21.3% vs 11.6%; P<.001). When adjusting for confounders, persistent hypotension remained significantly associated with an increased risk of having a small for gestational age neonate (adjusted odds ratio, 1.65; 95% confidence interval, 1.11-2.44). In multivariable analysis, transient hypotension was not associated with an increased risk of having a small for gestational age neonate. CONCLUSION: Persistent hypotension was significantly associated with small for gestational age among neonates born to low-risk nulliparous women.

Elevated Glucose Challenge Test in a Nondiabetic Index Pregnancy and Gestational Diabetes in a Subsequent Pregnancy.

OBJECTIVE: The aim of this study was to evaluate whether a 1-hour glucose challenge test (GCT) ≥140 mg/dL in a nondiabetic index pregnancy is associated with the development of gestational diabetes mellitus (GDM) in a subsequent pregnancy. STUDY DESIGN: We performed a retrospective cohort study from a single institution from June 2009 to December 2018. Women with a nondiabetic index singleton gestation who underwent a 1-hour GCT at 24 to 28 weeks and had a successive singleton delivery were included. GDM was defined by a 1-hour GCT of ≥ 200 mg/dL, ≥2 of 4 elevated values on a 3-hour GCT, or a diagnosis of GDM defined by International Classification of Disease codes in the electronic medical record. Univariable analyses were performed to evaluate the associations between an elevated 1-hour GCT result in the index pregnancy, maternal characteristics, and the development of GDM in the subsequent pregnancy. Variables found to be significant (p < 0.05) were included in multivariable analysis. RESULTS: A total of 2,423 women were included. Of these, 340 (14.0%) had an elevated 1-hour GCT in the index pregnancy. Women with an elevated 1-hour GCT in the index pregnancy compared with those without were significantly more likely to be older, married, privately insured, of Hispanic ethnicity or Asian race, chronically hypertensive, have a higher body mass index (BMI), have a shorter inter-pregnancy interval, and to develop GDM in the subsequent pregnancy (14.4 vs. 3.3%, p < 0.001). In multivariable analysis, an elevated 1-hour GCT (adjusted odds ratio [aOR]: 4.54, 95% confidence interval [CI]: 3.02-6.81), first-trimester BMI ≥30 kg/m2 in the index pregnancy (aOR: 3.10, 95% CI: 2.03-4.71), Asian race (aOR: 2.96, 95% CI: 1.70-5.12), Hispanic ethnicity (aOR: 2.11, 95% CI: 1.12-4.00), and increasing age (aOR: 1.07, 95% CI: 1.02-1.12) were significantly associated with an increased risk of GDM in the subsequent pregnancy. CONCLUSION: An elevated 1-hour GCT in a nondiabetic index pregnancy is associated with a fourfold increased risk of GDM in a subsequent pregnancy. KEY POINTS: · An abnormal 1 hour GCT in an index pregnancy is associated with GDM in a subsequent pregnancy.. · An abnormal 1 hour GCT may be an independent risk factor for GDM in a subsequent pregnancy.. · An abnormal 1 hour GCT is associated with a 4 fold increased risk of GDM in a subsequent pregnancy..

Association of Breastfeeding and Child IQ Score at Age 5 Years.

OBJECTIVE: To evaluate whether breastfeeding and its duration are associated with a reduced risk of low IQ scores or other neurodevelopmental problems. METHODS: We conducted a secondary analysis of two parallel multicenter, double-blinded randomized controlled trials in which participants with a singleton pregnancy and either subclinical hypothyroidism or hypothyroxinemia were treated with thyroxine or placebo. Our primary outcome was a low IQ score (less than 85 on the WPPSI-III [Wechsler Preschool and Primary Scale of Intelligence III] at age 5 years). Secondary outcomes included performance measures on other validated neurodevelopmental tests. Univariable and multivariable analyses were performed to evaluate the association between breastfeeding and neurodevelopmental outcomes. Stepwise backward proceeding linear and logistic regression models were used to develop the final adjusted models. RESULTS: Of the 772 participants studied, 614 (80%) reported breastfeeding. Of these, 31% reported breastfeeding for less than 4 months, 19% for 4-6 months, 11% for 7-9 months, 15% for 10-12 months and 23% for more than 12 months. IQ scores were available for 756 children; mean age-5 scores were higher with any breastfeeding (96.7±15.1) than without (91.2±15.0, mean difference 5.5, 95% CI 2.8-8.2), and low IQ scores were less frequent with any breastfeeding (21.5%) than with no breastfeeding (36.2%, odds ratio 0.48, 95% CI 0.33-0.71). In adjusted analyses, breastfeeding remained associated with reduced odds of low IQ score (adjusted odds ratio [aOR] 0.62, 95% CI 0.41-0.93), and each additional month of breastfeeding was associated with lower odds of a low IQ scores (aOR 0.97, 95% CI 0.939-0.996). No significant associations between breastfeeding and other neurodevelopmental outcomes were identified in adjusted analyses. CONCLUSION: Breastfeeding and its duration are associated with lower odds of low IQ score at age 5 years.

Post-Cesarean Opioid Use after Implementation of Enhanced Recovery after Surgery Protocol.

OBJECTIVE: This study aimed to evaluate whether implementation of an enhanced recovery after surgery (ERAS) protocol is associated with lower maternal opioid use after cesarean delivery (CD). STUDY DESIGN: We performed a pre- and postimplementation (PRE and POST, respectively) study of an ERAS protocol for cesarean deliveries. ERAS is a multimodal, multidisciplinary perioperative approach. The four pillars of our protocol include education, pain management, nutrition, and early ambulation. Patients were counseled by their outpatient providers and given an educational booklet. Pain management included gabapentin and acetaminophen immediately prior to spinal anesthesia. Postoperatively patients received scheduled acetaminophen and ibuprofen. Oxycodone was initiated as needed 24 hours after spinal analgesia. Preoperative diet consisted of clear carbohydrate drink consumed 2 hours prior to scheduled operative time with advancement as tolerated immediately postoperation. Women with a body mass index (BMI) <40 kg/m2 and scheduled CD were eligible for ERAS. PRE patients were randomly selected from repeat cesarean deliveries (RCDs) at a single site from October 2017 to September 2018, BMI <40 kg/m2, without trial of labor. The POST cohort included women who participated in ERAS from October 2018 to June 2019. PRE and POST demographic and clinical characteristics were compared. Primary outcome was total postoperative morphine milligram equivalents (MMEs). Secondary outcomes included length of stay (LOS) and maximum postoperative day 2 (POD2) pain score. RESULTS: All women in PRE (n = 70) had RCD compared with 66.2% (49/74) in POST. Median total postoperative MMEs were 140.0 (interquartile range [IQR]: 87.5-182.5) in PRE compared with 0.0 (IQR: 0.0-72.5) in POST (p < 0.001). Median LOS in PRE was 4.02 days (IQR: 3.26-4.27) compared with 2.37 days (IQR: 2.21-3.26) in POST (p < 0.001). Mean maximum POD2 pain score was 5.28 (standard deviation [SD] = 1.86) in PRE compared with 4.67 (SD = 1.63) in POST (p = 0.04). CONCLUSION: ERAS protocol was associated with decreased postoperative opioid use, shorter LOS, and decreased pain after CD. KEY POINTS: · ERAS protocol was associated with decreased postoperative opioid use after CD.. · ERAS protocol was associated with shorter length of stay after CD.. · ERAS protocol was associated with decreased postoperative pain after CD..

The association between personal weight gain goals, provider recommendations, and appropriate gestational weight gain.

BACKGROUND: Nearly half of all women exceed the 2009 Institute of Medicine guidelines for gestational weight gain. Excess gestational weight gain is associated with adverse pregnancy outcomes. OBJECTIVE: Our objective was to determine whether having a personal gestational weight gain goal consistent with the Institute of Medicine's recommendations for appropriate gestational weight gain and whether having a discussion with one's obstetrical provider regarding that goal were associated with appropriate gestational weight gain. STUDY DESIGN: This is a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be study, a prospective cohort study of nulliparous women. We asked women at their first study visit (between 6 and 13 weeks' gestation) whether they had a gestational weight gain goal and what that goal was. Furthermore, we asked whether their provider discussed a gestational weight gain goal and what that goal was. We classified personal and provider-recommended gestational weight gain goals as consistent or inconsistent with the Institute of Medicine guidelines, taking into account a woman's initial body mass index category (underweight, normal weight, overweight, and obese). We included women with live singleton term deliveries (between 37 and 43 weeks' gestation) in this analysis. We classified the primary outcome, which was gestational weight gain (defined as the difference between first visit weight and final weight before delivery), as inadequate, appropriate, or excessive, based on the Institute of Medicine guidelines and initial body mass index category. We used Student t, Wilcoxon rank-sum, and chi-square tests for bivariable analyses, and multinomial logistic regression was performed to control for confounding variables. RESULTS: Of 6727 eligible women, 3799 (56.5% of all eligible women) stated they had a gestational weight gain goal. Of the 3799 women with a stated goal, 2589 (38.5% of all women) had a goal consistent with the Institute of Medicine's recommendations. In addition, of the 6727 eligible women, 2188 (32.5%) reported that they discussed gestational weight gain with their provider, and 1548 of these (23.0% of all women) recalled that their provider gave a gestational weight gain goal in accordance with the Institute of Medicine guidelines. Although having any gestational weight gain goal was not associated with appropriate gestational weight gain, having a gestational weight gain goal that was consistent with the Institute of Medicine's recommendations was associated with a reduced risk of excessive (adjusted relative risk ratio, 0.77; 95% confidence interval, 0.64-0.92) and inadequate weight gain (adjusted relative risk ratio, 0.66; 95% confidence interval, 0.53-0.82). Conversely, discussing gestational weight gain goals with a provider was not associated with either inadequate or excessive gestational weight gain even if the provider's recommendations for gestational weight gain were consistent with the guidelines. CONCLUSION: Nulliparas who delivered singleton pregnancies at term who had a personal gestational weight gain goal consistent with the Institute of Medicine's recommendations were less likely to have excessive or inadequate gestational weight gain. Further study is required to evaluate the most effective way to communicate this information to patients.

Complications associated with second trimester inductions of labor requiring greater than five doses of misoprostol.

OBJECTIVE: To evaluate outcomes associated with induction at 14 weeks 0 days-23 weeks 6 days gestation that require five or less vs. six or more misoprostol doses. STUDY DESIGN: We performed a retrospective study of vaginal misoprostol inductions from January 2003 to February 2016 to assess complications based on number of misoprostol doses. RESULTS: Among 390 women receiving five or fewer doses and 78 women receiving six or more doses, we found similar rates of chorioamnionitis, postpartum hemorrhage, transfusion and retained placenta. CONCLUSION: Complication rates were comparable in women receiving more than five versus less than five misoprostol doses for labor induction in the second trimester. IMPLICATIONS: Women undergoing second trimester induction undelivered after five doses of misoprostol can receive additional doses without any concern for increased complications.

Association of Labor With Neonatal Respiratory Outcomes at 36-40 Weeks of Gestation.

OBJECTIVE: To evaluate whether labor is associated with lower odds of respiratory morbidity among neonates born from 36 to 40 weeks of gestation and to assess whether this association varies by gestational age and maternal diabetic status. METHODS: We conducted a secondary analysis of women in the Assessment of Perinatal Excellence obstetric cohort who delivered across 25 U.S. hospitals over a 3-year period. Women with a singleton liveborn nonanomalous neonate who delivered from 36 to 40 weeks of gestation were included in our analysis. Those who received antenatal corticosteroids, underwent amniocentesis for fetal lung maturity, or did not meet dating criteria were excluded. Our primary outcome was composite neonatal respiratory morbidity, which included respiratory distress syndrome, ventilator support, continuous positive airway pressure, or neonatal death. Maternal characteristics and neonatal outcomes between women who labored and those who did not were compared. Multivariable logistic regression models were used to evaluate the association between labor and the primary outcome. Interactions between labor and diabetes mellitus and labor and gestational age were tested. RESULTS: Our analysis included 63,187 women who underwent labor and 10,629 who did not. There was no interaction between labor and diabetes mellitus (P=.90). However, there was a significant interaction between labor and gestational age (P=.01). In the adjusted model, labor was associated with lower odds of neonatal respiratory morbidity compared with no labor for neonates delivered from 36-39 weeks of gestation. A 1-week increase in gestational age was associated with a 1.2 times increase in the adjusted odds ratio for the neonatal outcome comparing labor and no labor. CONCLUSION: Labor was associated with lower odds of the composite outcome among neonates delivered from 36-39 weeks of gestation. The magnitude of this association varied by gestational age. The association was similar for women with or without diabetes mellitus.

Tissue Adhesive Compared With Sterile Strips After Cesarean Delivery: A Randomized Controlled Trial.

OBJECTIVE: To assess whether tissue adhesive after closure of Pfannenstiel incision for cesarean delivery lowers the risk of wound complications when compared with sterile strips. METHODS: In this multicenter randomized controlled trial, women undergoing cesarean delivery using Pfannenstiel skin incision were randomized to receive tissue adhesive (2-octyl cyanoacrylate) compared with sterile strips after closure of the skin incision. The primary outcome was a composite of wound complications (drainage, cellulitis, abscess, seroma, hematoma, or isolated wound separation) within 8 weeks of delivery. Secondary outcomes included operative time, readmission, office or emergency department visits, or antibiotic use for wound complications, and patient satisfaction with the cesarean scar. With 80% power and a 95% CI, a sample size of 432 per group (n=864) was required to detect a 50% reduction in the primary outcome. A planned interim analysis was performed after 500 patients delivered. A conditional power analysis revealed that the probability of showing a benefit with tissue adhesive was extremely low (6.2%), and the study was halted owing to futility. RESULTS: Between November 2016 and April 2018, 504 patients were randomized, and follow-up was achieved in 479 (95%). Wound complications occurred in 18 out of 238 patients (7.6%) in the tissue adhesive group and 19 out of 241 patients (7.9%) in the sterile strips group (relative risk 0.96; 95% CI 0.51-1.78). There were no significant differences with regard to types of wound complications, operative time, readmission, office or emergency department visits, antibiotics prescribed for wound complications, or patient scar assessment scores of pain, stiffness, and irregularity between the two groups. However, tissue adhesive performed slightly better in regard to itchiness of scar and overall scar satisfaction. CONCLUSION: Compared with sterile strips, tissue adhesive after closure of Pfannenstiel incision for cesarean delivery is unlikely to lower the risk of wound complications. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02838017.