Periviable Premature Rupture of Membranes-Maternal and Neonatal Risks: A Systematic Review and Meta-analysis.

OBJECTIVE: Periviable premature rupture of membranes (PROM) counseling should describe maternal and neonatal outcomes associated with both immediate delivery and expectant management. Unfortunately, most published data focuses on neonatal outcomes and maternal risk estimates vary widely. We performed a meta-analysis to describe outcomes associated with expectant management compared with immediate delivery of periviable PROM. STUDY DESIGN: We performed a search on PubMed, MEDLINE, Web of Science, PROSPERO, Cochrane library, and ClinicalTrials.gov utilizing a combination of key terms. Published clinical trials and observational cohorts were included if published after 2000. Publications were selected if they included maternal and/or neonatal outcomes for both expectant management and immediate delivery. Gestational age range was limited from 14 to 25 weeks. The primary outcome was maternal sepsis. Secondary outcomes included chorioamnionitis, hemorrhage, laparotomy, and neonatal survival. Pooled risk differences (RDs) were calculated for each outcome using a random-effects model. Publication bias was assessed using funnel plots and Harbord test. RESULTS: A total of 2,550 studies were screened. After removal of duplicates and filtering by abstract, 44 manuscripts were reviewed. A total of five publications met inclusion for analysis: four retrospective and one prospective. Overall, 364 (68.0%) women underwent expectant management and 171 (32.0%) underwent immediate delivery. Maternal sepsis was significantly more frequent in the expectant group (RD, 4%; 95% confidence interval, 2-7%) as was chorioamnionitis (RD 30%; p < 0.01) and any laparotomy (RD, 28%; p < 0.01). Neonatal survival in the expectant group was 39% compared with 0% in the immediate group (p < 0.01). CONCLUSION: Women who undergo expectant management following periviable rupture of membranes experience significantly increased risks of sepsis, chorioamnionitis, and laparotomy. Overall, 39% of neonates survive to discharge. Knowledge of these risks is critical to counseling patients with this diagnosis. KEY POINTS: · Expectant management associated with 4% increased risk of sepsis.. · Expectant management associated with 30% increased risk of chorioamnionitis.. · A total of 39% of neonates survived to discharge with expectant management..

Elective Induction of Labor Following Prior Cesarean Delivery.

OBJECTIVE: Following the release of A Randomized Trial of Induction versus Expectant Management (ARRIVE) trial, the induction of labor at 39 weeks has increased in the United States. The risk of uterine rupture and optimal timing of elective induction in those patients with a prior cesarean delivery is not well-described, and they were not included in the original trial. We aimed to determine the risk of uterine rupture in those patients undergoing elective induction of labor with prior cesarean delivery. STUDY DESIGN: This was a retrospective cohort of participants with prior cesarean delivery from 1996 to 2000. Participants were included if they had two or more prior cesareans. Participants were excluded if they had a history of an unknown prior incision, a classical incision, gestational age <39 weeks, any diabetes, chronic hypertension, twin gestation, collagen or vascular disease, or HIV. Those undergoing expectant management were compared with those undergoing elective induction with no medical or obstetrical indications for delivery. Analysis was performed at three gestational age groups: 39 weeks, 40 weeks, and 41 weeks. The primary outcomes were uterine rupture, rates of successful vaginal delivery, and a composite major morbidity risk. Multivariable logistic regression was performed. RESULTS: At 39 weeks, 618 (10.3%) elective inductions were compared with 5,365 (89.7%) undergoing expectant management; uterine rupture occurred more frequently (13 patients [2.1%] vs. 49 patients [0.9%]; adjusted odds ratio [aOR], 2.5; 95% confidence interval, 1.3-4.6) with fewer successful vaginal birth after cesarean [VBAC; 66.8 vs. 75%; aOR, 0.6; 95% confidence interval, 0.5-0.7]. The risk of uterine rupture was similar between groups at 40 weeks (5 patients [0.8%] vs. 21 patients [1.2%]; p = 0.387) and 41 weeks (7 patients [1.4%] vs. 2 patients (0.8%); p = 0.448). CONCLUSION: Patients undergoing elective induction of labor with a prior cesarean scar had an increased risk of uterine rupture when compared with expectant management at 39 weeks, with fewer successful VBAC. KEY POINTS: · TOLAC elective induction at 39 weeks has an increased risk of uterine rupture.. · TOLAC elective induction at 39 weeks has a less successful chance of vaginal delivery.. · Awaiting spontaneous labor in this cohort does not increase the risk of uterine rupture..

First and Second Stage Risk Factors Associated with Perineal Lacerations.

OBJECTIVE: To determine intrapartum factors associated with perineal laceration at delivery. METHODS: This was a planned secondary analysis of a multicenter randomized clinical trial of delayed versus immediate pushing among term nulliparous women in labor with neuraxial analgesia conducted in the United States. Intrapartum characteristics were extracted from the medical charts. The primary outcome was perineal laceration, defined as second degree or above, characterized at delivery in women participating in longer term pelvic floor assessments post-delivery. Multivariable logistic regression was used to refine risk estimates while adjusting for randomization group, birth weight, and maternal age. RESULTS: Among the 941 women participating in the pelvic floor follow-up, 40.6% experienced a perineal laceration. No first stage labor characteristics were associated with perineal laceration, including type of labor or length of first stage. Receiving an amnioinfusion appeared protective of perineal laceration (adjusted odds ratio, 0.48; 95% confidence interval 0.26-0.91; P = 0.01). Second stage labor characteristics associated with injury were length of stage (2.01 h vs. 1.50 h; adjusted odds ratio, 1.36; 95% confidence interval 1.18-1.57; P < 0.01) and a prolonged second stage (adjusted odds ratio, 1.64; 95% confidence interval 1.06-2.56; P < 0.01). Operative vaginal delivery was strongly associated with perineal laceration (adjusted odds ratio, 3.57; 95% confidence interval 1.85-6.90; P < 0.01). CONCLUSION: Operative vaginal delivery is a modifiable risk factor associated with an increased risk of perineal laceration. Amnioinfusion appeared protective against injury, which could reflect a spurious finding, but may also represent true risk reduction similar to the mechanism of warm perineal compress.

Optimal misoprostol dosing among patients with a body mass index greater than 30: a randomized controlled trial.

BACKGROUND: Patients with obesity experience an increased duration of labor with an increased risk for perinatal morbidity. When compared with parturients without obesity, they also experience fewer uterine contractions after administration of misoprostol. It is unclear if the same dose of misoprostol should be used for induction of labor in patients with obesity compared to non-obese patients. Therefore, we sought to investigate if a higher dose of misoprostol for patients with obesity is more effective. OBJECTIVE: This study aimed to determine if 50 µg compared with 25 µg of vaginal misoprostol reduced the time from induction start to delivery among patients with obesity. STUDY DESIGN: We performed a double-blinded, pragmatic randomized controlled trial, between June 1, 2022, and July 17, 2023. Patients with a body mass index ≥30 kg/m2 who underwent labor induction at ≥ 36 weeks' gestation, had a singleton gestation, and a cervical dilation ≤3 cm at admission were included. Patients were excluded if they had a contraindication to vaginal delivery or misoprostol administration. Patients were randomized to 25 or 50 µg of vaginal misoprostol, stratified by parity, body mass index <40 kg/m2 or ≥40 kg/m2, and provider intent to use mechanical dilation at the onset of labor induction. Usual labor management was followed at the discretion of the provider. The primary outcome was time from induction to delivery. A priori, we estimated that 90 subjects per group (N=180) were needed for an 85% power to detect a 3-hour difference between groups with a type I error of 5%. Analysis was by intention-to-treat. A 2-sample t test was used for the primary outcome, Cohen's d was used as a measure of effect, and P values were reported. RESULTS: Of the 180 patients randomized, 88 were assigned to the 25 µg group and 92 were assigned to the 50 µg group. Of those, 96.1% of patients received the designated intervention. The baseline characteristics were similar between groups. No difference was found in the primary outcome of time to delivery (21.6 hours vs 18.6 hours; d=.28; 95% confidence interval, -0.02 to 0.57). In a planned subgroup analysis, multiparous patients delivered faster in the 50 µg group (15.2 hours vs 12.0 hours; d=.51; 95% confidence interval, 0.04-0.97). The risk for tachysystole associated with fetal heart tracing changes was rare overall (2.2%) and not significantly different between groups. No differences in maternal or neonatal adverse effects were observed. CONCLUSION: Patients with obesity who underwent cervical ripening with 50 µg of vaginal misoprostol experienced a similar time to delivery when compared with those who received 25 µg of misoprostol. However, multiparous patients had a significantly reduced time to delivery when 50 µg was used. A higher dose of misoprostol may be a promising intervention for reducing time in labor, which warrants further study.

Optimizing Management of the Second Stage of Labor: A Multicenter Randomized Controlled Trial.

To review the findings of the Optimizing Management of the Second Stage of Labor randomized controlled trial in the context of prior and subsequent obstetric literature. A multi-database search was performed in addition to a review of the parent trial and secondary studies. Nulliparous patients with neuraxial anesthesia randomized to either immediate or delayed pushing showed no difference in vaginal delivery rates. However, delayed pushing is associated with an increased duration of the second stage and perinatal morbidity. Patients should be appropriately counseled on the timing of second-stage pushing and the risks of prolonged second-stage labor.

Impact of household income and Special Supplemental Nutritional Program for Women, Infants, and Children on feeding decisions for infants in the United States.

BACKGROUND: Despite the known benefits of breastfeeding to infants and mothers, previous studies have demonstrated that underserved women are less likely to exclusively breastfeed. Existing studies on the impact of Special Supplemental Nutritional Program for Women, Infants, and Children enrollment on feeding decisions for infants have conflicting results with low-quality data and metrics. OBJECTIVE: This study aimed to examine infant feeding trends nationally in the first week postpartum over a 10-year period, comparing breastfeeding rates for primiparous women with low income who used Special Supplemental Nutritional Program for Women, Infants, and Children resources with those women who did not enroll. We hypothesized that although the Special Supplemental Nutritional Program for Women, Infants, and Children is an important resource for new mothers, free formula associated with enrollment in the Special Supplemental Nutritional Program for Women, Infants, and Children may disincentivize women to exclusively breastfeed. STUDY DESIGN: This was a retrospective cohort study of primiparous women with singleton gestations who gave birth at term and who responded to the Centers for Disease Control and Prevention Pregnancy Risk Assessment Monitoring System between 2009 and 2018. Data were extracted from phases 6, 7, and 8 of the survey. Women with low income were defined as those with a reported annual household income of $35,000 or less. The primary outcome was exclusive breastfeeding after 1 week postpartum. Secondary outcomes included ever breastfeeding, any breastfeeding after 1 week postpartum, and introduction of other liquids within 1 week postpartum. Multivariable logistic regression was used to refine risk estimates with adjustment for mode of delivery, household size, education level, insurance status, diabetes, hypertension, race, age, and BMI. RESULTS: Among the 42,778 women with low income who were identified, 29,289 (68%) of these women reported receiving Special Supplemental Nutritional Program for Women, Infants, and Children resources. There was no significant difference in the rates of exclusive breastfeeding after 1 week postpartum between those enrolled in the Special Supplemental Nutritional Program for Women, Infants, and Children and those not enrolled (adjusted risk ratio, 1.04; 95% confidence interval, 1.00-1.07; P=.10). However, those enrolled were less likely to ever breastfeed (adjusted risk ratio, 0.95; 95% confidence interval, 0.94-0.95; P<.01) and were more likely to introduce other liquids within 1 week postpartum (adjusted risk ratio, 1.16; 95% confidence interval, 1.11-1.21; P<.01). CONCLUSION: Although exclusive breastfeeding rates after 1 week postpartum were similar, women enrolled in the Special Supplemental Nutritional Program for Women, Infants, and Children were significantly less likely to ever breastfeed and more likely to introduce formula within the first week postpartum. This suggests that Special Supplemental Nutritional Program for Women, Infants, and Children enrollment may impact the decision to initiate breastfeeding and may represent an important window to test future interventions.

A comparison of criteria for defining metabolic acidemia in live-born neonates and its effect on predicting serious adverse neonatal outcomes.

BACKGROUND: Metabolic acidemia is a known risk factor for serious adverse neonatal outcomes in both preterm and term infants. OBJECTIVE: This study aimed to evaluate the clinical significance of delivery umbilical cord gas measurements with regard to serious adverse neonatal outcomes, and to determine if distinct thresholds for defining metabolic acidemia differ in their ability to predict such adverse neonatal complications. STUDY DESIGN: This is a retrospective cohort study of singleton live-born deliveries between January 2011 and December 2019. Stratification according to gestational age at birth (≥35 and <35 weeks of gestation) was performed, and comparisons of maternal characteristics, obstetrical complications, intrapartum events, and adverse neonatal outcomes were made between neonates with metabolic acidemia and those without. Metabolic acidemia (based on delivery umbilical cord gas analyses) was defined using both American College of Obstetricians and Gynecologists and Eunice Kennedy Shriver National Institute of Child Health and Human Development criteria. The primary outcome of interest was hypoxic-ischemic encephalopathy requiring whole-body hypothermia. RESULTS: A total of 91,694 neonates born at ≥35 weeks of gestation met the inclusion criteria. By American College of Obstetricians and Gynecologists criteria, 2659 (2.9%) infants had metabolic acidemia. Neonates with metabolic acidemia were at markedly increased risk for neonatal intensive care unit admission, seizures, need for respiratory support, sepsis, and neonatal death. Metabolic acidemia by American College of Obstetricians and Gynecologists criteria was associated with an almost 100-fold increased risk of hypoxic-ischemic encephalopathy requiring whole-body hypothermia (relative risk, 92.69; 95% confidence interval, 64.42-133.35) in neonates born at ≥35 weeks of gestation. Diabetes mellitus, hypertensive disorders of pregnancy, postterm deliveries, prolonged second stages, chorioamnionitis, operative vaginal deliveries, placental abruption and cesarean deliveries were associated with metabolic acidemia in neonates born ≥ 35 weeks of gestation. The highest relative risk was in those diagnosed with placental abruption (relative risk, 9.07; 95% confidence interval, 7.25-11.36). The neonatal cohort born <35 weeks of gestation had similar findings. When comparing those infants born ≥ 35 weeks of gestation with metabolic acidemia by American College of Obstetricians and Gynecologists criteria vs Eunice Kennedy Shriver National Institute of Child Health and Human Development criteria, the Eunice Kennedy Shriver National Institute of Child Health and Human Development criteria identified more neonates at risk for serious adverse neonatal outcomes. In particular, 4.9% more neonates were diagnosed with metabolic acidemia, and 16 more term neonates were identified as requiring whole-body hypothermia. Mean 1-minute and 5-minute Apgar scores were similar and reassuring among neonates born at ≥35 weeks of gestation with and without metabolic acidemia as defined by both American College of Obstetricians and Gynecologists and Eunice Kennedy Shriver National Institute of Child Health and Human Development criteria (8 vs 8 and 9 vs 9, respectively; P<.001). Sensitivity and specificity were 86.7% and 92.2%, respectively, with the Eunice Kennedy Shriver National Institute of Child Health and Human Development criteria, and 74.2% and 97.2% with the American College of Obstetricians and Gynecologists criteria. CONCLUSION: Infants with metabolic acidemia identified on cord gas collection at delivery are at considerably greater risk of serious adverse neonatal outcomes, including an almost 100-fold increased risk of hypoxic-ischemic encephalopathy requiring whole-body hypothermia. Use of the more sensitive Eunice Kennedy Shriver National Institute of Child Health and Human Development criteria for defining metabolic acidemia identifies more neonates born at ≥35 weeks of gestation at risk for adverse neonatal outcomes, including hypoxic-ischemic encephalopathy requiring whole-body hypothermia.

Evidence-Based Approaches to Labor Induction.

Importance: The induction rate continues to increase in the United States placing pressure on the health care system with increasing cost and time spent on labor and delivery. Most labor induction regimens have evaluated uncomplicated singleton-term gestations. Unfortunately, the optimal labor regimens of medically complicated pregnancies have not been well described. Objective: The aim of this study was to review the current available evidence regarding the various labor induction regimens and understand the evidence that exists for induction regimens in complicated pregnancies. Evidence Acquisition: Data were acquired by a literature search on PubMed, ClinicalTrials.gov, the Cochrane Review database, the most recent American College of Obstetricians and Gynecologists practice bulletin on labor induction, and a review of the most recent edition on widely used obstetric texts for key words related to labor induction. Results: Many heterogeneous clinical trials exist examining various labor induction regimens such as prostaglandin only, oxytocin only, or a combination of mechanical dilation with prostaglandins or oxytocin. Several Cochrane systematic reviews have been performed, which suggest a combination of prostaglandins and mechanical dilation results in an improved time to delivery when compared with single-use methods. Evaluating pregnancies complicated by maternal or fetal conditions, there exist retrospective cohorts describing significantly different labor outcomes. Although a few of these populations have planned or active clinical trials, most do not have an optimal labor induction regimen described. Conclusions and Relevance: Most induction trials are significantly heterogeneous and limited to uncomplicated pregnancies. A combination of prostaglandins and mechanical dilation may result in improved outcomes. Complicated pregnancies have significantly different labor outcomes; however, almost none have well-described labor induction regimens.

Intrapartum risk factors associated with pelvic organ prolapse at 6 months postpartum.

BACKGROUND: Pregnancy and childbirth are known risk factors associated with the development of pelvic organ prolapse; specific intrapartum risk factors are not well characterized. OBJECTIVE: This study aimed to determine intrapartum factors associated with increased risk of pelvic organ prolapse identified after delivery. STUDY DESIGN: A planned secondary analysis of a multicenter randomized clinical trial of delayed vs immediate pushing among nulliparous women at ≥37 weeks of gestation in labor with neuraxial analgesia was conducted at 6 academic and community hospitals in the United States. Intrapartum characteristics were identified, and Pelvic Organ Prolapse Quantification assessments at 6 weeks and 6 months after delivery were performed. The primary outcome was pelvic organ prolapse, defined as stage 2 or greater prolapse using the Pelvic Organ Prolapse Quantification assessment at 6 months. Multivariable logistic regression was used to refine risk estimates while adjusting for randomization group, macrosomia, and maternal age. RESULTS: Among the 941 women participating in the pelvic floor follow-up, 793 women had Pelvic Organ Prolapse Quantification assessments at 6 weeks with 91 of 793 women (11.5%) demonstrating stage 2 or greater prolapse. Of the 728 women followed up at 6 months, stage 2 or greater prolapse was identified in 58 of 728 women (8.0%). Prostaglandin use for induction of labor was associated with an increased risk at 6 months (adjusted odds ratio, 2.15; 95% confidence interval, 1.18-3.91; P<.01). The length and type (spontaneous vs induced) of the first stage of labor were not significantly associated with stage 2 or greater prolapse. Moreover, increased length of the second stage of labor and duration of pushing were not associated with stage 2 or greater prolapse. After adjusting for confounding factors, cesarean delivery was protective of pelvic organ prolapse at 6 months (adjusted odds ratio, 0.12; 95% confidence interval, 0.02-0.90). CONCLUSION: The management of the first and second stages of labor, including time length, was not associated with stage 2 or greater prolapse at 6 months. The findings that prostaglandin exposure was associated with increased risk likely were not directly affecting the risk of prolapse but may be surrogates for other labor features that deserve exploration. Cesarean delivery was associated with protection from stage 2 or greater pelvic organ prolapse at 6 months, consistent with previous literature.

Accessibility to postpartum tubal ligation after a vaginal delivery: When the Medicaid policy is not a limiting factor.

OBJECTIVE: To describe rates of postpartum sterilization and indications for unfulfilled requests when Medicaid policy is not a limiting factor. STUDY DESIGN: We conducted a single-institution, retrospective review. Women who requested postpartum tubal ligation after vaginal delivery from August 2015 to March 2019 were studied. Select demographic characteristics were compared between those who did and did not undergo the procedure. Reasons for why the procedure was cancelled, alternate contraceptive plans, and subsequent pregnancies were collected. Statistical analysis included the t test and chi-squared test, with p < 0.05 considered significant. RESULTS: A total of 4103 patients requested postpartum tubal ligation following vaginal delivery. About 3670 (89.4%) procedures were performed and 433 (10.6%) were canceled. Of the 433, 423 (98%) were not performed at patient request; 10 (2 %) were cancelled based on physician recommendation. Of these, 3 were due to significant maternal anemia in the setting of refusal of blood products, 1 due to anesthesia concerns, 1 for increased body mass index, and 1 due to delivery events. Alternative contraception methods were offered; 72 (28% of patients not receiving a tubal ligation) received Depo Provera prior to discharge. One-fourth (n = 110, 25.4%) did not keep the postpartum follow-up appointment. 83 (19.2%) of the 433 patients had at least one subsequent pregnancy. Although over half expressed interest at the time of discharge in long-acting reversible contraceptives, only 20% obtained this method at the postpartum visit. CONCLUSIONS: Postpartum sterilization was predominantly achieved, among women whose requests were unfulfilled, the majority (98%) were at patient request with a minority by physician recommendation. IMPLICATIONS: When the availability of postpartum tubal ligation is independent of Medicaid reimbursement and the hospital system and providers are organized to support timely access to permanent postpartum contraception, the majority of tubal ligations requests can be fulfilled following vaginal delivery.

Evaluation of Drug Labels Following the 2015 Pregnancy and Lactation Labeling Rule.

Importance: The US Food and Drug Administration (FDA) Pregnancy and Lactation Labeling Rule (PLLR), implemented in 2015, includes information on pregnancy, lactation, and women and men with reproductive potential. Objectives: To identify the drugs that have adhered to the new PLLR format; to shed light on the continued need for implementation of pregnancy, lactation, and reproduction into clinical studies; and to evaluate how many new therapeutic products have human and animal data specific to pregnancy and lactation. Design, Setting, and Participants: This cross-sectional study of 290 new therapeutic drugs reviewed labeling data for newly FDA-approved therapeutic products from January 2010 to December 2019. Therapeutic products submitted on or after June 30, 2015, were required to be in PLLR format; those approved from June 30, 2007, to June 29, 2015, had until June 30, 2019, to be in PLLR format. Approval data and subsequent labeling revision were evaluated for pregnancy and lactation data (human and animal), pregnancy registry, black-box warnings, and inclusion of PLLR labeling format. Exposures: Date of new drug approval by FDA. Main Outcomes and Measures: Compliance with PLLR; presence of animal or human data; presence of pregnancy registries; and presence of information regarding female and male reproductive potential. Results: A total of 290 new molecular entities or therapeutic products were approved by the FDA between 2010 and 2019 in 19 categories. Black-box warnings occurred in 89 drugs (30.7%; 95% CI, 25.4%-36.3%), with 3 (3.4%; 95% CI, 0.7%-9.5%) involving pregnancy. All products submitted after June 30, 2015, were in PLLR format; however, of the 138 submitted between 2010 and that date, 45 (32.6%; 95% CI, 24.9%-41.1%) were not in PLLR format by June 30, 2019. During the 10 years of data analyzed, significantly more were in PLLR format (P for trend < .001). Most approved therapeutic products have pregnancy data derived from animal studies (260 products; 89.7%; 95% CI, 85.6%-92.9%) but only 31 (10.7%; 95% CI, 7.4%-14.8%) derived data from human studies. Only 148 therapeutic products (51.0%; 95% CI, 45.1%-56.9%) had any data associated with lactation, 143 (49.3%; 95% CI, 43.4%-55.2%) originating from animal studies and 8 (2.8%; 95% CI, 1.2%-5.4%) from human studies. Conclusions and Relevance: The results of this study show that with the implementation of PLLR in the last decade, new therapeutic products were in compliance with the new rules; however, more than one-third of labels remain out of PLLR compliance. Human data on pregnancy and lactation are available in less than 20% of new product labeling.

Examining the Association of Obesity With Postpartum Tubal Ligation.

OBJECTIVE: To evaluate the association of increasing body mass index (BMI) on postpartum tubal ligation safety and estimate the rates of procedure complication. METHODS: We conducted a single-institution, retrospective review. Women undergoing postpartum permanent contraception after vaginal delivery from August 2015 to March 2019 were studied. Our primary outcome included a composite morbidity of intraoperative complications (bleeding requiring additional surgery, and extension of incision), blood transfusion, aborted procedure, anesthetic complication, readmission, wound infection, venous thromboembolism, ileus or small bowel obstruction, incomplete transection, and subsequent pregnancy. Statistical analysis included t test, χ test, and Wilcoxon rank-sum test, with P<0.05 considered significant. RESULTS: During the study period, 3,670 women were studied: 263 were underweight or normal weight (BMI 24.9 or lower), 1,044 were overweight (25-29.9), 1,371 had class I obesity (30-34.9), 689 had class II obesity (35-39.9), and 303 had class III obesity (40 or higher) at the time of admission. Composite morbidity occurred in 49 cases (1.3%) and was not significantly different across the BMI categories (P=.07). Twelve cases of incomplete transection were noted on pathology reports; however, none of these accounted for the six subsequent pregnancies that were identified. There were no deaths or events leading to death noted in the study population. The length of time to complete the procedure increased across BMI categories (23 minutes in women with normal weight, and 31 in women with class III obesity) (P<.001). CONCLUSION: There was no association between increased BMI and morbidity with women undergoing postpartum tubal ligation. Postpartum tubal ligation should be considered a safe and reasonable option for women, regardless of BMI.

Task force on research specific to pregnant and lactating women.

The Task Force on Research Specific to Pregnant Women and Lactating Women was established by the 21st Century Cures Act and charged with providing advice and guidance to the Secretary of Health and Human Services on activities related to identifying and addressing gaps in knowledge and research on safe and effective therapies for pregnant women and lactating women, including the development of, collaboration on, and coordination of such activities. The Task Force developed 15 recommendations based on information gleaned during four meetings and a public comment period. These recommendation include concrete actionable items to facilitate information and data for providers and the public.

Multimodal imaging of the tumor microenvironment and biological responses to immune therapy.

Beyond heterogeneous cancer cells, the tumor microenvironment includes stromal and immune cells, blood vessels, extracellular matrix and biologically active molecules. Abnormal signaling, uncontrolled proliferation and high interstitial pressure all contribute to a chaotic, non-hierarchical vascular organization. Using an immune competent 4T1 breast adenocarcinoma murine model, this study fully characterizes the architecture and immunocyte milieu of the tumor microenvironment. Heterogeneous vessel distribution, chaotic connectivity, limited perfusion, cancer cell density, immune phenotype, and biological responses to immune therapy are presented. Cancer cell density mirrored the distribution of large, perfusable vessels, both predominately in the tumor periphery. Intratumoral administration of the proinflammatory cytokine IL-12 led to an increase in CD45+ leukocytes, with a specific increase in CD4+ and CD8+ T cells, and a decrease in the percentage of Gr-llo myeloid-derived suppressor cells. Concomitantly, serum G-CSF, IL-10 and VEGF decreased, while CXCR9 and interferon gamma increased. The distribution pattern of infiltrating monocytes/macrophages, visualized using a fluorescent perfluorocarbon emulsion, indicated that macrophages predominately localize in the vicinity of large blood vessels. Electron microscopy supports the presence of dense tumor cell masses throughout the tumor, with the largest vessels present in the surrounding mammary fat pad. Overall, large vessels in the 4T1 tumor periphery support high, localized vascular perfusion and myeloid accumulation. The pro-inflammatory cytokine IL-12 stimulated a transition towards T helper 1 cytokines in serum, supporting suppression of tumor growth and angiostatic conditions.