BackgroundBisphenol A (BPA) is widely used in the manufacture of polycarbonate plastics, including infant formula bottles.ObjectivesBased on the reported endocrine disruptor activity of this polyphenol, we hypothesized that exposure to BPA early in life would elicit developmental changes in the mammary tissue and cause a predisposition for mammary cancer.MethodsWe exposed neonatal/prepubertal rats to BPA via lactation from nursing dams treated orally with 0, 25, and 250 μg BPA/kg body weight/day. For tumorigenesis studies, female offspring were exposed to 30 mg dimethylbenzanthracene (DMBA)/kg body weight at 50 days of age.ResultsThe combination of DMBA treatment with lactational exposure to BPA demonstrated a dose-dependent increase in mammary tumor multiplicity and reduced tumor latency compared with controls. In the absence of DMBA treatment, lactational BPA exposure resulted in increased cell proliferation and decreased apoptosis at 50 but not 21 days postpartum (shortly after last BPA treatment). Using Western blot analysis, we determined that steroid receptor coactivators (SRCs) 1–3, Akt, phosphorylated Akt, progesterone receptor A (PR-A), and erbB3 proteins were significantly up-regulated at 50 days of age.ConclusionsThe data presented here provide the first evidence that maternal exposure to BPA during lactation increases mammary carcinogenesis in a DMBA-induced model of rodent mammary cancer. Changes in PR-A, SRC 1–3, erbB3, and Akt activity are consistent with increased cell proliferation and decreased apoptosis playing a role in mammary cancer susceptibility. These alterations provide an explanation of enhanced mammary carcinogenesis after lactational BPA exposure.

No abstract

Background A number of evidence-based interventions have been proposed to reduce post cesarean wound complications. Examples of such interventions include appropriate timing of preoperative antibiotics, appropriate choice of skin antisepsis, closure of the subcutaneous layer if subcutaneous depth is ≥ 2 cm, and subcuticular skin closure with suture rather than staples. However, the collective impact of these measures is unclear. Objective We sought to estimate the impact of a group of evidence-based surgical measures (prophylactic antibiotics administered prior to skin incision, chlorhexidine-alcohol for skin antisepsis, closure of subcutaneous layer, and subcuticular skin closure with suture) on wound complications after cesarean, and to estimate residual risk factors for wound complications. Study Design We conducted a secondary analysis of data from a randomized controlled trial of chlorhexidine-alcohol versus iodine-alcohol for skin antisepsis at cesarean from 2011–2015. The primary outcome for this analysis was a composite of wound complications, including surgical site infection (SSI), cellulitis, seroma, hematoma, and separation within 30 days. Risk of wound complications in women who received all four evidence-based measures (prophylactic antibiotics within 60 minutes of cesarean and prior to skin incision, chlorhexidine-alcohol for skin antisepsis with three minutes of drying time prior to incision, closure of subcutaneous layer if ≥ 2 cm of depth and subcuticular skin closure with suture) were compared to those who did not. We performed logistic regression analysis limited to patients who received all the evidence-based measures to estimate residual risk factors for wound complications and SSI. Results Of 1082 patients with follow-up, 349 (32.3%) received all the evidence-based measures and 733 (67.7%) did not. The risk of wound complications was significantly lower in patients who received all the evidence-based measures compared to those who did not (20.3% vs 28.1%; aRR 0.75, 95% CI 0.58, 0.95). The impact appeared to be largely driven by a reduction in surgical site infections. Among patients who received all the evidence-based measures, unscheduled cesarean was the only significant risk factor for wound complications (27.5% vs. 16.1%, aRR 1.71, 95% CI 1.12, 2.47) and SSI (6.9% vs. 1.6%, RR 3.74, 95% CI 1.18, 11.92). Other risk factors, including obesity, smoking, diabetes, chorioamnionitis, surgical experience, and skin incision type were not significant among patients who received all of the four evidence-based measures. Conclusion Implementation of evidence-based measures significantly reduces wound complications, but the residual risk remains high. This suggests the need for additional interventions, especially in patients undergoing unscheduled cesareans, who are at risk for wound complications even after receiving current evidence-based measures.

ObjectiveAngiogenic factors are strongly associated with adverse maternal and fetal outcomes among women with preterm preeclampsia (PE) in developed countries. We evaluated the role of angiogenic factors and their relationship to adverse outcomes among Haitian women with PE.Material and MethodsWe measured plasma antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt1) and proangiogenic placental growth factor (PlGF) levels in women with PE (n=35) compared to controls with no hypertensive disorders (NHD) (n=43) among subjects with singleton pregnancies that delivered at Hospital Albert Schweitzer (HAS) in Haiti. We divided the preeclamptic women into two groups, early onset (≤ 34 weeks) and late onset (>34 weeks) and examined relationships between sFlt1/PlGF ratios on admission and adverse outcomes (abruption, respiratory complications, stroke, renal insufficiency, eclampsia, maternal death, birth weight <2500 grams, or fetal/neonatal death) in women with PE subgroups as compared to NHD groups separated by week of admission. Data are presented as median (25th-75th centile), n (%), and proportions.ResultsAmong patients with PE, most (24/35) were admitted at term. Adverse outcome rates in PE were much higher among the early onset group compared to the late onset group (100.0% vs. 54.2%, P=0.007). Plasma angiogenic factors were dramatically altered in both subtypes of PE. Angiogenic factors also correlated with adverse outcomes in both subtypes of PE. The median sFlt1/PlGF ratios for subjects with early onset PE with any adverse outcome vs. NHD <=34 weeks with no adverse outcome were 703.1 (146.6, 1614.9) and 9.6 (3.5, 58.6); P<0.001). Among late onset group the median sFlt1/PlGF ratio for women with any adverse outcome was 130.7 (56.1, 242.6) versus 22.4 (10.2, 58.7; P=0.005) in NHD >34 weeks with no adverse outcome.ConclusionPE-related adverse outcomes are common in women in Haiti and are associated with profound angiogenic imbalance regardless of gestational age at presentation.

Objective The possible connection between COVID-19 and hypertensive disorders of pregnancy (HDP) remains unclear (1). Elucidating these outcomes is important both to better understand COVID-19 pathophysiology and to improve patient care in pregnant patients with COVID-19. Our objectives were to test the hypothesis that COVID-19 infection is associated with an increased risk of HDP and to examine the association between the gestational age at COVID-19 infection and delivery and HDP risk. Study Design This was a retrospective cohort study at Barnes-Jewish Hospital in St. Louis, which has a universal COVID-19 testing policy on admission to labor and delivery. All women admitted for delivery from June 1, 2020-November 30, 2020, with a positive Sars-CoV-2 test at any time during pregnancy were compared 1:2 with randomly selected controls who had a negative SARS-CoV-2 test and were matched for race and parity. COVID-19 was diagnosed with nasopharyngeal RT-PCR or rapid antigen testing. HDP was diagnosed using standard criteria. Cox proportional hazards models with left truncation to account for the varying gestational age at COVID-19 diagnosis, and random effects (frailty) to account for the matching design and small cluster sizes, were used to examine the association between COVID-19 and HDP (2). As a sensitivity analysis we also examined early (before 32 weeks gestation) vs. late COVID-19 infection and HDP development. The study was deemed exempt from review by the Institutional Review Board. Results Of 1856 births, there were 83 women (4.5%) with COVID-19 infection. There was no significant difference in baseline characteristics between COVID-19 infected women and controls. Patients with COVID-19 infection had almost a two-fold risk of HDP (HR 1.93 (95%CI 1.13, 3.31). However, COVID-19 infection was not associated with severity of HDP, and severity of COVID-19 (3) was not associated with HDP development. Among patients with COVID-19 and HDP at delivery, the median interval from COVID-19 diagnosis to delivery was 3.8 weeks (IQR 0.29, 11.5). In additional analysis, early, but not late, COVID-19 infection was associated with HDP development (HR for early COVID-19 2.17 (95%CI 1.11, 4.24), HR for late COVID-19 1.68, (95%CI 0.79, 3.57). Conclusions Early COVID-19 infections are associated with HDP, even when accounting for differential exposure and delivery times, suggesting that COVID-19 infection may alter pregnancy physiology and increase the risk of HDP development over time. Infection closer to term is not associated with HDP, which likely reflects our high proportion of asymptomatic infections found at the time of delivery from a universal testing policy (4) and insufficient time to develop HDP in these cases. Furthermore, emerging evidence suggests that COVID-19 modulates placental ACE2 expression, which may be related to HDP development (5). Our study is limited by sampling in a single institution with a high HD...

IMPORTANCE Two-thirds of women in labor receive supplemental oxygen to reverse perceived fetal hypoxemia and prevent acidemia. Oxygen is routinely administered for category II fetal heart tracings, a class of fetal tracing used to designate intermediate risk for acidemia. This liberal use of oxygen may not be beneficial, particularly because neonatal hyperoxygenation is harmful. OBJECTIVE To test the hypothesis that room air is noninferior to oxygen in improving fetal metabolic status among patients with category II fetal heart tracings. DESIGN, SETTING, AND PARTICIPANTS This was a randomized, unblinded noninferiority clinical trial conducted between June 2016 and July 2017 in the labor and delivery ward of a single tertiary care center. Women with singleton pregnancies at 37 weeks' gestational age or more who were admitted for delivery were eligible. Of those who met inclusion criteria, the patients who developed category II tracings in labor that necessitated intrauterine resuscitation were randomized in a 1:1 ratio to room air or oxygen. Analyses were intention-to-treat. INTERVENTIONS The oxygen group received 10 L of oxygen per minute by nonrebreather facemask until delivery. The room air group was exposed to room air only without a facemask. MAIN OUTCOMES AND MEASURES The primary outcome was umbilical artery lactate, a marker of metabolic acidosis and neonatal morbidity. Noninferiority was defined as a mean difference between groups of less than 9.0 mg/dL (1.0 mmol/L). Secondary outcomes were other umbilical artery gases, cesarean delivery for nonreassuring fetal status, and operative vaginal delivery. RESULTS Of the 705 patients who met inclusion criteria, 277 (39.3%) were enrolled on admission. During labor, 114 patients (41.2% of the enrolled patients) developed category II tracings and were randomized to room air (57 patients; 50.0% of the randomized patients) or oxygen (57 patients; 50.0% of the randomized patients). A total of 99 patients (86.8% of the randomized patients) with paired cord gases were included in the modified intention-to-treat analysis. The 99 patients included 76 African American women (77%); mean (SD) age was 27.3 (6.3) years in the oxygen group and 27.8 (5.3) years in the room air group. There was no difference in umbilical artery lactate between the group on oxygen and the group on room air (mean, 30.6 mg/dL [95% CI, 27.0 to 34.2 mg/dL] vs 31.5 mg/dL [95% CI, 27.9 to 36.0 mg/dL]); P = .69). The mean difference in lactate was 0.9 mg/dL (95% CI, −4.5 to 6.3 mg/dL), which was within the noninferiority margin. There was no difference in other umbilical artery gas components or mode of delivery between groups. CONCLUSIONS AND RELEVANCE Among patients with category II fetal heart tracings, intrauterine resuscitation with room air is noninferior to oxygen in improving umbilical artery lactate. The results of this trial challenge the efficacy of a ubiquitous obstetric practice and suggest that room air may be an acceptable alternative.

more than 11 million people have been infected with coronavirus disease 2019 and almost 250,000 people have died from the disease in the United States, less than 1 year since its discovery. Although literature is beginning to emerge on pregnancy as a risk factor for severe coronavirus disease 2019, these studies are heterogeneous and use primary outcomes such as intensive care unit admission or hospitalization as surrogate markers that may subject analyses to misclassification bias in pregnant patients. OBJECTIVE: This study aimed to determine the risk of severe coronavirus disease 2019 among pregnant women with symptomatic coronavirus disease 2019 compared with nonpregnant women using nonadmissionbased, standardized clinical criteria for severe disease. STUDY DESIGN: This is a retrospective cohort study of women aged 13 to 45 years and diagnosed as having symptomatic coronavirus disease 2019 between May 28, 2020, and July 22, 2020. The primary outcome was severe coronavirus disease 2019 as defined by 2 sets of nonadmission-based, clinical criteria: the World Health Organization Ordinal Scale for Clinical Improvement and the Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. Adjusted risk ratios were estimated using multivariable logistic regression analyses. RESULTS: Of 262 women aged 13 to 45 years with symptomatic coronavirus disease 2019, 22 (8.4%) were pregnant and 240 (91.6%) were nonpregnant. After adjusting for covariates potentially associated with the primary outcome, symptomatic pregnant women were at a significantly increased risk of severe coronavirus disease 2019 compared with nonpregnant women using both the World Health Organization Ordinal Scale for Clinical Improvement (adjusted relative risk, 3.59; 95% confidence interval, 1.49−7.01) and Novel Coronavirus Pneumonia Emergency Response Epidemiology Team (adjusted relative risk, 5.65; 95% confidence interval, 1.36−17.31) criteria. CONCLUSION: Pregnancy significantly increases the risk of severe coronavirus disease 2019 as defined by nonadmission-based, clinical criteria.

Observing successful pain treatment in others can induce anticipatory neural processes that, in turn, relieve pain. Previous studies have suggested that social learning and observation influence placebo hypoalgesia. Here, we used electroencephalography (EEG) to determine the neurophysiological changes associated with pain relief acquired through the observation. Thirty-one participants observed a demonstrator undergo painful heat stimulations paired with a “control” cream and non-painful ones paired with a “treatment” cream, which actually were both Vanicreams. After their observation, the participants then received the same creams and stimulations. We found that the treatment cream led to lower self-reported pain intensity ratings than the control cream. Anticipatory treatment cues elicited smaller P2 in electrodes F1, Fz, FC1, and FCz than the control condition. The P2 component localization indicated a higher current density in the right middle frontal gyrus, a region associated with attentional engagement. In placebo responders, the sensorimotor cortex activity captured in electrodes C3, Cz, and C4 indicated that hypoalgesia was positively correlated with resting state peak alpha frequency (PAF). These results suggest that observationally-induced placebo hypoalgesia may be driven by anticipatory mechanisms that modulate frontal attentional processes. Furthermore, resting state PAF could serve as a predictor of observationally-induced hypoalgesia.