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Background Standard treatment for placental site trophoblastic tumor is hysterectomy. This may be unacceptable to women desiring fertility. Cells aberrant in placental site trophoblastic tumor display an ability to invade normal tissue while evading the immune system. Case We present a case of a 23-year-old woman with stage I placental site trophoblastic tumor who declined hysterectomy. Tumor assay for program cell death-ligand 1 staining was performed and suggestive of an immune-responsive tumor. The patient initiated intravenous pembrolizumab 200 mg every 2 weeks, and by cycle 3 her β-hCG level fell to undetectable. She subsequently conceived and went on to have an uncomplicated term vaginal birth after cesarean. At 6 weeks postpartum, she remained without evidence of disease. Conclusion Immunotherapy can eliminate early program cell death-ligand 1-positive placental site trophoblastic tumor with subsequent normal pregnancy.

Objective There is wide variation in the management of pregnancies complicated by abnormal placental cord insertion (PCI), which includes velamentous cord insertion (VCI) and marginal cord insertion (MCI). We tested the hypothesis that abnormal PCI is associated with small for gestational age (SGA) infants. Study Design This is a retrospective cohort study of all pregnant patients undergoing anatomic ultrasound at a single institution from 2010 to 2017. Patients with abnormal PCI were matched in a 1:2 ratio by race, parity, gestational age at the time of ultrasound, and obesity to patients with normal PCIs. The primary outcome was SGA at delivery. Secondary outcomes were cesarean delivery, preterm delivery, cesarean delivery for nonreassuring fetal status, 5-minute Apgar score Results Abnormal PCI was associated with an increased risk of SGA (relative risk [RR]: 2.43; 95% confidence interval [CI]: 1.26–4.69), increased risk of preterm delivery Conclusion Abnormal PCI is associated with an increased risk of SGA and preterm delivery. These results suggest that serial fetal growth assessments in this population may be warranted. Key Points

Use of maternal oxygen for intrauterine resuscitation is contentious because of the lack of evidence for its efficacy and the possibility of fetal harm through oxidative stress. Because the developing brain is rich in lipids and low in antioxidants, it remains vulnerable to oxidative stress. Here, we tested this hypothesis in a term pregnant rat model with oxytocin-induced fetal distress followed by treatment with either room air or 100% oxygen for 6 h. Fetal brains from both sexes were subjected to assays for biomarkers of oxidative stress (4-hydroxynonenal, protein carbonyl, or 8-hydroxy-2ʹ-deoxyguanosine), expression of genes mediating oxidative stress, and mitochondrial oxidative phosphorylation. Contrary to our hypothesis, maternal hyperoxia was not associated with increased biomarkers of oxidative stress in the fetal brain. However, there was significant upregulation of the expression of select genes mediating oxidative stress, of which some were male-specific. These observations, however, were not accompanied by changes in the expression of proteins from the mitochondrial electron transport chain. In summary, maternal hyperoxia in the setting of acute uteroplacental ischemia-hypoxia does not appear to cause oxidative damage to the developing brain.

IMPORTANCE: Supplemental oxygen is commonly administered to pregnant women at the time of delivery to prevent fetal hypoxia and acidemia. There is mixed evidence on the utility of this practice. OBJECTIVE: To compare the association of peripartum maternal oxygen administration with room air on umbilical artery (UA) gas measures and neonatal outcomes. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials were searched from February 18 to April 3, 2020. Search terms included labor or obstetric delivery and oxygen therapy and fetal blood or blood gas or acid-base imbalance. STUDY SELECTION: Studies were included if they were randomized clinical trials comparing oxygen with room air at the time of scheduled cesarean delivery or labor in patients with singleton, nonanomalous pregnancies. Studies that did not collect paired umbilical cord gas samples or did not report either UA pH or UA Pao(2) results were excluded. DATA EXTRACTION AND SYNTHESIS: Data were extracted by 2 independent reviewers. The analysis was stratified by the presence or absence of labor at the time of randomization. Data were pooled using random-effects models. MAIN OUTCOMES AND MEASURES: The primary outcome for this review was UA pH. Secondary outcomes included UA pH less than 7.2, UA Pao(2), UA base excess, 1- and 5-minute Apgar scores, and neonatal intensive care unit admission. RESULTS: The meta-analysis included 16 randomized clinical trials (n = 1078 oxygen group and n = 974 room air group). There was significant heterogeneity among the studies (I(2) = 49.88%; P = .03). Overall, oxygen administration was associated with no significant difference in UA pH (weighted mean difference, 0.00; 95% CI, −0.01 to 0.01). Oxygen use was associated with an increase in UA Pao(2) (weighted mean difference, 2.57 mm Hg; 95% CI, 0.80-4.34 mm Hg) but no significant difference in UA base excess, UA pH less than 7.2, Apgar scores, or neonatal intensive care unit admissions. Umbilical artery pH values remained similar between groups after accounting for the risk of bias, type of oxygen delivery device, and fraction of inspired oxygen. After stratifying by the presence or absence of labor, oxygen administration in women undergoing scheduled cesarean delivery was associated with increased UA Pao(2) (weighted mean difference, 2.12 mm Hg; 95% CI, 0.09-4.15 mm Hg) and a reduction in the incidence of UA pH less than 7.2 (relative risk, 0.63; 95% CI, 0.43-0.90), but these changes were not noted among those in labor (Pao(2): weighted mean difference, 3.60 mm Hg; 95% CI, −0.30 to 7.49 mm Hg; UA pH

The aim of this study is to determine the association between mild acidemia (umbilical artery [UA] pH: 7.11-7.19) and neonatal morbidity in neonates at term.This is a secondary analysis of a prospective cohort of women admitted for labor at ≥37 weeks of gestation within a single institution from 2010 to 2015. Universal umbilical cord blood gas assessment was performed and validated. A composite neonatal morbidity index was created including respiratory distress, mechanical ventilation, meconium aspiration syndrome, suspected or confirmed sepsis, hypoxic-ischemic encephalopathy, need for therapeutic hypothermia, seizures and death. The cohort was stratified by UA pH into normal (≥7.20), mild acidemia (7.11-7.19), acidemia (7.00-7.10), and severe acidemia (≤7.00). A subanalysis was also performed where neonates with UA pH between 7.11 and 7.19 were further stratified into two groups (7.11-7.14 and 7.15-7.19) to determine if mildly acidotic infants at the lower end of the pH range were at increased risk of morbidity. Multivariable logistic regression was used to estimate the association between UA pH and neonatal morbidity.Among 6,341 participants, 614 (9.7%) had mild acidemia. These infants were more likely to experience morbidity compared with those with normal UA pH (adjusted odds ratio [aOR]: 2.14; [1.68-2.73]). Among neonates with mild acidemia, UA pH 7.11 to 7.14 was associated with increased risk of composite neonatal morbidity (aOR: 3.02; [1.89-4.82]), as well as respiratory distress and suspected or confirmed sepsis when compared with UA pH 7.15 to 7.19.These data demonstrate that term neonates with mild acidemia at birth are at higher odds for short-term morbidity compared with neonates with normal UA pH. Furthermore, among neonates with mild acidemia, those with lower UA pH had worse neonatal outcomes than those with higher UA pH. This suggests that closer evaluation of neonates with UA pH higher than traditionally used could allow for earlier detection of morbidity and possible intervention.· Neonates with mild acidemia (umbilical artery [UA] pH: 7.11-7.19) demonstrated an increased risk of composite morbidity compared with those with normal UA pH (≥7.20).. · Among neonates with mild acidemia, those with lower UA pH (7.11-7.14) had a greater risk of morbidity compared with those with higher UA pH (7.15-7.19), suggesting a progression of risk of morbidity as UA pH decreases.. · The majority of prior research has focused on severe acidemia (UA pH ≤ 7.00) using outcomes of severe neurologic morbidity and mortality. These data suggest that an increased risk of morbidity exists at higher pH values when more proximal and less severe outcomes are included, such as respiratory distress and neonatal sepsis..

OBJECTIVE The primary objective of this study was to evaluate coronavirus 2019 (COVID-19) pandemic-related changes in the antenatal utilization of high-risk obstetric services. Our secondary objective was to characterize change in stillbirth rate during the pandemic. STUDY DESIGN This is a retrospective, observational study performed at a single, tertiary care center. Maternal-Fetal Medicine (MFM) visits, ultrasounds, and antenatal tests of fetal well-being during the pandemic epoch (2020), which spans the first 12 weeks of the year to include pandemic onset and implementation of mitigation efforts, were compared with the same epoch of the three preceding years visually and using general linear models to account for week and year effect. An analysis of stillbirth rate comparing the pandemic time period to prepandemic was also performed. RESULTS While there were decreased MFM visits and antenatal tests of fetal well-being during the pandemic epoch compared with prepandemic epochs, only the decrease in MFM visits by year was statistically significant (p

Objective Idiopathic polyhydramnios is among the most common etiologies of polyhydramnios. However, conflicting evidence exists regarding the relationship between polyhydramnios and neonatal morbidity. We investigated the association between pregnancies with and without idiopathic polyhydramnios and neonatal morbidity at term.Study Design This is a retrospective cohort study of singleton, term (i.e., ≥370/7 weeks) pregnancies from 2014 to 2018. Pregnancies complicated by fetal anomalies, pregestational diabetes, and multifetal gestation were excluded. Pregnancies complicated by idiopathic polyhydramnios were defined by the deepest vertical pocket (DVP) ≥8 cm or amniotic fluid index (AFI) ≥24 cm after 20 weeks' gestation and were compared with women without polyhydramnios at time of delivery. These groups were matched 1:2 by gestational age within 7 days at delivery and maternal race. The primary outcome was a composite neonatal morbidity (neonatal death, respiratory morbidity, hypoxic–ischemic encephalopathy, therapeutic hypothermia, seizures, and umbilical artery pH Results Idiopathic polyhydramnios was diagnosed in 192 pregnancies and were matched to 384 pregnancies without polyhydramnios. After adjustment for obesity, women with pregnancies complicated by idiopathic polyhydramnios had an increased risk of composite neonatal morbidity 21.4 versus 5.5% (adjusted risk ratio [aRR] = 4.0, 95% confidence interval [CI]: 2.3–6.7). Term neonatal respiratory morbidity was the primary driver 20.3 versus 4.2%, (aRR = 4.8, 95% CI: 2.7–8.7) and included higher use of continuous positive airway pressure 19.8 versus 3.4%, p 12 hours of newborn life 6.8 versus 1.8%, p Conclusion Idiopathic polyhydramnios is associated with term neonatal respiratory morbidity at delivery and during the subsequent hours of newborn life, compared with pregnancies without idiopathic polyhydramnios. Further studies are needed to minimize neonatal morbidity at term.Key Points

To assess the predictive value of middle cerebral artery Doppler peak systolic velocity (MCA-PSV) for moderate-severe fetal anemia following one intrauterine transfusion (IUT) and test the performance of alternate cutoffs to the recommended threshold ≥1.69 multiples of the median (MoM).This was a retrospective cohort study of patients with pregnancies affected by alloimmunization who underwent percutaneous umbilical blood sampling (PUBS) procedures from 2000 to 2020. An MCA-PSV ≥1.69 MoM was the indication for the second IUT. The primary outcome was recurrent moderate-severe fetal anemia. Receiver-operating characteristic (ROC) curves assessed the predictive ability of MCA-PSV for the primary outcome and the Youden index identified the "optimal" cutoff value. Predictive characteristics of MCA-PSV ≥1.69 MoM and the "optimal" cutoff were compared.Of the 58 patients who underwent IUT during the study period, 36 (62%) did not meet inclusion criteria. Of the remaining 22 patients who underwent a second PUBS, 12 (54.6%) fetuses had moderate or severe anemia. Following one IUT, the AUC for MCA-PSV was 0.86 (95% CI 0.70-1.00) for the primary outcome. The "optimal" cutoff MCA-PSV value was 1.74 MoM, which had a greater specificity than ≥1.69 MoM (90Raising the recommended MCA-PSV cutoff to ≥1.74 MoM for recurrent moderate-severe fetal anemia after one IUT would decrease the number of unnecessary procedures without significantly changing the sensitivity of this screening test.

Objective: Investigate marked variability in fetal heart rate (FHR) patterns before delivery and its association with neonatal morbidity and abnormal arterial cord gases. Study Design: Prospective cohort of laboring patients at term. Composite neonatal morbidity (respiratory distress, mechanical ventilation, suspected sepsis, meconium aspiration syndrome, therapeutic hypothermia, hypoxic-ischemic encephalopathy, seizure and death) and abnormal arterial cord gases (pH

OBJECTIVES To evaluate the effect of parity on performance characteristics of midtrimester cervical length (CL) in predicting spontaneous preterm birth (sPTB) before 37 weeks. METHODS This was a retrospective cohort study of 13,508 women with no history of sPTB undergoing universal transvaginal CL screening at 17 to 23 weeks' gestation from 2011 to 2016. Patients who declined screening or with unknown delivery outcomes were excluded. Areas under the receiver operator characteristic curves were used to assess and compare the predictive ability of CL screening for sPTB. The sensitivity, specificity, and positive and negative predictive values were estimated for specific CL cutoffs for prediction of sPTB. RESULTS There were 20,100 patients, of whom 2087 (10%) declined screening and 4505 (22%) did not meet inclusion criteria. Of the remaining 13,508 patients, 43% were nulliparous. The incidence rates of sPTB were 6.5% in nulliparas and 4.9% in multiparas (P

Background Worldwide, 10% of babies are born preterm, defined as a live birth before 37 weeks of gestation. Preterm birth is the leading cause of neonatal death, and survivors face lifelong risks of adverse outcomes. New approaches with large sample sizes are needed to identify strategies to predict and prevent preterm birth. The primary aims of the Washington University Prematurity Research Cohort Study were to conduct three prospective projects addressing possible causes of preterm birth and provide data and samples for future research. Study design Pregnant patients were recruited into the cohort between January 2017 and January 2020. Consenting patients were enrolled into the study before 20 weeks’ gestation and followed through delivery. Participants completed demographic and lifestyle surveys; provided maternal blood, placenta samples, and cord blood; and participated in up to three projects focused on underlying physiology of preterm birth: cervical imaging (Project 1), circadian rhythms (Project 2), and uterine magnetic resonance imaging and electromyometrial imaging (Project 3). Results A total of 1260 participants were enrolled and delivered during the study period. Of the participants, 706 (56%) were Black/African American, 494 (39%) were nulliparous, and 185 (15%) had a previous preterm birth. Of the 1260 participants, 1220 (97%) delivered a live infant. Of the 1220 with a live birth, 163 (14.1%) had preterm birth, of which 74 (6.1%) were spontaneous preterm birth. Of the 1220 participants with a live birth, 841 participated in cervical imaging, 1047 contributed data and/or samples on circadian rhythms, and 39 underwent uterine magnetic resonance imaging. Of the 39, 25 underwent electromyometrial imaging. Conclusion We demonstrate feasibility of recruiting and retaining a diverse cohort in a complex prospective, longitudinal study throughout pregnancy. The extensive clinical, imaging, survey, and biologic data obtained will be used to explore cervical, uterine, and endocrine physiology of preterm birth and can be used to develop novel approaches to predict and prevent preterm birth.

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 HDP incidence. However, our results suggest that monitoring of patients with antepartum COVID-19 infection should encompass precautions for HDP development.

Chronic hypertension complicates up to 5% of pregnancies and is increasing in prevalence. Women with hypertension have increased risks of serious maternal morbidity and mortality in pregnancy, including the development of preeclampsia. In 2017, new guidelines reclassified blood pressure into the following 4 categories: normal (120/80 mm Hg), elevated (120-129/80 mm Hg), stage 1 hypertension (130-139/80-89 mm Hg), and stage 2 hypertension (140/90 mm Hg). This new classification doubles the number of reproductive-aged women with hypertension. Furthermore, studies have demonstrated that women entering pregnancy with stage 1 hypertension have an increased risk of developing hypertensive disorders of pregnancy compared with their normotensive counterparts, but the time course to the development of hypertensive disorders of pregnancy in these women remains uncertain.We sought to evaluate the risk of developing a hypertensive disorder of pregnancy and the time to the development of these disorders in women with stage 1 hypertension vs both normotensive women and those with stage 2 hypertension.This was a retrospective cohort study of all patients from a single tertiary care center with singleton gestations from 2014 to 2016. Patients at prenatal visits before 20 weeks of gestation were classified into 3 blood pressure groups: normotensive (130/80 mm Hg), stage 1 hypertension (130-139/80-89 mm Hg), or stage 2 hypertension (≥140/90 or a history of chronic hypertension). The primary outcome, time to the development of a hypertensive disorder of pregnancy, was compared among groups using Kaplan-Meier curves and the log-rank test. Cox proportional-hazards models were used to adjust for age, race and ethnicity, pregestational diabetes mellitus, and body mass index. In addition, multiple secondary obstetrical, maternal, and neonatal outcomes were assessed.Of the 3000 women in our cohort, 2370 (79.0%) were categorized in the normotensive group, 315 (10.5%) were categorized in the stage 1 hypertension group, and 315 (10.5%) were categorized in the stage 2 hypertension group. The gestational age at diagnosis was significantly earlier in gestation among blood pressure groups (normotensive [38.7 (37.0-39.7)] vs stage 1 hypertension [38.0 (36.4-39.4)] vs stage 2 hypertension [36.4 (33.7-37.8)]; P.001). When the analysis was restricted to only those patients diagnosed with preeclampsia with severe features, the same findings were observed. Women with stage 1 hypertension exhibited a 2-fold increased risk of developing hypertensive disorders of pregnancy compared with normotensive women. Compared with women with stage 2 hypertension, women with stage 1 hypertension exhibited a milder phenotype of hypertensive disorders of pregnancy and exhibited significantly less risk of maternal and neonatal morbidities.Women with stage 1 hypertension are at increased risk of developing hypertensive disorders of pregnancy at earlier gestational ages compared with normotensive women; however, their development of a hypertensive disorder of pregnancy is skewed toward milder diseases compared with women with stage 2 hypertension. These new insights into the graded risk profile of obstetrical hypertensive diseases associated with new blood pressure categories can better inform our antepartum counseling and monitoring and surveillance plans near term and in the postpartum period.

This article provides a concise summary of a landmark paper from the field of Maternal-Fetal Medicine on antenatal fetal testing. The authors describe a novel approach to identify fetuses that are at risk of perinatal mortality. Combining ultrasonographic features and fetal heart rate monitoring, a biophysical profile (BPP) score was assigned to each fetus and the rates of perinatal mortality for each range of BPP score were determined. The article reviews the research question, funding sources, study design and outcomes. It places these findings in contemporary context and reviews relevant literature. The authors provide a clinical case to highlight the study’s applicable findings.

Anemia is one of the most commonly diagnosed comorbidities in pregnancy and is known to increase the risk of obstetrical complications. However, little is known about the effect of anemia on placental oxygen transfer and fetal oxygenation.This study examined the relationship between maternal anemia and fetal oxygenation status at delivery as measured by umbilical cord partial pressure of oxygen.This is a secondary analysis of a prospective cohort study of singleton term deliveries with universal admission complete blood count and umbilical cord gases between 2010 and 2014. Maternal anemia was defined as hemoglobin of ≤10 g/dL on admission. The primary outcomes were umbilical artery and vein partial pressure of oxygen; the secondary outcomes were acidemia (umbilical artery pH of7.1), hypoxemia (umbilical artery or umbilical vein partial pressure of oxygen at the5th percentile), and hyperoxemia (umbilical artery/umbilical vein partial pressure of oxygen at the90th percentile). Outcomes were compared between patients with and without anemia.Maternal anemia was associated with a significantly higher umbilical artery partial pressure of oxygen (median [interquartile range], 20 [16-24] vs 19 [15-24] mm Hg; P=.01) and umbilical vein partial pressure of oxygen (median [interquartile range], 30 [25-36] vs 29 [23-34] mm Hg; P.01). Neonates born to anemic mothers were more likely to have umbilical vein hyperoxemia (15.7% vs 10.9%; adjusted odds ratio, 1.51; 95% confidence interval, 1.26-1.81) with no difference in umbilical artery hyperoxemia. There was no difference in the rates of umbilical artery or umbilical vein hypoxemia. Although maternal anemia was associated with a significant difference in umbilical artery pH (7.28±0.060 vs 7.27±0.065; P.01), there was no difference in the rate of neonatal acidemia between groups (1.6% vs 1.9%; adjusted odds ratio, 0.93; 95% confidence interval, 0.55-1.55).Umbilical cord oxygen content is higher in anemic mothers. Maternal anemia may lead to adaptations in maternal, placental, and fetal physiology, allowing for easier unloading of oxygen to the placenta and increased oxygen transfer to the fetus.

No large-cohort studies that examine potential racial effects on placebo hypoalgesic effects exist. To fill this void, we studied placebo effects in healthy and chronic pain participants self-identified as either African American/black (AA/black) or white. We enrolled 372 study participants, 186 with a diagnosis of temporomandibular disorder (TMD) and 186 race-, sex-, and age-matched healthy participants to participate in a placebo experiment. Using a well-established paradigm of classical conditioning with verbal suggestions, each individual pain sensitivity was measured to calibrate the temperatures for high- and low-pain stimuli in the conditioning protocol. These 2 temperatures were then paired with a red and green screen, respectively, and participants were told that the analgesic intervention would activate during the green screens to reduce pain. Participants then rated the painfulness of each stimulus on a visual analog scale ranging from 0 to 100. Racial influences were tested on conditioning strength, reinforced expectations, and placebo hypoalgesia. We found that white participants reported greater conditioning effects, reinforced relief expectations, and placebo effects when compared with their AA/black counterparts. Racial effects on placebo were observed in TMD, although negligible, short-lasting, and mediated by conditioning strength. Secondary analyses on the effect of experimenter-participant race and sex concordance indicated that same experimenter-participant race induced greater placebo hypoalgesia in TMDs while different sex induced greater placebo hypoalgesia in healthy participants. This is the first and largest study to analyze racial effects on placebo hypoalgesia and has implications for both clinical research and treatment outcomes.

Background Maternal oxygen administration is a widely used intrauterine resuscitation technique for fetuses with category II electronic fetal monitoring patterns, despite a paucity of evidence on its ability to improve electronic fetal monitoring patterns. Objective This study investigated the effect of intrapartum oxygen administration on Category II electronic fetal monitoring patterns. Study Design This is a secondary analysis of a randomized trial conducted in 2016–2017, in which patients with fetuses at ≥37 weeks’ gestation in active labor with category II electronic fetal monitoring patterns were assigned to 10 L/min of oxygen by face mask or room air until delivery. Trained obstetrical research nurses blinded to allocation extracted electronic fetal monitoring data. The primary outcome was a composite of high-risk category II features including recurrent variable decelerations, recurrent late decelerations, prolonged decelerations, tachycardia, or minimal variability 60 minutes after randomization to room air or oxygen. Secondary outcomes included individual components of the composite high-risk category II features, resolution of recurrent decelerations within 60 minutes of randomization, and total deceleration area. The outcomes between the room air and oxygen groups were compared using univariable statistics. Time-to-event analysis was used to compare time to resolution of recurrent decelerations between the groups. Paired analysis was used to compare the pre- and postrandomization outcomes within each group. Results All 114 randomized patients (57 room air and 57 oxygen) were included in this analysis. There was no difference in resolution of recurrent decelerations within 60 minutes between the oxygen and room air groups (75.4% vs 86.0%; P=.15). The room air and oxygen groups had similar rates of composite high-risk category II features including recurrent variable decelerations, recurrent late decelerations, prolonged decelerations, tachycardia, and minimal variability 60 minutes after randomization. Time to resolution of recurrent decelerations and total deceleration area were similar between the room air and oxygen groups. Among patients who received oxygen, there was no difference in the electronic fetal monitoring patterns pre- and postrandomization. Similar findings were observed in the electronic fetal monitoring patterns pre- and postrandomization in room air patients. Conclusion Intrapartum maternal oxygen administration for category II electronic fetal monitoring patterns did not resolve high-risk category II features or hasten the resolution of recurrent decelerations. These results suggest that oxygen administration has no impact on improving category II electronic fetal monitoring patterns.

Background Maternal oxygen (O2) administration is a commonly performed intrauterine resuscitation technique though to improve fetal oxygenation. However, hyperoxygenation is known to be harmful in both neonates and adults. Currently, there are no formal recommendations on whether a certain dose or duration of O2 may be most helpful in improving umbilical cord gases or neonatal outcomes. Objective We tested the hypothesis that prolonged supplemental O2 exposure during labor is associated with increased umbilical cord O2 concentrations. Study Design This was a planned secondary analysis of a randomized noninferiority trial comparing O2 with room air in laboring patients. Patients were randomized to receive either 10 L/min O2 or room air at any point during active labor when they developed a category II fetal heart tracing that would otherwise require resuscitation. The primary outcome variable for this analysis was partial pressure of O2 in the umbilical vein. The secondary outcome variable was partial pressure of O2 in the umbilical artery. These outcome variables were compared between patients with short durations of O2 exposure and those with long durations of O2 exposure, defined as Results Among the 99 patients with paired and validated cord gases who were included in this analysis, the partial pressure of O2 in the umbilical vein was significantly lower in patients who received O2 supplementation for longer durations than in those who received O2 for shorter durations (median interquartile range 25.5 [21.5–33] vs 32.5 [26.5–37.5] mm Hg; P Conclusion Longer durations of O2 exposure are not associated with a higher partial pressure of O2 in the umbilical cord. In fact, patients with longer durations of O2 exposure had lower partial pressure of O2 in the umbilical vein, suggesting impaired placental O2 transfer with prolonged O2 exposure.

Background Contemporary guidelines for labor management do not characterize abnormal labor on the basis of maternal and/or neonatal morbidity. Objective In this study, we aimed to evaluate the association of abnormal duration of the first stage of term labor and the risk of maternal and neonatal morbidity. Study Design We conducted a retrospective analysis of prospectively collected data of all consecutive women admitted for delivery at a single center at ≥37 weeks and 0 to 7 days of gestation with singleton, nonanomalous, vertex infants from 2010 to 2015, who reached 10 cm cervical dilation. Multivariable logistic regression compared odds ratios for maternal and neonatal outcomes among women above and below the 90th, 95th, and 97th percentiles for first stage of labor duration. Receiver operating characteristic curves estimated the association between first stage of labor duration and maternal morbidity. Maternal morbidity was a composite of maternal fever, hemorrhage, transfusion, or endomyometritis; prolonged second stage of labor duration; and third- or fourth-degree perineal laceration. Neonatal morbidity was a composite of hypothermic therapy, need for mechanical ventilation, respiratory distress syndrome, meconium aspiration syndrome, birth injury or trauma, and neonatal seizure or sepsis. Results Of 6823 women included in this study, 682 were anticipated to have first stage of labor duration above the 90th percentile cutoff point, which was associated with an increased risk of composite maternal morbidity, maternal fever, postpartum transfusion, prolonged second stage of labor duration, third- or fourth-degree perineal laceration, and cesarean or operative vaginal delivery (P≤.02) and an increased risk of composite neonatal morbidity, respiratory distress syndrome, need for mechanical ventilation, and neonatal sepsis (P≤.03). Composite maternal morbidity was 2.2 (95% confidence interval, 1.8–2.7), 1.9 (95% confidence interval, 1.4–2.4), and 1.8 (95% confidence interval, 1.3–2.5) times more likely to occur among women above the 90th, 95th, and 97th percentile, respectively, for first stage of labor duration from 4 to 10 cm. Composite neonatal morbidity was 2.6 (95% confidence interval, 2.1–3.2), 2.2 (95% confidence interval, 1.7–2.9), and 1.9 (95% confidence interval, 1.3–2.8) times more likely to occur among infants delivered by women above the 90th, 95th, and 97th percentiles for first stage of labor duration from 4 to 10 cm. Receiver operating characteristic curves among all women from 4 to 10 cm and 6 to 10 cm, including when stratified by parity and type of labor onset, had an area under the curve of 0.51 to 0.62 and 0.53 to 0.71 for maternal and neonatal morbidity, respectively. Thus, duration of labor has moderate predictive ability, at best, for composite maternal or neonatal morbidity. No curve demonstrated a clear point at which adverse maternal or neonatal outcomes increased that could be used to define abnormal labor. Conclusion The benefit of expectantly managing a prolonged first stage of labor with duration above the 90th percentile in anticipation of vaginal delivery must be weighed against the increased risk of composite maternal and neonatal morbidity. Risks associated with performing cesarean delivery as an alternative management for women with prolonged first stage of labor duration must also be considered.

Successfully predicting the susceptibility of individuals to placebo analgesics will aid in developing more effective pain medication and therapies, as well as aiding potential future clinical use of placebos. In pursuit of this goal, we analyzed healthy and chronic pain patients' patterns of responsiveness during conditioning rounds and their links to conditioned placebo analgesia and the mediating effect of expectation on those responses. We recruited 579 participants (380 healthy, 199 with temporomandibular disorder [TMD]) to participate in a laboratory placebo experiment. Individual pain sensitivity dictated the temperatures used for high- and low-pain stimuli, paired with red or green screens, respectively, and participants were told there would be an analgesic intervention paired with the green screens. Over two conditioning sessions and one testing session, participants rated the painfulness of each stimulus on a visual analogue scale from 0 to 100. During the testing phase, the same temperature was used for both red and green screens to assess responses to the placebo effect, which was defined as the difference between the average of the high-pain-cue stimuli and low-pain-cue stimuli. Delta scores, defined as each low-pain rating subtracted from its corresponding high-pain rating, served as a means of modeling patterns of conditioning strength and placebo responsiveness. Latent class analysis (LCA) was then conducted to classify the participants based on the trajectories of the delta values during the conditioning rounds. Classes characterized by persistently greater or increasing delta scores during conditioning displayed greater placebo analgesia during testing than those with persistently lower or decreasing delta scores. Furthermore, the identified groups' expectation of pain relief acted as a mediator for individual placebo analgesic effects. This study is the first to use LCA to discern the relationship between patterns of learning and the resultant placebo analgesia in chronic pain patients. In clinical settings, this knowledge can be used to enhance clinical pain outcomes, as chronic pain patients with greater prior experiences of pain reduction may benefit more from placebo analgesia.

Genomic studies on the placebo hypoalgesic effects highlight a promising link between single nucleotide polymorphisms (SNPs) in the dopamine, opioid, and endocannabinoid genes and placebo hypoalgesia. Yet, epistasis, replication, GWAS, and omics studies are missing. In this chapter, we elaborate upon the state-of-the-science of the genomics of the placebo and nocebo effect across pain conditions and populations with a focus on current challenges and areas of future discovery. We indicate directions for future research that will help fully understand the complexity of placebo effects and molecular mechanisms that predict individuals who may display a placebo effect.

Background The safest mode of delivery to use for very preterm infants is an ongoing topic of debate. There are many reasons to perform a cesarean delivery in cases of extremely preterm and very preterm infants, including indication for labor, fetal distress, maternal indications, and malpresentation. Objective This study aimed to determine whether cesarean delivery is associated with a considerable improvement in neonatal morbidity. Study Design This study is a retrospective cohort study of all singleton pregnancies, delivered from 22 to 29 weeks’ gestation between 2010 and 2015, admitted for preterm labor or preterm premature rupture of membranes and excluded neonates with a delivery weight ≤500 g, multiple gestations, cases with intrauterine fetal demise, and induced terminations. The primary outcome for the study was a neonatal morbidity composite (Apgar score of 28 days), intraventricular hemorrhage, necrotizing enterocolitis, coagulopathy, discharged on home ventilator support, or discharged with enteric feeding tube). Cesarean deliveries were performed for standard obstetrical indications. Regression models were used and adjusted for nulliparity, delivery year, and presentation at the time of delivery to determine whether cesarean delivery is associated with neonatal morbidity or neonatal death. Results There were 271 eligible deliveries, which included 128 cesarean deliveries and 143 vaginal deliveries. The cesarean delivery group had fewer nulliparous patients and more fetuses presenting in breech position at the time of delivery. The overall composite neonatal morbidity occurred in 202 of the 271 (74.5%) deliveries and mortality occurred in 26 of the 271 (9.59%) deliveries. When adjusting for nulliparity, delivery year, and fetal presentation at the time of delivery, cesarean delivery was associated with a decreased risk for death in the delivery room or within 24 hours after delivery (adjusted risk ratio, 0.18; 95% confidence interval, 0.05–0.63; P=.03). Cesarean delivery was associated with an increased use of exogenous surfactant (adjusted risk ratio, 1.20; 95% confidence interval, 1.05–1.38; P=.01) and bag mask ventilation (adjusted risk ratio, 1.17; 95% confidence interval, 1.01–1.37; P=.03). In a secondary analysis that included only patients who received a complete course of steroids, there were no differences in the composite morbidity or mortality. Conclusion Cesarean delivery performed for standard obstetrical indications in cases of very preterm neonates is associated with a decreased risk for death in the delivery room or within 24 hours of delivery but is not associated with an improvement in the overall morbidity or mortality.

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. Trial Registration ClinicalTrials.gov Identifier:NCT02741284

OBJECTIVE The COVID-19 pandemic has had a disproportionate effect on pregnant women, with higher rates of viral infection and disease severity. 1 The development of highly effective vaccines has significantly reduced SARS-CoV-2 transmission and clinical disease. 2 However, vaccine uptake has been low in the pregnant population. 3 The Centers for Disease Control and Prevention guidance suggests that limited vaccine access, not vaccine hesitancy, has driven the lower uptake rates in at-risk populations. 4 We describe our experience with vaccination uptake rates among high-risk obstetrical patients before and after onsite BNT162b2 messenger RNA vaccination availability in outpatient clinics as part of a pilot program to improve vaccine access among pregnant patients. STUDY DESIGN This was a quality improvement project at a single academic medical center. Onsite vaccination was available once a week at 2 high-risk obstetrical clinics staffed by obstetrical residents, maternal-fetal medicine (MFM) fellows, and MFM attendings were selected for our vaccine pilot program. Onsite vaccinations were immediately available for use in the clinic starting May 11, 2021. Data were collected over a 4-week period (April 27, 2021, to May 20, 2021), which included 4 clinic days before onsite vaccine availability (April 27, 2021 to May 10, 2021) and 4 days with onsite vaccine availability (May 11, 2021, to May 20, 2021). Patients were considered exposed to onsite vaccination if they had any clinic visits during the latter 2 weeks of the study period. All patients were counseled by providers at each visit using our institution's standardized COVID-19 vaccination discussion tool designed for pregnant and breastfeeding patients. 5 Counseling was documented in each patient's chart per the American College of Obstetricians and Gynecologists. Before and throughout the study period, pregnancy was listed as a qualifying condition for priority vaccination in Missouri and Illinois. At this time, vaccinations were readily available in the local area surrounding our clinical space. Data on vaccine administration were collected via the Missouri and Illinois state databases over a period of 1 month after the pilot program was closed, allowing for the collection of data on patients who pursued vaccination offsite for scheduling or personal reasons. This project was deemed exempt by the Office for Human Research Protections. RESULTS We reviewed data from 124 clinic visits, where a total of 93 individual patients were seen in the 4-week period; 6 had previously been vaccinated at external sites and the remaining 87 were eligible (Figure). The majority of our patient population was non-Hispanic Black women with public or no insurance ( Table ). Of the 32 eligible patients seen and counseled before onsite vaccination availability, 1 (3%) proceeded to receive the vaccination offsite. Of the 55 eligible patients seen and counseled after onsite vaccination availability, 2 (3%) proceeded with onsite vaccination and an additional 4 (7%) proceeded with vaccination offsite. Onsite vaccination availability did not significantly increase the vaccination rates (3% vs 11%; P=.22). Of the 55 eligible patients counseled during onsite vaccination availability, 25 were seen and counseled exclusively during the onsite vaccination pilot period and none of these patients accepted onsite vaccination or pursued vaccination offsite. CONCLUSION Because only 3% of eligible, high-risk obstetrical patients proceeded with onsite vaccination, our experience suggests that vaccine hesitancy, not availability, is a critical driver of the low vaccination rates in this population. Although a larger sample size may have demonstrated statistical difference, the overall low vaccination uptake rate forced the closure of our pilot program over concerns for wasted vaccination doses. In a population at high risk for progression to severe COVID-19, only 14% of our study population was vaccinated, whereas Missouri reported a 41% vaccination rate during this time. 6 These findings suggest that increased access alone may not improve vaccination rates in obstetrical patients even after counseling by expert clinicians. These findings are limited by the pre/post nature of the comparison, exposing the sample to bias as vaccination recommendations and population sentiment was rapidly evolving during this time period. However, the consistency of counseling and patient population provided by a single clinical setting limited other sources of bias during the study period. Vaccine hesitancy is multifactorial and complex and urgently requires more evaluation in this high-risk population. Vaccine hesitancy in pregnancy is well documented, but early reports suggest that the COVID-19 vaccination uptake rate is markedly lower than that of other vaccines during pregnancy. Our finding that none of the women who were seen exclusively during the onsite vaccination period accepted vaccination may suggest that repeat clinic visits and the associated establishment of rapport and trust is a vital part of vaccine decision making. Earlier intervention, before patient views on novel therapeutics such as vaccinations can be formulated and fixed, may aid in uptake. Further qualitative work and inclusion of pregnant women in vaccine trials is an initial step.

Objective Many research studies in the United States came to an abrupt halt when the World Health Organization declared the Coronavirus 2019 (COVID-19) pandemic in March 2020, including ongoing perinatal studies addressing national rates of maternal and fetal morbidity. Research on Labor & Delivery units (L&D) was particularly vulnerable to setbacks due to universal COVID-19 testing policies and asymptomatic infection rates almost 16 times higher than that of other surgical units. 1 We evaluated the impact of the COVID-19 pandemic on L&D research operations and recruitment at a single center. Study Design This cross-sectional study, performed at a tertiary care academic center, evaluated temporal trends in research recruitment among women admitted for labor or induction of labor at ≥37 weeks gestation. This study was IRB exempt. Onsite research recruitment was paused on March 16, 2020 with phased resumption starting July 6, 2020. By August 6, 2020, all L&D studies resumed recruitment. Universal COVID-19 testing on L&D started in May 2020. Upon resuming recruitment, only patients with negative COVID-19 tests were approached by research staff. Patients with pending COVID-19 results at time of active labor or those who declined COVID-19 tests were not approached. We calculated approach rates as the number of women approached for enrollment among all women admitted for delivery and consent rates as the number of women who consented for participation in at least one study among those admitted for delivery. Univariate analyses were used to compare the approach and consent rates pre-research pause (November 2019-March 2020) to the rates post-pause (August-December 2020). A single approach process was used for all studies both pre- and post- research pause. Results Four studies (3 randomized trials and 1 prospective cohort study) recruited patients pre-research pause. Post-pause, the same four studies resumed recruitment and 2 additional studies (1 randimized trial and 1 prospective cohort study) intiated recruitment. The inclusion criteria for all six studies was singleton pregnancies admitted for spontaneous labor or induction of labor at ≥37 weeks gestation. More than 75% of the principal investigators for all studies were trainees or pretenure faculty. The number of research staff was the same pre- and post-pause. There were 1213 and 1219 deliveries in the pre- and post-periods respectively, with no differences in patient demographics between periods. The majority of patients who delivered in both periods were Black (53.3% pre vs 52.5% post, p=0.50). The COVID-19 positivity rate was 5% during and after the research pause.There was a lower proportion of women approached for enrollment in the post period (46.1% vs 33.8%, p Conclusion The pandemic poses a threat to L&D research recruitment. Despite stable delivery volume and research staff capacity, fewer patients were approached and consented for research participation during the pandemic. These results are likely explained by COVID-19 status and testing protocols as patients with pending, unknown, or positive COVID-19 tests were not approached. An alternate consideration for lower approach rates during the pandemic is research staff apprehension. Decreased research participation during the pandemic is less likely to be attributed to patient apprehension, as the proportion of women who consented among those approached remained stable.

Physical activity in pregnancy is associated with decreased risks of adverse pregnancy outcomes such as gestational diabetes and preeclampsia. However, the relationship between the amount and type of physical activity during pregnancy and subsequent labor outcomes remains unclear.This study aimed to test the hypothesis that higher levels of physical activity across different lifestyle domains in pregnancy are associated with a shorter duration of labor.This study is a secondary analysis of a prospective cohort study in which patients with singleton pregnancies without a major fetal anomaly were administered the Kaiser Physical Activity Survey in each trimester. The Kaiser Physical Activity Survey was designed specifically to quantify various types of physical activities in women and includes 4 summative indices-housework/caregiving, active living habits, sports, and occupation. The study included women at full-term gestations admitted for induction of labor or spontaneous labor. The primary outcome of this analysis was duration of the second stage of labor. Secondary outcomes were duration of the active stage, prolonged first and second stage, mode of delivery, rates of second-stage cesarean delivery, operative vaginal delivery, severe perineal lacerations, and postpartum hemorrhage. These outcomes were compared between patients with and without high physical activity levels, defined as overall Kaiser Physical Activity Survey score ≥75th percentile in the third trimester. Multivariable logistic regression was used to adjust for obesity and epidural use. In addition, a subgroup analysis of nulliparous patients was performed.A total of 811 patients with complete Kaiser Physical Activity Survey data in the third trimester were included in this analysis. The median Kaiser Physical Activity Survey score was 9.5 (8.2-10.8). Of the 811 patients, 203 (25%) had higher levels of physical activity in pregnancy. There was no difference in the duration of the second stage of labor between patients with and without higher physical activity levels (1.29±2.94 vs 0.97±2.08 hours; P=.15). The duration of active labor was significantly shorter in patients with higher levels of physical activity (5.77±4.97 vs 7.43±6.29 hours; P=.01). Patients with higher physical activity levels were significantly less likely to have a prolonged first stage (9.8% vs 19.4%; P.01; adjusted relative risk, 0.55; 95% confidence interval, 0.34-0.83). However, rates of prolonged second-stage cesarean delivery, operative vaginal deliveries, and perineal lacerations were similar between the 2 groups.Patients who are more physically active during pregnancy have a shorter duration of active labor.