Intrapartum exposure to synthetic oxytocin, maternal BMI, and neurodevelopmental outcomes in children within the ECHO consortium.

BACKGROUND: Synthetic oxytocin (sOT) is frequently administered during parturition. Studies have raised concerns that fetal exposure to sOT may be associated with altered brain development and risk of neurodevelopmental disorders. In a large and diverse sample of children with data about intrapartum sOT exposure and subsequent diagnoses of two prevalent neurodevelopmental disorders, i.e., attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), we tested the following hypotheses: (1) Intrapartum sOT exposure is associated with increased odds of child ADHD or ASD; (2) associations differ across sex; (3) associations between intrapartum sOT exposure and ADHD or ASD are accentuated in offspring of mothers with pre-pregnancy obesity. METHODS: The study sample comprised 12,503 participants from 44 cohort sites included in the Environmental Influences on Child Health Outcomes (ECHO) consortium. Mixed-effects logistic regression analyses were used to estimate the association between intrapartum sOT exposure and offspring ADHD or ASD (in separate models). Maternal obesity (pre-pregnancy BMI ≥ 30 kg/m2) and child sex were evaluated for effect modification. RESULTS: Intrapartum sOT exposure was present in 48% of participants. sOT exposure was not associated with increased odds of ASD (adjusted odds ratio [aOR] 0.86; 95% confidence interval [CI], 0.71-1.03) or ADHD (aOR 0.89; 95% CI, 0.76-1.04). Associations did not differ by child sex. Among mothers with pre-pregnancy obesity, sOT exposure was associated with lower odds of offspring ADHD (aOR 0.72; 95% CI, 0.55-0.96). No association was found among mothers without obesity (aOR 0.97; 95% CI, 0.80-1.18). CONCLUSIONS: In a large, diverse sample, we found no evidence of an association between intrapartum exposure to sOT and odds of ADHD or ASD in either male or female offspring. Contrary to our hypothesis, among mothers with pre-pregnancy obesity, sOT exposure was associated with lower odds of child ADHD diagnosis.

Oxytocin-induced birth causes sex-specific behavioral and brain connectivity changes in developing rat offspring.

Despite six decades of the use of exogenous oxytocin for management of labor, little is known about its effects on the developing brain. Motivated by controversial reports suggesting a link between oxytocin use during labor and autism spectrum disorders (ASDs), we employed our recently validated rat model for labor induction with oxytocin to address this important concern. Using a combination of molecular biological, behavioral, and neuroimaging assays, we show that induced birth with oxytocin leads to sex-specific disruption of oxytocinergic signaling in the developing brain, decreased communicative ability of pups, reduced empathy-like behaviors especially in male offspring, and widespread sex-dependent changes in functional cortical connectivity. Contrary to our hypothesis, social behavior, typically impaired in ASDs, was largely preserved. Collectively, our foundational studies provide nuanced insights into the neurodevelopmental impact of birth induction with oxytocin and set the stage for mechanistic investigations in animal models and prospective longitudinal clinical studies.

Treatment of acute-onset hypertension in pregnancy: A network meta-analysis of randomized controlled trials comparing anti-hypertensives and route of administration.

BACKGROUND: Consensus on the relative efficacy of available antihypertensive agents used in pregnancy is lacking. OBJECTIVE: To compare treatment success with antihypertensives and categorize by route of administration. SEARCH STRATEGY: MEDLINE, Embase, PubMed, Web of Science, Scopus, CINAHL, and clinicaltrials.gov were searched without date restriction. DATA COLLECTION: Peer-reviewed randomized controlled trials (RCTs) comparing pharmacologic agents used to treat hypertension in parturients were included. Evaluated treatment groups included IV-labetalol (BBIV), IV-hydralazine (DIV), oral-nifedipine (CCBPO), sublingual nifedipine (CCBSL), IV-calcium channel blocker (nonspecific)(CCBIV), IV-nitroglycerine (NTG), epoprostenol infusion (PRO), IV-ketanserin (5HT2B), IV-diazoxide (BZO), oral-nifedipine + methyldopa (CCBAG), oral-methyl-dopa (AAG), and oral prazosin (ABPO). ANALYSIS: Seventy-four studies (8324 patients) were eligible post PRISMA guidelines screening. Results were pooled using a Bayesian-approach for success of treatment (study defined target blood pressure), time to achieve target pressure, and neonatal intensive-care admissions. RESULTS: Treatment success (primary outcome, 55 trials with 5518 patients) was analyzed. Surface under the cumulative ranking curve (SUCRA) was categorized for 13 drugs, CCBPO (0.84) followed by CCBSL (0.78) were most likely to be effective in achieving target blood pressure. After sub-grouping by presence/absence of preeclampsia, CCB-PO ranked highest for both [(0.82) vs. (0.77), respectively]. Serotonin antagonists (0.99) and nitroglycerin (0.88) ranked highest for time to target pressure. NICU admissions were lowest for alpha-2 agonists (0.89), followed by BB PO (0.82) and hydralazine IV (0.49). CONCLUSION: Oral calcium-channel blockers ranked highest for treatment success. Ketanserin achieved target blood pressure fastest, warranting additional research. The results should be interpreted with caution as SUCRA values may not indicate whether the differences between interventions have clinically meaningful effect sizes.

Pregnancy-induced differential expression of SARS-CoV-2 and influenza a viral entry factors in the lower respiratory tract.

Despite differences in the clinical presentation of coronavirus disease-19 and pandemic influenza in pregnancy, fundamental mechanistic insights are currently lacking because of the difficulty in recruiting critically ill pregnant subjects for research studies. Therefore, to better understand host-pathogen interaction during pregnancy, we performed a series of foundational experiments in pregnant rats at term gestation to assess the expression of host entry factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) and genes associated with innate immune response in the lower respiratory tract. We report that pregnancy is characterized by a decrease in host factors mediating SARS-CoV-2 entry and an increase in host factors mediating IAV entry. Furthermore, using flow cytometric assessment of immune cell populations and immune provocation studies, we show an increased prevalence of plasmacytoid dendritic cells and a Type I interferon-biased environment in the lower respiratory tract of pregnancy, contrary to the expected immunological indolence. Our findings, therefore, suggest that the dissimilar clinical presentation of COVID-19 and pandemic influenza A in pregnancy could partly be due to differences in the extent of innate immune activation from altered viral tropism and indicate the need for comparative mechanistic investigations with live virus studies.

Anesthetics inhibit phosphorylation of the ribosomal protein S6 in mouse cultured cortical cells and developing brain.

Introduction: The development and maintenance of neural circuits is highly sensitive to neural activity. General anesthetics have profound effects on neural activity and, as such, there is concern that these agents may alter cellular integrity and interfere with brain wiring, such as when exposure occurs during the vulnerable period of brain development. Under those conditions, exposure to anesthetics in clinical use today causes changes in synaptic strength and number, widespread apoptosis, and long-lasting cognitive impairment in a variety of animal models. Remarkably, most anesthetics produce these effects despite having differing receptor mechanisms of action. We hypothesized that anesthetic agents mediate these effects by inducing a shared signaling pathway. Methods: We exposed cultured cortical cells to propofol, etomidate, or dexmedetomidine and assessed the protein levels of dozens of signaling molecules and post-translational modifications using reverse phase protein arrays. To probe the role of neural activity, we performed separate control experiments to alter neural activity with non-anesthetics. Having identified anesthetic-induced changes in vitro, we investigated expression of the target proteins in the cortex of sevoflurane anesthetized postnatal day 7 mice by Western blotting. Results: All the anesthetic agents tested in vitro reduced phosphorylation of the ribosomal protein S6, an important member of the mTOR signaling pathway. We found a comparable decrease in cortical S6 phosphorylation by Western blotting in sevoflurane anesthetized neonatal mice. Using a systems approach, we determined that propofol, etomidate, dexmedetomidine, and APV/TTX all similarly modulate a signaling module that includes pS6 and other cell mediators of the mTOR-signaling pathway. Discussion: Reduction in S6 phosphorylation and subsequent suppression of the mTOR pathway may be a common and novel signaling event that mediates the impact of general anesthetics on neural circuit development.

Readability, Content, and Quality of Online Patient Education Materials on Anesthesia and Neurotoxicity in the Pediatric Population.

OBJECTIVE: Internet-based patient education materials (PEMs) are often above the recommended sixth grade reading level recommended by the U.S. Department of Health and Human Services. In 2016 the U.S. Food and Drug Administration (FDA) released a warning statement against use of general anesthetic drugs in children and pregnant women due to concerns about neurotoxicity. The aim of this study is to evaluate readability, content, and quality of Internet-based PEMs on anesthesia in the pediatric population and neurotoxicity. STUDY DESIGN: The websites of U.S. medical centers with pediatric anesthesiology fellowship programs were searched for PEMs pertaining to pediatric anesthesia and neurotoxicity. Readability was assessed. PEM content was evaluated using matrices specific to pediatric anesthesia and neurotoxicity. PEM quality was assessed with the Patient Education Material Assessment Tool for Print. A one-sample t-test was used to compare the readability of the PEMs to the recommended sixth grade reading level. RESULTS: We identified 27 PEMs pertaining to pediatric anesthesia and eight to neurotoxicity. Mean readability of all PEMs was greater than a sixth grade reading (p <0.001). While only 13% of PEMs on anesthesia for pediatric patient mentioned the FDA warning, 100% of the neurotoxicity materials did. PEMs had good understandability (83%) and poor actionability (60%). CONCLUSION: The readability, content, and quality of PEMs are poor and should be improved to help parents and guardians make informed decisions about their children's health care. KEY POINTS: · The FDA issued a warning statement against the use of general anesthetic drugs in children and pregnant women.. · Readability, content, and quality of Internet-based patient education materials on the topic of neurotoxicity are poor.. · Improving the readability, content, and quality of PEMs could aid parents in making important health care decisions..

A randomized feasibility pilot-study of intravenous and subcutaneous administration of ketamine to prevent postpartum depression after planned cesarean delivery under neuraxial anesthesia.

BACKGROUND: Evidence suggests ketamine may prevent postpartum depression (PPD) after cesarean delivery (CD) although intolerability and inconvenience of administration are problematic. We assessed the feasibility of studying ketamine (0.5 mg/kg, via subcutaneous injection or 40-min intravenous infusion) to prevent PPD after CD. METHODS: Twenty-three women scheduled for cesarean delivery under neuraxial anesthesia were randomized to one of three groups: subcutaneous ketamine (SC Group, n = 8), intravenous ketamine (IV Group, n = 8) or placebo (n = 7). We measured depression (Edinburgh Postpartum Depression Scale [EPDS]) scores pre-operatively and at 1, 2, 21 and 42 days postoperatively. Anxiety, adverse effects, surgical site pain and analgesic consumption were also assessed. Feasibility was assessed based on acceptability, burden of disease, ability to collect study data and, tolerability of interventions. RESULTS: Baseline characteristics of groups were similar, however, more women in the placebo group had pre-existing anxiety disorder (p = 0.03). 20.7% (25/121) of those approached consented to participate and 34.8% (8/23), of those assessed, screened positive for depression in the postpartum (EPDS > 12). PPD screening data was complete in 78.3% (18/23). No differences were observed for any adverse effect outcomes except for fewer incidences of intraoperative shivering with ketamine (SC: 25%, IV: 0% and Placebo: 85.7%, p = 0.01). No statistically significant difference in positive screening for PPD was observed (SC: 14.3%, IV: 50% and Placebo: 42.9%, p = 0.58). CONCLUSION: An RCT was judged to be feasible and there was no evidence of intolerability of either route of ketamine administration. Dispensing with the need for intravenous access makes the subcutaneous route a particularly attractive option for use in the postpartum population. Further examination of these interventions to prevent, and possibly treat, postpartum depression is warranted. TRIAL REGISTRATION: NCT04227704, January 14th, 2020.

Upregulated influenza A viral entry factors and enhanced interferon-alpha response in the nasal epithelium of pregnant rats.

Despite the increased severity of influenza A infection in pregnancy, knowledge about the expression of cell entry factors for influenza A virus (IAV) and the innate immune response in the nasal epithelium, the primary portal of viral entry, is limited. Here, we compared the expression of IAV cell entry factors and the status of the innate immune response in the nasal epithelium of pregnant vs. non-pregnant female rats. IAV cell entry factors - sialic acid [SA] α-2,3- and α-2,6-linked glycans for avian and human IAV, respectively - were detected and quantified with lectin-based immunoblotting and flow cytometry. Baseline frequencies of innate immune cell phenotypes in single cell suspensions of the nasal epithelium were studied with flow cytometry. Subsequently, the magnitude of interferon and cytokine responses was studied with ELISA and cytokine arrays after intranasal resiquimod, a Toll-like receptor 7/8 agonist that mimics IAV infection. We noted substantially increased expression of cell entry factors for both avian and human IAV in the nasal epithelium during pregnancy. Assessment of the innate immune state of the nasal epithelium during pregnancy revealed two previously unreported features: (i) increased presence of tissue-resident plasmacytoid dendritic cells, and (ii) markedly enhanced release of interferon-α but not of the other interferons or cytokines 2 h after intranasal resiquimod. Collectively, our findings challenge the conventional notion of pregnancy-induced immunosuppression as a cause for severe influenza A disease and suggest the need for focused studies on viral tropism during pregnancy to better understand the proximate cause for the observed immunopathology.

The association of fetal acidemia with adverse neonatal outcomes at time of scheduled cesarean delivery.

BACKGROUND: Fetal acidemia at the time of a scheduled cesarean delivery is generally unexpected. In the setting of reassuring preoperative monitoring, the duration of fetal acidemia in this scenario is presumably brief. The neonatal sequelae and risks associated with brief fetal acidemia in this setting are unknown. OBJECTIVE: We aimed to assess whether fetal acidemia at the time of a scheduled prelabor cesarean delivery is associated with adverse neonatal outcomes. STUDY DESIGN: This was a retrospective cohort study of singleton, term, nonanomalous, liveborn neonates delivered by scheduled cesarean delivery that was performed under regional anesthesia from 2004 to 2014 at a single tertiary care center with a universal umbilical cord gas policy. Neonates born to laboring gravidas and those whose cesarean delivery was performed for nonreassuring fetal status were excluded. All included patients had reassuring preoperative fetal monitoring. The primary outcome was a composite adverse neonatal outcome that included neonatal death, encephalopathy, therapeutic hypothermia, seizures, intubation, and respiratory distress. This outcome was compared between patients with and those without fetal acidemia (umbilical artery pH <7.2). A multivariable logistic regression was used to adjust for confounders. Cases of fetal acidemia were further characterized as respiratory, metabolic, or mixed acidemia based on additional umbilical cord gas values. Secondary analyses examining the association between the type of acidemia and neonatal outcomes were also performed. RESULTS: Of 2081 neonates delivered via scheduled cesarean delivery, 252 (12.1%) had fetal acidemia at the time of delivery. Acidemia was more common in breech neonates and in neonates born to gravidas with obesity and gestational diabetes mellitus. Compared with fetuses with normal umbilical artery pH, those with fetal acidemia were at a significantly increased risk for adverse neonatal outcome (adjusted relative risk, 2.95; 95% confidence interval, 2.03-4.12). This increased risk was similar regardless of the type of acidemia. CONCLUSION: Even a brief period of mild acidemia is associated with adverse neonatal outcomes at the time of a scheduled cesarean delivery despite reassuring preoperative monitoring. Addressing modifiable intraoperative factors that may contribute to fetal acidemia at the time of a scheduled cesarean delivery, such as maternal hypotension and prolonged operative time, is an important priority to potentially decrease neonatal morbidity in full-term gestations.

Labor induction with oxytocin in pregnant rats is not associated with oxidative stress in the fetal brain.

Despite the widespread use of oxytocin for induction of labor, mechanistic insights into fetal/neonatal wellbeing are lacking because of the absence of an animal model that recapitulates modern obstetric practice. Here, we create and validate a hi-fidelity pregnant rat model that mirrors labor induction with oxytocin in laboring women. The model consists of an implantable preprogrammed microprocessor-controlled infusion pump that delivers a gradually escalating dose of intravenous oxytocin to induce birth at term gestation. We validated the model with molecular biological experiments on the uterine myometrium and telemetry-supported assessment of changes in intrauterine pressure. Finally, we applied this model to test the hypothesis that labor induction with oxytocin would be associated with oxidative stress in the newborn brain. Analysis of biomarkers of oxidative stress and changes in the expression of associated genes were no different between oxytocin-exposed and saline-treated pups, suggesting that oxytocin-induced labor was not associated with oxidative stress in the developing brain. Collectively, we provide a viable and realistic animal model for labor induction and augmentation with oxytocin that would enable new lines of investigation related to the impact of perinatal oxytocin exposure on the mother-infant dyad.

Preventing postpartum hemorrhage after cesarean delivery: a network meta-analysis of available pharmacologic agents.

BACKGROUND: Postpartum hemorrhage causes a quarter of global maternal deaths. The World Health Organization recommends oxytocin as the first line agent to prevent hemorrhage during cesarean delivery. However, some randomized controlled trials suggest that other uterotonics are superior. OBJECTIVE: We conducted a network meta-analysis comparing the ability of pharmacologic agents to reduce blood loss and minimize the need for additional uterotonics during cesarean delivery. DATA SOURCES: We searched the Cochrane Central Register of Controlled Trials, Embase, and MEDLINE databases from inception to May 2020. STUDY ELIGIBILITY CRITERIA: We included randomized controlled trials that compared oxytocin, carbetocin, misoprostol, ergometrine, carboprost, or combinations of these in the prevention of postpartum hemorrhage during cesarean delivery. METHODS: We performed a systematic review followed by an NMA in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Quality of the evidence was assessed with the Confidence in Network Meta-Analysis approach and Grading of Recommendations, Assessment, Development and Evaluations tool within the summary of findings table. Our primary outcomes were the estimated blood loss and need for additional uterotonics. Secondary outcomes included nausea and postpartum hemorrhage of >1000 mL. We performed sensitivity analyses to explore the influence of surgical context and oxytocin administration strategy. RESULTS: A total of 46 studies with 7368 participants were included. Of those, 21 trials (6 agents and 3665 participants) formed the "estimated blood loss" network and, considering the treatment effects, certainty in the evidence, and surface under the cumulative ranking curve scores, carbetocin was assessed to probably be superior to oxytocin, but only in reducing the estimated blood loss by a clinically insignificant volume (54.83 mL; 95% confidence interval, 26.48-143.78). Misoprostol, ergometrine, and the combination of oxytocin and ergometrine were assessed to probably be inferior, whereas the combination of oxytocin and misoprostol was assessed to definitely be inferior to oxytocin. A total of 37 trials (8 agents and 6193 participants) formed the "additional uterotonic" network and, again, carbetocin was assessed to probably be superior to oxytocin, requiring additional uterotonics 185 (95% confidence interval, 130-218) fewer times per 1000 cases. Oxytocin plus misoprostol, oxytocin plus ergometrine, and misoprostol were assessed to probably be inferior, whereas carboprost, ergometrine, and the placebo were definitely inferior to oxytocin. For both primary outcomes, oxytocin administration strategies had a higher probability of being the best uterotonic, if initiated as a bolus. CONCLUSION: Carbetocin is probably the most effective agent in reducing blood loss and the need for additional uterotonics. Oxytocin appears to be more effective when initiated as a bolus.

Birth with synthetic oxytocin and the risk of being overweight or obese during childhood.

BACKGROUND: Despite the importance of oxytocinergic signalling for satiety regulation and energy balance, the impact of exposure to synthetic oxytocin during childbirth on obesity during childhood remains unknown. OBJECTIVES: To examine the association between oxytocin exposure during labour and the risk of being overweight or obese during childhood. METHODS: Synthetic oxytocin exposure data of mothers from the Danish Medical Birth Registry were linked with self-reported anthropometric data of their children from the Danish National Birth Cohort (5 months-11 years of age). Multinomial logistic regression and latent class growth analyses were performed to determine the association between oxytocin exposure and obesity during childhood. RESULTS: With the exception of the normal weight-to-overweight group between ages 5 and 12 months, none of the other analyses revealed a significant association between synthetic oxytocin use and the risk of being overweight until the age of 11 years. Furthermore, latent class growth analysis did not reveal an association between oxytocin exposure at birth and the risk of being overweight or obese during childhood. CONCLUSIONS: Our analysis of a large cohort of children who varied in their synthetic oxytocin exposure status at childbirth did not reveal an association between oxytocin exposure and the risk of childhood overweight/obesity.

Impact of intrauterine fetal resuscitation with oxygen on oxidative stress in the developing rat brain.

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-2'-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.

The Society for Obstetric Anesthesia and Perinatology Coronavirus Disease 2019 Registry: An Analysis of Outcomes Among Pregnant Women Delivering During the Initial Severe Acute Respiratory Syndrome Coronavirus-2 Outbreak in the United States.

BACKGROUND: Early reports associating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection with adverse pregnancy outcomes were biased by including only women with severe disease without controls. The Society for Obstetric Anesthesia and Perinatology (SOAP) coronavirus disease 2019 (COVID-19) registry was created to compare peripartum outcomes and anesthetic utilization in women with and without SARS-CoV-2 infection delivering at institutions with widespread testing. METHODS: Deliveries from 14 US medical centers, from March 19 to May 31, 2020, were included. Peripartum infection was defined as a positive SARS-CoV-2 polymerase chain reaction test within 14 days of delivery. Consecutive SARS-CoV-2-infected patients with randomly selected control patients were sampled (1:2 ratio) with controls delivering during the same day without a positive test. Outcomes were obstetric (eg, delivery mode, hypertensive disorders of pregnancy, and delivery <37 weeks), an adverse neonatal outcome composite measure (primary), and anesthetic utilization (eg, neuraxial labor analgesia and anesthesia). Outcomes were analyzed using generalized estimating equations to account for clustering within centers. Sensitivity analyses compared symptomatic and asymptomatic patients to controls. RESULTS: One thousand four hundred fifty four peripartum women were included: 490 with SARS-CoV-2 infection (176 [35.9%] symptomatic) and 964 were controls. SARS-CoV-2 patients were slightly younger, more likely nonnulliparous, nonwhite, and Hispanic than controls. They were more likely to have diabetes, obesity, or cardiac disease and less likely to have autoimmune disease. After adjustment for confounders, individuals experiencing SARS-CoV-2 infection exhibited an increased risk for delivery <37 weeks of gestation compared to controls, 73 (14.8%) vs 98 (10.2%) (adjusted odds ratio [aOR], 1.47; 95% confidence interval [CI], 1.03-2.09). Effect estimates for other obstetric outcomes and the neonatal composite outcome measure were not meaningfully different between SARS-CoV-2 patients versus controls. In sensitivity analyses, compared to controls, symptomatic SARS-CoV-2 patients exhibited increases in cesarean delivery (aOR, 1.57; 95% CI, 1.09-2.27), postpartum length of stay (aOR, 1.89; 95% CI, 1.18-2.60), and delivery <37 weeks of gestation (aOR, 2.08; 95% CI, 1.29-3.36). These adverse outcomes were not found in asymptomatic women versus controls. SARS-CoV-2 patients (asymptomatic and symptomatic) were less likely to receive neuraxial labor analgesia (aOR, 0.52; 95% CI, 0.35-0.75) and more likely to receive general anesthesia for cesarean delivery (aOR, 3.69; 95% CI, 1.40-9.74) due to maternal respiratory failure. CONCLUSIONS: In this large, multicenter US cohort study of women with and without peripartum SARS-CoV-2 infection, differences in obstetric and neonatal outcomes seem to be mostly driven by symptomatic patients. Lower utilization of neuraxial analgesia in laboring patients with asymptomatic or symptomatic infection compared to patients without infection requires further investigation.

Pregnancy as a risk factor for severe coronavirus disease 2019 using standardized clinical criteria.

BACKGROUND: As of November 18, 2020, 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 nonadmission-based, 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.

Maternal Oxygen Supplementation Compared With Room Air for Intrauterine Resuscitation: A Systematic Review and Meta-analysis.

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 Pao2 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 Pao2, 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 (I2 = 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 Pao2 (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 Pao2 (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 (Pao2: weighted mean difference, 3.60 mm Hg; 95% CI, -0.30 to 7.49 mm Hg; UA pH<7.2: relative risk, 1.34; 95% CI, 0.58-3.11). Conclusions and Relevance: This systematic review and meta-analysis suggests that studies to date showed no association between maternal oxygen and a clinically relevant improvement in UA pH or other neonatal outcomes.