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As of December 1, 2020, nearly 64 million people have been infected with the severe acute respiratory syndrome coronavirus 2 worldwide with nearly 1.5 million global deaths. The impact of this virus has continued to overwhelm hospital infrastructure and demanded remodeling of healthcare systems. With rising concerns for a third, and possibly the largest, wave of individuals infected with the virus, national leaders are continuing to seek avenues by which we can further limit disease transmission and prevent infection with the use of vaccination. To our knowledge, no clinical trial evaluating vaccines to prevent coronavirus disease 2019 has included pregnant women. In December 2020, it was anticipated that the Food and Drug Administration will approve at least 1 or 2 mRNA-based coronavirus disease 2019 vaccine under the Emergency Use Authorization based on phase 3 clinical trial efficacy data. Both Pfizer and Moderna have manufactured mRNA-based vaccines with 95% and 94.1% efficacy against the severe acute respiratory syndrome coronavirus 2. AstraZeneca has manufactured a vaccine using a viral vector demonstrating early efficacy as well, and this next-generation platform has previously been utilized with the Ebola vaccine and safely administered during pregnancy with an acceptable safety profile. Approval of these vaccines will have a tremendous impact on the ongoing pandemic, yet there remains a lack of data for use of coronavirus disease 2019 vaccine in pregnant women. In this article, we seek to discuss the available data regarding treatment and prevention of coronavirus disease 2019 in pregnancy and address the growing questions regarding how best to approach vaccine access and administration in the pregnant population., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Understanding the pathophysiology, management, and prevention of emerging infectious diseases among pregnant women is imperative to achieve a successful response from the medical community. Ebola and Zika viruses represent infections with profound public health implications. In particular, Ebola virus is associated with high case fatality and pregnancy and neonatal loss rates, while Zika virus has been associated with multiple congenital anomalies; these features present critical clinical dilemmas for management of pregnant and reproductive aged women. The objective of this article is to summarize key background information and best practices for management of Ebola and Zika virus in pregnancy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Treatment of viral infections is geared toward ameliorating maternal symptoms and minimizing perinatal transmission. Multidisciplinary teams often are required to manage sequelae due to viral diseases in patients with preterm premature rupture of membranes (PPROM). although data are scarce regarding the antepartum management of common viruses in PPROM, essential principles may be extrapolated from national guidelines and studies in gravid patients. The well-established risks of prematurity are weighed against the often unclear risks of vertical transmission., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Chorioamnionitis can have a highly variable definition with substantial maternal and fetal morbidity, with higher frequencies in preterm births. With the recently updated intraamniotic infection diagnostic criteria by the American College of Obstetricians and Gynecologists, fewer women experiencing preterm delivery may qualify for intrapartum antibiotic treatment, potentially resulting in higher postpartum infectious morbidity., Objective: This study aimed to estimate whether the proportion of women delivering preterm who develop postpartum endometritis differs between subjects diagnosed as having clinical chorioamnionitis and those meeting the American College of Obstetricians and Gynecologists' criteria for intraamniotic infection., Study Design: Secondary analysis was conducted using a randomized controlled trial of antenatal magnesium sulfate for the prevention of cerebral palsy. Subjects were included if they had a clinical diagnosis of chorioamnionitis and maternal temperature of ≥37.8°C and excluded if maternal temperature data were missing. The exposure group included women who met the criteria for intraamniotic infection, defined as a single maternal temperature of ≥39.0°C or maternal temperature of 38.0°C to 38.9°C plus 1 additional clinical risk factor (leukocytosis, purulent cervical drainage, or fetal tachycardia). The primary outcome was postpartum endometritis. The odds of postpartum endometritis were compared between women with intraamniotic infection and women with clinical chorioamnionitis, after adjusting for potential confounders using multivariate logistic regression., Results: Of the original study population, 258 of 2241 (11.8%) subjects met the criteria for chorioamnionitis. Nearly all subjects (98.5%) received antibiotic treatment between randomization and delivery. A total of 144 subjects (55.8%) met the criteria for intraamniotic infection, whereas 114 (44%) only met the criteria for clinical chorioamnionitis. A total of 40 women (15.5%) experienced postpartum endometritis. Women with intraamniotic infection had higher parity (P=.02) and higher maximum maternal temperature (P<.001) and were more likely to have received antibiotic treatment (P=.04). Postpartum endometritis rates were similar between subjects with chorioamnionitis and intraamniotic infection (12% vs 18%; P=.50). After adjustment for potential confounders, the odds of developing postpartum endometritis did not differ between subjects who met the criteria for intraamniotic infection and those who did not (adjusted odds ratio, 1.28; 95% confidence interval, 0.62-2.62)., Conclusion: Patients delivering preterm who receive a diagnosis of clinical chorioamnionitis in the intrapartum period seem to have similar odds of developing postpartum endometritis as those meeting the American College of Obstetricians and Gynecologists' criteria for intraamniotic infection, suggesting that this group remains at a high risk for postpartum infectious complications., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The optimal antibiotic regimen to prevent maternal postpartum infection among high-risk women treated for chorioamnionitis delivering by cesarean delivery remains to be defined. Emerging data suggest that cefazolin decreases the risk of cesarean surgical site infection., Objective: To investigate whether intrapartum antibiotic therapy with cefazolin versus the current standard clindamycin or metronidazole decreases the risk of postpartum infectious morbidity among women delivering by cesarean delivery who were receiving a base regimen of ampicillin or penicillin with gentamicin for chorioamnionitis., Materials and Methods: A secondary analysis from the Maternal-Fetal Medicine Units Network (MFMU) Cesarean Registry. We included women who delivered by cesarean delivery with presumptive chorioamnionitis (intrapartum fever >100.4°F and receipt of intrapartum antibiotics). All women received a base regimen of penicillin or ampicillin with gentamicin. We compared antibiotic therapy with cefazolin versus clindamycin or metronidazole. The primary outcome was a composite of postpartum maternal infection, including endometritis and surgical site infection. Multivariable logistic regression was used, adjusting for age, parity, race/ethnicity, insurance, body mass index at delivery, tobacco use, pregestational diabetes, American Society of Anesthesiologists classification, trial of labor prior to cesarean delivery, and postpartum antibiotics., Results: Among 1105 women with presumptive chorioamnionitis who delivered by cesarean delivery, 22.0% (n = 244) received cefazolin and 77.9% (n = 861) received clindamycin or metronidazole. Most women were in labor prior to cesarean delivery (93.8%) and received postpartum antibiotics (88.4%). Almost one-tenth (9.5%) were diagnosed with a postpartum infection, most commonly endometritis (80.9%), followed by surgical site infection (20.9%) (not mutually exclusive). Women treated with cefazolin rather than clindamycin or metronidazole had lower odds of postpartum infectious morbidity (adjusted odds ratio, 0.49; 95% confidence interval, 0.26-0.90). This association held when the outcome was restricted to surgical site infection (adjusted odds ratio, 0.11; 95% confidence interval, 0.01-0.92) but not endometritis. Similar results were observed with propensity score analysis., Conclusion: Among women delivering by cesarean delivery who were treated for chorioamnionitis, additional antibiotic therapy with cefazolin decreased the risk of postpartum infection, primarily surgical site infection, compared to the current standard clindamycin or metronidazole., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To determine threshold cytomegalovirus (CMV) infectious rates and treatment effectiveness to make universal prenatal CMV screening cost-effective., Study Design: Decision analysis comparing cost-effectiveness of two strategies for the prevention and treatment of congenital CMV: universal prenatal serum screening and routine, risk-based screening. The base case assumptions were a probability of primary CMV of 1% in seronegative women, hyperimmune globulin (HIG) effectiveness of 0%, and behavioral intervention effectiveness of 85%. Screen-positive women received monthly HIG and screen-negative women received behavioral counseling to decrease CMV seroconversion. The primary outcome was the cost per maternal quality-adjusted life year (QALY) gained with a willingness to pay of $100,000 per QALY., Results: In the base case, universal screening is cost-effective, costing $84,773 per maternal QALY gained. In sensitivity analyses, universal screening is cost-effective only at a primary CMV incidence of more than 0.89% and behavioral intervention effectiveness of more than 75%. If HIG is 30% effective, primary CMV incidence can be 0.82% for universal screening to be cost-effective., Conclusion: The cost-effectiveness of universal maternal screening for CMV is highly dependent on the incidence of primary CMV in pregnancy. If efficacious, HIG and behavioral counseling allow universal screening to be cost-effective at lower primary CMV rates., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To investigate the association of chorioamnionitis, and secondarily its duration, on neonatal adverse outcomes for infants born <34 weeks vs. ≥34 weeks., Study Design: A secondary analysis from the observational U.S. Consortium on Safe Labor Study. The exposure was chorioamnionitis, and secondarily, its estimated duration. The composite outcome included pneumonia, seizure, necrotizing enterocolitis, sepsis, periventricular/intraventricular/cerebral hemorrhage, mechanical ventilation, and neonatal death. Multivariable logistic regression with generalized estimating equations was used, stratified by gestational age at delivery., Results: Among 221,274 deliveries, the odds of the neonatal adverse outcome <34 weeks was 2-fold higher among infants exposed to chorioamnionitis vs. those who were not (62.0 vs. 47.7%; AOR: 1.86; 95%CI: 1.25-2.75), and was ~3.5-fold higher ≥34 weeks (9.2 vs. 2.5%; AOR: 3.34; 95% CI: 2.35-4.76). The estimated duration of chorioamnionitis did not change the above associations., Conclusions: Chorioamnionitis was associated with an approximately 2- and 3.5-fold increased odds of neonatal adverse outcomes <34 and ≥34 weeks, respectively, regardless of its estimated duration.

Objective  To examine the association between perioperative Beta ( β ))-lactam versus non- β -lactam antibiotics and cesarean delivery surgical site infection (SSI). Study Design  Retrospective cohort of women undergoing cesarean delivery from January 1 to December 31, 2014. All women undergoing cesarean after 34 weeks with a postpartum visit were included. Prevalence of SSI was compared between women receiving β -lactam versus non- β -lactam antibiotics. Bivariate analyses were performed using Pearson's Chi-square, Fisher's exact, or Wilcoxon's rank-sum tests. Logistic regression models were fit controlling for possible confounders. Results  Of the 929 women included, 826 (89%) received β -lactam prophylaxis and 103 (11%) received a non- β -lactam. Among the 893 women who reported a non-type I (low risk) allergy, 819 (92%) received β -lactam prophylaxis. SSI occurred in 7% of women who received β -lactam antibiotics versus 15% of women who received a non- β -lactam ( p  = 0.004). β -Lactam prophylaxis was associated with lower odds of SSI compared with non- β -lactam antibiotics (odds ratio [OR] = 0.43; 95% confidence interval [CI] = 0.22-0.83; p  = 0.01) after controlling for chorioamnionitis in labor, postlabor cesarean, endometritis, tobacco use, and body mass index (BMI). Conclusion   β -Lactam perioperative prophylaxis is associated with lower odds of a cesarean delivery surgical site infection compared with non- β -lactam antibiotics.

Objective: The objective of this study was to evaluate the negative predictive value (NPV) of a rapid influenza diagnostic test (RIDT) compared with polymerase chain reaction (PCR) in pregnant women., Study Design: Retrospective cohort study of pregnant women with a negative RIDT followed by confirmatory PCR for influenza A, H1N1, and B during the influenza seasons from 2012 to 2015., Results: The NPV of the RIDT was 85.4% (211 of 247), 93.5% (231 of 247), and 97.9% (242 of 247) for influenza A, H1N1, and B, respectively. Antiviral treatment was administered to 47.2% (17 of 36) of women with a false-negative RIDT for influenza A compared with 9.0% (19 of 211) of women with a true-negative RIDT ( p < 0.001). Patients were more likely to receive antiviral treatment if they were feverish (adjusted odds ratio [aOR]: 6.05, 95% confidence interval [CI]: 1.83-20.03), had cough (aOR: 6.43, 95% CI: 1.06-39.26), dyspnea (aOR: 6.41, 95% CI: 1.63-25.29), or had a subsequently positive PCR (aOR: 9.41, 95% CI: 3.13-28.31)., Conclusion: Up to 14.5% of women with a negative RIDT in pregnancy had positive influenza A by PCR of whom more than half did not receive antiviral treatment., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To evaluate the risk of preterm birth in low-risk women with cervical length (CL) ≤25 mm on transvaginal ultrasound (TVUS) managed with vaginal progesterone (VagP) therapy versus cerclage., Study Design: This is a retrospective cohort of women with no prior history of preterm birth or cervical insufficiency and CL ≤ 25 mm on TVUS, managed with either VagP therapy alone or cerclage (with or without VagP). The primary outcome was rate of preterm delivery < 37 weeks gestational age (GA). Secondary outcomes included delivery at ≤ 32 or ≤ 28 weeks GA, premature preterm rupture of membranes, pregnancy latency, GA at delivery, and composite neonatal outcome., Results: Women undergoing cerclage placement ( n  = 31) were older and had an earlier GA at the time of diagnosis of short cervix compared with women receiving VagP ( n  = 62). Delivery at < 37 weeks occurred in 21/62 (33.9%) in the VagP group and 14/31 (45.2%) in the cerclage group (adjusted odds ratio: 1.72, 95% confidence interval: 0.52, 5.66). There were no differences in secondary outcomes., Conclusion: Cerclage compared with VagP therapy did not decrease risk of preterm birth in women with CL ≤ 25 mm. Further research is needed to determine optimal management in such women given a residual 40% risk of preterm birth despite optimal therapy., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

The objective of this commentary is to describe the background, rationale, and methods of the PROLONG (Progestin's Role in Optimizing Neonatal Gestation) trial, which is a multicenter, multinational, placebo-controlled, randomized clinical trial (RCT) designed to assess the safety and efficacy of Makena (hydroxyprogesterone caproate injection, 250 mg/mL) in reducing the risk of preterm birth (PTB) and neonatal morbidity/mortality in women pregnant with a singleton gestation who had a previous singleton spontaneous PTB. The total sample size of the RCT will include 1,707 women. The trial has two coprimary outcomes: PTB less than 35 weeks and a composite neonatal morbidity and mortality index. This study sample size will provide 90% power to assess for a 35% reduction in neonatal morbidity and mortality. Secondary outcomes will include 2-year follow-up of infants. The trial is ongoing and targeted to complete recruitment in 2018., Competing Interests: C.G.-B. reports grants from AMAG Pharmaceuticals, during the conduct of the study. A.F.D. reports personal fees from InClin, personal fees from personal consulting, during the conduct of the study; personal fees from Hologic, outside the submitted work. R.B. and M.J.J. report being employed by AMAG Pharmaceuticals, who sponsored this clinical trial. J.R.B., S.P.C., B.L.H., J.M.L., T.M., S.C.B., and H.S.M. have nothing to disclose., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Cytomegalovirus (CMV) is the most common infectious cause of fetal malformations and childhood hearing loss. CMV is more common among socially disadvantaged groups, and geographically clusters in poor communities. The Area Deprivation Index (ADI) is a neighborhood-level index derived from census data that reflects material disadvantage., Methods: We performed a geospatial analysis to determine if ADI predicts the local odds of CMV seropositivity. We analyzed a dataset of 3527 women who had been tested for CMV antibodies during pregnancy. We used generalized additive models to analyze the spatial distribution of CMV seropositivity. Adjusted models included individual-level age and race and neighborhood-level ADI., Results: Our dataset included 1955 CMV seropositive women, 1549 who were seronegative, and 23 with recent CMV infection based on low avidity CMV antibodies. High ADI percentiles, representing greater neighborhood poverty, were significantly associated with the nonwhite race (48 vs. 22, p < 0.001) and CMV seropositivity (39 vs. 28, p < 0.001). Our unadjusted spatial models identified clustering of high CMV odds in poor, urban neighborhoods and clustering of low CMV odds in more affluent suburbs (local odds ratio 0.41 to 1.90). Adjustment for both individual race and neighborhood ADI largely eliminated this spatial variability. ADI remained a significant predictor of local CMV seroprevalence even after adjusting for individual race., Conclusions: Neighborhood-level poverty as measured by the ADI is a race-independent predictor of local CMV seroprevalence among pregnant women.

Congenital cytomegalovirus is the most common viral congenital infection, and affects up to 2% of neonates. Significant sequelae may develop after congenital cytomegalovirus, including hearing loss, cognitive defects, seizures, and death. Zika virus is an emerging virus with perinatal implications; a congenital Zika virus syndrome has been identified, and includes findings such as microcephaly, fetal nervous system abnormalities, and neurologic sequelae after birth. Screening, diagnosis, prevention, and treatment of these perinatal infections are reviewed in this article., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Sepsis accounts for up to 28% of all maternal deaths. Prompt, appropriate treatment improves maternal and fetal morbidity and mortality. To date, there are no validated tools for identification of sepsis in pregnant women, and tools used in the general population tend to overestimate mortality. Once identified, management of pregnancy-associated sepsis is goal-directed, but because of the lack of studies of sepsis management in pregnancy, it must be assumed that modifications need to be made on the basis of the physiologic changes of pregnancy. Key to management is early fluid resuscitation and early initiation of appropriate antimicrobial therapy directed toward the likely source of infection or, if the source is unknown, empiric broad-spectrum therapy. Efforts directed at identifying the source of infection and appropriate source control measures are critical. Development of an illness severity scoring system and treatment algorithms validated in pregnant women needs to be a research priority.