The Mortality of Congenital Syphilis.

OBJECTIVES: To document the case-fatality rate (CFR) of congenital syphilis diagnosed by molecular tools and rabbit infectivity testing (RIT) of clinical specimens in addition to standard evaluation and to compare that with the CFR using the Centers for Disease Control and Prevention (CDC) surveillance case definition. STUDY DESIGN: Prospective, single site, cohort study of all cases of syphilis among mothers and their infants from 1984 to 2002. The diagnosis of congenital syphilis was determined using IgM immunoblotting, polymerase chain reaction, and RIT of fetal or infant specimens in addition to clinical, laboratory, and radiographic criteria. Data were retrospectively reviewed to ascertain fetal and neonatal mortality. RESULTS: During the 18-year study, there were 191 cases of congenital syphilis confirmed by abnormalities on clinical, laboratory, or radiographic evaluation and/or positive serum IgM immunoblot, blood polymerase chain reaction, or blood/cerebrospinal fluid RIT. Of the 191 cases, 59 died for a CFR of 31%. Of the 59 deaths, 53 (90%) were stillborn and 6 (10%) died in the neonatal period. The majority (74%, 39/53) of stillbirths occurred in the third trimester. The CDC surveillance case definition correctly identified all infants with congenital syphilis, but the CDC CFR was 10% which underestimated the CFR by more than 300%. CONCLUSIONS: Our findings corroborate the high sensitivity of the CDC surveillance definition for congenital syphilis but highlight its poor estimation of its associated mortality. The CFR among infected progeny of pregnant women with syphilis was 31%, due mostly to demise in the third trimester and as such highlights the need for detection and appropriate treatment of syphilis during pregnancy.

Long-Term Fine Particulate Matter Concentrations and Prevalence of Severe Acute Respiratory Syndrome Coronavirus 2: Differential Relationships by Socioeconomic Status Among Pregnant Individuals in New York City.

We aimed to determine whether long-term ambient concentrations of fine particulate matter (particulate matter with an aerodynamic diameter less than or equal to 2.5 µm (PM2.5)) were associated with increased risk of testing positive for coronavirus disease 2019 (COVID-19) among pregnant individuals who were universally screened at delivery and whether socioeconomic status (SES) modified this relationship. We used obstetrical data collected from New-York Presbyterian Hospital/Columbia University Irving Medical Center in New York, New York, between March and December 2020, including data on Medicaid use (a proxy for low SES) and COVID-19 test results. We linked estimated 2018-2019 PM2.5 concentrations (300-m resolution) with census-tract-level population density, household size, income, and mobility (as measured by mobile-device use) on the basis of residential address. Analyses included 3,318 individuals; 5% tested positive for COVID-19 at delivery, 8% tested positive during pregnancy, and 48% used Medicaid. Average long-term PM2.5 concentrations were 7.4 (standard deviation, 0.8) µg/m3. In adjusted multilevel logistic regression models, we saw no association between PM2.5 and ever testing positive for COVID-19; however, odds were elevated among those using Medicaid (per 1-µg/m3 increase, odds ratio = 1.6, 95% confidence interval: 1.0, 2.5). Further, while only 22% of those testing positive showed symptoms, 69% of symptomatic individuals used Medicaid. SES, including unmeasured occupational exposures or increased susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due to concurrent social and environmental exposures, may explain the increased odds of testing positive for COVID-19 being confined to vulnerable pregnant individuals using Medicaid.

Compassionate Use of Remdesivir in Pregnant Women With Severe Coronavirus Disease 2019.

BACKGROUND: Remdesivir is efficacious for severe coronavirus disease 2019 (COVID-19) in adults, but data in pregnant women are limited. We describe outcomes in the first 86 pregnant women with severe COVID-19 who were treated with remdesivir. METHODS: The reported data span 21 March to 16 June 2020 for hospitalized pregnant women with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection and room air oxygen saturation ≤94% whose clinicians requested remdesivir through the compassionate use program. The intended remdesivir treatment course was 10 days (200 mg on day 1, followed by 100 mg for days 2-10, given intravenously). RESULTS: Nineteen of 86 women delivered before their first dose and were reclassified as immediate "postpartum" (median postpartum day 1 [range, 0-3]). At baseline, 40% of pregnant women (median gestational age, 28 weeks) required invasive ventilation, in contrast to 95% of postpartum women (median gestational age at delivery 30 weeks). By day 28 of follow-up, the level of oxygen requirement decreased in 96% and 89% of pregnant and postpartum women, respectively. Among pregnant women, 93% of those on mechanical ventilation were extubated, 93% recovered, and 90% were discharged. Among postpartum women, 89% were extubated, 89% recovered, and 84% were discharged. Remdesivir was well tolerated, with a low incidence of serious adverse events (AEs) (16%). Most AEs were related to pregnancy and underlying disease; most laboratory abnormalities were grade 1 or 2. There was 1 maternal death attributed to underlying disease and no neonatal deaths. CONCLUSIONS: Among 86 pregnant and postpartum women with severe COVID-19 who received compassionate-use remdesivir, recovery rates were high, with a low rate of serious AEs.

Pregnancy alters interleukin-1 beta expression and antiviral antibody responses during severe acute respiratory syndrome coronavirus 2 infection.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2, the disease-causing pathogen of the coronavirus disease 2019 pandemic, has resulted in morbidity and mortality worldwide. Pregnant women are more susceptible to severe coronavirus disease 2019 and are at higher risk of preterm birth than uninfected pregnant women. Despite this evidence, the immunologic effects of severe acute respiratory syndrome coronavirus 2 infection during pregnancy remain understudied. OBJECTIVE: This study aimed to assess the impact of severe acute respiratory syndrome coronavirus 2 infection during pregnancy on inflammatory and humoral responses in maternal and fetal samples and compare antibody responses to severe acute respiratory syndrome coronavirus 2 among pregnant and nonpregnant women. STUDY DESIGN: Immune responses to severe acute respiratory syndrome coronavirus 2 were analyzed using samples from pregnant (n=33) and nonpregnant (n=17) women who tested either positive (pregnant, 22; nonpregnant, 17) or negative for severe acute respiratory syndrome coronavirus 2 (pregnant, 11) at Johns Hopkins Hospital. We measured proinflammatory and placental cytokine messenger RNAs, neonatal Fc receptor expression, and tetanus antibody transfer in maternal and cord blood samples. In addition, we evaluated antispike immunoglobulin G, antispike receptor-binding domain immunoglobulin G, and neutralizing antibody responses to severe acute respiratory syndrome coronavirus 2 in serum or plasma collected from nonpregnant women, pregnant women, and cord blood. RESULTS: Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection expressed more interleukin-1 beta, but not interleukin 6, in blood samples collected within 14 days vs >14 days after performing severe acute respiratory syndrome coronavirus 2 test. Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection also had reduced antispike receptor-binding domain immunoglobulin G titers and were less likely to have detectable neutralizing antibody than nonpregnant women. Although severe acute respiratory syndrome coronavirus 2 infection did not disrupt neonatal Fc receptor expression in the placenta, maternal transfer of severe acute respiratory syndrome coronavirus 2 neutralizing antibody was inhibited by infection during pregnancy. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of coronavirus disease 2019 treatment in pregnancy. In addition, the long-term implications of placental inflammation for neonatal health require greater consideration.

Single versus Double-Balloon Transcervical Catheter for Labor Induction: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate for difference in outcomes between single- and double-balloon catheters for labor induction. STUDY DESIGN: We searched CINAHL, Embase, Cochrane Register, MEDLINE, ISI Web of Sciences, LILACs, and Google Scholar and retrieved studies through May 2017. Selection criteria included randomized controlled trials comparing single- versus double-balloon catheters. The primary outcome was time from catheter insertion to delivery. Heterogeneity of the results among studies was tested with the quantity I2 . For I2 values ≥50%, a random effects model was used to pool data across studies. Summary measures were reported as adjusted odds ratios (aORs) or as a mean difference (MD) with 95% confidence interval (CI). RESULTS: Four trials including a total of 682 patients were included: 340 patients were randomized to induction with a single-balloon catheter and 342 to induction with a double-balloon catheter. There was no significant difference between groups with respect to time to delivery (18.8 vs. 19.6 hours; MD: 0.40; 95% CI: -1.56 to 0.76), vaginal delivery rate (65.3 vs. 62.3%; aOR: 1.04; 95% CI: 0.56-1.92), cesarean delivery rate (25.6 vs. 27.5%; aOR: 0.98; 95% CI: 0.55-1.73), or epidural use (58.4 vs. 62%; aOR: 0.81; 95% CI: 0.56-1.18). CONCLUSION: Double-balloon catheters have no apparent advantage over single-balloon catheters for labor induction.

Infections complicating cesarean delivery.

PURPOSE OF REVIEW: Cesarean sections are common surgical procedures performed in a healthy population and are unique because of a relatively high rate of postoperative infection. There have been many important advances in understanding the pathogenesis of infection and evaluation of interventions to prevent post cesarean section infections in the last few years. Our purpose in this review is to analyze these new data, discuss unanswered questions, and propose changes in standard of care. RECENT FINDINGS: Wound closure techniques including subcuticular sutures and subcutaneous suturing have been shown to be effective at reducing surgical site infections. Wound dressings including negative pressure dressings likely do not decrease infection rates. The type, timing, and duration of preoperative prophylactic antibiotics, including adjunctive azithromycin for laboring women and multidose antibiotics in obese women, have also yielded mixed results. Our understanding of normal uterine microbiome and the impact of intrapartum antibiotics on the newborn is emerging. SUMMARY: The pathogenesis of surgical site infections after Cesarean section is complex and multifactorial. Many interventions to reduce infections have been studied with varying degrees of effectiveness. Despite advances in the area, important questions remain unanswered.

SMFM Special Report: Putting the "M" back in MFM: Addressing education about disparities in maternal outcomes and care.

At the 36th Annual meeting of the Society for Maternal-Fetal Medicine (SMFM), leaders in the field of maternal-fetal medicine (MFM) convened to address maternal outcome and care inequities from 3 perspectives: (1) education, (2) clinical care, and (3) research. Meeting attendees identified knowledge gaps regarding disparities within the provider community; reviewed possible frameworks to address these knowledge gaps; and identified models with which to address key clinical issues. Collaboration and communication between all stakeholders will be needed to gain a better understanding of these prevailing disparities and formulate strategies to eliminate them.

Zika Virus Infection in the Pregnant Woman.

Zika virus is a single-stranded RNA virus from the Flaviviridae family. Transmission is typically from the bite of an infected mosquito though mother-to-child, sexual and blood donation transmissions can occur. Although maternal symptoms are uncommon and rarely severe, the consequences of congenital infections are devastating. The emergence of congenital Zika syndrome is a world-wide public health crisis. The Centers for Disease Control and Prevention, ACOG, and SMFM have developed algorithms for screening and managing women exposure to and diagnosed with Zika virus infection. Prevention is the mainstay of infection control as there is currently no vaccine or therapy available.

Updated Etiology and Significance of Elevated Bilirubin During Pregnancy: Changes Parallel Shift in Demographics and Vaccination Status.

BACKGROUND: The most common cause of jaundice during pregnancy in the United States (US) is still attributed to viral hepatitis, despite the dramatic drop in incidence of viral hepatitis in the US. OBJECTIVE: We hypothesized that viral hepatitis is no longer a frequent etiology of jaundice among the pregnant population in the US and sought to identify the contemporary causes of elevated bilirubin during pregnancy as well as to quantify the associated risk to the mother and fetus. STUDY DESIGN: Clinical data from all pregnant women who delivered an infant between 2005 and 2011 at a single hospital in Dallas, Texas, were ascertained using prospectively collected computerized databases. Women with elevated total bilirubin (>1.2 mg/dl) were analyzed to determine the cause of hyperbilirubinemia and maternal and fetal outcomes. RESULTS: Out of a total of 80,857 consecutive deliveries, there were 397 (0.5 %) pregnancies with hyperbilirubinemia. The most common etiology was gallstones (98/397 = 25 %), followed by preeclampsia/eclampsia/HELLP (94/397 = 24 %) and intrahepatic cholestasis of pregnancy (53/397 = 13 %). Adverse infant outcomes, including stillbirths, fetal malformations, neonatal deaths, and small for gestational age births, were more common in the women with hyperbilirubinemia during pregnancy, but there were no maternal deaths. CONCLUSIONS: Acute viral hepatitis is no longer a common cause of jaundice in pregnant women in the US. In the current era, gallstones and preeclampsia-related disorders are the most common causes of jaundice in pregnant women. Disorders that cause elevated maternal bilirubin during pregnancy are associated with increased risk for the fetus.

Maternal titers after adequate syphilotherapy during pregnancy.

BACKGROUND: We aimed to construct a timeline for nontreponemal titer decline specific to pregnancy and evaluate factors associated with inadequate decline by delivery. METHODS: This was a retrospective medical records review from September 1984 to June 2011 of women diagnosed with syphilis after 18 weeks of gestation. Women were treated according to stage of syphilis per Centers for Disease Control and Prevention guidelines. Patients with both pretreatment and delivery titers were included for data analysis. Demographics, stage of syphilis, maternal titers, delivery, and infant outcomes were recorded. Standard statistical analyses were performed for categorical and continuous data. The titer decline was analyzed using mixed-effects regression modeling. RESULTS: A total of 166 patients met inclusion criteria. Mean gestational age at treatment was 29.1 ± 5 weeks, and 93 (56%) women were diagnosed with early-stage syphilis. For all stages of syphilis, maternal titers declined after syphilotherapy. Pretreatment titers were higher and declined more rapidly in primary and secondary disease than in latent-stage disease and syphilis of unknown duration. Sixty-three (38%) patients achieved a 4-fold decline by delivery. Patients without a 4-fold decline by delivery were older (24.6 vs 21.5 years; P < .001), treated later in pregnancy (30.3 vs 27.3 weeks; P < .001), diagnosed with latent syphilis or syphilis of unknown duration, and had less time from treatment to delivery (7.8 vs 11.1 weeks; P < .001). CONCLUSIONS: Maternal serologic response during pregnancy after adequate syphilotherapy varied by stage of disease. Failure to achieve a 4-fold decline in titers by delivery is more a reflection of treatment timing than of treatment failure.

Association of influenza vaccination on decreased stillbirth rate.

OBJECTIVE: We have previously shown a decrease in the overall stillbirth rate at our institution in women receiving the seasonal influenza vaccine during pregnancy. The goal of this study was to ascertain factors associated with this decrease. STUDY DESIGN: This was a retrospective cohort study examining the stillbirth rate, etiology, autopsy findings, and placental pathology in pregnant women receiving the seasonal trivalent inactive influenza vaccine during five influenza seasons between 2003 and 2008. All stillbirths at our institution are investigated by a committee and an etiology is assigned. Autopsy is offered to all patients and placental evaluation is performed routinely. RESULTS: During the study period, 8,690 pregnant women received the seasonal influenza vaccine antepartum and delivered at our institution. Thirty of these births were complicated by stillbirth as compared with 436 stillbirths in the 76,153 women not vaccinated (0.35 vs. 0.57%, p = 0.006). No association was identified between assigned causes of stillbirth when comparing vaccinated and nonvaccinated women. CONCLUSION: No specific etiology commonly associated with stillbirth was identified to have been affected by maternal antepartum influenza vaccination.

Designing drug trials: considerations for pregnant women.

Clinical pharmacology studies that describe the pharmacokinetics and pharmacodynamics of drugs in pregnant women are critical for informing on the safe and effective use of drugs during pregnancy. That being said, multiple factors have hindered the ability to study drugs in pregnant patients. These include concerns for maternal and fetal safety, ethical considerations, the difficulty in designing appropriate trials to assess the study objectives, and funding limitations. This document summarizes the recommendations of a panel of experts convened by the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, National Institutes of Health. These experts were charged with reviewing the issues related to the development of preclinical and clinical drug studies in pregnant women and to develop strategies for addressing these issues. These findings may also be utilized in the development of future drug studies involving pregnant women and their fetus/neonate.

Recruitment and retention of pregnant women into clinical research trials: an overview of challenges, facilitators, and best practices.

Pregnant women are a vulnerable group who are needed in clinical research studies to advance prevention and treatment options for this population. Yet, pregnant women remain underrepresented in clinical research. Through the lens of the socioecological model, we highlight reported barriers and facilitators to recruitment and retention of pregnant women in studies that sought their participation. We trace historical, policy-based reasons for the exclusion of pregnant women in clinical studies to present-day rationale for inclusion of this group. The findings highlight why it has been difficult to recruit and retain this population over time. A body of literature suggests that integrative sampling and recruitment methods that leverage the influence and reach of prenatal providers will overcome recruitment challenges. We argue that these strategies, in combination with building strong engagement with existing community-based organizations, will enable teams to more effectively promote and retain pregnant women in future longitudinal cohort studies.

Progression of ultrasound findings of fetal syphilis after maternal treatment.

OBJECTIVE: The purpose of this study was to evaluate ultrasound findings of fetal syphilis and to describe their progression after maternal treatment. STUDY DESIGN: This was a retrospective cohort study from September 1981 to June 2011 of seropositive women after 18 weeks of gestation who had an ultrasound before treatment to evaluate for fetal syphilis. Only those women who received treatment after the initial ultrasound scan, but before delivery, were included. If the initial ultrasound scan was abnormal, serial sonography was performed until resolution of the abnormality or delivery. Patient demographics, ultrasound findings, stage of syphilis, delivery, and infant outcomes were recorded. Standard statistical analyses were performed. Kaplan-Meier estimates were constructed to estimate time to resolution. RESULTS: Two hundred thirty-five women met the inclusion criteria; 73 of them (30%) had evidence of fetal syphilis on initial ultrasound scan. Abnormalities included hepatomegaly (79%), placentomegaly (27%), polyhydramnios (12%), ascites (10%) and abnormal middle cerebral arterial Doppler assessment (33%). After treatment, middle cerebral arterial Doppler assessment abnormalities, ascites, and polyhydramnios resolved first, followed by placentomegaly and finally hepatomegaly. Infant outcomes were available for 173 deliveries; of these, 32 infants (18%) were diagnosed with congenital syphilis. Congenital syphilis was more common when antenatal ultrasound abnormalities were present (39% vs 12%; P < .001). Infant examination findings at delivery were similar between women with and without an abnormal pretreatment ultrasound scan. However, in those infants with congenital syphilis, hepatomegaly was the most frequent abnormality found, regardless of antenatal ultrasound findings. CONCLUSION: Sonographic signs of fetal syphilis confer a higher risk of congenital syphilis at delivery for all maternal stages. Hepatomegaly develops early and resolves last after antepartum treatment.

Benefit of interpregnancy HIV viral load suppression on subsequent maternal and infant outcomes.

OBJECTIVE: The objective of the study was to determine whether interpregnancy human immunodeficiency virus (HIV) viral load suppression affects outcomes in subsequent pregnancies. STUDY DESIGN: This is a retrospective review of all women who delivered 2 consecutive pregnancies while diagnosed with HIV from Jan. 1, 1984, until Jan. 1, 2012. Medical records were reviewed for maternal, infant, and delivery data. Pregnancies were divided into index and subsequent pregnancy and analyzed for outcomes. RESULTS: During the study period, 172 HIV-infected women who delivered 2 pregnancies at our institution were identified. There was no difference in median HIV viral load at presentation or delivery between the index and subsequent pregnancies. During the subsequent pregnancy, more women presented on antiretroviral therapy (ART) and more often remained compliant with ART; however, there was no difference in vertical transmission risk between the pregnancies. Of those with a viral load less than 1000 copies/mL at the end of their index pregnancy (n = 103), 57 (55%) presented for their subsequent pregnancy with a viral load still less than 1000 copies/mL. Those women who maintained the viral load suppression between pregnancies were more likely to present for their subsequent pregnancy on ART, maintained a greater viral load suppression and CD4 counts during the pregnancy, and had fewer vertical transmissions compared with those who presented with higher viral loads in their subsequent pregnancy (0% vs 9%, P = .02). CONCLUSION: Maintaining an HIV viral load suppression between pregnancies is associated with improved HIV disease status at delivery in subsequent pregnancies. Interpregnancy HIV viral load suppression is associated with less vertical transmission, emphasizing the importance of maintaining HIV disease control between pregnancies.

The obstetrical and neonatal impact of maternal opioid detoxification in pregnancy.

OBJECTIVE: The purpose of this study was to analyze the obstetric and neonatal impact of an opioid detoxification program during pregnancy, as well as to examine variables associated with successful opioid detoxification. STUDY DESIGN: This is a retrospective cohort study of women electing inpatient detoxification and subsequently delivering at our hospital from Jan. 1, 2006, through Dec. 31, 2011. Detoxification was considered successful if women had no illicit drug supplementation at the time of delivery. Maternal characteristics were ascertained by chart review and analyzed for variables associated with success. Obstetric and neonatal outcomes were also assessed based on maternal success at delivery. RESULTS: Of the 95 women during the study period with complete data, 53 (56%) were successful. There were no demographic or social risk factors identified associated with success. Women with successful detoxification at delivery had longer inpatient detoxification admissions (median 25 vs 15 days, P < .001) and were less likely to leave prior to completion of the program than women who had relapsed at delivery (9% vs 33%, respectively, P < .001). Infants of mothers who were successfully detoxified had shorter hospitalizations (median 3 vs 22 days, P < .001), lower maximum neonatal abstinence syndrome scores (0 vs 8.3, P < .001), and were less likely to be treated for withdrawal (10% vs 80%, P < .001). CONCLUSION: Opiate detoxification in pregnancy requires a significant time commitment and extended treatment, however, can be successfully achieved in compliant parturients. Importantly, maternal demographics and drug histories do not portend success, supporting continued opiate detoxification being offered to all women expressing intent.

Methicillin-resistant Staphylococcus aureus in obstetrics.

Methicillin-resistant Staphylococcus aureus (MRSA) remains one of the major multiple antibiotic-resistant bacterial pathogens causing serious community-associated and health care-associated infections. It is now pervasive in the obstetric population associated with skin and soft tissue infections, mastitis, episiotomy, and cesarean wound infections and urinary tract infections. This review addresses the epidemiology, definitions, microbiology, and pathogenesis as well as common clinical presentations. A discussion of the 2011 Infectious Diseases Society of America MRSA treatment guidelines details available antibiotics, invasive and noninvasive MRSA management, and specific factors related to obstetrics. Finally, prevention strategies including decolonization are discussed.

Trends in emergency peripartum hysterectomy at a single institution: 1988-2009.

OBJECTIVE: To evaluate trends of emergency peripartum hysterectomy over two decades. STUDY DESIGN: This was a retrospective cohort study of peripartum hysterectomies at one institution from 1988 to 2009. Medical records were reviewed and data from the first 11 years were compared with data from the second 11 years. RESULTS: During the study period, 558 emergent peripartum hysterectomies were performed with full records available for 553 to review: 280 in the first period, 273 in the second (p = 0.19). In the second period, prior cesarean deliveries, length of surgery, estimated blood loss, blood transfusions, and the number of units transfused were all increased (p < 0.001). Also in the second period, there were twice as many hysterectomies for suspected placental invasion, and an almost threefold increase in pathologically confirmed placental invasion (both p < 0.001). CONCLUSION: Although emergent peripartum hysterectomies are not increasing in frequency, the risk factors and morbidities have changed.