Theiler, Regan N.

INTRODUCTION: Several methods exist for diagnosis of preterm premature rupture of membranes (PPROM), including pooling on speculum exam, nitrazine test, arborization under microscopy, immunoassay, and amnio-dye test. Diagnostic accuracy is particularly important for PPROM because a missed diagnosis may result in life-threatening maternal and fetal consequences. We present a novel method for evaluating PPROM in equivocal cases using a menstrual cup. METHODS: Written informed consent was obtained for submission of a case report. A 36-year-old G6P5005 at 29 2/7 weeks presented with leakage of fluid. She was found to have negative pooling on speculum exam, negative arborization on microscopy, a maximum vertical pocket (MVP) of 4.0 cm, and a negative urinalysis. She was discharged with precautions and returned 2 days later with persistent symptoms. Workup again showed no pooling, no arborization, and a normal MVP. The patient suggested using a menstrual cup to capture her intermittent leakage of fluid. She wore a menstrual cup for 30 minutes in triage. A sample of the fluid tested positive for arborization. She was admitted to labor and delivery for latency antibiotics, betamethasone, and fetal and maternal monitoring. CONCLUSION: Preterm premature rupture of membranes can occur without overt vaginal pooling due to small volume leakage. Conventional testing is less sensitive when pooling is absent. In these cases, a menstrual cup may help facilitate diagnosis and avoid invasive tests such as the amnio-dye test. Care must be taken to use a clean menstrual cup without gel, limit the duration of menstrual cup use to avoid infection, and to distinguish arborization of amniotic fluid from that of cervical mucus.

Objective: To implement use of obstetric (OB) hospitalist telemedicine services (TeleOB) to support clinicians facing OB emergencies in low-resource hospital settings. Methods: TeleOB was staffed by OB hospitalists working at a tertiary maternity center. The service was available via real-time high-definition audio/video technology for providers at 17 outlying hospitals across a health system spanning two states. The initial 25 service activations are described. Results: TeleOB supported 17 deliveries, two postpartum emergency department (ED) consultations, and four antenatal ED consultations. In 10 of 17 (59%) deliveries, teleneonatology was jointly activated to support neonatal resuscitation. Sixteen (94%) deliveries occurred in multiparas, and five (29%) resulted from spontaneous preterm labor. Eighty percent (20/25) of activations occurred in facilities without maternity services. Conclusions: A TeleOB service staffed by OB hospitalists successfully supports hospitals in an integrated health care system. TeleOB is feasible for support of hospitals with no delivery facilities or with limited maternity care resources.

Objective To evaluate maternal risk factors associated with chronic villitis of unknown etiology (VUE) and to describe cooccurring placental pathologies. Study Design A retrospective case–control study was conducted using placental pathology records from deliveries ≥ 20 weeks between 2010 and 2018. Cases were placentas with documented chronic villitis without infectious cause, hereafter called VUE. Controls were placentas without this diagnosis, matched to the cases 2:1. Maternal and neonatal demographic and clinical data were collected. Descriptive statistics are reported with Fisher's exact test or a chi-squared test, as appropriate, and multivariable conditional logistic regression was conducted. Results Our study included 352 cases with VUE and 657 controls. A diagnosis of gestational diabetes (p = 0.03) and gestational hypertension (p = 0.06) was 1.5 times more likely to occur in those with a VUE diagnosis. A trend was also seen for chronic hypertension (odds ratio [OR] = 1.7, p = 0.07) and preeclampsia (OR = 1.5, p = 0.09) compared with controls. Placentas with VUE, specifically high-grade VUE, were more likely to be small for gestational age (p = 0.01), and to be diagnosed with other placental findings including lymphoplasmacytic or chronic deciduitis (p < 0.01), maternal (p < 0.01) and fetal vascular malperfusion (p = 0.02), and chorionitis (acute or chronic; p < 0.01). Conclusion Gestational diabetes and hypertension were associated with a diagnosis of VUE, and overall, VUE placentas have more abnormal placental findings compared with control. Understanding VUE risk factors may facilitate prenatal care strategies and counseling to achieve the best outcomes for pregnant patients and their neonates. Key Points

Abstract Despite intensive characterization of immune responses after COVID-19 infection and vaccination, research examining protective correlates of vertical transmission in pregnancy are limited. Herein, we profiled humoral and cellular characteristics in pregnant women infected or vaccinated at different trimesters and in their corresponding newborns. We noted a significant correlation between spike S1–specific IgG antibody and its RBD-ACE2 blocking activity (receptor-binding domain–human angiotensin-converting enzyme 2) in maternal and cord plasma (P &lt; .001, R &gt; 0.90). Blocking activity of spike S1–specific IgG was significantly higher in pregnant women infected during the third trimester than the first and second trimesters. Elevated levels of 28 cytokines/chemokines, mainly proinflammatory, were noted in maternal plasma with infection at delivery, while cord plasma with maternal infection 2 weeks before delivery exhibited the emergence of anti-inflammatory cytokines. Our data support vertical transmission of protective SARS-CoV-2–specific antibodies. This vertical antibody transmission and the presence of anti-inflammatory cytokines in cord blood may offset adverse outcomes of inflammation in exposed newborns.

Congenital rubella syndrome is a constellation of birth defects that can have devastating consequences, impacting approximately 100,000 births worldwide each year. The incidence is much lower in countries that routinely vaccinate their population. In the US, postnatal immunization of susceptible women is an important epidemiological strategy for the prevention of rubella as the Center for Disease Control (CDC) does not recommend administering this vaccine during pregnancy due to its nature as a live attenuated virus vaccine. However, concerns that the co-administration of rubella vaccine with other immunoglobins (i.e., Rhogam) could compromise vaccine efficacy has produced warnings that can delay the administration of rubella vaccination postpartum, leaving women susceptible to the disease in subsequent pregnancies. We aimed to address whether the co-administration of the measles, mumps, and rubella (MMR) vaccine and Rhogam decreased antibody responses compared to those receiving only MMR vaccination. This retrospective cohort study utilized clinical data from 78 subjects who received the MMR vaccine and Rhogam after delivery and 45 subjects who received the MMR vaccine alone. Maternal demographics, pregnancy complications and rubella status at the start of a subsequent pregnancy were recorded for analysis. Overall, the two cohorts had similar baseline characteristics; however, lower parity was noted in the participants that received both MMR vaccination and Rhogam. Making assessments based on maternal antibody IgG index for rubella during the next pregnancy, we observed that 88% of the Rhogam + MMR vaccine group had positive serology scores, which was not significantly different from the 80% rate in the MMR-vaccine-only cohort (p = 0.2). In conclusion, no differences were observed in rubella immunity status in subsequent pregnancies in those mothers given both the MMR vaccine and Rhogam concurrently. Given these findings, warnings against co-administration of vaccines in combination with Rhogam appear unwarranted.

Background: The incidence of Clostridioides difficile infection (CDI) in peripartum women is rising, but limited data on its effect on maternal and neonatal outcomes are available. Objective: To study the effect of peripartum CDI on pregnancy and neonatal outcomes. Design: Retrospective cohort study. Methods: Patients with peripartum CDI 12 weeks before pregnancy through 6 weeks postpartum (January 1996–February 2018) were matched with controls (peripartum women without CDI) 1:1 by age, year of delivery, and prior pregnancies. McNemar’s test and conditional logistic regression were used to analyze the effect of CDI on pregnancy and neonatal outcomes (complications, mode of delivery). p < 0.05 was considered statistically significant. Results: Overall, 101 cases and 100 controls (1997–2018) were included; median age 27 (range, 20–41) years. Timing of CDI was as follows: pre-pregnancy: 15.8% ( n = 16), during pregnancy: 51.5% ( n = 52), and postpartum: 32.7% ( n = 33). The commonest risk factor was outpatient/emergency room visits. Pregnancy and neonatal outcomes were analyzed for 67 matched pairs with CDI before or during pregnancy. Cases had higher odds of cesarean delivery ( p = 0.02) and lower odds of Group B Streptococcus (GBS) infection/colonization ( p = 0.03). Odds of cesarean delivery remained high after controlling for labor arrest disorders [odds ratio (OR): 17.23 (95% confidence interval (CI), 2.19–543.19; p = 0.004)]; odds of GBS remained low after controlling for antibiotic use (OR: 0.25, 95% CI, 0.04–0.99; p = 0.049). Neonatal outcomes were similar in cases and controls. CDI treatment did not affect treatment-related or delivery outcomes. Conclusion: Peripartum CDI was associated with higher odds of cesarean delivery and lower odds of GBS infections. Larger studies exploring the effect of CDI on pregnancy and neonatal outcomes are needed.

In 1989, one in four (25%) infants born to women living with HIV were infected; by the age of 2 years, there was 25% mortality among them due to HIV. These and other pieces of data prompted the development of interventions to offset vertical transmission, including the landmark Pediatric AIDS Clinical Trial Group Study (PACTG 076) in 1994. This study reported a 67.5% reduction in perinatal HIV transmission with prophylactic antenatal, intrapartum, and postnatal zidovudine. Numerous studies since then have provided compelling evidence to further optimize interventions, such that annual transmission rates of 0% are now reported by many health departments in the US and elimination has been validated in several countries around the world. Despite this success, the elimination of HIV’s vertical transmission on the global scale remains a work in progress, limited by socioeconomic factors such as the prohibitive cost of antiretrovirals. Here, we review some of the key trials underpinning the development of guidelines in the US as well as globally, and discuss the evidence through a historic lens.

Abstract Background Despite extensive studies of human immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination, research examining protective correlates of vertical transmission following maternal exposure in pregnancy remain limited. Here, we characterized antibody and cytokine responses in maternal and cord blood following infection or vaccination at various timepoints during gestation. Methods Spike S1 protein-specific binding antibodies and antibodies capable of blocking the interaction between the receptor binding domain (RBD) and the angiotensin converting enzyme 2 (ACE2) were measured in maternal and cord blood by ELISA. Serum concentrations of 74 cytokines/chemokines were measured by multiplex assay. Humoral responses and cytokine levels from matched maternal and fetal cord sera were compared and examined for potential correlations. Results We observed a highly significant correlation between Spike S1-specific antibody titer and RBD-ACE2 blocking antibody activity between maternal and fetal cord serum (p &lt; 2.2e-16, R &gt; 0.90). Blocking antibody activity was significantly higher for mothers infected during the 3rd trimester compared to earlier trimesters; however, vaccinated mothers developed and transferred higher antibody titers with greater RBD-ACE2 blocking antibody activity to their neonates than infected mothers. Furthermore, vaccine-induced Spike S1 IgG transfer ratios (fetal cord/maternal) were significantly higher than those induced by infection (p = 0.002). Multiplex assay showed significantly elevated levels of 33 cytokines/chemokines, mainly pro-inflammatory in infected maternal serum samples, while the paired fetal cord samples exhibited an anti-inflammatory cytokine predominance. Conclusion Our data support selective vertical transmission of potentially protective humoral responses against SARS-CoV-2, especially following vaccination in the 3rd trimester. The anti-inflammatory cytokine predominance in cord blood that persists despite maternal SARS-CoV-2 infection may offset the adverse outcomes of inflammation in pregnancy for the neonate. Disclosures All Authors: No reported disclosures.

Abstract Background Pemphigoid gestationis (PG) and polymorphic eruption of pregnancy (PEP) are pregnancy‐related dermatoses. Definitive diagnosis often relies upon histopathology and direct immunofluorescence (DIF). PG is associated with fetal and neonatal risks, while PEP confers minimal risk. Objective We aimed to compare histopathologic features to determine key differentiators. Methods A retrospective cohort study of PG and PEP cases, with accompanying DIF, conducted from 1995 to 2020. Skin biopsies were examined independently in a blinded fashion by two dermatopathologists for a list of histopathological features. Results Twenty‐one cases of PG and 10 cases of PEP were identified. PG had significantly denser eosinophils than PEP (mean 155 vs. 48 cells/5 hpf; p < 0.018). PG was also noted to have eosinophilic spongiosis and eosinophils at the dermal–epidermal junction more frequently compared to PEP (80% PG vs. 10% PEP; p < 0.001). A mean cutoff value of 86 eosinophils and a mean optimal sensitivity and specificity of 81% and 83%, respectively, for eosinophils density's diagnostic power of PEP versus PG were achieved. Subepithelial separation was exclusively seen in PG (40% vs. 0%; p < 0.007). Conclusion Eosinophilic spongiosis, eosinophilic epitheliotropism, and dense superficial dermal eosinophils were diagnostic of PG. Given overlapping clinicopathologic features, however, DIF results with clinicopathologic correlation, remain the gold standard.