MFM Guidance for COVID-19

The World Health Organization (WHO) has declared COVID-19 a global pandemic. Healthcare providers should prepare internal guidelines covering all aspect of the organization in order to have their unit ready as soon as possible. This document addresses the current COVID-19 pandemic for maternal-fetal medicine (MFM) practitioners. The goals the guidelines put forth here are two fold- first to reduce patient risk through healthcare exposure, understanding that asymptomatic health systems/healthcare providers may become the most common vector for transmission, and second to reduce the public health burden of COVID-19 transmission throughout the general population. Box 1 outlines general guidance to prevent spread of COVID-19 and protect our obstetric patients. Section 1 outlines suggested modifications of outpatient obstetrical (prenatal) visits. Section 2 details suggested scheduling of obstetrical ultrasound. Section 3 reviews suggested modification of nonstress tests (NST) and biophysical profiles (BPP). Section 4 reviews suggested visitor policy for obstetric outpatient office. Section 5 discusses the role of trainees and medical education in the setting of a pandemic. These are suggestions, which can be adapted to local needs and capabilities. Guidance is changing rapidly, so please continue to watch for updates

The Utility of Performing Cervical Length Follow-Up in Lower Risk Singleton

Introduction: Short cervical length (\u3c25 mm) during pregnancy is known to be an increased risk factor for preterm birth (\u3c37 weeks). While interventions exist for women who have had prior preterm births, it is important to investigate the cost effectiveness of screening low risk women with an intermediate cervical length (26-29 mm). Objective: To quantify the association between change in cervical length on follow up and the incidence of preterm birth in otherwise low risk women with an initial intermediate cervical length. Methods: A retrospective cohort study was conducted, reviewing 108 charts of women who had an initial screening between 26 and 29 mm. Charts were reviewed for whether or not a follow-up ultrasound was recommended, whether or not the follow-up was performed, and the outcome of their deliveries. Results: 93.5% (N=101) of women were recommended to get a follow-up ultrasound and 84% (N=85) completed their follow-up. 9.3% (N=10) had a CL of \u3c25mm on followup. 9.3% (N=10) had preterm deliveries. A significant difference was found between cervical length on followup and the incidence of early preterm birth (\u3c34 weeks) (p-value = .015). On univariate analysis, a significant difference was found between cervical length difference (initial cervical length-followup) and the incidence of preterm birth (p-value=.021). Conclusion: Cervical Length Followup for low risk women is a worthwhile investment to decrease the incidence of preterm birth and allows for the implementation of timely interventions for women whose cervixes spontaneously shorten to less than 25 mm

Time from Dose to Delivery and Efficacy of Maternal Azithromycin Prophylaxis in Planned Vaginal Births

Objective A Multicenter international placebo controlled randomized trial (APLUS) found that 2g oral azithromycin in labor reduced risk of maternal sepsis and death, but not newborn sepsis Efficacy in prevention of maternal or neonatal infections may be impacted by timing of antibiotics in laborhttps://jdc.jefferson.edu/obgynposters/1020/thumbnail.jp

Noninvasive amniotic fluid sampling to establish PK of azithromycin in pregnancy

Background PK studies to guide dosing of azithromycin (AZ) for pregnancy specific conditions, such as preterm premature rupture of membranes (PPROM), and data on accumulation of AZ in fetal compartment are lacking. We aim to evaluate feasibility of non-invasive collection of amniotic fluid (AF), validate an assay for AZ in AF, and describe concentration of AZ in the amniotic cavity over one week following a single maternal dose. Methods Patients with PPROM treated with 1g AZ PO once and wore underwear lining pads to collect AF as it leaked. AF strained from each pad, up to 10cc collected, centrifuged and frozen. Calibration curve established using range of 1 to 200 ng/mL, with Azithromycin-D3 as internal standard. Spiked standards and samples were extracted with plasma to ACN ratio as 1:2, and centrifuged. The clean supernatant was subjected to LCMS runs using Thermo-Orbitrap coupled with Dionex 3000 UHPLC system under +ve ion mode and sample 5µL injection volume. The chromatographic separations were done using HSS XSelect C18 reverse phase column using 50:50 water and ACN with 0.1% FA as mobile phase, flow rate of 0.250 mL/min. The linearity equation (y= 10945x, r2\u3e0.99) established using average of 8 injections over 4 days; 2 injections per day. AZ from AF samples was quantitated in duplicate and expressed as concentration/time profile. Results Five patients were enrolled. Mean gestational age on admission with PPROM was 27.5 ±2.3wk with a median latency of 7 days [IQR 4-13]. A median of 2 samples/day [IQR 1-3] were collected per participant. Azithromycin was quantified in duplicate; intra-assay coefficient of variation was 17%. Azithromycin concentration was \u3c60ng/ml after day 3. Azithromycin concentration was positively correlated with IL-8 (r=0.38, p=0.03), IL1a (r=0.39, p=0.03), and IL-1b (r=0.36, p=0.04) in amniotic fluid. Conclusion This simple technique for noninvasive collection of AF allows for precise quantification of AZ in AF with LCMS. AZ persists in the fetal compartment for at least seven days after a single maternal dose, although not necessarily at an adequate inhibitory concentration.https://jdc.jefferson.edu/obgynposters/1014/thumbnail.jp

Effects of Intravenous Iron Versus Oral Iron for Treatment of Anemia in Pregnancy on Maternal and Fetal Outcomes: A Systematic Review and Meta-analysis

Introduction: Anemia during pregnancy can lead to preterm birth, low fetal birthweight, and poorer neonatal neurological outcomes. The purpose of this study was to compare maternal and fetal outcomes following intravenous (IV) versus oral iron supplementation for iron-deficiency anemia during pregnancy. Methods: We searched MEDLINE, OVID, Scopus, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials (RCTs) comparing IV versus oral iron supplementation for iron-deficiency anemia during pregnancy. Studies were included in this meta-analysis if they reported maternal and fetal hematologic outcomes. The relative risk (RR) or standard mean difference (SMD) of IV iron supplementation was calculated for notable outcomes. Results: Eleven studies, with a total of 1621 women in the IV group and 1640 women in the oral group, were included in this meta-analysis. Fetal birthweight, was higher in the IV iron group (SMD 58.60g, 95% confidence interval (CI) 2.63,114.58). There was no significant difference in the rate of preterm birth or gestational age at birth between the two groups. Maternal hemoglobin at delivery was significantly higher in the IV group compared to the oral group (SMD 0.85 g/dL (95% CI (0.15, 1.55)). The IV group experienced 40 (2.5%) cases of gastrointestinal distress, compared to 69 (4.2%) cases in the oral group (RR 0.60 (95% CI (0.40,0.89)). Discussion: Intravenous iron supplementation for iron-deficiency anemia during pregnancy results in higher neonatal birthweight, higher maternal hemoglobin levels, and minimal adverse effects. Future studies are needed to investigate the cost-effectiveness of IV iron

Oral progesterone for the prevention of recurrent preterm birth: systematic review and metaanalysis

Objective The purpose of this study was to perform a systematic review and metaanalysis of randomized controlled trials on oral progesterone compared with placebo or other interventions for preterm birth prevention in singleton pregnancies with previous spontaneous preterm birth. The primary outcome was preterm birth at <37 weeks gestation; the secondary outcomes included preterm birth rate at <34 weeks gestation, neonatal morbidity/death, and maternal side-effects. Study Searches were performed in PubMed, Scopus, ClinicalTrials.gov, PROSPERO, EMBASE, and the Cochrane Register with the use of a combination of words related to “preterm birth,” “preterm delivery,” “progesterone,” “progestogens,” and “oral” from inception of each database to April 2018. Additionally, systematic reviews on progesterone for preterm birth prevention that were identified in our search were also reviewed for additional studies. We included all randomized trials of asymptomatic singleton gestations with previous spontaneous singleton preterm birth that had been randomized to prophylactic treatment with oral progesterone vs placebo, no treatment, or other preterm birth intervention. Exclusion criteria included quasirandomized trials, trials that involved women with preterm labor/membrane rupture at the time of randomization or multiple gestations. Study Appraisal and Synthesis Methods The risk of bias and quality of evidence were assessed for each study. All analyses were done with an intention-to-treat approach. The primary outcome was incidence of preterm birth at 30% was used to identify heterogeneity. Results The search strategy identified 79 distinct studies. Three trials on oral progesterone vs placebo (involved 386 patients: 196 in oral progesterone and 190 in placebo) met the inclusion criteria; there were no studies on oral progesterone vs other intervention that met inclusion criteria. Metaanalysis demonstrated a significantly decreased risk of preterm birth at <37 weeks gestation (42% vs 63%; P=.0005; relative risk, 0.68; 95% confidence interval, 0.55–0.84), preterm birth at <34 weeks gestation (29% vs 53%; P<.00001; relative risk, 0.55; 95% confidence interval, 0.43–0.71), and increased gestational age of delivery (mean difference, 1.71 weeks; 95% confidence interval, 1.11–2.30) with oral progesterone compared with placebo. There was a significantly lower rate of perinatal death (5% vs 17%; P=.001; relative risk 0.32; 95% confidence interval, 0.16–0.63), neonatal intensive care admission (relative risk, 0.39; 95% confidence interval, 0.25–0.61), respiratory distress syndrome (relative risk, 0.21; 95% confidence interval, 0.05–0.93), and higher birthweight (mean difference, 435.06 g; 95% confidence interval, 324.59–545.52) with oral progesterone. There was a higher rate of maternal adverse effects with oral progesterone that included dizziness (relative risk, 2.95; 95% confidence interval, 1.47–5.90), somnolence (relative risk, 2.06; 95% confidence interval, 1.29–3.30), and vaginal dryness (relative risk, 2.37; 95% confidence interval, 1.10–5.11); no serious adverse effects were noted. Conclusion Oral progesterone appears to be effective for the prevention of recurrent preterm birth and a reduction in perinatal morbidity and mortality rates in asymptomatic singleton gestations with a history of previous spontaneous preterm birth compared with placebo. There were also increased adverse effects with oral progesterone therapy compared with placebo, although none were serious. Further randomized study on oral progesterone compared with other established therapies for the prevention of recurrent preterm birth are warranted

Reduced maternal immunity and vertical transfer of immunity against SARS-CoV-2 variants of concern with COVID-19 exposure or initial vaccination in pregnancy

IntroductionAs the SARS-CoV-2 pandemic continues to evolve, we face new variants of concern with a concurrent decline in vaccine booster uptake. We aimed to evaluate the difference in immunity gained from the original SARS-CoV-2 mRNA vaccine series in pregnancy versus SARS-CoV-2 exposure during pregnancy against recent variants of concern.Study DesignThis is a retrospective analysis of previously collected samples from 192 patients who delivered between February 2021 and August 2021. Participants were categorized as 1) COVID vaccine: mRNA vaccine in pregnancy, 2) COVID-exposed, and 3) controls. The primary outcome was neutralizing capacity against wild-type, Delta, and Omicron-B1 between cohorts. Secondary outcomes include a comparison of cord-blood ID50 as well as the efficiency of vertical transfer, measured by cord-blood:maternal blood ID50 for each variant.ResultsPregnant women with COVID-19 vaccination had a greater spike in IgG titers compared to both those with COVID-19 disease exposure and controls. Both COVID exposure and vaccination resulted in immunity against Delta, but only COVID vaccination resulted in significantly greater Omicron ID-50 versus controls. The neutralizing capacity of serum from newborns was lower than that of their mothers, with COVID-vaccination demonstrating higher cord-blood ID50 vs wildtype and Delta variants compared to control or COVID-exposed, but neither COVID-exposure nor vaccination demonstrated significantly higher Omicron ID50 in cord-blood compared to controls. There was a 0.20 (0.07-0.33, p=0.004) and 0.12 (0.0-0.24, p=0.05) increase in cord-blood:maternal blood ID50 with COVID vaccination compared to COVID-19 exposure for wild-type and Delta respectively. In pair-wise comparison, vertical transfer of neutralization capacity (cord-blood:maternal blood ID50) was greatest for wild-type and progressively reduced for Delta and Omicron ID50.ConclusionPregnant patients with either an initial mRNA vaccination series or COVID-exposure demonstrated reduced immunity against newer variants compared to wild-type as has been reported for non-pregnant individuals; however, the COVID-vaccination series afforded greater cross-variant immunity to pregnant women, specifically against Omicron, than COVID-disease. Vertical transfer of immunity is greater in those with COVID vaccination vs COVID disease exposure but is reduced with progressive variants. Our results reinforce the importance of bivalent booster vaccination in pregnancy for both maternal and infant protection and also provide a rationale for receiving updated vaccines as they become available

Association of operative approach with postoperative outcomes in neonates undergoing surgical repair of esophageal atresia and tracheoesophageal fistula

Introduction: Minimally invasive surgery (MIS) is gaining traction as a first-line approach to repair congenital anomalies. This study aims to evaluate outcomes for neonates undergoing open versus MIS repairs for esophageal atresia/tracheoesophageal fistula (EA/TEF). Methods: Neonates undergoing EA/TEF repair from 2013-2020 were identified using the National Surgical Quality Improvement Program-Pediatric database. Proportions of operative approach (open vs. MIS) over time were analyzed. A propensity score-matched analysis using preoperative characteristics was performed and outcomes were compared including composite morbidity and reintervention rates (overall, major [thoracoscopy, thoracotomy], and minor [chest/feeding tube placement, endoscopy]) between operative approaches. Pearson’s chi-square or Fisher’s exact test were used as appropriate. Results: We identified 1738 neonates who underwent EA/TEF repair. MIS utilization increased over time (p=0.019). Pre-match, neonates undergoing open repair were more likely premature, lower weight, and higher ASA class. Post-match, the groups were similar and included 183 neonates per group. MIS repair was associated with longer median operative time (206 vs. 180 minutes, p\u3c0.001), increased overall reintervention rates (MIS 9.8% vs. open 3.3%, p=0.011), and increased minor reintervention rates (MIS 7.7% vs. open 2.2%, p=0.016). There were no differences in composite morbidity (MIS 20.2% vs. open 26.8%, p=0.14) or major reinterventions (MIS 2.2% vs. open 1.1%, p=0.41). Discussion: MIS is gaining traction as a first-line approach for neonates with EA/TEF but appears to be associated with a higher rate of reinterventions. Further studies evaluating MIS approaches for the repair of EA/TEF are needed to better define short and long-term outcomes to optimize patient selection

Health disparities among pregnant women diagnosed with COVID-19 in Philadelphia

Introduction: The CDC has cited language barriers and racial discrimination as some of the social determinants of health during the COVID-19 pandemic. This study aims to investigate the socioeconomic factors that affect COVID-19 diagnosis and outcomes in pregnant women. We hypothesize that women whose primary language is not English will have higher rates of COVID-19 compared to women whose primary language is English. Methods: This is a retrospective cohort study of women who delivered at TJUH between 04/13/2020 and 06/31/2020. Data on demographics, SARS-CoV-2 PCR, maternal, fetal, neonatal outcomes were collected. The primary outcome was the proportion of English vs Non-English-speaking patients with and without SARS-CoV-2 positive PCR. Data were analyzed using a Chi-squared test. Multivariable logistic regression will be used to control for the effect of factors including comorbidities and income level. The study was approved by TJUH Institutional Review Board. Results: Preliminary data are herein reported. 473 women have been included thus far (of 713 eligible), 106 tested positive and 367 tested negative. Overall, the preferred language was English in 78.4%, Spanish in 12.9%, Other in 8.7%. There were significantly more Non-English-speaking patients in the COVID-19 positive group than in the COVID-19 negative group (36.8% vs 17.2%, p\u3c0.001). Discussion: Non-English-speaking pregnant women are disproportionally represented in the COVID positive patient population, which supports our hypothesis. This suggest that language is significant barrier to SARS-CoV-2 care, this may be related to other sociodemographic factors. Further analysis will provide data on the impact of this disparity. Data collection will be completed in January 2021

Labor and Delivery Guidance for COVID-19

This document addresses the current coronavirus disease 2019 (COVID-19) pandemic for providers and patients in labor and delivery (L&D). The goals are to provide guidance regarding methods to appropriately screen and test pregnant patients for COVID-19 prior to, and at admission to L&D reduce risk of maternal and neonatal COVID-19 disease through minimizing hospital contact and appropriate isolation and provide specific guidance for management of L&D of the COVID-19-positive woman, as well as the critically ill COVID-19-positive woman. The first 5 sections deal with L&D issues in general, for all women, during the COVID-19 pandemic. These include Section 1: Appropriate screening, testing, and preparation of pregnant women for COVID-19 before visit and/or admission to L&D Section 2: Screening of patients coming to L&D triage; Section 3: General changes to routine L&D work flow; Section 4: Intrapartum care; Section 5: Postpartum care; Section 6 deals with special care for the COVID-19-positive or suspected pregnant woman in L&D and Section 7 deals with the COVID-19-positive/suspected woman who is critically ill. These are suggestions, which can be adapted to local needs and capabilities