Placental SARS-CoV-2 Infection and Its Implications for Increased Risk of Adverse Pregnancy Outcomes.

OBJECTIVE: Pregnant women are at increased risk of coronavirus disease 2019 (COVID-19). This could be explained through the prism of physiologic and immunologic changes in pregnancy. In addition, certain immunological reactions originate in the placenta in response to viral infections.This study aimed to investigate whether severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can infect the human placenta and discuss its implications in the pathogenesis of adverse pregnancy outcomes. STUDY DESIGN: We conducted a retrospective cohort study in which we collected placental specimens from pregnant women who had a laboratory-confirmed SARS-CoV-2 infection. We performed RNA in situ hybridization assay on formalin-fixed paraffin-embedded tissues to establish the in vivo evidence for placental infectivity by this corona virus. In addition, we infected trophoblast isolated from uninfected term human placenta with SARS-CoV-2 variants to further provide in vitro evidence for such an infectivity. RESULTS: There was a total of 21 cases enrolled, which included 5 cases of spontaneous preterm birth (SPTB) and 2 intrauterine fetal demises (IUFDs). Positive staining of positive-sense strand of SARS-CoV-2 virions was detected in 15 placentas including 4 SPTB and both IUFDs. In vitro infection assay demonstrated that SARS-CoV-2 virions were highly capable of infecting both cytotrophoblast and syncytiotrophoblast. CONCLUSION: This study implies that placental SARS-CoV-2 infection may be associated with an increased risk of adverse obstetrical outcomes. KEY POINTS: · SARS-CoV-2 can effectively infect human placenta.. · Such infectivity is confirmed by in vitro experiments.. · Placental SARS-CoV-2 corelates with adverse obstetrical outcomes..

COVID-19 is associated with early emergence of preeclampsia: results from a large regional collaborative.

Objective: To investigate the relationship between preeclampsia and SARS-CoV-2 infection during pregnancy. Methods: This was a retrospective cohort study of pregnant women between March and October 2020. Pregnant patients admitted to 14 obstetrical centers in Michigan, USA formed the study population. Of the N = 1458 participants, 369 had SARS-CoV-2 infection (cases). Controls were uninfected pregnancies that were delivered in the same obstetric unit within 30 days of the index case. Robust Poisson regression was used to estimate relative risk (RR) of preterm and term preeclampsia and preeclampsia involving placental lesions. The analysis included adjustment for relevant clinical and demographic risk factors.Results: SARS-CoV-2 infection during pregnancy increased the risk of preeclampsia [adjusted aRR = 1.69 (1.26-2.26)], preeclampsia involving placental lesions [aRR = 1.97(1.14-3.4)] and preterm preeclampsia 2.48(1.48-4.17). Although the highest rate of preeclampsia was observed in patients infected with SARS-CoV-2 who were symptomatic (18.4%), there was increased risk even in asymptomatic SARS-CoV-2 infected patients (14.2%) relative to non-infected controls (8.7%) (p < 0.05). This association with symptomatology was also noted with preterm preeclampsia for which the rate doubled from 2.7% in controls to 5.2% in asymptomatic cases and reached 11.8% among symptomatic cases (p < 0.05). The rate of preterm preeclampsia among cases of pregnant people self-identified as Black reached 10.1% and was almost double the rate of the reminder of the group of infected pregnancies (5.3%), although the rate among uninfected was almost the same (2.7%) for both Black and non-Black groups (interaction p = 0.05).Conclusions: Infection with SARS-CoV-2 increases the risk of preeclampsia even in the absence of symptoms, although symptomatic persons are at even higher risk. Racial disparities in the development of preterm preeclampsia after SARS-CoV-2 infection may explain discrepancies in prematurity between different populations.

Placental Cortisol Dysregulation in Mothers with Experiences of Childhood Adversity: Potential Mechanisms and Clinical Implications.

Adverse childhood experiences (ACEs) are extremely prevalent in the United States population. Although ACEs occurs in childhood, exposure to them has been associated with adverse future pregnancy outcomes and an increased risk of poorer social determinants of health, which further drive the risk of negative pregnancy outcomes. In addition, maternal ACE exposure has been linked to poor infant and child outcomes, highlighting the intergenerational transmission of risk from mother to child. While alterations along the Maternal-Placental-Fetal Hypothalamic-pituitary-adrenal (HPA) axis is hypothesized to be involved, the exact biological pathway underlying this intergenerational passage of risk is mostly unknown. This present work will highlight what is known about pregnancy-related stress hormone physiology, discuss the potential mechanisms of action of ACEs on cortisol regulation, and suggest opportunities for further clinical and translational studies.

Substance Use in Pregnancy and Its Impact on Communities of Color.

Stigma toward pregnant and postpartum people who use drugs is common and seeks to define addiction as a moral weakness rather than a chronic medical illness that requires resources and treatment. More concerning is the additive impact of substance use and racial discrimination, whose intersections present particularly challenging circumstances. In this article, the authors review the history of substance use in the United States and focus on 3 substances of abuse that illustrate the inequity faced by pregnant person of color who use drugs.

Drivers of variation in postpartum opioid prescribing across hospitals participating in a statewide maternity care quality collaborative.

BACKGROUND: We describe variation in postpartum opioid prescribing across a statewide quality collaborative and assess the proportion due to practitioner and hospital characteristics. METHODS: We assessed postpartum prescribing data from nulliparous, term, singleton, vertex births between January 2020 and June 2021 included in the clinical registry of a statewide obstetric quality collaborative funded by Blue Cross Blue Shield of Michigan. Data were summarized using descriptive statistics. Mixed effect logistic regression and linear models adjusted for patient characteristics and assessed practitioner- and hospital-level predictors of receiving a postpartum opioid prescription and prescription size. Relative contributions of practitioner and hospital characteristics were assessed using the intraclass correlation coefficient. RESULTS: Of 40,589 patients birthing at 68 hospitals, 3.0% (872/29,412) received an opioid prescription after vaginal birth and 87.8% (9812/11,177) received one after cesarean birth, with high variation across hospitals. In adjusted models, the strongest patient-level predictors of receiving a prescription were cesarean birth (aOR 899.1, 95% CI 752.8-1066.7) and third-/fourth-degree perineal laceration (aOR 25.7, 95% CI 17.4-37.9). Receiving care from a certified nurse-midwife (aOR 0.63, 95% CI 0.48-0.82) or family medicine physician (aOR 0.60, 95%CI 0.39-0.91) was associated with lower prescribing rates. Hospital-level predictors included receiving care at hospitals with <500 annual births (aOR 4.07, 95% CI 1.61-15.0). A positive safety culture was associated with lower prescribing rates (aOR 0.37, 95% CI 0.15-0.88). Much of the variation in postpartum prescribing was attributable to practitioners and hospitals (prescription receipt: practitioners 25.1%, hospitals 12.1%; prescription size: practitioners 5.4%, hospitals: 52.2%). DISCUSSION: Variation in postpartum opioid prescribing after birth is high and driven largely by practitioner- and hospital-level factors. Opioid stewardship efforts targeted at both the practitioner and hospital level may be effective for reducing opioid prescribing harms.

Partnering for the future clinic: A multidisciplinary perinatal substance use program.

OBJECTIVE: The current model of obstetric care does not integrate multiple subspecialty services for high-risk pregnancies with substance use disorder (SUD), resulting in fragmented care. We describe the framework of our multidisciplinary and integrated perinatal substance use clinic and provide recent clinical outcomes. METHODS: We detail the Partnering for the Future (PFF) clinic, which integrates numerous subspecialty and support services for patients with SUDs and complex mental health needs. Additionally, a retrospective chart review of patients receiving care in the PFF clinic from 2017 to 2021 was completed. RESULTS: Seven integrated services are detailed with a focus on reducing stigma, providing trauma-informed care and mitigating harm. During the study period, 182 patients received care in PFF clinic, with opioid use disorder the most common indication for care. Co-occurring mental illness was common (81%). NICU admissions and severe NOWS diagnosis declined after the implementation of Eat-Sleep-Console. Social services identified care coordination, transportation assistance and adjustment counseling as the most common needs. A novel virtual behavioral health consultation service was successfully launched. CONCLUSIONS: Our integrated care model supports the holistic care of pregnant people with SUD and mental health disease. Patient-centered care and co-located services have improved perinatal outcomes, particularly for opioid-exposed pregnancies.

The Impact of Spontaneous versus Indicated Preterm Birth on Neonatal Outcomes among Extremely Premature Neonates.

OBJECTIVE: This study aimed to investigate whether neonatal morbidity differs in spontaneous compared with indicated preterm births in extremely premature neonates. STUDY DESIGN: This is a retrospective cohort study including births ≤28 weeks at a single institution from 2011 to 2020. Births were categorized as either medically indicated or spontaneous preterm deliveries. The primary outcome was inhospital mortality and serious morbidity in survivors. t-tests, Fisher's exact tests, chi-square tests, and logistic regression models were utilized as appropriate. p < 0.05 was significant. RESULTS: Two hundred and twenty-seven births were included, with two-thirds representing spontaneous births (65.6%, 149/227) and one-third categorized as medically indicated births (34.4%, 78/227). Inhospital mortality was more common in the spontaneous preterm birth group (p = 0.04), while inhospital morbidity did not significantly vary between the medically indicated and spontaneous birth groups (p = 0.32). There was no difference in inhospital morbidity or mortality by maternal race. In multivariate models of inhospital morbidity and mortality, gestational age was the only significant predictor of adverse outcomes. CONCLUSION: Despite inhospital mortality being more common in spontaneous preterm births, inhospital mortality and significant morbidity are best accounted for by gestational age alone. KEY POINTS: · Inhospital death is more common in spontaneous preterm births.. · Perinatal outcomes do not differ on the basis of racial/ethnic group.. · Gestational age is the best predictor of inhospital morbidity and mortality..

Epigenetics and the Exposome: DNA Methylation as a Proxy for Health Impacts of Prenatal Environmental Exposures.

The accumulation of every day exposures can impact health across the life course, but our understanding of such exposures is impeded by our ability to delineate the relationship between an individual's early life exposome and later life health effects. Measuring the exposome is challenging. Exposure assessed at a given time point captures a snapshot of the exposome but does not represent the full spectrum of exposures across the life course. In addition, the assessment of early life exposures and their effects is often further challenged by lack of relevant samples and the time gap between exposures and related health outcomes in later life. Epigenetics, specifically DNA methylation, has the potential to overcome these barriers as environmental epigenetic perturbances can be retained through time. In this review, we describe how DNA methylation can be framed in the world of the exposome. We offer three compelling examples of common environmental exposures, including cigarette smoke, the endocrine active compound bisphenol A (BPA), and the metal lead (Pb), to illustrate the application of DNA methylation as a proxy to measure the exposome. We discuss areas for future explorations and current limitations of this approach. Epigenetic profiling is a promising and rapidly developing tool and field of study, offering us a unique and powerful way to assess the early life exposome and its effects across different life stages.

Use of Opioid-Sparing Protocols and Perceived Postpartum Pain in Patients with Opioid Use Disorder and Chronic Prenatal Opioid Exposure.

INTRODUCTION: Opioid-sparing protocols reduce postpartum opioid prescribing in opioid-naïve patients; however, patients with opioid use disorder (OUD) and complex pain needs who may benefit from these protocols are typically excluded from them. We assessed postpartum pain experiences of patients with OUD and chronic prenatal opioid exposure after implementation of an opioid-sparing protocol. METHODS: A phone survey assessed postpartum pain experiences for people with chronic prenatal opioid exposure who delivered between January 2020 and August 2021 at an academic hospital. Analyses included descriptive statistics, qualitative content analysis, and a joint display comparing themes. RESULTS: Of 25 patients, 18 (72%) participated; most were non-Hispanic White (100%, 18/18), publicly insured (78%, 14/18), multiparous (78%, 14/18), with OUD (100%, 18/18). No patients with a vaginal birth received an opioid prescription; half (4/8) with a cesarean birth received one at discharge. Over one-third (7/18, 39%) reported poor pain control (≥ 5/10) in the hospital and one week post-discharge; scores were higher for cesarean versus vaginal birth. Qualitative sub-analyses of open-ended responses revealed patient perceptions of postpartum pain and treatment. The most effective strategies, stratified by birth type and pain level, ranged from non-opioid medications for vaginal births and minor pain to prescription opioids for cesarean births and moderate-to-intense pain. DISCUSSION: Postpartum opioid prescribing for patients with chronic prenatal opioid use was low for vaginal and cesarean birth following implementation of an opioid-sparing protocol. Patients with OUD reported good pain management with opioid-sparing pain regimens; however, many reported poorly controlled pain immediately postpartum. Future work should assess approaches to postpartum pain management that minimize the risks of opioid medication-particularly in at-risk groups.

What is already known on this subject? Opioid-sparing protocols can reduce postpartum opioid prescribing in opioid-naïve patients; however, there are currently no clear guidelines for opioid prescribing for people with opioid use disorder (OUD) in the postpartum period.What this study adds?Postpartum opioid prescribing for patients with chronic prenatal opioid use was less than the national average and one-third of patients reported poor pain control. Opioid-sparing protocols postpartum should be expanded to patients with OUD to improve pain control and minimize risks associated with opioid medication.

Maternal SARS-COV-2 infection and prematurity: the Southern Michigan COVID-19 collaborative.

OBJECTIVE: COVID-19 has been reported to increase the risk of prematurity, however, due to the frequent absence of unaffected controls as well as inadequate accounting for confounders in many studies, the question requires further investigation. We sought to determine the impact of COVID-19 disease on preterm birth (PTB) overall, as well as related subcategories such as early prematurity, spontaneous, medically indicated preterm birth, and preterm labor (PTL). We assessed the impact of confounders such as COVID-19 risk factors, a-priori risk factors for PTB, symptomatology, and disease severity on rates of prematurity. METHODS: This was a retrospective cohort study of pregnant women from March 2020 till October 1st, 2020. The study included patients from 14 obstetric centers in Michigan, USA. Cases were defined as women diagnosed with COVID-19 at any point during their pregnancy. Cases were matched with uninfected women who delivered in the same unit, within 30 d of the delivery of the index case. Outcomes of interest were frequencies of prematurity overall and subcategories of preterm birth (early, spontaneous/medically indicated, preterm labor, and premature preterm rupture of membranes) in cases compared to controls. The impact of modifiers of these outcomes was documented with extensive control for potential confounders. A p value <.05 was used to infer significance. RESULTS: The rate of prematurity was 8.9% in controls, 9.4% in asymptomatic cases, 26.5% in symptomatic COVID-19 cases, and 58.8% among cases admitted to the ICU. Gestational age at delivery was noted to decrease with disease severity. Cases were at an increased risk of prematurity overall [adjusted relative risk (aRR) = 1.62 (1.2-2.18)] and of early prematurity (<34 weeks) [aRR = 1.8 (1.02-3.16)] when compared to controls. Medically indicated prematurity related to preeclampsia [aRR = 2.46 (1.47-4.12)] or other indications [aRR = 2.32 (1.12-4.79)], were the primary drivers of overall prematurity risk. Symptomatic cases were at an increased risk of preterm labor [aRR = 1.74 (1.04-2.8)] and spontaneous preterm birth due to premature preterm rupture of membranes [aRR = 2.2(1.05-4.55)] when compared to controls and asymptomatic cases combined. The gestational age at delivery followed a dose-response relation with disease severity, as more severe cases tended to deliver earlier (Wilcoxon p < .05). CONCLUSIONS: COVID-19 is an independent risk factor for preterm birth. The increased preterm birth rate in COVID-19 was primarily driven by medically indicated delivery, with preeclampsia as the principal risk factor. Symptomatic status and disease severity were significant drivers of preterm birth.

Postpartum Opioid Prescribing in Patients with Opioid Use Prior to Birth.

OBJECTIVE: This study aimed to describe opioid prescribing patterns for pregnant patients with a history of or active opioid use to inform postpartum pain management strategies. STUDY DESIGN: We conducted a retrospective cohort analysis of all patients with a history of opioid use disorder (OUD) or chronic pain seen at a single outpatient clinic specializing in opioid use and OUD in pregnancy from January 2019 to August 2021. Patient characteristics, delivery outcomes, and opioid prescribing information were collected through electronic health record fields. We used descriptive statistics to characterize differences in receipt of an opioid prescription, prescription size, and receipt of a prescription refill across three patient groups: patients with OUD on medication, patients with OUD maintaining abstinence, and patients with chronic pain using opioids. In the study period, the institutional average rate of opioid prescribing after cesarean and vaginal birth were 80.0 and 2.8%, respectively. RESULTS: Of the 69 patients included in this study, 46 (66.7%) had a history of OUD on medication, 14 (20.3%) had a history of OUD maintaining abstinence, and 9 (13.0%) had a history of chronic pain. Receipt of an opioid prescription after childbirth was more common after cesarean birth (12/23, 52.2%) than vaginal birth (3/46, 6.5%). Refills were common in patients who received an opioid proscription (cesarean: 5/12, 41.7%; vaginal: 1/3, 33.3%). CONCLUSION: Compared with institutional averages, postpartum opioid prescribing rates for people with a history of OUD or chronic pain were 50 to 60% lower for cesarean birth and three times higher for vaginal birth. Future work is needed to balance opioid stewardship and harm reduction with adequate pain control in these high-risk populations. KEY POINTS: · Opioid prescribing rates for patients with OUD/chronic pain were 60% lower for cesarean birth than institutional averages.. · Opioid prescribing rates for patients with OUD/chronic pain were three times higher for vaginal birth than institutional averages.. · Refill rates following birth were high overall for cesarean (40%) and vaginal (33%) birth.. · More work is needed to balance opioid prescribing with adequate pain control in high-risk patients..

Experiences, risk perceptions, and COVID-19 vaccination outcomes among hospital workers.

BACKGROUND: Although COVID-19 vaccinations have been available to hospital workers in the U.S. since December 2020, coverage is far from universal, even in groups with patient contact. The aim of this study was to describe COVID-19-related experiences at work and in the personal lives of nurses, allied health workers, and non-clinical staff with patient contact, and to assess whether these experiences relate to COVID-19 vaccination. METHODS: Health care workers at a large Midwestern hospital in the U.S. were contacted to participate in an online cross-sectional survey during February 2021. A logistic regression model was used to estimate odds ratios (OR) for vaccination by different experiences, and we assessed mediation through models that also included measures of risk perceptions. RESULTS: Among 366 nurse practitioners / nurse midwives / physician assistant, 1,698 nurses, 1,798 allied health professionals, and 1,307 non-clinical staff with patient contact, the proportions who had received or intended to receive a COVID-19 vaccination were 94 %, 87 %, 82 %, and 88 %, respectively. Working and being physically close to COVID-19 patients was not significantly associated with vaccine intent. Vaccination intent was significantly lower among those with a previous COVID-19 diagnosis vs not (OR = 0.33, 95 % CI: 0.27, 0.40) and higher for those who knew close family members of friends hospitalized or died of COVID-19 (OR = 1.33, 95 % CI: 1.10, 1.60). CONCLUSION: Even when COVID-19 vaccination was available in February 2021, a substantial minority of hospital workers with patient contact did not intend to be vaccinated. Moreover, their experiences working close to COVID-19 patients were not significantly related to vaccination intent. Instead, personal experiences with family members and friends were associated with vaccination intent through changes in risk perceptions. Interventions to increase uptake among hospital workers should emphasize protection of close family members or friends and the severity of COVID-19.

Disparities in Emergency Department Utilization Among Women with Postpartum Mood Disorders (2006-2016).

INTRODUCTION: Postpartum mood disorders are associated with adverse outcomes for newborns and mothers and may require urgent evaluation. The emergency department is often a healthcare entry point, but factors associated with these emergency department visits are unknown. METHODS: A longitudinal retrospective analysis using the Nationwide Emergency Department Sample to assess national estimates of emergency department visits by women ages 15-49 with primary diagnosis of a postpartum mood disorder between 2006 and 2016. Emergency department visit rates for postpartum mood disorders per 100,000 live births were calculated. RESULTS: Emergency department visits related to postpartum mood disorders remained stable from 2006 to 2016 (5153 to 5390 respectively). Two-thirds of visits were by patients younger than 30. Approximately half of visits for postpartum mood disorders were funded by Medicaid (42.4-56.7%) compared to 27.4-41.2% funded by Medicaid for all other age-matched women. Of postpartum mood disorder visits 30.3% were by women from the lowest income quartile. The highest rate of emergency department visits occurred in the youngest patients (ages 15-19: 231 visits versus ages 35-49: 105 visits). Postpartum mood disorder admissions were higher than those for age-matched women with all other diagnoses (19.8% vs. 6.5%). DISCUSSION: The high rate of women that are young and with public insurance visiting the emergency department for postpartum mood disorders demonstrates an increased risk for these disorders in these populations and an opportunity for targeted intervention by policymakers and providers. Higher admission rates for postpartum mood disorders compared to all other diagnoses reveals a chance to optimize outpatient screening and treatment.

Number of buprenorphine induction attempts impacts maternal and neonatal outcomes: a multicenter cohort study.

BACKGROUND: Buprenorphine can be used to treat maternal opioid use disorder effectively and decrease obstetrical risks. Compared with the use of other medications to treat opioid use disorder, the use of buprenorphine results in improved neonatal outcomes; however, its use is associated with higher rates of treatment attrition. Initiation of buprenorphine, termed "induction," is a high-risk time for treatment dropout and can require repeated attempts. OBJECTIVE: This study aimed to evaluate the effect of multiple buprenorphine induction attempts on maternal and neonatal outcomes. STUDY DESIGN: This was a retrospective cohort study of all pregnant patients who underwent sublingual buprenorphine induction for the treatment of opioid use disorder from June 18, 2018, to January 1, 2021, at 3 tertiary care centers. Patients who required only 1 attempt for successful buprenorphine induction were compared with those who required multiple attempts but ultimately were successful in the treatment initiation during pregnancy, confirmed by urine drug screening. The primary outcome was nonprescribed opioid use at the time of delivery. The secondary outcomes included obstetrical and neonatal outcomes associated with opioid use disorder. Background characteristics were compared using Fisher exact, chi-square, Mann-Whitney U, and Student t tests. The outcomes were compared using multivariable logistic regression, and time to delivery after initiation of prenatal care was compared between groups using Kaplan-Meier curves and a Cox proportional-hazards model. RESULTS: Overall, 63 patients undergoing buprenorphine induction during pregnancy were included, with 38 (60.3%) patients with 1 attempt and 25 patients (39.7%) with multiple attempts. There was no statistical difference between the 2 groups in terms of background characteristics. Compared with a single successful attempt, multiple attempts at buprenorphine induction were associated with a significantly increased odds of nonprescribed opioid use at the time of delivery (76.0% vs 15.8%; adjusted odds ratio, 30.00; 95% confidence interval, 5.50-163.90), increased risk of preterm birth (48.0% vs 15.8%; adjusted hazard ratio, 3.24; 95% confidence interval, 1.17-8.95), and decreased rate of breastfeeding at both maternal discharge (24.0% vs 78.9%; adjusted odds ratio, 0.06; 95% confidence interval, 0.00-0.30) and infant discharge (24.0% vs 55.3%; adjusted odds ratio, 0.23; 95% confidence interval, 0.10-0.80). CONCLUSION: Requiring multiple attempts for buprenorphine induction significantly increases the odds of nonprescribed opioid use at the time of delivery and preterm birth and decreases the odds of breastfeeding. As the buprenorphine induction process may affect obstetrical outcomes for patients induced during pregnancy, investigating the techniques that increase the likelihood of successful induction is crucially needed to improve outcomes in patients with maternal opioid use disorder.

Emergency Department Utilization for Substance Use Disorder During Pregnancy and Postpartum in the United States (2006-2016).

OBJECTIVES: We aimed to better understand emergency department (ED) use, admission patterns, and demographics for substance use disorder in pregnancy and postpartum (SUDPP). METHODS: In this longitudinal study, the United States Nationwide Emergency Department Sample was queried for all ED visits by 15- to 50-year-old women with a primary diagnosis defined by International Classification of Diseases, 9th or 10th edition Clinical Modification, codes of SUDPP between 2006 and 2016. Patterns of ED visit counts, rates, admissions, and ED charges were analyzed. RESULTS: Annual national estimated ED visits for SUDPP increased from 2,919 to 9,497 between 2006 and 2016 (a 12.4% annual average percentage change), whereas admission rates decreased (from 41.9% to 32.0%). ED visits were more frequent among women who were 20-29 years old, using Medicaid insurance, in the lowest income quartile, living in the South, and in metropolitan areas. Compared with the proportion of ED visits, 15- to 19-year-olds had significantly lower admission rates, whereas women with Medicaid and in the lowest income quartile had higher admission rates (p < .001). Opioid use, tobacco use, and mental health disorders were most commonly associated with SUDPP. The ED average inflation-adjusted charges for SUDPP increased from $1,486 to $3,085 between 2006 and 2016 (7.1% annual average percentage change; p < .001), yielding total annual charges of $4.02 million and $28.53 million. CONCLUSIONS: Despite the decrease in admissions, the number and charges for ED visits for SUDPP increased substantially between 2006 and 2016. These increasing numbers suggest a continuous need to implement preventive public health measures and provide adequate outpatient care for this condition in this population specifically.

More than grit: growing and sustaining physician-scientists in obstetrics and gynecology.

Obstetricians know the statistics-1 out of every 10 babies is born premature; preeclampsia affects 1 in 25 pregnant people; the United States has the highest rate of maternal mortality in the developed world. Yet, physicians and scientists still do not fully understand the biology of normal pregnancy, let alone what causes these complications. Obstetrics and gynecology-trained physician-scientists are uniquely positioned to fill critical knowledge gaps by addressing clinically-relevant problems through fundamental research and interpreting insights from basic and translational studies in the clinical context. Within our specialty, however, physician-scientists are relatively uncommon. Inadequate guidance, lack of support and community, and structural barriers deter fellows and early stage faculty from pursuing the physician-scientist track. One approach to help cultivate the next generation of physician-scientists in obstetrics and gynecology is to demystify the process and address the common barriers that contribute to the attrition of early stage investigators. Here, we review major challenges and propose potential pathways forward in the areas of mentorship, obtaining protected research time and resources, and ensuring diversity, equity, and inclusion, from our perspective as early stage investigators in maternal-fetal medicine. We discuss the roles of early stage investigators and leaders at the institutional and national level in the collective effort to retain and grow our physician-scientist workforce. We aim to provide a framework for early stage investigators initiating their research careers and a starting point for discussion with academic stakeholders. We cannot afford to lose the valuable contributions of talented individuals due to modifiable factors or forfeit our voices as advocates for the issues that impact pregnant populations.

There is reduced immunohistochemical staining of placental aromatase in severe neonatal opioid withdrawal syndrome.

BACKGROUND: Placental cytochrome p450 (CYP450) enzymes and efflux transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), are critical for transfer of drugs from the placenta to maternal circulation. CYP19A1 (aromatase) is the enzyme responsible for metabolizing methadone and buprenorphine in the human placenta. OBJECTIVE: We sought to determine if differences exist in CYP19A1 and efflux transporter immunostaining intensity and density within the syncytiotrophoblast in opioid-exposed and unexposed pregnancies. Additionally, we sought to investigate whether CYP19A1 and efflux transporter expression was different in placentas of infants who developed severe neonatal opioid withdrawal syndrome (NOWS) and those who did not. STUDY DESIGN: This was a retrospective nested case control study from 2014 to 2019 at a single tertiary care center. The opioid-exposed cohort included pregnant women aged ≥18 years on maintenance methadone or buprenorphine with non-anomalous singleton fetuses and gestational age ≥33 weeks. Controls included pregnant women with no medication exposure delivering at ≥37 weeks. De-paraffinized placental sections, inclusive of the apical syncytiotrophoblast membrane, were labeled with monoclonal antibodies for aromatase, P-gp, and BCRP. Placentas were scored for the presence and intensity of staining using the Allred scoring schema. Data were analyzed using descriptive, parametric, and nonparametric statistics. p < .05 was considered significant. RESULTS: One hundred and ten opioid-exposed neonates were included in this analysis (51 opioid-exposed cases and 59 opioid-exposed controls), with 68/110 delivering at term. Ten unexposed controls delivering at term were also included. The median placental Allred scores for aromatase were significantly lower in the opioid-exposed cohort compared with the unexposed controls (exposed 6.8 ± 1.4 vs. unexposed 7.5 ± 0.7, p = .03). The median placental Allred scores for aromatase were significantly lower in opioid-exposed cases that developed severe NOWS compared to opioid-exposed controls (p = .03) that did not develop severe NOWS. There were no differences in P-gp and BCRP scores between groups. CONCLUSIONS: Syncytiotrophoblast aromatase immunostaining scores were reduced in opioid-exposed cases compared to unexposed controls. Additionally, infants who developed severe NOWS had significantly lower placental aromatase in the apical syncytiotrophoblast compared with those without severe NOWS.

Fetal gastric area ratio to predict severe neonatal opioid withdrawal syndrome.

OBJECTIVE: Neonatal opioid withdrawal syndrome (NOWS) can occur in newborns exposed to opioids in pregnancy. Opioids delay gastric emptying and inhibit gastric motility in adults, but little is known about their effect in the fetus. We sought to assess gastric area ratio (GAR) in opioid-exposed fetuses. STUDY DESIGN: Retrospective cohort study including opioid-exposed maternal-neonatal dyads between 2007-2017. Primary outcome: severe NOWS (three consecutive Finnegan scores ≥8 or three scores totaling ≥24 within 96 h of life). GAR: (gastric area)/(transverse abdominal area) × 100. Data analysis was by descriptive, parametric, and non-parametric tests. RESULTS: Forty-nine maternal-neonatal dyads were included, 67% (n = 33) with severe NOWS. GAR <95th percentile for gestational age was seen in 80% of neonates (n = 39). However, GAR was not different between groups (p = .90) and did not predict severe NOWS. CONCLUSION: Fetal GAR was <95th percentile in 80% of opioid-exposed neonates. However, fetal GAR may not predict NOWS treatment.

Investigating the origin of the fetal gut and placenta microbiome in twins.

OBJECTIVE: It is widely accepted that the microbiota is critical for human well-being; however, the origin of microbiota in the newborn is not well understood. In this study, we hypothesized that within a maternal-twin dyad (MTD) the meconium microbiome will be similar to the placenta microbiome and the meconium microbiome of within MTD will be similar to one another. METHODS: Prospectively, meconium (proxy for fetal gut), placenta and maternal buccal, skin, vaginal, stool samples were collected from a cohort of MTDs at time of delivery hospitalization. We performed gene sequencing using the V4 region of 16S rRNA with rigorous negative controls. Alpha and beta diversity indices were computed to characterize the microbial community of MTD samples. A p value of <.05 was considered significant. RESULTS: From 17 MTD, 87/132 samples were successfully sequenced. The alpha diversity of the microbiome collected from all the body sites were different (p ≤ .001). The meconium samples when compared to other samples in the MTD microbial community were different (p = .009) and the Bray-Curtis dissimilarity was greater than 0.95 for all of the comparisons (beta diversity). The MTD within-twin placenta microbiome samples were also different, confirmed by Bray-Curtis pairwise dissimilarity distance, 0.83. CONCLUSION: The fetal gut microbiome is different from placenta and maternal buccal, skin, vaginal and stool microbiome. We clearly identified a distinct placenta microbiome. Furthermore, placentas in the same MTD have distinct microbiomes, suggesting that fetal gut and placenta origin is complex and remains unclear.