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.

Risk Identification in Perinatal Health Care Settings via Technology-Based Recruitment Methods: Comparative Study.

BACKGROUND: Digital screening and intervention tools have shown promise in the identification and reduction of substance use in health care settings. However, research in this area is impeded by challenges in integrating recruitment efforts into ongoing clinical workflows or staffing multiple study clinics with full-time research assistants, as well as by the underreporting of substance use. OBJECTIVE: The aim of the study is to evaluate pragmatic methods for facilitating study recruitment in health care settings by examining recruitment rates and participant characteristics using in-person-based versus flyer approaches. METHODS: This study compared recruitment rates at a Women's Health clinic in the Midwest under 2 different recruitment strategies: in person versus via a flyer with a QR code. We also examined the disclosure of substance use and risk screener positivity for the 2 strategies. We also obtained information about the current use of technology and willingness to use it for study participation. RESULTS: A greater percentage of patients recruited in person participated than those recruited via flyers (57/63, 91% vs 64/377, 17%). However, the final number recruited in each group was roughly equal (n=57 vs n=64). Additionally, participants recruited via flyers were more likely to screen positive for alcohol use risk on the Tolerance, Annoyed, Cut Down, Eye-Opener alcohol screen than those recruited at the clinic (24/64, 38% vs 11/57, 19%; χ21=4.9; P=.03). Participants recruited via flyers were also more likely to screen positive for drug use risk on the Wayne Indirect Drug Use Screener than those recruited at the clinic (20/64, 31% vs 9/57, 16%; χ21=4.0; P=.05). Furthermore, of the 121 pregnant women, 117 (96.7%) reported owning a smartphone, 111 (91.7%) had an SMS text message plan on their phone, and 94 (77.7%) reported being willing to receive SMS text messages or participate in a study if sent a link to their phone. CONCLUSIONS: The distribution of flyers with a QR code by medical staff appears to be an efficient and cost-effective method of recruitment that also facilitates disclosure while reducing the impact on clinic workflows. This method of recruitment can be useful for data collection at multiple locations and lead to larger samples across and between health systems. Participant recruitment via technology in perinatal health care appears to facilitate disclosure, particularly when participants can learn about the research and complete screening using their own device at a place and time convenient for them. Pregnant women in an urban Midwestern hospital had access to and were comfortable using technology.

ALK Rearrangement Positive Lung Adenocarcinoma in Pregnancy Treated With Alectinib: A Case Report.

There are few reported cases of ALK gene rearranged (ALK+) non-small cell lung cancer (NSCLC) during pregnancy. There is a lack of information on the safety of ALK inhibitors in pregnant patients. We present a 25-year-old African American woman who was diagnosed with metastatic ALK+ lung adenocarcinoma at 15 weeks of gestation. Treatment with alectinib was initiated at 18 weeks' gestation with resultant radiological treatment response. The patient did not experience any adverse effects from alectinib during her pregnancy. An elective induction of labor at 39 weeks resulted in an uncomplicated vaginal delivery. This case adds to available data and provides insight on the safety of using alectinib in a pregnant, ALK+ NSCLC patient, allowing the patient to continue her pregnancy to term while treating advanced lung adenocarcinoma.

Provider adherence to aspirin prophylaxis prescription guidelines for preeclampsia.

OBJECTIVE: To evaluate provider adherence to aspirin prophylaxis prescription guidelines for patients at risk. STUDY DESIGN: A retrospective chart review was performed at Henry Ford Health (HFH) between October 2015 and December 2020. In October 2015, low-dose aspirin was recommended for women who met high risk criteria for preeclampsia at HFH; in February 2019, aspirin recommendation expanded to include women who met either moderate or high-risk criteria. A total of 46,016 pregnancies occurred between Oct 2015 and Dec 2020 of which 15,167 (33.0%) met high and moderate risk criteria. RESULTS: From the population at risk, 1,255 (8.3%) had a history of preeclampsia, 2,534 (16.7%) had a history of chronic hypertension, 1,418 (9.3%) had a history of diabetes, 7,470 (49.3%) were nulliparous, 4,038 (26.6%) were 35 years of age or older, 6,395 (42.2%) had a body mass index greater than 30 kg/m2, and 8,174 (54.5%) were African Americans. Only 630 out of 3,584 (17.6%) of women meeting the high-risk criteria for preeclampsia between Oct 2015 and Jan 2019 received low-dose aspirin and only 891 out of 5,874 (15.2%) of women meeting the high or moderate risk criteria for preeclampsia between Feb 2019 and Dec 2020 received low-dose aspirin prophylaxis. CONCLUSION: Adherence to aspirin prophylaxis guidelines was low. Most urban healthcare systems serve diverse, high-risk populations with multiple comorbidities rendering many women at risk for preeclampsia. Educational efforts to improve provider knowledge regarding this important preventative measure are indicated. Recommendation for implementing universal aspirin in such high-risk populations should also be considered.

Efficacy and Safety of Aspirin 162 mg for Preeclampsia Prophylaxis in High-Risk Patients.

OBJECTIVE: The aim of this study was to compare the safety and efficacy of aspirin 162 mg to the standard recommended dose of 81 mg for preeclampsia prevention. STUDY DESIGN: A retrospective cohort study of patients at risk for preeclampsia who delivered between January 2013 and December 2020 at Henry Ford Health was performed. Patients were divided into three groups: a no aspirin group, a group treated under an 81 mg aspirin preeclampsia prophylaxis protocol, and a group treated under a 162 mg protocol. Univariate and multivariable logistic regression analyses compared rates of preeclampsia and secondary outcomes between groups. Clinical side effects traditionally associated with aspirin use were also assessed. RESULTS: Of 3,597 patients, 2,266 (63%) were in the no aspirin group, 944 (26%) were in the 81 mg group, and 387 (11%) were in the 162 mg group. The rate of preeclampsia was significantly lower in the 162 mg group (10.1%, odds ratio, 0.68; 95% confidence interval, 0.46-0.99) compared with the 81 mg group (14.2%). The rate of preeclampsia was identical in the no aspirin and 81 mg groups. The rate for postpartum hemorrhage, postpartum hematoma, and intraventricular hemorrhage of the newborn were not significantly different between patients in the 162 and 81 mg groups. CONCLUSION: We observed a significantly lower rate of preeclampsia in high-risk patients who were treated with the 162 mg dose of aspirin for preeclampsia prophylaxis, and bleeding complications were not seen with the higher dose. Our study suggests that aspirin 162 mg may be considered for prophylaxis in patients at high risk for preeclampsia. KEY POINTS: · Aspirin 81 mg is currently standard for preeclampsia prophylaxis.. · Preeclampsia rate is significantly lower among high-risk patients taking aspirin 162 mg compared with 81 mg.. · Bleeding complications are not increased among those taking aspirin 162 mg..

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.

The impact of COVID-19 vaccinations on stillbirth rates among pregnant women in the Metro-Detroit area.

Infection by COVID-19 increases maternal morbidity and mortality prompting both the American College of Obstetrics and Gynecology and the Society of Maternal Fetal Medicine to strongly recommend vaccination during pregnancy. Limited data exist assessing the risk of intrauterine fetal death (IUFD) associated with COVID vaccination during pregnancy. This was a retrospective chart review at a large multisite hospital system in Metro Detroit which reviewed data from 13,368 pregnancies. We compared IUFD rates between vaccinated and unvaccinated patients. The rate of stillbirths among unvaccinated women (0.75%) was not statistically different from those who were vaccinated (0.60%). Individuals with government insurance were less likely to be vaccinated and more likely to have IUFD in comparison to patients with private insurance. The rate of stillbirths among Black women was significantly higher than among White women at a rate of 1.1% compared to 0.53% (p=0.008) with no difference in stillbirth rates among vaccinated vs unvaccinated racial distribution. Lastly, it is worth noting that the overall vaccination rate at our healthcare system in pregnancy was very poor (0.26%). In conclusion, this is a large population of highly diverse patients which indicates that COVID-19 vaccination does not lead to IUFD. We plan to use this data to help drive an educational vaccination campaign to try to increase our COVID-19 vaccination rate in our pregnant patients. Systemic racism and social determinants of health have played a large factor in COVID-19 outcomes, and our data highlights that this is the case for IUFD in Black women. Improvements must be made to identify barriers for these women to allow for better pregnancy outcomes. We acknowledge that individuals with government insurance may also have other barriers to healthcare or face healthcare inequity which leaves room for improvement on getting these individuals vaccinated and getting the resources they need to have better pregnancy outcomes.

Online randomised factorial trial of electronic Screening and Brief Intervention for alcohol use in pregnancy: a study protocol.

INTRODUCTION: Approximately 1 in 7 pregnant women in the USA report past-month alcohol use. Strong evidence connects prenatal alcohol exposure with a range of adverse perinatal outcomes, including the spectrum of conditions known as fetal alcohol spectrum disorders. Screening and Brief Intervention (SBI) has been recommended for pregnant women but has proven difficult to implement. This study will test the efficacy of single-session technology-delivered SBI (electronic SBI) for alcohol use in pregnancy, while simultaneously evaluating the possible additional benefit of tailored text messages and/or booster sessions in a 3×2 factorial trial. METHOD AND ANALYSIS: This full factorial trial will use online advertising and clinic-based flyers to recruit pregnant women meeting criteria for unhealthy alcohol use, and randomly assign them to one of six conditions crossing three levels of brief intervention (none, single 120-minute session and single session plus two 5-minute boosters) with two levels of tailored text messaging (none vs twice weekly messages). The primary analysis will test for dose-response effects of the brief intervention on alcohol abstinence, defined as no self-report of alcohol use in the 90 days prior to 34 weeks' gestation, and negative results for ethyl glucuronide analysis of fingernail samples. Secondary analyses will examine main and interaction effects of tailored text messaging as well as intervention effects on birth outcomes. ETHICS AND DISSEMINATION: Ethical approval was provided by the Michigan State University Biomedical and Health Institutional Review Board (STUDY00005298). Results will be presented at conferences and community forums, in addition to being published in a peer-reviewed journal. Intervention content demonstrating sufficient efficacy and safety will be made publicly available. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04332172).

Postpartum bilateral lung transplantation in COVID-19 associated respiratory failure.

In critically ill patients with COVID-19, established therapies in the setting of respiratory failure include invasive mechanical ventilation and extracorporeal membrane oxygenation (ECMO). This case report describes a pregnant woman in her 30s who was hospitalised at 35 weeks gestation with moderate COVID-19 disease. Her condition worsened following delivery, and she required intubation, maximum ventilatory support and ECMO. Because of the severe and irreversible nature of her lung disease, she ultimately underwent bilateral lung transplantation. This case showcases lung transplantation as an alternative life-saving option for patients with severe COVID-19 associated respiratory failure refractory to ECMO and mechanical ventilation. Further studies are needed to develop a multidisciplinary approach for patient selection for transplantation within the context of COVID-19 and to assess long-term outcomes.

A multidisciplinary approach to caring for a pregnant patient with blue rubber bleb nevus syndrome: A case report.

Blue rubber bleb nevus syndrome (BRBNS) is a rare vascular disorder characterized by recurrent, multifocal venous malformations throughout the skin, soft tissue, and numerous internal organs. Pregnant women with BRBNS are at high risk of morbidity and mortality, and thus their care requires careful planning and surveillance. This report highlights the case of a 21-year-old woman, gravida 1, para 0, with BRBNS who was cared for by a multidisciplinary team of providers in obstetrics, maternal-fetal medicine, obstetric anesthesia, hematology, dermatology, gastroenterology, and otorhinolaryngology. The report provides a comprehensive guide to the multidisciplinary management of pregnancy and delivery for patients with BRBNS.

Severe COVID-19 infection in pregnancy requiring intubation without preterm delivery: A case report.

BACKGROUND: Coronavirus-2019 (COVID-19) is a global health crisis, but there is limited guidance for the critical care management of pregnant patients experiencing respiratory collapse. We describe our management of a peri-viable pregnant patient requiring intubation; discussion includes pharmacologic interventions, mechanical ventilation adjustments, and consideration of fetal interventions, including delivery timing. CASE: A 36-year-old, gravida 2, para 1 woman positive for COVID-19 at 23 weeks of gestation with severe disease required admission to the intensive care unit and intubation. She completed 5 days of hydroxychloroquine and 7 days of prednisone. She was successfully intubated after 8 days and discharged home in a stable condition without preterm delivery on hospital day 11. CONCLUSION: Fortunately, the patient responded to aggressive respiratory support with intubation and mechanical ventilation early upon presentation. It is unclear whether our institution's empiric use of hydroxychloroquine and prednisone facilitated her recovery. We hope that our report helps other institutions navigate the complex care surrounding pregnant patients with severe COVID-19 pneumonia requiring intensive care.

Accuracy of five self-report screening instruments for substance use in pregnancy.

BACKGROUND AND AIMS: The accuracy of current screening instruments for identification of substance use in pregnancy is unclear, particularly given methodological shortcomings in existing research. This diagnostic accuracy study compared five existing instruments for ability to identify illicit drug, opioid and alcohol use, under privacy expectations consistent with applied practice and using a gold standard incorporating toxicological analysis. DESIGN: Prospective cross-sectional screening accuracy study. SETTING: Three sites encompassing four prenatal care clinics in the United States. PARTICIPANTS: Convenience sample of 1220 racially, ethnically and socio-economically diverse pregnant women aged 18 years and over. MEASUREMENTS: In Phase I, participants completed the five screening instruments in counterbalanced order. Instruments included the Substance Use Risk Profile-Pregnancy (SURP-P), CRAFFT (acronym for five-item screener with items related to car, relax, alone, forget, friends and trouble), 5Ps (parents, peers, partner, pregnancy, past), Wayne Indirect Drug Use Screener (WIDUS) and the National Institute on Drug Abuse (NIDA) Quick Screen. In Phase II, participants provided a urine sample and completed a calendar recall-based interview regarding substance use. These screeners were tested, using receiver operating characteristic (ROC) analysis and accuracy statistics, against a reference standard consisting of substance use in three classes (illicit drugs, opioids and alcohol), considered positive if use was evident via 30-day calendar recall or urine analysis. FINDINGS: Three hundred and fifteen of 1220 participants (26.3%) met reference standard criteria for positivity. The single-item screening questions from the NIDA Quick Screen showed high specificity (0.99) for all substances, but very poor sensitivity (0.10-0.27). The 5Ps showed high sensitivity (0.80-0.88) but low specificity (0.35-0.37). The CRAFFT, SURP-P and 5Ps had the highest area under the curve (AUC) for alcohol (0.67, 0.66 and 0.62, respectively), and the WIDUS had the highest AUC for illicit drugs and opioids (0.70 and 0.69, respectively). Performance of all instruments varied significantly with race, site and economic status. CONCLUSIONS: Of five screening instruments for substance use in pregnancy tested (Substance Use Risk Profile-Pregnancy (SURP-P), CRAFFT, 5Ps, Wayne Indirect Drug Use Screener (WIDUS) and the National Institute on Drug Abuse (Quick Screen), none showed both high sensitivity and high specificity, and area under the curve was low for nearly all measures.

Folate and phototherapy: What should we inform our patients?

BACKGROUND: Ultraviolet (UV) degradation of folate has been studied in vitro and in vivo, but comprehensive reviews of the subject and recommendations for supplementing folate are lacking, especially for women of childbearing age, in whom decreases in folate predisposes newborns to neural tube defects. OBJECTIVE: We reviewed the effects of phototherapy on folate and provide a recommendation for women of childbearing age on phototherapy. METHODS: PubMed was searched for in vivo studies comparing folate levels before and after phototherapy. RESULTS: There is no evidence of decreased folate levels after UVA exposure. Decreased folate levels after sun exposure were limited to subjects taking folate supplements. Studies using narrowband UVB showed mixed results, potentially explained by dose-dependent degradation of folate; exposure >40 J/cm2 cumulatively and >2 J/cm2 per treatment were associated with 19%-27% decreases in serum folate levels, while lower doses did not affect folate levels. LIMITATIONS: Extensive variability in results from studies and lack of considering confounders. CONCLUSIONS: We recommend all women of childbearing age on phototherapy take 0.8 mg/day of folate supplements, as suggested by current guidelines for women of childbearing age, to reduce the risk of neural tube defects in unplanned pregnancy.

Metastatic Colorectal Cancer Resembling Severe Preeclampsia in Pregnancy.

Although colorectal cancer (CRC) is the third most common cancer in women, it is a rare malignancy in pregnancy. Symptoms of CRC such as fatigue, malaise, nausea, vomiting, rectal bleeding, anemia, altered bowel habits, and abdominal mass are often considered typical symptoms of pregnancy. Many cases of CRC are diagnosed in advanced stages due to missed warning signs of CRC, which may be misinterpreted as normal symptoms related to pregnancy. This report reviews 2 cases of CRC diagnosed within a 4-month interval at our institution. Both cases were initially thought to be atypical presentations of preeclampsia. Prenatal history, hospital course, and postpartum course were reviewed for both patients. CRC is often diagnosed at advanced stages in pregnancy. Common physiological symptoms of pregnancy should be scrutinized carefully and worked up appropriately, especially if symptoms remain persistent or increase in intensity or severity.

The dilemma of inherited dysfibrinogenemia during pregnancy.

Inherited dysfibrinogenemia is a rare disorder caused by mutations in the fibrinogen gene, described in approximately 400 families to date. We present the case of a 20-year-old woman at 7 weeks of pregnancy with a history of two first-trimester spontaneous abortions and a family history of thrombotic events. Her testing revealed evidence of dysfibrinogenemia, necessitating multidisciplinary management planning including Hematology, OB-GYN, Maternal-Fetal Medicine, Blood Bank Services and Anesthesia. Antenatal care included a combination of intravenous fibrinogen infusions to maintain fibrinogen levels above 100 mg/dl and anticoagulation with low molecular weight heparin. She had an uneventful full-term delivery and continued fibrinogen infusions and thromboprophylaxis for 6 weeks postpartum. The combination of fibrinogen infusions and anticoagulation maintained the balance between bleeding and clotting in our patient during pregnancy. We recommend a multidisciplinary team approach for the management of dysfibrinogenemia during pregnancy to provide successful pregnancy outcomes.

Impact of robotic surgery on obstetric-gynecologic resident training.

OBJECTIVE: To compare the volume and type of surgical techniques for hysterectomies performed prior to and after the introduction of robotic surgery at our institution and to assess the potential impact on obstetric-gynecologic resident training. STUDY DESIGN: A retrospective study examined the number and types of hysterectomies performed at our institution during the 18 months prior to, and the 18 months after, the introduction of a robotic surgical system. Procedures performed during both time periods were compared by number and percentage using the chi2 or Fisher's exact test for counts < 5. RESULTS: A total of 903 hysterectomies were performed from July 1, 2005, to July 1, 2008. There were 444 hysterectomies in the prerobotic surgical system group and 459 hysterectomies in the postrobotic surgical system group. There was a statistically significant decrease in the number of laparoscopically assisted vaginal hysterectomies (94 vs. 36; p < 0.001) and total abdominal hysterectomies (249 vs. 203; p < 0.001) performed. CONCLUSION: This study demonstrated a significant impact on the volume and type of surgical techniques for hysterectomies performed prior to and after the introduction of robotic surgery at our institution. This observation may have direct consequences for obstetric-gynecologic resident surgical experience.