Higher severe acute respiratory syndrome coronavirus 2 infection rate in pregnant patients.

BACKGROUND: During the early months of the coronavirus disease 2019 pandemic, risks associated with severe acute respiratory syndrome coronavirus 2 in pregnancy were uncertain. Pregnant patients can serve as a model for the success of clinical and public health responses during public health emergencies as they are typically in frequent contact with the medical system. Population-based estimates of severe acute respiratory syndrome coronavirus 2 infections in pregnancy are unknown because of incomplete ascertainment of pregnancy status or inclusion of only single centers or hospitalized cases. Whether pregnant women were protected by the public health response or through their interactions with obstetrical providers in the early months of pandemic is not clearly understood. OBJECTIVE: This study aimed to estimate the severe acute respiratory syndrome coronavirus 2 infection rate in pregnancy and to examine the disparities by race and ethnicity and English language proficiency in Washington State. STUDY DESIGN: Pregnant patients with a polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection diagnosed between March 1, 2020, and June 30, 2020 were identified within 35 hospitals and clinics, capturing 61% of annual deliveries in Washington State. Infection rates in pregnancy were estimated overall and by Washington State Accountable Community of Health region and cross-sectionally compared with severe acute respiratory syndrome coronavirus 2 infection rates in similarly aged adults in Washington State. Race and ethnicity and language used for medical care of pregnant patients were compared with recent data from Washington State. RESULTS: A total of 240 pregnant patients with severe acute respiratory syndrome coronavirus 2 infections were identified during the study period with 70.7% from minority racial and ethnic groups. The principal findings in our study were as follows: (1) the severe acute respiratory syndrome coronavirus 2 infection rate was 13.9 per 1000 deliveries in pregnant patients (95% confidence interval, 8.3-23.2) compared with 7.3 per 1000 (95% confidence interval, 7.2-7.4) in adults aged 20 to 39 years in Washington State (rate ratio, 1.7; 95% confidence interval, 1.3-2.3); (2) the severe acute respiratory syndrome coronavirus 2 infection rate reduced to 11.3 per 1000 deliveries (95% confidence interval, 6.3-20.3) when excluding 45 cases of severe acute respiratory syndrome coronavirus disease 2 detected through asymptomatic screening (rate ratio, 1.3; 95% confidence interval, 0.96-1.9); (3) the proportion of pregnant patients in non-White racial and ethnic groups with severe acute respiratory syndrome coronavirus disease 2 infection was 2- to 4-fold higher than the race and ethnicity distribution of women in Washington State who delivered live births in 2018; and (4) the proportion of pregnant patients with severe acute respiratory syndrome coronavirus 2 infection receiving medical care in a non-English language was higher than estimates of pregnant patients receiving care with limited English proficiency in Washington State (30.4% vs 7.6%). CONCLUSION: The severe acute respiratory syndrome coronavirus 2 infection rate in pregnant people was 70% higher than similarly aged adults in Washington State, which could not be completely explained by universal screening at delivery. Pregnant patients from nearly all racial and ethnic minority groups and patients receiving medical care in a non-English language were overrepresented. Pregnant women were not protected from severe acute respiratory syndrome coronavirus 2 infection in the early months of the pandemic. Moreover, the greatest burden of infections occurred in nearly all racial and ethnic minority groups. These data coupled with a broader recognition that pregnancy is a risk factor for severe illness and maternal mortality strongly suggested that pregnant people should be broadly prioritized for coronavirus disease 2019 vaccine allocation in the United States similar to some states.

Disease severity, pregnancy outcomes, and maternal deaths among pregnant patients with severe acute respiratory syndrome coronavirus 2 infection in Washington State.

BACKGROUND: Evidence is accumulating that coronavirus disease 2019 increases the risk of hospitalization and mechanical ventilation in pregnant patients and for preterm delivery. However, the impact on maternal mortality and whether morbidity is differentially affected by disease severity at delivery and trimester of infection are unknown. OBJECTIVE: This study aimed to describe disease severity and outcomes of severe acute respiratory syndrome coronavirus 2 infections in pregnancy across the Washington State, including pregnancy complications and outcomes, hospitalization, and case fatality. STUDY DESIGN: Pregnant patients with a polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection between March 1, 2020, and June 30, 2020, were identified in a multicenter retrospective cohort study from 35 sites in Washington State. Sites captured 61% of annual state deliveries. Case-fatality rates in pregnancy were compared with coronavirus disease 2019 fatality rates in similarly aged adults in Washington State using rate ratios and rate differences. Maternal and neonatal outcomes were compared by trimester of infection and disease severity at the time of delivery. RESULTS: The principal study findings were as follows: (1) among 240 pregnant patients in Washington State with severe acute respiratory syndrome coronavirus 2 infections, 1 in 11 developed severe or critical disease, 1 in 10 were hospitalized for coronavirus disease 2019, and 1 in 80 died; (2) the coronavirus disease 2019-associated hospitalization rate was 3.5-fold higher than in similarly aged adults in Washington State (10.0% vs 2.8%; rate ratio, 3.5; 95% confidence interval, 2.3-5.3); (3) pregnant patients hospitalized for a respiratory concern were more likely to have a comorbidity or underlying conditions including asthma, hypertension, type 2 diabetes mellitus, autoimmune disease, and class III obesity; (4) 3 maternal deaths (1.3%) were attributed to coronavirus disease 2019 for a maternal mortality rate of 1250 of 100,000 pregnancies (95% confidence interval, 257-3653); (5) the coronavirus disease 2019 case fatality in pregnancy was a significant 13.6-fold (95% confidence interval, 2.7-43.6) higher in pregnant patients than in similarly aged individuals in Washington State with an absolute difference in mortality rate of 1.2% (95% confidence interval, -0.3 to 2.6); and (6) preterm birth was significantly higher among women with severe or critical coronavirus disease 2019 at delivery than for women who had recovered from coronavirus disease 2019 (45.4% severe or critical coronavirus disease 2019 vs 5.2% mild coronavirus disease 2019; P<.001). CONCLUSION: Coronavirus disease 2019 hospitalization and case-fatality rates in pregnant patients were significantly higher than in similarly aged adults in Washington State. These data indicate that pregnant patients are at risk of severe or critical disease and mortality compared to nonpregnant adults, and also at risk for preterm birth.

Clinical characteristics of 46 pregnant women with a severe acute respiratory syndrome coronavirus 2 infection in Washington State.

BACKGROUND: The impact of coronavirus disease 2019 on pregnant women is incompletely understood, but early data from case series suggest a variable course of illness from asymptomatic or mild disease to maternal death. It is unclear whether pregnant women manifest enhanced disease similar to influenza viral infection or whether specific risk factors might predispose to severe disease. OBJECTIVE: To describe maternal disease and obstetrical outcomes associated with coronavirus disease 2019 in pregnancy to rapidly inform clinical care. STUDY DESIGN: This is a retrospective study of pregnant patients with a laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection from 6 hospital systems in Washington State between Jan. 21, 2020, and April 17, 2020. Demographics, medical and obstetrical history, and coronavirus disease 2019 encounter data were abstracted from medical records. RESULTS: A total of 46 pregnant patients with a severe acute respiratory syndrome coronavirus 2 infection were identified from hospital systems capturing 40% of births in Washington State. Nearly all pregnant individuals with a severe acute respiratory syndrome coronavirus 2 infection were symptomatic (93.5%, n=43) and the majority were in their second or third trimester (43.5% [n=20] and 50.0% [n=23], respectively). Symptoms resolved in a median of 24 days (interquartile range, 13-37). Notably, 7 women were hospitalized (16%) including 1 admitted to the intensive care unit. A total of 6 cases (15%) were categorized as severe coronavirus disease 2019 with nearly all patients being either overweight or obese before pregnancy or with asthma or other comorbidities. Of the 8 deliveries that occurred during the study period, there was 1 preterm birth at 33 weeks' gestation to improve pulmonary status in a woman with class III obesity, and 1 stillbirth of unknown etiology. CONCLUSION: Severe coronavirus disease 2019 developed in approximately 15% of pregnant patients and occurred primarily in overweight or obese women with underlying conditions. Obesity and coronavirus disease 2019 may synergistically increase risk for a medically indicated preterm birth to improve maternal pulmonary status in late pregnancy. These findings support categorizing pregnant patients as a higher-risk group, particularly those with chronic comorbidities.

The North American Fetal Therapy Network Consensus Statement: prenatal management of uncomplicated monochorionic gestations.

Owing to vascular connections within a single placenta, monochorionic gestations present distinctive prenatal management challenges. Complications that can arise as a result of unbalanced hemodynamic exchange (twin-twin transfusion syndrome and twin anemia polycythemia sequence) and unequal placental sharing (selective fetal growth restriction) should be kept in mind while prenatal management is being planned. Because of unique monochorionic angioarchitecture, what happens to one twin can directly affect the other. Death of one twin can result in death or permanent disability of the co-twin. Early detection of these unique disease processes through frequent ultrasonographic surveillance may allow the opportunity for earlier referral, intervention, or both and potentially better outcomes. Therefore, monochorionic gestations should be managed differently than dichorionic gestations or singletons. The purpose of this document is to present in detail methods for monitoring and management of uncomplicated monochorionic gestations and to review the evidence for the roles of these methods for detection of complications in clinical practice. Finally, we present evidence-based and expert opinion-supported recommendations developed by the North American Fetal Therapy Network for the diagnosis, surveillance, and delivery of uncomplicated monochorionic gestations.

The North American Fetal Therapy Network consensus statement: prenatal surveillance of uncomplicated monochorionic gestations.

Because they share a common placenta, monochorionic gestations are subject to unique pregnancy complications that can threaten the life and health of both fetuses and therefore impose a disproportionate disease burden on overall perinatal morbidity and mortality. Early detection of these unique disease processes may allow for prompt referral to a regional treatment center, comprehensive counseling, and better patient outcomes. The North American Fetal Therapy Network is a consortium of 30 medical institutions in the United States and Canada with established expertise in fetal surgery and other forms of multidisciplinary care for complex fetal disorders. The goal of this publication is to briefly describe complications of monochorionic gestations and to provide multidisciplinary, evidence-based, and consensus-driven recommendations for surveillance of uncomplicated monochorionic gestations.

Multifetal gestation--maternal and perinatal outcome of 112 pregnancies.

PURPOSE: Multifetal pregnancy reduction is a widespread "therapy" to diminish the risk of prematurity and adverse outcome for the survivors in higher order multiple gestation. The aim of our study was to determine the maternal and neonatal outcome of multifetal pregnancies under a conservative pregnancy management. STUDY DESIGN: A retrospective review of 112 multifetal pregnancies is presented. All higher order multiple pregnancies delivered after 25 weeks of gestation and managed at a single institution between 1982 and 1999 are included. RESULTS: Triplets, quadruplets and quintuplets were delivered at a mean gestational age of 31 + 5, 29 + 5 and 28 + 4 weeks, respectively. The perinatal mortality was 14 for triplets and 36 for quadruplets. No quintuplet died in the perinatal period. Respiratory distress syndrome occurred in 23% of triplets, 65% of quadruplets and 75% of quintuplets, intracranial hemorrhage was diagnosed in 14% of triplets, 15% of quadruplets and 10% of quintuplets and retinopathy of prematurity was found in 10% of triplets, 9% of quadruplets and 25% of quintuplets. DISCUSSION: Despite a low neonatal mortality, morbidity of higher order multiple gestations remains significant. Mortality and morbidity are related to preterm delivery but do not exceed the rates of singletons or twins of an identical gestational age. Favorable prognostic landmarks are a gestational age >30 weeks and a number of fetuses per pregnancy < or =4. CONCLUSION: The risks of multifetal pregnancies are significant. Therefore, evidence-based counseling of couples seeking treatment for infertility and prevention of higher order multiple pregnancies through the prudent use of reproductive techniques attains paramount importance.

Fetal surgery for repair of myelomeningocele allows normal development of the rectum in sheep.

To determine whether fetal surgery in a fetus with myelomeningocele (MMC) allows normal development of rectal muscles and nerves, we analyzed the rectum after fetal surgery in a sheep model. An MMC lesion was surgically created in 13 fetal sheep at 75 days of gestation. One fetal sheep died after the lesion was created. Eight fetal sheep were repaired at 100 days of gestation; the others were not repaired, as a control (n=4). Three methods were used for fetal surgery of MMC: standard neurosurgical repair (4 fetal sheep), covering of the MMC lesion by Alloderm (2 fetal sheep), and covering of the MMC lesion by Gore-Tex (2 fetal sheep). At 140 days of gestation, fetal sheep were harvested and histo-pathological analysis was performed on the rectum using hematoxylin and eosin staining for muscles and S-100 protein staining for nerves. One fetal sheep treated by standard neurosurgical repair died before harvesting. The four untreated fetal sheep had hypoplastic longitudinal muscles of the rectum but well developed-circular muscles. In addition, the untreated fetuses had a hypoplastic submucosal nerve plexus but a well-developed intermuscular nerve plexus. In contrast, treated fetal sheep had well-developed longitudinal and circular muscles except for one sheep treated with standard neurosurgical repair. In addition, except for the same fetal sheep, treated fetal sheep had well-developed nerve plexuses. There was no difference in muscle and nerve development of the rectum among the three repair methods. Fetal surgery for repair of MMC allows normal development of rectal muscles and nerves.

Fetal surgery for repair of myelomeningocele allows normal development of anal sphincter muscles in sheep.

One major problem for patients with myelomeningocele (MMC) is fecal incontinence. To prevent this problem, fetal surgery for repair of MMC has been recently undertaken. The strategy behind this surgery is to allow normal development of anal sphincter muscles. The purpose of this study was to determine whether fetal surgery for repair of MMC allows normal development of anal sphincter muscles. Myelomeningocele was surgically created in fetal sheep at 75 days of gestation. At 100 days of gestation, fetal surgery for repair of the MMC lesion was performed. Three repair methods were used: standard neurosurgical repair (4 fetal sheep), covering the MMC lesion with Alloderm (2 fetal sheep), and covering the MMC lesion with Gore-Tex (2 fetal sheep). After the sheep were delivered (140 days of gestation), external and internal anal sphincter muscles were analyzed histopathologically. In control fetal sheep (not repaired) anal sphincter muscles did not develop normally. In contrast, in fetal sheep that underwent repair of the MMC, the external and internal anal sphincter muscles developed normally. Histopathologically, in the external sphincter muscles, muscle fibers were dense. In the internal sphincter muscles, endomysial spaces were small, myofibrils were numerous, and fascicular units were larger than those in unrepaired fetal sheep. There was no difference in muscle development for the repair methods. Fetal surgery for repair of MMC allows normal development of anal sphincter muscles.

Tissue ablation using high-intensity focused ultrasound in the fetal sheep model: potential for fetal treatment.

OBJECTIVE: The aim of this study was to investigate the efficacy of high-intensity focused ultrasound (HIFU) ablation of fetal tissue in a sheep model. HIFU can deliver large amounts of thermal energy by using ultrasonic waves to induce tissue necrosis, without damaging intervening tissues. In contrast to diagnostic ultrasound where intensity levels are below 0.1 W/cm(2), HIFU can deliver 1,000 to 10,000 W/cm(2) at the focal spot. STUDY DESIGN: A protocol for HIFU-induced tissue coagulation in the fetus was developed in the ovine model. The fetal liver, lung, kidney, muscle, and placenta were targets for ultrasound-guided tissue ablation by a HIFU beam. All lesions were assessed macroscopically and by histologic analysis. RESULTS: In all animals, a necrotic lesion, similar in size to the HIFU focus (approximately 1x9 mm), was achieved. The fetal heart rate remained stable immediately after the procedure. CONCLUSION: In conclusion, HIFU ablation seems to be an effective means to coagulate even highly vascularized tissues in the fetus. This procedure shows promise as a transcutaneous, minimally invasive technique to decrease blood flow through fetal tumors or vascular anastomoses. We are currently conducting further studies to refine the HIFU technique and assess safety for fetus and mother.

Giant fetal hepatic hemangioma. Case report and literature review.

The purpose of this case report is to demonstrate the importance of prenatal imaging for treatment management of fetal giant hepatic hemangiomas. Prenatal ultrasound revealed an abdominal mass with several cystic areas and punctate calcifications in a fetus at 29 weeks' gestation. Doppler scans confirmed the highly vascular nature of the mass. In this case, ultrasound diagnosed the mass was of hepatic origin, while magnetic resonance imaging at 32 weeks' gestation was more equivocal with respect to the anatomy source of the lesion. Imminent hydrops caused by a rapidly enlarged liver tumor was sonographically demonstrated at 34 weeks' gestation. An elective C-section and immediate tumor resection was performed. At the age of 20 months the infant is thriving. This case supports the notion that the survival rates for giant hepatic hemangiomas improve when fetal hydrops is averted and specific pre- and postnatal treatment is applied based on correct prenatal imaging diagnostics.