Ethical Lessons Learned from the COVID-19 Pandemic in Perinatal Medicine

The COVID-19 pandemic is unprecedented in our lifetime, especially in perinatology. The gold standard is to strongly recommend COVID-19 vaccinations to those trying to get pregnant, to those who are pregnant, and to those who are postpartum. When the benefits of vaccines far outweigh the risks, it is unethical to disseminate wrong information and discourage patients from becoming vaccinated. COVID-19 vaccinations and boosters prevent severe diseases and adverse pregnancy and neonatal outcomes. A pregnant patient's vaccination also protects the newborn infant because maternal antibodies protect the fetus and newborn. COVID-19 vaccinations and boosters in pregnancy are safe for the pregnant patient and her fetus. The three root causes of physician hesitancy-misapplication of therapeutic nihilism, misapplication of shared decision-making, and misapplication of respect for autonomy should not be ignored and need to be addressed. It is important that we heed Brent 's insightful recommendations. Doing nothing with respect to vaccination is not an option, whether it applies to COVID-19 vaccines or to future pandemics. Physician hesitation is not an option. When there is sufficient evidence of vaccine safety and effectiveness without documented risks, vaccine recommendations before, during, and after pregnancy should be explicitly made to prevent maternal, fetal, and neonatal morbidity and mortality.Copyright © The Author(s). 2023.

Maternal and perinatal outcomes with COVID-19: A systematic review of 108 pregnancies.

INTRODUCTION: The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has exposed vulnerable populations to an unprecedented global health crisis. The knowledge gained from previous human coronavirus outbreaks suggests that pregnant women and their fetuses are particularly susceptible to poor outcomes. The objective of this study was to summarize the clinical manifestations and maternal and perinatal outcomes of COVID-19 during pregnancy. MATERIAL AND METHODS: We searched databases for all case reports and series from 12 February to 4 April 2020. Multiple terms and combinations were used including COVID-19, pregnancy, maternal mortality, maternal morbidity, complications, clinical manifestations, neonatal morbidity, intrauterine fetal death, neonatal mortality and SARS-CoV-2. Eligibility criteria included peer-reviewed publications written in English or Chinese and quantitative real-time polymerase chain reaction (PCR) or dual fluorescence PCR-confirmed SARS-CoV-2 infection. Unpublished reports, unspecified date and location of the study or suspicion of duplicate reporting, cases with suspected COVID-19 that were not confirmed by a laboratory test, and unreported maternal or perinatal outcomes were excluded. Data on clinical manifestations, maternal and perinatal outcomes including vertical transmission were extracted and analyzed. RESULTS: Eighteen articles reporting data from 108 pregnancies between 8 December 2019 and 1 April 2020 were included in the current study. Most reports described women presenting in the third trimester with fever (68%) and coughing (34%). Lymphocytopenia (59%) with elevated C-reactive protein (70%) was observed and 91% of the women were delivered by cesarean section. Three maternal intensive care unit admissions were noted but no maternal deaths. One neonatal death and one intrauterine death were also reported. CONCLUSIONS: Although the majority of mothers were discharged without any major complications, severe maternal morbidity as a result of COVID-19 and perinatal deaths were reported. Vertical transmission of the COVID-19 could not be ruled out. Careful monitoring of pregnancies with COVID-19 and measures to prevent neonatal infection are warranted.

Examining the impact of trimester of diagnosis on COVID-19 disease progression in pregnancy.

BACKGROUND: COVID-19 infection is associated with increased morbidity in pregnancy and adverse maternal and neonatal outcomes. Little is currently known about how the timing of infection during pregnancy affects these outcomes. OBJECTIVE: This study aimed to evaluate the effect of trimester of COVID-19 infection on disease progression and severity in pregnant patients. STUDY DESIGN: This was a prospective cohort study of pregnant patients diagnosed with COVID-19 infection who delivered at a single urban hospital. Universal testing for SARS-CoV-2 was performed at hospital admission and for symptomatic patients in inpatient, emergency department, and outpatient settings. Disease severity was defined as asymptomatic, mild, moderate, severe, or critical on the basis of National Institutes of Health criteria. We evaluated disease progression from asymptomatic to symptomatic infection and from asymptomatic or mild infection to moderate, severe, or critical illness, and stratified by trimester of COVID-19 diagnosis. Primary outcomes included progression of COVID-19 disease severity and a composite obstetrical outcome, which included delivery at <37 weeks, preeclampsia with severe features, abruption, excess blood loss at delivery (>500 mL for vaginal or >1000 mL for cesarean delivery), and stillbirth. RESULTS: From March 18, 2020 to September 30, 2021, 1326 pregnant patients were diagnosed with COVID-19 and delivered at our institution, including 103 (8%) first-, 355 (27%) second-, and 868 (65%) third-trimester patients. First-trimester patients were older and had more medical comorbidities; 86% of patients in all trimesters were Hispanic. Among patients admitted within 14 days of a positive test, 3 of 18 (17%) first-trimester, 20 of 47 (43%) second-trimester, and 34 of 574 (6%) third-trimester patients were admitted for the indication of COVID-19 illness. Across all trimesters, 1195 (90%) of 1326 COVID-19 infections were asymptomatic or mild, and 45 (10%) of 436 initially asymptomatic patients developed symptoms. Of patients with asymptomatic or mild symptoms at diagnosis, 4 (4%) of 93 first-, 18 (5%) of 337 second-, and 49 (6%) of 836 third-trimester patients developed moderate, severe, or critical illness (P=.80). There was no significant difference in composite obstetrical outcome with respect to trimester of COVID-19 diagnosis (24% first-trimester, 28% second-trimester, 28% third-trimester patients; P=.69). CONCLUSION: Moderate, severe, or critical illness develops in almost 10% of pregnant patients. The frequency of COVID-19 disease progression in pregnancy does not differ by trimester of diagnosis.

Reversing physician hesitancy to recommend COVID-19 vaccination for pregnant patients.

Physician hesitancy is said to occur when physicians do not recommend COVID-19 vaccination, and it is a contributing factor for the low vaccination rate for COVID-19 in pregnant women. Physician hesitancy has become a major, unaddressed problem with regard to the quality and safety of obstetrical care. We identify 3 root causes of physician hesitancy and describe how professional ethics in obstetrics should guide in reversing these root causes. They are clinical misapplications of key components of professionally responsible obstetrical practice: therapeutic nihilism, shared decision-making, and respect for patient autonomy. Therapeutic nihilism directs the obstetrician to avoid any clinical interventions during pregnancy to prevent teratogenic effects that might be unknown. Therapeutic nihilism is misapplied when there is a documented net clinical benefit with no evidence of clinical harm. Shared decision directs the obstetrician to only offer but not recommend clinical management. Shared decision-making plays a major role when there is uncertainty in clinical judgment but is misapplied when it becomes a universal model. It does not apply when there is a net clinical benefit. When there is a net clinical benefit, clinical management should be recommended, not simply offered. The ethical principle of respect for patient autonomy plays an indispensable role in decision-making with patients. It is misapplied when it is assumed that respect for autonomy requires physicians not to make recommendations and to defer to and implement patients' decisions without exception. There is evidence that the obstetrician's recommendations about the management of pregnancy are the most important factor in a pregnant woman's decision-making. Simply deferring to the patient's decisions makes for misapplied respect for patient autonomy. Obstetricians must end physician hesitancy about COVID-19 vaccination of pregnant women by reversing these 3 root causes of physician hesitancy. Reversing the root causes of physician hesitancy is an urgent matter of patient safety. The longer physician hesitancy continues and the longer the low vaccine acceptance rate of pregnant women lasts, preventable serious diseases, deaths of pregnant women, intensive care unit admissions, stillbirths, and other maternal and fetal complications of unvaccinated women will continue to occur. Physician hesitancy should not be permitted to influence the response to future pandemics.

Outcomes of pregnant patients treated with REGEN-COV during the COVID-19 pandemic.

BACKGROUND: Pregnant patients with SARS-CoV-2 infection are at increased risk for severe disease including hospitalization, intensive care admission, ventilatory support, and death. Although pregnant patients were excluded from investigational trials for pharmacologic treatments for COVID-19 illness, the National Institutes of Health treatment guidelines state that efficacious treatments should not be withheld from pregnant patients. An infusion of casirivimab and imdevimab (REGEN-COV), a monoclonal antibody therapy, was shown to reduce the risk of COVID-19-related hospitalization or death from any cause and resolved symptoms and reduced SARS-CoV-2 viral load more rapidly than placebo. In July of 2021, the Food and Drug Administration released an Emergency Use Authorization for REGEN-COV. Although pregnant persons were not included in the original trials, given the higher risk of morbidity and mortality in the pregnant population, our institution offered REGEN-COV to our pregnant patients beginning in August of 2021. Side effects after REGEN-COV administration are rare and thought to be secondary to COVID-19 rather than REGEN-COV. OBJECTIVE: This study aimed to track safety and clinical outcomes in unvaccinated pregnant patients who received REGEN-COV and to compare these outcomes with those of a contemporary cohort of patients who tested positive for SARS-CoV-2 and were eligible but did not receive REGEN-COV. Our hypothesis was that REGEN-COV administration during pregnancy is safe, and that pregnant persons who received REGEN-COV would experience less severe COVID-19 respiratory illness, with decreased length of hospital stay, rates of intensive care unit admission, and need for oxygen and other COVID-19 therapeutics. STUDY DESIGN: This is a retrospective cohort study of pregnant patients who either tested positive for SARS-CoV-2 or had a known exposure to a COVID-19-positive person, and were therefore eligible for REGEN-COV at our institution. Within this cohort, we compared those who received REGEN-COV with those who did not between March and October of 2021 at Grady Memorial Hospital in Atlanta, Georgia. The main outcomes studied were perinatal outcomes, safety data, and the clinical course of SARS-CoV-2 infection. RESULTS: From March to October of 2021, 86 pregnant people tested positive for SARS-CoV-2 via real-time polymerase chain reaction or had a confirmed exposure. In this group, 36 received REGEN-COV and 50 did not. There were no instances of infusion rate adjustment or discontinuation, anaphylaxis, or death among individuals who received REGEN-COV. One individual experienced worsening shortness of breath >24 hours after administration, which was classified as an infusion-related reaction. There were no significant differences in perinatal outcomes, length of hospitalization, rates of intensive care unit admission, additional pharmacologic treatment for COVID-19, or oxygen requirement between the 2 groups. CONCLUSION: Administration of REGEN-COV is safe in pregnancy and did not increase adverse maternal, neonatal, or obstetrical outcomes. There was not a statistically significant difference in COVID-19-related outcomes in our high-risk population. Given the likely safety of this drug in pregnancy and its known benefits in the nonpregnant population, we advocate for the continued use of this therapy and encourage the development of future studies to enroll a larger and more diverse cohort to explore its efficacy further.

Covid-19 infection in pregnant women in Dubai: a case-control study.

BACKGROUND: Whilst the impact of Covid-19 infection in pregnant women has been examined, there is a scarcity of data on pregnant women in the Middle East. Thus, the aim of this study was to examine the impact of Covid-19 infection on pregnant women in the United Arab Emirates population. METHODS: A case-control study was carried out to compare the clinical course and outcome of pregnancy in 79 pregnant women with Covid-19 and 85 non-pregnant women with Covid-19 admitted to Latifa Hospital in Dubai between March and June 2020. RESULTS: Although Pregnant women presented with fewer symptoms such as fever, cough, sore throat, and shortness of breath compared to non-pregnant women; yet they ran a much more severe course of illness. On admission, 12/79 (15.2%) Vs 2/85 (2.4%) had a chest radiograph score [on a scale 1-6] of ≥3 (p-value = 0.0039). On discharge, 6/79 (7.6%) Vs 1/85 (1.2%) had a score ≥3 (p-value = 0.0438). They also had much higher levels of laboratory indicators of severity with values above reference ranges for C-Reactive Protein [(28 (38.3%) Vs 13 (17.6%)] with p < 0.004; and for D-dimer [32 (50.8%) Vs 3(6%)]; with p < 0.001. They required more ICU admissions: 10/79 (12.6%) Vs 1/85 (1.2%) with p=0.0036; and suffered more complications: 9/79 (11.4%) Vs 1/85 (1.2%) with p=0.0066; of Covid-19 infection, particularly in late pregnancy. CONCLUSIONS: Pregnant women presented with fewer Covid-19 symptoms but ran a much more severe course of illness compared to non-pregnant women with the disease. They had worse chest radiograph scores and much higher levels of laboratory indicators of disease severity. They had more ICU admissions and suffered more complications of Covid-19 infection, such as risk for miscarriage and preterm deliveries. Pregnancy with Covid-19 infection, could, therefore, be categorised as high-risk pregnancy and requires management by an obstetric and medical multidisciplinary team.

Effects of COVID-19 pandemic period on neonatal mortality and morbidity.

BACKGROUND: Corona Virus Disease 2019 (COVID-19) in pregnant women has important impacts on perinatal and neonatal outcomes. However, there are a limited number of studies investigating the effect of the pandemic period on newborns. With this study, we aimed to determine the impact of the 2020 COVID-19 outbreak on prenatal care, obstetric outcomes, neonatal mortality and morbidity. METHODS: The retrospective results of patients hospitalized to the Tertiary Neonatal Intensive Care Unit between 1 March and 30 May 2020, the first peak period of the pandemic in our country, were compared with the data of the same period of the previous year. RESULTS: A total of 307 cases were included in our study. The mean gestational weeks of the neonates hospitalized in the Neonatal Intensive Care Unit during the COVID-19 period were higher than those in the control group (p: 0.003). During the pandemic period, an increase was found in the frequency of pregnant women presenting to obstetric emergency services in emergencies requiring acute intervention (p: 0.01). Compared to the control group, there was an increase in the number of infants with small for gestational age (SGA) diagnosis, 5th-minute Apgar score of <7, and newborns with a diagnosis of hypoxic-ischemic encephalopathy who were treated with hypothermia in the study group (p < 0.05). No difference was found in terms of maternal and neonatal mortality (p > 0.05). CONCLUSIONS: During the COVID-19 pandemic, it was shown that pregnant women disrupted their regular antenatal care, and more pregnant women were admitted to the obstetric emergency department with emergencies requiring acute intervention. This led to an increase in the number of cases diagnosed with SGA and hypoxic-ischemic encephalopathy in newborns. Our results will be useful for better management of current and future pandemic periods.

Maternal COVID-19 infection, clinical characteristics, pregnancy, and neonatal outcome: A prospective cohort study.

OBJECTIVE: To study the effect of COVID-19 on pregnancy and neonatal outcomes. STUDY DESIGN: Prospective cohort study in a large tertiary maternity unit within a university hospital with an average annual birth of over 10,000 births. We prospectively collected and analysed data for a cohort of 23 pregnant patients including singleton and multiple pregnancies tested positive for COVID-19 between February 2020 and April 2020 inclusive to assess the effect of COVID-19 on pregnancy, and neonatal outcomes. RESULTS: Twenty-three pregnant patients tested positive for COVID-19, delivering 20 babies including a set of twins, with four ongoing pregnancies at the time of manuscript submission. 16/23 (70 %) whom tested positive were patients from Asian (Indian sub-continent) background. The severity of the symptoms ranged from mild in 13/23 (65.2 %) of the patients, moderate in 2/23 (8.7 %), and severe in 8/23 (34.8 %). Four out of total 23 COVID-19 pregnant patients (17.4 %) developed severe adult respiratory distress syndrome complications requiring ICU support, one of whom led to maternal death 1/23 (4.3 %). 11/23 (48 %) of the patients had pre-existing co-morbidities, with morbid obesity 5/23 (21.7 %) and diabetes 4/23 (17.4 %) being the more commonly represented. Of the 23 pregnant patients 19 were in their third trimester of pregnancy and delivered; 7/19 (36.8 %) had preterm birth, 3/19 (15.8 %) developed adult respiratory distress syndrome before delivery, and 2/19 (10.5 %) had pre-eclampsia. 16/19 (84 %) of patients delivered by C-section. Out of the 20 new-borns, 18 were singletons with a set of twin. CONCLUSION: COVID-19 is associated with high prevalence of preterm birth, preeclampsia, and caesarean section compared to non-COVID pregnancies. COVID-19 infection was not found in the newborns and none developed severe neonatal complications.

COVID-19 and Adverse Pregnancy Outcome: A Systematic Review of 104 Cases.

(1) Background: Until now, several reports about pregnant women with confirmed coronavirus disease 2019 (COVID-19) have been published. However, there are no comprehensive systematic reviews collecting all case series studies on data regarding adverse pregnancy outcomes, especially association with treatment modalities. (2) Objective: We aimed to synthesize the most up-to-date and relevant available evidence on the outcomes of pregnant women with laboratory-confirmed infection with COVID-19. (3) Methods: PubMed, Scopus, MEDLINE, Google scholar, and Embase were explored for studies and papers regarding pregnant women with COVID-19, including obstetrical, perinatal, and neonatal outcomes and complications published from 1 January 2020 to 4 May 2020. Systematic review and search of the published literature was done using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). (4) Results: In total, 11 case series studies comprising 104 pregnant women with COVID-19 were included in our review. Fever (58.6%) and cough (30.7%) were the most common symptoms. Other symptoms included dyspnea (14.4%), chest discomfort (3.9%), sputum production (1.0%), sore throat (2.9%), and nasal obstruction (1.0%). Fifty-two patients (50.0%) eventually demonstrated abnormal chest CT, and of those with ground glass opacity (GGO), 23 (22.1%) were bilateral and 10 (9.6%) were unilateral. The most common treatment for COVID-19 was administration of antibiotics (25.9%) followed by antivirals (17.3%). Cesarean section was the mode of delivery for half of the women (50.0%), although no information was available for 28.8% of the cases. Regarding obstetrical and neonatal outcomes, fetal distress (13.5%), pre-labor rupture of membranes (9.6%), prematurity (8.7%), fetal death (4.8%), and abortion (2.9%) were reported. There are no positive results of neonatal infection by RT-PCR. (5) Conclusions: Although we have found that pregnancy with COVID-19 has significantly higher maternal mortality ratio compared to that of pregnancy without the disease, the evidence is too weak to state that COVID-19 results in poorer maternal outcome due to multiple factors. The number of COVID-19 pregnancy outcomes was not large enough to draw a conclusion and long-term outcomes are yet to be determined as the pandemic is still unfolding. Active and intensive follow-up is needed in order to provide robust data for future studies.

Clinical characteristics, prognostic factors, and maternal and neonatal outcomes of SARS-CoV-2 infection among hospitalized pregnant women: A systematic review.

BACKGROUND: Pregnant women represent a potentially high-risk population in the COVID-19 pandemic. OBJECTIVE: To summarize clinical characteristics and outcomes among pregnant women hospitalized with COVID-19. SEARCH STRATEGY: Relevant databases were searched up until May 29, 2020. SELECTION CRITERIA: Case series/reports of hospitalized pregnant women with laboratory-confirmed COVID-19. DATA COLLECTION AND ANALYSIS: PRISMA guidelines were followed. Methodologic quality was assessed via NIH assessment tools. MAIN RESULTS: Overall, 63 observational studies of 637 women (84.6% in third trimester) with laboratory-confirmed SARS-CoV-2 infection were included. Most (76.5%) women experienced mild disease. Maternal fatality, stillbirth, and neonatal fatality rates were 1.6%, 1.4%, and 1.0%, respectively. Older age, obesity, diabetes mellitus, and raised serum D-dimer and interleukin-6 were predictive of poor outcomes. Overall, 33.7% of live births were preterm, of which half were iatrogenic among women with mild COVID-19 and no complications. Most women underwent cesarean despite lacking a clear indication. Eight (2.0%) neonates had positive nasopharyngeal swabs after delivery and developed chest infection within 48 hours. CONCLUSIONS: Advanced gestation, maternal age, obesity, diabetes mellitus, and a combination of elevated D-dimer and interleukin-6 levels are predictive of poor pregnancy outcomes in COVID-19. The rate of iatrogenic preterm birth and cesarean delivery is high; vertical transmission may be possible but has not been proved.