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.

SARS CoV-2 infection as a risk factor of preeclampsia and pre-term birth. An interplay between viral infection, pregnancy-specific immune shift and endothelial dysfunction may lead to negative pregnancy outcomes.

BACKGROUND: Since SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) was first identified as the cause of Coronavirus disease 19 (COVID-19) it has caused over 649,147,421 infections and over 6,730,382 deaths worldwide. SARS-CoV-2 presents higher infectivity than other coronaviridae (MERS-CoV and SARS-CoV). Pregnant patients, according to previous studies are at high risk of severe COVID-19 course and negative pregnancy outcomes (pre-term birth, low birth weight, preeclampsia, operative delivery and ICU admission with need for mechanical ventilation). METHODS: In this review we focus on the pathophysiology of subcellular changes in COVID-19 and try bring to light the aspects that occur in physiological pregnancy that may cause higher risk of SARS-CoV-2 infection and severe COVID-19 course. RESULTS: Knowledge of potential interplay between viral infection and physiological changes in pregnancy may point us in the direction of future prophylaxis and treatment in this special population.Key MessagesSARS-CoV-2 having affinity to ACE-2 and causing it's downregulation receptor may cause endothelial injury leading to compliment activation and formation of NETs, together with RAS dysregulation this may cause preeclampsia to develop in pregnant patients.PTB may occur in patients as an effect of SARS-CoV-2 infection in first or second trimester as an effect of TLR4 pathway dysregulation with lower levels of IFNß.

Pregnancy Outcomes in Patients After Completion of the mRNA Coronavirus Disease 2019 (COVID-19) Vaccination Series Compared With Unvaccinated Patients.

OBJECTIVE: To compare frequency of perinatal death between pregnant patients who completed the mRNA coronavirus disease 2019 (COVID-19) vaccination series and unvaccinated patients. METHODS: This retrospective cohort study included 15,865 pregnant patients who delivered 16,132 newborns after 20 weeks of gestation within a large regional health system between January 1, 2021, and December 31, 2021. Patients who received two doses of mRNA vaccine (Pfizer-BioNTech [BNT162b2] or Moderna [mRNA-1273]) were included in the vaccinated group and were compared with unvaccinated patients. Exclusions included partial vaccination, viral-vector vaccine, major congenital anomalies, and higher-order multiple gestation. Our primary outcome was perinatal death, including stillbirth and neonatal death, which was evaluated by logistic regression. Unadjusted odds ratios and adjusted odds ratios (aORs) were reported, controlling for age, body mass index (BMI), diabetes, hypertension, smoking, twin gestation, and insurance status. Propensity score matching was also performed. RESULTS: A total of 15,865 patients were included in the final analysis: 2,069 in the vaccination group and 13,796 in the control group. Only 13.0% of the cohort was included in the vaccination group; however, the vaccination rate increased over the course of the study period as the vaccine became more widely available and accepted. Vaccinated patients were older, with higher rates of people of non-Black racial non-Hispanic ethnic backgrounds, people with private insurance, and those with higher BMIs. Vaccination was associated with a lower incidence of perinatal death (0.5% vaccinated group vs 0.8% unvaccinated group, aOR 0.20 0.05-0.88). Vaccination against COVID-19 was also associated with lower rates of preterm delivery (aOR 0.63, 0.48-0.82), neonates with very low birth weight (aOR 0.35, 0.15-0.84), and neonatal intensive care unit (NICU) admission (aOR 0.66, 0.52-0.85). The association between vaccination and lower rates of perinatal death was no longer significant after propensity score matching. CONCLUSION: In a large retrospective cohort study, receipt of the primary mRNA COVID-19 vaccination series was associated with a lower rate of several adverse pregnancy outcomes, including perinatal death, preterm delivery, neonates with very low birth weight, and NICU admission. Although the decreased rates of perinatal death did not remain significant after propensity score matching, there was evidence of directional benefit for vaccinated patients.

Risk of preterm birth, small for gestational age at birth, and stillbirth after covid-19 vaccination during pregnancy: population based retrospective cohort study.

OBJECTIVE: To assess the risk of preterm birth, small for gestational age at birth, and stillbirth after covid-19 vaccination during pregnancy. DESIGN: Population based retrospective cohort study. SETTING: Ontario, Canada, 1 May to 31 December 2021. PARTICIPANTS: All liveborn and stillborn infants from pregnancies conceived at least 42 weeks before the end of the study period and with gestational age ≥20 weeks or birth weight ≥500 g. MAIN OUTCOME MEASURES: Using Cox regression, hazard ratios and 95% confidence intervals were estimated for preterm birth before 37 weeks (overall and spontaneous preterm birth), very preterm birth (<32 weeks), small for gestational age at birth (<10th centile), and stillbirth. Vaccination against covid-19 was treated as a time varying exposure in the outcome specific risk window, and propensity score weighting was used to adjust hazard ratios for potential confounding. RESULTS: Among 85 162 births, 43 099 (50.6%) occurred in individuals who received one dose or more of a covid-19 vaccine during pregnancy-42 979 (99.7%) received an mRNA vaccine. Vaccination during pregnancy was not associated with any increased risk of overall preterm birth (6.5% among vaccinated v 6.9% among unvaccinated; adjusted hazard ratio 1.02, 95% confidence interval 0.96 to 1.08), spontaneous preterm birth (3.7% v 4.4%; 0.96, 0.90 to 1.03), or very preterm birth (0.59% v 0.89%; 0.80, 0.67 to 0.95). No increase was found in risk of small for gestational age at birth (9.1% v 9.2%; 0.98, 0.93 to 1.03) or stillbirth (0.25% v 0.44%; 0.65, 0.51 to 0.84). Findings were similar by trimester of vaccination, mRNA vaccine product, and number of doses received during pregnancy. CONCLUSION: The findings suggest that vaccination against covid-19 during pregnancy is not associated with a higher risk of preterm birth, small for gestational age at birth, or stillbirth.

Association between COVID-19 lockdown measures and the incidence of iatrogenic versus spontaneous very preterm births in the Netherlands: a retrospective study.

BACKGROUND: The COVID-19 pandemic led to regional or nationwide lockdowns as part of risk mitigation measurements in many countries worldwide. Recent studies suggest an unexpected and unprecedented decrease in preterm births during the initial COVID-19 lockdowns in the first half of 2020. The objective of the current study was to assess the effects of the two months of the initial national COVID-19 lockdown period on the incidence of very and extremely preterm birth in the Netherlands, stratified by either spontaneous or iatrogenic onset of delivery, in both singleton and multiple pregnancies. METHODS: Retrospective cohort study using data from all 10 perinatal centers in the Netherlands on very and extremely preterm births during the initial COVID-19 lockdown from March 15 to May 15, 2020. Incidences of very and extremely preterm birth were calculated using an estimate of the total number of births in the Netherlands in this period. As reference, we used data from the corresponding calendar period in 2015-2018 from the national perinatal registry (Perined). We differentiated between spontaneous versus iatrogenic onset of delivery and between singleton versus multiple pregnancies. RESULTS: The incidence of total preterm birth < 32 weeks in singleton pregnancies was 6.1‰ in the study period in 2020 versus 6.5‰ in the corresponding period in 2015-2018. The decrease in preterm births in singletons was solely due to a significant decrease in iatrogenic preterm births, both < 32 weeks (OR 0.71; 95%CI 0.53 to 0.95) and < 28 weeks (OR 0.53; 95%CI 0.29 to 0.97). For multiple pregnancies, an increase in preterm births < 28 weeks was observed (OR 2.43; 95%CI 1.35 to 4.39). CONCLUSION: This study shows a decrease in iatrogenic preterm births during the initial COVID-19-related lockdown in the Netherlands in singletons. Future studies should focus on the mechanism of action of lockdown measures and reduction of preterm birth and the effects of perinatal outcome.

Assessing the feasibility of passive surveillance for maternal immunization safety utilizing archival medical records in Kinshasa, Democratic Republic of the Congo.

INTRODUCTION: Since the establishment of the Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) case definitions in 2015, there has been an urgent need for field validation of pharmacovigilance feasibility in low- and middle-income countries. In this study, we assess the availability and quality of archival medical records at ten randomly selected high-traffic maternity wards in Kinshasa province, Democratic Republic of Congo (DRC). METHODS: A retrospective cohort of mother-child pairs was established from all recorded births taking place at study sites between July 1, 2019 to February 28, 2020 through digitization of medical records. Adverse birth outcomes and maternal vaccination status, where available and linkable, were defined according to GAIA. Basic demographic information on mothers and newborns was also tabulated; birth outcomes were assessed for both intra-site prevalence and a pooled prevalence. RESULTS: A total of 7,697 mother-newborn pair records were extracted, with 37% of infants screening positive as cases of adverse outcomes. Maternal vaccination information was linkable to 67% of those cases. In total, 51% of stillbirths, 98% of preterm births, 100% of low birthweight infants, 90% of small for gestational age infants, 100% of microcephalic infants, and 0% of neonatal bloodstream infections were classifiable according to GAIA standards following initial screening. Forty percent of case mothers had some indication of tetanus vaccination prior to delivery in their medical records, but only 26% of case mothers met some level of GAIA definition for maternal vaccination during the pregnancy of interest. CONCLUSIONS: Archival birth records from delivery centers can be feasibly utilized to screen for stillbirth and maternal tetanus vaccination, and to accurately classify preterm birth, low birthweight, small for gestational age, and congenital microcephaly. Assessment of other neonatal outcomes were limited by inconsistent postpartum infant follow-up and records keeping.

Decreases in preterm birth during the first COVID-19 lockdown in France by gestational age sub-groups and regional COVID-19 incidence.

PURPOSE: Given contradictory evidence about preterm birth (PTB) decreases during COVID-19 lockdowns, we investigate PTB rates during France's strict nationwide lockdown (March 17, 2020 to May 10, 2020). METHODS: This is an interrupted time series analysis using data on maternal delivery hospitalizations in France from January 01, 2016 to July 31, 2020 (3,448,286 singleton births ≥22 weeks' gestational age (GA)). Outcomes were weekly PTB rates (overall and by GA sub-group: <28, 28-31, 32-34, 35-36 weeks), stillbirth and cesarean birth. We estimate odds ratios (OR) using the lockdown period as exposed and other weeks as unexposed, nationally and for districts grouped by COVID-19 incidence. RESULTS: Of 96,076 singleton live births during the lockdown, 4,799 were preterm. PTB rates were 6% (OR: 0.94, 95% CI: 0.90-0.98) lower than expected over this period. This decrease occurred among births 35-36 weeks' GA (OR: 0.92, 95% CI: 0.87-0.98), with no detectable reductions for other GA groups. Cesarean and stillbirth rates were stable. Larger differences were observed in districts with low (OR: 0.92, 95% CI 0.87-0.98) versus moderate/high COVID-19 incidence (OR: 0.97, 95% CI 0.92-1.03). CONCLUSIONS: Late preterm births decreased during France's first lockdown without concurrent change in cesareans and stillbirths. Effects were not more pronounced in moderate/high-COVID-19 districts, contradicting expectations if healthcare disruption were a principal cause.

Maternal and neonatal outcomes of pregnancies with COVID-19 after medically assisted reproduction: results from the prospective COVID-19-Related Obstetrical and Neonatal Outcome Study.

BACKGROUND: Severe acute respiratory syndrome coronavirus type 2 infections in pregnancy have been associated with maternal morbidity, admission to intensive care, and adverse perinatal outcomes such as preterm birth, stillbirth, and hypertensive disorders of pregnancy. It is unclear whether medically assisted reproduction additionally affects maternal and neonatal outcomes in women with COVID-19. OBJECTIVE: To evaluate the effect of medically assisted reproduction on maternal and neonatal outcomes in women with COVID-19 in pregnancy. STUDY DESIGN: A total of 1485 women with COVID-19 registered in the COVID-19 Related Obstetric and Neonatal Outcome Study (a multicentric, prospective, observational cohort study) were included. The maternal and neonatal outcomes in 65 pregnancies achieved with medically assisted reproduction and in 1420 spontaneously conceived pregnancies were compared. We used univariate und multivariate (multinomial) logistic regressions to estimate the (un)adjusted odds ratios and 95% confidence intervals for adverse outcomes. RESULTS: The incidence of COVID-19-associated adverse outcomes (eg, pneumonia, admission to intensive care, and death) was not different in women after conceptions with COVID-19 than in women after medically assisted reproduction pregnancies. Yet, the risk of obstetrical and neonatal complications was higher in pregnancies achieved through medically assisted reproduction. However, medically assisted reproduction was not the primary risk factor for adverse maternal and neonatal outcomes including pregnancy-related hypertensive disorders, gestational diabetes mellitus, cervical insufficiency, peripartum hemorrhage, cesarean delivery, preterm birth, or admission to neonatal intensive care. Maternal age, multiple pregnancies, nulliparity, body mass index >30 (before pregnancy) and multiple gestation contributed differently to the increased risks of adverse pregnancy outcomes in women with COVID-19 independent of medically assisted reproduction. CONCLUSION: Although women with COVID-19 who conceived through fertility treatment experienced a higher incidence of adverse obstetrical and neonatal complications than women with spontaneous conceptions, medically assisted reproduction was not the primary risk factor.

The influence of structural racism, pandemic stress, and SARS-CoV-2 infection during pregnancy with adverse birth outcomes.

BACKGROUND: Structural racism and pandemic-related stress from the COVID-19 pandemic may increase the risk of adverse birth outcomes. OBJECTIVE: Our objective was to examine associations between neighborhood measures of structural racism and pandemic stress with 3 outcomes: SARS-CoV-2 infection, preterm birth, and delivering small-for-gestational-age newborns. Our secondary objective was to investigate the joint association of SARS-CoV-2 infection during pregnancy and neighborhood measures with preterm birth and delivering small-for-gestational-age newborns. STUDY DESIGN: We analyzed data of 967 patients from a prospective cohort of pregnant persons in New York City, comprising 367 White (38%), 169 Black (17%), 293 Latina (30%), and 87 Asian persons (9%), 41 persons of other race or ethnicity (4%), and 10 of unknown race or ethnicity (1%). We evaluated structural racism (social/built structural disadvantage, racial-economic segregation) and pandemic-related stress (community COVID-19 mortality, community unemployment rate increase) in quartiles by zone improvement plan code. SARS-CoV-2 serologic enzyme-linked immunosorbent assay was performed on blood samples from pregnant persons. We obtained data on preterm birth and small-for-gestational-age newborns from an electronic medical record database. We used log-binomial regression with robust standard error for clustering by zone improvement plan code to estimate associations of each neighborhood measure separately with 3 outcomes: SARS-CoV-2 infection, preterm birth, and small-for-gestational-age newborns. Covariates included maternal age, parity, insurance status, and body mass index. Models with preterm birth and small-for-gestational-age newborns as the dependent variables additionally adjusted for SARS-CoV-2 infection. RESULTS: A total of 193 (20%) persons were SARS-CoV-2-seropositive, and the overall risks of preterm birth and small-for-gestational-age newborns were 8.4% and 9.8%, respectively. Among birthing persons in neighborhoods in the highest quartile of structural disadvantage (n=190), 94% were non-White, 50% had public insurance, 41% were obese, 32% were seropositive, 11% delivered preterm, and 12% delivered a small-for-gestational-age infant. Among birthing persons in neighborhoods in the lowest quartile of structural disadvantage (n=360), 39% were non-White, 17% had public insurance, 15% were obese, 9% were seropositive, 6% delivered preterm, and 10% delivered a small-for-gestational-age infant. In adjusted analyses, structural racism measures and community unemployment were associated with both SARS-CoV-2 infection and preterm birth, but not small-for-gestational-age infants. High vs low structural disadvantage was associated with an adjusted relative risk of 2.6 for infection (95% confidence interval, 1.7-3.9) and 1.7 for preterm birth (95% confidence interval, 1.0-2.9); high vs low racial-economic segregation was associated with adjusted relative risk of 1.9 (95% confidence interval, 1.3-2.8) for infection and 2.0 (95% confidence interval, 1.3-3.2) for preterm birth; high vs low community unemployment increase was associated with adjusted relative risk of 1.7 (95% confidence interval, 1.2-1.5) for infection and 1.6 (95% confidence interval, 1.0-2.8) for preterm birth. COVID-19 mortality rate was associated with SARS-CoV-2 infection but not preterm birth or small-for-gestational-age infants. SARS-CoV-2 infection was not independently associated with birth outcomes. We found no interaction between SARS-CoV-2 infection and neighborhood measures on preterm birth or small-for-gestational-age infants. CONCLUSION: Neighborhood measures of structural racism were associated with both SARS-CoV-2 infection and preterm birth, but these associations were independent and did not have a synergistic effect. Community unemployment rate increases were also associated with an increased risk of preterm birth independently of SARS-CoV-2 infection. Mitigating these factors might reduce the impact of the pandemic on pregnant people.

SARS-CoV-2 infection in the first trimester and the risk of early miscarriage: a UK population-based prospective cohort study of 3041 pregnancies conceived during the pandemic.

STUDY QUESTION: Does maternal infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the first trimester affect the risk of miscarriage before 13 week's gestation? SUMMARY ANSWER: Pregnant women with self-reported diagnosis of SARS-CoV-2 in the first trimester had a higher risk of early miscarriage. WHAT IS KNOWN ALREADY: Viral infections during pregnancy have a broad spectrum of placental and neonatal pathology. Data on the effects of the SARS-CoV-2 infection in pregnancy are still emerging. Two systematic reviews and meta-analyses reported an increased risk of preterm birth, caesarean delivery, maternal morbidity and stillbirth. Data on the impact of first trimester infection on early pregnancy outcomes are scarce. This is the first study, to our knowledge, to investigate the rates of early pregnancy loss during the SARS-CoV-2 outbreak among women with self-reported infection. STUDY DESIGN, SIZE, DURATION: This was a nationwide prospective cohort study of pregnant women in the community recruited using social media between 21 May and 31 December 2020. We recruited 3545 women who conceived during the SARS-CoV-2 pandemic who were <13 week's gestation at the time of recruitment. PARTICIPANTS/MATERIALS, SETTING, METHODS: The COVID-19 Contraception and Pregnancy Study (CAP-COVID) was an on-line survey study collecting longitudinal data from pregnant women in the UK aged 18 years or older. Women who were pregnant during the pandemic were asked to complete on-line surveys at the end of each trimester. We collected data on current and past pregnancy complications, their medical history and whether they or anyone in their household had symptoms or been diagnosed with SARS-CoV-2 infection during each trimester of their pregnancy. RT-PCR-based SARS-CoV-2 RNA detection from respiratory samples (e.g. nasopharynx) is the standard practice for diagnosis of SARS-CoV-2 in the UK. We compared rate of self-reported miscarriage in three groups: 'presumed infected', i.e. those who reported a diagnosis with SARS-CoV-2 infection in the first trimester; 'uncertain', i.e. those who did not report a diagnosis but had symptoms/household contacts with symptoms/diagnosis; and 'presumed uninfected', i.e. those who did not report any symptoms/diagnosis and had no household contacts with symptoms/diagnosis of SARS-CoV-2. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 3545 women registered for the CAP-COVID study at <13 weeks gestation and were eligible for this analysis. Data for the primary outcome were available from 3041 women (86%). In the overall sample, the rate of self-reported miscarriage was 7.8% (238/3041 [95% CI, 7-9]). The median gestational age (GA) at miscarriage was 9 weeks (interquartile range 8-11). Seventy-seven women were in the 'presumed infected' group (77/3041, 2.5% [95% CI 2-3]), 295/3041 were in the uncertain group (9.7% [95% CI 9-11]) and the rest in the 'presumed uninfected' (87.8%, 2669/3041 [95% CI 87-89]). The rate of early miscarriage was 14% in the 'presumed infected' group, 5% in the 'uncertain' and 8% in the 'presumed uninfected' (11/77 [95% CI 6-22] versus 15/295 [95% CI 3-8] versus 212/2669 [95% CI 7-9], P = 0.02). After adjusting for age, BMI, ethnicity, smoking status, GA at registration and the number of previous miscarriages, the risk of early miscarriage appears to be higher in the 'presumed infected' group (relative rate 1.7, 95% CI 1.0-3.0, P = 0.06). LIMITATIONS, REASONS FOR CAUTION: We relied on self-reported data on early pregnancy loss and SARS-CoV-2 infection without any means of checking validity. Some women in the 'presumed uninfected' and 'uncertain' groups may have had asymptomatic infections. The number of 'presumed infected' in our study was low and therefore the study was relatively underpowered. WIDER IMPLICATIONS OF THE FINDINGS: This was a national study from the UK, where infection rates were one of the highest in the world. Based on the evidence presented here, women who are infected with SARS-CoV-2 in their first trimester may be at an increased risk of a miscarriage. However, the overall rate of miscarriage in our study population was 8%. This is reassuring and suggests that if there is an effect of SARS-CoV-2 on the risk of miscarriage, this may be limited to those with symptoms substantial enough to lead to a diagnostic test. Further studies are warranted to evaluate a causal association between SARS-CoV-2 infection in early pregnancy and miscarriage risk. Although we did not see an overall increase in the risk of miscarriage, the observed comparative increase in the presumed infected group reinforces the message that pregnant women should continue to exercise social distancing measures and good hygiene throughout their pregnancy to limit their risk of infection. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by a grant from the Elizabeth Garrett Anderson Hospital Charity (G13-559194). The funders of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report. J.A.H. is supported by an NIHR Advanced Fellowship. A.L.D. is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support to J.A.H. and A.L.D. as above; no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work. TRIAL REGISTRATION NUMBER: N/A.

Safety of third SARS-CoV-2 vaccine (booster dose) during pregnancy.

BACKGROUND: COVID-19 during pregnancy is associated with adverse outcomes for both the mother and fetus. SARS-CoV-2 vaccination has significantly reduced the risk for symptomatic disease. Several studies have reported on the safety of SARS-CoV-2 vaccination during pregnancy, with no adverse effects on the obstetrical outcomes. However, data regarding the obstetrical outcomes following a booster dose of the SARS CoV-2 vaccination during pregnancy have not yet to be published. OBJECTIVE: This study aimed to examine the association between the booster dose of the SARS CoV-2 vaccination during pregnancy and obstetrical outcomes. STUDY DESIGN: This was a retrospective cohort study of women who delivered between July and October 2021 at a large tertiary medical center. We compared women who received the booster vaccination dose during pregnancy with women who were not vaccinated and with those who only received 2 vaccination doses. Primary outcomes were the incidence of preterm labor and of small for gestational age neonates. Secondary outcomes were other maternal and neonatal complications. A secondary analysis investigating the association between the time from vaccination to delivery and the outcomes was also performed. Multivariable logistic regression models were used to adjust for potential confounders. RESULTS: There were 6507 women who met the inclusion criteria: 294 women received 3 doses of the vaccination, 2845 women received only 2 doses, and 3368 were unvaccinated. Patients receiving 3 doses of the vaccine were older and more likely to smoke than unvaccinated patients. No differences were noted among the triple-vaccinated, twice-vaccinated, and unvaccinated groups with regards to preterm birth and the incidence of small for gestational age neonates. Regarding the secondary outcomes, women in the triple-vaccinated group had higher rates of postpartum hemorrhage (9.5% vs 3.21%; P<.001) and gestational diabetes mellitus (12.2% vs 8.3%; P=.02) and were less likely to have hypertensive disorders of pregnancy (0% vs 1.4%; P=.041) than the unvaccinated group. Compared with the twice-vaccinated patients, patients with 3 doses of the vaccine were more likely to experience postpartum hemorrhage (9.5% vs 3.5%; P<.001) and were less likely to have a low umbilical artery pH (0.7% vs 6.1%; P<.001). In the sensitivity analysis comparing patients who delivered within 2 weeks of the third vaccination dose (n=53) with those who delivered at least 6 weeks after vaccination (n=96), there were no differences in the rates of small for gestational age neonates, preterm birth, postpartum hemorrhage, or cesarean delivery. CONCLUSION: Receiving the booster dose of the SARS-CoV-2 vaccination during pregnancy was not associated with adverse obstetrical outcomes when compared with unvaccinated or twice-vaccinated women. However, higher rates of postpartum hemorrhage were observed. Further studies on a larger scale are needed to confirm these findings.

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.

Association of SARS-CoV-2 Vaccination During Pregnancy With Pregnancy Outcomes.

Importance: Data about the safety of vaccines against SARS-CoV-2 during pregnancy are limited. Objective: To examine the risk of adverse pregnancy outcomes after vaccination against SARS-CoV-2 during pregnancy. Design, Setting, and Participants: This registry-based retrospective cohort study included 157 521 singleton pregnancies ending after 22 gestational weeks from January 1, 2021, until January 12, 2022 (Sweden), or January 15, 2022 (Norway). The Pregnancy Register in Sweden and the Medical Birth Registry of Norway were linked to vaccination and other registries for identification of exposure and background characteristics. Exposures: Data on mRNA vaccines-BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)-and 1 viral vector vaccine-AZD1222 (AstraZeneca)-were collected from national vaccination registries. Main Outcomes and Measures: The risk of preterm birth and stillbirth was evaluated using Cox regression models, with gestational day as the time metric and vaccination as a time-dependent exposure variable. The risk of small for gestational age, low Apgar score, and neonatal care admission was evaluated using logistic regression. Random-effects meta-analysis was used to combine results between countries. Results: Among the 157 521 singleton births included in the study (103 409 in Sweden and 54 112 in Norway), the mean maternal age at the time of delivery was 31 years, and 28 506 (18%) were vaccinated against SARS-CoV-2 (12.9% with BNT162b2, 4.8% with mRNA-1273, and 0.3% with AZD1222) while pregnant. A total of 0.7%, 8.3%, and 9.1% of individuals delivering were vaccinated during the first, second, and third trimester, respectively. Vaccination against SARS-CoV-2 was not significantly associated with increased risk of preterm birth (6.2 vs 4.9 per 10 000 pregnancy days; adjusted hazard ratio [aHR], 0.98 [95% CI, 0.91 to 1.05]; I2 = 0%; P for heterogeneity = .60), stillbirth (2.1 vs 2.4 per 100 000 pregnancy days; aHR, 0.86 [95% CI, 0.63 to 1.17]), small for gestational age (7.8% vs 8.5%; difference, -0.6% [95% CI, -1.3% to 0.2%]; adjusted OR [aOR], 0.97 [95% CI, 0.90 to 1.04]), low Apgar score (1.5% vs 1.6%; difference, -0.05% [95% CI, -0.3% to 0.1%]; aOR, 0.97 [95% CI, 0.87 to 1.08]), or neonatal care admission (8.5% vs 8.5%; difference, 0.003% [95% CI, -0.9% to 0.9%]; aOR, 0.97 [95% CI, 0.86 to 1.10]). Conclusions and Relevance: In this population-based study conducted in Sweden and Norway, vaccination against SARS-CoV-2 during pregnancy, compared with no SARS-CoV-2 vaccination during pregnancy, was not significantly associated with an increased risk of adverse pregnancy outcomes. The majority of the vaccinations were with mRNA vaccines during the second and third trimesters of pregnancy, which should be considered in interpreting the findings.

Maternal infection with COVID-19 and increased risk of adverse pregnancy outcomes: a meta-analysis.

Background: The Coronavirus disease 2019 (COVID-19) pandemic has become worldwide, posing particularly severe challenges. Pregnancy brings changes that might make individuals more vulnerable to this viral infection. To date, the impact of COVID-19 infection on pregnancy outcomes remains controversial.Method: We performed a meta-analysis to address the impact of COVID-19 infection on pregnancy outcomes. We searched the PubMed and China National Knowledge infrastructure (CNKI) databases for related articles. The odds ratio (OR) corresponding to the 95% confidence interval (95% CI) was used to define the impact of INFECTION and severity of COVID-19 on pregnancy outcomes. The statistical heterogeneity among studies was batched with the Q-test and I2 statistics.Results: We collected 38 studies including 127,805 pregnancy women. Our meta-analysis revealed that pregnant women with COVID-19 have been linked to an increased risk of premature birth (OR = 1.66, 95% CI = 1.41-1.96), stillbirth (OR = 1.98, 95% CI = 1.22-3.21), pre-eclampsia (OR = 1.46, 95% CI = 1.18-1.80), and PROM (OR = 1.39, 95% CI = 1.07-1.81).Conclusions: Our meta-analysis showed that infection with COVID-19 increases the risk of preterm birth, stillbirth, pre-eclampsia, and PROM. Screening and early care for pregnant women to intervene with COVID-19 is important, given the increased risk of adverse pregnancy outcomes.

Maternal-Newborn Health System Changes and Outcomes in Ontario, Canada, During Wave 1 of the COVID-19 Pandemic-A Retrospective Study.

OBJECTIVE: To determine the population-level impact of COVID-19 pandemic-related obstetric practice changes on maternal and newborn outcomes. METHODS: Segmented regression analysis examined changes that occurred 240 weeks pre-pandemic through the first 32 weeks of the pandemic using data from Ontario's Better Outcomes Registry & Network. Outcomes included birth location, length of stay, labour analgesia, mode of delivery, preterm birth, and stillbirth. Immediate and gradual effects were modelled with terms representing changes in intercepts and slopes, corresponding to the start of the pandemic. RESULTS: There were 799 893 eligible pregnant individuals included in the analysis; 705 767 delivered in the pre-pandemic period and 94 126 during the pandemic wave 1 period. Significant immediate decreases were observed for hospital births (relative risk [RR] 0.99; 95% CI 0.98-0.99), length of stay (median change -3.29 h; 95% CI -3.81 to -2.77), use of nitrous oxide (RR 0.11; 95% CI 0.09-0.13) and general anesthesia (RR 0.69; 95% CI 0.58- 0.81), and trial of labour after cesarean (RR 0.89; 95% CI 0.83-0.96). Conversely, there were significant immediate increases in home births (RR 1.35; 95% CI 1.21-1.51), and use of epidural (RR 1.02; 95% CI 1.01-1.04) and regional anesthesia (RR 1.01; 95% CI 1.01-1.02). There were no significant immediate changes for any other outcomes, including preterm birth (RR 0.99; 95% CI 0.93-1.05) and stillbirth (RR 1.11; 95% CI 0.87-1.42). CONCLUSION: Provincial health system changes implemented at the start of the pandemic resulted in immediate clinical practice changes but not insignificant increases in adverse outcomes.

Preterm birth, stillbirth and early neonatal mortality during the Danish COVID-19 lockdown.

Using provisional or opportunistic data, three nationwide studies (The Netherlands, the USA and Denmark) have identified a reduction in preterm or extremely preterm births during periods of COVID-19 restrictions. However, none of the studies accounted for perinatal deaths. To determine whether the reduction in extremely preterm births, observed in Denmark during the COVID-19 lockdown, could be the result of an increase in perinatal deaths and to assess the impact of extended COVID-19 restrictions, we performed a nationwide Danish register-based prevalence proportion study. We examined all singleton pregnancies delivered in Denmark during the COVID-19 strict lockdown calendar periods (March 12-April 14, 2015-2020, N = 31,164 births) and the extended calendar periods of COVID-19 restrictions (February 27-September 30, 2015-2020, N = 214,862 births). The extremely preterm birth rate was reduced (OR 0.27, 95% CI 0.07 to 0.86) during the strict lockdown period in 2020, while perinatal mortality was not significantly different. During the extended period of restrictions in 2020, the extremely preterm birth rate was marginally reduced, and a significant reduction in the stillbirth rate (OR 0.69, 0.50 to 0.95) was observed. No changes in early neonatal mortality rates were found.Conclusion: Stillbirth and extremely preterm birth rates were reduced in Denmark during the period of COVID-19 restrictions and lockdown, respectively, suggesting that aspects of these containment and control measures confer an element of protection. The present observational study does not allow for causal inference; however, the results support the design of studies to ascertain whether behavioural or social changes for pregnant women may improve pregnancy outcomes. What is Known: • The aetiologies of preterm birth and stillbirth are multifaceted and linked to a wide range of socio-demographic, medical, obstetric, foetal, psychosocial and environmental factors. • The COVID-19 lockdown saw a reduction in extremely preterm births in Denmark and other high-income countries. An urgent question is whether this reduction can be explained by increased perinatal mortality. What is New: • The reduction in extremely preterm births during the Danish COVID-19 lockdown was not a consequence of increased perinatal mortality, which remained unchanged during this period. • The stillbirth rate was reduced throughout the extended period of COVID-19 restrictions.

Multiprofessional perinatal care in a pregnant patient with acute respiratory distress syndrome due to COVID-19.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has caused ongoing challenges in health services worldwide. Despite the growing body of literature on COVID-19, reports on perinatal care in COVID-19 cases are limited. CASE PRESENTATION: We describe a case of severe acute respiratory distress syndrome (ARDS) in a 36-year-old G5/P2 pregnant woman with morbid obesity, confirmed severe acute respiratory syndrome coronavirus 2 infection, and fulminant respiratory failure. At 28+ 1 gestational weeks, the patient delivered an uninfected newborn. Using ImmunoCAP ISAC® technology, we found no immunoglobulin (Ig) M antibodies, suggesting that no mother-to-child viral transmission occurred during pregnancy or delivery. The maternal respiratory state improved rapidly after delivery; both maternal and neonatal outcomes were encouraging given the early gestational age and fulminant course of respiratory failure in our patient. CONCLUSIONS: The management of ARDS in pregnant women with COVID-19 is complex and requires an individualized, multidisciplinary approach, while considering maternal and fetal outcomes.

Placental lesions and SARS-Cov-2 infection: Diffuse placenta damage associated to poor fetal outcome.

INTRODUCTION: Pregnant women with covid-19 are more likely to experience preterm birth. The virus seems to be associated with a wide range of placental lesions, none of them specific. METHOD: We collected cases of Covid-19 maternal infection during pregnancy associated with poor pregnancy outcomes, for which we received the placenta. We studied clinical data and described pathological findings of placenta and post-mortem examination of fetuses. We performed an immunohistochemical study and RT-PCR of SARS-Cov-2 on placenta samples. RESULTS: We report 5 cases of poor fetal outcome, 3 fetal deaths and 2 extreme premature neonates, one with growth restriction, without clinical and biological sign of SARS-Cov-2 infection. All placenta presented massive perivillous fibrin deposition and large intervillous thrombi associated with strong SARS-Cov-2 expression in trophoblast and SARS-CoV-2 PCR positivity in amniotic fluid or on placenta samples. Chronic histiocytic intervillositis was present in 4/5 cases. Placental ultrasound was abnormal and the sFLT1-PIGF ratio was increased in one case. Timing between mothers' infection and the poor fetal outcome was ≤10 days in 4 cases. The massive placental damage are directly induced by the virus whose receptors are expressed on trophoblast, leading to trophoblast necrosis and massive inflammation in villous chamber, in a similar way it occurs in diffuse alveolar damage in adults infected by SARS-Cov-2. DISCUSSION: SARS-Cov-2 can be associated to a rare set of placental lesions which can lead to fetal demise, preterm birth, or growth restriction. Stronger surveillance of mothers infected by SARS-Cov-2 is required.

The Society for Obstetric Anesthesia and Perinatology Coronavirus Disease 2019 Registry: An Analysis of Outcomes Among Pregnant Women Delivering During the Initial Severe Acute Respiratory Syndrome Coronavirus-2 Outbreak in the United States.

BACKGROUND: Early reports associating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection with adverse pregnancy outcomes were biased by including only women with severe disease without controls. The Society for Obstetric Anesthesia and Perinatology (SOAP) coronavirus disease 2019 (COVID-19) registry was created to compare peripartum outcomes and anesthetic utilization in women with and without SARS-CoV-2 infection delivering at institutions with widespread testing. METHODS: Deliveries from 14 US medical centers, from March 19 to May 31, 2020, were included. Peripartum infection was defined as a positive SARS-CoV-2 polymerase chain reaction test within 14 days of delivery. Consecutive SARS-CoV-2-infected patients with randomly selected control patients were sampled (1:2 ratio) with controls delivering during the same day without a positive test. Outcomes were obstetric (eg, delivery mode, hypertensive disorders of pregnancy, and delivery <37 weeks), an adverse neonatal outcome composite measure (primary), and anesthetic utilization (eg, neuraxial labor analgesia and anesthesia). Outcomes were analyzed using generalized estimating equations to account for clustering within centers. Sensitivity analyses compared symptomatic and asymptomatic patients to controls. RESULTS: One thousand four hundred fifty four peripartum women were included: 490 with SARS-CoV-2 infection (176 [35.9%] symptomatic) and 964 were controls. SARS-CoV-2 patients were slightly younger, more likely nonnulliparous, nonwhite, and Hispanic than controls. They were more likely to have diabetes, obesity, or cardiac disease and less likely to have autoimmune disease. After adjustment for confounders, individuals experiencing SARS-CoV-2 infection exhibited an increased risk for delivery <37 weeks of gestation compared to controls, 73 (14.8%) vs 98 (10.2%) (adjusted odds ratio [aOR], 1.47; 95% confidence interval [CI], 1.03-2.09). Effect estimates for other obstetric outcomes and the neonatal composite outcome measure were not meaningfully different between SARS-CoV-2 patients versus controls. In sensitivity analyses, compared to controls, symptomatic SARS-CoV-2 patients exhibited increases in cesarean delivery (aOR, 1.57; 95% CI, 1.09-2.27), postpartum length of stay (aOR, 1.89; 95% CI, 1.18-2.60), and delivery <37 weeks of gestation (aOR, 2.08; 95% CI, 1.29-3.36). These adverse outcomes were not found in asymptomatic women versus controls. SARS-CoV-2 patients (asymptomatic and symptomatic) were less likely to receive neuraxial labor analgesia (aOR, 0.52; 95% CI, 0.35-0.75) and more likely to receive general anesthesia for cesarean delivery (aOR, 3.69; 95% CI, 1.40-9.74) due to maternal respiratory failure. CONCLUSIONS: In this large, multicenter US cohort study of women with and without peripartum SARS-CoV-2 infection, differences in obstetric and neonatal outcomes seem to be mostly driven by symptomatic patients. Lower utilization of neuraxial analgesia in laboring patients with asymptomatic or symptomatic infection compared to patients without infection requires further investigation.

A decline in planned, but not spontaneous, preterm birth rates in a large Australian tertiary maternity centre during COVID-19 mitigation measures.

BACKGROUND: Reports from around the world suggest that rates of preterm birth decreased during COVID-19 lockdown measures. AIMS: To compare the prevalence of preterm birth and stillbirth rates during COVID-19 restriction measures with infants born at the same maternity centre during the same weeks in 2013-2019. MATERIALS AND METHODS: Deidentified data were extracted from the Mater Mothers' healthcare records database. This is a supra-regional tertiary perinatal centre. Logistic regressions were used to examine singleton live preterm birth rates during the beginning of COVID-19 restrictions (16 March-17 April; 'early'; 6955 births) and during the strictest part of COVID-19 restrictions (30 March-1 May; 'late'; 6953 births), according to gestational age subgroups and birth onset (planned or spontaneous). We adjusted for multiple covariates, including maternal age, body mass index, ethnicity, parity, socioeconomic status, maternal asthma, diabetes mellitus and/or hypertensive disorder. Singleton stillbirth rates were also examined between 16 March-1 May. RESULTS: Planned moderate/late preterm births declined by more than half during early COVID-19 restrictions compared with the previous seven years (29 vs an average of 64 per 1000 births; adjusted odds ratio 0.39, 95% CI 0.22-0.71). There was no effect on extremely or very preterm infants, spontaneous preterm births, or stillbirth rates. Rolling averages from January to June revealed a two-week non-significant spike in spontaneous preterm births from late April to early May, 2020. CONCLUSIONS: Together with evidence from other nations, the pandemic provides a unique opportunity to identify causal and preventative factors for preterm birth.