Covid-19: Is the placenta a safe space

Problem: Several large studies have demonstrated that COVID-19 pregnant individuals are at a significant risk for severe disease and adverse pregnancy outcomes. The mechanisms underlying these phenomena remain to be elucidated and are the focus of our project. Although fetal and placental infection is rare, placental abnormalities and adverse pregnancy outcomes associated with placental dysfunction in COVID-19 cases have been widely reported. In particular, placental thrombosis and lesions consistent with maternal vascular malperfusion (MVM) of the placenta are common in individuals with COVID-19. Since thrombotic complications have been associated with COVID-19, it is not surprising that pregnant individuals with COVID- 19 are at risk for placental thrombosis. Method of Study: Placentas were evaluated histologically. Extracellular vesicles were isolated by serial centrifugation. Result(s): Adverse pregnancy outcomes associated with these placental lesions, including hypertensive disorders of pregnancy (gestational hypertension and preeclampsia), small for gestational age (SGA, birthweight < 10th percentile for gestational age), and preterm birth (PTB, < 37 weeks) are significantly increased among pregnant individuals with COVID-19. Placental infection with SARSCoV- 2 is uncommon, but multiple inflammatory and metabolic factors are likely to affect the placenta, including circulating extracellular vesicles (EVs) derived from various organs that have been associated with COVID-19 pathology and disease severity.We have analyzed over 500 placentas from COVID-19 pregnancies and found marked changes in placental morphology, characterized by abnormal maternal and fetal vessels, intervillous thrombi, and fibrin deposition, even in the face of mild or asymptomatic disease. We detected increased levels of small EVs in maternal serum from COVID-19 cases compared to controls and increased levels of mitochondrial DNA in EVs from COVID-19 cases. In in vitro experiments, we found increased oxidative stress in uterine endothelial cells and primary trophoblasts. Syncytialization of trophoblast cells following exposure to EVs from pregnant COVID-19 patients was markedly reduced. RNAseq of trophoblast cells exposed to EVs from pregnant COVID-19 patients revealed disruption of multiple pathways related to mitochondria function, oxidative stress, coagulation defects, and inflammation. Timing of infection during pregnancy (first, second, and third trimester) altered EV size distribution, cargo content, and functional consequences of trophoblast EV exposure. Conclusion(s): Our studies show that COVID-19 infection during pregnancy has profound effects on placenta morphology and function. It remains to be determined what the long-term consequences are on the offspring.

Paxlovid Prophylaxis or Treatment in Pregnancy: Data from the Organization of Teratology Information Specialists (OTIS) Pregnancy Registry

Background: The US Food and Drug Administration under an Emergency Use Authorization approved use of Paxlovid (nirmatrelavir and ritonavir) for the treatment of mild-to-moderate COVID-19 in adults and children with a positive test for SARS-Co-2 and who are at high risk for progression to severe COVID-19. Pregnant women are at increased risk of severe complications resulting from COVID-19 infection;however, minimal data on the safety of Paxlovid in human pregnancy are available. Objective(s): The objectives of this study are to assess risks of major congenital malformations, spontaneous abortion, elective termination, stillbirth, preterm delivery, small for gestational age infants at birth, or infants who were small for age at one year in pregnancies/infants prenatally exposed to Paxlovid in pregnancy compared to individuals who did not receive this treatment. Design(s): This study involves prospective data from the Organization of Teratology Information Specialists (OTIS) Pregnancy Registry which enrolls pregnant women residing in the US or Canada and captures data through maternal interviews and ion of medical records. Result(s): Among pregnant women participating in the OTIS Pregnancy Registry as of February 1, 2023, 59 reported exposure to Paxlovid in pregnancy;25.4% exposed within 30 days prior to the last menstrual period and through the first trimester, 42.4% exposed in second trimester, and 32.2% exposed in the third trimester. As of January 2023, 17 of those enrolled have completed pregnancy outcomes. One was lost to follow-up. Of the remainder, there were no adverse pregnancy outcomes reported. Conclusion(s): Very limited data are available on this potentially beneficial treatment in pregnancy. To date, no serious signals for this exposure have been detected.

A Cross-Sectional Study Comparing the Efficacy of Various Growth Charts in Evaluating the Incidences of Small for Gestational Age and Large for Gestational Age at Birth Among Liveborn Neonates Delivered at a Tertiary Teaching Hospital.

Background and objective Growth charts are important in monitoring the growth of neonates. The growth of Indian fetuses is understood to be different from the Western population due to multiple factors. In this study, we aimed to analyze the utility of the application of various growth charts in evaluating the birth weights of liveborn neonates at a tertiary teaching hospital. Methodology A total of 729 liveborn neonates between 24 to 42 weeks of gestation delivered at the study institute during the study period were included. Birth weights were plotted on three growth charts - Fenton 2013, INTERGROWTH-21st (IG-21), and Kandraju et al. chart - and classified as small for gestational age (SGA), or appropriate for gestational age (AGA), or large for gestational age (LGA) according to the respective centiles and sex. The incidences of SGA and LGA were calculated with respect to various charts and compared. Statistical analysis was done using the McNemar Chi-square test for paired categorical variables. Cohen's kappa (K) was used to analyze the concordance between the growth charts. A p-value <0.005 was considered statistically significant. Results Among 668 term neonates, the number of neonates classified as SGA was 313 (46.86%), 236 (35.33%), and 219 (32.78%) according to Fenton 2013, IG-21, and Kandraju et al. chart respectively. The difference in incidences of SGA between Fenton 2013 and IG-21 for term neonates was significant (p=0.0001). The difference between incidences of SGA among term neonates according to Fenton 2013 and Kandraju et al. and IG-21 vs. Kandraju et al. was significant (p=0.0001). Among 61 preterm neonates, the number of neonates classified as SGA was 15, 11, and five according to Fenton 2013, IG-21, and Kandraju et al. respectively. There was no statistically significant difference between the three charts. Among 729 neonates, the number of neonates classified as LGA was 10 (1.37%), 22 (3.02%), and 32 (4.39%) according to Fenton 2013, IG-21, and Kandraju, et al. respectively. The difference in incidences of LGA between Fenton 2013 and IG-21 was significant (p=0.0015). The difference in incidences of LGA between Fenton 2013 and Kandraju et al. was significant (p=0.0001). The difference in incidences of LGA between IG-21 and Kandraju et al. was also significant (p=0.0044). Conclusion Fenton 2013, IG-21, and Kandraju et al. growth charts vary significantly in detecting the incidence of SGA and LGA among term neonates. Among term neonates, IG-21 and Kandraju et al. growth charts are comparable in terms of the estimation of SGA. The Fenton 2013 growth chart showed a higher incidence of SGA among term neonates. The incidence of LGA was highest according to Kandraju et al. growth chart and least according to Fenton 2013. Among preterm neonates, the incidence of SGA as per birth weight was comparable across the three growth charts.

COVID-19 in pregnancy may significantly affect fetal growth

Objective. Whilst most cases of COVID-19 in pregnancy evolve uneventfully, some others have a poor outcome, such as preterm birth and HDP. The effect of COVID-19 on fetal growth still has to be addressed and appears controversial. Our study aims to focus on fetal growth velocity across the trimesters in pregnancy affected with COVID-19. Materials and Methods. This is a multicentric prospective observational study on data from COVID-19 pregnancies referred to the centers of Careggi University Hospital and S. Stefano Hospital in Prato from 2020 to 2022, included in the local branch of ItOSS surveillance. Fetal growth was evaluated across the three trimesters of pregnancy by abdominal circumference (AC) and expected fetal weight (EFW). Both AC, and EFW plus birthweight were used to calculate growth velocity (Vannuccini et al., 2017). Results. Data from a cohort of 211 cases was collected. The majority (80%) of COVID-19 cases occurred in the third trimester. Of note, the percentage of gestational diabetes (12.3%) and preterm births (7.1%) was comparable to the general population. Mean birthweight was 3259 +/- 509 g. The percentage of cesarean sections was acceptable (13.7%). Concerning the velocity of growth, AC decreased from the second to third trimester to reach values < 10th centile in 24% of cases and < 5th percentile in 17% of cases, even in presence of 2% of hypertensive disorders (HDP). Fetal growth restriction according to Gordjin et al. (2015) was antenatally identified in 4.7% of cases. Fetal growth > 95th centile occurred in 5.7% of cases. At birth, the cumulative percentage of small for gestational age newborns defined as birth weight < 2500 g resulted 5.2%. A significant percentage of newborns required NICU assistance (7.8%). Conclusions. Regardless of the association and prevalence of preterm birth, SGA and HDP in pregnant women, fetal growth appears to be affected by COVID-19 with a higher incidence of impaired growth velocity compared to the general population.

Undetected Fetal Growth Restriction during the Coronavirus Disease 2019 (COVID-19) Pandemic

This was a retrospective cohort study of patients who delivered singleton, small-for-gestational-Age (SGA) neonates between April and June 2019, before the coronavirus disease 2019 (COVID-19) pandemic (pre-COVID-19), and between April and July 2020, during the pandemic (COVID-19 epoch). The primary outcome was the rate of undetected antenatal fetal growth restriction (FGR) in the two periods. A total of 268 patients met inclusion criteria. Patients who delivered small-for-gestational-Age neonates during the COVID-19 epoch were significantly more likely to have undetected FGR compared with those who delivered pre-COVID-19 (70.1% vs 58.1%, P=.04). Patients who delivered SGA neonates during the COVID-19 epoch had more telehealth visits but fewer in-person prenatal visits, recorded fundal height measurements, and growth ultrasonograms. As telemedicine continues to be incorporated into prenatal care, these data may lend further support toward self-Assessment of fundal height or routine third-Trimester growth ultrasonograms to identify fetal growth abnormalities. Copyright © 2023 Lippincott Williams and Wilkins. All rights reserved.

Insights into Prevention of Health Complications in Small for Gestational Age (SGA) Births in Relation to Maternal Characteristics: A Narrative Review.

Small for gestational age (SGA) births are a significant clinical and public health issue. The objective of this review was to summarize maternal biological and socio-demographic factors and preventive strategies used to reduce the risk of SGA births. A literature search encompassing data from the last 15 years was conducted using electronic databases MEDLINE/PubMed, Google Scholar and Scopus to review risk factors and preventive strategies for SGA. Current evidence shows that primiparity, previous stillbirths, maternal age ≤24 and ≥35 years, single motherhood, low socio-economic status, smoking and cannabis use during pregnancy confer a significant risk of SGA births. Studies on alcohol consumption during pregnancy and SGA birth weight are inconclusive. Beneficial and preventive factors include the "Mediterranean diet" and dietary intake of vegetables. Periconceptional folic acid supplementation, maternal 25-hydroxyvitamin D, zinc and iron levels are partly associated with birth weight. No significant associations between COVID-19 vaccinations and birthweight are reported. A midwifery-led model based on early and extensive prenatal care reduces the risk of SGA births in women with low socio-economic status. Major preventive measures relate to the awareness of modifiable and non-modifiable risk factors of SGA, leading to changes in parents' lifestyles. These data support that education, monitoring during pregnancy, and implementing preventive strategies are as important as biological determinants in risk reduction of SGA births.

Clinical risk factors of adverse outcomes among women with COVID-19 in the pregnancy and postpartum period: A sequential, prospective meta-analysis.

OBJECTIVE: This sequential, prospective meta-analysis (sPMA) sought to identify risk factors among pregnant and postpartum women with COVID-19 for adverse outcomes related to: disease severity, maternal morbidities, neonatal mortality and morbidity, adverse birth outcomes. DATA SOURCES: We prospectively invited study investigators to join the sPMA via professional research networks beginning in March 2020. STUDY ELIGIBILITY CRITERIA: Eligible studies included those recruiting at least 25 consecutive cases of COVID-19 in pregnancy within a defined catchment area. STUDY APPRAISAL AND SYNTHESIS METHODS: We included individual patient data from 21 participating studies. Data quality was assessed, and harmonized variables for risk factors and outcomes were constructed. Duplicate cases were removed. Pooled estimates for the absolute and relative risk of adverse outcomes comparing those with and without each risk factor were generated using a two-stage meta-analysis. RESULTS: We collected data from 33 countries and territories, including 21,977 cases of SARS-CoV-2 infection in pregnancy or postpartum. We found that women with comorbidities (pre-existing diabetes, hypertension, cardiovascular disease) versus those without were at higher risk for COVID-19 severity and pregnancy health outcomes (fetal death, preterm birth, low birthweight). Participants with COVID-19 and HIV were 1.74 times (95% CI: 1.12, 2.71) more likely to be admitted to the ICU. Pregnant women who were underweight before pregnancy were at higher risk of ICU admission (RR 5.53, 95% CI: 2.27, 13.44), ventilation (RR 9.36, 95% CI: 3.87, 22.63), and pregnancy-related death (RR 14.10, 95% CI: 2.83, 70.36). Pre-pregnancy obesity was also a risk factor for severe COVID-19 outcomes including ICU admission (RR 1.81, 95% CI: 1.26,2.60), ventilation (RR 2.05, 95% CI: 1.20,3.51), any critical care (RR 1.89, 95% CI: 1.28,2.77), and pneumonia (RR 1.66, 95% CI: 1.18,2.33). Anemic pregnant women with COVID-19 also had increased risk of ICU admission (RR 1.63, 95% CI: 1.25, 2.11) and death (RR 2.36, 95% CI: 1.15, 4.81). CONCLUSION: We found that pregnant women with comorbidities including diabetes, hypertension, and cardiovascular disease were at increased risk for severe COVID-19-related outcomes, maternal morbidities, and adverse birth outcomes. We also identified several less commonly-known risk factors, including HIV infection, pre-pregnancy underweight, and anemia. Although pregnant women are already considered a high-risk population, special priority for prevention and treatment should be given to pregnant women with these additional risk factors.

The effect of the Covid pandemic and lockdown on stillbirth rates in a South Indian perinatal centre.

OBJECTIVES: The Covid-19 pandemic affected antenatal care in many parts of the world. It brought about many changes as part of control and containment measures. We examined the effect of the first and second waves of the pandemic in India on stillbirth rates, as indicators of quality of maternity care. METHODS: Observational study at a tertiary referral perinatal centre with approximately 10,000 births annually. The Covid-19 first wave period was taken as January to December 2020 with lockdown March to June 2020, which included complete shut down of clinics and ultrasound services. The second wave was from January to September 2021. All women with singleton pregnancy who had hospital based antenatal care were included. We investigated monthly trends in obstetric load (new antenatal registrations, total obstetric clinic numbers and total births) with stillbirth numbers as the pandemic continued (daily Covid case trend). We compared first and second wave stillbirth rates, overall as well as those that were small for gestational age (<10th centile) at delivery. RESULTS: There were 9,251 births with 32 stillbirths in the first wave (rate 3.46/1,000) and 6,228 births with 14 stillbirths in the second wave (2.25/1,000). This represented a 54% higher rate in the first phase and extended lockdown period (p=0.08). The incidence of stillbirths that were SGA was significantly higher in the first wave: 14 vs. 2, (p=0.03). CONCLUSIONS: Reduced access to planned antenatal care during Covid-19 pandemic lockdown was associated with a significant increase in SGA stillbirths.

Severe maternal infectious morbidity during the second half of pregnancy is an independent risk factor for a small for gestational age neonate.

OBJECTIVE: The effect of severe maternal infectious morbidity on fetal growth during the second half of pregnancy is under debate. Preliminary evidence suggests that such association may be plausible. The objectives of this study were to determine: 1) The association between severe maternal infectious morbidity and adverse pregnancy outcome; and 2) The effect of maternal infection during pregnancy on fetal growth. STUDY DESIGN: This retrospective population - based cohort study included 4771 women who gave birth at our medical center during the study period. Parturients were allocated into two groups: 1) patients with severe maternal infection during the second half of pregnancy (n = 368); and 2) control group comprised of normal pregnant women who were matched to the study group by maternal age, gravidity and parity (n = 4403). RESULTS: The severe maternal infection group included women with pneumonia (n = 198), pyelonephritis (n = 131), and viral pneumonitis (n = 39). In comparison to the normal patients group: 1) having had pneumonia during the second half of pregnancy was associated with increased rates of fetal growth restriction, placental abruption, fetal demise (P < 0.001, for all comparisons) and preeclampsia (P = 0.041); 2) Pyelonephritis during the second half of gestation was associated with higher rates of fetal growth restriction (P < 0.001), placental abruption (P = 0.006) and labor induction (P = 0.039). As a group, women with severe maternal infection had higher rates of small for gestational age neonates compared to normal parturients (P < 0.001). Among women with infections, only those who had pyelonephritis (P = 0.032) or pneumonia (P = 0.008), had a higher rate of small for gestational age neonates than those in the control group. After adjustment to confounding factors, maternal infection (OR = 1.42, 95% CI 1.085-1.85) and previous delivery of a small for gestational age neonate (OR = 2.54, 95% CI 2.02-3.19), were independent risk factors for the delivery of a small for gestational age neonate. CONCLUSION: Severe maternal infectious morbidity during the second half of pregnancy is an independent risk factor for the delivery of a small for gestational age neonate and is associated with adverse pregnancy outcomes. Both, pneumonia and pyelonephritis, during the second half of gestation affect fetal growth and are related to higher rates of small for gestational age neonates.

The best response to US criminalisation of abortion is decriminalisation elsewhere

[...]with the US Supreme Court overturning Roe v Wade, sexual and reproductive rights are under threat globally.23 The US is polarised on abortion, but criminalising abortion, as many states in the US are now doing,4 is harmful and costs lives.5 It disproportionately affects the poorest, most marginalised, and most vulnerable. Despite many US states following the Supreme Court ruling, the Republican state of Kansas recently voted to allow abortion.7 In the UK, although the public and politicians are supportive of abortion, it remains a criminal act under certain circumstances.8 Only Northern Ireland in the UK has decriminalised abortion, but that sea change in law is not yet matched by provision of services. Risk of preterm birth, small for gestational age at birth, and stillbirth after covid-19 vaccination during pregnancy: population based retrospective cohort study.

COVID-19 vaccine and pregnancy outcomes: A systematic review and meta-analysis.

OBJECTIVES: To explore perinatal outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-vaccinated pregnant women compared with unvaccinated counterparts. METHODS: Search was conducted using Web of Science, Scopus, ClinicalTrial.gov, MEDLINE, Embase, OVID, and Cochrane Library as electronic databases. We included observational studies evaluating pregnant women undergoing SARS-CoV-2 vaccination and compared pregnancy and perinatal outcomes with those in unvaccinated women. Categorical variables were assessed using odds ratio (OR) with 95% confidence interval (CI), whereas for continuous variables, the results were expressed as mean difference with their 95% CI. All analyses were performed by adopting the random effect model of DerSimonian and Laird. RESULTS: There was no difference in the probability of having a small-for-gestational-age fetus (OR 0.97, 95% CI 0.85-1.09; P = 0.570), but we observed a reduced probability of a non-reassuring fetal monitoring, a reduced gestational age at delivery, and a reduced probability of premature delivery in vaccinated pregnant women versus unvaccinated ones. CONCLUSION: The probability of small for gestational age is similar between vaccinated and unvaccinated pregnant women, and the former also had a slightly reduced rate of premature delivery.

The Impacts of Prenatal Mental Health Issues on Birth Outcomes during the COVID-19 Pandemic: A Scoping Review.

BACKGROUND: The severity of the COVID-19 pandemic is likely to exacerbate mental health problems during the prenatal period and increase the risk of adverse birth outcomes. This review assessed the published literature related to the impacts of prenatal mental health issues on birth outcomes during the COVID-19 pandemic. METHODS: This scoping review was conducted using PROSPERO, Cochrane Library, OVID Medline, Ovid EMBASE, OVID PsycInfo, EBSCO CINAHL, and SCOPUS. The search was conducted using controlled vocabulary and keywords representing the concepts "COVID19", "mental health" and "birth outcomes". The main inclusion criteria were peer-reviewed published articles from late 2019 to the end of July 2021. RESULTS AND DISCUSSION: After removing duplicates, 642 articles were identified, of which two full texts were included for analysis. Both articles highlighted that pregnant women have experienced increasing prenatal mental health issues during the COVID-19 pandemic and, further, increased the risk of developing adverse births. This scoping review highlighted that there is a lack of research on the impact of prenatal mental health issues on birth outcomes during the pandemic. CONCLUSION: Given the severity of the COVID-19 pandemic and the burdens of prenatal mental health issues and adverse birth outcomes, there is an urgent need to conduct further research.

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.

Effects of prenatal exposure to maternal COVID-19 and perinatal care on neonatal outcome: results from the INTERCOVID Multinational Cohort Study.

BACKGROUND: The effect of COVID-19 in pregnancy on maternal outcomes and its association with preeclampsia and gestational diabetes mellitus have been reported; however, a detailed understanding of the effects of maternal positivity, delivery mode, and perinatal practices on fetal and neonatal outcomes is urgently needed. OBJECTIVE: To evaluate the impact of COVID-19 on fetal and neonatal outcomes and the role of mode of delivery, breastfeeding, and early neonatal care practices on the risk of mother-to-child transmission. STUDY DESIGN: In this cohort study that took place from March 2020 to March 2021, involving 43 institutions in 18 countries, 2 unmatched, consecutive, unexposed women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. COVID-19 in pregnancy was determined by laboratory confirmation and/or radiological pulmonary findings or ≥2 predefined COVID-19 symptoms. The outcome measures were indices of neonatal and perinatal morbidity and mortality, neonatal positivity and its correlation with mode of delivery, breastfeeding, and hospital neonatal care practices. RESULTS: A total of 586 neonates born to women with COVID-19 diagnosis and 1535 neonates born to women without COVID-19 diagnosis were enrolled. Women with COVID-19 diagnosis had a higher rate of cesarean delivery (52.8% vs 38.5% for those without COVID-19 diagnosis, P<.01) and pregnancy-related complications, such as hypertensive disorders of pregnancy and fetal distress (all with P<.001), than women without COVID-19 diagnosis. Maternal diagnosis of COVID-19 carried an increased rate of preterm birth (P≤.001) and lower neonatal weight (P≤.001), length, and head circumference at birth. In mothers with COVID-19 diagnosis, the length of in utero exposure was significantly correlated to the risk of the neonate testing positive (odds ratio, 4.5; 95% confidence interval, 2.2-9.4 for length of in utero exposure >14 days). Among neonates born to mothers with COVID-19 diagnosis, birth via cesarean delivery was a risk factor for testing positive for COVID-19 (odds ratio, 2.4; 95% confidence interval, 1.2-4.7), even when severity of maternal conditions was considered and after multivariable logistic analysis. In the subgroup of neonates born to women with COVID-19 diagnosis, the outcomes worsened when the neonate also tested positive, with higher rates of neonatal intensive care unit admission, fever, gastrointestinal and respiratory symptoms, and death, even after adjusting for prematurity. Breastfeeding by mothers with COVID-19 diagnosis and hospital neonatal care practices, including immediate skin-to-skin contact and rooming-in, were not associated with an increased risk of newborn positivity. CONCLUSION: In this multinational cohort study, COVID-19 in pregnancy was associated with increased maternal and neonatal complications. Cesarean delivery was significantly associated with newborn COVID-19 diagnosis. Vaginal delivery should be considered the safest mode of delivery if obstetrical and health conditions allow it. Mother-to-child skin-to-skin contact, rooming-in, and direct breastfeeding were not risk factors for newborn COVID-19 diagnosis, thus well-established best practices can be continued among women with COVID-19 diagnosis.

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.

Maternal Risk Factors for Small-for-Gestational-Age Newborns in Mexico: Analysis of a Nationwide Representative Cohort.

Background: Small for gestational age (SGA) is a key contributor to premature deaths and long-term complications in life. Improved characterization of maternal risk factors associated with this adverse outcome is needed to inform the development of interventions, track progress, and reduce the disease burden. This study aimed to identify socioeconomic, demographic, and clinical factors associated with SGA in Mexico. Methods: We analyzed administrative data from 1,841,477 singletons collected by the National Information Subsystem of Livebirths during 2017. Small-for-gestational-age was defined as being <10th centiles according to the INTERGROWTH-21st standards. The comparison group was defined as being in ≥10th centiles. We fitted logistic regression models to determine odds ratios for the maternal factors associated with SGA. Results: Among the 1,841,477 singletons, 51% were male, 6.7% were SGA, 6.1% were term-SGA, and 0.5% were preterm-SGA. Maternal education presented a protective gradient of being SGA among mothers who achieved 1 to 6 years of education (adjusted odds ratio (aOR)0.95; 95% CI:0.91,0.99), 7 to 9 years (aOR 0.86; 95% CI:0.83,0.89), 10 to 12 years (aOR 0.75; 95% CI: 0.72, 0.79) and > 12 years (aOR 0.63; 95% CI:0.6,0.66) compared with those without education. SGA was particularly likely to occur among primiparous (aOR 1.42; 95% CI: 1.39, 1.43), mothers living in very high deprivation localities (aOR 1.39; 95% CI: 1.36, 1.43), young (aOR 1.04; 95% CI: 1.02, 1.06), advanced age (aOR 1.14; 95% CI 1.09, 1.19), and mothers living in areas above 2,000 m (aOR 1.69; 95% CI: 1.65, 1.73). Antenatal care was associated with a reduced risk of SGA by 30% (aOR 0.7; 95% CI:0.67,0.73), 23% (OR 0.77; 95% CI:0.74,0.8), and 21% (OR 0.79; 95% CI:0.75,0.83), compared with those mothers who never received antenatal care, when women visited the clinic at the first, second and third trimester, respectively. Conclusion: Almost 7% of live births were found to be SGA. Parity, maternal age, education, place of residence, and social deprivation were significantly associated with this outcome. Antenatal care was protective. These findings imply that interventions focusing on early and adequate contact with health care facilities, reproductive health counseling, and maternal education should reduce SGA in Mexico.

Safety of SARS-CoV-2 vaccination during pregnancy- obstetric outcomes from a large cohort study.

BACKGROUND: COVID-19 during pregnancy is associated with adverse outcomes for mother and fetus. SARS-CoV-2 vaccination has significantly reduced the risk of symptomatic disease. Several small studies have reported the safety of SARS-CoV-2 vaccination during pregnancy, with no adverse effect on obstetric outcomes. OBJECTIVE: To examine the association between SARS-CoV-2 vaccination during pregnancy and maternal and neonatal outcomes in a large cohort study. Furthermore, to evaluate if timing of vaccination during pregnancy is related to adverse outcomes. METHODS: A retrospective cohort study of women who delivered between December 2020 and July 2021 at a large tertiary medical center. Excluded were women with multiple pregnancy, vaccination prior to pregnancy, COVID-19 infection during or before pregnancy, or unknown timing of vaccination. Primary outcomes were the incidence of preterm labor and of small for gestational age. Secondary outcomes were other maternal and neonatal complications. A secondary analysis investigating the association between time of vaccination and outcomes was also performed. Multivariable logistic regression models were used to adjust for potential confounders. RESULTS: There were 5618 women who met the inclusion criteria: 2,305 (41%) women were vaccinated and 3,313 (59%) were unvaccinated. There were no differences between vaccinated and non-vaccinated patients with respect to primary outcomes. The rate of preterm birth was 5.5% in the vaccinated group compared to 6.2% in the unvaccinated group (p = 0.31). Likewise, the rates of small for gestational age were comparable between the two groups (6.2% vs. 7.0% respectively, p = 0.2). In a secondary analysis focusing on time of vaccination and its relationship with outcomes, patients vaccinated in the second trimester (n = 964) and in the third trimester (n = 1329) were independently compared to their unvaccinated counterparts. Women who were vaccinated in the second trimester were more likely to have a preterm birth (8.1% vs. 6.2%, p < 0.001). This association persisted after adjusting for potential confounders (adjusted odds ratio 1.49, 95%CI 1.11, 2.01). CONCLUSIONS: SARS-CoV-2 vaccine appears to be safe during pregnancy with no increase in incidence of preterm labor and small for gestational age compared to unvaccinated women. However, in women vaccinated during the second trimester there may be an increase in the rate of preterm birth.

Ultrasound and Doppler findings in pregnant women with SARS-CoV-2 infection.

OBJECTIVES: To describe and compare ultrasound and Doppler findings in pregnant women who were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with findings in those who were SARS-CoV-2-negative, evaluated during the pandemic period. METHODS: In this retrospective case-control study, we analyzed data from 106 pregnant women who tested positive for SARS-CoV-2 at the time of, or within 1 week of, an ultrasound scan between 1 May and 31 August 2020. Scans were either performed for routine fetal evaluation or indicated due to a positive SARS-CoV-2 test. Forty-nine women were symptomatic and 57 were asymptomatic. For comparison, we analyzed data from 103 pregnant women matched for maternal age, parity, body mass index and gestational age at the time of the ultrasound scan. These control women did not report symptoms of SARS-CoV-2 infection at the time of the ultrasound scan or at the time of admission for delivery and had a negative SARS-CoV-2 test at admission for delivery. Fetal biometry, fetal anatomy, amniotic fluid volume and Doppler parameters, including umbilical and fetal middle cerebral artery pulsatility indices, cerebroplacental ratio and biophysical profile (BPP), were evaluated as indicated. Biometric and Doppler values were converted to Z-scores for comparison. Our primary outcome, an adverse prenatal composite outcome (APCO) included any one or more of: small-for-gestational-age (SGA) fetus, oligohydramnios, abnormal BPP, abnormal Doppler velocimetry and fetal death. Comorbidities, delivery information and neonatal outcome were compared between the two groups. RESULTS: Eighty-seven (82.1%) women who were positive for SARS-CoV-2 had a body mass index > 25 kg/m2 . SARS-CoV-2-positive women had a higher prevalence of diabetes (26/106 (24.5%) vs 13/103 (12.6%); P = 0.03), but not of pre-eclampsia (21/106 (19.8%) vs 11/103 (10.7%); P = 0.08), compared with controls. The prevalence of APCO was not significantly different between SARS-CoV-2-positive women (19/106 (17.9%)) and controls (9/103 (8.7%)) (P = 0.06). There were no differences between SARS-CoV-2-positive women and controls in the prevalence of SGA fetuses (12/106 (11.3%) vs 6/103 (5.8%); P = 0.17), fetuses with abnormal Doppler evaluation (8/106 (7.5%) vs 2/103 (1.9%); P = 0.08) and fetuses with abnormal BPP (4/106 (3.8%) vs 0/103 (0%); P = 0.14). There were two fetal deaths in women who were positive for SARS-CoV-2 and these women had a higher rate of preterm delivery ≤ 35 weeks of gestation (22/106 (20.8%) vs 9/103 (8.7%); odds ratio, 2.73 (95% CI, 1.19-6.3); P = 0.01) compared with controls. CONCLUSIONS: There were no significant differences in abnormal fetal ultrasound and Doppler findings observed between pregnant women who were positive for SARS-CoV-2 and controls. However, preterm delivery ≤ 35 weeks was more frequent among SARS-CoV-2-positive women. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Preeclampsia and COVID-19: results from the INTERCOVID prospective longitudinal study.

BACKGROUND: It is unclear whether the suggested link between COVID-19 during pregnancy and preeclampsia is an independent association or if these are caused by common risk factors. OBJECTIVE: This study aimed to quantify any independent association between COVID-19 during pregnancy and preeclampsia and to determine the effect of these variables on maternal and neonatal morbidity and mortality. STUDY DESIGN: This was a large, longitudinal, prospective, unmatched diagnosed and not-diagnosed observational study assessing the effect of COVID-19 during pregnancy on mothers and neonates. Two consecutive not-diagnosed women were concomitantly enrolled immediately after each diagnosed woman was identified, at any stage during pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed until hospital discharge using the standardized INTERGROWTH-21st protocols and electronic data management system. A total of 43 institutions in 18 countries contributed to the study sample. The independent association between the 2 entities was quantified with the risk factors known to be associated with preeclampsia analyzed in each group. The outcomes were compared among women with COVID-19 alone, preeclampsia alone, both conditions, and those without either of the 2 conditions. RESULTS: We enrolled 2184 pregnant women; of these, 725 (33.2%) were enrolled in the COVID-19 diagnosed and 1459 (66.8%) in the COVID-19 not-diagnosed groups. Of these women, 123 had preeclampsia of which 59 of 725 (8.1%) were in the COVID-19 diagnosed group and 64 of 1459 (4.4%) were in the not-diagnosed group (risk ratio, 1.86; 95% confidence interval, 1.32-2.61). After adjustment for sociodemographic factors and conditions associated with both COVID-19 and preeclampsia, the risk ratio for preeclampsia remained significant among all women (risk ratio, 1.77; 95% confidence interval, 1.25-2.52) and nulliparous women specifically (risk ratio, 1.89; 95% confidence interval, 1.17-3.05). There was a trend but no statistical significance among parous women (risk ratio, 1.64; 95% confidence interval, 0.99-2.73). The risk ratio for preterm birth for all women diagnosed with COVID-19 and preeclampsia was 4.05 (95% confidence interval, 2.99-5.49) and 6.26 (95% confidence interval, 4.35-9.00) for nulliparous women. Compared with women with neither condition diagnosed, the composite adverse perinatal outcome showed a stepwise increase in the risk ratio for COVID-19 without preeclampsia, preeclampsia without COVID-19, and COVID-19 with preeclampsia (risk ratio, 2.16; 95% confidence interval, 1.63-2.86; risk ratio, 2.53; 95% confidence interval, 1.44-4.45; and risk ratio, 2.84; 95% confidence interval, 1.67-4.82, respectively). Similar findings were found for the composite adverse maternal outcome with risk ratios of 1.76 (95% confidence interval, 1.32-2.35), 2.07 (95% confidence interval, 1.20-3.57), and 2.77 (95% confidence interval, 1.66-4.63). The association between COVID-19 and gestational hypertension and the direction of the effects on preterm birth and adverse perinatal and maternal outcomes, were similar to preeclampsia, but confined to nulliparous women with lower risk ratios. CONCLUSION: COVID-19 during pregnancy is strongly associated with preeclampsia, especially among nulliparous women. This association is independent of any risk factors and preexisting conditions. COVID-19 severity does not seem to be a factor in this association. Both conditions are associated independently of and in an additive fashion with preterm birth, severe perinatal morbidity and mortality, and adverse maternal outcomes. Women with preeclampsia should be considered a particularly vulnerable group with regard to the risks posed by COVID-19.

Impact of mitigation measures against the COVID 19 pandemic on the perinatal results of the reference maternity hospital in Uruguay.

INTRODUCTION: Social consequences of pandemics, impacts on perinatal results, especially those who are the most vulnerable. OBJECTIVE: Determine effect of mitigation measures of the COVID 19 pandemic on perinatal results in the maternity hospital of the Pereira Rossell Hospital Center (CHPR). METHODS: A retrospective cross-sectional cohort study, with a comparative analysis of the semesters of March 15-30 September 2019 versus the same period in 2020 based on three variables low birth weight (LBW), preterm birth (PB), and small for gestational age (SGA). RESULTS: Incidence of PB (14.5%), LBW (12%) and SGA (6.9%) was higher in the 2020 semester during COVID 19 pandemic compared to the same period of 2019 (12.2%; 9.8%; 5.5%). PB showed a statistically significant increase of 21% in our hospital. CONCLUSION: Mitigation measures of the COVID 19 pandemic, aggravate the effects of the global syndemic on the reproductive process of the social sectors most violated in their rights.