SARS-CoV-2 infection among preterm deliveries: frequency, determinants, effects. A retrospective cohort study in 2022.

OBJECTIVE: Pregnant women infected with SARS-CoV-2 are more likely to have obstetric complications, particularly preterm births, increasing the likelihood of maternal and neonatal morbidity and mortality. We tested the hypothesis by using a multivariable logistic regression analysis to take into account the effects of known confounding variables. PATIENTS AND METHODS: A retrospective cohort study targeted a random sample of 89 preterm deliveries at the Obstetrics and Gynecology Department, Zagazig University Hospital, from January 2022 to April 2022, who fulfilled the selection criteria using a pretested, well-structured questionnaire that was composed of three main parts. The collected data were coded and analyzed using appropriate statistical methods. RESULTS: This retrospective cohort study included 89 participants with a mean age of 26.6 years, 44.9% were middle-educated, 73% were not working, and the majority were not smoking or abusing substances. Regarding the frequency of COVID-19, dividing the studied participants into two groups, 22.5% had been infected, and there was no statistically significant difference between the two groups as regards the demographic characteristics, but smoking statistically increased the smoking (p-value = 0.034). Regarding the relationship between the history of COVID-19 and the past and present obstetric histories, there was no statistically significant difference between them. Even though the SARS-CoV-2 infection is significant (p-value = 0.037), pregnant women who are COVID-19 positive are more likely to have a cesarean section (16/80) than pregnant women who test positive. CONCLUSIONS: Pregnant and preterm women were more likely to get SARS-CoV-2 if they smoked, had comorbidities, or were overweight or obese. Among COVID-19 preterm pregnancies, substance misuse and comorbidity were risk factors for a poor neonatal outcome, while women who had a previous history of PPH, were smokers, or had comorbid illnesses had a significantly increased risk of having a poor maternal outcome.

Transient Decrease in Incidence Rate of Maternal Primary Cytomegalovirus Infection during the COVID-19 Pandemic in Japan.

This study evaluated the impact of the coronavirus disease 2019 (COVID-19) pandemic on the occurrence of maternal primary cytomegalovirus (CMV) infection in Japan. We performed a nested case-control study using data from maternal CMV antibody screening under the Cytomegalovirus in Mother and infant-engaged Virus serology (CMieV) program in Mie, Japan. Pregnant women with negative IgG antibodies at ≤20 weeks of gestation who were retested at ≥28 weeks were enrolled. The study period was divided into 2015-2019 as the pre-pandemic and 2020-2022 as the pandemic period, and the study site included 26 institutions conducting the CMieV program. The incidence rate of maternal IgG seroconversion was compared between the pre-pandemic (7008 women enrolled) and pandemic (2020, 1283 women enrolled; 2021, 1100 women; and 2022, 398 women) periods. Sixty-one women in the pre-pandemic period and five, four, and five women during 2020, 2021, and 2022, respectively, showed IgG seroconversion. The incidence rates in 2020 and 2021 were lower (p < 0.05) than that in the pre-pandemic period. Our data suggest a transient decrease in the incidence of maternal primary CMV infection in Japan during the COVID-19 pandemic, which could be due to prevention and hygiene measures taken at the population level.

Mother-to-child transmission of SARS-CoV-2 infection in high-income countries: a systematic review and meta-analysis of prospective observational studies.

Mother-to-child transmission of SARS-CoV-2 has been reported since the onset of the COVID-19 pandemic. We conducted a study to summarize evidence on the risk of mother-to-child transmission in the first 30 days after birth in high-income countries and to evaluate the association between preventive measures and the risk of infection for the neonate. A systematic review and meta-analysis were undertaken following PRISMA guidelines. The National Library of Medicine, Web of Science, and Excerpta Medica databases were screened on February 26, 2022. All prospective observational studies addressing the frequency of infection in infants born to mothers SARS-CoV-2 positive were included. Twenty-six studies were included, reporting data of 2653 mothers with SARS-CoV-2 and 2677 neonates. The proportion meta-analysis pointed out an overall estimate of SARS-CoV-2 infection among infants of 2.3% (95% CI: 1.4-3.2%). Data from studies with (1.4%, 95% CI: 0.8-2) and without (1.3%, 95% CI: 0.0-2.7%) rooming-in provided similar risk of infection. Adopting at least two prevention measures during rooming-in resulted in a rate of mother-to-child infection of 1.0% (95%CI: 0.3-1.7%). The results of this study show a low rate of perinatal infection, support the rooming-in and confirm the effectiveness of preventive measures in reducing the risk of mother-to-child viral transmission.

Influenza and pertussis vaccine coverage in pregnancy in Australia, 2016-2021.

Vaccination in pregnancy is the best strategy to reduce complications from influenza or pertussis infection in infants who are too young to be protected directly from vaccination. Pregnant women are also at risk of influenza complications preventable through antenatal vaccination. Both vaccines are funded under the National Immunisation Program for pregnant women in Australia, but coverage is not routinely reported nationally. We reviewed all reported Australian maternal influenza and pertussis vaccine coverage data for the period 2016-2021, to identify gaps and information needs. Maternal influenza vaccine coverage was suboptimal at < 58% for 2016-2018, with higher coverage of 62-75% reported in two states (Victoria and Western Australia) for 2019-2021. Maternal pertussis vaccine coverage from 2016 was generally higher than for influenza at > 70%, with the highest jurisdictional coverage of 89% reported in Western Australia in 2020. Vaccination rates were often suboptimal among First Nations pregnant women and up to 20% lower than among non-First Nations Australian women; while data were limited, coverage was low among culturally and linguistically diverse women and among women of lower socio-economic status. Jurisdictional perinatal data collections were the best source of information on antenatal vaccine coverage but were only available for a minority of the population; a nationally consistent systematic approach is lacking. Timely and comprehensive data are needed to provide feedback to improve maternal vaccination coverage, particularly among groups with higher risk and/or low uptake, and as new vaccines are recommended, including COVID-19 vaccination.

The impact of the COVID-19 pandemic on adverse fetal outcomes: A cross-sectional study.

The coronavirus disease 2019 (COVID-19) pandemic has been one of the most damaging pandemics in all of human history. Some of the most vulnerable groups within society such as pregnant women and children have also been affected. This observational research, cross-sectional study was conducted to investigate if there was any difference in the incidence of unfavorable outcomes in pregnancy such as miscarriage, intrauterine fetal demise, and early neonatal death during the year prior to the pandemic and the year of the COVID-19 pandemic. This retrospective study was conducted at the University Hospital of Split at the Department of Pathology, Forensic and Cytology and Department of Obstetrics and Gynecology of the same hospital. All data was collected in the time period from March 1st, 2019, to March 1st, 2021. The study included all pregnant women who had an unfavorable pregnancy outcome such as miscarriage and intrauterine fetal demise, as well as early neonatal death at the University Hospital of Split within the time frame mentioned previously. There was no statistically significant difference in the incidence of adverse pregnancy outcomes in the year prior to the pandemic and during the year of the COVID-19 pandemic. Our study showed that the pandemic did not have a negative effect on pregnant women and their fetuses; there was no increase in miscarriage, intrauterine fetal demise, or perinatal death during the year of the pandemic.

The effect of coronavirus disease 2019 on newborns.

PURPOSE OF REVIEW: To evaluate the available literature regarding effects of coronavirus disease 2019 (COVID-19) on newborns, ranging from effects related to in utero and perinatal exposure to maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, to pandemic-related stress and socioeconomic changes. RECENT FINDINGS: Several large studies and national registries have shown that the risk of vertical transmission from SARS-CoV-2-infected mothers to newborns is rare and does not appear to be related to postnatal care policies such as mother-newborn separation and breastfeeding. Newborns exposed to SARS-CoV-2 in utero are at higher risk for preterm delivery for reasons still under investigation. When newborns do acquire SARS-CoV-2 infection, their disease course is usually mild. Long-term follow-up data are lacking, but preliminary reports indicate that, similarly to prior natural disasters, being born during the pandemic may be associated with developmental risk. SUMMARY: Although risk of vertical or perinatal transmission is low across a range of postnatal care practices, early indicators suggest developmental risk to the generation born during the pandemic. Long-term follow-up data are critically needed to determine the developmental impact of in utero and early life exposure to SARS-CoV-2 and the COVID-19 pandemic.

Prevalence and impact of SARS-CoV-2 infection on maternal and infant health in African populations: protocol of a multicentre prospective cohort study (MA-CoV project).

INTRODUCTION: Pregnant women are currently considered a vulnerable population to SARS-CoV-2 infection, with increased risk of severe COVID-19, preterm birth and maternal mortality. There is, however, a paucity of data on the burden of maternal SARS-CoV-2 infection in sub-Saharan countries. The objective of this study is to determine the prevalence and health effects of maternal SARS-CoV-2 infection in selected sites from Gabon and Mozambique. METHODS AND ANALYSIS: MA-CoV (MAternal CoVid) is an observational, multicentre prospective cohort study where 1000 pregnant women (500 per country) will be enrolled at the antenatal clinic visits. Participants will undergo monthly follow-up at each antenatal care visit, delivery and postpartum visit. The primary study outcome is the prevalence of SARS-CoV-2 infection during pregnancy. The clinical presentation of COVID-19 in pregnancy will also be characterised, and incidence of infection during pregnancy will be evaluated, as well as the risk factors of maternal and neonatal morbidity and mortality associated with SARS-CoV-2 infection and the risk of mother to child transmission of SARS-CoV-2. SARS-CoV-2 infection screening will be performed through PCR diagnosis. ETHICS AND DISSEMINATION: The protocol was reviewed and approved by the Comité National d'Éthique pour la Recherche au Gabon, Comité Nacional de Bioética para Saúde de Moçambique and the Ethics Committee of the Hospital Clinic of Barcelona (Spain). Project results will be presented to all stakeholders and published in open access journals. TRIAL REGISTRATION NUMBER: NCT05303168.

Effect of COVID-19 on Pregnancy and Neonate's Vital Parameters: A Systematic Review.

Background: COVID-19 is a new pandemic, which was declared by the World Health Organization in 2019 as a threat to public health. According to numerous reports, it can have negative consequences for pregnant women, labour, and neonates born to infected mothers. The aim of this paper was to gather the evidence and to present a summary of the results of studies concerning COVID-19 in pregnant women and their neonates. Methods: Articles from prestigious journals covering the period from 2020 to February 2023, relevant review papers, and original research articles from PubMed were analysed. In order to analyse the available research literature, the Web of Science, Scopus, and PubMed databases were used, in which the search for articles was conducted using terms ("pregnancy," "coronavirus," "SARS-CoV-2," and "newborn") and using PRISMA (Preferred Reporting Items for Systemic Reviews and Meta-Analysis) guidelines for clinical trials. Meta-analyses and systematic reviews (2022-2023) on symptoms, neonatal course, and risk of COVID-19 infection have been summarized. Summary of meta-analyses and systematic reviews (2022-2023) on the effect and adverse reaction of the COVID-19 vaccination is presented. Results: As a result of the research conducted, it was confirmed that in most pregnant women, no serious signs of the infection were observed, although isolated cases of death related to COVID-19 in pregnant women were reported. Several authors called attention to the more severe course of the infection in pregnant women with obesity. It seemed that no vertical transmission from mother to child was occurring. Nevertheless, the information was not clinching. The condition of the neonates born to mothers with COVID-19 was in most cases described as normal; however, some papers reported deaths of infected neonates. Conclusions: Due to insufficient data, further research is necessary. Further studies and follow-up are recommended, which would make possible an assessment of remote effects of COVID-19 on pregnancy and vital parameters of the newborn.

Outcomes Following Extracorporeal Membrane Oxygenation for Severe COVID-19 in Pregnancy or Post Partum.

Importance: Existing reports of pregnant patients with COVID-19 disease who require extracorporeal membrane oxygenation (ECMO) are limited, with variable outcomes noted for the maternal-fetal dyad. Objective: To examine maternal and perinatal outcomes associated with ECMO used for COVID-19 with respiratory failure during pregnancy. Design, Setting, and Participants: This retrospective multicenter cohort study examined pregnant and postpartum patients who required ECMO for COVID-19 respiratory failure at 25 hospitals across the US. Eligible patients included individuals who received care at one of the study sites, were diagnosed with SARS-CoV-2 infection during pregnancy or up to 6 weeks post partum by positive nucleic acid or antigen test, and for whom ECMO was initiated for respiratory failure from March 1, 2020, to October 1, 2022. Exposures: ECMO in the setting of COVID-19 respiratory failure. Main outcome and measures: The primary outcome was maternal mortality. Secondary outcomes included serious maternal morbidity, obstetrical outcomes, and neonatal outcomes. Outcomes were compared by timing of infection during pregnancy or post partum, timing of ECMO initiation during pregnancy or post partum, and periods of circulation of SARS-CoV-2 variants. Results: From March 1, 2020, to October 1, 2022, 100 pregnant or postpartum individuals were started on ECMO (29 [29.0%] Hispanic, 25 [25.0%] non-Hispanic Black, 34 [34.0%] non-Hispanic White; mean [SD] age: 31.1 [5.5] years), including 47 (47.0%) during pregnancy, 21 (21.0%) within 24 hours post partum, and 32 (32.0%) between 24 hours and 6 weeks post partum; 79 (79.0%) had obesity, 61 (61.0%) had public or no insurance, and 67 (67.0%) did not have an immunocompromising condition. The median (IQR) ECMO run was 20 (9-49) days. There were 16 maternal deaths (16.0%; 95% CI, 8.2%-23.8%) in the study cohort, and 76 patients (76.0%; 95% CI, 58.9%-93.1%) had 1 or more serious maternal morbidity events. The largest serious maternal morbidity was venous thromboembolism and occurred in 39 patients (39.0%), which was similar across ECMO timing (40.4% pregnant [19 of 47] vs 38.1% [8 of 21] immediately postpartum vs 37.5% postpartum [12 of 32]; P > .99). Conclusions and Relevance: In this multicenter US cohort study of pregnant and postpartum patients who required ECMO for COVID-19-associated respiratory failure, most survived but experienced a high frequency of serious maternal morbidity.

Fetal death as an outcome of acute respiratory distress in pregnancy, during the COVID-19 pandemic: a population-based cohort study in Bahia, Brazil.

BACKGROUND: Fetal loss is one of the most serious adverse outcomes of pregnancy. Since the onset of the COVID-19 pandemic, Brazil has recorded an unprecedented number of hospitalizations of pregnant women due to acute respiratory distress (ARD), thereby, we aimed to assess the risk of fetal deaths associated to ARD during pregnancy in Bahia state, Brazil, in the context of the COVID-19 pandemic. METHODS: This is an observational population-based retrospective cohort study, developed with women at or after 20 weeks of pregnancy, residents in Bahia, Brazil. Women who had acute respiratory distress (ARD) in pregnancy during the COVID-19 pandemic (Jan 2020 to Jun 2021) were considered 'exposed'. Women who did not have ARD in pregnancy, and whose pregnancy occurred before the onset of the COVID-19 pandemic (Jan 2019 to Dec 2019) were considered 'non-exposed'. The main outcome was fetal death. We linked administrative data (under mandatory registration) on live births, fetal deaths, and acute respiratory syndrome, using a probabilistic linkage method, and analyzed them with multivariable logistic regression models. RESULTS: 200,979 pregnant women participated in this study, 765 exposed and 200,214 unexposed. We found four times higher chance of fetal death in women with ARD during pregnancy, of all etiologies (adjusted odds ratio [aOR] 4.06 confidence interval [CI] 95% 2.66; 6.21), and due to SARS-CoV-2 (aOR 4.45 CI 95% 2.41; 8.20). The risk of fetal death increased more when ARD in pregnancy was accompanied by vaginal delivery (aOR 7.06 CI 95% 4.21; 11.83), or admission to Intensive Care Unit (aOR 8.79 CI 95% 4.96; 15.58), or use of invasive mechanical ventilation (aOR 21.22 CI 95% 9.93; 45.36). CONCLUSION: Our findings can contribute to expanding the understanding of health professionals and managers about the harmful effects of SARS-CoV-2 on maternal-fetal health and alerts the need to prioritize pregnant women in preventive actions against SARS-CoV-2 and other respiratory viruses. It also suggests that pregnant women, infected with SARS-CoV-2, need to be monitored to prevent complications of ARD, including a careful assessment of the risks and benefits of early delivery to prevent fetal death.

Pregnancy outcomes after SARS-CoV-2 infection in periods dominated by delta and omicron variants in Scotland: a population-based cohort study.

BACKGROUND: Evidence suggests that the SARS-CoV-2 omicron (B.1·1.529) is associated with lower risks of adverse outcomes than the delta (B.1.617.2) variant among the general population. However, little is known about outcomes after omicron infection in pregnancy. We aimed to assess and compare short-term pregnancy outcomes after SARS-CoV-2 delta and omicron infection in pregnancy. METHODS: We did a national population-based cohort study of women who had SARS-CoV-2 infection in pregnancy between May 17, 2021, and Jan 31, 2022. The primary maternal outcome was admission to critical care within 21 days of infection or death within 28 days of date of infection. Pregnancy outcomes were preterm birth and stillbirth within 28 days of infection. Neonatal outcomes were death within 28 days of birth, and low Apgar score (<7 of 10, for babies born at term) or neonatal SARS-CoV-2 infection in births occurring within 28 days of maternal infection. We used periods when variants were dominant in the general Scottish population, based on 50% or more of cases being S-gene positive (delta variant, from May 17 to Dec 14, 2021) or S-gene negative (omicron variant, from Dec 15, 2021, to Jan 31, 2022) as surrogates for variant infections. Analyses used logistic regression, adjusting for maternal age, deprivation quintile, ethnicity, weeks of gestation, and vaccination status. Sensitivity analyses included restricting the analysis to those with first confirmed SARS-CoV-2 infection and using periods when delta or omicron had 90% or more predominance. FINDINGS: Between May 17, 2021, and Jan 31, 2022, there were 9923 SARS-CoV-2 infections in 9823 pregnancies, in 9817 women in Scotland. Compared with infections in the delta-dominant period, SARS-CoV-2 infections in pregnancy in the omicron-dominant period were associated with lower maternal critical care admission risk (0·3% [13 of 4968] vs 1·8% [89 of 4955]; adjusted odds ratio 0·25, 95% CI 0·14-0·44) and lower preterm birth within 28 days of infection (1·8% [37 of 2048] vs 4·2% [98 of 2338]; 0·57, 95% CI 0·38-0·87). There were no maternal deaths within 28 days of infection. Estimates of low Apgar scores were imprecise due to low numbers (5 [1·2%] of 423 with omicron vs 11 [2·1%] of 528 with delta, adjusted odds ratio 0·72, 0·23-2·32). There were fewer stillbirths in the omicron-dominant period than in the delta-dominant period (4·3 [2 of 462] per 1000 births vs 20·3 [13 of 639] per 1000) and no neonatal deaths during the omicron-dominant period (0 [0 of 460] per 1000 births vs 6·3 [4 of 626] per 1000 births), thus numbers were too small to support adjusted analyses. Rates of neonatal infection were low in births within 28 days of maternal SARS-CoV-2 infection, with 11 cases of neonatal SARS-CoV-2 in the delta-dominant period, and 1 case in the omicron-dominant period. Of the 15 stillbirths, 12 occurred in women who had not received two or more doses of COVID-19 vaccination at the time of SARS-CoV-2 infection in pregnancy. All 12 cases of neonatal SARS-CoV-2 infection occurred in women who had not received two or more doses of vaccine at the time of maternal infection. Findings in sensitivity analyses were similar to those in the main analyses. INTERPRETATION: Pregnant women infected with SARS-CoV-2 were substantially less likely to have a preterm birth or maternal critical care admission during the omicron-dominant period than during the delta-dominant period. FUNDING: Wellcome Trust, Tommy's charity, Medical Research Council, UK Research and Innovation, Health Data Research UK, National Core Studies-Data and Connectivity, Public Health Scotland, Scottish Government Health and Social Care, Scottish Government Chief Scientist Office, National Research Scotland.

COVID-19, maternal, and neonatal outcomes: National Mother-Child Cohort (NMCC) of K-COV-N cohort in South Korea.

Throughout the COVID-19 pandemic, pregnant women have been classified as a vulnerable population. However, the evidence on the effect of infection during pregnancy on maternal and neonatal outcomes is still uncertain, and related research comprising a large population of pregnant women in Asian countries is limited. We constructed a national cohort including mothers and children (369,887 pairs) registered in the Prevention Agency-COVID-19-National Health Insurance Service (COV-N), from January 1, 2020 to March 31, 2022. We performed propensity score matchings and generalized estimation equation models to estimate the effect of COVID-19 on maternal and neonatal outcomes. In summary, we found little evidence of the effect of COVID-19 infection during pregnancy on maternal and neonatal outcomes; however, a relationship between COVID-19 infection in the second trimester and postpartum hemorrhages was discovered (Odds ratio (OR) of Delta period: 2.26, 95% Confidence intervals (CI): 1.26, 4.05). In addition, neonatal intensive care unit (NICU) admissions increased due to COVID-19 infection (pre-Delta period: 2.31, 95% CI: 1.31, 4.10; Delta period: 1.99, 95% CI: 1.47, 2.69; Omicron period: 2.36, 95% CI: 1.75, 3.18). Based on the national retrospective cohort study data, this study investigated the effects of COVID-19 infection on maternal and neonatal outcomes in Korea from the pre-Delta to the initial Omicron epidemic periods. Our evidence suggests that the timely and successful policies of the government and academia in response to COVID-19 infections in newborns in Korea may cause an increase in NICU admissions, but nonetheless, they prevent adverse maternal and neonatal outcomes simultaneously.

Factors associated with having COVID-19 among unvaccinated pregnant and non-pregnant women in Metro Manila, Philippines: a multicentre longitudinal cohort study.

OBJECTIVE: To determine the potential risk factors associated with having COVID-19 among unvaccinated pregnant and non-pregnant women. DESIGN: A multicentre prospective cohort study among eligible women in Metro Manila, Philippines, from 2020 to 2022. SETTING: Five national and local hospital research sites altogether recruited and screened 500 consenting eligible individuals. PARTICIPANTS: Pregnant and non-pregnant participants meeting the eligibility criteria were admitted for a reverse-transcription PCR determination of SARS-CoV-2, pregnancy testing and ultrasound, and an interview with an administered questionnaire. EXPOSURES: Primary exposure was pregnancy; secondary exposures involve sociodemographic, lifestyle and obstetric-gynaecologic factors. OUTCOME MEASURE: Outcome being measured was COVID-19 status. RESULTS: The significant COVID-19 risk factors were: pregnancy (PR=1.184, 95% CI 1.096, 1.279), having a white-collar job (PR=1.123, 95% CI 1.02, 1.235), travelling abroad (PR=1.369, 95% CI 1.083, 1.173) and being infected by at least one vaccine-preventable disease (VPD) (PR=1.208, 95% CI 1.113, 1.310). Protective factors included having graduate-level education (PR=0.787, 95% CI 0.649, 0.954), immunisation against a VPD (PR=0.795, 95% CI 0.733, 0.862) and practising contraception (PR=0.889, 95% CI 0.824, 0.960). CONCLUSION: This study is the first in the country to determine the risks influencing COVID-19 infection among unvaccinated pregnant and non-pregnant women. Pregnancy is a significant risk for COVID-19 among women in Metro Manila. Educational attainment and positive health behaviours seem to confer protection. Occupations and activities that increase the frequency of interactions, as well as history of communicable diseases may predispose women to COVID-19. Further studies are needed to elucidate the development of the disease in pregnant women, including the maternal and neonatal effects of COVID-19 via potential vertical mechanisms of transmission.

Incidence of congenital complications related to COVID-19 infection during pregnancy.

PURPOSE: Infection with COVID-19 during pregnancy has been associated with a hypercoagulable state. It is unknown if maternal COVID-19 infection results in congenital anomalies secondary to intrauterine vascular accidents. This study sought to determine if the rate of in-utero vascular complications (intestinal atresia and limb abnormalities) that may be attributable to the hypercoagulable states associated with COVID-19 and pregnancy increased after the onset of the pandemic. METHODS: Pregnancy, neonatal, and congenital defect data from a single academic medical center and the partner's children's hospital were collected and compared to the period prior to onset of the pandemic. A subanalysis including pregnant woman 18 years or greater with documented COVID-19 infection during gestation between March 2020-2021 was performed. RESULTS: Rates of intestinal atresia did not differ prior to or after the onset of the pandemic (3.78% vs 7.23%, p = 0.21) nor did rates of limb deficiency disorders (4.41% vs 9.65%, p = 0.09). On subanalysis, there were 194 women with COVID-19 infection included in analysis: 135 (69.6%) were positive during delivery admission and 59 (30.4%) were positive earlier in their pregnancy. There was one infant born with intestinal atresia. CONCLUSION: We report a low incidence of congenital anomalies in infants born to mothers with COVID-19 infection. It remains unclear if the impact of COVID-19 on the coagulative state augments the normal pro-thrombotic state of pregnancy; ongoing surveillance is warranted.

Assessment of Neurodevelopment in Infants With and Without Exposure to Asymptomatic or Mild Maternal SARS-CoV-2 Infection During Pregnancy.

Importance: Associations between prenatal SARS-CoV-2 exposure and neurodevelopmental outcomes have substantial public health relevance. A previous study found no association between prenatal SARS-CoV-2 infection and parent-reported infant neurodevelopmental outcomes, but standardized observational assessments are needed to confirm this finding. Objective: To assess whether mild or asymptomatic maternal SARS-CoV-2 infection vs no infection during pregnancy is associated with infant neurodevelopmental differences at ages 5 to 11 months. Design, Setting, and Participants: This cohort study included infants of mothers from a single-site prospective cross-sectional study (COVID-19 Mother Baby Outcomes [COMBO] Initiative) of mother-infant dyads and a multisite prospective cohort study (Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2 in Pregnancy and Infancy [ESPI]) of pregnant individuals. A subset of ESPI participants was subsequently enrolled in the ESPI COMBO substudy. Participants in the ongoing COMBO study were enrolled beginning on May 26, 2020; participants in the ESPI study were enrolled from May 7 to November 3, 2021; and participants in the ESPI COMBO substudy were enrolled from August 2020 to March 2021. For the current analysis, infant neurodevelopment was assessed between March 2021 and June 2022. A total of 407 infants born to 403 mothers were enrolled (204 from Columbia University Irving Medical Center in New York, New York; 167 from the University of Utah in Salt Lake City; and 36 from the University of Alabama in Birmingham). Mothers of unexposed infants were approached for participation based on similar infant gestational age at birth, date of birth, sex, and mode of delivery to exposed infants. Exposures: Maternal symptomatic or asymptomatic SARS-CoV-2 infection. Main Outcomes and Measures: Infant neurodevelopment was assessed using the Developmental Assessment of Young Children, second edition (DAYC-2), adapted for telehealth assessment. The primary outcome was age-adjusted standard scores on 5 DAYC-2 subdomains: cognitive, gross motor, fine motor, expressive language, and receptive language. Results: Among 403 mothers, the mean (SD) maternal age at delivery was 32.1 (5.4) years; most mothers were of White race (240 [59.6%]) and non-Hispanic ethnicity (253 [62.8%]). Among 407 infants, 367 (90.2%) were born full term and 212 (52.1%) were male. Overall, 258 infants (63.4%) had no documented prenatal exposure to SARS-CoV-2 infection, 112 (27.5%) had confirmed prenatal exposure, and 37 (9.1%) had exposure before pregnancy or at an indeterminate time. In adjusted models, maternal SARS-CoV-2 infection during pregnancy was not associated with differences in cognitive (ß = 0.31; 95% CI, -2.97 to 3.58), gross motor (ß = 0.82; 95% CI, -1.34 to 2.99), fine motor (ß = 0.36; 95% CI, -0.74 to 1.47), expressive language (ß = -1.00; 95% CI, -4.02 to 2.02), or receptive language (ß = 0.45; 95% CI, -2.15 to 3.04) DAYC-2 subdomain scores. Trimester of exposure and maternal symptom status were not associated with DAYC-2 subdomain scores. Conclusions and Relevance: In this study, results of a novel telehealth-adapted observational neurodevelopmental assessment extended a previous finding of no association between prenatal exposure to maternal SARS-CoV-2 infection and infant neurodevelopment. Given the widespread and continued high prevalence of COVID-19, these data offer information that may be helpful for pregnant individuals who experience asymptomatic or mild SARS-CoV-2 infections.

Residual risk of mother-to-child transmission of HBV despite timely Hepatitis B vaccination: a major challenge to eliminate hepatitis B infection in Cambodia.

BACKGROUND: In countries with intermediate or high hepatitis B virus (HBV) endemicity, mother-to-child transmission (MTCT) represents the main route of chronic HBV infection. There is a paucity of information on HBV MTCT in Cambodia. This study aimed to investigate the prevalence of HBV infection among pregnant women and its MTCT rate in Siem Reap, Cambodia. METHODS: This longitudinal study included two parts, study-1 to screen HBsAg among pregnant women and study-2 to follow up babies of all HBsAg-positive and one-fourth of HBsAg-negative mothers at their delivery and six-month post-partum. Serum or dried blood spot (DBS) samples were collected to examine HBV sero-markers by chemiluminescent enzyme immunoassay (CLEIA), and molecular analyses were performed on HBsAg-positive samples. Structured questionnaires and medical records were used to examine the risk factors for HBV infection. MTCT rate was calculated by HBsAg positivity of 6-month-old babies born to HBsAg-positive mothers and ascertained by the homology of HBV genomes in mother-child pair at 6-month-old. RESULTS: A total of 1,565 pregnant women were screened, and HBsAg prevalence was 4.28% (67/1565). HBeAg positivity was 41.8% and was significantly associated with high viral load (p < 0.0001). Excluding subjects who dropped out due to restrictions during COVID-19, one out of 35 babies born to HBsAg-positive mothers tested positive for HBsAg at 6 months of age, despite receiving timely HepB birth dose and HBIG, followed by 3 doses of HepB vaccine. Hence the MTCT rate was 2.86%. The mother of the infected baby was positive for HBeAg and had a high HBV viral load (1.2 × 109 copies/mL). HBV genome analysis showed 100% homology between the mother and the child. CONCLUSIONS: Our findings illustrate the intermediate endemicity of HBV infection among pregnant women in Siem Reap, Cambodia. Despite full HepB vaccination, a residual risk of HBV MTCT was observed. This finding supports the recently updated guidelines for the prevention of HBV MTCT in 2021, which integrated screening and antiviral prophylaxis for pregnant women at risk of HBV MTCT. Furthermore, we strongly recommend the urgent implementation of these guidelines nationwide to effectively combat HBV in Cambodia.

Analysis of placental pathology after COVID-19 by timing and severity of infection.

BACKGROUND: COVID-19 during pregnancy can have serious effects on pregnancy outcomes. The placenta acts as an infection barrier to the fetus and may mediate adverse outcomes. Increased frequency of maternal vascular malperfusion has been detected in the placentas of patients with COVID-19 compared with controls, but little is known about how the timing and severity of infection affect placental pathology. OBJECTIVE: This study aimed to examine the effects of SARS-CoV-2 infection on placental pathology, specifically whether the timing and severity of COVID-19 affect pathologic findings and associations with perinatal outcomes. STUDY DESIGN: This was a descriptive retrospective cohort study of pregnant people diagnosed with COVID-19 who delivered between April 2020 and September 2021 at 3 university hospitals. Demographic, placental, delivery, and neonatal outcomes were collected through medical record review. The timing of SARS-CoV-2 infection was noted, and the severity of COVID-19 was categorized on the basis of the National Institutes of Health guidelines. The placentas of all patients with positive nasopharyngeal reverse transcription-polymerase chain reaction COVID-19 testing were sent for gross and microscopic histopathologic examinations at the time of delivery. Nonblinded pathologists categorized histopathologic lesions according to the Amsterdam criteria. Univariate linear regression and chi-square analyses were used to assess how the timing and severity of SARS-CoV-2 infection affected placental pathologic findings. RESULTS: This study included 131 pregnant patients and 138 placentas, with most patients delivered at the University of California, Los Angeles (n=65), followed by the University of California, San Francisco (n=38) and Zuckerberg San Francisco General Hospital (n=28). Most patients were diagnosed with COVID-19 in the third trimester of pregnancy (69%), and most infections were mild (60%). There was no specific placental pathologic feature based on the timing or severity of COVID-19. There was a higher frequency of placental features associated with response to infection in the placentas from infections before 20 weeks of gestation than that from infections after 20 weeks of gestation (P=.001). There was no difference in maternal vascular malperfusion by the timing of infection; however, features of severe maternal vascular malperfusion were only found in the placentas of patients with SARS-CoV-2 infection in the second and third trimesters of pregnancy, not in the placentas of patients with COVID-19 in the first trimester of pregnancy. CONCLUSION: Placentas from patients with COVID-19 showed no specific pathologic feature, regardless of the timing or severity of the disease. There was a higher proportion of placentas from patients with COVID-19-positive tests in earlier gestations with evidence of placental infection-associated features. Future studies should focus on understanding how these placental features in SARS-CoV-2 infections go on to affect pregnancy outcomes.