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.

Pyroptosis: A Promising Mechanism Linking SARS-CoV-2 Infection to Adverse Pregnancy Outcomes.

Pregnancy is characterized by a delicate immune balance; therefore, infectious diseases might increase the risk of adverse pregnancy outcomes (APOs). Here, we hypothesize that pyroptosis, a unique cell death pathway mediated by the NLRP3 inflammasome, could link SARS-CoV-2 infection, inflammation, and APOs. Two blood samples were collected from 231 pregnant women at 11-13 weeks of gestation and in the perinatal period. At each time point, SARS-CoV-2 antibodies and neutralizing antibody titers were measured by ELISA and microneutralization (MN) assays, respectively. Plasmatic NLRP3 was determined by ELISA. Fourteen miRNAs selected for their role in inflammation and/or pregnancy were quantified by qPCR and further investigated by miRNA-gene target analysis. NLRP3 levels were positively associated with nine circulating miRNAs, of which miR-195-5p was increased only in MN+ women (p-value = 0.017). Pre-eclampsia was associated with a decrease in miR-106a-5p (p-value = 0.050). miR-106a-5p (p-value = 0.026) and miR-210-3p (p-value = 0.035) were increased in women with gestational diabetes. Women giving birth to small for gestational age babies had lower miR-106a-5p and miR-21-5p (p-values = 0.001 and 0.036, respectively), and higher miR-155-5p levels (p-value = 0.008). We also observed that neutralizing antibodies and NLRP3 concentrations could affect the association between APOs and miRNAs. Our findings suggest for the first time a possible link between COVID-19, NLRP3-mediated pyroptosis, inflammation, and APOs. Circulating miRNAs might be suitable candidates to gain a comprehensive view of this complex interplay.

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.

COVID-19 Booster Vaccination in Early Pregnancy and Surveillance for Spontaneous Abortion.

Importance: Adherence to COVID-19 booster vaccine recommendations has lagged in pregnant and nonpregnant adult populations. One barrier to booster vaccination is uncertainty regarding the safety of booster doses among pregnant people. Objective: To evaluate whether there is an association between COVID-19 booster vaccination during pregnancy and spontaneous abortion. Design, Setting, and Participants: This observational, case-control, surveillance study evaluated people aged 16 to 49 years with pregnancies at 6 to 19 weeks' gestation at 8 health systems in the Vaccine Safety Datalink from November 1, 2021, to June 12, 2022. Spontaneous abortion cases and ongoing pregnancy controls were evaluated during consecutive surveillance periods, defined by calendar time. Exposure: Primary exposure was receipt of a third messenger RNA (mRNA) COVID-19 vaccine dose within 28 days before spontaneous abortion or index date (midpoint of surveillance period in ongoing pregnancy controls). Secondary exposures were third mRNA vaccine doses in a 42-day window or any COVID-19 booster in 28- and 42-day windows. Main Outcomes and Measures: Spontaneous abortion cases and ongoing pregnancy controls were identified from electronic health data using a validated algorithm. Cases were assigned to a single surveillance period based on pregnancy outcome date. Eligible ongoing pregnancy time was assigned to 1 or more surveillance periods as an ongoing pregnancy-period control. Generalized estimating equations were used to estimate adjusted odds ratios (AOR) with gestational age, maternal age, antenatal visits, race and ethnicity, site, and surveillance period as covariates and robust variance estimates to account for inclusion of multiple pregnancy periods per unique pregnancy. Results: Among 112 718 unique pregnancies included in the study, the mean (SD) maternal age was 30.6 (5.5) years. Pregnant individuals were Asian, non-Hispanic (15.1%); Black, non-Hispanic (7.5%); Hispanic (35.6%); White, non-Hispanic (31.2%); and of other or unknown (10.6%); and 100% were female. Across eight 28-day surveillance periods, among 270 853 ongoing pregnancy-period controls, 11 095 (4.1%) had received a third mRNA COVID-19 vaccine in a 28-day window; among 14 226 cases, 553 (3.9%) had received a third mRNA COVID-19 vaccine within 28 days of the spontaneous abortion. Receipt of a third mRNA COVID-19 vaccine was not associated with spontaneous abortion in a 28-day window (AOR, 0.94; 95% CI, 0.86-1.03). Results were consistent when using a 42-day window (AOR, 0.97; 95% CI, 0.90-1.05) and for any COVID-19 booster in a 28-day (AOR, 0.94; 95% CI, 0.86-1.02) or 42-day (AOR, 0.96; 95% CI, 0.89-1.04) exposure window. Conclusions and Relevance: In this case-control surveillance study, COVID-19 booster vaccination in pregnancy was not associated with spontaneous abortion. These findings support the safety of recommendations for COVID-19 booster vaccination, including in pregnant populations.

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.

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.

Indirect effects of the COVID-19 pandemic on risk of gestational diabetes and factors contributing to increased risk in a multiethnic population: a retrospective cohort study.

BACKGROUND: The COVID-19 pandemic has had indirect effects on pregnancy outcomes. There is limited data on the impact on gestational diabetes (GDM) in diverse populations and the possible underlying mediators. This study aimed to assess the risk of GDM pre-COVID-19 and in two distinct pandemic exposure periods, and to determine the potential factors contributing to increased risk in a multiethnic population. METHODS: A multicentre, retrospective cohort study was performed of women with singleton pregnancy receiving antenatal care at three hospitals two years pre-COVID-19 (January 2018 - January 2020), first year of COVID-19 with limited pandemic-mitigating restrictions (February 2020 - January 2021) and second year of COVID-19 with stringent restrictions (February 2021 - January 2022). Baseline maternal characteristics and gestational weight gain (GWG) were compared between cohorts. The primary outcome was GDM, assessed using univariate and multivariate generalised estimating equations models. RESULTS: 28,207 pregnancies met the inclusion criteria, 14,663 pregnancies two years pre-COVID-19, 6,890 in COVID-19 Year 1 and 6,654 in COVID-19 Year 2. Maternal age increased across exposure periods (30.7 ± 5.0 years pre-COVID-19 vs 31.0 ± 5.0 years COVID-19 Year 1 vs 31.3 ± 5 years COVID-19 Year 2; p < 0.001). There were increases in pre-pregnancy body mass index (BMI) (25.5 ± 5.7 kg/m2 vs 25.7 ± 5.6 kg/m2 vs 26.1 ± 5.7 kg/m2; p < 0.001), proportion who were obese (17.5% vs 18.1% vs 20.7%; p < 0.001) and proportion with other traditional risk factors for GDM including South Asian ethnicity and prior history of GDM. Rate of GWG and proportion exceeding recommended GWG increased with pandemic exposure (64.3% vs 66.0% vs 66.6%; p = 0.009). GDM diagnosis increased across exposure periods (21.2% vs 22.9% vs 24.8%; p < 0.001). Both pandemic exposure periods were associated with increased risk of GDM on univariate analysis, only COVID-19 Year 2 remaining significantly associated after adjusting for maternal baseline characteristics and GWG (OR 1.17 [1.06, 1.28], p = 0.01). CONCLUSIONS: Diagnosis of GDM increased with pandemic exposure. Progressive sociodemographic changes and greater GWG may have contributed to increased risk. However, exposure to the second year of COVID-19 remained independently associated with GDM after adjusting for shifts in maternal characteristics and GWG.

Changes in birth outcomes and utilization of prenatal care during the COVID-19 pandemic in 2020: a secondary analysis of vital statistics in Colombia.

BACKGROUND: Birth outcomes could have been affected by the COVID-19 pandemic through changes in access to prenatal services and other pathways. The aim of this study was to examine the effects of the COVID-19 pandemic on fetal death, birth weight, gestational age, number of prenatal visits, and caesarean delivery in 2020 in Colombia. METHODS: We conducted a secondary analysis of data on 3,140,010 pregnancies and 2,993,534 live births from population-based birth certificate and fetal death certificate records in Colombia between 2016 and 2020. Outcomes were compared separately for each month during 2020 with the same month in 2019 and pre-pandemic trends were examined in regression models controlling for maternal age, educational level, marital status, type of health insurance, place of residence (urban/rural), municipality of birth, and the number of pregnancies the mother has had before last pregnancy. RESULTS: We found some evidence for a decline in miscarriage risk in some months after the pandemic start, while there was an apparent lagging increase in stillbirth risk, although not statistically significant after correction for multiple comparisons. Birth weight increased during the onset of the pandemic, a change that does not appear to be driven by pre-pandemic trends. Specifically, mean birth weight was higher in 2020 than 2019 for births in April through December by about 12 to 21 g (p < 0.01). There was also a lower risk of gestational age at/below 37 weeks in 2020 for two months following the pandemic (April, June), but a higher risk in October. Finally, there was a decline in prenatal visits in 2020 especially in June-October, but no evidence of a change in C-section delivery. CONCLUSIONS: The study findings suggest mixed early effects of the pandemic on perinatal outcomes and prenatal care utilization in Colombia. While there was a significant decline in prenatal visits, other factors may have had counter effects on perinatal health including an increase in birth weight on average.

COVID-19 vaccination during pregnancy: a systematic review and meta-analysis.

BACKGROUND: SARS-CoV-2 exposure during pregnancy is related to adverse effects for both the mother and the infant. SARS-CoV-2 vaccination has lowered the risk of symptomatic disease substantially. Recently published studies have evaluated the outcomes of women who received the COVID-19 vaccine during pregnancy; systematic evidence regarding vaccination safety is crucial to ensure that COVID-19 vaccination is not associated with adverse pregnancy and neonatal outcomes. METHODS: Pubmed/MEDLINE, EMBASE, Scopus, Web of Science, and Clinicaltrials.gov were searched from each database's inception through April 7, 2022. All interventional and observational studies comparing neonatal or pregnancy outcomes between pregnant women who received COVID-19 vaccines during their pregnancy and unvaccinated pregnant women were included. The random-effects model was used in the meta-analyses. RESULTS: A total of 11 studies comprising 756,098 pregnant mothers were included. The rate of neonates with 5-min Apgar score ≤ 7 (log RR -0.08 (95% CI: -0.15 to -0.00), (P = 0.03)) and pregnant mothers with preterm birth (log RR -0.11 (95% CI: -0.21 to -0.01), (P = 0.02)) was significantly lower among vaccinated group. No significant difference was observed in adverse neonatal outcomes (log RR -0.07 (95% CI: -0.17 to 0.03)), small for gestational age (log RR -0.06 (95% CI: -0.14 to 0.02)), caesarean delivery (log RR 0.05 (95% CI: -0.05 to 0.15)), postpartum hemorrhage (log RR -0.05 (95% CI: -0.13 to 0.02)), stillbirth (log RR -0.05 (95% CI: -0.54 to 0.45)). CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis, no evident differences were observed when comparing vaccinated pregnant mothers with those who had not received COVID-19 vaccines. Based on low certainty of evidence, vaccination during pregnancy was accompanied by a favorable Apgar score in neonates and fewer preterm births.

Impact of COVID-19 mandatory lockdown on maternal gestational weight gain and neonatal macrosomia rate at an academic medical center in Israel.

BACKGROUND: In an effort to prevent the spread of coronavirus disease 2019 (COVID-19), governments restricted outdoor activities and imposed lockdown quarantine. This change in lifestyle probably affected individuals' eating habits and physical activity. OBJECTIVE: To examine the effect of lockdown due to the COVID-19 pandemic on maternal antenatal weight gain, neonatal macrosomia, and other maternal and neonatal outcomes of women delivering at an academic medical center in Israel. METHOD: A retrospective, two-period cohort study conducted at a university teaching medical center in Afula, Israel. The study period was between April and September 2020. This period signifies worsening in pandemic situations, during which citizens experienced strict prolonged lockdown measures. The parallel unexposed period (control period) was between April and September 2019. Singleton pregnancies delivered at >24 weeks were eligible. Primary outcome was incidence of macrosomia. Secondary outcomes included gestational weight gain, body mass index (BMI) at delivery, rates of gestational diabetes mellitus (GDM), mode of delivery, postpartum hemorrhage (PPH), and neonatal outcomes reflecting neonatal birth weight and condition at delivery. RESULTS: A total of 4,765 women were included, 2,442 in the study group and 2,323 in the control group. The incidence of macrosomia was significantly higher in 2020 (6.2%) than in 2019 (4.9%), (p = .048; OR: 1.29; 95% CI: 1.002- 1.65). Women gained significantly more weight (median 1 kg more), weighed more at delivery (median 1 kg), and had higher BMI at delivery in 2020 compared with those in 2019 (p < .01). The incidence of GDM was 9.5% and 8.5% in the study and control groups respectively (p = .26; OR: 1.12; 95% CI: 0.92-1.37). Greater percentage of women did not perform the glucose challenge test in 2020 (9.9%) compared with those in 2019 (7.5%) (p = .003, OR: 1.36; 95% CI: 1.11-1.67). The incidence of any hypertension related to pregnancy was significantly higher in 2020 compared to 2019 (5.8% vs 4.4% respectively, (p = .042; OR: 1.32; 95% CI: 1.02-1.71). The proportion of women who smoked during pregnancy was also significantly higher in 2020 than in 2019 (5.1% vs 3.7%, respectively, p = .02; OR: 1.40; 95% CI: 1.06-1.86). Delivery mode did not differ, while the incidence of PPH was significantly higher in 2020 than in 2019 (5.6% vs 3.4%, respectively, p = .001; OR: 1.65; 95% CI: 1.25-2.19). Neonatal condition at delivery was comparable. CONCLUSION: COVID-19-related lockdown was associated with the increased rate of macrosomic infants. This indirect effect of the pandemic is probably related to poorer maternal antenatal metabolic health status. Long-term consequences should be further examined.

Anxiety and depression among pregnant women undergoing IVF-ET and WeChat group peer support during the COVID-19 pandemic: Study protocol for a randomized controlled trial.

INTRODUCTION: The psychological well-being of pregnant women following assisted reproductive has increasingly gained attention in recent years. Anxiety and depression may be associated to pregnancy outcomes. This study aims to determine whether peer support and the WeChat group platform will reduce anxiety and depression among in vitro fertilization and embryo transfer (IVF-ET) women. METHODS AND ANALYSIS: In the present randomized controlled study, 296 patients with confirmed clinical pregnancy following IVF-ET will be randomly assigned to receive standard intervention support or WeChat peer support on a 1:1 basis. The levels of anxiety and depression are the primary endpoints. Assessments will be performed at baseline measurements, first trimester, second trimester, and third trimester, and data will be collected. ETHICS AND DISSEMINATION: This study has been approved as ethical by the affiliated hospital of Shandong University of Traditional Chinese Medicine's Reproductive Ethics Committee. Each patient will sign a written statement of informed permission. All information and biological samples will be legally protected. A peer-reviewed academic journal will publish the findings of this investigation. DISCUSSION: Given the inconvenience of visits due to the current pandemic of COVID-19, this study addresses the patient's visit needs by combining WeChat, the most widely used social software in China, with peer support, while helping improve maternal anxiety, depression, and pregnancy outcomes following IVF-ET.

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.

Comparison of the clinical characteristics, glycemic control, and pregnancy outcomes between women with gestational diabetes mellitus in waves I and III of the COVID-19 pandemic: a reference center report.

OBJECTIVES: The medical care of patients with gestational diabetes mellitus (GDM) during the COVID-19 pandemic was influenced by changing epidemiological conditions and government regulations. Aim - To compare the clinical pregnancy data of GDM women between waves I and III of the pandemic. MATERIAL AND METHODS: We performed a retrospective analysis of medical records from the GDM clinic and compared the periods of March-May 2020 (wave I) and March-May 2021 (wave III). RESULTS: Women with GDM during wave I (n = 119) compared to wave III (n = 116) were older (33.0 ± 4.7 vs 32.1 ± 4.8 years; p = 0.07), booked later (21.8 ± 8.4 vs 20.3 ± 8.5 weeks; p = 0.17), and had their last appointment earlier (35.5 ± 2.0 vs 35.7 ± 3.2 weeks; p < 0.01). Telemedicine consultations were used more frequently during wave I (46.8% vs 24.1%; p < 0.01), while insulin therapy was used less often (64.7% vs 80.2%; p < 0.01). Mean fasting self-measured glucose did not differ (4.8 ± 0.3 vs 4.8 ± 0.3 mmol/L; p = 0.49), but higher postprandial glucose was reported during wave I (6.6 ± 0.9 vs 6.3 ± 0.6 mmol/l; p < 0.01). Pregnancy outcome data were available for 77 wave I pregnancies and 75 wave III pregnancies. The groups were similar in terms of gestational week of delivery (38.3 ± 1.4 vs 38.1 ± 1.6 weeks), cesarean sections (58.4% vs 61.3%), APGAR scores (9.7 ± 1.0 vs 9.7 ± 1.0 pts), and birth weights (3306.6 ± 457.6 g vs 3243.9 ± 496.8 g) (p = NS for all). The mean wave I neonate length was slightly higher (54.3 ± 2.6 cm vs 53.3 ± 2.6 cm; p = 0.04). CONCLUSIONS: We identified differences between wave I and wave III pregnancies for several clinical characteristics. However, nearly all pregnancy outcomes were found to be similar.

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.

Immunology of pregnancy and reproductive health in autoimmune rheumatic diseases. Update from the 11th International Conference on Reproduction, Pregnancy and Rheumatic Diseases.

Autoimmune rheumatic diseases (ARD) can affect women and men during fertile age, therefore reproductive health is a priority issue in rheumatology. Many topics need to be considered during preconception counselling: fertility, the impact of disease-related factors on pregnancy outcomes, the influence of pregnancy on disease activity, the compatibility of medications with pregnancy and breastfeeding. Risk stratification and individualized treatment approach elaborated by a multidisciplinary team minimize the risk of adverse pregnancy outcomes (APO). Research has been focused on identifying biomarkers that can be predictive of APO. Specifically, preeclampsia and hypertensive disorders of pregnancy tend to develop more frequently in women with ARD. Placental insufficiency can lead to intrauterine growth restriction and small-for-gestational age newborns. Such APO have been shown to be associated with maternal disease activity in different ARD. Therefore, a key message to be addressed to the woman wishing for a pregnancy and to her family is that treatment with compatible drugs is the best way to ensure maternal and fetal wellbeing. An increasing number of medications have entered the management of ARD, but data about their use in pregnancy and lactation are scarce. More information is needed for most biologic drugs and their biosimilars, and for the so-called small molecules, while there is sufficient evidence to recommend the use of TNF inhibitors if needed for keeping maternal disease under control. Other issues related to the reproductive journey have emerged as "unmet needs", such as sexual dysfunction, contraception, medically assisted reproduction techniques, long-term outcome of children, and they will be addressed in this review paper. Collaborative research has been instrumental to reach current knowledge and the future will bring novel insights thanks to pregnancy registries and prospective studies that have been established in several Countries and to their joint efforts in merging data.

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.

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.

Maternal and neonatal outcomes following SARS-CoV-2 infection.

Infection with SARS-CoV-2 causing COVID-19 in pregnancy is known to confer risks to both the pregnant patient and fetus. A review of the current literature demonstrates that pregnant individuals with SARS-CoV-2 infection are at risk for higher composite morbidity, intensive care unit admission, ventilatory support, pre-eclampsia, preterm birth, and neonatal intensive care unit admissions compared to pregnant individuals without SARS-CoV-2. Worse obstetric morbidity and mortality generally correlate with the severity of COVID-19. Comorbidities such as diabetes increase the risk of severe COVID-19. An increased risk of stillbirth appears to be predominantly confined to pregnancies affected in the Delta variant time period. Further, vaccination against SARS-CoV-2 has been demonstrated to be safe and effective in pregnancy and while breastfeeding. Therefore, continued counseling encouraging vaccination remains imperative. The long-term maternal and neonatal consequences of pregnancies affected by SARS-CoV-2 remain unknown, and therefore continued research in this regard is warranted.

No association of vaccination with inactivated COVID-19 vaccines before conception with pregnancy complications and adverse birth outcomes: A cohort study of 5457 Chinese pregnant women.

Data on the safety of inactivated COVID-19 vaccines in pregnant women is limited and monitoring pregnancy outcomes is required. We aimed to examine whether vaccination with inactivated COVID-19 vaccines before conception was associated with pregnancy complications or adverse birth outcomes. We conducted a birth cohort study in Shanghai, China. A total of 7000 healthy pregnant women were enrolled, of whom 5848 were followed up through delivery. Vaccine administration information was obtained from electronic vaccination records. Relative risks (RRs) of gestational diabetes mellitus (GDM), hypertensive disorders in pregnancy (HDP), intrahepatic cholestasis of pregnancy (ICP), preterm birth (PTB), low birth weight (LBW), and macrosomia associated with COVID-19 vaccination were estimated by multivariable-adjusted log-binomial analysis. After exclusion, 5457 participants were included in the final analysis, of whom 2668 (48.9%) received at least two doses of an inactivated vaccine before conception. Compared with unvaccinated women, there was no significant increase in the risks of GDM (RR = 0.80, 95% confidence interval [CI], 0.69, 0.93), HDP (RR = 0.88, 95% CI, 0.70, 1.11), or ICP (RR = 1.61, 95% CI, 0.95, 2.72) in vaccinated women. Similarly, vaccination was not significantly associated with any increased risks of PTB (RR = 0.84, 95% CI, 0.67, 1.04), LBW (RR = 0.85, 95% CI, 0.66, 1.11), or macrosomia (RR = 1.10, 95% CI, 0.86, 1.42). The observed associations remained in all sensitivity analyses. Our findings suggested that vaccination with inactivated COVID-19 vaccines was not significantly associated with an increased risk of pregnancy complications or adverse birth outcomes.