Transaminitis as a predictor of poor clinical outcomes in pregnant patients infected with COVID-19: retrospective case series (preprint)

Objective: The objective of this study is to identify the effects of Coronavirus Disease 2019 (COVID-19) on liver enzymes in pregnant patients and to determine the significance of transaminitis as a predictor of worse clinical outcomes. Design: Case series. Setting: Tertiary care medical center. Population: 31 pregnant patients with a positive COVID-19 polymerase chain reaction (PCR) test and 20 infants who presented during March 25, 2020, to May 26, 2020. Methods: Maternal and neonatal outcomes were compared between patients with transaminitis and without transaminitis using one tailed Mann-Whitney test for nonparametric data and the fisher’s exact test for categorical data. Main outcome measures: Worse maternal outcomes between the groups were defined as need for intubation, oxygen supplementation, intensive care unit (ICU) admission, maternal death, and length of hospital stay. Results: Of the 31 patients with COVID-19, 10/29 (34.5%) were found to have transaminitis. The patients with transaminitis had increased oxygen requirements, increased rate of intubation and ICU admissions. Neonatal outcomes in patients with transaminitis included earlier gestational age at delivery and lower birth weights, but neither were statistically significant. Conclusion: Our study revealed that patients with COVID-19 and concomitant transaminitis had worse clinical outcomes in the mother when compared to those without transaminitis. Further studies should be conducted to explore this link between abnormal liver studies and poor outcomes in pregnant patients diagnosed with COVID-19. Keywords: Coronavirus, COVID-19, transaminitis, pregnancy Tweetable abstract: Pregnant patients with COVID-19 and transaminitis had worse outcomes than ones without transaminitis.

Analysis of pathogenic factors of retinopathy of prematurity in Heilongjiang Province (preprint)

Background and purpose Retinopathy of prematurity is a vascular development disorder in immature retinas of premature infants, which is the leading cause of blindness in children worldwide. Because the screening delay may lead to the occurrence of blindness in children, it is particularly important to conduct timely screening for children with high risk factors. Currently, the pathogenesis of ROP may be related to multiple factors such as gestational age and birth weight of premature infants. In this study, the prevalence and risk factors of ROP in Heilongjiang Province were determined through screening for premature infants in the region, aiming to proceed early prevention of the disease. Methods Retrospectively analyzed 714 premature infants admitted to the Ophthalmology Clinic of the Second Affiliated Hospital of Harbin Medical University from January 2016 to February 2022. 12 related factors was recorded including patients’ gender, gestational age, birth weight, oxygen duration, blood transfusions, anemia, neonatal infections, respiratory distress syndrome, maternal feeding way, childbirth way, pregnancy age and parity. The prevalence of ROP and the differences in related factors between ROP patientsand non-ROP patients were found. Results Among 714 premature infants, 188 had ROP of which the incidence is 26.3%，and 61 patients received treatment. There were statistically significance(P<0.05) in gestational age, birth weight, oxygen duration, blood transfusion, anemia, neonatal infection, respiratory distress syndrome and childbirth way between the 188 ROP patients and non-ROP patients in univariate regression analysis. Variables with statistical significance for single factor were selected and conducted by multivariate regression analysis, which showed that gestational age, birth weight, and oxygen duration had remarkable statistical significance(P<0.05) with the occurrence of ROP. Gestational age and birth weight were the protective factors of disease (OR=0.43 and OR=0.8), while oxygen duration was the risk factor of disease (OR=1.02), and the diagnostic value of the model was high (AUC=0.776). five of the 61 patients who received treatment for ROP accepted two treatments, with gestational age < 32 weeks, birth weight < 1500g, and oxygen inhalation time > 20 days. The Kendall grade relative analysis of 188 patients with ROP showed that disease severity was significantly correlated with gestational age, birth weight, oxygen duration, anemia, blood transfusion and respiratory distress syndrome(P<0.05), in which the gestational age, birth weight, anemia, blood transfusion and respiratory distress syndrome were negatively correlated with the severity of the disease, while oxygen duration was positively correlated with severity of the disease. 507 children were screened from 2016 to December 31th in 2019, 138 of which were ROP patients, 36 children were treated (7.1%). Due to the spread of the COVID-19, 207 children were screened after January 1th in 2020, 50 children were ROP patients, and 25 of whom got treatment (12%), 21were treated after 8 weeks of birth or more than 37 weeks of corrected gestational age. Four out of five children who received the second treatment happened after the epidemic, and three of them missed treatment due to the epidemic. Conclusions The gestational age, birth weight and oxygen duration are significantly correlated with the incidence and severity of the disease in premature infants screening of Heilongjiang Province. Premature infants screening and subsequent visit were affected due to the spread of the COVID-19 in the past two years, the proportion of children needed to be cured augmented apparently, therefore, it matters a lot for premature infants to be screened standardly and timely.

The frequency of respiratory care among neonates who had perinatal exposure to Sars-COV-2 at Ayatollah Mousavi Hospital in Zanjan 2020-2022 (preprint)

Background A significant heterogeneity of the complications is evident among neonates who had perinatal exposure to Sars-COV-2 in different countries. The purpose of this study was to determine the frequency of respiratory care among neonates who had perinatal exposure to Sars-COV-2 at Ayatollah Mousavi Hospital in Zanjan 2020–2022Methods A descriptive cross-sectional study was conducted on 78 infants who had prenatal exposure to Sars-COV-2 at Ayatollah Mousavi Hospital in Zanjan from the beginning of from April 2020 to the end of March 2022. The data was collected using a researcher-made checklist and analyzed using descriptive statistics test and chi -Square test at a 95% confidence level.Results Out of 78 eligible babies the Polymerase Chain Reaction (PCR) test of 9 infants (11.5%) was positive after birth. More than 60 percent of infants needed a variety of respiratory care, with the highest percentage related to using an oxygen hood. The need to get respiratory care was not significantly related to infants' test status for COVID-19 but had a significant relationship with birth weight (p = 0.016).Conclusion The results showed a high rate of respiratory care needs in infants born to mothers with known Sars-COV-2 infection. Implementation of training programs to prevent infection and access to intensive care is recommended to improve neonatal outcomes.

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.

National data linkage assessment of live births and deaths in Mexico: Estimating under-five mortality rate ratios for vulnerable newborns and trends from 2008 to 2019.

BACKGROUND: Linked datasets that enable longitudinal assessments are scarce in low and middle-income countries. OBJECTIVES: We aimed to assess the linkage of administrative databases of live births and under-five child deaths to explore mortality and trends for preterm, small (SGA) and large for gestational age (LGA) in Mexico. METHODS: We linked individual-level datasets collected by National statistics from 2008 to 2019. Linkage was performed based on agreement on birthday, sex, residential address. We used the Centre for Data and Knowledge Integration for Health software to identify the best candidate pairs based on similarity. Accuracy was assessed by calculating the area under the receiver operating characteristic curve. We evaluated completeness by comparing the number of linked records with reported deaths. We described the percentage of linked records by baseline characteristics to identify potential bias. Using the linked dataset, we calculated mortality rate ratios (RR) in neonatal, infants, and children under-five according to gestational age, birthweight, and size. RESULTS: For the period 2008-2019, a total of 24,955,172 live births and 321,165 under-five deaths were available for linkage. We excluded 1,539,046 records (6.2%) with missing or implausible values. We succesfully linked 231,765 deaths (72.2%: range 57.1% in 2009 and 84.3% in 2011). The rate of neonatal mortality was higher for preterm compared with term (RR 3.83, 95% confidence interval, [CI] 3.78, 3.88) and for SGA compared with appropriate for gestational age (AGA) (RR 1.22 95% CI, 1.19, 1.24). Births at <28 weeks had the highest mortality (RR 35.92, 95% CI, 34.97, 36.88). LGA had no additional risk vs AGA among children under five (RR 0.92, 95% CI, 0.90, 0.93). CONCLUSIONS: We demonstrated the utility of linked data to understand neonatal vulnerability and child mortality. We created a linked dataset that would be a valuable resource for future population-based research.

The impact of the COVID-19 lockdown on retinopathy of prematurity screening and management in the United States: a multicenter study.

PURPOSE: To study the effect of the pandemic-related lockdown (physical distance measures and movement restrictions) on the characteristics and management of retinopathy of prematurity (ROP). METHODS: In this controlled, multicenter cohort study, the medical records of patients born prematurely and screened for ROP in the neonatal intensive care unit during four time periods were reviewed retrospectively: (1) November 1, 2018, to March 15, 2019; (2) March 16, 2019, to August 2, 2019 (lockdown control period); (3) November 1, 2019, to March 15, 2020; and (4) March 16, 2020-August 2, 2020. RESULTS: A total of 1,645 patients met inclusion criteria. Among the 1,633 patients with complete data, mean gestational age (GA) at birth was 28.2, 28.4, 28.0, and 28.3 weeks across time periods 1 to 4, respectively (P = 0.16). The mean birth weight of all patients was 1079.1 ± 378.60 g, with no significant variation across time periods (P = 0.08). There were fewer patients screened during the lockdown period (n = 411) compared with the period immediately before (n = 491) and the same period in the prior year (n = 533). Significantly more patients were screened using indirect ophthalmoscopy, compared to digital imaging (telemedicine), during the lockdown (P < 0.01). There were 11.7%, 7.7%, 9.0%, and 8.8% of patients requiring treatment in each time period, respectively (P = 0.42), with a median postmenstrual age at initial treatment of 37.2, 36.45, 37.1, and 36.3 weeks, respectively (P = 0.32). CONCLUSIONS: We recorded a decrease in the number of infants meeting criteria for ROP screening during the lockdown. The GA at birth and birth weight did not differ. Significantly more infants were screened with indirect ophthalmoscopy, compared to digital imaging, during the lockdown.

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.

Birthweight is increasing in the United States.

OBJECTIVE: The rates of obesity and diabetes mellitus have increased over the last several decades.1,2 This has resulted in a higher number of large-for-gestational-age (LGA) neonates.3 The US cesarean delivery rate has increased over the same period; LGA fetuses may be a contributing factor.4 This study aimed to establish whether birthweights in the United States have increased over time. STUDY DESIGN: This was a retrospective cohort study conducted using live birth data of singleton pregnancies from the US National Vital Statistics between January 1972 and December 2020. These data are deidentified and publicly available; therefore, the study was deemed exempt from our institutional review board. Singleton births between 37 0/7 and 42 6/7 weeks of gestation were included. Multiple pregnancies and deliveries which had unknown gestational age or birthweight, were excluded. The mean birthweight by each gestational age week for the years 1972-2020 was calculated at selected years (1972, 1982, 1992, 2002, 2012, 2018, and 2020). Of note, 2018 was included to account for differences in the dataset that might be due to the COVID-19 pandemic. Using R statistical software, a linear model was fit for each gestational age week. A t test was performed to determine whether the slope was statistically different from zero (indicating whether there was a trend of rising or decreasing birthweights over time). RESULTS: A total of 19,730,588 individuals met the inclusion criteria. However, <1% of the data were excluded because of missing data. Birthweight at 39, 40, 41, and 42 weeks of gestation showed a statistically significant increase over time (Figure). There was a significant decrease in birthweight at 37 weeks of gestation. Data on Hispanic ethnicity became available in 1992. After 1992, birthweight by race or ethnicity group was examined. Each race or ethnicity group echoes the overall trends observed. However, for 39, 40, 41, and 42 weeks of gestation, the non-Hispanic Black and Hispanic groups have higher increases in birthweight than the non-Hispanic White group. There were fluctuations in the overall combined mean for 37 to 42 weeks of gestation (Table). CONCLUSION: Although the overall mean birthweight did not increase over the study period, it increased for each gestational age week at ≥39 weeks of gestation. The birthweight at 37 weeks of gestation decreased. The reason for the decrease in birthweight is unclear. Contributing factors may include changes in guidelines on the timing of delivery and method of calculation of gestational age. Increases in the rates of obesity and diabetes mellitus could be contributing to the birthweight increase from 39 weeks of gestation.1,2 There was an increase in the rate of gestational diabetes mellitus from 3% to 8% in our study population from 1992 to 2020 and an increase in mean body mass index from 26.3 to 27.5 from 2012 to 2020. The publicly available birthweight data have limitations. Data collection evolved during the study period. The estimates for gestational age have become more accurate with first-trimester dating ultrasounds. In summary, birthweight is increasing among those born from 39 to 42 weeks of gestation. These increasing birthweights may be a factor in persistently high cesarean delivery rates despite national campaigns.5.

The impact of the COVID-19 lockdown on birthweight among singleton term birth in Denmark.

In Denmark, a nationwide COVID-19 lockdown was implemented on March 12, 2020 and eased on April 14, 2020. The COVID-19 lockdown featured reduced prevalence of extremely preterm or extremely low birthweight births. This study aims to explore the impact of this COVID-19 lockdown on term birthweights in Denmark. We conducted a nationwide register-based cohort study on 27,870 live singleton infants, born at term (weeks 37-41), between March 12 and April 14, 2015-2020, using data from the Danish Neonatal Screening Biobank. Primary outcomes, corrected for confounders, were birthweight, small-for-gestational-age (SGA), and large-for-gestational-age (LGA), comparing the COVID-19 lockdown to the previous five years. Data were analysed using linear regression to assess associations with birthweight. Multinomial logistic regression was used to assess associations with relative-size-for-gestational-age (xGA) categories. Adjusted mean birthweight was significantly increased by 16.9 g (95% CI = 4.1-31.3) during the lockdown period. A dip in mean birthweight was found in gestational weeks 37 and 38 balanced by an increase in weeks 40 and 41. The 2020 lockdown period was associated with an increased LGA prevalence (aOR 1.13, 95% CI = 1.05-1.21). No significant changes in proportions of xGA groups were found between 2015 and 2019. The nationwide COVID-19 lockdown resulted in a small but significant increase in birthweight and proportion of LGA infants, driven by an increase in birthweight in gestational weeks 40 and 41.

Clinical outcome in newborns of perinatally COVID-19 infected women.

OBJECTIVE: Maternal COVID-19 infection during pregnancy has been associated with adverse neonatal outcomes, such as prematurity and neonatal morbidity. Those adverse events are mainly attributed to maternal factors, rather than to the neonatal infection itself. Our aim is to add our experience and present the neonatal outcome of neonates born to mothers with perinatal SARS-CoV-2 infection. METHODS: This is a prospective case-control study with data from two Academic Tertiary Referral Hospitals in Greece. Electronic records of all births from SARS-CoV-2 positive mothers between March 2020 and April 2021 were analyzed. Demographic data, the severity of maternal COVID-19 disease, gestational age (GA), mode of delivery, birth weight (BW), need for resuscitation and/or supplemental oxygen and duration of hospitalization were recorded. A comparison with 2:1 matched neonates according to sex, GA, and BW born to SARS-CoV-2 negative mothers during the same period was performed. Chi-square and Mann-Whitney U test were used for categorical and non-categorical variables respectively. RESULTS: A total of eighty-one neonates were born to SARS-CoV-2 positive mothers during this period. Forty-three percent of pregnant mothers were asymptomatic. Median GA and median BW were 38 weeks (Interquantile range (IQR): 36-39 weeks) and 2940 gr (IQR: 2560-3340 gr) respectively. Prematurity was observed in 24.7% of the cases. Only 2 (2.4%) neonates were PCR positive after delivery. SARS-CoV-2 positive women were more likely to undergo Cesarean section. APGAR score at 5 min and the need for resuscitation did not differ between the two groups. In comparison with the control group, neonates born to SARS-CoV-2 positive mothers presented with gastrointestinal symptoms (53.6% vs 5.1%, p-value= <.001) and hospitalization was longer, mostly due to maternal factors. CONCLUSION: In our study neonatal positivity was limited and no vertical transmission was noted. Neonatal outcomes were comparable to the control group. However, the presence of gastrointestinal symptoms in neonates born to PCR-positive women compared to controls needs further investigation.

The relationship between maternal health and neonatal low birth weight in Amman, Jordan: a case-control study.

This study aimed to examine the relationship between maternal health during pregnancy and low birth weight (LBW), as well as the impact of COVID-19 on the socio-economic status of pregnant women and its effect on LBW. The study was conducted in Amman, Jordan, and included 2260 mothers who visited Abu-Nusair comprehensive health center between January and December 2020. A matched case-control design was used with 72 cases and 148 controls selected for data collection through medical records and face-to-face interviews. Results showed that factors such as a monthly income of 400 JD or less, living with an extended family, exposure to passive smoking, maternal weight gain of 6-10 kg, maternal anemia, maternal hypertension, delivery by cesarean section, and previous history of LBW newborns were positively associated with an increased risk of LBW. Conversely, factors such as a monthly income above 700 JD, living with a core family, daily intake of iron, calcium, and vitamin D, prenatal visits, healthy food intake, and planning for pregnancy were associated with a lower risk of LBW. COVID-19 infection and its effects on work, family finances, antenatal care visits, and food supply were also positively linked with LBW. In conclusion, socioeconomic status, maternal health, COVID-19, and its impacts were significant risk factors for LBW.

Weight gain in pregnancy and infant birthweight after the onset of the COVID-19 pandemic: an interrupted time series analysis.

BACKGROUND: Increased weight gain and decreased physical activity have been reported in some populations since the coronavirus disease 2019 (COVID-19) pandemic, but this has not been well characterized in pregnant populations. OBJECTIVES: Our objective was to characterize the impact of the COVID-19 pandemic and associated countermeasures on pregnancy weight gain and infant birthweight in a US cohort. METHODS: Washington State pregnancies and births (1 January, 2016 to 28 December, 2020) from a multihospital quality improvement organization were examined for pregnancy weight gain, pregnancy weight gain z-score adjusted for pregestational BMI and gestational age, and infant birthweight z-score, using an interrupted time series design that controls for underlying time trends. We used mixed-effect linear regression models, controlled for seasonality and clustered at the hospital level, to model the weekly time trends and changes on 23 March, 2020, the onset of local COVID-19 countermeasures. RESULTS: Our analysis included 77,411 pregnant people and 104,936 infants with complete outcome data. The mean pregnancy weight gain was 12.1 kg (z-score: -0.14) during the prepandemic time period (March to December 2019) and increased to 12.4 kg (z-score: -0.09) after the onset of the pandemic (March to December 2020). Our time series analysis found that after the pandemic onset, the mean weight gain increased by 0.49 kg (95% CI: 0.25, 0.73 kg) and weight gain z-score increased by 0.080 (95% CI: 0.03, 0.13), with no changes in the baseline yearly trend. Infant birthweight z-scores were unchanged (-0.004; 95% CI: -0.04, 0.03). Overall, the results were unchanged in analyses stratified by pregestational BMI categories. CONCLUSIONS: We observed a modest increase in weight gain after the onset of the pandemic among pregnant people but no changes in infant birthweights. This weight change could be more important in high BMI subgroups.

Multisystem inflammatory syndrome in neonates (MIS-N): a systematic review.

Recently, a new pattern of multisystem inflammatory syndrome following an infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged globally. The initial cases were described in the adult population followed by sporadic cases in the pediatric population also. By the end of 2020, similar reports were recognised in the neonatal age group. The purpose of this study was to systematically review clinical characteristics, laboratory parameters, treatment, and outcomes of neonates with multisystem inflammatory syndrome in neonates (MIS-N). A systematic review was conducted after registering with PROSPERO and electronic databases including MEDLINE, EMBASE, PubMed, SCOPUS, Google Scholar, and Web of Science were searched from January 1st 2020 till September 30th 2022. A total of 27 studies describing 104 neonates were analysed. The mean gestation age and birth weight was 35.9 ± 3.3 weeks and 2255.7 ± 783.7 g respectively. A large proportion (91.3%) of the reported cases belonged to the South-East Asian region. The median age of presentation was 2 days (range: 1-28 days) with cardiovascular system being the predominant system involved in 83.65% followed by respiratory (64.42%). Fever was noted in only 20.2%. Commonly elevated inflammatory markers were IL-6 in 86.7% and D-dimer in 81.1%. Echocardiographic evaluation suggested ventricular dysfunction in 35.8% and dilated coronary arteries in 28.3%. Evidence of SARS-CoV-2 antibodies (IgG or IgM) was seen in 95.9% neonates and evidence of maternal SARS-CoV-2 infection, either as history of COVID infection or positive antigen or antibody test, was noted in 100% of the cases. Early MIS-N was reported in 58 (55.8%) cases, late MIS-N in 28 (26.9%), and 18 cases (17.3%) did not report the timing of presentation. There was a statistically increased proportion of preterm infants (67.2%, p < 0.001), and a trend towards increased low birth weight infants, in the early MIS-N group when compared to the infants with late MIS-N. Fever (39.3%), central nervous system (50%), and gastrointestinal manifestations (57.1%) were significantly higher in the late MIS-N group (p = 0.03, 0.02, 0.01 respectively). The anti-inflammatory agents used for the treatment of MIS-N included steroids 80.8% which were given for a median of 10 (range 3-35) days and IVIg in 79.2% with a median of 2 (range 1-5) doses. The outcomes were available for 98 cases, of whom 8 (8.2%) died during treatment in hospital and 90 (91.8%) were successfully discharged home.   Conclusion: MIS-N has a predilection for late preterm males with predominant cardiovascular involvement. The diagnosis is challenging in neonatal period due to overlap with neonatal morbidities and a high risk of suspicion is warranted, especially in presence of supportive maternal and neonatal clinical history. The major limitation of the review was inclusion of case reports and case series, and highlights need of global registries for MIS-N. What is Known: • A new pattern of multisystem inflammatory syndrome following SARS-CoV-2 infection has emerged in adult population with sporadic cases now being reported in neonates. What is New: • MIS-N is an emerging condition with a heterogeneous spectrum and has a predilection for late preterm male infants. Cardiovascular system is the predominant system involved  followed by respiratory, however fever remains an uncommon presentation unlike other age-groups. There are two subtypes based on timing of presentation, with early MIS-N being reported more in preterm and low-birth weight infants.

The causal effect of being born extremely preterm or extremely low birthweight on neurodevelopment and social-emotional development at 2 years.

AIM: To assess the causal effect of being born extremely preterm (EP; <28 weeks' gestation) or extremely low birthweight (ELBW; <1000 g), compared with being born at term, on neurodevelopment and social-emotional development at 2 years' corrected age. METHODS: Prospective geographical cohort study of children born EP/ELBW over 12 months in 2016 from Victoria, Australia, and term-born controls. Children were assessed at 2 years' corrected age with the Bayley Scales of Infant and Toddler Development-3rd edition and the Infant-Toddler Social and Emotional Assessment. Delay was defined as <-1 standard deviation relative to the mean of controls. The estimand of interest was the mean difference/odds ratio (OR) between the EP/ELBW and control groups estimated using linear/logistic regression, adjusted for multiple pregnancy and social risk. RESULTS: A total of 205 EP/ELBW and 201 controls were assessed at 2 years. Delay/concerns were more common in the EP/ELBW group compared with controls, for cognitive (OR 3.7 [95% confidence interval 2.3, 6.0]), language (5.3 [3.1, 9.0]) and motor (3.9 [2.3, 6.3]) development, and social-emotional competence (4.1 [1.6, 10.2]). CONCLUSION: Being born EP/ELBW has an adverse effect on cognitive, language and motor development, and social-emotional competence at 2 years' corrected age. Close developmental surveillance, including social-emotional development, is recommended.

Comparing maternal substance use and perinatal outcomes before and during the COVID-19 pandemic.

OBJECTIVE: To examine the effect of the COVID-19 pandemic on maternal substance abuse and neonatal outcomes. STUDY DESIGN: Cross-sectional observational study of neonates admitted to the NICU and born to mothers with evidence of substance abuse pre-pandemic compared to during the COVID-19 pandemic. RESULT: We noted a significant increase in fentanyl (12% vs. 0.6%, p < 0.001) and tobacco use (64% vs. 33%, p < 0.001) during the pandemic compared to pre-pandemic, including an increase in fentanyl use among mothers enrolled in opioid maintenance therapy (OMT) during the pandemic (32.3% vs. 1.5%, p < 0.001). There was a significant increase in preterm births (58% vs. 48%, p = 0.022) and lower birth weight (2315 ± 815 vs. 2455 ± 861 g, p = 0.049) during pandemic. CONCLUSION: There was a significant increase in maternal fentanyl use during the pandemic, even with OMT enrollment, with an increase in preterm births and lower birth weights among infants born to mothers with substance use.

Mechanical ventilation and death in pregnant patients admitted for COVID-19: a prognostic analysis from the Brazilian COVID-19 registry score.

BACKGROUND: The assessment of clinical prognosis of pregnant COVID-19 patients at hospital presentation is challenging, due to physiological adaptations during pregnancy. Our aim was to assess the performance of the ABC2-SPH score to predict in-hospital mortality and mechanical ventilation support in pregnant patients with COVID-19, to assess the frequency of adverse pregnancy outcomes, and characteristics of pregnant women who died. METHODS: This multicenter cohort included consecutive pregnant patients with COVID-19 admitted to the participating hospitals, from April/2020 to March/2022. Primary outcomes were in-hospital mortality and the composite outcome of mechanical ventilation support and in-hospital mortality. Secondary endpoints were pregnancy outcomes. The overall discrimination of the model was presented as the area under the receiver operating characteristic curve (AUROC). Overall performance was assessed using the Brier score. RESULTS: From 350 pregnant patients (median age 30 [interquartile range (25.2, 35.0)] years-old]), 11.1% had hypertensive disorders, 19.7% required mechanical ventilation support and 6.0% died. The AUROC for in-hospital mortality and for the composite outcome were 0.809 (95% IC: 0.641-0.944) and 0.704 (95% IC: 0.617-0.792), respectively, with good overall performance (Brier = 0.0384 and 0.1610, respectively). Calibration was good for the prediction of in-hospital mortality, but poor for the composite outcome. Women who died had a median age 4 years-old higher, higher frequency of hypertensive disorders (38.1% vs. 9.4%, p < 0.001) and obesity (28.6% vs. 10.6%, p = 0.025) than those who were discharged alive, and their newborns had lower birth weight (2000 vs. 2813, p = 0.001) and five-minute Apgar score (3.0 vs. 8.0, p < 0.001). CONCLUSIONS: The ABC2-SPH score had good overall performance for in-hospital mortality and the composite outcome mechanical ventilation and in-hospital mortality. Calibration was good for the prediction of in-hospital mortality, but it was poor for the composite outcome. Therefore, the score may be useful to predict in-hospital mortality in pregnant patients with COVID-19, in addition to clinical judgment. Newborns from women who died had lower birth weight and Apgar score than those who were discharged alive.

Third trimester suppression in low-risk pregnancy in the SARS-CoV-2 pandemic / Supresión de la visita de tercer trimestre en embarazo de bajo riesgo en la pandemia de SARS-CoV-2

Resumen Objetivo: La pandemia de SARS-CoV-2 ha obligado a una reorganización de las visitas presenciales, y por ese motivo se han minimizado hasta el punto de reconsiderar la realización de la visita del tercer trimestre. Nuestro centro suprimió dicha visita obstétrica y obtuvo datos propios para comparar los resultados perinatales logrados con dicho manejo. Método: Se realizó un estudio de cohortes retrospectivo, en marzo de 2020, con una cohorte con visita presencial única en la semana 40 de gestación (122 gestantes) frente a una cohorte con seguimiento convencional con visita presencial en la semana 36 de gestación (162 gestantes). Se evaluaron la restricción del crecimiento fetal, la edad gestacional al nacimiento, el peso neonatal y las tasas de inducciones, partos eutócicos y cesáreas urgentes en trabajo de parto. Resultados: Se encontraron diferencias leves en la tasa de nuliparidad (p < 0,04), sin hallarlas en el resto de las variables maternas. No hubo diferencias entre las dos cohortes en los resultados neonatales. Conclusiones: No hay diferencias entre los resultados materno-fetales obtenidos en gestantes con seguimiento gestacional con restricción de la visita del tercer trimestre respecto del seguimiento tradicional, excepto en el diagnóstico de las alteraciones de la estática fetal al término de la gestación.

Abstract Objective: The SARS-CoV-2 pandemic has forced a reorganization of face-to-face visits, for this reason they have been minimized to the point of reconsidering the completion of the third trimester visit. Our center eliminated the performance of this obstetric visit and obtained its own data to compare the perinatal results obtained with such management. Method: A retrospective cohort study was carried out in March 2020, with a cohort with a single face-to-face visit at 40th week of gestation (122 pregnant women), versus a cohort with conventional follow-up with face-to-face visit at 36th week of gestation (162 pregnant women). The following were evaluated fetal growth restriction, gestational age at birth, neonatal weight, rate of inductions, of eutocic deliveries, and of urgent cesarean sections in labor. Results: Slight differences were found in the nulliparity rate (p < 0.04), without finding them in the rest of the maternal variables. There were no differences between the two cohorts in neonatal outcomes. Conclusions: There were no differences between the maternal-fetal results obtained in pregnant women with gestational follow-up with restriction of the third trimester visit compared to traditional follow-up, except in the diagnosis of alterations in fetal statics at the end of pregnancy.

Antepartum SARS-CoV-2 infection and adverse birth outcomes in South African women.

Background: SARS-CoV-2 infection in pregnant women has been associated with severe illness in the women and higher rates of premature delivery. There is, however, paucity of data on the impact of the timing of SARS-CoV-2 infection and on symptomatic or asymptomatic infections on birth outcomes. Data from low-middle income settings is also lacking. Methods: We conducted a longitudinal study from April 2020 to March 2021, in South Africa, where symptomatic or asymptomatic pregnant women were investigated for SARS-CoV-2 infection during the antepartum period. We aimed to evaluate if there was an association between antepartum SARS-CoV-2 infection on birth outcomes. SARS-CoV-2 infection was investigated by nucleic acid amplification test (NAAT), histological examination was performed in a sub-set of placentas. Results: Overall, 793 women were tested for SARS-CoV-2 antenatally, including 275 (35%) who were symptomatic. SARS-CoV-2 infection was identified in 138 (17%) women, of whom 119 had symptoms (COVID-19 group) and 19 were asymptomatic. The 493 women who were asymptomatic and had a negative SARS-CoV-2 NAAT were used as the referent comparator group for outcomes evaluation. Women with COVID-19 compared with the referent group were 1.66-times (95% confidence interval (CI) = 1.02-2.71) more likely to have a low-birthweight newborn (30% vs 21%) and 3.25-times more likely to deliver a very low-birthweight newborn (5% vs 2%). Similar results for low-birthweight were obtained comparing women with SARS-CoV-2 confirmed infection (30%) with those who had a negative NAAT result (22%) independent of symptoms presentation. The placentas from women with antenatal SARS-CoV-2 infection had higher percentage of chorangiosis (odds ratio (OR) = 3.40, 95% CI = 1.18-.84), while maternal vascular malperfusion was more frequently identified in women who tested negative for SARS-CoV-2 (aOR = 0.28, 95% CI = 0.09-0.89). Conclusions: Our study demonstrates that in a setting with high HIV infection prevalence and other comorbidities antenatal SARS-CoV-2 infection was associated with low-birthweight delivery.

Impact of prenatal COVID-19 vaccination on delivery and neonatal outcomes: Results from a New York City cohort.

Research suggest prenatal vaccination against coronavirus disease-19 (COVID-19) is safe. However, previous studies utilized retrospectively collected data or examined late pregnancy vaccinations. We investigated the associations of COVID-19 vaccination throughout pregnancy with delivery and neonatal outcomes. We included 1,794 mother-neonate dyads enrolled in the Generation C Study with known prenatal COVID-19 vaccination status and complete covariate and outcome data. We used multivariable quantile regressions to estimate the effect of prenatal COVID-19 vaccination on birthweight, delivery gestational age, and blood loss at delivery; and Poisson generalized linear models for Caesarean delivery (CD) and Neonatal Intensive Care Unit (NICU) admission. Using the above methods, we estimated effects of trimester of vaccine initiation on these outcomes. In our sample, 13.7% (n = 250) received at least one prenatal dose of any COVID-19 vaccine. Vaccination was not associated with birthweight (ß = 12.42 g [-90.5, 114.8]), gestational age (ß = 0.2 days [-1.1, 1.5]), blood loss (ß = -50.6 ml [-107.0, 5.8]), the risks of CD (RR = 0.8; [0.6, 1.1]) or NICU admission (RR = 0.9 [0.5, 1.7]). Trimester of vaccine initiation was also not associated with these outcomes. Our findings suggest that there is no associated risk between prenatal COVID-19 vaccination and adverse delivery and neonatal outcomes in a cohort sample from NYC.

The Influence of Maternal Psychological Manifestations on the Mother-Child Couple during the Early COVID-19 Pandemic in Two Hospitals in Timisoara, Romania.

BACKGROUND AND OBJECTIVES: The postpartum maternal physical and psychological state played a fundamental role in the mother-child relationship at the beginning of the COVID-19 pandemic. The aim of the study is to analyze the influence of maternal psychological manifestations on the mother-child couple through three objectives (briefly expressed): (I) Determination of the main acute and chronic conditions of newborns/infants. (II) Verification of the hypothesis of the existence of a link between the following neonatal variables: gestational age, birth weight, number of days of hospitalization, and specific neonatal therapies (oxygen, surfactant, and blood products' transfusion). (III) Verification of the influence of postpartum maternal psychological status on the mother-child couple through three hypotheses. MATERIALS AND METHODS: This cross-sectional study was conducted in two hospitals in Timișoara, Romania, between 1 March and 1 September 2020, and included 165 mothers and their 175 newborns. Mothers answered the Edinburgh Postnatal Depression Scale, Spielberger's Inventory of State-Trait Anxiety, and the Collins and Read Revised Adult Attachment Scale. RESULTS: (I) The acute and chronic pathology of the infants in the study group was polymorphic. (II) Large correlations were identified between the following infant variables: gestational age with birth weight, and number of hospitalization days with birth weight, gestational age, and use of blood product transfusion (all p < 0.001). (III) (1) State anxiety was the only significant predictor of number of hospitalization days (p = 0.037), number of acute disorders (p = 0.028), and number of infant chronic diseases (p = 0.037). (2) Maternal depressive symptoms were the only predictor of postpartum maternal attachment (p = 0.018). (3) Depressive symptoms, state, and trait anxiety were non-significant in all models studied (all p > 0.05). CONCLUSIONS: Postpartum maternal physical and psychological state plays a fundamental role on the mother-child relationship in the new social and complex family conditions.