Coronavirus disease 2019 pandemic and pregnancy and neonatal outcomes in general population: A living systematic review and meta-analysis (updated Aug 14, 2021).

INTRODUCTION: Conflicting reports of increases and decreases in rates of preterm birth (PTB) and stillbirth in the general population during the coronavirus disease 2019 (COVID-19) pandemic have surfaced. The objective of our study was to conduct a living systematic review and meta-analyses of studies reporting pregnancy and neonatal outcomes by comparing the pandemic and pre-pandemic periods. MATERIAL AND METHODS: We searched PubMed and Embase databases, reference lists of articles published up until August 14, 2021 and included English language studies that compared outcomes between the COVID-19 pandemic time period and the pre-pandemic time periods. Risk of bias was assessed using the Newcastle-Ottawa scale. We conducted random-effects meta-analysis using the inverse variance method. RESULTS: Forty-five studies with low-to-moderate risk of bias, reporting on 1 843 665 pregnancies during the pandemic period and 23 564 552 pregnancies during the pre-pandemic period, were included. There was significant reduction in unadjusted estimates of PTB (35 studies, unadjusted odds ratio [uaOR] 0.95, 95% CI 0.92-0.98), but not in adjusted estimates (six studies, adjusted OR [aOR] 0.95, 95% CI 0.80-1.13). This reduction was noted in studies from single centers/health areas (25 studies, uaOR 0.90, 95% CI 0.86-0.96) but not in regional/national studies (10 studies, uaOR 0.99, 95% CI 0.95-1.02). There was reduction in spontaneous PTB (six studies, uaOR 0.89, 95% CI 0.81-0.96) and induced PTB (five studies, uaOR 0.89, 95% CI 0.81-0.97). There was no difference in the odds of stillbirth between the pandemic and pre-pandemic time periods (24 studies, uaOR 1.11, 95% CI 0.97-1.26 and four studies, aOR 1.06, 95% CI 0.81-1.38). There was an increase in mean birthweight during the pandemic period compared with the pre-pandemic period (six studies, mean difference 17 g, 95% CI 7-28 g). The odds of maternal mortality were increased (four studies, uaOR 1.15, 95% CI 1.05-1.26); however, only unadjusted estimates were available and the result was mostly influenced by one study from Mexico. There was significant publication bias for the outcome of PTB. CONCLUSIONS: The COVID-19 pandemic may be associated with a reduction in PTB; however, referral bias cannot be excluded. There was no statistically significant difference in stillbirth between pandemic and pre-pandemic periods.

Clinical signs of possible serious infection and associated mortality among young infants presenting at first-level health facilities.

BACKGROUND: The World Health Organization recommends inpatient hospital treatment of young infants up to two months old with any sign of possible serious infection. However, each sign may have a different risk of death. The current study aims to calculate the case fatality ratio for infants with individual or combined signs of possible serious infection, stratified by inpatient or outpatient treatment. METHODS: We analysed data from the African Neonatal Sepsis Trial conducted in five sites in the Democratic Republic of the Congo, Kenya and Nigeria. Trained study nurses classified sick infants as pneumonia (fast breathing in 7-59 days old), severe pneumonia (fast breathing in 0-6 days old), clinical severe infection [severe chest indrawing, high (> = 38°C) or low body temperature (<35.5°C), stopped feeding well, or movement only when stimulated] or critical illness (convulsions, not able to feed at all, or no movement at all), and referred them to a hospital for inpatient treatment. Infants whose caregivers refused referral received outpatient treatment. The case fatality ratio by day 15 was calculated for individual and combined clinical signs and stratified by place of treatment. An infant with signs of clinical severe infection or severe pneumonia was recategorised as having low- (case fatality ratio ≤2%) or moderate- (case fatality ratio >2%) mortality risk. RESULTS: Of 7129 young infants with a possible serious infection, fast breathing (in 7-59 days old) was the most prevalent sign (26%), followed by high body temperature (20%) and severe chest indrawing (19%). Infants with pneumonia had the lowest case fatality ratio (0.2%), followed by severe pneumonia (2.0%), clinical severe infection (2.3%) and critical illness (16.9%). Infants with clinical severe infection had a wide range of case fatality ratios for individual signs (from 0.8% to 11.0%). Infants with pneumonia had similar case fatality ratio for outpatient and inpatient treatment (0.2% vs. 0.3%, p = 0.74). Infants with clinical severe infection or severe pneumonia had a lower case fatality ratio among those who received outpatient treatment compared to inpatient treatment (1.9% vs. 6.5%, p<0.0001). We recategorised infants into low-mortality risk signs (case fatality ratio ≤2%) of clinical severe infection (high body temperature, or severe chest indrawing) or severe pneumonia and moderate-mortality risk signs (case fatality ratio >2%) (stopped feeding well, movement only when stimulated, low body temperature or multiple signs of clinical severe infection). We found that both categories had four times lower case fatality ratio when treated as outpatient than inpatient treatment, i.e., 1.0% vs. 4.0% (p<0.0001) and 5.3% vs. 22.4% (p<0.0001), respectively. In contrast, infants with signs of critical illness had nearly two times higher case fatality ratio when treated as outpatient versus inpatient treatment (21.7% vs. 12.1%, p = 0.097). CONCLUSIONS: The mortality risk differs with clinical signs. Young infants with a possible serious infection can be grouped into those with low-mortality risk signs (high body temperature, or severe chest indrawing or severe pneumonia); moderate-mortality risk signs (stopped feeding well, movement only when stimulated, low body temperature or multiple signs of clinical severe infection), or high-mortality risk signs (signs of critical illness). New treatment strategies that consider differential mortality risks for the place of treatment and duration of inpatient treatment could be developed and evaluated based on these findings. CLINICAL TRIAL REGISTRATION: This trial was registered with the Australian New Zealand Clinical Trials Registry under ID ACTRN 12610000286044.

Global, regional, and national progress towards Sustainable Development Goal 3.2 for neonatal and child health: all-cause and cause-specific mortality findings from the Global Burden of Disease Study 2019.

BACKGROUND: Sustainable Development Goal 3.2 has targeted elimination of preventable child mortality, reduction of neonatal death to less than 12 per 1000 livebirths, and reduction of death of children younger than 5 years to less than 25 per 1000 livebirths, for each country by 2030. To understand current rates, recent trends, and potential trajectories of child mortality for the next decade, we present the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 findings for all-cause mortality and cause-specific mortality in children younger than 5 years of age, with multiple scenarios for child mortality in 2030 that include the consideration of potential effects of COVID-19, and a novel framework for quantifying optimal child survival. METHODS: We completed all-cause mortality and cause-specific mortality analyses from 204 countries and territories for detailed age groups separately, with aggregated mortality probabilities per 1000 livebirths computed for neonatal mortality rate (NMR) and under-5 mortality rate (U5MR). Scenarios for 2030 represent different potential trajectories, notably including potential effects of the COVID-19 pandemic and the potential impact of improvements preferentially targeting neonatal survival. Optimal child survival metrics were developed by age, sex, and cause of death across all GBD location-years. The first metric is a global optimum and is based on the lowest observed mortality, and the second is a survival potential frontier that is based on stochastic frontier analysis of observed mortality and Healthcare Access and Quality Index. FINDINGS: Global U5MR decreased from 71·2 deaths per 1000 livebirths (95% uncertainty interval [UI] 68·3-74·0) in 2000 to 37·1 (33·2-41·7) in 2019 while global NMR correspondingly declined more slowly from 28·0 deaths per 1000 live births (26·8-29·5) in 2000 to 17·9 (16·3-19·8) in 2019. In 2019, 136 (67%) of 204 countries had a U5MR at or below the SDG 3.2 threshold and 133 (65%) had an NMR at or below the SDG 3.2 threshold, and the reference scenario suggests that by 2030, 154 (75%) of all countries could meet the U5MR targets, and 139 (68%) could meet the NMR targets. Deaths of children younger than 5 years totalled 9·65 million (95% UI 9·05-10·30) in 2000 and 5·05 million (4·27-6·02) in 2019, with the neonatal fraction of these deaths increasing from 39% (3·76 million [95% UI 3·53-4·02]) in 2000 to 48% (2·42 million; 2·06-2·86) in 2019. NMR and U5MR were generally higher in males than in females, although there was no statistically significant difference at the global level. Neonatal disorders remained the leading cause of death in children younger than 5 years in 2019, followed by lower respiratory infections, diarrhoeal diseases, congenital birth defects, and malaria. The global optimum analysis suggests NMR could be reduced to as low as 0·80 (95% UI 0·71-0·86) deaths per 1000 livebirths and U5MR to 1·44 (95% UI 1·27-1·58) deaths per 1000 livebirths, and in 2019, there were as many as 1·87 million (95% UI 1·35-2·58; 37% [95% UI 32-43]) of 5·05 million more deaths of children younger than 5 years than the survival potential frontier. INTERPRETATION: Global child mortality declined by almost half between 2000 and 2019, but progress remains slower in neonates and 65 (32%) of 204 countries, mostly in sub-Saharan Africa and south Asia, are not on track to meet either SDG 3.2 target by 2030. Focused improvements in perinatal and newborn care, continued and expanded delivery of essential interventions such as vaccination and infection prevention, an enhanced focus on equity, continued focus on poverty reduction and education, and investment in strengthening health systems across the development spectrum have the potential to substantially improve U5MR. Given the widespread effects of COVID-19, considerable effort will be required to maintain and accelerate progress. FUNDING: Bill & Melinda Gates Foundation.

Preterm birth and stillbirth rates during the COVID-19 pandemic: a population-based cohort study.

BACKGROUND: Conflicting reports have emerged for rates of preterm births and stillbirths during the COVID-19 pandemic. Most of these reports did not account for natural variation in these rates. We aimed to evaluate variations in preterm birth and stillbirth rates before and during the COVID-19 pandemic in Ontario, Canada. METHODS: We conducted a retrospective cohort study using linked population health administrative databases of pregnant people giving birth in any hospital in Ontario between July 2002 and December 2020. We calculated preterm birth and stillbirth rates. We assessed preterm birth at 22-28, 29-32 and 33-36 weeks' gestation, and stillbirths at term and preterm gestation. We used Laney control P' charts for the 18-year study period (6-mo observation periods) and interrupted time-series analyses for monthly rates for the most recent 4 years. RESULTS: We evaluated 2 465 387 pregnancies, including 13 781 that resulted in stillbirth. The mean preterm birth rate for our cohort was 7.96% (range 7.32%-8.59%). From January to December 2020, we determined that the preterm birth rate in Ontario was 7.87%, with no special cause variation. The mean stillbirth rate for the cohort was 0.56% (range 0.48%-0.70%). From January to December 2020, the stillbirth rate was 0.53%, with no special cause variation. We did not find any special cause variation for preterm birth or stillbirth subgroups. We found no changes in slope or gap between prepandemic and pandemic periods using interrupted time-series analyses. INTERPRETATION: In Ontario, Canada, we found no special cause variation (unusual change) in preterm birth or stillbirth rates, overall or by subgroups, during the first 12 months of the COVID-19 pandemic compared with the previous 17.5 years.

Newborns and Under-5 Mortality in Ethiopia: The Necessity to Revitalize Partnership in Post-COVID-19 Era to Meet the SDG Targets.

The Sustainable Development Goals (SDGs) were adopted during the United Nations meeting in 2015 to succeed Millennium Development Goals. Among the health targets, SDG 3.2 is to end preventable deaths of newborns and children under 5 years of age by 2030. These 2 targets aim to reduce neonatal mortality to at least as low as 12 per 1000 live births and under-5 mortality to at least as low as 25 per 1000 live births. Ethiopia is demonstrating a great reduction in child mortality since 2000. In the 2019 child mortality estimation which is nearly 5 years after SDGs adoption, Ethiopia's progress toward reducing the newborns and under-5 mortality lie at 27 and 50.7 per 1000 live births, respectively. The generous financial and technical support from the global partners have helped to achieve such a significant reduction. Nevertheless, the SDG targets for newborns and under-5 mortality reduction are neither attained yet nor met the national plan to achieve by the end of 2019/2020. The partnership dynamics during COVID-19 crisis and the pandemic itself may also be taken as an opportunity to draw lessons and spur efforts to achieve SDG targets. This urges the need to reaffirm a comprehensive partnership and realignment with other interconnected development goals. Therefore, collective efforts with strong partnerships are required to improve the determinants of child health and achieving SDG target reduction until 2030.

Impact of COVID-19 on maternal and neonatal outcomes: a systematic review and meta-analysis.

BACKGROUND: Previous outbreaks of severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and Middle East respiratory syndrome coronavirus (MERS-CoV) have been associated with unfavourable pregnancy outcomes. SARS-CoV-2 belongs to the human coronavirus family, and since this infection shows a pandemic trend it will involve many pregnant women. AIMS: This systematic review and meta-analysis aimed to assess the impact of coronavirus disease 19 (COVID-19) on maternal and neonatal outcomes. SOURCES: PubMed, EMBASE, MedRxiv, Scholar, Scopus, and Web of Science databases were searched up to 8th May 2020. Articles focusing on pregnancy and perinatal outcomes of COVID-19 were eligible. Participants were pregnant women with COVID-19. CONTENT: The meta-analysis was conducted following the PRISMA and MOOSE reporting guidelines. Bias risk was assessed using the Joanna Briggs Institute (JBI) manual. The protocol was registered with PROSPERO (CRD42042020184752). Twenty-four articles, including 1100 pregnancies, were selected. The pooled prevalence of pneumonia was 89% (95%CI 70-100), while the prevalence of women admitted to the intensive care unit was 8% (95%CI 1-20). Three stillbirths and five maternal deaths were reported. A pooled prevalence of 85% (95%CI 72-94) was observed for caesarean deliveries. There were three neonatal deaths. The prevalence of COVID-19-related admission to the neonatal intensive care unit was 2% (95%CI 0-6). Nineteen out of 444 neonates were positive for SARS-CoV-2 RNA at birth. Elevated levels of IgM and IgG Serum antibodies were reported in one case, but negative swab. IMPLICATIONS: Although adverse outcomes such as ICU admission or patient death can occur, the clinical course of COVID-19 in most women is not severe, and the infection does not significantly influence the pregnancy. A high caesarean delivery rate is reported, but there is no clinical evidence supporting this mode of delivery. Indeed, in most cases the disease does not threaten the mother, and vertical transmission has not been clearly demonstrated. Therefore, COVID-19 should not be considered as an indication for elective caesarean section.

The impact of the Covid-19 pandemic on maternity services: A review of maternal and neonatal outcomes before, during and after the pandemic.

OBJECTIVE: To explore any apparent trends in maternal or neonatal outcomes during the Covid-19 pandemic by comparing the maternity outcomes before, during and after the pandemic. STUDY DESIGN: A retrospective review was performed of maternity statistics recorded on the hospital database of a large tertiary referral centre in Dublin with over 8000 deliveries per annum from 1st January to 31st July 2020. This time period represented the months prior to, during the peak and following the pandemic in Ireland. RESULTS: There was no correlation between the monthly number of Covid deaths and the monthly number of perinatal deaths (r = 0.465, NS), preterm births (r = 0.339, NS) or hypertensive pregnancies (r = 0.48, NS). Compared to the combined numbers for the same month in 2018 and 2019, there were no significant changes in perinatal deaths or preterm births in the months when Covid deaths were at their height. The rate of preterm birth was significantly less common in January-July 2020 compared to January-July in 2018/2019 (7.4 % v 8.6 %, chi-sq 4.53, P = 0.03). CONCLUSION: The was no evidence of a negative impact of the Covid-19 pandemic on maternity services, as demonstrated by maternal and neonatal outcomes.

Effect of the COVID-19 pandemic response on intrapartum care, stillbirth, and neonatal mortality outcomes in Nepal: a prospective observational study.

BACKGROUND: The COVID-19 pandemic response is affecting maternal and neonatal health services all over the world. We aimed to assess the number of institutional births, their outcomes (institutional stillbirth and neonatal mortality rate), and quality of intrapartum care before and during the national COVID-19 lockdown in Nepal. METHODS: In this prospective observational study, we collected participant-level data for pregnant women enrolled in the SUSTAIN and REFINE studies between Jan 1 and May 30, 2020, from nine hospitals in Nepal. This period included 12·5 weeks before the national lockdown and 9·5 weeks during the lockdown. Women were eligible for inclusion if they had a gestational age of 22 weeks or more, a fetal heart sound at time of admission, and consented to inclusion. Women who had multiple births and their babies were excluded. We collected information on demographic and obstetric characteristics via extraction from case notes and health worker performance via direct observation by independent clinical researchers. We used regression analyses to assess changes in the number of institutional births, quality of care, and mortality before lockdown versus during lockdown. FINDINGS: Of 22 907 eligible women, 21 763 women were enrolled and 20 354 gave birth, and health worker performance was recorded for 10 543 births. From the beginning to the end of the study period, the mean weekly number of births decreased from 1261·1 births (SE 66·1) before lockdown to 651·4 births (49·9) during lockdown-a reduction of 52·4%. The institutional stillbirth rate increased from 14 per 1000 total births before lockdown to 21 per 1000 total births during lockdown (p=0·0002), and institutional neonatal mortality increased from 13 per 1000 livebirths to 40 per 1000 livebirths (p=0·0022). In terms of quality of care, intrapartum fetal heart rate monitoring decreased by 13·4% (-15·4 to -11·3; p<0·0001), and breastfeeding within 1 h of birth decreased by 3·5% (-4·6 to -2·6; p=0·0032). The immediate newborn care practice of placing the baby skin-to-skin with their mother increased by 13·2% (12·1 to 14·5; p<0·0001), and health workers' hand hygiene practices during childbirth increased by 12·9% (11·8 to 13·9) during lockdown (p<0·0001). INTERPRETATION: Institutional childbirth reduced by more than half during lockdown, with increases in institutional stillbirth rate and neonatal mortality, and decreases in quality of care. Some behaviours improved, notably hand hygiene and keeping the baby skin-to-skin with their mother. An urgent need exists to protect access to high quality intrapartum care and prevent excess deaths for the most vulnerable health system users during this pandemic period. FUNDING: Grand Challenges Canada.

COVID-19 and pregnancy: A review of clinical characteristics, obstetric outcomes and vertical transmission.

BACKGROUND: Since its emergence in December 2019, COVID-19 has spread to over 210 countries, with an estimated mortality rate of 3-4%. Little is understood about its effects during pregnancy. AIMS: To describe the current understanding of COVID-19 illness in pregnant women, to describe obstetric outcomes and to identify gaps in the existing knowledge. METHODS: Medline Ovid, EMBASE, World Health Organization COVID-19 research database and Cochrane COVID-19 in pregnancy spreadsheet were accessed on 18/4, 18/5 and 23/5 2020. Articles were screened via Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The following were excluded: reviews, opinion pieces, guidelines, articles pertaining solely to other viruses, single case reports. RESULTS: Sixty articles were included in this review. Some pregnant participants may have been included in multiple publications, as admission dates overlap for reports from the same hospital. However, a total of 1287 confirmed SARS-CoV-2 positive pregnant cases are reported. Where universal testing was undertaken, asymptomatic infection occurred in 43.5-92% of cases. In the cohort studies, severe and critical COVID-19 illness rates approximated those of the non-pregnant population. Eight maternal deaths, six neonatal deaths, seven stillbirths and five miscarriages were reported. Nineteen neonates were SARS-CoV-2 positive, confirmed by reverse transcription polymerase chain reaction of nasopharyngeal swabs. [Correction added on 2 September 2020, after first online publication: the number of neonates indicated in the preceding sentence has been corrected from 'Thirteen' to 'Nineteen'.] CONCLUSIONS: Where universal screening was conducted, SARS-CoV-2 infection in pregnancy was often asymptomatic. Severe and critical disease rates approximate those in the general population. Vertical transmission is possible; however, it is unclear whether SARS-CoV-2 positive neonates were infected in utero, intrapartum or postpartum. Future work should assess risks of congenital syndromes and adverse perinatal outcomes where infection occurs in early and mid-pregnancy.