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

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

The relationship between markers of antenatal iron stores and birth outcomes differs by malaria prevention regimen-a prospective cohort study.

BACKGROUND: Iron deficiency (ID) has been associated with adverse pregnancy outcomes, maternal anaemia, and altered susceptibility to infection. In Papua New Guinea (PNG), monthly treatment with sulphadoxine-pyrimethamine plus azithromycin (SPAZ) prevented low birthweight (LBW; <2500 g) through a combination of anti-malarial and non-malarial effects when compared to a single treatment with SP plus chloroquine (SPCQ) at first antenatal visit. We assessed the relationship between ID and adverse birth outcomes in women receiving SPAZ or SPCQ, and the mediating effects of malaria infection and haemoglobin levels during pregnancy. METHODS: Plasma ferritin levels measured at antenatal enrolment in a cohort of 1892 women were adjusted for concomitant inflammation using C-reactive protein and α-1-acid glycoprotein. Associations of ID (defined as ferritin <15 µg/L) or ferritin levels with birth outcomes (birthweight, LBW, preterm birth, small-for-gestational-age birthweight [SGA]) were determined using linear or logistic regression analysis, as appropriate. Mediation analysis assessed the degree of mediation of ID-birth outcome relationships by malaria infection or haemoglobin levels. RESULTS: At first antenatal visit (median gestational age, 22 weeks), 1256 women (66.4%) had ID. Overall, ID or ferritin levels at first antenatal visit were not associated with birth outcomes. There was effect modification by treatment arm. Amongst SPCQ recipients, ID was associated with a 81-g higher mean birthweight (95% confidence interval [CI] 10, 152; P = 0.025), and a twofold increase in ferritin levels was associated with increased odds of SGA (adjusted odds ratio [aOR] 1.25; 95% CI 1.06, 1.46; P = 0.007). By contrast, amongst SPAZ recipients, a twofold increase in ferritin was associated with reduced odds of LBW (aOR 0.80; 95% CI 0.67, 0.94; P = 0.009). Mediation analyses suggested that malaria infection or haemoglobin levels during pregnancy do not substantially mediate the association of ID with birth outcomes amongst SPCQ recipients. CONCLUSIONS: Improved antenatal iron stores do not confer a benefit for the prevention of adverse birth outcomes in the context of malaria chemoprevention strategies that lack the non-malarial properties of monthly SPAZ. Research to determine the mechanisms by which ID protects from suboptimal foetal growth is needed to guide the design of new malaria prevention strategies and to inform iron supplementation policy in malaria-endemic settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT01136850 .

"An unnecessary cut?" multilevel health systems analysis of drivers of caesarean sections rates in Italy: a systematic review.

BACKGROUND: Improvements in medical technologies have seen over-medicalization of childbirth. Caesarean section (CS) is a lifesaving procedure proven effective in reducing maternal and perinatal mortality across the globe. However, as with any medical procedure, the CS intrinsically carries some risk to its beneficiaries. In recent years, CS rates have risen alarmingly in high-income countries. Many exceeding the World Health Organisation (WHO) recommendation of a 10 to 15% annual CS rate. While this situation poses an increased risk to women and their children, it also represents an excess human and financial burden on health systems. Therefore, from a health system perspective this study systematically summarizes existing evidence relevant to the factors driving the phenomenon of increasing CS rates using Italy as a case study. METHODS: Employing the WHO Health System Framework (WHOHSF), this systematic review used the PRISMA guidelines to report findings. PubMed, SCOPUS, MEDLINE, Cochrane Library and Google Scholar databases were searched up until April 1, 2020. Findings were organised through the six dimensions of the WHOHSF framework: service delivery, health workforce, health system information; medical products vaccine and technologies, financing; and leadership and governance. RESULTS: CS rates in Italy are affected by complex interactions among several stakeholder groups and contextual factors such as the hyper-medicalisation of delivery, differences in policy and practice across units and the national context, issues pertaining to the legal and social environment, and women's attitudes towards pregnancy and childbirth. CONCLUSION: Mitigating the high rates of CS will require a synergistic multi-stakeholder intervention. Specifically, with processes able to attract the official endorsement of policy makers, encourage concensus between regional authorities and local governments and guide the systematic compliance of delivery units with its clinical guidelines.

Risk factors associated with severe perineal lacerations during vaginal delivery: a 10-year propensity score-matched observational study.

BACKGROUND: Severe perineal lacerations are rare obstetrical complications in high-income countries. However, the prevention of obstetric anal sphincter injuries is crucial because of their long-term consequences on a woman's digestive function, sexual-mental health, and well-being. The probability of obstetric anal sphincter injuries can be predicted by assessing antenatal and intrapartum risk factors. OBJECTIVE: This study aimed to assess the incidence of obstetric anal sphincter injuries at a single institution for 10 years and to identify women more at risk by evaluating the relationship between antenatal and intrapartum risk factors and severe perineal tears. The main outcome measured in this study was the occurrence of obstetric anal sphincter injuries during vaginal delivery. STUDY DESIGN: This was an observational retrospective cohort study conducted at a University Teaching Hospital in Italy. The study was conducted from 2009 to 2019 using a prospectively maintained database. The study cohort included all women with singleton pregnancy at term who delivered via vaginal delivery in cephalic presentation. Of note, data analysis was performed in 2 stages: a propensity score matching to balance possible differences between patients with obstetric anal sphincter injuries and those without and a stepwise univariate and multivariate logistic regression. A secondary analysis was performed to further evaluate the effect of parity, epidural anesthesia, and duration of the second stage of labor by adjusting for potential confounders. RESULTS: Of 41,440 patients screened for eligibility, 22,156 met the inclusion criteria, and 15,992 were balanced after propensity score matching. Obstetric anal sphincter injuries occurred in 81 cases (0.4%), 67 (0.3%) after spontaneous delivery and 14 (0.8%) after vacuum delivery(P=.002). There was an increased odds of severe lacerations of nearly 2-fold for nulliparous women delivering by vacuum delivery (adjusted odds ratio, 2.85; 95% confidence interval, 1.19-6.81; P=.019), with a reciprocal reduction in women with spontaneous vaginal delivery (adjusted odds ratio, 0.35; 95% confidence interval, 0.15-0.84; P=.019) and at least 1 previous delivery (adjusted odds ratio, 0.51; 95% confidence interval, 0.31-0.85; P=.005). Epidural anesthesia was associated with a lower incidence of obstetric anal sphincter injuries (adjusted odds ratio, 0.54; 95% confidence interval, 0.33-0.86; P=.011). The risk of severe lacerations was independent of the duration of the second stage of labor (adjusted odds ratio, 1.00; 95% confidence interval, 0.99-1.00; P=.3), whereas the risk was reduced when mediolateral episiotomy was performed (adjusted odds ratio, 0.20; 95% confidence interval, 0.11-0.36; P<.001). Neonatal risk factors include head circumference (odds ratio, 1.50; 95% confidence interval, 1.18-1.90; P=.001) and vertex malpresentation (adjusted odds ratio, 2.71; 95% confidence interval, 1.08-6.78; P=.033). Induction of labor (adjusted odds ratio, 1.13; 95% confidence interval, 0.72-1.92; P=.6), frequent obstetrical examinations (adjusted odds ratio, 1.17; 95% confidence interval, 0.72-1.90), and women's supine position at birth (adjusted odds ratio, 1.25; 95% confidence interval, 0.61-2.55; P=.5) were further evaluated. Among severe obstetrical complications, shoulder dystocia increased the risk of obstetric anal sphincter injuries by nearly 4 times (adjusted odds ratio, 3.92; 95% confidence interval, 0.50-30.74; P=.2), whereas postpartum hemorrhage occurred 3 times more often in cases of delivery complicated by severe lacerations (adjusted odds ratio, 3.35; 95% confidence interval, 1.76-6.40; P<.001). The relationship among obstetric anal sphincter injuries, parity, and the use of epidural anesthesia was further confirmed in a secondary analysis. We found that primiparas who delivered without epidural anesthesia had the highest risk of obstetric anal sphincter injuries (adjusted odds ratio, 2.53; 95% confidence interval, 1.46-4.39; P=.001). CONCLUSION: Severe perineal lacerations were found to be a rare complication of vaginal delivery. By using a robust statistical model, such as propensity score matching, we were able to investigate a broad range of antenatal and intrapartum risk factors, including use of epidural anesthesia, number of obstetrics examinations, and patient position at birth, which are usually underreported. Moreover, we found that women who delivered for the first time without epidural anesthesia had the highest risk of obstetric anal sphincter injuries.

Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis.

INTRODUCTION: Despite a growing body of research on the risks of SARS-CoV-2 infection during pregnancy, there is continued controversy given heterogeneity in the quality and design of published studies. METHODS: We screened ongoing studies in our sequential, prospective meta-analysis. We pooled individual participant data to estimate the absolute and relative risk (RR) of adverse outcomes among pregnant women with SARS-CoV-2 infection, compared with confirmed negative pregnancies. We evaluated the risk of bias using a modified Newcastle-Ottawa Scale. RESULTS: We screened 137 studies and included 12 studies in 12 countries involving 13 136 pregnant women.Pregnant women with SARS-CoV-2 infection-as compared with uninfected pregnant women-were at significantly increased risk of maternal mortality (10 studies; n=1490; RR 7.68, 95% CI 1.70 to 34.61); admission to intensive care unit (8 studies; n=6660; RR 3.81, 95% CI 2.03 to 7.17); receiving mechanical ventilation (7 studies; n=4887; RR 15.23, 95% CI 4.32 to 53.71); receiving any critical care (7 studies; n=4735; RR 5.48, 95% CI 2.57 to 11.72); and being diagnosed with pneumonia (6 studies; n=4573; RR 23.46, 95% CI 3.03 to 181.39) and thromboembolic disease (8 studies; n=5146; RR 5.50, 95% CI 1.12 to 27.12).Neonates born to women with SARS-CoV-2 infection were more likely to be admitted to a neonatal care unit after birth (7 studies; n=7637; RR 1.86, 95% CI 1.12 to 3.08); be born preterm (7 studies; n=6233; RR 1.71, 95% CI 1.28 to 2.29) or moderately preterm (7 studies; n=6071; RR 2.92, 95% CI 1.88 to 4.54); and to be born low birth weight (12 studies; n=11 930; RR 1.19, 95% CI 1.02 to 1.40). Infection was not linked to stillbirth. Studies were generally at low or moderate risk of bias. CONCLUSIONS: This analysis indicates that SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction. As more data become available, we will update these findings per the published protocol.

The Effect of Epidural Analgesia on Labour and Neonatal and Maternal Outcomes in 1, 2a, 3, and 4a Robson's Classes: A Propensity Score-Matched Analysis.

Background: Lumbar epidural analgesia (EA) is the most commonly used method for reducing labour pain, but its impact on the duration of the second stage of labour and on neonatal and maternal outcomes remains a matter of debate. Our aim was to examine whether EA affected the course and the outcomes of labour among patients divided according to the Robson-10 group classification system. Methods: Patients of Robson's classes 1, 2a, 3, and 4a were divided into either the EA group or the non-epidural analgesia (NEA) group. A propensity score-matching analysis was performed to balance the intergroup differences. The primary goal was to analyse the duration of the second stage of labour. The secondary goals were to evaluate neonatal and maternal outcomes. Results: In total, 21,808 cases were analysed. The second stage of labour for all groups was prolonged using EA (p < 0.05) without statistically significant differences in neonatal outcomes. EA resulted in a lower rate of episiotomies in nulliparous patients, with a higher rate of operative vaginal deliveries (OVD) (p < 0.05) and Caesarean sections (CS) (p < 0.05) in some classes. Conclusions: EA prolonged the duration of labour without affecting neonatal outcomes and reduced the rate of episiotomies, but also increased the rate of OVDs.

Protocol for a sequential, prospective meta-analysis to describe coronavirus disease 2019 (COVID-19) in the pregnancy and postpartum periods.

We urgently need answers to basic epidemiological questions regarding SARS-CoV-2 infection in pregnant and postpartum women and its effect on their newborns. While many national registries, health facilities, and research groups are collecting relevant data, we need a collaborative and methodologically rigorous approach to better combine these data and address knowledge gaps, especially those related to rare outcomes. We propose that using a sequential, prospective meta-analysis (PMA) is the best approach to generate data for policy- and practice-oriented guidelines. As the pandemic evolves, additional studies identified retrospectively by the steering committee or through living systematic reviews will be invited to participate in this PMA. Investigators can contribute to the PMA by either submitting individual patient data or running standardized code to generate aggregate data estimates. For the primary analysis, we will pool data using two-stage meta-analysis methods. The meta-analyses will be updated as additional data accrue in each contributing study and as additional studies meet study-specific time or data accrual thresholds for sharing. At the time of publication, investigators of 25 studies, including more than 76,000 pregnancies, in 41 countries had agreed to share data for this analysis. Among the included studies, 12 have a contemporaneous comparison group of pregnancies without COVID-19, and four studies include a comparison group of non-pregnant women of reproductive age with COVID-19. Protocols and updates will be maintained publicly. Results will be shared with key stakeholders, including the World Health Organization (WHO) Maternal, Newborn, Child, and Adolescent Health (MNCAH) Research Working Group. Data contributors will share results with local stakeholders. Scientific publications will be published in open-access journals on an ongoing basis.