Prophylactic exchange-transfusion in sickle cell disease pregnancy: TAPS2 feasibility randomized controlled trial.

Serial prophylactic exchange blood transfusion (SPEBT) is increasingly used in pregnant women with sickle cell disease (SCD), despite a lack of robust evidence. TAPS2 (Transfusion Antenatally in Pregnant Women with Sickle Cell Disease) study assessed the feasibility and acceptability of conducting a definitive randomized controlled trial of SPEBT (intervention) versus standard care (control) in pregnant women with SCD. Women ≥18 years with SCD, between 6+0 and 18+0 weeks of singleton gestation, were randomized 1:1 to control or intervention every 6-10 weeks throughout pregnancy in seven hospitals in England. The main outcomes evaluated were recruitment rate (primary outcome), acceptability, and retention. Secondary outcomes were safety, maternal and infant clinical outcomes. 194 women were screened over 42 months (extended due to the pandemic), 88 were eligible, and 35 (39.8%) consented to participate. Eighteen participants were randomized to intervention and 17 to control. Follow-up data were collected on all participants. Twelve patients in the intervention group received at least one SPEBT, of these, 11 received  3. The remaining patient was withdrawn from SPEBT due to transfusion reaction. Sixteen control participants required at least one transfusion. There were no statistically significant differences in terms of maternal, infant, or postnatal outcomes. A trend towards a lower incidence of vaso-occlusive crisis, preterm delivery and improved birthweight was observed in the intervention group. Despite the pandemic, this study achieved satisfactory recruitment and retention, confirming its acceptability to participants. TAPS2 demonstrates that it is feasible to perform a definitive international trial of SPEBT in pregnant women with SCD. Trial registration: NIH registry (www.clinicaltrials.gov), registration number NCT03975894 (registered 05/06/19); ISRCTN (www.isrctn.com), registration number ISRCTN52684446 (retrospectively registered 02/08/19). TAPS2 trial Protocol: available at https://rdcu.be/drlwc.

Association between breastfeeding duration and educational attainment in rural Southwest Uganda: a population-based cohort study.

BACKGROUND: Breastfeeding is important for early childhood nutrition and health. The positive effects on educational outcomes may be attributed to socioeconomic factors. Socioeconomic status is not a strong predictor of breastfeeding in sub-Saharan African countries. Yet, few studies have investigated the association between breastfeeding and educational outcomes in these countries. OBJECTIVE: This study investigated the association between breastfeeding duration and children's educational attainment in rural Southwest Uganda. METHODS: We analysed longitudinal data on 3018 children who had information on breastfeeding and were followed for at least 5 years, with at least one primary school grade recorded by 2005. Data on breastfeeding duration were collected from mothers. The highest school grade was recorded repeatedly between ages 6 and 12 years. We calculated age-for-grade based on whether a child was on, over, or under the official age for a grade. Generalised estimating equations and binary logistic regression estimated the effect of breastfeeding duration on being 2 years, 3 or more years, or any years over-age for grade in primary school, adjusting for socioeconomic status and maternal-child characteristics. RESULTS: Most mothers breastfed for more than a year. Just over one-third breastfed for 18-23 months, and 30% breastfed for longer. By age eight, 42% of the children were two years over-age for their grade. Three or more years over-age for grade increased from 19% at age nine to 56% at age 12. Both adjusted and unadjusted estimates were consistent in showing reduced odds for children being 2 years, 3 or more years, or any years over-age for grade among children breastfed for 7-12, 13-17, 18-23, and > 23 months compared to those breastfed for 0-6 months. There was no evidence to support an overall association between breastfeeding duration and being over-age for grade. There was no evidence of association in the sex and age sub-group analyses. CONCLUSION: Although we found no association between breastfeeding duration and educational attainment, breastfeeding remains important for children's health and nutrition, and mothers should be encouraged and supported to breastfeed for the recommended duration.

Main findings: We found no clear evidence of an association between breastfeeding duration and educational attainment in rural Uganda.Added knowledge: The findings of this study contribute to a better understanding of the relationship between breastfeeding and educational outcomes in sub-Saharan African countries, where evidence on this topic is limited.Global health impact for policy and action: Our findings should not discourage breastfeeding, as it is essential for infant health and nutrition.

Statistical analysis plan and protocol updates for Gestational diabetes in Uganda and India: Design and Evaluation of Educational Films for Improving Screening and Self-management (GUIDES) trial.

BACKGROUND: Timely detection and management of gestational diabetes mellitus (GDM) have been identified as a high priority for policymakers in low- and middle-income countries (LMICs). The GUIDES trial will evaluate a package of three interconnected film-based interventions aimed at improving the timely detection and management of GDM. The protocol for this trial has previously been published; this publication outlines the statistical analysis plan for the trial. METHODS AND DESIGN: The GUIDES study is a multi-country cluster-randomised controlled trial consisting of one trial conducted in Uganda and one in India (30 clusters in each country). Mixed effects models will be used to compare the primary study outcomes of the proportion of women who are tested for GDM between 24 and 32 weeks of pregnancy and the mean fasting blood sugar of women with GDM at 34-week follow-up while accounting for clustering. Secondary analyses will compare the proportion of women with self-reported GDM diagnosis at 32 weeks of pregnancy and the proportion of women with adverse perinatal outcomes related to GDM up to 4 weeks after birth in each trial arm. TRIAL STATUS AND DISCUSSION: Follow-up is expected to end in March 2023 in Uganda and in May 2023 in India. Analyses will be carried out following this statistical analysis plan in the month following trial completion. TRIAL REGISTRATION: ClinicalTrials.gov NCT03937050. Registered on 3 May 2019. Clinical Trials Registry India CTRI/2020/02/023605. Registered on 26 February 2020.

Effects of exclusive breastfeeding on educational attainment and longitudinal trajectories of grade progression among children in a 13-year follow-up study in Malawi.

The benefits of exclusive breastfeeding (EBF) for infant health and survival are well documented. However, its impact on educational outcomes has been contested and poorly researched in Africa. It has been hypothesised that positive associations reported in high-income countries can be attributed to residual confounding by socioeconomic status (SES). Our study investigated whether EBF duration in infancy is associated with educational attainment and age-for-grade attainment trajectories at school-age in rural Malawi. Longitudinal data on 1021 children at the Karonga demographic surveillance site in Malawi were analysed. Breastfeeding data were collected 3 months after birth and again at age one. The school grade of each child was recorded each year from age 6 until age 13. We calculated age-for-grade based on whether a child was at, over, or under the official expected age for a grade. Generalised estimating equations estimated the average effect of breastfeeding on age-for-grade. Latent class growth analysis identified age-for-grade trajectories, and multinomial logistic regression examined their associations with EBF. Maternal-child characteristics, SES, and HIV status were controlled. Overall, 35.9% of the children were exclusively breastfed for 6 months. Over-age for grade steadily increased from 9.6% at age 8 to 41.9% at age 13. There was some evidence that EBF for 6 months was associated with lower odds of being over-age for grade than EBF for less than 3 months (aOR = 0.82, 95%CI = 0.64-1.06). In subgroup analyses, children exclusively breastfed for 6 months in infancy were less likely to be over-age for grades between ages 6-9 (aOR = 0.64, 95%CI = 0.43-0.94). Latent class growth analysis also provided some evidence that EBF reduced the odds of falling behind in the early school grades (aOR = 0.66, 95%CI = 0.41-1.08) but not later. Our study adds to the growing evidence that EBF for 6 months has benefits beyond infant health and survival, supporting the WHO's recommendation on EBF.

Contraceptive use and pregnancy planning in Britain during the first year of the COVID-19 pandemic: findings from a large, quasi-representative survey (Natsal-COVID).

BACKGROUND: Contraceptive services were significantly disrupted during the COVID-19 pandemic in Britain. We investigated contraception-related health inequalities in the first year of the pandemic. METHODS: Natsal-COVID Wave 2 surveyed 6658 adults aged 18-59 years between March and April 2021, using quotas and weighting to achieve quasi-representativeness. Our analysis included sexually active participants aged 18-44 years, described as female at birth. We analysed contraception use, contraceptive switching due to the pandemic, contraceptive service access, and pregnancy plannedness. RESULTS: Of 1488 participants, 1619 were at risk of unplanned pregnancy, of whom 54.1% (51.0%-57.1%) reported routinely using effective contraception in the past year. Among all participants, 14.3% (12.5%-16.3%) reported switching or stopping contraception due to the pandemic. 3.2% (2.0%-5.1%) of those using effective methods pre-pandemic switched to less effective methods, while 3.8% (2.5%-5.9%) stopped. 29.3% (26.9%-31.8%) of at-risk participants reported seeking contraceptive services, of whom 16.4% (13.0%-20.4%) reported difficulty accessing services. Clinic closures and cancelled appointments were commonly reported pandemic-related reasons for difficulty accessing services. This unmet need was associated with younger age, diverse sexual identities and anxiety symptoms. Of 199 pregnancies, 6.6% (3.9%-11.1%) scored as 'unplanned'; less planning was associated with younger age, lower social grade and unemployment. CONCLUSIONS: Just under a third of participants sought contraceptive services during the pandemic and most were successful, indicating resilience and adaptability of service delivery. However, one in six reported an unmet need due to the pandemic. COVID-induced inequalities in service access potentially exacerbated existing reproductive health inequalities. These should be addressed in the post-pandemic period and beyond.

Serial prophylactic exchange blood transfusion in pregnant women with sickle cell disease (TAPS-2): statistical and qualitative analysis plan for a randomised controlled feasibility trial.

BACKGROUND: There are significant knowledge gaps regarding the effectiveness of serial prophylactic exchange blood transfusion (SPEBT) for pregnant women with sickle cell disease (SCD). The protocol for the randomised feasibility trial assessing SPEBT versus usual care in women with SCD (TAPS2 trial) has previously been published. This publication outlines the statistical and qualitative analysis plan for the study. METHODS AND DESIGN: TAPS2 is a randomised two-arm phase 2 feasibility trial with a nested qualitative study and health economic evaluation. Up to 50 pregnant women with SCD and a singleton pregnancy will be recruited and individually randomised to either SPEBT approximately every 6-10 weeks until delivery (intervention arm) or to usual care (control arm). Information will be collected on a range of feasibility and clinical outcomes. RESULTS: Due to the impact of COVID-19 on study recruitment, the initial study period of 24 months was extended to 48 months. Other protocol updates designed to mitigate the impact of COVID-19-related disruption included allowing for remote consent and conducting all qualitative interviews by telephone. The primary outcome for the trial is the overall recruitment rate. The number of women screened, eligible, consented, randomised and withdrawn will be summarised as a CONSORT flow diagram. Differences in clinical outcomes will additionally be presented as an initial assessment of efficacy and to inform sample size calculations for a future definitive trial. Qualitative interviews with trial participants and clinicians will be analysed using reflexive thematic analysis; data from interviews with participants who declined to participate in the trial will be extracted and incorporated into summary tables to report key findings. The health economic analysis plan is not covered by this update. CONCLUSION: The publication of this analysis plan is designed to aid transparency and to reduce the potential for reporting bias. TRIAL REGISTRATION: NIH registry ( www. CLINICALTRIALS: gov ), registration number NCT03975894 (registered 05/06/19); ISRCTN ( www.isrctn.com ), registration number ISRCTN52684446 (retrospectively registered 02/08/19).

Fetal death after the introduction of COVID-19 mitigation measures in Sweden, Denmark and Norway: a registry-based study.

It remains unclear whether the rate of fetal death has changed during the COVID-19 pandemic. We assessed the impact of COVID-19 mitigation measures on fetal death in Sweden (449,347 births), Denmark (290,857 pregnancies) and Norway (261,057 pregnancies) using robust population-based registry data. We used Cox regression to assess the impact of the implementation of pandemic mitigation measures on March 12th, 2020, on miscarriage (fetal loss before gestational week 22) and stillbirth (fetal loss after gestational week 22). A total of 11% of 551,914 pregnancies in Denmark and Norway ended in miscarriage, while the proportion of stillbirths among 937,174 births across the three countries was 0.3%. There was no difference in the risk of fetal death during the year following pandemic mitigation measures. For miscarriage, the combined hazard ratio (HR) for Norway and Denmark was 1.01 (95% CI 0.98, 1.03), and for stillbirth, the combined HR for all three countries was 0.99 (95% CI 0.89, 1.09). We observed a slightly decreased risk of miscarriage during the first 4 months, with an HR of 0.94 (95% CI 0.90, 0.99) after lockdown. In conclusion, the risk of fetal death did not change after the implementation of COVID-19 pandemic mitigation measures in the three Scandinavian countries.

Impact of COVID-19 on pregnancy-related healthcare utilisation: a prospective nationwide registry study.

OBJECTIVE: To assess the impact of COVID-19 on pregnancy-related healthcare utilisation and differences across social groups. DESIGN: Nationwide longitudinal prospective registry-based study. SETTING: Norway. PARTICIPANTS: Female residents aged 15-50 years (n=1 244 560). MAIN OUTCOME MEASURES: Pregnancy-related inpatient, outpatient and primary care healthcare utilisation before the COVID-19 pandemic (prepandemic: 1 January to 11 March 2020), during the initial lockdown (first wave: 12 March to 3 April 2020), during the summer months of low restrictions (summer period: 4 April to 31 August 2020) and during the second wave to the end of the year (second wave: 1 September to 31 December 2020). Rates were compared with the same time periods in 2019. RESULTS: There were 130 924 inpatient specialist care admissions, 266 015 outpatient specialist care consultations and 2 309 047 primary care consultations with pregnancy-related diagnostic codes during 2019 and 2020. After adjusting for time trends and cofactors, inpatient admissions were reduced by 9% (adjusted incidence rate ratio (aIRR)=0.91, 95% CI 0.87 to 0.95), outpatient consultations by 17% (aIRR=0.83, 95% CI 0.71 to 0.86) and primary care consultations by 10% (aIRR=0.90, 95% CI 0.89 to 0.91) during the first wave. Inpatient care remained 3%-4% below prepandemic levels throughout 2020. Reductions according to education, income and immigrant background were also observed. Notably, women born in Asia, Africa or Latin America had a greater reduction in inpatient (aIRR=0.87, 95% CI 0.77 to 0.97) and outpatient (aIRR 0.90, 95% CI 0.86 to 0.95) care during the first wave, compared with Norwegian-born women. We also observed that women with low education had a greater reduction in inpatient care during summer period (aIRR=0.88, 95% CI 0.83 to 0.92), compared with women with high educational attainment. CONCLUSION: Following the introduction of COVID-19 mitigation measures in Norway in March 2020, there were substantial reductions in pregnancy-related healthcare utilisation, especially during the initial lockdown and among women with an immigrant background.

The association of breastfeeding with cognitive development and educational achievement in sub-Saharan Africa: A systematic review.

Background: Systematic reviews and meta-analyses of studies mainly from high-income countries suggest that breastfeeding improves cognitive function and educational achievement. However, these associations may be a manifestation of who breastfeeds in these settings rather than an actual effect of breastfeeding. We investigated the association of breastfeeding with cognitive development and educational achievements in sub-Saharan Africa, where breastfeeding is the norm, and socioeconomic status is not strongly correlated with ever breastfeeding. Methods: We searched Medline, Embase, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), and Africa-Wide Information in January 2021 for studies that assessed the cognitive and educational benefits of breastfeeding in children and adolescents in sub-Saharan Africa. Two reviewers independently screened, extracted, and critically appraised the included studies. Results: After reviewing 5552 abstracts and 151 full-text articles, seventeen studies on cognitive development and two on educational achievements met our predefined inclusion criteria. The included studies were from ten sub-Saharan African countries and published between 2013 and 2021, with sample sizes ranging from 54 to 6573. Most of the studies (n = 14) were prospective cohort studies, but only nine collected data on breastfeeding prospectively. The studies differed in analytic approaches and cognitive and educational achievements measurements. Of the 17 studies on cognitive development, only four adjusted sufficiently for key confounders. None of these four studies found an overall association between breastfeeding and cognitive development in children or adolescents in sub-Saharan Africa. The two studies on education measured achievements based on the highest grade of school attained, 12 or more years of education, or grade repetition at age 7-11 years. Both studies adjusted for a range of sociodemographic factors and found no evidence that children exclusively breastfed or breastfed for a longer duration have a better educational outcome than sub-optimally breastfed children. Conclusions: The current evidence from sub-Saharan Africa is limited but does not corroborate previous findings that breastfeeding is associated with improved cognitive development and educational achievement. Registration: This study is registered with PROSPERO, CRD42021236009.

Risk of preterm birth, small for gestational age at birth, and stillbirth after covid-19 vaccination during pregnancy: population based retrospective cohort study.

OBJECTIVE: To assess the risk of preterm birth, small for gestational age at birth, and stillbirth after covid-19 vaccination during pregnancy. DESIGN: Population based retrospective cohort study. SETTING: Ontario, Canada, 1 May to 31 December 2021. PARTICIPANTS: All liveborn and stillborn infants from pregnancies conceived at least 42 weeks before the end of the study period and with gestational age ≥20 weeks or birth weight ≥500 g. MAIN OUTCOME MEASURES: Using Cox regression, hazard ratios and 95% confidence intervals were estimated for preterm birth before 37 weeks (overall and spontaneous preterm birth), very preterm birth (<32 weeks), small for gestational age at birth (<10th centile), and stillbirth. Vaccination against covid-19 was treated as a time varying exposure in the outcome specific risk window, and propensity score weighting was used to adjust hazard ratios for potential confounding. RESULTS: Among 85 162 births, 43 099 (50.6%) occurred in individuals who received one dose or more of a covid-19 vaccine during pregnancy-42 979 (99.7%) received an mRNA vaccine. Vaccination during pregnancy was not associated with any increased risk of overall preterm birth (6.5% among vaccinated v 6.9% among unvaccinated; adjusted hazard ratio 1.02, 95% confidence interval 0.96 to 1.08), spontaneous preterm birth (3.7% v 4.4%; 0.96, 0.90 to 1.03), or very preterm birth (0.59% v 0.89%; 0.80, 0.67 to 0.95). No increase was found in risk of small for gestational age at birth (9.1% v 9.2%; 0.98, 0.93 to 1.03) or stillbirth (0.25% v 0.44%; 0.65, 0.51 to 0.84). Findings were similar by trimester of vaccination, mRNA vaccine product, and number of doses received during pregnancy. CONCLUSION: The findings suggest that vaccination against covid-19 during pregnancy is not associated with a higher risk of preterm birth, small for gestational age at birth, or stillbirth.

Time trends in the prevalence and determinants of age-appropriate breast feeding among children aged 0-23 months in Ghana: a pooled analysis of population-based surveys, 2003-2017.

OBJECTIVE: We assessed the sociodemographic and maternal-child characteristics associated with age-appropriate breast feeding among children aged 0-23 months in Ghana. METHODS: We pooled data on 12 743 children aged 0-23 months from three Demographic and Health Surveys (2003, 2008 and 2014) and three Multiple Indicator Cluster Surveys (2006, 2011 and 2017-2018). The outcome was age-appropriate breast feeding from birth to 23 months, with age-appropriate breast feeding defined as exclusive breast feeding at 0-5 months (ie, at less than 6 months) and breastfeeding alongside appropriate complementary feeding at 6-23 months. Potential determinants were maternal-child sociodemographic, obstetric and healthcare factors. Logistic regression was used to determine the factors associated with age-appropriate breast feeding. We accounted for the complex sampling design of the cross-sectional surveys in the analysis. RESULTS: Most children aged 0-3 months were exclusively breastfed. Among children aged 4-5 months, the most common feeding pattern was breastfeeding alongside water and/or solid foods. Exclusive breastfeeding prevalence in children less than 6 months peaked in 2008 at 62.8% and declined to 42.9% in 2017. For 6-11 month olds, the percentage experiencing age-appropriate breast feeding has been stable over the last four surveys, ranging from 79.3% in 2008 to 81.1% in 2017. Age-appropriate breast feeding in 12-23 month olds declined from 77.8% in 2003 to 61.2% in 2017. Rural residence, younger age, non-facility births and multiple births were associated with decreased odds of exclusively breast feeding. For 6-11 month olds, age-appropriate breast feeding was less likely if the woman did not receive postnatal care. Younger age, being unmarried, high income, wanting a child later and earlier birth order were associated with decreased odds of age-appropriate breast feeding in 12-23 month olds. CONCLUSION: Ghanaian children are now less likely to be exclusively breastfed than they were a decade ago. To succeed, breastfeeding promotion programmes should adopt approaches that address the predictors of suboptimal breast feeding at each age, as identified in this study.

Association of COVID-19 Vaccination During Pregnancy With Incidence of SARS-CoV-2 Infection in Infants.

Importance: Pregnant women are recommended to receive COVID-19 vaccination to reduce risk of severe COVID-19. Whether vaccination during pregnancy also provides passive protection to infants after birth remains unclear. Objective: To determine whether COVID-19 vaccination in pregnancy was associated with reduced risk of COVID-19 in infants up to age 4 months during COVID-19 pandemic periods dominated by Delta and Omicron variants. Design, Setting, and Participants: This nationwide, register-based cohort study included all live-born infants born in Norway between September 1, 2021, and February 28, 2022. Exposures: Maternal messenger RNA COVID-19 vaccination during second or third trimester compared with no vaccination before or during pregnancy. Main Outcomes and Measures: The risk of a positive polymerase chain reaction test result for SARS-CoV-2 during an infant's first 4 months of life by maternal vaccination status during pregnancy with either dose 2 or 3 was estimated, as stratified by periods dominated by the Delta variant (between September 1 and December 31, 2021) or Omicron variant (after January 1, 2022, to the end of follow-up on April 4, 2022). A Cox proportional hazard regression was used, adjusting for maternal age, parity, education, maternal country of birth, and county of residence. Results: Of 21 643 live-born infants, 9739 (45.0%) were born to women who received a second or third dose of a COVID-19 vaccine during pregnancy. The first 4 months of life incidence rate of a positive test for SARS-CoV-2 was 5.8 per 10 000 follow-up days. Infants of mothers vaccinated during pregnancy had a lower risk of a positive test compared with infants of unvaccinated mothers and lower risk during the Delta variant-dominated period (incidence rate, 1.2 vs 3.0 per 10 000 follow-up days; adjusted hazard ratio, 0.29; 95% CI, 0.19-0.46) compared with the Omicron period (incidence rate, 7.0 vs 10.9 per 10 000 follow-up days; adjusted hazard ratio, 0.67; 95% CI, 0.57-0.79). Conclusions and Relevance: The results of this Norwegian population-based cohort study suggested a lower risk of a positive test for SARS-CoV-2 during the first 4 months of life among infants born to mothers who were vaccinated during pregnancy. Maternal COVID-19 vaccination may provide passive protection to young infants, for whom COVID-19 vaccines are currently not available.

The association between maternal characteristics and SARS-CoV-2 in pregnancy: a population-based registry study in Sweden and Norway.

The objectives of the current study were to identify risk factors for SARS-CoV-2 positivity, and to address how different testing strategies, choice of comparison group, and population background characteristics may influence observed associations. National registries data for 107,627 pregnant women in Sweden and 81,195 in Norway, were used to identify risk factors for SARS-CoV-2, separately for women under non-universal testing (testing by indication) and universal testing (testing of all pregnant women in contact with a delivery ward). We also investigated underlying characteristics associated with testing for SARS-CoV-2. Overall, 2.1% of pregnant women in Sweden and 1.1% in Norway were test-positive during the pandemic's first 18 months. We show that the choice of test strategy for SARS-CoV-2 provided different associations with risk factors for the disease; for instance, women who were overweight, obese or had gestational diabetes had increased odds of being test-positive under non-universal testing, but not under universal testing. Nevertheless, a consistent pattern of association between being born in the Middle East and Africa and test-positivity was found independent of test strategy and in both countries. These women were also less likely to get tested. Our results are useful to consider for surveillance and clinical recommendations for pregnant women during the current and future pandemics.

Association of SARS-CoV-2 Vaccination During Pregnancy With Pregnancy Outcomes.

Importance: Data about the safety of vaccines against SARS-CoV-2 during pregnancy are limited. Objective: To examine the risk of adverse pregnancy outcomes after vaccination against SARS-CoV-2 during pregnancy. Design, Setting, and Participants: This registry-based retrospective cohort study included 157 521 singleton pregnancies ending after 22 gestational weeks from January 1, 2021, until January 12, 2022 (Sweden), or January 15, 2022 (Norway). The Pregnancy Register in Sweden and the Medical Birth Registry of Norway were linked to vaccination and other registries for identification of exposure and background characteristics. Exposures: Data on mRNA vaccines-BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)-and 1 viral vector vaccine-AZD1222 (AstraZeneca)-were collected from national vaccination registries. Main Outcomes and Measures: The risk of preterm birth and stillbirth was evaluated using Cox regression models, with gestational day as the time metric and vaccination as a time-dependent exposure variable. The risk of small for gestational age, low Apgar score, and neonatal care admission was evaluated using logistic regression. Random-effects meta-analysis was used to combine results between countries. Results: Among the 157 521 singleton births included in the study (103 409 in Sweden and 54 112 in Norway), the mean maternal age at the time of delivery was 31 years, and 28 506 (18%) were vaccinated against SARS-CoV-2 (12.9% with BNT162b2, 4.8% with mRNA-1273, and 0.3% with AZD1222) while pregnant. A total of 0.7%, 8.3%, and 9.1% of individuals delivering were vaccinated during the first, second, and third trimester, respectively. Vaccination against SARS-CoV-2 was not significantly associated with increased risk of preterm birth (6.2 vs 4.9 per 10 000 pregnancy days; adjusted hazard ratio [aHR], 0.98 [95% CI, 0.91 to 1.05]; I2 = 0%; P for heterogeneity = .60), stillbirth (2.1 vs 2.4 per 100 000 pregnancy days; aHR, 0.86 [95% CI, 0.63 to 1.17]), small for gestational age (7.8% vs 8.5%; difference, -0.6% [95% CI, -1.3% to 0.2%]; adjusted OR [aOR], 0.97 [95% CI, 0.90 to 1.04]), low Apgar score (1.5% vs 1.6%; difference, -0.05% [95% CI, -0.3% to 0.1%]; aOR, 0.97 [95% CI, 0.87 to 1.08]), or neonatal care admission (8.5% vs 8.5%; difference, 0.003% [95% CI, -0.9% to 0.9%]; aOR, 0.97 [95% CI, 0.86 to 1.10]). Conclusions and Relevance: In this population-based study conducted in Sweden and Norway, vaccination against SARS-CoV-2 during pregnancy, compared with no SARS-CoV-2 vaccination during pregnancy, was not significantly associated with an increased risk of adverse pregnancy outcomes. The majority of the vaccinations were with mRNA vaccines during the second and third trimesters of pregnancy, which should be considered in interpreting the findings.

Influenza hospitalizations during childhood in children born preterm.

OBJECTIVE: The objective is to determine if children born preterm were at increased risk of influenza hospitalization up to age five. METHODS: National registry data on all children born in Norway between 2008 and 2011 were used in Cox regression models to estimate adjusted hazard ratios (aHRs) for influenza hospitalizations up to age five in children born preterm (<37 pregnancy weeks). HRs were also estimated separately for very preterm (<32 weeks), early term (37-38 weeks), and post-term (≥42 weeks) children. RESULTS: Among 238,628 children born in Norway from January 2008 to December 2011, 15,086 (6.3%) were born preterm. There were 754 (0.3%) children hospitalized with influenza before age five. The rate of hospitalizations in children born preterm was 13.8 per 10,000 person-years (95% confidence interval [CI] [11.3, 16.7]), and 5.9 per 10,000 person-years (95% CI [5.5, 6.4]) in children born at term (≥37 weeks). Children born preterm had a higher risk of influenza hospitalization before age 5: aHR 2.33 (95% CI [1.85, 2.93]). The risk increased with decreasing gestational age and was highest among those born extremely/very preterm; aHR 4.07 (95% CI [2.63, 6.31]). Compared with children born at 40-41 weeks, children born early term also had an elevated risk of influenza hospitalization; aHR (37 weeks) 1.89 (95% CI [1.43, 2.50]), aHR (38 weeks) 1.43 (95% CI [1.15, 1.78]). CONCLUSION: Children born preterm had a higher risk of influenza hospitalizations before age five. An elevated risk was also present among children born at an early term. Children born preterm could benefit from influenza vaccinations.

Childhood seizures after prenatal exposure to maternal influenza infection: a population-based cohort study from Norway, Australia and Canada.

OBJECTIVE: To assess whether clinical and/or laboratory-confirmed diagnosis of maternal influenza during pregnancy increases the risk of seizures in early childhood. DESIGN: Analysis of prospectively collected registry data for children born between 2009 and 2013 in three high-income countries. We used Cox regression to estimate country-level adjusted HRs (aHRs); fixed-effects meta-analyses were used to pool adjusted estimates. SETTING: Population-based. PARTICIPANTS: 1 360 629 children born between 1 January 2009 and 31 December 2013 in Norway, Australia (New South Wales) and Canada (Ontario). EXPOSURE: Clinical and/or laboratory-confirmed diagnosis of maternal influenza infection during pregnancy. MAIN OUTCOME MEASURES: We extracted data on recorded seizure diagnosis in secondary/specialist healthcare between birth and up to 7 years of age; additional analyses were performed for the specific seizure outcomes 'epilepsy' and 'febrile seizures'. RESULTS: Among 1 360 629 children in the study population, 14 280 (1.0%) were exposed to maternal influenza in utero. Exposed children were at increased risk of seizures (aHR 1.17, 95% CI 1.07 to 1.28), and also febrile seizures (aHR 1.20, 95% CI 1.07 to 1.34). There was no strong evidence of an increased risk of epilepsy (aHR 1.07, 95% CI 0.81 to 1.41). Risk estimates for seizures were higher after influenza infection during the second and third trimester than for first trimester. CONCLUSIONS: In this large international study, prenatal exposure to influenza infection was associated with increased risk of childhood seizures.

Preterm birth after the introduction of COVID-19 mitigation measures in Norway, Sweden, and Denmark: a registry-based difference-in-differences study.

BACKGROUND: Although some studies have reported a decrease in preterm birth following the start of the COVID-19 pandemic, the findings are inconsistent. OBJECTIVE: This study aimed to compare the incidences of preterm birth before and after the introduction of COVID-19 mitigation measures in Scandinavian countries using robust population-based registry data. STUDY DESIGN: This was a registry-based difference-in-differences study using births from January 2014 through December 2020 in Norway, Sweden, and Denmark. The changes in the preterm birth (<37 weeks) rates before and after the introduction of COVID-19 mitigation measures (set to March 12, 2020) were compared with the changes in preterm birth before and after March 12 from 2014 to 2019. The differences per 1000 births were calculated for 2-, 4-, 8-, 12-, and 16-week intervals before and after March 12. The secondary analyses included medically indicated preterm birth, spontaneous preterm birth, and very preterm (<32 weeks) birth. RESULTS: A total of 1,519,521 births were included in this study. During the study period, 5.6% of the births were preterm in Norway and Sweden, and 5.7% were preterm in Denmark. There was a seasonal variation in the incidence of preterm birth, with the highest incidence during winter. In all the 3 countries, there was a slight overall decline in preterm births from 2014 to 2020. There was no consistent evidence of a change in the preterm birth rates following the introduction of COVID-19 mitigation measures, with difference-in-differences estimates ranging from 3.7 per 1000 births (95% confidence interval, -3.8 to 11.1) for the first 2 weeks after March 12, 2020, to -1.8 per 1000 births (95% confidence interval, -4.6 to 1.1) in the 16 weeks after March 12, 2020. Similarly, there was no evidence of an impact on medically indicated preterm birth, spontaneous preterm birth, or very preterm birth. CONCLUSION: Using high-quality national data on births in 3 Scandinavian countries, each of which implemented different approaches to address the pandemic, there was no evidence of a decline in preterm births following the introduction of COVID-19 mitigation measures.

Perinatal outcomes in women with sickle cell disease: a matched cohort study from London, UK.

There are limited data on contemporary outcomes for women with sickle cell disease (SCD) in pregnancy. We conducted a single-site matched cohort study, comparing 131 pregnancies to women with SCD between 2007 and 2017 to a comparison group of 1310 pregnancies unaffected by SCD. Restricting our analysis to singleton pregnancies that reached 24 weeks of gestation, we used conditional Poisson regression to estimate adjusted risk ratios (aRRs) for perinatal outcomes. Infants born to mothers with SCD were more likely to be small for gestational age [aRR 1·69, 95% confidence interval (CI) 1·13-2·48], preterm (aRR 2·62, 95% CI 1·82-3·78) and require Neonatal Unit (NNU) admission (aRR 3·59, 95% CI 2·18-5·90). Pregnant women with SCD were at higher risk of pre-eclampsia/eclampsia (aRR 3·53, 95% CI 2·00-6·24), more likely to receive induction of labour (aRR 2·50, 95% CI 1·82-1·76) and caesarean birth (aRR 1·44, 95% CI 1·18-1·76). In analysis stratified by genotype, the risk of adverse outcomes was highest in haemoglobin SS (HbSS) pregnancies (n = 80). There was no strong evidence that haemoglobin SC (HbSC) pregnancies (n = 46) were at higher risk of preterm birth, caesarean delivery, or NNU admission. Pre-eclampsia/eclampsia was more frequently observed in HbSC pregnancies. Despite improvements in the care of pregnant women with SCD, the increased risk of adverse perinatal outcomes remains.