infant

Importance: The incidence and risk (predictive) factors for early life food allergy development remain uncertain.

Objective: To estimate the incidence and quantify risk factors for food allergy development.

Data sources: MEDLINE and Embase were systematically searched to January 1, 2025. Data were analyzed from June 1, 2025, to November 25, 2025.

Study selection: Incidence estimates included studies confirming food allergy via food challenge. Risk factor analyses included cohort, case-control, and cross-sectional studies in any language assessing children younger than 6 years using multivariable analyses.

Data extraction and synthesis: Paired reviewers independently extracted data. Random-effects meta-analyses pooled incidence and adjusted odds ratios (ORs). Risk of bias was assessed using the QUIPS tool, and certainty of evidence assessed using GRADE.

Main outcome and measure: The primary outcome was food allergy to age 6 years.

Results: A total of 190 studies involving 2.8 million participants across 40 countries were analyzed. Among studies using food challenge, overall food allergy incidence was likely 4.7% (moderate certainty). Among 176 studies identifying 342 risk factors with varying certainty, the strongest and most certain factors included prior allergic conditions (eg, atopic dermatitis [eczema] within the first year of life [OR, 3.88; risk difference [RD], 12.0%; 95% CI, 8.8%-15.7%], allergic rhinitis [OR, 3.39; RD, 10.1%; 95% CI, 6.7%-14.4%], and wheeze [OR, 2.11; RD, 5.0%; 95% CI, 2.1%-8.8%]), severity of atopic dermatitis (OR, 1.22; RD, 1.0%; 95% CI, 0.6%-1.6%), increased skin transepidermal water loss (OR, 3.36; RD, 10.0%; 95% CI, 6.3%-14.8%), filaggrin gene sequence variations (OR, 1.93; RD, 4.2%; 95% CI, 2.4%-6.4%), delayed solid food introduction (eg, peanut after age 12 months [OR, 2.55; RD, 6.8%; 95% CI, 1.9%-14.6%]), infant antibiotic use (first month [OR, 4.11; RD, 12.8%; 95% CI, 0.4%-40%], first year [OR, 1.39; RD, 1.8%; 95% CI, 0.8%-3.1%], during pregnancy [OR, 1.32; RD, 1.5%; 95% CI, 0.6%-2.5%]), male sex (OR, 1.24; RD, 1.1%; 95% CI, 0.7%-1.6%), firstborn child (OR, 1.13; RD, 0.6%; 95% CI, 0.3%-1.0%), family history of food allergy (eg, mother [OR, 1.98; RD, 4.4%; 95% CI, 2.5%-6.8%], father [OR, 1.69; RD, 3.2%; 95% CI, 1.3%-5.5%], both parents [OR, 2.07; RD, 4.8%; 95% CI, 1.3%-5.5%], siblings [OR, 2.36; RD, 6.0%; 95% CI, 4.4%-8.0%]), parental migration (OR, 3.28; RD, 9.7%; 95% CI, 4.9%-16.3%), self-identification as Black (vs White [OR, 3.93; RD, 12.1%; 95% CI, 5.2%-22.5%], vs non-Hispanic White [OR, 2.23; RD, 5.5%; 95% CI, 3.0%-8.7%]), and cesarean delivery (OR, 1.16; RD, 1.0%; 95% CI, 0.3%-1.2%). Factors like low birth weight, postterm birth, maternal diet, and stress during pregnancy showed no significant risk difference.

Conclusions and relevance: In this meta-analysis, the most credible risk factors associated with development of childhood food allergy are a combination of major and minor risk factors, including early allergic conditions (atopic march/diathesis), delayed allergen introduction, genetics, antibiotic exposure, demographic factors, and birth-related variables.

Importance: Gaps in knowledge exist about the impact of COVID-19 and vaccination on pregnancy outcomes.

Objective: To investigate the impact of vaccination on maternal and perinatal outcomes associated with SARS-CoV-2 infection in pregnancy.

Design, setting, and population: Population-level surveillance of pregnant individuals infected with SARS-CoV-2 and their infants using the CANCOVID-Preg database between April 5, 2021 (beginning of the Delta variant time period and initiation of recommendations for vaccination in pregnancy in Canada), and December 31, 2022. Cases were identified based on COVID-19 diagnoses in pregnancy in 9 of 13 Canadian provinces/territories. Cases occurring through 2022 were followed up into 2023 for pregnancy conclusion and infant outcomes.

Exposure: SARS-CoV-2 infection in pregnancy, with or without prior vaccination.

Main outcomes and measures: COVID-19-associated hospitalization, critical care unit admission, and preterm birth.

Results: Of 26 584 cases identified, 19 899 cases were eligible for analysis. Among these, most infections occurred among those aged 30 to 35 years (46.3%) and among those of White race (55.9%). A total of 72% (n = 14 367) of cases were vaccinated and 28% (n = 5532) were unvaccinated prior to their COVID-19 diagnosis. Among those vaccinated prior to COVID-19 diagnosis, 80% (n = 11 425) were vaccinated prior to pregnancy and 20% (n = 2942) were vaccinated during pregnancy. Cases occurred during both Delta (n = 6120) and Omicron (n = 13 799) variant time periods. Vaccination was associated with lower risk of hospitalization (Delta: relative risk [RR], 0.38 [95% CI, 0.30-0.48]; absolute risk difference [ARD], 8.7% [95% CI, 7.3%-10.2%]; Omicron: RR, 0.38 [95% CI, 0.27-0.53]; ARD, 3.8% [95% CI, 2.4%-5.2%]), critical care unit admission (Delta: RR, 0.10 [95% CI, 0.04-0.26]; ARD, 2.4% [95% CI, 1.8%-2.9%]; Omicron: RR, 0.10 [95% CI, 0.03-0.29]; ARD, 0.85% [95% CI, 0.27%-1.44%]), and preterm birth (Delta: RR, 0.80 [95% CI, 0.66-0.98]; ARD, 1.8% [95% CI, 0.3%-3.4%]; Omicron: RR, 0.64 [95% CI, 0.52-0.77]; ARD, 4.1% [95% CI, 2.0%-6.2%]). In multivariable analyses, vaccination was still associated with lower hospitalization risk in both variant time periods after controlling for comorbid conditions. In Omicron, compared with the vaccinated group, those unvaccinated had an adjusted RR of hospitalization of 2.43 (95% CI, 1.72-3.43). In Delta, those unvaccinated had an adjusted RR of hospitalization of 3.82 (95% CI, 2.38-6.14).

Conclusions and relevance: Vaccination against SARS-CoV-2 prior to and during pregnancy, before COVID-19 diagnosis, was associated with a lower risk of severe maternal disease and preterm birth regardless of variant time period.

Approximately 1 in 7 individuals are affected by perinatal depression, defined as a depressive episode occurring during pregnancy or within 12 months after delivery. Although the diagnostic criteria are similar to those of major depressive disorder, perinatal depression may also include symptoms such as difficulty forming an emotional attachment with the fetus or infant, persistent doubts about parenting abilities, and intrusive thoughts of harm to self or infant.1 Mental health conditions are leading contributors to maternal mortality in the US; among reporting states, the rate of death from perinatal suicide ranges from 4.2 to 21.4 per 100 000 pregnancies.2 Untreated or undertreated perinatal depression increases other maternal risks, including limited engagement in care, impaired relationships, substance use, preeclampsia, and suicide, as well as fetal or neonatal risks, including preterm birth, low birth weight, and disrupted attachment with long-term developmental consequences.3 Individuals from marginalized communities, such as those who are non–English speaking, uninsured, or geographically isolated, experience a higher prevalence of perinatal depression and are at increased risk of underdiagnosis and undertreatment.3

Risk factors for perinatal depression include a personal or family history of depression, abuse, stressful life events, low socioeconomic status, adolescent or single parenthood, and pregnancy complications, such as preterm birth or pregnancy loss. Each factor individually confers only a small increase in risk, making accurate prediction based on clinical factors challenging.4 Therefore, to facilitate early identification and treatment, universal screening during and after pregnancy is recommended. The American College of Obstetricians and Gynecologists (ACOG) recently issued 2 Clinical Practice Guidelines on perinatal mental health, 1 on screening and diagnosis5 and 1 on treatment and management,3 highlighting opportunities for obstetricians to address existing health gaps.

Rationale: Respiratory syncytial virus (RSV) is a highly transmissible pathogen that causes varying degrees of respiratory illness across all age groups. The safety and efficacy profiles of available RSV vaccines, a critical consideration for their integration into public health strategies and clinical practice, remain uncertain.

Objectives: To assess the benefits and harms of RSV vaccines compared to placebo, no intervention, vaccines for other respiratory infections, other RSV vaccines, or monoclonal antibodies (mAbs) across all human populations.

Search methods: We conducted a comprehensive literature search of CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and the WHO ICTRP following standard systematic review methodology from 2000 to April 2024.

Eligibility criteria: We included both randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) involving all human populations comparing RSV vaccines with placebo, no intervention, vaccines for other respiratory infections, other RSV vaccines, or mAbs. We excluded studies focused on dose-finding schedules and immunogenicity assessment.

Outcomes: Benefits included frequency of RSV illness (both lower and upper respiratory illness) confirmed by laboratory tests (RSV-associated lower respiratory tract illness and RSV-associated acute respiratory illness); hospitalisation due to RSV disease (both lower and upper respiratory illness) confirmed by laboratory tests; mortality from illness caused by RSV (confirmed by laboratory test); all-cause mortality; and admission to an intensive care unit. Harms included serious adverse events (SAEs) related to vaccination, including neurological disorders such as Guillain-Barré syndrome.

Risk of bias: We assessed risk of bias in RCTs using Cochrane's RoB 2 tool.

Synthesis methods: We used standard Cochrane methods.

Included studies: We identified 14 RCTs: five trials (101,825 participants) on older adults; three trials (12,010 participants) on maternal vaccination and effects on infants; one trial (300 participants) on women of childbearing age; and five trials (192 participants) on infants and children. We identified no NRSIs.

Synthesis of results: RSV prefusion vaccine versus placebo in older adults These vaccines reduced RSV-associated lower respiratory tract illness with vaccine efficacy (VE) of 77% (95% confidence interval (CI) 0.70 to 0.83; risk ratio (RR) 0.23, 95% CI 0.17 to 0.30; 4 RCTs, 99,931 participants; high-certainty evidence) and RSV-associated acute respiratory illness with VE of 67% (95% CI 0.60 to 0.73; RR 0.33, 95% CI 0.27 to 0.40; 3 RCTs, 94,339 participants; high-certainty evidence). There may be little to no difference in mortality from illness caused by RSV, all-cause mortality, and SAEs related to vaccination (low-certainty evidence). RSV postfusion F protein-based vaccine versus placebo in older adults There is probably little to no difference in RSV-associated lower respiratory tract illness with VE of -0.37% (95% CI -1.96 to 0.37; RR 1.37, 95% CI 0.63 to 2.96; 1 RCT, 1894 participants; moderate-certainty evidence) and RSV-associated acute respiratory illness with VE of -0.07% (95% CI -1.15 to 0.47; RR 1.07, 95% CI 0.53 to 2.15; 1 RCT, 1894 participants; moderate-certainty evidence). There may be little to no difference in mortality from illness caused by RSV, all-cause mortality, and SAEs related to vaccination (low-certainty evidence). Maternal RSV F protein-based vaccine versus placebo in infants These vaccines reduced medically attended RSV-associated lower respiratory tract illness with VE of 54% (95% CI 0.28 to 0.71; RR 0.46, 95% CI 0.29 to 0.72; 3 RCTs, 12,010 participants; high-certainty evidence), medically attended RSV-associated severe lower respiratory tract illness with VE of 74% (95% CI 0.44 to 0.88; RR 0.26, 95% CI 0.12 to 0.56; 3 RCTs, 12,010 participants; high-certainty evidence), and hospitalisation due to RSV disease with VE of 54% (95% CI 0.27 to 0.71; RR 0.46, 95% CI 0.29 to 0.73; 2 RCTs, 11,502 participants; high-certainty evidence) in infants. There may be little to no difference in mortality from illness caused by RSV, all-cause mortality, and SAEs related to vaccination in mothers and infants (low-certainty evidence). Live-attenuated RSV vaccines versus placebo in infants and children The evidence is very uncertain regarding all-cause medically attended acute respiratory illness (MAARI) with VE of 26% (95% CI -0.01 to 0.46; RR 0.74, 95% CI 0.54 to 1.01; 5 RCTs, 171 participants; very low-certainty evidence) and RSV-associated MAARI with VE of 38% (95% CI -0.24 to 0.69; RR 0.62, 95% CI 0.31 to 1.24; 5 RCTs, 192 participants; very low-certainty evidence). There may be little to no difference in SAEs related to vaccination (low-certainty evidence). RSV recombinant F nanoparticle vaccine versus placebo in women of childbearing age The evidence is very uncertain regarding new RSV infections with VE of 50% (95% CI 0.08 to 0.73; RR 0.50, 95% CI 0.27 to 0.92; 1 RCT, 300 participants; very low-certainty evidence). There may be little to no difference in mortality from illness caused by RSV, all-cause mortality, and SAEs related to vaccination (low-certainty evidence). Phase III trials consistently demonstrated low risk of bias. Whilst phase I and II trials occasionally raised concerns about selection bias in the randomisation process, the overall evidence was deemed robust.

Authors' conclusions: RSV prefusion vaccines reduced RSV-associated lower respiratory tract illness and acute respiratory illness in older adults. There may be little to no difference in SAEs related to vaccination in older adults. Maternal vaccination with RSV F protein-based vaccines reduced medically attended RSV-associated lower respiratory tract illness and severe cases in infants. There may be little to no difference in SAEs related to vaccination in mothers and infants. The evidence is very uncertain regarding the effects of RSV vaccine on women of childbearing age, and the effects of live-attenuated RSV vaccines on infants and children; there may be little to no difference in SAEs related to vaccination.

Funding: This review was funded by the EU4Health Programme under a service contract with the European Health and Digital Executive Agency (HaDEA).

Registration: The review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42023439128).