infant

The Role of Vaccination in Maternal and Perinatal Outcomes Associated With COVID-19 in Pregnancy

Author/s: 
Sandra Blitz, Elisabeth McClymont, Lucia Forward

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.

Stillbirth

Author/s: 
Adina R. Kern-Goldberger, Uma M. Reddy, Jennifer L. Bailit

Stillbirth, defined as fetal death at 20 or more weeks of gestation or 350 g or greater in birth weight, is a tragic outcome for families and clinicians.1 Stillbirth affects approximately 5.7 per 1000 births in the US—equivalent to 21 000 annually—and can occur antenatally (83%) or intrapartum (17%).2 This rate has remained relatively stable over the past 2 decades, despite substantial reductions in infant and childhood mortality.3,4 Stillbirth prevention is complex because many cases of stillbirth are unexplained, and there are substantial disparities in incidence by geographic region, socioeconomic status, and maternal race.5

Pharmacologic Treatment of Perinatal Depression

Author/s: 
Emily S. Miller, S. Karlene Cunningham, Lauren M. Osborne

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.

Efficacy and safety of respiratory syncytial virus vaccines

Author/s: 
K M Saif-Ur-Rahman, Catherine King, Seán Olann Whelan, Matthew Blair, Seán Donohue, Caoimhe Madden, Kavita Kothari, Isolde Sommer, Thomas Harder, Nicolas Dauby, Ida Rask Moustsen-Helms, Simona Ruta, Julie Frère, Viktoria Schönfeld, Eero Poukka, Irja Lutsar, Kate Olsson, Angeliki Melidou, Karam Adel Ali, Kerry Dwan, Declan Devane

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).

2024 edition of the Rourke Baby Record

Author/s: 
Anne Rowan-Legg, Patricia Li, Bruce Kwok, Leslie Rourke, Denis Leduc, James Rourke, Imaan Bayoumi

Objective: To assist busy primary care providers caring for infants and young children and their families by providing them with the most recent recommendations and supportive evidence included in the 2024 edition of the Rourke Baby Record (RBR).

Quality of evidence: Articles from pediatric preventive care literature (January 2019 to March 2023) were reviewed for relevance and quality of evidence. When available, evidence from systematic reviews, relevant clinical guidelines, and clinical trials were incorporated. In the absence of high-level evidence, observational studies and expert opinion on the topic were included. Primary research studies were reviewed and critically appraised using a modified protocol.

Main message: Notable updates in the 2024 edition of the RBR include the promotion of early relational health for families; identification of targeted support and resources as opposed to labelling of high-risk groups; guidance on culturally safe care; clarification and evidence-based adjustments of the age of achievement of some developmental surveillance milestones; recommendations on plant-based beverages, vegetarian, and vegan diets; screening considerations for iron deficiency; dangers of ingestion of button batteries and cannabis edibles; literacy and socioemotional benefits of reading, singing, and storytelling; the importance of unstructured outdoor play; the environment's effect on children's health; the significance of sentinel injuries; acholic stools; and the normal presence and abnormal persistence of developmental (primitive) reflexes.

Conclusion: Building on its 40-year history, the 2024 RBR provides freely available, evidence-informed recommendations to guide clinicians in providing effective, up-to-date, and comprehensive preventive pediatric care. Despite the challenging and evolving landscape of primary health care delivery, the RBR will continue to support primary care providers.

Keywords 

2024 edition of the Rourke Baby Record

Author/s: 
Anne Rowan-Legg, Patricia Li, Bruce Kwok, Leslie Rourke, Denis Leduc, James Rourke, Imaan Bayoumi

Objective: To assist busy primary care providers caring for infants and young children and their families by providing them with the most recent recommendations and supportive evidence included in the 2024 edition of the Rourke Baby Record (RBR).

Quality of evidence: Articles from pediatric preventive care literature (January 2019 to March 2023) were reviewed for relevance and quality of evidence. When available, evidence from systematic reviews, relevant clinical guidelines, and clinical trials were incorporated. In the absence of high-level evidence, observational studies and expert opinion on the topic were included. Primary research studies were reviewed and critically appraised using a modified protocol.

Main message: Notable updates in the 2024 edition of the RBR include the promotion of early relational health for families; identification of targeted support and resources as opposed to labelling of high-risk groups; guidance on culturally safe care; clarification and evidence-based adjustments of the age of achievement of some developmental surveillance milestones; recommendations on plant-based beverages, vegetarian, and vegan diets; screening considerations for iron deficiency; dangers of ingestion of button batteries and cannabis edibles; literacy and socioemotional benefits of reading, singing, and storytelling; the importance of unstructured outdoor play; the environment's effect on children's health; the significance of sentinel injuries; acholic stools; and the normal presence and abnormal persistence of developmental (primitive) reflexes.

Conclusion: Building on its 40-year history, the 2024 RBR provides freely available, evidence-informed recommendations to guide clinicians in providing effective, up-to-date, and comprehensive preventive pediatric care. Despite the challenging and evolving landscape of primary health care delivery, the RBR will continue to support primary care providers.

Keywords 

Prenatal Cannabis Use and Neonatal Outcomes A Systematic Review and Meta-Analysis

Author/s: 
Jamie O Lo, Chelsea K Ayers, Snehapriya Yeddala, Beth Shaw, Shannon Robalino, Rachel Ward, Devan Kansagara

Importance: Prenatal cannabis use continues to increase, and cannabis remains the most commonly used illegal substance in pregnancy. Accumulating evidence suggests potential adverse effects on fetal and neonatal outcomes following cannabis use in pregnancy.

Objective: To update a living systematic review and meta-analysis to provide a timely understanding regarding cannabis use in pregnancy and fetal and neonatal outcomes.

Data sources: The previous review was updated by searching bibliographic databases MEDLINE, CINAHL, PsycInfo, Global Health, and Evidence-Based Medicine Reviews Cochrane Database of Systematic Reviews from November 1, 2021, through April 4, 2024.

Study selection: Cohort or case-control studies comparing pregnancies with and without prenatal cannabis use on prespecified fetal or neonatal outcomes with adjustment for confounders, such as co-use of tobacco products, were included. Two independent reviewers screened studies, with disagreements resolved through discussion.

Data extraction and synthesis: Included studies were extracted by 1 reviewer and confirmed by a second. Risk of bias was assessed with the Newcastle-Ottawa Scale. Random-effects meta-analyses of unadjusted and adjusted odds ratios (ORs) were performed for all primary outcomes. Results were synthesized using the Grading of Recommendations Assessment, Development, and Evaluation approach.

Main outcomes and measures: Primary outcomes were preterm birth (PTB; <37 weeks of gestation), small for gestational age (SGA), low birth weight (LBW; <2500 g), and perinatal mortality.

Results: For this update, 8 new studies with 1 709 998 participants were added, for a total of 51 studies synthesized (N = 21 146 938). From meta-analyses of adjusted effect sizes, moderate-certainty evidence indicated that cannabis use in pregnancy was associated with increased odds of LBW (20 studies; OR, 1.75; 95% CI, 1.41-2.18), PTB (20 studies; OR, 1.52; 95% CI, 1.26-1.83), and SGA (12 studies; OR, 1.57; 95% CI, 1.36-1.81), and low-certainty evidence indicated that it was associated with greater odds of perinatal mortality (6 studies; OR, 1.29; 95% CI, 1.07-1.55). Previously, the evidence was rated as very low or low certainty.

Conclusions and relevance: Cannabis use in pregnancy was associated with greater odds of PTB, SGA, and LBW even after adjusting for co-use of tobacco products, and confidence in these findings increased from low in the prior review to moderate in the current meta-analysis. The findings of this study may help inform patient counseling and future public health policies.

Breastfeeding and Health Outcomes for Infants and Children

Objectives. To review the evidence on the association between breastfeeding and infant and child health outcomes, including the extent to which these associations vary by the intensity, duration, mode, and source of breastmilk consumption. In this review, breastfeeding refers to feeding breastmilk whether directly from the breast or other means and includes breastmilk from pasteurized donor milk.

Data sources. Systematic literature searches in MEDLINE, Embase and CINAHL for English-language articles published from 2006 to August 14, 2024. We identified additional studies from reference lists and technical experts.

Review methods. We worked with our sponsor and a panel of technical experts to identify the outcomes of interest for this review. The evidence for more than 20 outcomes was synthesized, including outcomes related to infectious diseases, asthma and allergic conditions, oral health, autoimmune gastrointestinal conditions, endocrine conditions, cardiovascular disease (CVD), childhood cancer, cognitive development, and infant mortality. We relied on existing systematic reviews (ESRs) for all outcomes and conducted bridge searches for newer primary studies since the search date of the most recent and relevant ESR. Studies were evaluated for eligibility and quality, and data were abstracted on study design, demographics, breastfeeding exposures and referents, and outcomes. We synthesized the evidence by outcome, summarizing the results of ESRs alongside those of newer primary studies. No meta-analyses were conducted given the combination of ESR and primary study evidence and heterogeneity in exposures and outcomes; but figures were created to visually display point estimates across studies.

Results. A total of 29 ESRs and 145 primary studies were included. The cumulative number of studies included for each outcome varied from only 4 studies examining the relationship between breastfeeding and type 2 diabetes to more than 180 studies reporting on the relationship between breastfeeding and obesity-related outcomes. We rated the strength of evidence as “Low” or “Moderate” for most outcomes, given limitations of the underlying evidence base, along with concerns related to heterogeneity of the study designs, and the consistency and precision of results. An association indicating a reduced risk from “more” versus “less” breastfeeding was most apparent for otitis media, asthma, obesity in childhood, and childhood leukemia. A protective association of breastfeeding was also found for severe respiratory and gastrointestinal infections in younger children, allergic rhinitis, malocclusion, inflammatory bowel disease, type 1 diabetes, rapid weight gain and growth, systolic blood pressure, and infant mortality, including sudden unexpected infant death, although our confidence in these findings was lower. There was no apparent association for the outcomes of atopic dermatitis, celiac disease, and cognitive ability. An association indicating an increased risk of dental caries was noted for breastfeeding 12 months or longer. There was insufficient evidence to draw conclusions about the relationship with food allergies and type 2 diabetes and no data on coronavirus disease 2019 (COVID-19) or CVD endpoint outcomes (i.e., events or mortality). While nearly all outcomes had evidence on ever (versus never) breastfeeding, exclusive (versus nonexclusive or no) breastfeeding, and longer durations (versus shorter or no) of any or exclusive breastfeeding, the exposure comparisons and categorizations reported in the ESRs and primary evidence made it extremely difficult to examine the nuances of these relationships. There was no clear “threshold” of breastfeeding that appeared to be most beneficial for any outcome. Furthermore, there were little data on how the relationships varied by mode of breastfeeding or source of breastmilk.

Conclusions. Breastfeeding is associated with beneficial effects for several infant and child outcomes, although there are limitations to the data that preclude high certainty in the findings. Further research that addresses the limitations of existing studies is needed to continue to inform national guidelines and initiatives.

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