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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.

Keywords 
breast feeding infant child health breastmilk

Omalizumab for the Treatment of Multiple Food Allergies

Author/s: 
Wood RA, Togias A, Sicherer SH, Shreffler WG, Kim EH, Jones SM

BACKGROUND
Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy.
METHODS
In this trial, we assessed whether omalizumab, a monoclonal anti-IgE antibody, would be effective and safe as monotherapy in patients with multiple food allergies. Persons 1 to 55 years of age who were allergic to peanuts and at least two other trial-specified foods (cashew, milk, egg, walnut, wheat, and hazelnut) were screened. Inclusion required a reaction to a food challenge of 100 mg or less of peanut protein and 300 mg or less of the two other foods. Participants were randomly assigned, in a 2:1 ratio, to receive omalizumab or placebo administered subcutaneously (with the dose based on weight and IgE levels) every 2 to 4 weeks for 16 to 20 weeks, after which the challenges were repeated. The primary end point was ingestion of peanut protein in a single dose of 600 mg or more without dose-limiting symptoms. The three key secondary end points were the consumption of cashew, of milk, and of egg in single doses of at least 1000 mg each without dose-limiting symptoms. The first 60 participants (59 of whom were children or adolescents) who completed this first stage were enrolled in a 24-week open-label extension.

RESULTS
Of the 462 persons who were screened, 180 underwent randomization. The analysis population consisted of the 177 children and adolescents (1 to 17 years of age). A total of 79 of the 118 participants (67%) receiving omalizumab met the primary end-point criteria, as compared with 4 of the 59 participants (7%) receiving placebo (P<0.001). Results for the key secondary end points were consistent with those of the primary end point (cashew, 41% vs. 3%; milk, 66% vs. 10%; egg, 67% vs. 0%; P<0.001 for all comparisons). Safety end points did not differ between the groups, aside from more injection-site reactions in the omalizumab group.
CONCLUSIONS
In persons as young as 1 year of age with multiple food allergies, omalizumab treatment for 16 weeks was superior to placebo in increasing the reaction threshold for peanut and other common food allergens. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT03881696.)

What Is Perinatal Depression?

Author/s: 
Rebecca Voelker

Perinatal depression can occur during pregnancy and the first 12 months after childbirth.

Perinatal depression, also called postpartum depression, affects about 1 in 7 perinatal individuals. More than 75% of these individuals receive no treatment for perinatal depression. Onset of perinatal depression may occur prepregnancy or may develop over the course of pregnancy and the postpartum period. Untreated perinatal depression is associated with an increased risk of suicide and has additional negative effects on the perinatal individual, the fetus (preterm birth, low birth weight), and the child (impaired attachment, which may affect neurodevelopment) and may negatively affect relationships with partners and other family members.

Keywords 
Depressive Disorders Psychiatry and Behavioral Health Patient Information Reproductive Health Pregnancy Postpartum Depression Perinatal Depression

Age and Probability of Spontaneous Umbilical Hernia Closure

Author/s: 
Katherine He, Dionne A Graham, Louis Vernacchio, Jonathan Hatoun, Laura Patane, Shannon L Cramm, Shawn J Rangel

This cohort study of children younger than 6 years uses electronic health records to investigate whether a child’s age is associated with the probability of spontaneous umbilical hernia closure and to refine guidelines for surgical repair.

Keywords 
Neonatology pediatrics infants children's health newborns umbilical hernia

Timing of Allergenic Food Introduction and Risk of Immunoglobulin E-Mediated Food Allergy: A Systematic Review and Meta-analysis

Author/s: 
Scarpone, R., Kimkool, P., Ierodiakonou, D., Leonardi-Bee, J., Garcia-Larsen, V., Perkin, M. R., Boyle, R. J.

Importance: Earlier egg and peanut introduction probably reduces risk of egg and peanut allergy, respectively, but it is uncertain whether food allergy as a whole can be prevented using earlier allergenic food introduction.

Objective: To investigate associations between timing of allergenic food introduction to the infant diet and risk of food allergy.

Data sources: In this systematic review and meta-analysis, Medline, Embase, and CENTRAL databases were searched for articles from database inception to December 29, 2022. Search terms included infant, randomized controlled trial, and terms for common allergenic foods and allergic outcomes.

Study selection: Randomized clinical trials evaluating age at allergenic food introduction (milk, egg, fish, shellfish, tree nuts, wheat, peanuts, and soya) during infancy and immunoglobulin E (IgE)-mediated food allergy from 1 to 5 years of age were included. Screening was conducted independently by multiple authors.

Data extraction and synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was used. Data were extracted in duplicate and synthesized using a random-effects model. The Grading of Recommendations, Assessment, Development, and Evaluation framework was used to assess certainty of evidence.

Main outcomes and measures: Primary outcomes were risk of IgE-mediated allergy to any food from 1 to 5 years of age and withdrawal from the intervention. Secondary outcomes included allergy to specific foods.

Results: Of 9283 titles screened, data were extracted from 23 eligible trials (56 articles, 13 794 randomized participants). There was moderate-certainty evidence from 4 trials (3295 participants) that introduction of multiple allergenic foods from 2 to 12 months of age (median age, 3-4 months) was associated with reduced risk of food allergy (risk ratio [RR], 0.49; 95% CI, 0.33-0.74; I2 = 49%). Absolute risk difference for a population with 5% incidence of food allergy was -26 cases (95% CI, -34 to -13 cases) per 1000 population. There was moderate-certainty evidence from 5 trials (4703 participants) that introduction of multiple allergenic foods from 2 to 12 months of age was associated with increased withdrawal from the intervention (RR, 2.29; 95% CI, 1.45-3.63; I2 = 89%). Absolute risk difference for a population with 20% withdrawal from the intervention was 258 cases (95% CI, 90-526 cases) per 1000 population. There was high-certainty evidence from 9 trials (4811 participants) that introduction of egg from 3 to 6 months of age was associated with reduced risk of egg allergy (RR, 0.60; 95% CI, 0.46-0.77; I2 = 0%) and high-certainty evidence from 4 trials (3796 participants) that introduction of peanut from 3 to 10 months of age was associated with reduced risk of peanut allergy (RR, 0.31; 95% CI, 0.19-0.51; I2 = 21%). Evidence for timing of introduction of cow's milk and risk of cow's milk allergy was very low certainty.

Conclusions and relevance: In this systematic review and meta-analysis, earlier introduction of multiple allergenic foods in the first year of life was associated with lower risk of developing food allergy but a high rate of withdrawal from the intervention. Further work is needed to develop allergenic food interventions that are safe and acceptable for infants and their families.

Keywords 
Shellfish nuts Food Allergies allergen introduction egg

Food Allergy Prevention: Early Versus Late Introduction of Food Allergens in Children

Author/s: 
Djossi, S. K., Khedr, A., Neupane, B., Proskuriakova, E., Jada, K., Mostafa, J. A.

The emergence of food allergies in children is crucial for various medical fields seeking a viable strategy for allergy prevention. The most well-recognized approach adopted by numerous health care and government institutions hinges on the delay in the introduction of food allergens, which supposedly protects infants from sensitization and decreases the possibility of allergy development. However, recent experimental findings indicate that the benefits of this approach might be overestimated, as early exposure to allergenic foods has been shown to yield more advantageous outcomes. Multiple investigations on the causes of allergic diseases report that avoiding food allergies might be related to early consumption of these allergens. Alternatively, delaying the contact with allergenic nourishments, explored in contemporary research, has been proven to result in a higher prevalence of allergies among children, originating such conditions as atopic diseases and extreme sensitization to foods. The current paper compares the two prominent strategies of allergenic food introduction, gathering the most pertinent modern evidence to distinguish whether exposure to food allergens should be delayed or advanced.

Keywords 
Food Allergy children Allergens Allergy Prevention

Screening and Interventions to Prevent Dental Caries in Children Younger Than 5 Years US Preventive Services Task Force Recommendation Statement

Author/s: 
US Preventative Services task Force

IMPORTANCE Dental caries is the most common chronic disease in children in the US.
According to the 2011-2016 National Health and Nutrition Examination Survey, approximately
23% of children aged 2 to 5 years had dental caries in their primary teeth. Prevalence is higher
in Mexican American children (33%) and non-Hispanic Black children (28%) than in
non-Hispanic White children (18%). Dental caries in early childhood is associated with pain,
loss of teeth, impaired growth, decreased weight gain, negative effects on quality of life, poor
school performance, and future dental caries.
OBJECTIVE To update its 2014 recommendation, the US Preventive Services Task Force
(USPSTF) commissioned a systematic review on screening and interventions to prevent
dental caries in children younger than 5 years.
POPULATION Asymptomatic children younger than 5 years.
EVIDENCE ASSESSMENT The USPSTF concludes with moderate certainty that there is a
moderate net benefit of preventing future dental caries with oral fluoride supplementation at
recommended doses in children 6 months or older whose water supply is deficient in
fluoride. The USPSTF concludes with moderate certainty that there is a moderate net benefit
of preventing future dental caries with fluoride varnish application in all children younger
than 5 years. The USPSTF concludes that the evidence is insufficient on performing routine
oral screening examinations for dental caries by primary care clinicians in children younger
than 5 years and that the balance of benefits and harms of screening cannot be determined.
RECOMMENDATION The USPSTF recommends that primary care clinicians prescribe oral fluoride
supplementation starting at age 6 months for children whose water supply is deficient in
fluoride. (B recommendation) The USPSTF recommends that primary care clinicians apply
fluoride varnish to the primary teeth of all infants and children starting at the age of primary
tooth eruption. (B recommendation) The USPSTF concludes that the current evidence is
insufficient to assess the balance of benefits and harms of routine screening examinations for
dental caries performed by primary care clinicians in children younger than 5 years. (I statement)

Keywords 
Dental Caries screening Intervention children

Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society

Author/s: 
Glauser, T., Shinnar, S., Gloss, D., Alldredge, B., Arya, R., Bainbridge, J., Bare, M., Bleck, T., Dodson, W. E., Garrity, L., Jagoda, A., Lowenstein, D., Pellock, J., Riviello, J., Sloan, E., Treiman, D. M.

CONTEXT: The optimal pharmacologic treatment for early convulsive status epilepticus is unclear. OBJECTIVE: To analyze efficacy, tolerability and safety data for anticonvulsant treatment of children and adults with convulsive status epilepticus and use this analysis to develop an evidence-based treatment algorithm. DATA SOURCES: Structured literature review using MEDLINE, Embase, Current Contents, and Cochrane library supplemented with article reference lists. STUDY SELECTION: Randomized controlled trials of anticonvulsant treatment for seizures lasting longer than 5 minutes. DATA EXTRACTION: Individual studies were rated using predefined criteria and these results were used to form recommendations, conclusions, and an evidence-based treatment algorithm. RESULTS: A total of 38 randomized controlled trials were identified, rated and contributed to the assessment. Only four trials were considered to have class I evidence of efficacy. Two studies were rated as class II and the remaining 32 were judged to have class III evidence. In adults with convulsive status epilepticus, intramuscular midazolam, intravenous lorazepam, intravenous diazepam and intravenous phenobarbital are established as efficacious as initial therapy (Level A). Intramuscular midazolam has superior effectiveness compared to intravenous lorazepam in adults with convulsive status epilepticus without established intravenous access (Level A). In children, intravenous lorazepam and intravenous diazepam are established as efficacious at stopping seizures lasting at least 5 minutes (Level A) while rectal diazepam, intramuscular midazolam, intranasal midazolam, and buccal midazolam are probably effective (Level B). No significant difference in effectiveness has been demonstrated between intravenous lorazepam and intravenous diazepam in adults or children with convulsive status epilepticus (Level A). Respiratory and cardiac symptoms are the most commonly encountered treatment-emergent adverse events associated with intravenous anticonvulsant drug administration in adults with convulsive status epilepticus (Level A). The rate of respiratory depression in patients with convulsive status epilepticus treated with benzodiazepines is lower than in patients with convulsive status epilepticus treated with placebo indicating that respiratory problems are an important consequence of untreated convulsive status epilepticus (Level A). When both are available, fosphenytoin is preferred over phenytoin based on tolerability but phenytoin is an acceptable alternative (Level A). In adults, compared to the first therapy, the second therapy is less effective while the third therapy is substantially less effective (Level A). In children, the second therapy appears less effective and there are no data about third therapy efficacy (Level C). The evidence was synthesized into a treatment algorithm. CONCLUSIONS: Despite the paucity of well-designed randomized controlled trials, practical conclusions and an integrated treatment algorithm for the treatment of convulsive status epilepticus across the age spectrum (infants through adults) can be constructed. Multicenter, multinational efforts are needed to design, conduct and analyze additional randomized controlled trials that can answer the many outstanding clinically relevant questions identified in this guideline.

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