Allergy Tests Should Only Verify Diagnosis in Children

From Medscape Education Clinical Briefs News Author: Ricki Lewis, PhD CME Author: Désirée Lie, MD, MSEd 01/10/2012 Clinical Context According to the current study by Sicherer and Wood, most allergic responses are mediated by immunoglobulin E (IgE) antibodies specific to the trigger allergen, which can be detected with in vitro or skin tests. Quantification of in vitro allergen-specific IgE (sIgE) levels is becoming more common. The 3 detection systems approved by the US Food and Drug Administration have excellent performance characteristics to identify different IgE antibodies but do not measure IgE antibodies with similar efficiencies. Therefore, a test for an allergen in 1 of 3 test systems may not be equivalent to the same allergen test in a different system. This is a review of different tests available for allergen testing in children and indications for use. Study Synopsis and Perspective Allergy tests should be used only to confirm a diagnosis that has already been made on the basis of symptoms and medical history, advise 2 leading allergists in an article published in the January issue of Pediatrics. Scott Sicherer, MD, from Mount Sinai Hospital in New York City, and Robert Wood, MD, from the Johns Hopkins Children's Center in Baltimore, Maryland, reviewed the benefits and limitations of blood tests and skin-prick tests in the detection of allergic diseases. For blood tests, enzymatic assays for IgE antibodies (in vitro sIgE) tests have replaced radioallergosorbent tests, but the 3 products approved by the US Food and Drug Administration either detect different antibody populations or do not measure them with comparable efficiencies. Both the skin-prick test (SPT) and sIgE test detect a sensitized state. "However, detection of sensitization to an allergen is not equivalent to a clinical diagnosis. In fact, many children with positive tests have no clinical illness when exposed to the allergen," Dr. Sicherer and Dr. Wood write. They further point out that testing for allergens that do not make sense (because they would never be encountered in the patient's environment or because the patient is obviously not allergic to them) could lead to "detrimental actions of unnecessary allergen avoidance." They also warn against a false-negative on an SPT or sIgE test when a child is obviously allergic to a particular trigger. The allergists identify circumstances in which SPT and sIgE are warranted: to confirm a suspected allergic trigger after observing a child react, to monitor the course of a food allergy to detect when it might be waning or outgrown, to confirm allergy to an insect after an anaphylactic response, and to identify allergies to vaccines (SPT only). SPT and sIgE tests should not be used, Dr. Sicherer and Dr. Wood write, to screen for allergies in nonsymptomatic children or to diagnose food allergies or drug allergies. Food allergies should be assessed with food challenges, they write, and skin and blood tests do not detect antibodies to drugs. The tests might be useful for identifying the trigger of a respiratory allergy (allergic asthma or seasonal or perennial allergic rhinitis) that is ubiquitous but not obvious in the patient's environment: for example, SPT or sIgE can detect allergy to dust mites, animal dander, cockroaches, molds, or pollen. The authors have disclosed no relevant financial relationships. Pediatrics. 2012;129:193-97. Abstract

Antiretroviral Safe in Reducing HIV-1 Transmission via Breast-Feeding

m Medscape Education Clinical Briefs News Author: Laurie Barclay, MD CME Author: Hien T. Nghiem, MD 01/10/2012 Clinical Context Breast-feeding in sub-Saharan Africa is an important source of nutrition for infants between birth and age 24 months, leading to improved overall survival duration. However, breast-feeding for infants exposed to HIV can account for 30% to 40% of all mother-to-child transmissions. Strategies for prevention of mother-to-child transmission are needed. Guidelines from the World Health Organization recommend extended breast-feeding for infants exposed to HIV-1 until age 12 months, together with antiretroviral prophylaxis for the mother or infant for the duration of breast-feeding. Nevirapine given once daily for the first 6, 14, or 28 weeks of life to infants exposed to HIV-1 via breast-feeding reduces transmission through this route vs single-dose nevirapine at birth or neonatally. The aim of this study by Coovadia and colleagues was to assess the incremental safety and efficacy of extension of such prophylaxis to 6 months. Study Synopsis and Perspective A daily oral dose of nevirapine given to infants up to 6 months of age can safely reduce mother-to-child transmission of HIV-1 via breast-feeding, according to the results of a phase 3, double-blind, randomized, placebo-controlled trial published online December 23 in the Lancet. "Nevirapine given once-daily for the first 6, 14, or 28 weeks of life to infants exposed to HIV-1 via breastfeeding reduces transmission through this route compared with single-dose nevirapine at birth or neonatally," write Professor Hoosen M. Coovadia, MD, from the University of Witwatersrand in Johannesburg and the Nelson Mandela School of Medicine at the University of Kwazulu-Natal in Durban, South Africa, and colleagues. "We aimed to assess incremental safety and efficacy of extension of such prophylaxis to 6 months." Within 7 days of birth, breast-feeding infants born to mothers with HIV-1 in 4 African countries were enrolled and given once-daily nevirapine from birth to 6 weeks. Using a computer-generated permuted block algorithm with random block sizes allowing stratification by site and maternal antiretroviral treatment status, 6-week-old infants without HIV infection were assigned to receive extended nevirapine prophylaxis or placebo either until 6 months or until breast-feeding stopped, whichever came first. Kaplan-Meier analyses allowed between-group comparison of the primary efficacy outcome of HIV-1 infection in infants at 6 months. Adverse reactions were also recorded in both groups as safety endpoints. Of 1527 infants randomly assigned between June 19, 2008, and March 12, 2010, 762 were assigned to receive nevirapine, and 765 to receive placebo. Five of these patients were excluded from the primary analyses because they had HIV-1 infection at randomization. HIV-1 infection occurred between 6 weeks and 6 months in 1.1% (95% confidence interval [CI], 0.3% - 1.8%) of infants who received extended nevirapine, and in 2.4% (95% CI, 1.3% - 3.6%) of those who received placebo. Reduction in transmission associated with extended nevirapine was 54% (difference, 1.3%; 95% CI, 0% - 2.6%; P = .049). At 6 months, both groups had similar mortality rates (1.2% with nevirapine vs 1.1% with placebo; P = .81) and combined HIV infection and mortality rates (2.3% vs 3.2%; P = .27). The treatment groups had no significant differences in frequency of adverse events, serious adverse events (16% vs 15%), and deaths. Limitations of this study include a lack of adjustment for multiple statistical tests, which could increase the risk for false-positive findings. "After 6 weeks of treatment with once-daily nevirapine, continued use of nevirapine to age 6 months in uninfected infants of breastfeeding mothers with HIV-1 is safe, and results in a greater than 50% reduction in mother-to-child transmission from breastfeeding compared with placebo," the study authors write. "No other study has directly assessed the incremental benefit of extension of nevirapine from age 6 weeks until 6 months to establish whether the extended period is more efficacious and whether there are increased safety issues associated with long-term treatment with nevirapine." The National Institutes of Health supported this study. The study authors have disclosed no relevant financial relationships. Lancet. Published online December 23, 2011. Abstract

Bacterial Bronchitis Frequent in Children With Chronic Wet Cough

From Medscape Education Clinical Briefs News Author: Laura Newman, MA CME Author: Désirée Lie, MD, MSEd 01/11/2012 Clinical Context According to the current study by Zgherea and colleagues, chronic wet cough, defined as a wet cough that lasts for 4 weeks or more, is easily recognized by parents and pediatricians. Also, it is a major debilitating finding in children with pulmonary disorders such as cystic fibrosis or ciliary dyskinesia and immunodeficiency disorders. However, the diagnosis of chronic bronchitis is not easily accepted in pediatric practice as in adult practice, and it is uncertain what the prevalence of purulent and nonpurulent bronchitis is among children with wet cough. This retrospective study determines the frequency of bacterial infections among children with wet cough, using medical charts and bronchoscopic findings. Study Synopsis and Perspective Purulent bronchitis is common among children with chronic wet cough, according to a retrospective study published online January 9, 2012, in Pediatrics. In addition, 56% of the children in the study, all of whom had been referred to a pediatric pulmonary clinic because of an intractable wet cough, had bacterial infections of the lower airway. The investigators, led by Daniela Zgherea, MD, from the Department of Pediatrics, Maimonides Infants and Children's Hospital, Brooklyn, New York, also found that tracheomalacia was identified on bronchoscopy far more frequently in the 0- to 3-year-old children in their study (30.3%) than in the general pediatric population. The authors raise the need to better understand the etiology and best treatments for these lingering coughs (lasting 4 weeks or more). "The diagnosis of 'chronic bacterial bronchitis' is not readily accepted in the pediatric population, however, as many physicians assume that is an 'adult' respiratory illness associated with tobacco smoking," the authors write. In the study, investigators reviewed the charts and bronchoscopy findings of 197 children referred by their primary care physician to a pediatric pulmonary clinic at Maimonides Infants and Children's Hospital because of a persistent chronic wet cough. More than half of the study patients (55%) were aged 0 to 3 years, 36% were aged 3 to 7 years, and 9% were older than 7 years of age. One third of the children in the youngest group had bronchoscopy-confirmed laryngomalacia or tracheomalacia. However, the frequency of laryngomalacia and tracheomalacia did not appear to be associated with purulent or nonpurulent bronchitis. Bacterial cultures were positive in 91 children (46%). Of these, nontypable Haemophilus influenzae accounted for nearly half (49%) of the positive cultures, Streptococcus pneumoniae accounted for 20%, Moraxella catarrhalis accounted for 17%, and Staphylococcus aureus accounted for 12%. Bacterial infections were more frequently associated with purulent bronchitis (84%) than with nonpurulent bronchitis (16%; P < .001). Regarding the 16% of children with purulent bronchitis who had negative cultures, the authors hypothesize these may be false-negatives, in part resulting from the timing of sputum collection relative to antibiotics use. "The presence of a relatively large group of children with nonpurulent bronchitis and negative bacterial cultures among our study patients may point out the existing connection between chronic wet cough and asthma, which is also suggested by findings of [bronchoalveolar lavage] eosinophilia seen in some children in our study," the authors write. However, the study was unable to determine whether asthma contributed to the persistent cough. They recommend further prospective studies of the relationship between chronic wet cough, bacterial infections, and asthma in children. The authors have disclosed no relevant financial relationships. Pediatrics. Published online January 9, 2012. Abstract

Acute Macular Degeneration

From Medscape Education Clinical Briefs Frequent Aspirin Use Linked With Early and Wet Late AMD CME/CE Daniel M. Keller, PhD CME Author: Laurie Barclay, MD 01/12/2012 Clinical Context Previous findings have been inconsistent regarding associations between aspirin use and age-related macular degeneration (AMD). Several studies suggested a harmful effect of aspirin on AMD, whereas other studies showed no evidence of an association, or possibly a nonsignificant benefit. Aspirin use is widespread and is often indicated for its antiplatelet activity as well as for its analgesic effect. The objectives of the European Eye Study by de Jong and colleagues were to estimate the prevalence of AMD across Europe and to investigate possible risk factors, particularly exposure to solar radiation and antioxidant vitamin use. This analysis aimed to study associations between aspirin use and early and late AMD. Study Synopsis and Perspective The risks for early AMD and wet late AMD are associated with frequent aspirin use, and the risk increases with greater aspirin consumption, European researchers reported in an article published in the January 2012 issue of Ophthalmology. The results, from the large, population-based, cross-sectional European Eye Study, suggest caution in recommending aspirin to patients with early or late AMD who may take it for other conditions, such as prevention of cardiovascular disease (CVD). When adjusted for all potential confounders of age, sex, education, smoking, body mass index, diabetes, CVD, angina, cholesterol, and systolic blood pressure, daily aspirin users had a greater than 2-fold increased risk for wet AMD when compared with participants who never consumed aspirin. The research, led by Paulus T.V.M. de Jong, MD, PhD, emeritus professor of ophthalmic epidemiology at the Academic Medical Center and a member of the Netherlands Institute of Neuroscience in Amsterdam involved 4691 participants aged 65 years or older who were chosen by taking a random sampling from population registers in 7 countries. Field workers interviewed the participants about sociodemographic, health, and lifestyle factors. Aspirin use was quantified as never (n = 2760), monthly or less (n = 766), weekly but not daily (n = 326), or daily (n = 839). Digitized color fundus images were recorded at each participating center and sent to Rotterdam, the Netherlands, where 2 staff members graded them according to the International Classification and Grading System for Age-Related Maculopathy and AMD. Grades 1, 2, and 3 corresponded to early AMD, and grade 4 corresponded to late AMD, which was subdivided into dry or wet AMD. Wet AMD was defined as serous or hemorrhagic detachment of the retinal pigment epithelium, a subretinal neovascular membrane, subretinal hemorrhage, or other signs. Participants with grade 0 (macula free of drusen or pigmentary irregularities or with hard drusen) were the control patients. The main outcome measure was the odds ratio (OR) for AMD in aspirin users. Daily aspirin users were older, were less likely to smoke, and had lower blood pressure and cholesterol levels, but more CVD and angina. Among all participants, 36.4% had early AMD, and 3.3% had late AMD, of whom about two thirds had wet and one third dry AMD. More frequent aspirin use was associated with higher grades of AMD. One third of the individuals with wet AMD consumed aspirin daily compared with only 16% of control participants. Similar trends in ORs were seen when investigators adjusted only for age and sex, or for age, sex, and CVD (both P < .001 for the trends). There was no significant association for aspirin with wet AMD according to the presence or absence of CVD or angina (ie, AMD was independent of CVD or angina). For the 42 cases of dry AMD with information on aspirin use and potential confounders, dry AMD was not associated with aspirin use after adjustment for age and sex. Limitations of the study include its cross-sectional and retrospective nature, with the possibility of recall error about aspirin use and possible confounders. In addition, there were no data on the doses of aspirin or the use of other antiplatelet or anticoagulant drugs. Dr. de Jong told Medscape Medical News that "people should be aware that aspirin, often just bought over the counter without prescription, may have adverse effects — apart from major gastrointestinal and other bleeds, also for AMD." He said future randomized trials will be necessary to find out whether there is a critical dose of aspirin in relation to the risk for AMD. On the basis of this study and the body of literature, he said, he would advise people who have early or late AMD not to take aspirin for pain, and if they are taking it for primary prevention of CVD to discuss with their physicians whether it is wise to continue doing so. "For secondary prevention...the benefits of daily aspirin outweigh the risks," Dr. de Jong said. George Williams, MD, chairman of the Department of Ophthalmology and director of the Beaumont Eye Institute at William Beaumont Hospital in Royal Oak, Michigan; clinical professor of ophthalmology and biomedical sciences at Oakland University William Beaumont School of Medicine; and an expert correspondent for the American Academy of Ophthalmology, commented to Medscape Medical News that the study "raises some interesting questions" but "does not provide a definitive answer on the role of aspirin in the development of AMD." There has not been a consistent trend among studies looking at this question, and differing inclusion criteria and definitions of AMD severity make it difficult to compare studies. "The strength of this study is that they have photographic documentation of the status of the macular degeneration," Dr. Williams said. "In some of the other studies, we know exactly how much aspirin people were on because they were randomized to aspirin. However, in those studies we are relying upon less robust data to determine the degree of macular degeneration." Another potential confounder is that aspirin is a component of many over-the-counter medications that people do not recognize as containing the drug. Dr. Williams said he is concerned that although the study started with almost 4700 patients, in the end there were only 36 patients in the wet AMD group who had been taking daily aspirin. He said he would want to see larger numbers before becoming more comfortable with an association of aspirin with wet AMD. He noted that the value of prophylactic aspirin for the prevention of CVD is coming under increasing scrutiny. "It's going to require physicians to take the time to talk to their patients about the possibility that there may be an association [of aspirin with the development of AMD]," he said. "So patients who are on aspirin should discuss with their prescribing physician the reasons why they're on aspirin, what the benefits are, and then make a decision as to whether they wish to continue. But at this point I certainly see no definitive reason for people to stop aspirin when it's indicated for their overall health." A disadvantage for primary care physicians is that most will not have a comprehensive knowledge of the status of their patients' macular degeneration, "so it will require communication between primary care providers and ophthalmologists to come up with the best solution for a specific patient," Dr. Williams advised. Dr. de Jong has disclosed no relevant financial relationships. Dr. Williams is a consultant/advisor to Alcon Laboratories, Allergan, Neurotech, OptiMedica, Pfizer, and Thrombogenics. He also has received grant support from Alcon Laboratories, Allergan, Genentech, and Neurotech, is an equity owner of Nu-Vue Technologies, OptiMedica, and Thrombogenics, and has patent/royalty income from Nu-Vue Technologies. Ophthalmology. 2012;119:112-118. Abstract

Most US Teenagers Lack Hepatitis A Immunization

From Medscape Medical News Daniel M. Keller, PhD January 23, 2012 — Most adolescents in the United States lacked immunization for hepatitis A in 2009, leaving them susceptible to hepatitis A infection going into adulthood. In the first study to evaluate hepatitis A vaccine (HepA) coverage in the United States, using data from healthcare providers, researchers from the US Centers for Disease Control and Prevention in Atlanta, Georgia, reported in an article published online January 23 and in the February print issue of Pediatrics that nationally, 1-dose coverage with HepA among adolescents was 42.0%. Of those teenagers who were vaccinated, approximately 70% completed the 2-dose series, which is equivalent to 29.5% of the entire cohort of adolescents surveyed. Using data from the 2009 National Immunization Survey-Teen (N = 20,066) to determine HepA coverage among 13- to 17-year-olds, Christina Dorell, MD, MPH, and coauthors found that among states in which the Advisory Committee on Immunization Practices (ACIP) has recommended universal child vaccination at 2 years since 1999 (group 1), 1-dose coverage was 74.3%. Among states with an ACIP recommendation for consideration for child vaccination at 2 years since 1999 (group 2), the rate was 54.0%, and among states with a recommendation of universal child vaccination at 1 year of age since 2006 (group 3), the rate was 27.8%. The researchers noted that 1 dose of vaccine induces protective levels of antibodies in more than 97% of infants and children, and a second dose is thought to confer long-lasting immunity. Because hepatitis A virus is highly infectious and will probably continue to be introduced to the United States through imported food, international travel, international adoption, and other means, the authors recommend continued vaccination of adolescents to protect them during this period, and as they mature into adults. In this way, the prevalence of significant hepatitis A disease may be minimized, lowering morbidity, hospitalizations, lost work, and the large expense of containment efforts. The authors have disclosed no relevant financial relationships. Pediatrics. 2012;129:213-221. Abstract

Adopting a Healthy Diet May Help ADHD

From Medscape Medical News > Psychiatry Megan Brooks January 17, 2012 — When drug therapy fails to control attention-deficit/hyperactivity disorder (ADHD) or is unacceptable, adopting a "healthy" diet, eliminating items known to predispose to ADHD, and adding omega-3 fatty acid supplementation may be worth trying, new research suggests. "The recent increase of interest in this form of therapy for ADHD, and especially in the use of omega supplements, significance of iron deficiency, and the avoidance of the 'Western pattern' diet, make the discussion timely," the authors write. Many parents and physicians continue to be interested in how diet and dietary changes, particularly parents wanting to find an alternative to stimulant medication or a complementary therapy. Nevertheless, it remains a "controversial" topic, the authors note. For their review, J. Gordon Millichap, MD, and Michelle M. Yee, CPNP, from Children’s Memorial Hospital in Chicago, Illinois, searched PubMed for relevant studies on the role of diet and dietary supplements for the treatment of children with ADHD. They note that their recommendations on diet and dietary supplements are based on a critical review of the data and their own experience in a neurology clinic for children and adolescents with ADHD. The study was published on January 9 in Pediatrics. Elimination Diets Not Advisable Perhaps the "most promising and practical" complementary or alternative treatment, write Dr. Millichap and Ms. Yee, is adopting a "healthy" dietary pattern, omitting items shown to predispose to ADHD or to make the condition worse. These items include fast foods, red meat, processed meat, potato chips, high-fat dairy foods, and soft drinks. They point to a "provocative" study published last year, which found a link between ADHD in adolescents and a "Western-style" dietary pattern that was high in fat, refined sugars, and sodium and low in fiber, folate, and omega-3 fatty acids (Howard et al, J Atten Disord. 2011;15:403-411). ADHD was not associated with a "healthy" dietary pattern rich in fish, vegetables, fruit, legumes, and whole-grain foods. Adopting a healthy dietary pattern "may offer an alternative method of treatment of ADHD and less reliance on medications," the authors of the current study write. They also note that although many parents report worsening of hyperactivity symptoms after consumption of foods and drinks containing sugar or aspartame — and isolated reports support the parents' observations — most controlled studies have failed to find a significant harmful effect of sugar or aspartame, the authors note. Additionally, they say that the elimination of sugar and aspartame and adapting additive-free diets are complicated, disruptive, and often impractical; such measures are indicated only in select cases. Fatty Acid Supplements May Be Helpful Low levels of long-chain polyunsaturated fatty acids (PUFA) have been reported in the plasma and red cells of children with ADHD in comparison with their ADHD-free peers, Dr. Millichap and Ms. Yee note. Some studies have demonstrated a reduction in ADHD symptoms with PUFA supplementation, although no definitive conclusions can be drawn. However, the authors note that "on the basis of reports of efficacy and safety, we use doses of 300 to 600 mg/day of omega-3, and 30 to 60 mg/day of omega-6 fatty acids, continued for 2 or 3 months, or longer if indicated." "As initial or add-on therapy, we have occasional reports of improved school grades and lessening of symptoms of ADHD, without occurrence of adverse effects. Most parents are enthusiastic about trying the diet supplements, despite our explanation of only possible benefit and lack of proof of efficacy," they note. They also note that iron and zinc supplementation is advisable when there is a known deficiency in these minerals, and this may "enhance the effectiveness" of stimulant therapy. Dr. Millichap and Ms. Yee have disclosed no relevant financial relationships. Pediatrics. Published online January 9, 2012. Abstract

No Benefit of Additional Foods, Fluids in Breast-Fed Infants

From Medscape Education Clinical Briefs News Author: Lara C. Pullen, PhD CME Author: Laurie Barclay, MD 12/21/2011 Clinical Context Breast-feeding provides all of the nutritional, immunologic, and psychological requirements needed for a healthy, term infant to thrive, and it also benefits maternal health and well-being. Health organizations throughout the world recommend exclusive breast-feeding for 6 months. However, mothers in many countries and communities supplement breast-feeding with other fluids or foods before the infant is 6 months old, suggesting perceived benefits of early supplementation or lack of awareness of the possible risks. The objective of this Cochrane review by Becker and colleagues was to evaluate the benefits and harms of supplementation for full-term healthy breast-fed infants and to examine the timing and type of supplementation. Study Synopsis and Perspective Current research supports the World Health Organization's recommendation for exclusive breast feeding for the first 6 months after birth, according to a Cochrane review that was designed to assess the benefits and harms of supplementation for full-term healthy breast-fed infants up to 6 months of age. The systematic literature review included 6 trials (814 infants) and was published online December 7 and in the December issue of the Cochrane Library. The review included randomized or quasi-randomized controlled trials in infants younger than 6 months of age and compared exclusive breast-feeding vs breast-feeding with any additional food or fluids. All of the studies were conducted many years ago (1982 - 1999). There was a significant difference favoring exclusive breast-feeding over fluid supplementation up to and including week 20 (risk ratio, 1.45; 95% confidence interval [CI], 1.05 - 1.99). The review also raised concerns that the addition of glucose water at 70 mL/kg/day might displace nutrients provided by breast milk. Three trials examined infant morbidity and found a statistically, but not clinically, significant difference in temperature at 72 hours (mean difference [MD], 0.10°; 95% CI, 0.01° - 0.19°) in glucose-supplemented infants compared with exclusively breast-fed infants. In addition, serum glucose levels were higher in glucose-supplemented infants at 24 hours, but not at 48 hours (−0.24 mmol/L; 95% CI, −0.51 to 0.03). In addition to finding no benefit from fluid supplementation of newborns or infants (up to age 6 months), the review found possible negative effects on the duration of breast-feeding from the brief use of additional water or glucose water. The studies were independently selected for inclusion in the review by 2 authors, and 3 authors extracted the data and assessed the risk for bias. The review was performed because although the World Health Organization and other organizations recommend exclusive breast-feeding for 6 months, the addition of other fluids or foods is common in many countries and communities. This practice suggests perceived benefits of early supplementation or lack of awareness of the possible risks. Although the review focused on the effects on the infant during the first 6 months of life, the authors noted that supplementation with nonhuman milk may have effects on the developing gastrointestinal, metabolic, and immune systems that persist through childhood and beyond. The review also did not include the effect of an artificial teat on infant sucking skills or its role as a potential source of infection. The review was also limited in that it only looked at effects on the infants and did not include the possible effects of supplementation on the mother. These could include engorgement, mastitis, earlier return to fertility, nutritional status, maternal use of time, and maternal mental health and financial effects. The authors have disclosed no relevant financial relationships. Cochrane Library. Published online December 7, 2011. Abstract Related Link Information about The Baby-Friendly Hospital Initiative, which discourages infant supplementation, was developed by WHO and UNICEF and is available online. Clinical Implications According to a Cochrane review of randomized controlled trials in healthy, breast-fed newborn infants, the benefits or harms of supplementation or the effect of timing and type of supplementation could not be determined. However, brief use of additional water or glucose water had no detectable benefit to newborn infants and possible negative effects on the duration of breast-feeding. For infants 4 to 6 months old, there was no detectable benefit from additional foods nor any detectable risks related to morbidity or weight change. This Cochrane review found no evidence to disagree with international health associations' recommendation for exclusive breast-feeding for healthy infants for the first 6 months.