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The effect of respiratory tract infections on reported asthma symptoms.

BACKGROUND: Wheezing and chest tightness is associated with respiratory tract infections. Thus the occurrence of respiratory tract infections may influence the prevalence of asthma. AIMS: To assess the strength of relation between two main symptoms of asthma and the prevalence of respiratory tract infections in children with and without asthma. METHODS: The study population was 3,796 children, four years of age, whose parents had answered a questionnaire on respiratory symptoms and asthma. The prevalence of wheezing and chest tightness in the last 12 months and four weeks was estimated according to the occurrence of respiratory tract infections during the corresponding time periods; 95% confidence intervals of the prevalence and the statistical significance of the differences in the prevalence by using chi-square test were calculated. RESULTS: The prevalence of wheezing and chest tightness was higher in children who had experienced respiratory tract infections than in those who had not. The prevalence of wheezing was 17.5% among children who had experienced bronchitis and 3.0% among children whom had not (p<0.001). The prevalence of chest tightness in the last 12 months was 3.7% (95% CI 3.1-4.1) among children without asthma and 59.3% (95% CI 53.4-65.2) among children with asthma (p<0.001). The prevalence of wheezing and chest tightness increased with increasing number of different types of respiratory tract infections among children without asthma (p<0.001) and tended to be so among children with asthma. CONCLUSIONS: These findings have implications for the interpretation of results from epidemiological studies using respiratory symptoms as a health-related outcome of asthma.

Asthma↗

Frequent detection of human rhinoviruses, paramyxoviruses, coronaviruses, and bocavirus during acute respiratory tract infections.

Viruses are the major cause of pediatric acute respiratory tract infection (ARTI) and yet many suspected cases of infection remain uncharacterized. We employed 17 PCR assays and retrospectively screened 315 specimens selected by season from a predominantly pediatric hospital-based population. Before the Brisbane respiratory virus research study commenced, one or more predominantly viral pathogens had been detected in 15.2% (n = 48) of all specimens. The Brisbane study made an additional 206 viral detections, resulting in the identification of a microbe in 67.0% of specimens. After our study, the majority of microbes detected were RNA viruses (89.9%). Overall, human rhinoviruses (HRVs) were the most frequently identified target (n = 140) followed by human adenoviruses (HAdVs; n = 25), human metapneumovirus (HMPV; n = 18), human bocavirus (HBoV; n = 15), human respiratory syncytial virus (HRSV; n = 12), human coronaviruses (HCoVs; n = 11), and human herpesvirus-6 (n = 11). HRVs were the sole microbe detected in 37.8% (n = 31) of patients with suspected lower respiratory tract infection (LRTI). Genotyping of the HRV VP4/VP2 region resulted in a proposed subdivision of HRV type A into sublineages A1 and A2. Most of the genotyped HAdV strains were found to be type C. This study describes the high microbial burden imposed by HRVs, HMPV, HRSV, HCoVs, and the newly identified virus, HBoV on a predominantly paediatric hospital population with suspected acute respiratory tract infections and proposes a new formulation of viral targets for future diagnostic research studies.

Acute Disease↗

Highlights on the appropriate use of fluoroquinolones in respiratory tract infections.

The impact of respiratory infections on public health is increasing, and lower respiratory tract infections are a major cause of morbidity and mortality. Moreover, most antibiotic prescriptions are related to respiratory infections and this is probably one of the main determinants of the increasing rate of bacterial resistance in both community and hospital settings. This has been the catalyst for the development of new drugs, such as the new fluoroquinolones. The new fluoroquinolones have an excellent spectrum providing cover for the most important respiratory pathogens, including atypical and "typical" pathogens. The pharmacokinetic and dynamic properties of the new fluoroquinolones have a significant impact on their clinical and bacteriological efficacy. They cause a concentration-dependent killing with a sustained post-antibiotic effect. Fluoroquinolones combine exceptional efficacy with cost-effectiveness. Not surprisingly, different guidelines have inserted these agents among the drugs of choice in the empirical therapy of LRTIs. This review discusses the most recent data on the bacteriological and clinical activity of the new fluoroquinolones and critically analyses the risks of a potential overuse of this valuable new class of drugs.

Anti-Infective Agents↗

Health-related quality of life of adults with upper respiratory tract infections.

OBJECTIVE: To determine the impact that upper respiratory tract infections have on patients' physical, social, and emotional functioning, we measured the health-related quality of life (HRQL) of adults with upper respiratory tract infections. SETTING: Acute care clinic from November 2001 to February 2002. DESIGN: Prospectively administered survey. To measure HRQL, we used the Acute Form of the Short Form-36, version 2 (SF-36). For all 8 SF-36 subscales, we used norm-based scoring, in which the general U.S. population has a mean of 50. PATIENTS: Adults who had symptoms for fewer than 30 days completed the SF-36; and were diagnosed with nonspecific upper respiratory infection, viral syndrome, otitis media, sinusitis, nonstreptococcal pharyngitis, streptococcal pharyngitis, or acute bronchitis. MEASUREMENTS AND MAIN RESULTS: The sample of 318 patients was 63% female, 81% white, and had a mean age of 35 years. The primary diagnoses were nonspecific upper respiratory infection (42%), acute bronchitis (16%), sinusitis (12%), viral syndrome (9%), nonstreptococcal pharyngitis (8%), otitis media (7%), and streptococcal pharyngitis (6%). Patients had a mean general health subscale score of 50.9, which is not significantly different from the mean population value of 50 (P =.09). However, there were significant decrements in the remaining 7 subscales of the SF-36: physical functioning (45.5), role-physical (38.5), bodily pain (42.6), vitality (40.8), social functioning (37.8), role-emotional (46.8), and mental health (46.8; P <.0001 for all 7 subscales compared with normative values). Results were similar for the subset of patients with no comorbid illnesses (P <.001 for the same 7 subscales) and patients diagnosed with nonspecific upper respiratory infection (P <.001 for the same 7 subscales). These decrements were similar in magnitude, but somewhat different in subscale pattern, to those of adults with chronic lung disease, osteoarthritis, and depression. CONCLUSIONS: Physicians should remember that adults who seek care for upper respiratory tract infections have measurable, significant decrements in HRQL. For researchers, HRQL is an attractive, potential measure of outcome in future trials of established and novel therapies for upper respiratory tract infections.

Adolescent↗

Therapeutic potential of the new quinolones in the treatment of lower respiratory tract infections.

The impact of respiratory infections on public health is increasing and lower respiratory tract infections are a major cause of morbidity and mortality. We are also facing a worldwide burst of antibiotic bacterial resistance. The new fluoroquinolones have an excellent spectrum covering the most important respiratory pathogens, including atypical and 'typical' pathogens. Pharmacokinetic and dynamic properties of the new fluoroquinolones have a significant impact on their clinical and bacteriological efficacy. They cause a concentration-dependent killing with a sustained postantibiotic effect. Fluoroquinolones combine exceptional efficacy with cost-effectiveness. Not surprisingly, different guidelines have inserted these agents among the drugs of choice in the empirical therapy of community-acquired pneumonia. This review discusses the more recent data on bacteriological and clinical activity and critically analyses the risks of a potential overuse of this valuable new class of drugs.

4-Quinolones↗

A novel pancoronavirus RT-PCR assay: frequent detection of human coronavirus NL63 in children hospitalized with respiratory tract infections in Belgium.

BACKGROUND: Four human coronaviruses are currently known to infect the respiratory tract: human coronaviruses OC43 (HCoV-OC43) and 229E (HCoV-229E), SARS associated coronavirus (SARS-CoV) and the recently identified human coronavirus NL63 (HCoV-NL63). In this study we explored the incidence of HCoV-NL63 infection in children diagnosed with respiratory tract infections in Belgium. METHODS: Samples from children hospitalized with respiratory diseases during the winter seasons of 2003 and 2004 were evaluated for the presence of HCoV-NL63 using a optimized pancoronavirus RT-PCR assay. RESULTS: Seven HCoV-NL63 positive samples were identified, six were collected during January/February 2003 and one at the end of February 2004. CONCLUSIONS: Our results support the notation that HCoV-NL63 can cause serious respiratory symptoms in children. Sequence analysis of the S gene showed that our isolates could be classified into two subtypes corresponding to the two prototype HCoV-NL63 sequences isolated in The Netherlands in 1988 and 2003, indicating that these two subtypes may currently be cocirculating.

Adolescent↗

Protective effects of immunoactive peptide, FK565 against systemic and local infections with herpes simplex virus and murine cytomegalovirus and respiratory tract infection with influenza virus in mice.

The protective effects of FK565 against systemic infections with herpes simplex virus (HSV) and murine cytomegalovirus (MCMV), respiratory tract infection with influenza virus and zosteriform rash with HSV investigated in mice. FK565 showed excellent protective activities against systemic infections with both acyclovir (ACV)-sensitive and -resistant HSV at intravenous and subcutaneous doses of 0.1 and 1 mg/kg and oral dose of 1 mg/kg. FK565 showed superior protective activities at subcutaneous doses of 0.01 and 0.1 mg/kg compared to ACV at subcutaneous dose of 15 mg/kg against MCMV infection. In respiratory tract infection with influenza virus, FK565 showed potent protective effects at intravenous, subcutaneous and oral doses of 0.001 to 1 mg/kg. FK565 markedly inhibited zosteriform spread of HSV on the flank skin at an intravenous dose of 0.1 mg/kg and the mice given FK565 survived longer than the control mice. The peritoneal exudate cells from FK565-treated mice suppressed the growth of HSV in mouse embryo fibroblast more strongly than those from the control mice, although FK565 had no direct antiviral activity against HSV. These findings suggest that FK565 enhanced the host defense ability against viral infections by nonspecific activation of macrophages.

Animals↗

Lower respiratory tract infection therapy--the role of ciprofloxacin.

Lower respiratory tract infections account for a large proportion of prescribed antibiotics and, with emerging resistance to standard agents, the introduction of the fluoroquinolones, in particular ciprofloxacin, has provided a further component in the armamentarium. This review encompasses 37 published clinical trials which featured ciprofloxacin; 3274 patients with lower respiratory tract infections were treated with this agent; in 94.1% of patients treatment was clinically successful and 90.9% of cases showed eradication of the causative pathogen. When these data were supplemented with previously unpublished information from the clinical trial database, specific organism eradication rates of 86.1%, 96.2% and 94.6% for Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, respectively, were observed. These findings suggest that the high respiratory tissue penetration of ciprofloxacin and the achievable minimum inhibitory concentrations lead to acceptable clinical outcomes in lower respiratory tract infections.

Adult↗

Randomized controlled multicenter trial of aerosolized ribavirin for respiratory syncytial virus upper respiratory tract infection in hematopoietic cell transplant recipients.

BACKGROUND: Respiratory syncytial virus infection of the upper airways may progress to fatal pneumonia in hematopoietic cell transplant recipients. The safety and efficacy of aerosolized ribavirin in preventing disease progression is unknown. METHODS: In a multicenter prospective trial, hematopoietic cell transplant recipients with respiratory syncytial virus infection of the upper airways were randomized to receive ribavirin (2 g 3 times daily) or supportive care for 10 days. The primary end point was progression to radiographically proven pneumonia. Secondary end points included virologically proven respiratory syncytial virus pneumonia, viral load changes, and safety. RESULTS: Fourteen patients were randomized to 1 of 2 treatment arms. The trial was discontinued after 5 years because of slow accrual. Pneumonia at 1 month after randomization occurred in 1 of 9 patients who received ribavirin and in 2 of 5 patients who received supportive care (P=.51); virologically proven respiratory syncytial virus pneumonia occurred in 0 of 9 and 2 of 5 patients, respectively (P=.11). At 10 days after randomization, the average viral load decreased by 0.75 log10 copies/mL in ribavirin recipients, compared with a viral load increase of 1.26 log10 copies/mL in untreated patients (P=.07). No discontinuations of ribavirin therapy because of adverse effects occurred during 84 drug administrations. Rates of adverse events were similar in both groups. CONCLUSIONS: Preemptive aerosolized ribavirin treatment appeared to be safe, and trends of decreasing viral load over time were observed. However, proof of efficacy remains elusive in hematopoietic cell transplant recipients.

Adolescent↗

Information leaflet and antibiotic prescribing strategies for acute lower respiratory tract infection: a randomized controlled trial.

CONTEXT: Acute lower respiratory tract infection is the most common condition treated in primary care. Many physicians still prescribe antibiotics; however, systematic reviews of the use of antibiotics are small and have diverse conclusions. OBJECTIVE: To estimate the effectiveness of 3 prescribing strategies and an information leaflet for acute lower respiratory tract infection. DESIGN, SETTING, AND PATIENTS: A randomized controlled trial conducted from August 18, 1998, to July 30, 2003, of 807 patients presenting in a primary care setting with acute uncomplicated lower respiratory tract infection. Patients were assigned to 1 of 6 groups by a factorial design: leaflet or no leaflet and 1 of 3 antibiotic groups (immediate antibiotics, no offer of antibiotics, and delayed antibiotics). INTERVENTION: Three strategies, immediate antibiotics (n = 262), a delayed antibiotic prescription (n = 272), and no offer of antibiotics (n = 273), were prescribed. Approximately half of each group received an information leaflet (129 for immediate antibiotics, 136 for delayed antibiotic prescription, and 140 for no antibiotics). MAIN OUTCOME MEASURES: Symptom duration and severity. RESULTS: A total of 562 patients (70%) returned complete diaries and 78 (10%) provided information about both symptom duration and severity. Cough rated at least "a slight problem" lasted a mean of 11.7 days (25% of patients had a cough lasting > or =17 days). An information leaflet had no effect on the main outcomes. Compared with no offer of antibiotics, other strategies did not alter cough duration (delayed, 0.75 days; 95% confidence intervals [CI], -0.37 to 1.88; immediate, 0.11 days; 95% CI, -1.01 to 1.24) or other primary outcomes. Compared with the immediate antibiotic group, slightly fewer patients in the delayed and control groups used antibiotics (96%, 20%, and 16%, respectively; P<.001), fewer patients were "very satisfied" (86%, 77%, and 72%, respectively; P = .005), and fewer patients believed in the effectiveness of antibiotics (75%, 40%, and 47%, respectively; P<.001). There were lower reattendances within a month with antibiotics (mean attendances for no antibiotics, 0.19; delayed, 0.12; and immediate, 0.11; P = .04) and higher attendance with a leaflet (mean attendances for no leaflet, 0.11; and leaflet, 0.17; P = .02). CONCLUSION: No offer or a delayed offer of antibiotics for acute uncomplicated lower respiratory tract infection is acceptable, associated with little difference in symptom resolution, and is likely to considerably reduce antibiotic use and beliefs in the effectiveness of antibiotics.

Acute Disease↗

Effect of rapid viral diagnosis on the management of children hospitalized with lower respiratory tract infection.

BACKGROUND: Although rapid viral tests are commonly used in children with lower respiratory tract infection, their effect on patient management has not been studied. OBJECTIVES: To examine how physicians utilize an enzyme immunoassay for respiratory syncytial virus (RSV EIA) and a centrifugation-enhanced cellular immunofluorescence assay for multiple viral pathogens [viral respiratory panel (VRP)] in children hospitalized with respiratory illness; to determine the effect of testing on length of stay, antibiotic use and costs; and to determine physician attitudes toward RSV testing. DESIGN AND SETTING: Prospective study and survey at a large children's hospital. PATIENTS: Previously healthy children < 24 months of age consecutively admitted between January 1 and February 11, 1995, with symptoms of lower respiratory tract infection. RESULTS: Of 200 patients 160 were tested by RSV EIA; 92 were positive and 68 were negative. Tested children were younger, more tachypneic and more likely to require oxygen than those not tested. Overall the length of stay was similar in RSV-positive and -negative patients. Although equal proportions of each group were given antibiotic therapy, RSV-positive children received antibiotic therapy for fewer days than RSV-negative children (median 2 vs. 3 days; P = 0.0387). However, a crude cost analysis did not support a strategy of testing all bronchiolitis patients for RSV. Sixty-five of the 68 RSV-negative children were tested for RSV and other pathogens by VRP. In 55 cases the results were not available until after patient discharge and could not have influenced their management. One hundred three physicians caring for children in the study were surveyed. Of 75 respondents almost all thought that RSV EIA results influenced their management of patients and were important to parents. CONCLUSIONS: Most children hospitalized with symptoms of lower respiratory tract infection were tested for viral pathogens. The VRP provided little clinically useful information. In contrast RSV EIA results may have been used by clinicians to make antibiotic decisions. Physicians felt that rapid testing for RSV was important.

Anti-Bacterial Agents↗

Viral etiology of acute respiratory tract infections in children presenting to hospital: role of polymerase chain reaction and demonstration of multiple infections.

BACKGROUND: Viral lower respiratory tract infections are a leading cause of hospitalization for young children. METHODS: We used polymerase chain reaction (PCR) and conventional methods of cell culture and antigen detection to establish the viral etiology of acute respiratory tract infections in 75 hospitalized children. RESULTS: One or more viral pathogens were detected in 65 (87%) children, with respiratory syncytial virus being the most commonly identified virus (36 children). Other viruses identified included influenza virus types A and B, parainfluenzavirus type 3, adenovirus, enterovirus, rhinovirus, coronavirus and human metapneumovirus. PCR increased the diagnostic yield significantly compared with antigen detection and culture, with 39 (21%) diagnoses identified by this method. Multiple infections were identified in 20 (27%) children. CONCLUSIONS: PCR-based methodologies offer increased sensitivity for the detection of most respiratory viruses in young children. The inclusion of PCR into diagnostic testing strategies is needed to broaden our understanding of the natural ecology of respiratory viruses and the significance of multiple infections.

Acute Disease↗

[Study of bacterial flora in the stomach and the upper and lower respiratory tracts--the mechanism of lower respiratory tract infection].

To evaluate the mechanism of lower respiratory tract infection in the hospital, gastric juice, throat secretions, secretions in tracheal cannulae or tubes and aspirated sputum were cultured simultaneously in seven patients with tracheostomy and seven patients with tracheal intubation. Thirty-six strains of bacteria were isolated from gastric juice and only 22.2% of them were the same bacteria as those in the throat secretions. This suggested that there was little correlation between gastric and oropharyngeal flora. The bacteria isolated from throat secretions and aspirated sputum showed 38.5% coincidence in tracheostomized patients and 80% coincidence in intubated patients. In addition, the rate of agreement was 33.3% in tracheostomized patients and 88.9% in intubated patients between throat secretions and tracheal cannulae or tubes. These findings suggested that the correlation of bacterial flora between the upper and lower respiratory tracts was high in intubated patients and low in tracheostomized patients. Identical bacteria in the stomach and the upper and lower respiratory tracts (which may cause nosocomial infection) were isolated in only four of the 14 patients. It has been suggested that bacterial flora in the lower respiratory tract are transmitted from the stomach to the oropharynx and then cause lower respiratory tract infection in hospital. However, our study suggested that this was not a common pathogenic mechanism.

Aged↗

[Clinical evaluation of the efficacy of cefmetazole in respiratory tract infections of patients with underlying respiratory diseases].

Respiratory infections of 10 subjects with underlying respiratory diseases were treated with cefmetazole (CMZ) and its clinical effects were studied. Five subjects of them were respiratory tract infection, 3 subjects were pneumonia and 2 subjects were pneumonia followed by empyema. The underlying diseases were chronic pulmonary emphysema in 4 subjects, diffuse panbronchiolitis in 3, chronic bronchitis in 2 and bronchial asthma in 1. The doses of CMZ were 4 to 8 grams per day and the durations of administration ranged 3 to 39 days. The clinical effects were judged from the changes of fever, cough, amount of sputum, dyspnea, rale, chest X-ray, white blood cell counts, erythrocyte sedimentation rates, sputum culture and PaO2. The clinical effects of 6 subjects were evaluated as good, those of 3 were fair and that of 1 was poor. In 3 subjects H. influenzae in the sputum was eliminated and in 1 subject both H. aphrophilus and alpha-Streptococcus found in the pleural effusion were eliminated. In 1 subject Klebsiella in the sputum was eliminated and replaced by Enterobacter. No side effects were observed. We conclude that CMZ is considerably useful in the treatment of respiratory infections of the patients with underlying respiratory diseases.

Adult↗

Multicenter trial of cefpodoxime proxetil vs. amoxicillin-clavulanate in acute lower respiratory tract infections in childhood. International Study Group.

Acute lower respiratory tract infections in children are a worldwide public health problem, with an estimated 4 million potentially preventable deaths every year. Until recently, penicillin and related drugs were the treatment of choice for empiric therapy of paediatric lower respiratory tract infections. However, concerns over the emergence of penicillin-resistant strains of Streptococcus pneumoniae and beta-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis have led physicians to turn increasingly towards alternatives, such as the third generation cephalosporins. The oral extended spectrum cephalosporin cefpodoxime proxetil is highly active against the bacterial pathogens commonly associated with childhood lower respiratory tract infections. In order to evaluate its clinical efficacy in children with acute febrile lower respiratory tract infections, an international, multicenter, comparative, randomized open study was conducted in children ages 3 months to 11.5 years. Of 348 cases enrolled, 234 were randomized to cefpodoxime proxetil (8 mg/kg/day twice daily) and 114 to amoxicilin/clavanulate (amoxicillin 40 mg/kg/day 3 times a day). The duration of treatment was 10 days. Pretreatment diagnosis was pneumonia in 292 patients, bronchiolitis in 19 patients and acute bronchitis in 37 patients. Pathogens isolated from 59 cases included H. influenzae (47.5%), S. pneumoniae (23.7%), M. catarrhalis (11.9%) and Haemophilus parainfluenzae (6.8%). Clinical efficacy was evaluable in 278 children at the end of treatment when 95.2% of patients in the cefpodoxime proxetil group and 96.7% of patients in the amoxicillin/clavanulate group showed a satisfactory clinical response (cured or improved). The improvement was sustained at the follow-up visit, 10 to 20 days after completion of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Appropriate management of lower respiratory tract infections in primary care.

Respiratory tract symptoms are one of the major reasons for consultations with general practitioners. Most patients present because of symptoms that distress them or their family, or for reassurance that the symptoms do not represent something serious, or in order to receive medication. Many patients believe that their symptoms are due to an infection and expect to receive an antibiotic. These expectations influence the doctor's prescribing such that many patients will receive antibiotics even if the general practitioner considers these not to be required. This article describes the principles of rational antibiotic prescribing for lower respiratory tract infections in primary care, including disorders such as acute bronchitis, acute exacerbations of chronic obstructive pulmonary disease (COPD) and community-acquired pneumonia.

Journal Article↗

Full breastfeeding duration and associated decrease in respiratory tract infection in US children.

OBJECTIVE: The American Academy of Pediatrics recommends exclusive breastfeeding for an infant's first 6 months of life. When compared with exclusive breastfeeding for 4 months, greater protection against gastrointestinal infection, but not respiratory tract infection, has been demonstrated for the 6-month duration. The objective of this study was to ascertain if full breastfeeding of > or = 6 months compared with 4 to < 6 months in the United States provides greater protection against respiratory tract infection. METHODS: Secondary analysis of data from the National Health and Nutrition Examination Survey III, a nationally representative cross-sectional home survey conducted from 1988 to 1994, was performed. Data from 2277 children aged 6 to < 24 months, who were divided into 5 groups according to breastfeeding status, were compared. Children who required neonatal intensive care were excluded. SUDAAN software was used to account for the complex sampling design. Logistic regression adjusted for confounding factors. Outcome measures included adjusted odds of acquiring pneumonia, > or = 3 episodes of cold/influenza, > or = 3 episodes of otitis media (OM), or wheezing in the past year or acquiring first OM at < 12 months of age. RESULTS: In unadjusted analyses, infants who were fully breastfed for 4 to < 6 months (n = 223) were at greater risk for pneumonia than those who were fully breastfed for > or = 6 months (n = 136) (6.5% vs 1.6%). There were not statistically significant differences in > or = 3 episodes of cold/influenza (45% vs 41%), wheezing (23% vs 24%), > or = 3 episodes of OM (27% vs 20%), or first OM at < 12 months of age (49% vs 47%). Adjusting for demographic variables, childcare, and smoke exposure revealed statistically significant increased risk for both pneumonia (odds ratio [OR]: 4.27; 95% confidence interval [CI]: 1.27-14.35) and > or = 3 episodes of OM (OR: 1.95; 95% CI: 1.06-3.59) in those who were fully breastfed for 4 to < 6 months compared with > or = 6 months. CONCLUSIONS: This nationally representative study documents increased risk of respiratory tract infection including pneumonia and recurrent OM in children who were fully breastfed for 4 vs 6 months. These findings support current recommendations that infants receive only breast milk for the first 6 months of life.

Birth Weight↗