Anti-inflammatory treatment for recurrent wheezing in the first five years of life

Medications identified for the treatment of recurrent wheezing in preschool children by the Expert Panel Report of the NHLBI Guidelines for the Diagnosis and Management of Asthma include inhaled corticosteroids, chromones, theophylline, and leukotriene pathway modifiers. However, these various agents differ in their mechanism, extent of action on the airway inflammatory process, and degree of clinical efficacy. Inhaled corticosteroids can control symptoms in many young children with even severe persistent wheezing, but data on their long-term safety when administered in preschool-age children are scarce. There is some information on the uninterrupted use of inhaled corticosteroids in school-age children and the absence of an adverse effect on ultimate adult height. Despite laboratory evidence of adrenal suppression in some studies, few pediatric cases of clinical adrenal insufficiency have been reported. Low-dose inhaled corticosteroid (<400 mcg/day for beclomethasone), which is adequate for controlling mild persistent symptoms, is generally safe. Chromones have a remarkable safety profile, but they are most effective for symptoms of mild severity. Promising data have been published on the efficacy and safety of leukotriene pathway modifiers when used in young children with persistent symptoms. It is uncertain whether early introduction and long-term administration of inhaled corticosteroids prevent development of irreversible airway obstruction. Nevertheless, they may be especially useful for patients with moderate to severe disease in whom other agents (chromones or leukotriene pathway modifiers) will most likely fail to control symptoms. Pediatr Pulmonol. 2003; 35:241-252.     

Risk of physician-diagnosed asthma in the first 6 years of life

OBJECTIVE: The objective of this cohort study was to determine if complications of pregnancy and labor, characteristics at birth, and exposure to infections influence the incidence of asthma in the first 6 years of life. DESIGN: We identified all children born between 1980 and 1990 in the Province of Manitoba, Canada. We used records of physician contacts (inpatient and outpatient) and services of the universal provincial health insurance plan to follow up 170,960 children from birth to the age of 6 years to identify the first diagnosis of asthma. Information on mothers and siblings was also obtained to determine family history of disease and exposure to infections. RESULTS: During the study period, a diagnosis of asthma was made in 14.1% of children by the age of 6 years. The incidence was higher in boys than in girls, in those with family history of allergic diseases. It was higher in urban than in rural areas, and lowest in those born in winter. Asthma was more likely in those with low birth weight and premature birth. Certain congenital abnormalities and complications of pregnancy and labor also increased the risk of asthma. The risk of asthma increased with maternal age. Both upper and lower respiratory infections increased the risk of subsequent asthma, and this effect was more important than exposure to familial respiratory infections, which also tended to increase asthma risk. The risk of asthma decreased with the number of siblings when siblings had a history of allergic disorders. CONCLUSIONS: In addition to genetic influences, intrauterine and labor conditions are determinants of asthma. Exposure to both upper and lower respiratory tract infections increases the risk; these infections do not explain the protective effect associated with the increasing number of siblings.     

Risk factors for recurrent wheezing in the first year of life in the city of Córdoba,Argentina

BackgroundWheezing is a very common respiratory symptom in infants. The prevalence of wheezing in infants, conducted in developed countries shows prevalence rates ranging between 20% and 30%. However, we do not know the risk factors in our population of wheezing infants.MethodsA standardised written questionnaire (WQ-P1-EISL) in infants between 12 and 18 months of age residing in the city of Cordoba was used; population/sample included 1031 infants. Recurrent wheezing (RW) was defined as three or more episodes of wheezing reported by the parents during the first 12 months of life. Data obtained were coded in Epi-Info™ (version 7) and statistically analysed with SPSS (version 17.5) software in Spanish. Parametric tests (one-way ANOVA) were performed for identifying significantly associated variables.ResultsThe prevalence of wheezing infants was 39.7%; recurrent wheezing 33%; and severe wheezing 14.7%; 13.7% had pneumonia before the first year and of these 6.3% were hospitalised, multiple variables as risk factors for wheezing were found such as: >6 high airway infections and bronchiolitis in the first three months of life, smokers who smoke in the home among other risk factors and protective factors in those who have an elevated socioeconomic status.ConclusionIt is known that persistent respiratory problems in children due to low socioeconomic status is a risk factor for wheezing, pneumonia and could be a determining factor in the prevalence and severity of RW in infants. Research suggests that there are areas for improvement in the implementation of new educational strategies.     

Outcome of asthma and wheezing in the first 6 years of life: follow-up through adolescence

RATIONALE: The effect of early life wheezing on respiratory function and continued symptoms through adolescence has not been fully described. Using data from a population-based birth cohort in Tucson, Arizona, we previously described four phenotypes based on the occurrence of wheezing lower respiratory illnesses before age 3 yr and active wheeze at age 6 yr: never wheezers (n = 425), transient early wheezers (n = 164), persistent wheezers (n = 113), and late-onset wheezers (n = 124). OBJECTIVE: We sought to determine the prognosis for these phenotypes, with reference to lung function and symptoms, through adolescence. METHODS: Current wheeze was assessed by questionnaire, lung function was measured by conventional spirometry, and atopy was determined by skin prick tests. RESULTS: The prevalence of atopy and wheeze by age 16 yr was similar for never and transient wheezers and for persistent and late-onset wheezers. Both transient early, and persistent wheezers had significantly lower FEF(25-75) (-259 ml/s, p < 0.001, and -260 ml/s, p = 0.001, respectively), FEV1 (-75 ml, p = 0.02, and -87 ml, p = 0.03, respectively), and FEV1:FVC ratio (-1.9%, p = 0.002, and -2.5%, p = 0.001, respectively) through age 16 yr compared with never wheezers. Late-onset wheezers had levels of lung function similar to those of never wheezers through age 16 yr. There was no significant change in lung function among subjects with any of the four phenotypes, relative to their peers, from age 6 to 16 yr. CONCLUSION: Patterns of wheezing prevalence and levels of lung function are established by age 6 yr and do not appear to change significantly by age 16 yr in children who start having asthma-like symptoms during the preschool years.     

Milk-induced wheezing in children with asthma

BackgroundFood allergy has been gaining increasing attention, mostly as causing gastrointestinal and cutaneous reactions. Its role in asthma seems to be under-recognised.ObjectivesThis study's aim is to explore the frequency of involvement of a common food, namely cow's milk, in childhood asthma.Methods32 children (5 months to 11 years; median 24 months; mean 34 months) with asthma and a suspected history of cow's milk allergy were studied. They underwent skin prick testing (SPT) and specific IgE (sIgE) testing to whole cow's milk (WCM), casein, α-lactalbumin, and β-lactoglobulin, followed by single-blind oral milk challenge.ResultsReactions to milk challenge occurred in 12 (37.5%) including wheezing in 5 (41.7%, or 15.6% of the whole group). Children who developed wheezing at the time of challenge were younger than those who had negative challenge (23.0 months vs. 34.8 months). Challenge was positive in 33.3% of subjects who had a positive SPT, and SPT was positive in 50% of challenge-positive subjects. Regarding sIgE, challenge was positive in 26.7% of sIgE-positive subjects, and sIgE was positive in 33.3% of challenge positive subjects. Skin or serum testing with individual protein fractions did not seem to add significant advantage over testing with WCM alone.ConclusionThis study shows that cow's milk can cause wheezing in children with asthma. Although SPT seemed to be more reliable than sIgE testing, both had suboptimal reliability. It is worth considering possible milk allergy in children with asthma, particularly when poorly controlled in spite of proper routine management.     

Risk factors associated with transient wheezing in young children.

Transient wheezing in young children has been reported to be independent of atopy. Although persistence of early wheezing has been associated with factors related to allergy in multiple studies, transient wheezing has not been similarly studied. The Childhood Allergy Study birth cohort was the source of these data. Transient wheezing was defined as history of wheezing in the past 12 months at ages 1, 2, and/or 4 years, but not at 6 years, and evaluated in relationship to aeroallergen-specific circulating IgE and positive skin testing as markers of an atopic profile. Testing for IgE and skin-prick testing to dust mites, dogs, cats, ragweed, and timothy were performed at the age of 6 years. Other variables in logistic regression analyses were sex; breast-feeding; birth order; parental allergy and smoking history; and household pets, daycare, fever, and antibiotic use in the 1st year of life. Of 372 children, 128 (34.4%) experienced transient wheezing and 175 (47.0%) never wheezed. Atopy was not associated with transient wheezing (adjusted odds ratio for a positive allergen-specific IgE test = 1.2, p = 0.66; skin-prick test = 0.8, p = 0.47). Boys were more likely to be transient wheezers (adjusted relative risk [RR] = 1.7; 95% confidence interval [CI], 1.1-2.8; p = 0.018). Transient wheeze was associated with antibiotic treatment in the first 6 months of life (adjusted RR = 1.6; 95% CI, 1.0-2.6; p = 0.048). We confirm previous observations that transient wheezing in young children is not associated with an atopic predisposition.     

Initial airway function is a risk factor for recurrent wheezing respiratory illnesses during the first three years of life. Group Health Medical Associates

We recently reported a significant relationship between lung function measured prior to any lower respiratory tract illness and subsequent wheezing illnesses during the first year of life (N Engl J Med 1988; 319:1112-7). Follow-up has continued for this group of infants during the second and third years of life. When compared with never wheezers, infants who wheezed during the first year of life and had at least one additional lower respiratory illness had 22% lower initial levels of an indirect index of airway conductance derived from the shape of tidal breathing curves (p less than or equal to 0.01), 22% lower respiratory conductance (p less than or equal to 0.05), 25% lower maximal flows at the end-expiratory point (p less than or equal to 0.01), and 10% lower functional residual capacity (p less than or equal to 0.05). Infants who wheezed only once during the first 3 yr of life or who started wheezing during the second year of life had normal tidal breathing curves but significantly lower maximal expiratory flows (p less than or equal to 0.05). Their functional residual capacity was also lower than that of never wheezers (p less than or equal to 0.05). We conclude that diminished initial airway function may be a predisposing factor for recurrent wheezing respiratory illnesses starting in the first year of life. Infants who will have only one wheezing respiratory illness or who will start wheezing after the first year of life seem to have lower levels for some but not for all lung function tests performed in this study.     

Exposure to cat allergen,maternal history of asthma,and wheezing in first 5 years of life

We looked for an association between early exposure to pets and asthma and wheezing in children whose mothers or fathers did or did not have a history of asthma. We followed up 448 children, who had at least one parent with a history of atopy, from birth to 5 years. Among children whose mothers had no history of asthma, exposure to a cat or a Fel d 1 concentration of at least 8 microg/g at the age of 2-3 months was associated with a reduced risk of wheezing between the ages of 1 and 5 years. However, among children whose mothers did have a history of asthma, such exposures were associated with an increased risk of wheezing at or after the age of 3 years. There was no association between wheezing and exposure to dog or dog allergen, and the father's allergy status had no effect on the relation between childhood wheezing and cat exposure.     

Bronchoalveolar cells in children < 3 years old with severe recurrent wheezing

STUDY OBJECTIVE: To determine the cell profile of BAL from infants with severe recurrent wheezing who were not acutely ill at the time of investigation, suggesting an ongoing inflammation. Design and patients: In a retrospective study, we determined BAL cell profiles for 83 children with wheezing aged 4 to 32 months (mean +/- SD, 11.3 +/- 5.5 months). Fiberoptic bronchoscopy was performed in children with severe recurrent wheezy bronchitis unresponsive to inhaled steroids. These children were compared with 17 children aged 6 to 36 months (mean, 15.1 +/- 7.5 months) with various nonwheezing pulmonary diseases. Children were included as control subjects if they had no endobronchial inflammation and no atopy. RESULTS: The BAL cell profile of young children with wheezing typically includes a significantly higher cell count (mean, 644.4 +/- 956.8 x 10(3)/mL vs 313 +/- 203.2 x 10(3)/mL, p = 0.008), a significantly higher percentage of neutrophils (mean, 9 +/- 12.1% vs 2.1 +/- 2.2%, p = 0.003), and a higher neutrophil count (mean, 43.2 +/- 81.6 x 10(3)/mL vs 7.9 +/- 11.8 x 10(3)/mL, p = 0.003), as compared with control subjects. The larger number of neutrophils in children with wheezing was not correlated with bacterial or viral infection, or with age, sex, or atopic status. In contrast to the situation in asthmatic adults, eosinophil levels were not higher in children with wheezing than in control subjects (mean, 0.09 +/- 0.27% vs 0.08 +/- 0.25%). CONCLUSION: Neutrophil-mediated inflammation in the airways appears to better characterize severe recurrent wheezing in children < 3 years old.     

5岁以下儿童反复喘息发作呼吸道病原分析

目的探讨5岁以下儿童反复喘息发作与呼吸道感染之间的关系。方法 2014年1月1日至2014年12月31日在我科住院治疗的525例5岁以下反复喘息儿童按年龄分三组:A组30天-1岁,B组1-3岁,C组3-5岁。收集急性喘息发作期血清,采用间接免疫荧光法同时检测:腺病毒(ADV)、呼吸道合胞病毒(RSV)、甲型流感病毒(IAV)、乙型流感病毒(IBV)、副流感病毒(PIVs)、嗜肺军团菌Ⅰ型(LP1)、肺炎支原体(MP)、Q热立克次体(COX)、肺炎衣原体(CP)9种呼吸道病原体Ig M抗体。结果呼吸道病原体Ig M检测阳性者233例(阳性率44.38%);MP检测阳性率最高,达24.38%;其次是ADV和RSV,阳性率分别为10.10%和9.90%。不同年龄组喘息儿童病原体检测种类亦不相同。A组以RSV检测阳性率最高,达18.10%,显著高于其他组患儿(P0.01);B组和C组患儿以MP检测阳性率最高,分别为31.15%和25.22%,高于A组(P0.05)。结论儿童喘息反复发作主要与呼吸道感染有关,MP、ADV和RSV是本地区引起5岁以下儿童喘息发作的主要病原体。     

Effects of inhaled fluticasone propionate in children less than 2 years old with recurrent wheezing

Our objective was to evaluate the efficacy and safety of two doses of fluticasone propionate (FP) in young children with recurrent wheezing and risk factors for asthma. Our study design was a randomized, double-blind, placebo-controlled comparison of inhaled FP 50 mcg twice daily (FP 100) and 125 mcg twice daily (FP 250), for 6 months. Outcome measures included number of wheezing episodes, days on albuterol, height standard deviation score (height SDS), osteocalcin (OC), bone alkaline phosphatase fraction (AKP), insulin-like growth factor-binding protein 3 (IGFBP-3), and serum levels of cortisol (SC). Our subjects were 30 patients, aged 7-24 months. Mean wheezing episodes were 6.0 +/- 1.9, 1.9 +/- 1.9, and 2.8 +/- 1.2; mean days of albuterol use were 24.3 +/- 1.3, 6.5 +/- 0.8, and 9.1 +/- 0.8, per patient for placebo, FP100, and FP250 groups, respectively. There was a significant reduction in clinical outcome in the two FP groups compared to placebo (P < 0.01). No significant correlations were found between FP dosage and height SDS, OC, AKP, IGFBP-3, and SC. In conclusion, in young children with asthmatic symptoms, FP at 50 and 125 mcg b.i.d. for 6 months significantly improved respiratory symptoms without causing significant side effects on growth and bone metabolism.     

Prevalence of recurrent wheezing during the first year of life in Setúbal district,Portugal

Background

Recurrent wheezing during the first year of life is a major cause of respiratory morbidity worldwide, yet there are no studies on its prevalence in Portugal.

Risk factors for intensive care in children with acute asthma

OBJECTIVE: A retrospective case-control study at Monash Medical Centre (MMC), a tertiary referral hospital in Melbourne, Australia, was conducted to identify risk factors associated with very severe asthma in paediatric patients. METHODOLOGY: Asthmatics admitted to an intensive care unit (ICU; n=52) were identified and considered to represent cases of very severe/near fatal asthma (NFA group). This group was compared to asthmatics who had been admitted on one occasion only to the emergency department at MMC (non-NFA controls, n=53). Patient files were examined and factors that may be linked to NFA were recorded. Information not on file was obtained from patients/parents during a structured telephone interview. Data for the two groups were compared, univariate and multivariate logistic regression analyses were performed, and odds ratios (OR) were calculated. RESULTS: Univariate analysis indicated that asthmatics with NFA were more likely to be older (P=0.01) and have a longer duration of asthma (P=0.02). They were also more likely to have hay fever (P=0.002; OR, 7.6), use inhaled corticosteroids (P=0.001), long acting beta(2) agonists (P=0.02), have an asthma management plan (P=0.006), and see a respiratory specialist (P=0.001). Parental smoking habits were not different between the groups. Multivariate logistic regression analysis identified male gender (P=0.05; OR, 5.7) and use of inhaled corticosteroids (P=0.07; OR, 7.2) as factors that may be predictive of NFA. CONCLUSIONS: This study identifies a number of factors associated with NFA; many are similar to those reported in adult patients. Asthma severity explains some findings, but the data also suggest that additional independent risk factors such as gender and duration of asthma may operate in children.     

Predictors for wheezing phenotypes in the first decade of life

Background and objective:   This study examined prenatal, perinatal and early childhood predictors of wheezing phenotypes in the first decade of life.
Methods:   Information on current wheezing, was collected prospectively from five surveys conducted every 2 years over the first decade of life. Five wheezing phenotypes were defined: non-wheezers, preschool, primary-school, intermittent and persistent wheezers. Logistic regression with adjustment for survey design was used to determine the predictors of wheezing phenotypes.
Results:   Data on 2711 children were used in the analysis. Early respiratory infection, the child's allergy and parental asthma were significant risk factors for preschool, intermittent and persistent wheeze. The child's allergy and parental asthma had stronger associations with persistent wheeze than with preschool wheeze. Breastfeeding was a significant predictor of both preschool and intermittent wheezing. Daycare attendance was a risk factor for preschool wheeze but a protective factor for primary-school wheezing. Crowding at home was a protective factor for both preschool and primary-school wheeze. Parental smoking was a significant factor for preschool wheeze.
Conclusion:   This study identified different predictors for each wheezing phenotype with some degree of overlap. The observed differential effects for these conditions raises the possibility that there are different aetiologies for asthma among children.     

Hair zinc and selenium levels in children with recurrent wheezing

The prevalence of asthma and other allergic diseases has increased markedly in the last few decades. Oxidative stress plays a central role in asthma pathogenesis, and reduced daily consumption of antioxidants is positively correlated with increased risk of asthma. Zinc (Zn) and selenium (Se) are the main antioxidant elements. In our study, we aimed to investigate hair Zn and Se levels in children with recurrent wheezing. The study included 65 patients with recurrent wheezing (RW) and 65 healthy children (HC). The hair Zn and Se levels (µg/g) of the RW group were lower in comparison with the HC group (162.43 ± 91.52 vs. 236.38 ± 126.44, P < 0.001, and 217.37 ± 83.01 vs. 280.53 ± 122.73, P < 0.001, respectively). Total antioxidant capacity (TAC) (mmol/L) of the RW group was found to be significantly lower in comparison with the HC group (1.38 ± 0.14 vs. 1.53 ± 0.20, respectively; P < 0.001). Number of wheezing episodes in the last 6 months were negatively correlated with serum TAC, hair Zn, and Se levels in RW group (r_p = ?0.291, P = 0.001; r_p = ?0.209, P = 0.017; r_p = ?0.206, P = 0.019, respectively). The number of acute respiratory tract infection (ARTI) episodes in the last 6 months was negatively correlated with serum TAC and hair Zn levels (r_p = ?0.316, P < 0.001, and r_p = ?0.196, P = 0.025, respectively). In this study, we found that TAC, hair Zn, and hair Se levels were lower in children with RW than HC and negatively correlated with wheezing episodes in the last 6 months. Also body Zn and Se levels can be reliably measured in hair samples. Pediatr Pulmonol. 2012; 47:1185–1191. © 2012 Wiley Periodicals, Inc.     

Risk factors for recurrent wheezing following acute bronchiolitis: a 12-month follow-up

The objective of this study was to identify wheezing recurrences and related risk factors in two groups of infants with bronchiolitis: respiratory syncytial virus (RSV)+ and RSV- as determined by RSV enzyme immunoassay. A 1-year prospective cohort study was conducted with infants younger than 2 years old. Follow-up was made monthly, by a clinical visit and/or by telephone, checking the number of wheezing episodes per month and possible related risk factors. There were 96 subjects enrolled, of whom 77 reached complete follow-up: 36 were RSV+ (46.8%), and 41 were RSV- (53.2%). In the RSV+ group, there were 17 males (47%), vs. RSV- with 30 males (73%) (P < 0.05); 22 RSV+ (61%) were admitted to hospital, vs.14 RSV- (34%) (P < 0.05). Mean age was not significantly different in both groups. The mean number of recurrences was 3.36 episodes/infant/year in the RSV+ and 2.34 in the RSV- group (P = 0.06). Crude relative risk (RR) for a new recurrence of an obstructive episode was 1.33 (95% CI, 0.99-1.79). After adjustment for several potential confounders, the RR was 1.41 (95% CI, 1.03-1.93). Hospitalization stay was longer in the RSV+ than the RSV- group (P < 0.05). In the RSV+ group, patients who had been hospitalized showed more recurrences (4.18) than those with outpatient treatment (2.07) (P < 0.05); this difference did not exist in the RSV- group. The related risk factors for recurrent wheeze in the RSV- group were male gender, number of siblings, and daycare attendance (P < 0.05). In the RSV+ group, the risk of recurrent wheeze was only increased by admission to hospital during the acute bronchiolitis episode (P < 0.05). We speculate that there may be a higher rate of increased airway reactivity and/or preexisting diminished lung function in RSV+ infants requiring hospitalization for their initial illness. In conclusion, RSV-proven bronchiolitis, particularly in those infants who are hospitalized, is associated with a higher recurrence of wheezing episodes in the subsequent 12 months. Other factors appear to account for recurrent wheeze in the RSV- group.     

Risk factors for asthma admissions in children.

Bronchial asthma is related to a high morbidity rate, leading to an increasing frequency of emergency room visits and hospital admissions. The aim of this study was to identify severity risk factors for childhood asthma related to hospitalization. The authors studied 124 children admitted to the hospital for asthma, during a 2-year period, correlating the obtained data with a sample of outpatients with asthma matched by age, gender, and socioeconomic status. A standardized questionnaire and skin-prick tests (SPTs) were performed on all children. The significant and independent risk factors identified for hospital admission were prior asthma hospitalization (OR = 7.63; 95% CI = 1.5-39.6; p = 0.01) and last-year admission (OR = 3.18; 95% CI = 1.1-8.9; p = 0.02), environmental tobacco-smoke exposure (OR = 6.63; 95% CI = 2.5-17.8; p = 0.002), allergen sensitization (OR = 3.86; 95% CI = 1.4-10.7; p = 0.009), family history of maternal asthma (OR = 3.58; 95% CI = 1.3-9.6; p = 0.01), and onset of symptoms before 12 months of age (OR = 2.76; 95% CI = 1.0-7.9; p = 0.06). Attendance at day care or kindergarten (OR = 0.38; 95% CI = 0.2-0.9; p = 0.04) and large family size (OR = 0.25; 95% CI = 0.1-0.8; p = 0.01) could be protective factors. Our results stress the importance of early diagnosis and specialized medical care of childhood asthma, mainly in high-risk children, with emphasis on medication planning and the establishment of preventive measures such as environmental tobacco smoke avoidance and limitation of aeroallergen exposure.     

Perinatal smoking exposure and risk of asthma in the first three years of life: A prospective prebirth cohort study

BackgroundThere is limited evidence on the association between prenatal smoking exposure and the risk of asthma in children. The aim of this prebirth cohort study was to investigate the association between prenatal and postnatal tobacco smoke exposure and the risk of asthma in Japanese children.MethodsStudy subjects were 1304 mother–child pairs. Information on the variables under study was obtained using repeated questionnaires that were completed by mothers, first prior to delivery, then shortly after birth and subsequently around 4, 12, 24, and 36 months after delivery. Ever asthma was defined as a maternal report of physician-diagnosed asthma at any time since birth. Current asthma was defined as the use of asthma medication at the time of the sixth survey.ResultsLogistic regression models revealed that maternal active smoking, either before pregnancy or during pregnancy, was not associated with the risk of ever asthma or current asthma. Further, no association was observed between postnatally living with at least one household smoker and the risk of asthma. Among children whose mothers are never smokers, maternal second-hand smoke (SHS) exposure at work and/or at home during pregnancy increased the risk of ever asthma and current asthma in children; adjusted odds ratio (95% confidence intervals) for ever asthma and current asthma were 2.41 (1.13–5.05) and 4.82 (1.68–13.43), respectively.ConclusionsOur findings suggest that maternal SHS exposure during pregnancy might be associated with an increased risk of ever asthma and current asthma in young children whose mothers have never smoked.     

Developmental potential in the first 5 years for children in developing countries

Many children younger than 5 years in developing countries are exposed to multiple risks, including poverty, malnutrition, poor health, and unstimulating home environments, which detrimentally affect their cognitive, motor, and social-emotional development. There are few national statistics on the development of young children in developing countries. We therefore identified two factors with available worldwide data--the prevalence of early childhood stunting and the number of people living in absolute poverty--to use as indicators of poor development. We show that both indicators are closely associated with poor cognitive and educational performance in children and use them to estimate that over 200 million children under 5 years are not fulfilling their developmental potential. Most of these children live in south Asia and sub-Saharan Africa. These disadvantaged children are likely to do poorly in school and subsequently have low incomes, high fertility, and provide poor care for their children, thus contributing to the intergenerational transmission of poverty.