Variability In Young Children Research Articles

Short-term weight variability in infants and toddlers: an observational study

AimsTo explore short-term weight variability in young children; (1) how it relates to expected weight gain and (2) how it is affected by age, time of day and dietary intakes...

Predicting children's internalizing symptoms across development from early emotional reactivity

AbstractCurrent methods of assessing children's emotional reactivity fail to capture individual differences in emotion across contexts that may be meaningfully related to youth psychopathology. We therefore explored the utility of modeling variability in young children's positive and negative emotion across emotionally evocative laboratory tasks to predict later adjustment. At age 3, 409 children completed a battery of laboratory tasks eliciting either positive or negative affect. We used latent difference score (LDS) modeling to predict children's caregiver‐reported internalizing symptoms across ages 3, 5, 8, and 11 from variability in their observer‐rated positive and negative emotion across laboratory tasks. We found that sex moderated the association between both average and variability measures of children's negative emotion at age 3 and trajectories of their anxious‐depressive symptoms across childhood. Measures of emotion variability predicted children's internalizing symptoms above and beyond measures of average emotion. Variability indices also provided unique information about the trajectories of children's symptoms. We discuss implications for the utility of LDS modeling in assessing children's emotional reactivity.

Hemoglobin EE disease in young Laotian children: Hematologic features and the contributions of genetic variations to Hb F expression.

The wide variation in hemoglobin (Hb) F levels has been observed in patients with Hb EE disease. This study aimed to describe hematologic features and determine the effect of genetic variants on Hb F expression in young children with Hb EE disease. Hematologic features and Hb profiles of Laotian children aged 6-23 months, who originally enrolled in the Lao-Zinc study, were retrospectively reviewed. Only children with Hb EE disease, as indicated by DNA analysis, were included in this current analysis. Genetic variants, including the G γ-XmnI polymorphism (C>T) of the HBG2 gene, the HBS1L-MYB intergenic region on chromosome 6, and the BCL11A on chromosome 2 as well as the mutations occurring on the Krüppel-like factor 1 (KLF1) gene, were examined. In total, 205 children were diagnosed as having Hb EE disease with Hb F ranged from 1.2 to 43.7%. Most of the children had mild to moderate anemia with a remarkable microcytosis. Analysis of the genetic variants revealed an extremely high frequency of the G γ-XmnI (93.7%). Applying multiple regression analysis adjusted for age, sex, and α-thal gene, a positive relation was observed for the rs4671393 (coefficient=3.87, p= .005) and the rs2297339 (coefficient=2.48, p= .046), but not the G γ-XmnI. A statistically non-significant relation was noted for the rs9399137 and the -154 (C>T) KLF1 mutation. Our findings provide insight into complex situation of Hb F variability in young children with Hb EE disease; and this can guide to appropriate care and counseling to affected families.

Inter and intra-limb coordination variability during walking in adolescents with autism spectrum disorder

BackgroundAutism spectrum disorder, a neurodevelopmental disorder, is difficult to characterize from a gait biomechanics perspective, possibly due to increased inter and intra-individual variability. Previous research illustrates increased gait variability in young children with autism, but assessments in older adolescents or at varying speeds are unavailable. The purpose of this study was to determine if adolescents with autism demonstrate increased intra-limb and inter-limb coordination variability during walking compared to age, sex, and body mass index matched controls. MethodsSeventeen adolescents with autism (age 13–18 years) and seventeen matched controls performed walking at two matched speeds: self-selected of adolescents with autism and at 1.3 m/s. Modified vector coding was used to determine the patterns of movement for foot-shank, left/right thigh, and contralateral thigh-arm coupling. Coordination variability, a measure of cycle-to-cycle variability, was determined across the full stride. Mixed-model analyses of variance were used to determine if group by speed interactions and/or main effects existed for coordination variability. FindingsA significant interaction existed for foot-shank variability (p = 0.039). Adolescents with autism had greater variability at self-selected speeds (p = 0.018), but not at 1.3 m/s (p = 0.593) compared to controls. Thigh-thigh coordination was greater for adolescents with ASD compared to controls at both speeds (p = 0.021). Variability was decreased at 1.3 m/s for both foot-shank (p = 0.016) and thigh-thigh (p = 0.021) coupling. InterpretationThis study illustrates that adolescents with autism perform walking with increased coordination variability at both proximal and distal segments. Thus, it is likely intra-individual variability drives the disparity of movement patterns in this population.

Reconsidering variability in child speech production

Child speech is highly variable between and within speakers. This pattern has traditionally been explained by a lack of motor routine and articulatory control in the developing speech-motor apparatus. But the assumption that child speech is inherently variable—and the result of motor development and control—may be premature. Recent work suggests that some child speech variation may instead be attributable to errors in measurement: children's high fundamental frequencies make many traditional acoustic measures, such as formant tracking, unreliable and variable. Additionally, child speech variation can often be explained by experiential factors, such as the size of the lexicon or the type and quantity of language exposure. This talk will report on these and other recent findings that suggest a need to reconsider the prevalence of, and reasons for, variability in young children's speech.

Assessing Child Postural Variability: Development, Feasibility, and Reliability of a Video Coding System

Aims Postural variability is central to children’s locomotion, motor control, and environmental exploration, and lacks standardized methods for systematic assessment. The purpose of this study was to develop and evaluate the feasibility and interrater reliability of Child Posture Variability Coding (CPVC), a method of quantifying postural variability in young children. Method Videos of parent-child play interactions obtained from a longitudinal study investigating language acquisition in typically developing (TD) children and children with autism spectrum disorder (ASD) were used to develop 33 codes for children’s voluntary changes in static and dynamic postures. Interrater reliability was calculated for three raters who independently coded 10 randomly selected videos of children aged 23 to 48 months (TD: n = 5, median = 35, IQR = 12.5; ASD: n = 5, median = 35, IQR = 6.75). Results Overall, CPVC demonstrated excellent interrater reliability (Krippendorff’s > 0.90). Among all codes developed, five codes (i.e., sit–half, sit–other, crawl, cruise, and supported walk) were not observed by any coders in the sample, but were kept in the coding scheme to reflect normal developmental milestones. Conclusions CPVC is a reliable, feasible method of quantifying postural variability in young children with and without neurodevelopmental disorders in naturalistic contexts.

The Association Between Glycemic Variability and Macronutrients in Young Children with T1D.

There is limited information regarding the potential effect macronutrients have on postprandial glycemic variability in young children with type 1 diabetes (T1D). To date, studies examining nutrition and glycemic outcomes either assess these factors at a single timepoint, or aggregate large datasets for group level analyses. This study examined how inter- and intraindividual fluctuations in carbohydrate, fat, and protein intake impact glycemic variability in the postprandial period for young children with T1D. Thirty-nine young children, aged 2-6 years, wore a continuous glucose monitor for 72 hr, while their parents completed detailed diet records of all food intake. The analyses tested three multilevel models to examine intra- and interindividual differences between food intake and postprandial glycemic variability. The results suggest carbohydrate intake, relates to greater postprandial glycemic variability. In contrast, the results reveal the inverse effect for protein, suggesting a tendency for young children who ate more protein at some meals to have lower postprandial glycemic variability, with the exception of lunch. There was no effect for fat on postprandial glycemic variability. These results suggest protein consumption may be an important consideration when aiming for optimal glycemic levels for some meals. When counseling parents of young children with T1D on common behaviors underlying glycemic excursion, pediatric psychologists may consider discussing the nutritional make up of children's meals. Further, the results demonstrate retaining longitudinal data at the person level, versus aggregating individual data for group level analyses, may offer new information regarding macronutrient intake and glycemic outcomes.

Associations Between Objective Sleep Behaviors and Blood Glucose Variability in Young Children With Type 1 Diabetes.

Young children with Type 1 diabetes (T1D) are at risk for extreme blood glucose variability, a risk factor for suboptimal glycated hemoglobin A1c (HbA1c) and long-term health complications. We know that a reciprocal relationship exists between sleep and glycemic outcomes in older youth with T1D; however, little research has examined objective sleep in young children (<7 years) with T1D. This study examines bidirectional associations between sleep behaviors and glycemic variability in young children with T1D. Thirty-nine young children with T1D (Mage 4.33 ± 1.46 years; MHbA1c 8.10 ± 1.06%) provided accelerometry data to objectively measure sleep onset latency, number of nighttime awakenings, and total sleep time. We also assessed HbA1c, average blood glucose, and glycemic variability (i.e., standard deviation of blood glucose from device downloads). We evaluated bidirectional relationships using multilevel modeling in SAS, with weekday/weekend as a Level 2 moderator. Children averaged 8.5 ± 1.44 hr of sleep per night, but only 12.8% met current sleep recommendations. Children experienced more nighttime awakenings, higher blood glucose, and more glycemic variability on weekends. Sleep onset latency and nighttime awakenings predicted greater glycemic variability on weekends, and weekend glycemic variability predicted increased nighttime awakenings. Most young children with T1D did not meet sleep recommendations. Young children experienced more nighttime awakenings, higher blood glucose, and increased glycemic variability on weekends only, when routines may be less predictable. Findings suggest that one way families of young children with T1D may be able to decrease glycemic variability is to keep consistent routines on weekdays and weekends.

Type 1 Diabetes in Children and Adolescents.

Type 1 Diabetes in Children and Adolescents.

Tibial impact accelerations in gait of primary school children: The effect of age and speed

Tibial stress fractures are associated with increased lower extremity loading at initial foot-ground contact, reflected in high peak positive acceleration (>8g) of the tibia in adults. There is no reported data on peak positive acceleration of the tibia in children during walking and running. The aim of this study was to establish tibial peak positive acceleration responses in children across a range of age and gait speeds. Twenty-four children aged 8.5±1.4years with no known gait pathology comprised two age groups; Young (7–9year, n=12) and Older (10–12 years, n=12). Wireless Inertial Measurement Unit comprising a tri-axial accelerometer was securely taped to the anteromedial aspect of the distal tibia to measure peak positive acceleration responses while walking and running on the treadmill at 3 different speeds (20% below baseline, baseline, and 20% above baseline). Results showed significant increase in peak positive acceleration with increased gait speed and greater variability in young children compared to older children. The study suggests that ground impact in walking, but not running, is mature by age 7 years. Future studies should explore strategies using peak positive acceleration responses to monitor ground impact during sport activities and its application in gait retraining.

An investigation of the stability and variability in young children's self-regulated learning behaviors in kindergarten

ABSTRACTThe authors examined the relative stability and variability of self-regulated learning (SRL) in kindergartners across various contexts (teacher-directed activities, small-group work, and independent work). They assessed the role of temperament and context on children's use of SRL while seeking to identify if there are optimal contexts for promoting SRL in particular children. The results revealed that although temperament was not related to SRL, children's regulation strategy usage was heavily dependent on context, contradicting the idea that children are either high or low self-regulators. The relative stability of SRL varied by child, with some children showing more sensitivity to context than did others. Optimal contexts for eliciting SRL also differed by children, with some children exhibiting elevated regulation during small-group activities and others during teacher-directed activities.

Eccentric Capitellar Ossification Limits the Utility of the Radiocapitellar Line in Young Children.

The radiocapitellar line (RCL) has long been used for the radiographic evaluation of elbow alignment. In children, the capitellar ossific nucleus serves as a proxy for the entire capitellum, but this substitution has not been verified. Using magnetic resonance imaging (MRI), we sought to understand how maturation of the ossific nucleus of the capitellum affects the utility of RCL throughout skeletal maturation of the elbow. The RCL was drawn on coronal and sagittal MRIs in 82 children (43 boys, 39 girls; age range, 1 to 13 y) with at least 3 patients in each 1-year interval age group. The perpendicular distance of the RCL from the center of both the cartilaginous capitellum and the capitellar ossific nucleus was measured relative to its total width, and a percent offset for each measurement was calculated. Logarithmic regression analysis was performed to analyze the effect of age and sex on percent offset. The RCL reliably intersected with the central third of the cartilaginous capitellum at all ages in both planes. Although the RCL intersected with the ossified capitellum in all but 3 measurements, it intersected with the central third of the ossified capitellum less often in younger children in both sagittal (B=0.47, P<0.001) and coronal (B=0.31, P=0.002) planes. Percent offset decreased significantly with age in a logarithmic manner in both sagittal (r=0.57, P<0.001) and coronal (r=-0.47, P<0.001) planes. 95% confidence intervals predict that the sagittal plane RCL will accurately intersect the central third of the ossified capitellum by age 10 years in girls and age 11 years in boys but not in the coronal plane. Eccentric ossification of the capitellum explains RCL variability in young children. The RCL does not reliably intersect the central third of the ossified capitellum until ages 10 years in girls and 11 years in boys in the sagittal plane. The RCL should be used within its limitations in skeletally immature children and should be combined with advanced imaging if necessary.

Persistently high glucose levels in young children with type 1 diabetes.

The aim of the study was to characterize glucose levels and variability in young children with type 1 diabetes (T1D). A total of 144 children of 4-10 yr old diagnosed with T1D prior to age 8 were recruited at five DirecNet centers. Participants used a continuous glucose monitor (CGM) every 3 months during an 18-month study. Among the 144 participants, 135 (mean age 7.0 yr, 47% female) had a minimum of 48 h of CGM data at more than five of seven visits and were included in analyses. CGM metrics for different times of day were analyzed. Mean hemoglobin A1c (HbA1c) at the beginning and end of the study was 7.9% (63 mmol/mol). Fifty percent of participants had glucose levels >180 mg/dL (10.0 mmol/L) for >12 h/d and >250 mg/dL (13.9 mmol/L) for >6 h/d. Median time <70 mg/dL (3.9 mmol/L) was 66 min/d and <60 mg/dL (3.3 mmol/L) was 39 min/d. Mean amplitude of glycemic excursions (MAGE) was lowest overnight (00:00-06:00 hours). The percent of CGM values 71-180 mg/dL (3.9-10.0 mmol/L) and the overall mean glucose correlated with HbA1c at all visits. There were no differences in CGM mean glucose or coefficient of variation between the age groups of 4 and <6, 6 and <8, and 8 and <10. Suboptimal glycemic control is common in young children with T1D as reflected by glucose levels in the hyperglycemic range for much of the day. New approaches to reduce postprandial glycemic excursions and increase time in the normal range for glucose in young children with T1D are critically needed. Glycemic targets in this age range should be revisited.

Stability and Variability in Young Children's Understanding of Floating and Sinking During One Single-Task Session

Intraindividual variability is a key component in explaining children's development and learning. Studying this type of variability on the micro-timescale can help us understand real-time constructive processes and the subsequent long-term development. The aim of this article is to study the process of children's understanding of floating and sinking during one single-task session. A total of 38 kindergartners were asked to explain the floating or sinking of 14 different objects. The results reveal that the majority of children showed a high degree of intraindividual variability. In general, most children had a decrease in variability of both content and complexity of explanations during one task session and stabilized in both complexity and content toward the end of the task. The analyses indicated that hypothesis testing was not related to changes in children's explanations. These results can be the starting point for further research about change on different, nested timescales.

Average Daily Risk Range (ADRR) in Young Children With Type 1 Diabetes

The objective was to examine the utility of the average daily risk range (ADRR) in young children with type 1 diabetes. Self-monitored blood glucose (BG) data and A1c values were collected from 134 children (ages 2-6). Other measures of BG variability and diabetes care were calculated using self-monitored BG data. ADRR, A1c, and other glycemic indices were compared to assess their distinctiveness and utility as measures of BG variability and glycemic control. Of young children's ADRR values, 72% were in the "high-risk" range using adult guidelines. ADRR and A1c were highly correlated with indicators of hyperglycemia but only weakly correlated with measures of hypoglycemia. ADRR was moderately correlated with minimum BG value in the past 30 days but not percentage of BG values below 70 mg/dL. A1c was not correlated with either measure of hypoglycemia. ADRR values confirm the high degree of BG variability present in young children with type 1 diabetes, particularly as compared with adults. New ADRR risk guidelines are needed for pediatric patients. ADRR and A1c are adequate indicators of hyperglycemia in young children. However, both ADRR and A1c failed to effectively capture hypoglycemia risk in this sample, and neither ADRR nor A1c can take the place of review of raw BG data to evaluate BG variability in young children.

Rational variability in children’s causal inferences: The Sampling Hypothesis

We present a proposal—“The Sampling Hypothesis”—suggesting that the variability in young children’s responses may be part of a rational strategy for inductive inference. In particular, we argue that young learners may be randomly sampling from the set of possible hypotheses that explain the observed data, producing different hypotheses with frequencies that reflect their subjective probability. We test the Sampling Hypothesis with four experiments on 4- and 5-year-olds. In these experiments, children saw a distribution of colored blocks and an event involving one of these blocks. In the first experiment, one block fell randomly and invisibly into a machine, and children made multiple guesses about the color of the block, either immediately or after a 1-week delay. The distribution of guesses was consistent with the distribution of block colors, and the dependence between guesses decreased as a function of the time between guesses. In Experiments 2 and 3 the probability of different colors was systematically varied by condition. Preschoolers’ guesses tracked the probabilities of the colors, as should be the case if they are sampling from the set of possible explanatory hypotheses. Experiment 4 used a more complicated two-step process to randomly select a block and found that the distribution of children’s guesses matched the probabilities resulting from this process rather than the overall frequency of different colors. This suggests that the children’s probability matching reflects sophisticated probabilistic inferences and is not merely the result of a naïve tabulation of frequencies. Taken together the four experiments provide support for the Sampling Hypothesis, and the idea that there may be a rational explanation for the variability of children’s responses in domains like causal inference.

Older Sibling Influences on the Language Environment and Language Development of Toddlers in Bilingual Homes.

Two separate studies examined older siblings' influence on the language exposure and language development of U.S.-born toddlers who were being raised in bilingual homes. The participants in Study 1 were 60 children between 16 and 30 months who had heard English and another language at home from birth; 26 had older siblings and 34 did not. The participants in Study 2 were 27 children, assessed at 22 and 30 months, who had heard English and Spanish from birth; 14 had school aged older siblings and 13 did not. Both studies found that older siblings used English more in talking to the toddlers than did other household members and that toddlers with older siblings were more advanced in English language development. Study 2 also found that the presence of a school aged older sibling increased mothers' use of English with their toddlers and that toddlers without a school aged older sibling were more advanced in Spanish than the toddlers with a school aged older sibling. These findings contribute to a picture of the complex processes that shape language use in bilingual homes and cause variability in young children's bilingual development.

A Comparison of Average Daily Risk Range Scores for Young Children with Type 1 Diabetes Mellitus Using Continuous Glucose Monitoring and Self-Monitoring Data

Young children with type 1 diabetes are vulnerable to glycemic excursion. Continuous glucose monitoring (CGM), combined with variability statistics, can offer a richer and more complete picture of glycemic variability in young children. In particular, we present data for the Average Daily Risk Range (ADRR) and compare ADRR scores calculated using CGM versus self-monitoring of blood glucose (SMBG) data for young children. CGM and SMBG data from 48 young children with type 1 diabetes (mean age, 5.1 years) were used to calculate two separate ADRR scores, using SMBG data (ADRRs) and CGM data (ADRRc), for each child. Additionally, we calculated mean amplitude of glycemic excursion (MAGE) scores for children to examine the concurrent validity of the ADRRs and ADRRc. Young children's mean ADRRc score was significantly greater than their ADRRs score (55±12 and 46±11, respectively; P<0.001). In addition, 74% of the time the children's ADRRc score reflected greater variability risk than their ADRRs score. Examining the concurrent validity, children's ADRRc scores correlated positively with MAGE scores calculated using their CGM and SMBG data, whereas their ADRRs scores only correlated with MAGE scores calculated using SMBG. ADRR scores generated for young children with type 1 diabetes demonstrate a high risk for glucose variability, but ADRR scores generated from CGM data may provide a more sensitive measure of variability than ADRR scores generated from SMBG. In young children with type 1 diabetes, ADRR scores calculated from CGM data may be superior to scores calculated from SMBG for measuring risk of excursion.

Screening for Potential Covariates Influencing the Pharmacokinetics of Intravenous Busulfan: Results From a Large Pediatric Cohort Undergoing Hematopoietic Stem-Cell Transplantation

AbstractAbstract 1811 Background:Busulfan (Bu) is a standard component of HSCT regimens and shows a narrow therapeutic range. In very young children, Bu exhibits large pharmacokinetic (PK) variability. Intravenous (IV) Bu clearance was demonstrated to be non-linearly related to body weight (BW) and thus BW is used to optimally define the IV Bu dosage in children [Vassal G. et al., CCP 2006]. Search for additional relevant covariates is still a topical question to further explain the variability in young children (Pts) and infants. Objective:to screen for the effect of heterogeneous patient characteristics on IV Bu PK disposition, and to evaluate the consistency of weight-based dosing strategy (as recommended in the European SmPC) in a large cohort of children, especially in patients with rare diseases and a BW less than 9 kg. Patients and Method:The prospective observational study included 115 patients (pts), mostly infants (median age: 13 months [0.3-148], median BW: 9 kg [3.5-58]). Main diagnoses were immunodeficiency (n=71, mainly SCID and lymphohistiocytosis) and inherited metabolic disorders (n=15). Additional data (90 pts, mostly malignant diseases) from two prospective clinical trials previously described [Nguyen L. et al., BMT 2004] [Vassal G. et al., CCP 2006] were pooled with the observational dataset. Altogether, 205 children aged from 10 days to 15 years (median of 30 months) and weighed from 3.5 to 62.5 kg (median of 11.0 kg) were analysed. IV Bu (Busilvex®) was given over 2 h q6h × 16 doses. For most of the pts (88%), the starting doses were given according to the European SmPC: 1.0 mg/kg, 1.2 mg/kg, 1.1 mg/kg, 0.95 mg/kg and 0.8 mg/kg for pts <9 kg, 9 – <16 kg, 16–23 kg, >23–34 kg, and >34 kg BW, respectively.PK was assessed on plasma samples from the 1st, 9th and 13th dose (536 PK datasets). PK analysis was performed using Non Linear Mixed Effect modelling with the NONMEM program. Results:A one-compartment PK model suitably fitted the concentrations vs time data. BW remained the main determinant of IV Bu PK disposition. Increase of IV Bu clearance with child's growth was observed to be faster in younger than in older children. For children < 9 kg, a doubling in BW is associated with a 2.4-fold increase in Bu clearance while a 1.7-fold increase in Bu clearance is observed in pts ≥ 9 kg for the same BW growth. To take into account this difference, the relationships between Clearance (CL) and BW was modelled using a different allometric exponent for children with a BW of < 9 kg and ≥ 9 kg.The predictive equations were: CL (L/h) = 2.18 × (BW/9)1.25 and CL(L/h) = 2.18 × (BW/9)0.76 in pts < 9 kg and ≥ 9 kg, respectively. The inter-individual variability decreased from 64% (covariate-free model) to 23% for Bu CL. No further significant impact was identified even when considering large fluctuations of the following covariates: creatinine clearance (up to 11 × Upper Normal Limit), bilirubin (up to 4 × UNL), ferritine (up to 43 × UNL), hepatic transaminases (up to 39 × UNL), alkaline phosphatases (up to 4 × UNL), gGT (up to 86 × UNL), total protein (0.5 to 1.4 × UNL) and lactate deshydrogenase (up to 3 × UNL). No PK difference was observed between patients under Benzodiazepine and those under Phenytoin prophylaxis, neither when comparing different groups of diagnoses. Similar performances for targeting an AUC range of 900 – 1500 μM.min were achieved when comparing Bu dosing either adjusted according to the model predictive equation or with the use of the European SmPC recommendations. The success rates were about 60% and 80% in pts < 9 kg and ≥ 9 kg respectively. Conclusion:BW is confirmed to be the only relevant predictor to optimally define the IV Bu dosing in children. The population PK model has established a higher allometric exponent for younger children (< 9kg) in order to take into account the faster maturation of clearance in this weight group. This model is consistent with the dosing strategy recommended in the EMA registration. Disclosures:Daher Abdi:Pierre Fabre Médicament: Employment. Pétain:Pierre Fabre Médicament: Employment. Nguyen:Pierre Fabre Médicament: Employment.

Development of a multiplexed bead-based immunoassay for the simultaneous detection of antibodies to 17 pneumococcal proteins

Presently, several pneumococcal proteins are being evaluated as potential vaccine candidates. Here, we gather novel insights in the immunogenicity of PLY, PsaA, PspA, PspC, NanA, Hyl, PpmA, SlrA, Eno, IgA1-protease, PdBD, BVH-3, SP1003, SP1633, SP1651, SP0189 and SP0376. We developed a multiplex bead-based immunoassay (xMAP® Technology, Luminex Corporation) to simultaneously quantify antibodies against these 17 pneumococcal proteins in serum. The median fluorescence intensity (MFI) values obtained for human pooled serum with the multiplex assay were between 82% and 111% (median 94%) of those obtained with the singleplex assays. For IgG, the coefficient of variation (CV) in serum ranged from 2% to 9%, for IgA, the CV ranged from 3% to 14% and for IgM, the CV ranged from 11% to 15%. Using this immunoassay, we showed that anti-pneumococcal antibody levels exhibited extensive inter-individual variability in young children suffering from invasive pneumococcal disease. All proteins, including the proteins with, as yet, unknown function, were immunogenic. In conclusion, the multiplex Streptococcus pneumoniae immunoassay based on proteins is reproducible. This assay can be used to monitor anti-S. pneumoniae antibody responses in a material- and time-saving manner.