Japanese Infants Research Articles

Cardiac mucosa in neonates

The histology of the cardiac mucosa at the esophagogastric junction (EGJ) at birth is still a controversy. We conducted a histopathological study of the EGJ to clarify the morphology, and to determine the presence or absence of cardiac mucosa at birth.We examined 43 Japanese neonates and infants that are born prematurely or at full term. Death had occurred between 1 and 231 days after birth.Cardiac mucosa without parietal cells showing positivity for anti-proton pump antibody, adjacent to the most distal squamous epithelium, was observed in 32 (74%) of the 43cases. Such mucosa was evident in neonates that were full-term and had died within 14 days after birth. On the other hand, cardiac mucosa with parietal cells adjacent to squamous epithelium was noted in 10 cases (23%); the remaining one (2%) had columnar-lined esophagus. Squamous and columnar islands were observed in a single histological section from the EGJ in 22 (51%) of the 43 cases. Parietal cells were sparsely or densely present in the gastric antral mucosa.On the basis of these histological findings, we consider that cardiac mucosa exists in neonates and infants and can be defined as such, irrespective of the presence or absence of parietal cells (so-called oxyntocardiac mucosa). Neonates born prematurely or at full-term have cardiac mucosa in the EGJ just after birth, as is the case for Caucasian neonates.

Safety, efficacy, and pharmacokinetics of delgocitinib ointment in infants with atopic dermatitis: A phase 3, open-label, and long-term study

BackgroundDelgocitinib ointment, a topical Janus kinase inhibitor, is used as treatment of patients with atopic dermatitis (AD) aged ≥2 years in Japan. Although initiating appropriate and early treatment upon the onset of AD in childhood is important, the safety and efficacy of delgocitinib ointment in infants with AD have not been established. MethodsThis phase 3 study was conducted from October 2020 to June 2022 (number JapicCTI-205412). Eligible Japanese infants with AD aged 6 to <24 months received 0.25% or 0.5% of delgocitinib ointment twice daily for 52 weeks in an open-label uncontrolled manner. Topical corticosteroids were allowed to apply for worsening AD during the treatment period at the investigators’ discretion. ResultsA total of 22 infants were enrolled. Adverse events (AEs) were reported in 21 (95.5%) infants and were mostly mild. No treatment-related AEs were reported. The Modified Eczema Area and Severity Index (mEASI) score continuously decreased until week 4, and the score reduction was maintained until week 52. The mean percent changes in the mEASI score from baseline were −73.5% at week 4, −81.7% at week 28, and −81.9% at week 52. Delgocitinib was not detected in the plasma of most infants (68.2%–95.2%). ConclusionsDelgocitinib ointment is well tolerated and effective for up to 52 weeks when applied to Japanese infants with AD.

Longitudinal gut mycobiota changes in Japanese infants during first three years of life

Although fungi can have a large impact on host health through the stimulation of the immune system and toxin production, few studies have investigated the gut mycobiota during infancy, a period during which sensitivity to internal and external stimuli is high. To capture the trend in fungal colonization during infancy, we evaluated the gut mycobiota of ten Japanese infants during the first 3 years of life. Infants had two major phyla, Ascomycota (68.9%) and Basidiomycota (29.6%), and the most abundant genus was Saccharomyces (26.8%), followed by Malassezia (18.5%), Candida (12.3%), Meyerozyma (8.5%), and Penicillium (8.3%). Alpha diversity analysis revealed a significant decrease in fungal richness and evenness with age, suggesting adaptive selection of the colonizing species in the gut environment. Beta diversity analysis divided infant mycobiota into age-related clusters and showed discrete separation before and after weaning, suggesting shift in microenvironment via weaning. In the initial stage, a variety of fungal species that likely originated from an environment, such as Malassezia spp., was highly colonized and were replaced by yeasts, such as Saccharomyces, after weaning. Further studies are needed to shed light on how the passage of the series of fungal colonizations in infancy affects the development of the host immune system and the other homeostasis involved in health later in life.

Weight-for-age z-scores of Japanese children using the World Health Organization Child Growth Standards.

Weight-for-age z-scores of Japanese children using the World Health Organization Child Growth Standards.

Trends in Primary Tooth Emergence Pattern and Associated Factors in Japanese Infants

The purposes of this study were to analyse trends in primary tooth emergence patterns and to identify physical factors potentially associated with them. The participants were 27,454 infants who underwent routine 18-month-old health examinations in Ebetsu City, Japan, between 1980 and 2012. This study was conducted using data from infants' 18-month-old health examinations over a 33-year period. The mean number of emerged primary teeth was analysed by sex using a general linear model. For logistic regression analysis, the proportion of infants with 16 emerged teeth or more at 18 months old was used as a dependent variable. Examination year; birth order; birth weight; weight, height, and chest girth at 18 months old; number of fused teeth; and mother's age were used as independent variables. The mean number of emerged primary teeth decreased over the 33-year period. Birth weight and weight and height at 18 months old decreased, and the proportion of low-birth-weight (<2500 g) infants increased over the 33-year period. On general linear model analysis, the yearly change in the mean number of emerged primary teeth was -0.0188 for boys and -0.0181 for girls. Birth weight and weight and height at 18 months old were significantly associated with the presence of 16 emerged primary teeth or more, according to the logistic regression analysis. The results demonstrated that, over the 33-year period examined, the mean number of emerged primary teeth decreased and birth weight and weight and height at 18 months old were associated with the pattern of tooth emergence.

Safety and immunogenicity of a 15-valent pneumococcal conjugate vaccine in Japanese healthy infants: A Phase I study (V114-028)

ABSTRACT This Phase I study evaluated the safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine (PCV), via subcutaneous (SC) or intramuscular (IM) administration, in healthy Japanese infants 3 months of age. A total of 133 participants were randomized to receive four doses (3 + 1 regimen) of V114-SC (n = 44), V114-IM (n = 45), or 13-valent PCV (PCV13)-SC (n = 44) at 3, 4, 5, and 12–15 months of age. Diphtheria, tetanus, and pertussis–inactivated poliovirus (DTaP–IPV) vaccine was administered concomitantly at all vaccination visits. The primary objective was to assess the safety and tolerability of V114-SC and V114-IM. Secondary objectives were to assess the immunogenicity of PCV and DTaP–IPV at 1-month post-dose 3 (PD3). On days 1–14 following each vaccination, the proportions of participants with systemic adverse events (AEs) were comparable across interventions, whereas injection-site AEs were higher with V114-SC (100.0%) and PCV13-SC (100.0%) than with V114-IM (88.9%). Most AEs were mild or moderate in severity and no vaccine-related serious AEs or deaths were reported. Serotype-specific immunoglobulin G (IgG) response rates at 1-month PD3 were comparable across groups for most shared serotypes between V114 and PCV13. For additional V114 serotypes 22F and 33F, IgG response rates were higher with V114-SC and V114-IM than with PCV13-SC. DTaP–IPV antibody response rates at 1-month PD3 for V114-SC and V114-IM were comparable with PCV13-SC. Findings suggest that vaccination with V114-SC or V114-IM in healthy Japanese infants is generally well tolerated and immunogenic.

Incidence and clinical risk factors of Bednar's aphthae in Japanese newborns.

The etiology of Bednar's aphthae remains unclear. Our aim was to investigate the incidence of, and factors associated with, Bednar's aphthae in a Japanese newborn cohort. A retrospective cross-sectional study was conducted on neonates discharged from the well-baby nursery at Saitama City Hospital, Japan. The principal investigator carefully examined each neonate's oral cavity, up to and including the pharynx, with a light-emitting diode (LED) headlight to determine the presence of Bednar's aphthae. Maternal and neonatal clinical characteristics were first compared between neonates with and those without Bednar's aphthae by univariate analysis. Variables with significant inter-group differences upon univariate analysis were entered into a multivariable logistic-regression model. This study enrolled 1996 infants. We observed Bednar's aphthae in 9.3% of the Japanese newborn infants who were included. When restricted to infants who were born via vaginal delivery, 13.2% of them had aphthae. Multivariable logistic regression analysis identified vaginal delivery (odds ratio = 6.19, p < 0.0001) in Model 1, and vaginal delivery (odds ratio = 6.73, p < 0.0001) and birth weight (odds ratio = 0.9995, p = 0.034) in Model 2 as independent risk factors for the disease. This is the first report of the prevalence of Bednar's aphthae among Japanese neonates. Vaginal delivery was identified as the strongest risk factor. Although confounding between mode of delivery and mechanical stimuli associated with sucking was not found in this study, the findings pave the way for a better understanding of the etiology of Bednar's aphthae.

Knee alignment and individual quadriceps femoris muscle thicknesses and their relationships with postnatal motor development and subcutaneous fat thickness: A cross-sectional study in Japanese infants

BackgroundPostnatal changes in individual quadriceps femoris muscle thicknesses and the relationships between knee alignment and quadriceps thicknesses, postnatal motor development, and subcutaneous fat thickness are unclear. This study investigated knee alignment and individual quadriceps thickness ratios in Japanese infants and investigated their relationships with postnatal motor development and subcutaneous fat thickness. MethodsOne-year-old (n = 28), 2-year-old (n = 26), and 3-year-old infants (n = 22) were included. Postnatal months when the infants began crawling, standing, and walking were assessed. The intercondylar distance was measured, and the individual quadriceps and subcutaneous fat thicknesses at the right mid-thigh were measured using ultrasonography. The individual quadriceps:total quadriceps muscle thickness ratios were calculated. Analysis of variance tests in the 3 groups were conducted for the intercondylar distances and individual quadriceps thickness ratios, and correlation coefficients between the parameters were evaluated in each group. FindingsIntercondylar distance was longer in 1-year-old infants than in 2-year-old infants (p < 0.001), without significant differences between 2-year-old and 3-year-old infants (p = 0.33). The rectus femoris thickness ratio was higher in 1-year-old infants than in 3-year-old infants (p = 0.013), whereas the vastus medialis thickness ratio was higher in 3-year-old infants than in 2-year-old infants (p = 0.024). In 3-year-old infants, a larger subcutaneous fat thickness, but not postnatal motor development, was correlated with a longer intercondylar distance and a lower vastus medialis thickness ratio (rs = 0.53, p = 0.012; rs = −0.46, p = 0.032, respectively). InterpretationFurther studies on the relationships between subcutaneous fat and knee alignment and vastus medialis in juveniles, adolescents, young adults, and elderly people are expected.

Evaluating Cranial Growth in Japanese Infants Using a Three-dimensional Scanner: Relationship between Growth-related Parameters and Deformational Plagiocephaly.

In this study, we aimed to evaluate the longitudinal changes in the cranial shape of healthy Japanese infants using a three-dimensional scanner and construct a normal values database for the growth process. Preterm infants (gestational age < 37 weeks), infants with neonatal asphyxia (5-minute Apgar score of <7), and patients who started helmet therapy for deformational plagiocephaly were excluded from this study. The first scan was performed at approximately 1 month of age, followed by two scans conducted at 3 and 6 months of age. The parameters considered were as follows: cranial length, width, height, circumference, volume, cranial vault asymmetry index, and cephalic index. A cranial vault asymmetry index >5% was defined as deformational plagiocephaly. Changes in each parameter were examined using repeated-measures analysis of variance classified by sex and deformational plagiocephaly status. The rate of increase in each parameter was also examined. In total, 88 infants (45 boys and 43 girls) were included in this study. All growth-related parameters were noted to increase linearly with time. Sex differences were observed in all parameters except cranial length. Deformational plagiocephaly was found to have no effect on growth-related parameters. Cranial volume increased by 60% from 1 to 6 months of age. The growth almost uniformly influenced the rate of increase in volume in each coordinate axis direction. Overall, the mean trends in three-dimensional parameters in infants up to 6 months of age were obtained using a three-dimensional scanner. These trends could be used as a guide by medical professionals involved in cranioplasty.

Exposure to House Dust Mite Allergen and Endotoxin in Early Life and Sensitization and Allergic Rhinitis: The JECS.

The association between endotoxin and allergic rhinitis (AR) is not conclusive. The aim of this study was to determine the association between endotoxin and house dust mite (HDM) allergens in dust, and HDM sensitization and AR among Japanese infants. This study included 4188 participants in the Sub-Cohort Study of the Japan Environment and Children's Study. Dust was collected from children's mattresses at age 18 months and endotoxin and HDM allergen levels were measured. A logistic regression model was used to analyze the association between endotoxin or HDM allergen and the sensitization to HDM (specific-IgE) at age 2 and AR at age 3. The median (interquartile range) endotoxin level was 375.1(186.9-826.5) EU/m2 and the Der 1 (Der p 1 + Der f 1) level was 51.2 (14.8-168.6) ng/m2. There were significant positive associations between endotoxin and HDM sensitization (Der f 1, adjusted odds ratio [aOR] quartile [Q] 4 vs. Q1, 1.44, 95% CI, 1.04-2.00; Der p 1, aOR Q4 vs. Q1, 1.56, 95% CI, 1.12-2.16). There were also significant positive associations between Der 1 exposure and HDM sensitization (Der f 1, aOR Q3 vs. Q1, 1.75, 95% CI, 1.26-2.44; aOR Q4 vs. Q1, 2.98, 95% CI, 2.15-4.13; Der p 1, aOR Q3 vs. Q1, 1.91, 95% CI, 1.37-2.66; aOR Q4 vs. Q1, 2.91, 95% CI, 2.09-4.05). There were, however, no associations between endotoxin or Der 1 and AR. In the population residing mostly in non-farming settings, both endotoxin and HDM allergens in dust were associated with an increased risk of HDM allergen sensitization, but not with AR.

Japanese infants' attachment insecurity and externalizing/internalizing problems: Using strange situation and attachment Q-sort methods.

According to attachment theory, an infant-mother attachment is universal, and infants who develop an insecure attachment relationship with their mother are likely to show mental health problems compared to those who develop a secure attachment relationship. These hypotheses have been empirically supported in Western cultures. However, the cross-cultural evidence is still insufficient. The purpose of this study was to examine the association between Japanese infants' attachment insecurity and mental health problems. We studied 81 Japanese infants (Mage =14.64 months, SD =1.43, females=54%) mostly from middle-class families. The Strange Situation Procedure (SSP) and Attachment Q-sort (AQS) assessed infant attachment security. Infant externalizing and internalizing problems were rated concurrently by the mother and 6 months later by the mother and another adult (father or grandmother). Japanese infants' attachment insecurity measured by the AQS was associated with their externalizing problems concurrently and 6 months later. Infants with insecure-resistant attachment measured by the SSP had higher externalizing problems compared to those with secure attachment concurrently (not 6 months later). Attachment insecurity was not related to internalizing problems. These findings partly supported the association between attachment insecurity and mental health problems. This research also recommends observing infant attachment at home.

Seasonal variation in vitamin D status of Japanese infants starts to emerge at 2 months of age: a retrospective cohort study.

Vitamin D seasonality has been reported in adults and children, suggesting that sunlight exposure has effects on 25(OH)D production. While vitamin D deficiency among infants has received significant attention, little is known about the extent to which vitamin D status during early infancy is affected by sunlight exposure. Here, we retrospectively analysed serum 25(OH)D levels of 692 samples obtained from healthy infants aged 1-2 months born at Saitama City Hospital, Japan (latitude 35·9° North) between August 2017 and September 2021. Data regarding the frequency of outdoor activities, formula intake and BMI were also collected and analysed. Month-to-month comparisons of vitamin D levels revealed significant variation in 25(OH)D levels in breastfed infants starting at 2 months, with maximal and minimal levels in September and January, respectively. An outdoor activity score of 0 was most common at 1 month (83·9 %) and a score of 3 was most common at 2 months (81·2 %), suggesting an increased amount of sunlight exposure at 2 months. Multiple linear regression analysis revealed the amount of formula intake to be significantly associated with vitamin D status at both 1 (t = 17·96) and 2 months (t = 16·30). Our results comprise the first evidence that seasonal variation of vitamin D begins at 2 months among breastfed infants from East Asia, though dietary intake appears to be the major determinant of vitamin D status. These findings provide new insights into the influence of dietary and non-dietary factors on vitamin D status during early infancy.

The cholestatic infant: updates on diagnosis and genetics.

Cholestasis in infants can indicate a serious hepatobiliary disease and requires timely assessment, diagnosis and intervention to prevent progression to serious liver decompensation. This report aims to highlight recently published studies regarding diagnosis and treatment of cholestasis in infants. The evaluation of neonatal cholestasis can be challenging, requiring the assessment of a broad differential diagnosis in timely fashion. The Italian Society of pediatric gastroenterology, hepatology, and nutrition position paper on the evaluation of neonatal cholestasis is reviewed and compared to other published guidelines. In biliary atresia, the most time-sensitive of these diagnoses, serum matrix metalloproteinase-7 was studied in Japanese infants with biliary atresia with excellent diagnostic performance characteristics. Genetic testing panels are an increasingly used tool to help identify causes of cholestasis. An American experience of genetic testing in large cohort of infants identified a definite or possible genetic diagnosis in 11% of cholestatic infants. In the treatment of prutitus in Alagille syndrome and progressive familial intrahepatic cholestasis the clinical studies of two newly Food and Drug Administration approved ileal bile acid transport inhibitors are discussed. New information on the prevalence of cytomegalovirus and idiopathic cholestasis as other etiologies of infant cholestasis is also reviewed. Lastly, new insight on potential maternal microbiome regulation on biliary disease in neonates on experimental biliary atresia models is discussed. Cholestasis in infants requires timely diagnosis and intervention. There are exciting new diagnostic and treatment options now being studied which could help minimize the likelihood of advanced liver disease and development of serious complications.

Not sleeping soundly in early infancy is not bad.

This study sought to determine whether not sleeping soundly in early infancy predicted poor development. This complemented earlier studies of children aged 12months or older. Sleep/wake patterns of 35 Japanese infants (23 males) with a gestational age of 37< weeks were recorded at home using actigraphy. Families were registered with a laboratory-based database for infant research. Follow-up recordings were conducted at 3, 4, 6, 12, and 24months. Crawling was rated by mothers at 12months and used to create regular and irregular crawling groups. Temperament was scaled using the Japanese Infant Behaviour Questionnaire-Revised Questionnaire and the Japanese Early Childhood Behaviour Questionnaire. At 4 months, infants with regular crawling style had shorter night-time sleep than infants with irregular crawling style. However, at 12months, the former had longer motionless sleep at night compared to the latter. Before 6 months, infants with regular crawling style showed lower sleep efficiency, especially during the day, compared to those with irregular crawling style. In addition, the amount of night-time active sleep at 3 and 4 months were positively correlated with day-time activity, but not at 6 months. Short fragmental sleep in early infancy did not always predict poor development.

Cranial shapes of Japanese preterm infants at one month of age using a three-dimensional scanner

BackgroundRecently, cranial shape measurements of preterm infants have been performed using handheld three-dimensional (3D) scanners and can now be objectively quantified. AimsTo measure the cranial shapes of Japanese preterm infants at one month of age using a 3D scanner, compare these values with those of healthy term infants, and examine the risk factors for dolichocephaly. Study designA multicenter, retrospective cohort study. SubjectsPreterm infants born at <37 weeks of gestation and staying in the neonatal intensive care unit or visiting an outpatient clinic for a one-month checkup between April 2020 and March 2022. Outcome MeasuresA 3D scanner was used to quantify cranial shape. Comparison was made with full-term, one-month-old infants. ResultsNinety-four preterm infants (42 boys) and 165 full-term infants were enrolled. Preterm infants had a significantly lower cephalic index (77.9% and 85.0%, p < 0.01) and a higher incidence of dolichocephaly (54.3% and 13.3%, p < 0.01) compared to term infants. No significant difference in incidence of deformational plagiocephaly was found between the groups (41.5% vs. 47.3%, p = 0.44). The risk of dolichocephaly was significantly higher for female sex (odds ratio [OR], 3.32; 95% confidence interval, 1.30–8.50), cesarean section (OR, 4.07; 95% confidence interval, 1.23–13.5), and use of mechanical ventilation (OR, 4.66; 95% confidence interval, 1.09–20.0). ConclusionsJapanese preterm infants at the first month of life had longer heads than full-term infants; the risk factors identified were female sex, cesarean section, and use of mechanical ventilation.

The cut-off values of vitamin D deficiency in early infancy.

Several cut-off points for 25-hydroxyvitamin D (25(OH)D) levels have been proposed to determine vitamin D deficiency or insufficiency. However, the level for 25(OH)D deficiency in early infancy remains unclear. The serum 25(OH)D value at which parathyroid hormone level plateaus, called the "inflection point," is considered the most appropriate criterion for defining an adequate vitamin D status. This was a single-center retrospective study involving 305 1-month-old and 252 2-month-old Japanese infants. Nonlinear segmented regression analysis was performed based on the correlation between 25(OH)D and parathyroid hormone levels to determine vitamin D deficiency cut-off points. Inflection points were 7.90ng/mL for 1-month-old (95% confidence interval, 6.31-9.49) and 6.74ng/mL for 2-month-old (95% confidence interval, 5.80-7.68) Japanese infants, which were lower than previously reported. Cut-off values were also lower in the high-body mass index (BMI) group than in the low-BMI group for both 1-month and 2-month-old infants. These results imply the need for nutritional rickets prevention via policy recommendations in most full-term newborns in Japan. Although validation studies are required, these results can still be used to guide vitamin D insufficiency treatment options in early infancy.

AEs after BCG vaccination in Japanese infants

AEs after BCG vaccination in Japanese infants

Reference Values for Cranial Morphology Based on Three-dimensional Scan Analysis in 1-month-old Healthy Infants in Japan.

Currently, molded helmet therapy is used to treat infants with deformational plagiocephaly. However, the indices of normal cranial shape remain unclear, and thus, the prevalence of deformational plagiocephaly is unknown, particularly in Japan. We investigated the reference values for cranial morphological characteristics in 1-month-old Japanese infants using a three-dimensional scanner, to determine the prevalence of deformational plagiocephaly. One hundred fifty-three healthy infants who visited three hospitals (from April 2020 to March 2021) were enrolled. Cranial shape was measured using a three-dimensional scanner and was analyzed using image analysis software. Outcome measures were cranial volume, length, width, length-width ratio, circumference, asymmetry, and vault asymmetry index; cephalic index; and anterior, posterior, and overall symmetry ratios. The cranial vault asymmetry index >3.5% or ≥10% were diagnosed as deformational or severe deformational plagiocephaly, respectively. The mean age at measurement was 35.7 days. The mean cranial volume was 559 mL; cranial length, 129 mm; cranial width, 110 mm; length-width ratio, 118%; cephalic index, 85.2%; cranial circumference, 377 mm, cranial asymmetry, 6.4 mm; cranial vault asymmetry index, 5.0%; and anterior, posterior, and overall asymmetry ratios, 93.1%, 91.3%, and 96.4%, respectively. The prevalence of deformational and severe deformational plagiocephaly was 64.7% and 6.6%, respectively. Sex-based differences were observed for cranial volume and width. The results obtained in this study can be considered standard values that can facilitate the differentiation of abnormal infant cranial morphological characteristics for Japanese medical practitioners.

Efficacy and safety of propranolol cream in infantile hemangioma: A prospective pilot study

Infantile hemangioma (IH) is a common tumor in infants that gradually resolves and is often untreated. However, for cosmetic reasons, parents often opt for treatment. Oral propranolol, the first-line therapy for IH, is sometimes associated with several side effects, including hypotension, bradycardia, and hypoglycemia. No clinical studies on topical propranolol have been conducted using standardized procedures. We evaluated the efficacy and safety of topical propranolol in patients with IH. This multicenter, prospective pilot study was conducted from June 2019 to October 2020 and involved eight Japanese infants aged 35–150 days with proliferating IH. Patients were treated with 5% propranolol cream twice daily. We examined the efficacy rate based on central evaluation (complete or near-complete healing of the target hemangioma) at weeks 24 and 12, respectively, compared to baseline values. The efficacy rate at week 24 was 68.8% (95% confidence interval: 44.1–85.9%). The surface area, maximum diameter, and color intensity of the target IH decreased over time. Adverse event and drug-related adverse event rates were 87.5% and 0%, respectively. Propranolol cream may be effective and safe in Japanese patients with IH and may be considered a first-choice treatment for small and superficial IHs in cosmetically problematic areas.

Achievement of Developmental Milestones Recorded in Real Time: A Mobile App-Based Study

To clarify the characteristics of milestone achievement of Japanese infants using data assessed and recorded in real time via a Web-based app by caregivers. Between 2014 and 2019, the achievement of developmental milestones of 16 627 Japanese infants were recorded via the mobile app Papatto Ikuji along with pertinent information including sex, birth date, anthropometric measurements, and information on feeding. The milestones consisted of 20 items belonging to 4 domains: personal-social, fine motor-adaptative, language, and gross motor. The distribution of age at milestone achievement was compared with 4 conventional normative data. Subgroup analyses according to sex, season of birth, and feeding methods were performed with restricted mean survival time analysis. Age distributions of milestone achievement were generally similar in the app-based and conventional data. The exception was "Smile responsively," for which the age at achievement seemed higher in the app-based data. Subgroup analyses showed female-dominant sex differences in the achievement of person-social and language milestones. The results also showed seasonality in achievement of gross motor milestones, with earlier achievement in infants born in winter compared with those born in summer. We describe mobile app-based data on developmental milestone achievements that were recordedin real time. The app-based data were generally comparable with conventional normative data, suggesting that its potential to assess the development of children in real time. This could be used complementarily with the current well-child visits at scheduled time points.