Association between infant breastfeeding practices and timing of peak height velocity: A nationwide longitudinal survey in Japan.

BACKGROUND: Several studies have discovered an association between infant feeding practices and puberty timing; however, most have involved female cohorts. We investigated the association between infant feeding practices and the timing of peak height velocity in boys and girls. METHODS: Data on infant feeding methods and anthropometric measurements were collected from a nationwide Japanese birth cohort study. The age at peak height velocity (APV, years) was estimated and compared. Subsequently, the effects of breastfeeding duration were analyzed. RESULTS: Of the 13,074 eligible participants, 650, 9455, and 2969 were formula-, mixed-, and exclusively breastfed, respectively. Among girls, the mean APV was significantly later in the mixed-fed (standardized regression coefficient (ß): 0.094, 95% confidence interval (CI): 0.004-0.180) and exclusively breastfed (ß: 0.150, 95% CI: 0.056-0.250) groups than in the formula-fed group. Among boys, the mean APV was not significantly different among the three groups; however, a sensitivity analysis that excluded preterm birth revealed more significantly delayed APV in the breastfed-only group compared to the formula-fed group. Furthermore, a multiple linear regression model revealed that a longer breastfeeding period was associated with later APV. CONCLUSIONS: Infant breastfeeding practices can affect the timing of peak height velocity in both boys and girls. IMPACT: Several studies have discovered an association between infant feeding practices and puberty timing; however, most have involved female cohorts. Age at peak height velocity, derived from longitudinal height measurements, is a useful marker of secondary sexual maturity milestones in boys and girls. A Japanese birth cohort study revealed that breastfed children had a later age at peak height velocity than their formula-fed counterparts; this was more prominent among girls than boys. Furthermore, a duration-effect relationship was observed, where longer breastfeeding duration was associated with a later age at peak height velocity.

Developmental trajectories at a high risk for childhood overweight/obesity.

BACKGROUND: The associations between developmental patterns (trajectories) in children and maternal factors have been widely investigated, but paternal effects on these trajectories are unclear. This study aimed to determine child and parental factors involved in developmental trajectories at high risk for causing adverse cardiovascular (CV) profiles in children. METHODS: We analyzed longitudinal anthropometric data from birth to the present and CV profiles of 1,832 healthy volunteers (51% girls) aged 3-15 years who participated in a nationwide study between July 2012 and January 2014. Six trajectory latent class growth models were developed using body mass index z- scores. Predictors for being in developmental trajectories at high risk for causing adverse CV profiles were determined by multivariate regression analysis. RESULTS: The mean±standard deviation number of anthropometric data points was 12±3 for both boys and girls. Among the six trajectories, the infantile onset and continual increase groups had significantly worse levels of many CV profiles than those in the remaining groups. Paternal overweight/obesity was an independent predictor for boys being in the infantile onset group and for girls being in the continual increase group. Additionally, maternal pre-pregnancy overweight/obesity in boys and maternal excessive gestational weight gain in girls were independent predictors for being in the infantile onset group. Having no sibling in boys and an older maternal age were independent predictors for being in the continual increase group. CONCLUSIONS: Interventions to prevent childhood obesity should include strategies that focus on fathers and mothers as well as those that focus on children with certain types of familial background.

A Boy Safely Treated with Tyrosine Kinase Inhibitors for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia with Osteolysis.

A three-year-old boy with Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukemia (Ph+ALL) presented with an osteolytic lesion in his right upper arm. Tyrosine kinase inhibitors (TKIs) such as imatinib and dasatinib are an essential component throughout the course of treatment for Ph+ALL. However, TKIs are reported to affect the bone metabolism. In the treatment course of the current patient, the osteolytic lesion quickly improved despite the continuous use of TKIs, even during the concomitant use of corticosteroids. This suggests that TKIs can be safely given with concomitant corticosteroids to children with Ph+ALL, even when osteolytic lesions are present.

Preterm birth and Kawasaki disease: a nationwide Japanese population-based study.

BACKGROUND: Previous studies showed that preterm birth increased the risk for hospital admissions in infancy and childhood due to some acute diseases. However, the risk of preterm children developing Kawasaki disease remains unknown. In the present study, we investigate whether preterm birth increased the morbidity of Kawasaki disease. METHODS: We included 36,885 (34,880 term and 2005 preterm) children born in 2010 in Japan. We examined the association between preterm birth and hospitalization due to Kawasaki disease using a large nationwide survey in Japan. RESULTS: In log-linear regression models that were adjusted for children's characteristics (sex, singleton birth, and parity), parental characteristics (maternal age, maternal smoking, paternal smoking, maternal education, and paternal income), and residential area, preterm infants were more likely to be hospitalized due to Kawasaki disease (adjusted risk ratio: 1·55, 95% confidence interval: 1.01-2.39). We then examined whether breastfeeding status modified the potential adverse effects of preterm birth on health outcome. Preterm infants with partial breastfeeding or formula feeding had a significantly higher risk of hospitalization due to Kawasaki disease compared with term infants with exclusive breastfeeding. CONCLUSIONS: Preterm infants were at a high risk for Kawasaki disease, and exclusive breastfeeding might prevent this disease among preterm infants. IMPACT: Previous studies showed that preterm birth increased the risk for hospital admissions in infancy and childhood due to some acute diseases, however, the risk of preterm children developing Kawasaki disease remains unknown. This Japanese large population-based study showed that preterm infants were at a high risk for Kawasaki disease for the first time. Furthermore, this study suggested that exclusively breastfeeding might prevent Kawasaki disease among preterm infants.

Catch-Up Growth and Neurobehavioral Development among Full-Term, Small-for-Gestational-Age Children: A Nationwide Japanese Population-Based Study.

OBJECTIVE: To examine the relationship between catch-up growth of full-term, small for gestational age (SGA) children and their neurobehavioral development. STUDY DESIGN: Data were obtained from a population-based nationwide Japanese longitudinal survey that started in 2001. Study participants were full-term children with information on height at 2 years of age (n = 32 533). Catch-up growth for SGA infants was defined as achieving a height at 2 years of age of more than -2.0 standard deviations for chronological age. Logistic regression analyses were used to estimate ORs and 95% CIs for the associations of SGA and catch-up growth status with neurobehavioral development at 2.5 and 8 years of age, adjusting for potential infant- and parent-related confounding factors. RESULTS: Fifteen percent of term SGA infants failed to catch up in height. At 2.5 years of age, SGA children without catch-up growth were more likely to be unable to climb stairs (OR, 10.42; 95% CI, 5.55-19.56) and unable to compose a 2-word sentence (OR, 3.58; 95% CI, 1.81-7.08) compared with children with normal growth at birth. Furthermore, SGA children without catch-up growth were at increased risk for aggressive behaviors (OR, 3.85; 95% CI, 1.19-12.47) at 8 years of age. CONCLUSIONS: Continuous follow-up for full-term SGA infants with failure of catch-up growth or poor postnatal growth may be beneficial for early detection and intervention for behavioral problems.

Breastfeeding and behavioral development: a nationwide longitudinal survey in Japan.

OBJECTIVE: To prospectively examine the prolonged effect of breastfeeding on behavioral development. STUDY DESIGN: We used a large, nationwide Japanese population-based longitudinal survey that began in 2001. We restricted participants to term singletons with birth weight >2500 g (n = 41 188). Infant feeding practice was queried at age 6-7 months. Responses to survey questions about age-appropriate behaviors at age 2.5 and 5.5 years were used as indicators of behavioral development. We conducted logistic regression analyses, controlling for potential child and parental confounding factors, with formula feeding as the reference group. RESULTS: We observed a dose-response relationship between breastfeeding status and an inability to perform age-appropriate behaviors at both ages. With a single exception, all ORs for outcomes for exclusive breastfeeding were smaller than those for partial feeding of various durations. The protective associations did not change after adjustment for an extensive list of confounders or in the sensitivity analyses. CONCLUSION: We observed prolonged protective effects of breastfeeding on developmental behavior skills surveyed at age 2.5 and 5.5 years. Beneficial effects were most likely in children who were breastfed exclusively, but whether a biological ingredient in breast milk or extensive interactions through breastfeeding, or both, is beneficial is unclear.

An Alternative Approach to Determining Metabolic Syndrome Component Cutoffs in Children and Adolescents Using Segmental Regression Analysis.

Background: The prevalence of metabolic syndrome is increasing in children and adolescents. Although some diagnostic criteria for metabolic syndrome exist, further research is needed to determine appropriate age-, sex-, and race-specific cutoffs for each component. Methods and Results: Health examinations were conducted in 1,679 children aged 6-15 years in 9 regions of Japan. Participants were divided into 3 age groups for each sex: 6-8, 9-11, and 12-15 years. For metabolic syndrome components in each group, inverse cumulative percentile graphs were drawn and approximated by 3 regression lines using segmented regression analysis. The intersection of each regression line was defined as the breakpoint, and the measured value corresponding to the breakpoint percentile as the breakpoint value. Breakpoint values for waist circumference were age dependent at approximately 60, 70, and 80 cm for ages 6-8, 9-11, and 12-15 years, respectively. Breakpoint values for blood pressure were age- and/or sex dependent, while those for triglycerides, high-density lipoprotein cholesterol, and fasting blood glucose were neither age nor sex dependent. Based on these results, we proposed new cutoffs for diagnosing metabolic syndrome in Japanese children and adolescents. Conclusions: Breakpoint values obtained by segmented regression analysis on inverse cumulative percentile graphs can be useful for determining metabolic syndrome component cutoffs in children and adolescents.

Enzyme replacement therapy in two Japanese siblings with Fabry disease, and its effectiveness on angiokeratoma and neuropathic pain.

Enzyme replacement therapy (ERT) for Fabry disease does not show a clear benefit in angiokeratoma. We describe two Japanese siblings with Fabry disease, who were diagnosed when angiokeratomas were found on the older sibling at the age of 13 years. Neither of the boys complained of pain, while both suffered from hypohidrosis. We evaluated the safety and efficacy of ERT with recombinant human agalsidase alfa (Replagal®, Dainippon-Sumitomo Pharma. Co., Osaka, Japan) in these siblings over a 5-year period. In both siblings, sweating was observed 3 months after the initiation of ERT, which motivated them to adhere to ERT. Pain sensation was regained after 12 to 36 months of ERT, followed by a decrease after 48 to 60 months. Angiokeratomas on the lateral side of the knee of the older sibling partially disappeared after 48 months of ERT. Although the height of both siblings at baseline was lower than the corresponding average age-related heights in the normal Japanese population, during ERT they were within, or close to, the average +1 standard deviation in the non-Fabry population. Their growth rate seemed to indicate catch-up growth. Other clinical symptoms were maintained at baseline levels. Immunoglobulin G anti-agalsidase alfa antibodies were not detected in both sibling during ERT, and no infusion-associated reaction was observed. The treatment was generally well tolerated. ERT was a safe and effective treatment for angiokeratoma and neuropathic pain for these two siblings with Fabry disease.

Early childhood exposure to maternal smoking and obesity: A nationwide longitudinal survey in Japan.

Involuntary exposure to tobacco smoke is suspected to be one of the risks factors that are associated with obesity in children. The purpose of this study was to examine the relationship between early childhood exposure to tobacco smoke and the risk of obesity and overweight in Japan. This study utilized a nationwide, population-based longitudinal survey. The participants were restricted to 32 081 children who had available information on maternal smoking history as well as childhood height and weight. We conducted a binomial log-linear regression analysis with children of non-smoking mothers as the reference group. The children with mothers who were smokers had a higher risk of developing obesity or being overweight compared to the children with mothers who were nonsmokers. The risk ratios were 1.20 (95% confidence interval [CI]: 1.09-1.32) for overweight and 1.17 (95% CI: 0.95-1.44) for obesity. Early exposure to maternal smoking increases the risk of being overweight and having obesity during childhood. The increased risk is more pronounced among children with mothers, smoked heavily, or parents, who were smokers.

Methionine adenosyltransferase I/III deficiency: neurological manifestations and relevance of S-adenosylmethionine.

Methionine adenosyltransferase I/III (MAT I/III) deficiency, caused by mutations in the MAT1A gene, is an inherited metabolic disorder characterized by persistent hypermethioninemia, usually detected by newborn mass screening. There is a wide range of clinical manifestations, from completely asymptomatic to neurological problems associated with brain demyelination. Physiological role of S-adenosylmethionine (SAM), the metabolic product of methionine catalyzed by MAT, in the central nervous system has been investigated in vivo and in vitro, and case reports demonstrated an effectiveness of supplementary treatment of SAM in the improvement of neurological development and myelination. Methionine restriction can be an additional therapeutic strategy because hypermethioninemia alone may be neurotoxic; however, lowering methionine carries a risk to decrease the synthesis of SAM.

S-adenosylmethionine treatment in methionine adenosyltransferase deficiency, a case report.

Reported is a female patient with methionine adenosyltransferase I/III (MAT I/III) deficiency, who was found to have pronounced hypermethioninemia on newborn mass spectroscopy screening, and had two compound heterozygous missense mutations in the gene encoding human MAT1A protein. Hypermethioninemia persisted and her mental development was deficient. At 4 years and 8 months, we started with the supplementary treatment of S-adenosylmethionine, the metabolic product of methionine catalyzed by MAT, which was effective in her neurological development.

The clinical course of Rathke's cleft cysts in pediatric patients: impact on growth and pubertal development.

Rathke's cleft cysts (RCCs) are non-neoplastic epithelial lesions in the sellar or suprasellar regions. RCCs are usually asymptomatic; however, some patients experience headaches, visual disturbances, and endocrine disorders. The best treatment for associated endocrinopathy remains elusive. We aimed to investigate the clinical course, magnetic resonance imaging findings, and response to therapy in 10 pediatric patients with RCCs and endocrinopathy. Growth impairment and precocious puberty were observed to be prevalent. One patient with suprasellar extension of RCC underwent surgery, while the others were treated medically. Of the nine patients, seven patients showed stable cyst size, while two patients displayed reduction in cyst size. Hormone replacement and gonadotropin suppression therapy were found to be effective. Imaging and endocrine follow-ups are warranted because of the potential for changes in the cyst size and hormonal changes.

Enzyme replacement therapy attenuates disease progression in two Japanese siblings with mucopolysaccharidosis type VI.

Mucopolysaccharidosis type VI (MPS VI) is a progressive, multisystem autosomal recessive lysosomal disorder resulting from deficient N-acetylgalactosamine-4-sulphatase (ASB) and the consequent accumulation of glycosaminoglycan (GAG). Preclinical and clinical studies had demonstrated clinical benefits of early initiation of systemic therapies in patients with MPS. In this case report, two siblings with MPS VI started enzyme replacement therapy (ERT) with weekly infusions of recombinant human ASB (Galsulfase) at 1mg/kg. Sibling 1 started ERT 5.6 years of age and Sibling 2 was 6 weeks old. The disease status in these two siblings prior to and for no less than 36 months of ERT was followed up and compared. The treatment was well tolerated by both siblings. During 36 months of ERT, symptoms typical of MPS VI including short stature, progressive dysmorphic facial features, hepatosplenomegaly, hearing impairment, corneal clouding, and dysostosis multiplex were largely absent in the younger sibling. Her cardiac functions and joint mobility were well preserved. On the other hand, her affected brother had typical MPS VI phenotypic features described above before commencing ERT at the equivalent age, of 3 years. There was significant improvement in the shoulder range of motion and hearing loss after 36 months of treatment and cardiac function was largely preserved. His skeletal deformity and short stature remained unchanged. The results showed that early ERT initiated at newborn is safe and effective in preventing or slowing down disease progression of MPS VI including bone deformities. These observations indicate that early diagnosis and treatment of MPS VI before development of an irreversible disease is critical for optimal clinical outcome.

Trajectory of body mass index and height changes from childhood to adolescence: a nationwide birth cohort in Japan.

To investigate the dynamics of body mass index (BMI) and height changes in childhood leading to obesity in adolescents. BMI Z-scores were calculated using the LMS (lambda-mu-sigma) method based on yearly height and weight information (age 1.5-15 years) from a nationwide Japanese birth cohort that started in 2001 (n = 26,711). We delineated the trajectories of BMI and height changes leading to obesity at age 15 years using mixed effect models. Children who became obese at the age of 15 years kept relatively high BMI z-scores through childhood for both genders, and had an increasing trend over time as opposed to the normal weight group, with an increasing slope during puberty. Early adiposity rebound was associated with overweight or obesity at the age of 15 years. Age at peak height velocity (APHV) occurred earlier in the obese/overweight group at age 15 years than in the normal weight group, and occurred later in the underweight group. Obese adolescents experienced early adiposity rebound timing and maintained a serial BMI z-score increase throughout childhood, with a greater slope at puberty. An earlier peak in height gain during puberty may have contributed to the observed patterns of BMI change.

Effect of growth hormone therapy on thyroid function in isolated growth hormone deficient and short small for gestational age children: a two-year study, including on assessment of the usefulness of the thyrotropin-releasing hormone (TRH) stimulation test.

Background The relationship between growth hormone (GH)-replacement therapy and the thyroid axis in GH-deficient (GHD) children remains controversial. Furthermore, there have been few reports regarding non-GHD children. We aimed to determine the effect of GH therapy on thyroid function in GHD and non-GHD children and to assess whether thyrotropin-releasing hormone (TRH) stimulation test is helpful for the identification of central hypothyroidism before GH therapy. Methods We retrospectively analyzed data from patients that started GH therapy between 2005 and 2015. The free thyroxine (FT4) and thyroid-stimulating hormone (TSH) concentrations were measured before and during 24 months of GH therapy. The participants were 149 children appropriate for gestational age with GHD (IGHD: isolated GHD) (group 1), 29 small for gestational age (SGA) children with GHD (group 2), and 25 short SGA children (group 3). Results In groups 1 and 2, but not in group 3, serum FT4 concentration transiently decreased. Two IGHD participants exhibited central hypothyroidism during GH therapy, and required levothyroxine (LT4) replacement. They showed either delayed and/or prolonged responses to TRH stimulation tests before start of GH therapy. Conclusions GH therapy had little pharmacological effect on thyroid function, similar changes in serum FT4 concentrations were not observed in participants with SGA but not GHD cases who were administered GH at a pharmacological dose. However, two IGHD participants showed central hypothyroidism and needed LT4 replacement therapy during GH therapy. TRH stimulation test before GH therapy could identify such patients and provoke careful follow-up evaluation of serum FT4 and TSH concentrations.

Catch-up growth and behavioral development among preterm, small-for-gestational-age children: A nationwide Japanese population-based study.

OBJECTIVE: To examine the relationship between the catch-up growth of preterm, SGA children and their behavioral development. METHODS: We analyzed data from a large Japanese, nationwide, population-based, longitudinal survey that started in 2001. We restricted the study participants to preterm children with information on height at 2 years of age (n = 1667). Catch-up growth for SGA infants was defined as achieving a height at 2 years of age above -2.0 standard deviations for chronological age. We then used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations of SGA/catch-up status with neurobehavioral development both at 5.5 and 8 years of age, adjusting for potential infant- and parent-related confounding factors. RESULTS: Twenty-six percent of preterm SGA infants failed to catch up. SGA children without catch-up growth were more likely to be unable to listen without fidgeting (OR 2.51, 95% CI: 1.06-5.93) and unable to focus on one task (OR 2.66, 95% CI: 1.09-6.48) compared with non-SGA children at 5.5 years of age. Furthermore, SGA children without catch-up growth were at significant risk for inattention at 8 years of age. CONCLUSIONS: SGA infants with poor postnatal growth were at risk for attention problems throughout preschool-age to school-age among preterm infants. Early detection and intervention for attention problems among these infants is warranted.

Predicting obesity in early adulthood in Japanese women.

AIM: We analysed the body measurements of Japanese women to determine which factors may forecast adult obesity and also performed a comparative study of the utility of body mass index (BMI), which is used widely in Western Europe, and percentage of overweight, which is used in Japan. METHODS: Subjects included 244 Japanese women who were born between 1983 and 1986. Using a questionnaire, we investigated anthropometric values from birth to present and parents' present anthropometric data, and analysed factors that correlate with current BMI data. RESULTS: (i) BMI after 10 years of age and BMI increase between ages 7 and 8 years correlated with BMI in adulthood. The carrying over rate of overweight increased with age. Meanwhile, percentage of overweight after 13 years onwards correlated with BMI in adulthood. (ii) Adult BMI positively correlated to both parents' BMI. CONCLUSIONS: (i) For a Japanese woman, BMI in childhood is a good indicator of young adult BMI, and has the possibility of becoming an important parameter to monitor obesity progression. (ii) Therefore, attempts to control obesity in elementary school girls are necessary. (iii) Parents' weights may potentially influence obesity in adulthood; however, further examination of other confounding factors is necessary.

Maternal smoking as a risk factor for childhood intussusception.

Risk factors for intussusception have only rarely been reported. We examined the association between the risk of hospital admission for intussusception and maternal smoking, using a nationwide population-based longitudinal survey begun in Japan in 2010. Maternal smoking status was queried at 6 months of age, and responses to questions at 18 months of age about history of hospitalization for intussusception during the previous year were used as an outcome of interest. We conducted logistic regression analyses controlling for potential confounding factors. Maternal smoking increased the risk of hospitalization for intussusception (adjusted OR = 2.75, 95% CI [1.09, 6.96]) compared with not smoking, and a dose-response relationship was observed for the association. Maternal smoking is associated with an increased risk of intussusception development in children between the ages of 6 and 18 months.