Lifelong cardiovascular care in Turner syndrome: two cases with review of literature.

Cardiovascular disease is one of the most important complications in girls and women with Turner syndrome (TS). Although the latest international guideline provides useful suggestions for the management of cardiovascular diseases in TS, some unknown cardiac conditions warrant physicians' attention and awareness. Here, we have reported two adult cases wherein significant cardiovascular diseases were detected during the transition period. The first case patient was diagnosed with aortic crank deformity and left subclavian artery aneurysm at 14 years based on the report of cardiac catheterization, computed tomography angiography, and cardiac magnetic resonance imaging, which had remained undetected by annual evaluations using transthoracic echocardiography (TTE). This case emphasizes the importance of cardiac reevaluation during the transition period. The second case patient was diagnosed with moderate mitral valve regurgitation (MR) due to mitral valve prolapse at 18 years through TTE, although the first evaluation at 7 years by TTE detected slight MR without any clinical concerns. The condition however progressed to severe MR at 28 years, requiring mitral valvuloplasty. MR is the most common valve disease worldwide, which makes it challenging to comprehend whether the condition is a complication. However, the condition requiring surgery at this age is extremely rare, which implies the possibility of early progression. Because almost all literature on cardiovascular complications in TS is cross-sectional, further information about longitudinal cardiovascular conditions is vital for optimal care for girls and women with TS. The two cases reported in this article provide significant information for improving lifelong cardiovascular health issues in TS.

Proposed reference intervals of serum insulin-like growth factor-1 (IGF-1) levels in older Japanese populations.

Measurements of serum insulin-like growth factor 1 (IGF-1) levels are useful surrogate markers for the diagnosis and management of patients with growth hormone-related disorders. We have previously published normative data of serum IGF-1 levels for the Japanese population aged 0-77 years by combining and analyzing previously reported references, which were separately and independently constructed, to properly reflect data in the transition period. Although the reference is widely used in both clinical and research settings, the reference did not include data for those aged >77 years, raising the question of how we would evaluate patients over those ages. In this study, we extended the age- and sex-specific reference ranges of serum IGF-1 levels to the age of 80 years by reanalyzing combined data on serum IGF-1 levels from previously published references. Based on our results, we proposed that individuals aged >80 years can be evaluated using the references set at the age of 80 years. However, our proposal was based on a very limited number of participants. Therefore, physicians should exercise caution when interpreting IGF-1 standard deviation scores for those aged >80 years because they are not exactly correct but acceptable.

Cortical bone development, maintenance and porosity: genetic alterations in humans and mice influencing chondrocytes, osteoclasts, osteoblasts and osteocytes.

Cortical bone structure is a crucial determinant of bone strength, yet for many years studies of novel genes and cell signalling pathways regulating bone strength have focused on the control of trabecular bone mass. Here we focus on mechanisms responsible for cortical bone development, growth, and degeneration, and describe some recently described genetic-driven modifications in humans and mice that reveal how these processes may be controlled. We start with embryonic osteogenesis of preliminary bone structures preceding the cortex and describe how this structure consolidates then matures to a dense, vascularised cortex containing an increasing proportion of lamellar bone. These processes include modelling-induced, and load-dependent, asymmetric cortical expansion, which enables the cortex's transition from a highly porous woven structure to a consolidated and thickened highly mineralised lamellar bone structure, infiltrated by vascular channels. Sex-specific differences emerge during this process. With aging, the process of consolidation reverses: cortical pores enlarge, leading to greater cortical porosity, trabecularisation and loss of bone strength. Each process requires co-ordination between bone formation, bone mineralisation, vascularisation, and bone resorption, with a need for locational-, spatial- and cell-specific signalling pathways to mediate this co-ordination. We will discuss these processes, and a number of cell-signalling pathways identified in both murine and human genetic studies to regulate cortical bone mass, including signalling through gp130, STAT3, PTHR1, WNT16, NOTCH, NOTUM and sFRP4.

Demographic characteristics of children with growth hormone deficiency from 1996 to 2015 in Japan: 20 years of data from the foundation for growth science in Japan.

Growth hormone (GH) deficiency (GHD) in children is a heterogeneous condition that includes several entities of various severities. GH treatment has been affected by various factors. Because comprehensive analyses for Japanese children with GHD over time are scarce, we investigated the baseline characteristics of patients with GHD at the start of GH treatment between 1996 and 2015 using data from the Foundation for Growth Science in Japan. During the registration period, 19,717 subjects were determined to be eligible for GH treatment as GHD. Overall analyses revealed that there were twice the number of male patients as female patients, and the etiology was idiopathic in 91.1%, central nervous system (CNS) tumor at the hypothalamus-pituitary area in 1.7%, CNS tumor distant from the hypothalamus-pituitary area in 0.68%, other tumors in 0.91%, congenital CNS malformations in 0.83%, and other diseases in 1.1% with their specific characteristics. The latest average age, height standard deviation score (SDS), insulin-like growth factor-1 SDS, and proportion of severe GHD at GH treatment initiation were 8.8 years, -2.76, -1.42, and 19.5%, respectively. The proportions of breech delivery and asphyxia gradually decreased, whereas that of caesarean section gradually increased during the registration period with the latest values of 2.2%, 4.9%, and 14.0%, respectively (all analyses: p < 0.0001). In contrast, the proportion of idiopathic GHD with breech delivery seemed to reach the lowest level among those with a birth year before 2000. This study identified the characteristics and changes of patients with GHD over 20 years.

Trace element levels in mature breast milk of recently lactating Japanese women.

BACKGROUND: Many trace elements are essential for infant growth and development during early life. Their concentrations in breast milk vary depending on social and economic factors. Nonetheless, the present available values in Japan were derived from lactating mothers approximately 15 years ago. METHODS: Healthy mothers who gave birth to a single infant after 37 weeks of gestation at Teikyo University Hospital were recruited between July 2016 and December 2017. They were encouraged to collect breast milk samples and a self-administered food frequency questionnaire at 1 and 3 months postpartum. Anthropometric data for the mothers and their infants were also collected. Overall, 79 subjects were analyzed after excluding subjects with inadequate data in the food frequency questionnaire, insufficient breast milk samples, and medication that could affect dietary intakes. Trace element concentrations were determined by inductively coupled plasma mass spectrometry, and their correlation with several factors were investigated. RESULTS: Trace element concentrations were widely distributed as previously reported. Median concentrations of Cr, Mn, Fe, Cu, Zn, Se, and Mo were 0.8, 0.8, 98, 50, 272, 2.2, and 0.7 µg/dL at 1 month postpartum and 0.6, 0.7, 55, 33, 177, 2.1, and 0.7 µg/dL at 3 months postpartum, respectively. There were no correlations between trace element concentrations and either mothers' intakes or infants' growth. In contrast, there were significant correlations between several trace elements and macronutrients in addition to inter-element correlations among almost all trace elements. CONCLUSIONS: Trace element concentrations in mature breast milk were determined from recently lactating mothers in Japan.

Changes in height standard deviation scores during early life are affected by nutrition.

BACKGROUND: Large changes in height standard deviation score (SDS) have been reported from birth to 3 years of age. We analyzed how early these changes start and whether they are affected by nutrition. METHODS: The longitudinal growth of 1,849 children born between March 1 2007 and August 31 2007 or between March 1, 2009 and August 31 2009 with five records from birth to 3 years of age was analyzed. RESULTS: The height SDS at birth was positively correlated with body mass index (BMI) SDS at birth (r = 0.224, P < 0.0001). The height SDS at birth decreased among children with a positive height SDS and increased among children with a negative height SDS. The changes occurred immediately after birth and became more modest as children aged. Regarding the change in the height SDS from birth to 3 years of age, 33.4% of children increased more than 0.5 SDs, 39.8% of children decreased more than 0.5 SDs, and 34.4% of children remained within ±0.5 SDs. The change in height SDS displayed a strong positive correlation with the change in weight during the four periods. From birth till 3 months, from 3 months till 6 months, from 6 months till 1.5 years, and from 1.5 years till 3 years. CONCLUSIONS: The significant positive correlation between height SDS and BMI SDS suggests an effect of children's nutrition status in utero. The height SDS change started immediately after birth and the change was largest from birth to 3 months. A positive correlation between changes in height SDS and weight suggest that growth during early childhood depends on nutritional status.

Reduced pubertal growth in children with obesity regardless of pubertal timing.

Childhood obesity affects both pubertal growth and pubertal timing. We evaluated pubertal timing-mediated effects of childhood obesity on pubertal growth. This retrospective, representative-population-based cohort study included 6,733 boys and 6,916 girls born between April 1975 and March 1976 in Akita Prefecture, Japan. Individual changes in height standard deviation score between 7 and 17 years (ΔHtSDS), body mass index Z-score at 7 years (BMIZ), and estimated age at peak height velocity (ÂPHV) were used as surrogate indicators of pubertal growth, childhood obesity and pubertal timing, respectively. ÂPHV-mediated effect of BMIZ on ΔHtSDS was evaluated, and non-ÂPHV-mediated effect was calculated. Based on BMIZ, participants were categorized into three groups (underweight, normal-weight and obese groups), and the differences in ΔHtSDS between obese and normal-weight or underweight groups and ratios of non-ÂPHV-mediated effect were determined. ΔHtSDS values in the obese group were lower by 1.23 in boys and 1.17 in girls than those in the underweight group and by 0.87 in boys and 0.85 in girls than those in the normal-weight group. Non-ÂPHV-mediated effect on the reduced ΔHtSDS in the obese group compared to the underweight and normal-weight groups accounted for 68% and 71% in boys and 59% and 64% in girls, respectively. Thus, childhood obesity is associated with reduced pubertal growth regardless of pubertal timing. This reduced pubertal growth observed in children with obesity could be more affected by non-pubertal timing-mediated effect rather than pubertal timing-mediated effect.

Nonosmotic secretion of arginine vasopressin and salt loss in hyponatremia in Kawasaki disease.

BACKGROUND: The precise mechanism of hyponatremia in Kawasaki disease (KD) remains elusive because assessment of volume status based on serial changes in body weight is lacking in previous reports. METHODS: Seventeen patients who were diagnosed with KD and hyponatremia (serum sodium levels <135 mmol/L) were analyzed. Volume status was assessed based on serial changes in body weight. Plasma arginine vasopressin (ADH), urine electrolytes, and serum cytokine levels were measured on diagnosis of hyponatremia. An increase in body weight by >3% was defined as hypervolemia and a decrease in body weight by >3% was defined as hypovolemia. RESULTS: The volume status was hypervolemic in three patients (18%), euvolemic in 14 (82%), and hypovolemic in none (0%). Five (29%) patients were diagnosed with "syndrome of inappropriate secretion of antidiuretic hormone" (SIADH) and no patients were diagnosed with hypotonic dehydration. The contribution of decreased total exchangeable cations (salt loss) to hyponatremia (5.9% [interquartile range, 4.3%, 6.7%]) was significantly larger than that of increased total body water (-0.7% [-1.8%, 3.1%]) (P = 0.004). Serum interleukin-6 levels were elevated in all of the nine patients who were evaluated. Among the 12 (71%) patients who did not meet the criteria of SIADH and hypotonic dehydration, plasma ADH levels were inappropriately high in ten patients. These patients were also characterized by euvolemic or hypervolemic hyponatremia and salt loss, which might be compatible with a diagnosis of SIADH. CONCLUSIONS: Our study shows that hyponatremia in KD is euvolemic or hypervolemic and is associated with nonosmotic secretion of ADH and salt loss in the majority of patients.

The value of anthropometric indices for childhood obesity in Japan.

Context: Childhood obesity is one of the most serious public health problems. The simplest method for the identification of adiposity in children involves measuring height and weight because these metrics are easy to obtain and are not greatly affected by observers. Objective: Body mass index (BMI) has been widely used as a surrogate marker of childhood obesity, particularly after the International Obesity Task Force recommended that BMI is appropriate for the determination of childhood obesity. However, in Japan, the percentage of overweight (POW) is more widely used for evaluating childhood obesity. Methods: This review discusses and summarises the situation in Japan regarding the use of various anthropometric indices for assessing childhood obesity, focusing on POW and BMI and including the situation with disease-specific indices. Results: There are two main reasons why POW is widely used in Japan instead of BMI. One reason is that the Japan Society for the Study of Obesity recommended that POW should be used for evaluating childhood obesity. The other reason is that BMI cut-off values for childhood obesity have not been determined in Japan. Conclusion: Individuals involved in child healthcare in Japan should keep in mind both the merits and drawbacks of various anthropometric indices.

Impact of the Great East Japan Earthquake on Body Mass Index, Weight, and Height of Infants and Toddlers: An Infant Survey.

BACKGROUND: The body mass index (BMI) of preschool children from 4 years of age through primary school has increased since the Great East Japan Earthquake, but that of children aged under 3 years has not been studied. This study evaluated how the anthropometrics of younger children changed following the earthquake. METHODS: Height and weight data of children living in northeast Japan were collected from 3-, 6-, 18-, and 42-month child health examinations. We compared the changes in BMI, weight, and height among infants affected by the earthquake between their 3- and 6-month health examinations, toddlers affected at 21-30 months of age (affected groups), and children who experienced the earthquake after their 42-month child health examination (unaffected group). A multilevel model was used to calculate the BMI at corresponding ages and to adjust for the actual age at the 3-month health examination, health examination interval, and gestational age. RESULTS: We recruited 8,479 boys and 8,218 girls living in Fukushima, Miyagi, and Iwate Prefectures. In the infants affected between their 3- and 6-month health examinations in Fukushima, the change in BMI at 42 months of age was greater than among the unaffected children. In the toddlers affected at 21-30 months of age in Fukushima, the change in BMI was greater, but changes in weight and height were less. CONCLUSIONS: Affected infants and toddlers in Fukushima suggested some growth disturbances and early adiposity rebound, which can cause obesity. The future growth of children affected by disasters should be followed carefully.

Spectrum of LMX1B mutations: from nail-patella syndrome to isolated nephropathy.

Nail-patella syndrome (NPS) is an autosomal-dominant disease caused by LMX1B mutations and is characterized by dysplastic nails, absent or hypoplastic patellae, elbow dysplasia, and iliac horns. Renal involvement is the major determinant of the prognosis for NPS. Patients often present with varying degrees of proteinuria or hematuria, and can occasionally progress to chronic renal failure. Recent genetic analysis has found that some mutations in the homeodomain of LMX1B cause isolated nephropathy without nail, patellar or skeletal abnormality (LMX1B-associated nephropathy). The classic term "nail-patella syndrome" would not represent disease conditions in these cases. This review provides an overview of NPS, and highlights the molecular genetics of NPS nephropathy and LMX1B-associated nephropathy. Our current understanding of LMX1B function in the pathogenesis of NPS and LMX1B-associated nephropathy is also presented, and its downstream regulatory networks discussed. This recent progress provides insights that help to define potential targeted therapeutic strategies for LMX1B-associated diseases.

Design of the health examination survey on early childhood physical growth in the Great East Japan Earthquake affected areas.

BACKGROUND: To investigate the impact of the Great East Japan Earthquake on preschool children's physical growth in the disaster-affected areas, the three medical universities in Iwate, Miyagi, and Fukushima Prefectures conducted a health examination survey on early childhood physical growth. METHODS: The survey was conducted over a 3-year period to acquire data on children who were born in different years. Our targets were as follows: 1) children who were born between March 1, 2007 and August 31, 2007 and experienced the disaster at 43-48 months of age, 2) children who were born between March 1, 2009 and August 31, 2009 and experienced the disaster at 19-24 months of age, and 3) children who were born between June 1, 2010 and April 30, 2011 and were under 10 months of age or not born yet when the disaster occurred. We collected their health examination data from local governments in Iwate, Miyagi, and Fukushima Prefectures. We also collected data from Aomori, Akita, and Yamagata Prefectures to use as a control group. The survey items included birth information, anthropometric measurements, and methods of nutrition during infancy. RESULTS: Eighty municipalities from Iwate, Miyagi, and Fukushima Prefectures and 21 from the control prefectures participated in the survey. As a result, we established three retrospective cohorts consisting of 13,886, 15,474, and 32,202 preschool children. CONCLUSIONS: The large datasets acquired for the present survey will provide valuable epidemiological evidence that should shed light on preschool children's physical growth in relation to the disaster.

Alterations in physique among young children after the Great East Japan Earthquake: Results from a nationwide survey.

BACKGROUND: Data for earthquake-related alterations in physique among young children in developed countries is lacking. The Great East Japan Earthquake caused severe damage in Iwate, Miyagi, and Fukushima Prefectures in northeastern Japan. METHODS: We retrospectively obtained anthropometric measurements in nursery school from 40,046 (cohort 1, historical control) and 53,492 (cohort 2) children aged 3.5-4.5 years without overweight in October 2008, and in October 2010, respectively. At the time of the earthquake in March, 2011, children in cohort 1 had already graduated from nursery school; however, children in cohort 2 were still enrolled in nursery school at this time. We compared the onset of overweight at 1 year after the baseline between children enrolled in their school located in one of the three target prefectures versus those in other prefectures using a logistic regression model, with adjustment for sex, age, history of disease, and obesity index at baseline. Overweight was defined as an obesity index of >+15%, which was calculated as (weight minus sex- and height-specific standard weight)/sex- and height-specific standard weight. RESULTS: The odds ratio (OR) for the onset of overweight in the three target prefectures was significant in cohort 2 (OR 1.25; 95% confidence interval [CI], 1.01-1.55) but not in cohort 1. When the two cohort were pooled (n = 93,538), the OR of the interaction term for school location × cohort was significant (OR 1.56; 95% CI, 1.09-2.23). CONCLUSIONS: Incident overweight in young children was significantly more common in the three prefectures affected by the Great East Japan Earthquake than in other prefectures after the disaster.

The response to growth hormone treatment in prepubertal children with growth hormone deficiency in Japan: Comparing three consecutive years of treatment data of The Foundation for Growth Science in Japan between the 1990s and 2000s.

Growth hormone (GH) treatment for children with GH deficiency (GHD) is effective in improving adult height. To achieve favorable effects, GH treatment before puberty is very important, because prepubertal height gain is highly correlated with total height gain. However, no report has studied the effects by analyzing a nationwide data from recent GHD patients in Japan. We investigated the response to GH treatment using data compiled in the Foundation for Growth Science in Japan, and compared the effects between the 1990s and 2000s using analysis of covariance. We analyzed 534 prepubertal GHD subjects treated in the 2000s with three consecutive years of data from the start and investigated predictive factors for the effects. The cumulative height standard deviation score (SDS) change over three years of GH treatment was 0.91 ± 0.57 and 1.20 ± 0.62 in the 1990s and 2000s, respectively. Subjects in the 2000s were divided into three groups by severity, and the cumulative height SDS was 1.60 ± 0.93, 1.20 ± 0.54, and 1.00 ± 0.40 indicating severe, moderate, and mild GHD, respectively. Age and height SDS at the start and severity were identified as independent predictive factors. We also found a significant difference in the effects between the two cohorts after adjusting for the different factors (regression coefficient: -0.069, 95% confidence interval: -0.11 to -0.030, p = 0.0006), which might be due to the GH dose effect. We conclude that the effects of GH treatment in the 2000s had improved compared with those in the 1990s.

Steroid-resistant nephrotic syndrome as the initial presentation of nail-patella syndrome: a case of a de novo LMX1B mutation.

BACKGROUND: Nail-patella syndrome (NPS) is an autosomal dominant disorder caused by mutations in the LMX1B gene and is characterized by nail dysplasia, skeletal abnormalities, and nephropathy. We herein report a case of steroid-resistant nephrotic syndrome (SRNS) prior to overt orthopedic symptoms in a patient with NPS. CASE PRESENTATION: A 24-year-old woman presented to our hospital with knee pain. She had poorly developed nails, hypoplastic patellas, dislocation of the elbows, and iliac horns in the pelvis. At the age of 7, she developed nephrotic syndrome and was diagnosed with primary focal segmental glomerulosclerosis by renal biopsy. She received long-term corticosteroid therapy with no obvious response. Her clinical course and orthopedic manifestations indicated NPS, and a genetic analysis showed a de novo mutation in the LMX1B gene (c.819 + 1G > A). Nephropathy in this case was considered to be associated with NPS. Therefore, we discontinued corticosteroids without the exacerbation of nephrotic syndrome. CONCLUSIONS: Patients with NPS may develop nephrotic syndrome prior to overt orthopedic symptoms and only show non-specific findings in renal biopsy at an early stage of NPS nephropathy. Hereditary nephrotic syndrome, often presenting as childhood-onset SRNS, may also be difficult to diagnose in patients with the following conditions: renal symptoms prior to overt extrarenal symptoms, de novo mutations, and non-specific findings in renal biopsy. Therefore, in the management of SRNS in children, we need to reconsider the possibility of hereditary diseases such as NPS even without a family history.

Partial monosomy of 10p and duplication of another chromosome in two patients.

Partial monosomy of 10p is a rare chromosomal abnormality. Common features are hypoparathyroidism, deafness, renal anomalies, distinctive facies, and mental retardation, with phenotypic variability. We report two patients with chromosomal abnormalities identified on single-nucleotide polymorphism (SNP) array analysis. Although patient 1 had common features of monosomy10p, G-banding indicated a normal karyotype. SNP array and fluorescence in situ hybridization (FISH), however, indicated unbalanced translocation of a 10p terminal deletion of 11.7 Mb and a 15q terminal duplication of 8.2 Mb. In patient 2, SNP array and FISH indicated a 10p terminal deletion of 12.6 Mb and a 7q terminal duplication of 1.9 Mb. This is the first case report of monosomy 10p combined with trisomy 15q (patient 1). Because the clinical heterogeneity of the 10p deletion syndrome would be affected by duplication of another chromosome, we emphasize that SNP/microarray analysis is necessary to confirm genotype-phenotype correlation.

Prolonged elevated body mass index in preschool children after the Great East Japan Earthquake.

BACKGROUND: The Great East Japan Earthquake followed by tsunamis and the Fukushima Daiichi Nuclear Power Plant (NPP) accident caused catastrophic damage. The effects of the disaster on the growth of affected children are of great concern but remain unknown. METHODS: The subject group was derived from two Japanese nationwide retrospective cohorts (historical control and exposure groups, respectively). The exposure group experienced the disaster at 47-59 months of age. We analyzed longitudinal changes in standard deviation score (SDS) for height and body mass index (BMI) using normal Japanese children's standards. Moreover, we analyzed the details of the affected children in Fukushima using Fukushima-specific growth charts established with the historical control data to clarify any indirect effect of the disaster on growth. RESULTS: Affected children in Fukushima had significantly higher BMI SDS than the historical control group (difference, 0.13; 95% CI: 0.044-0.21, P = 0.0029) and the regional controls (difference, 0.14; 95% CI: 0.074-0.20, P < 0.0001) 1.5 years after the disaster. Similar sustained increases in BMI SDS were also found with Fukushima-specific growth charts, but the phenomenon was detected only in boys. Notably, the BMI SDS of affected children who lived near the NPP had been increasing after the disaster, whereas those in distant areas had not changed. In contrast, height SDS had not changed throughout the analysis. CONCLUSIONS: Prolonged elevated BMI SDS was detected only in affected children in Fukushima. This phenomenon may be explained by an indirect effect of the NPP accident.

Growth references for Japanese individuals with Noonan syndrome.

BACKGROUND: Noonan syndrome (NS) is a clinically and genetically heterogeneous syndrome characterized by distinctive facial features, short stature, congenital heart diseases, and other comorbidities. NS-specific growth charts are essential for NS care, but currently no such charts are available for Asian populations. METHODS: We conducted a nationwide survey by collaborating with three academic societies in Japan. We obtained the data of 356 clinically diagnosed NS subjects from 20 hospitals. The Lambda-Mu-Sigma method was used for establishing growth charts. RESULTS: A total of 308 subjects (males: 159 and females: 149) were analyzed after excluding 48 subjects because of missing auxological data (26 subjects), presence of complications affecting growth (5 subjects), and extreme longitudinal growth aberrations which lay more than three standard deviation scores from the mean in this population (17 subjects). Genetic analyses were performed in 150 patients (48.7%); 103 (68.7%) were reported to have some abnormalities in the known causative genes. Cardiovascular diseases were found in 256 patients (83.1%). The NS-specific height, weight, and BMI charts were constructed with 3,249 mixed longitudinal and cross-sectional measurements. CONCLUSION: Growth standards for Japanese individuals with NS were established. These charts are expected to be used in various clinical settings.

Design of the Nationwide Nursery School Survey on Child Health Throughout the Great East Japan Earthquake.

BACKGROUND: The Great East Japan Earthquake inflicted severe damage on the Pacific coastal areas of northeast Japan. Although possible health impacts on aged or handicapped populations have been highlighted, little is known about how the serious disaster affected preschool children's health. We conducted a nationwide nursery school survey to investigate preschool children's physical development and health status throughout the disaster. METHODS: The survey was conducted from September to December 2012. We mailed three kinds of questionnaires to nursery schools in all 47 prefectures in Japan. Questionnaire "A" addressed nursery school information, and questionnaires "B1" and "B2" addressed individuals' data. Our targets were children who were born from April 2, 2004, to April 1, 2005 (those who did not experience the disaster during their preschool days) and children who were born from April 2, 2006, to April 1, 2007 (those who experienced the disaster during their preschool days). The questionnaire inquired about disaster experiences, anthropometric measurements, and presence of diseases. RESULTS: In total, 3624 nursery schools from all 47 prefectures participated in the survey. We established two nationwide retrospective cohorts of preschool children; 53,747 children who were born from April 2, 2004, to April 1, 2005, and 69,004 children who were born from April 2, 2006, to April 1, 2007. Among the latter cohort, 1003 were reported to have specific personal experiences with the disaster. CONCLUSIONS: With the large dataset, we expect to yield comprehensive study results about preschool children's physical development and health status throughout the disaster.