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Objective　This scoping review aimed to provide an overview of collaborative practices for children with medical complexities and their families by life stage.Methods　This scoping review was conducted based on the JBI scoping review manual using the PubMed, CINAHL, and Medical Journal databases. Search terms included "collaboration," "intersectoral collaboration," "children with medical complexity," and "children with special healthcare needs," whereas control words included "children with special healthcare needs," "children with medical care," "children with severe mental and physical disabilities," and "children with severe mental and physical disabilities." The inclusion criteria were articles in Japan that reported on practices for children (aged 0-18 years) with medical care needs and collaboration among other multiple professions, research articles, excluding review and protocol articles, and English or Japanese articles. For the analysis, collaboration-related practices were extracted from selected papers, categorized based on similarities in content, and further summarized according to the life stage. Three researchers discussed the selection of papers, data extraction, and analysis until a consensus was reached.Results　The analysis included 30 papers (27 Japanese and three English papers). Regarding publication year, 14 papers were published within the last 3 years. Additionally, 19 case and 26 practice reports and 11 studies (quantitative research; one, qualitative research; 10) were published by professionals. Regarding collaborative practices, 160 cases were extracted and classified into nine. In "discharge support," practices in all subcategories were reported for preschoolers, whereas only two of the five subcategories were reported for school-aged children. Contrastingly, in the "maintenance phase in preschool, daycare, and school," preschoolers reported practices in two of the seven subcategories. Additionally, various professionals from the fields of medicine, welfare, education, and administration were involved in the collaboration.Conclusion　There were differences in the reporting of collaborative practices at each life stage. Although numerous professionals were involved, reports of collaborative practices among them were unevenly distributed. Eventually, it will be necessary to investigate the nature of collaborative practices among various professionals, focusing on children and their families.

We have been developing protective equipment for portable radiography in neonatal intensive care units because the portable radiography's X-ray tube is in close proximity to the head of the nurse who is assisting the patient. Although our initial protective-equipment design was highly effective, there were some concerns that it obstructed the view of the patient and was difficult to handle. To overcome this problem, we have developed two new types of protective device: a narrow-type 0.13 mmPb device, 17 cm long and 45 cm wide (weight 200 g); and a wide type with a wider core material, 45 cm long and 25 cm wide (weight 300 g), both of which can be hung from the collimator cover of mobile X-ray equipment. The measured protective effectiveness was 80.6% at head height for the wide type and 76.8% for the narrow type. A survey of nurses regarding the new protective devices revealed no significant differences between the two types in terms of visibility and whether the devices would be an obstacle when assisting patients. The nurses preferred the wider type, which offered better protection. Radiological technologists also liked that both types were easy to handle because the irradiation field could be adjusted even after the device was fitted. Both types of the new protective device are thus expected to be useful in clinical practice in terms of their high protective effect and improved ease of handling.

Neonatal Fc receptor (FcRn) is involved in recycling of IgG. Recycling begins with IgG-uptake into the cell through pinocytosis. Subsequently, IgG binds to FcRn in acidic vesicles, which results in the recycling of the FcRn-IgG complex to cell surface, and the release of IgG in blood with neutral pH. Whereas IgG unbound to FcRn is not recycled and thus degraded in lysosomes. Therefore, FcRn plays a critical role in maintaining IgG levels in the blood. Recently, FcRn has been considered a therapeutic target for autoimmune diseases caused by IgG autoantibodies, and FcRn inhibitors are developed as therapeutic agents for the diseases. As one example, the administration of an FcRn inhibitor, efgartigimod, reduced IgG and anti-acetylcholine receptor antibody levels in patients with generalized myasthenia gravis (gMG), and improved Myasthenia Gravis Activities of Daily Living score in the phase III trial. In 2022, Efgartigimod Alfa was approved for the treatment of gMG (only when treatment with steroids or non-steroidal immunosuppressive drugs do not lead to sufficient response), regardless of antibody status in Japan. Since FcRn inhibitors have just begun to be used in clinical practice, it is important to accumulate real-world data regarding their efficacy and safety. (Received August 21, 2023; Accepted October 6, 2023; Published February 1, 2024).

A 27-year-old woman was diagnosed with idiopathic thrombocytopenic purpura in the neonatal period, and was admitted to our hospital after presenting with impaired consciousness, purpura, nausea and vomiting, with a platelet count of 10×10 9 /l. Congenital thrombotic thrombocytopenic purpura (cTTP) was suspected on the basis of recurrent thrombocytopenia and impaired consciousness, so tests for ADAMTS13 activity and inhibitor were performed. ADAMTS13 activity was severely decreased, ADAMTS13 inhibitor was negative, and platelet count increased after transfusion of fresh frozen plasma. These findings and the results of genetic testing done on all family members led to a diagnosis of cTTP. cTTP requires differential diagnosis even in adults. If a patient diagnosed with ITP in childhood has a history or findings that suggest cTTP during follow-up observation, it is necessary to actively consider ADAMTS13 testing.

Congenital protein C (PC) deficiency is one type of hereditary thrombosis. Patients with hereditary thrombosis are at high risk for thrombosis in the perioperative period, but a standard management strategy has not been established. Here we report a case of perioperative management of a fracture in a child with homozygous congenital PC deficiency. The patient was a 3-year-old boy who was diagnosed with congenital PC deficiency at birth. He sustained a traumatic supracondylar fracture of the right humerus and underwent emergency surgery. To prepare for open surgery for fixation of the fracture, warfarin was discontinued, and an activated PC (APC) concentrate was used in combination with vitamin K antagonism. However, warfarin was administered during the scheduled nail extraction because the operation was minimally invasive. No thrombotic or bleeding complications occurred in either operation. In emergency surgery in patients with congenital PC deficiency, the combination of vitamin K and APC concentrate is considered a maintenance option for PC deficiency. Postoperative PT-INR control was difficult in our patient due to the administration of vitamin K and withdrawal of warfarin, and this issue must be addressed in the future. Further case experience is desirable to standardize perioperative management.

A 19-year-old female, normal at birth, grew up without neck movement when getting up. She needed a handrail to climb stairs since the age of 10 years old, and walked slowly since the age of 16 years old. Neurological examination revealed loss of deep tendon reflexes, decreased vibratory sensation, weakness of distal muscles of the lower extremities, and weakness of mainly cervical trunk muscles suspected to be due to myopathy. Nerve conduction studies suggested axonal polyneuropathy, and needle EMG showed short duration MUP, myotonic discharge, and rimmed vacuoles on muscle biopsy. Genetic analysis revealed a previously reported pathological mutation (p.P209L, heterozygous) in Bcl2-Associated Athanogene 3 (BAG3), and a diagnosis of MFM6 was made. P209L is a poor prognosis myopathy that develops in childhood and is associated with cardiomyopathy. P209L is a solitary myopathy associated with axonal neuropathy and characterized by apex foot contracture and weak neck to trunk flexion. This disease is suspected in young-onset neuromyopathy.

A 25-year-old Japanese woman with a history of repeated episodes of rhabdomyolysis since the age of 12 presented with rhabdomyolysis caused by hyperemesis gravidarum. Blood tests showed an elevated serum CK level (11,755 ‍IU/l; normal: 30-180 ‍IU/l). Carnitine fractionation analysis revealed low levels of total carnitine (18.3 ‍μmol/l; normal: 45-91 ‍μmol/l), free carnitine (13.1 ‍μmol/l; normal: 36-74 ‍μmol/l), and acylcarnitine (5.2 ‍μmol/l; normal: 6-23 ‍μmol/l). Tandem mass spectrometry showed high levels of C14:1 acylcarnitine (0.84 ‍nmol/ml: normal: <0.4 ‍nmol/ml) and a high C14:1/C2 ratio of 0.253 (normal: <0.013), indicating a potential diagnosis of very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. Enzyme activity measurement in the patient's peripheral blood lymphocytes confirmed the diagnosis of VLCAD deficiency, with low palmitoyl-CoA dehydrogenase levels (6.5% of normal control value). With the patient's informed consent, acyl-CoA dehydrogenase very long-chain (ACADVL) gene analysis revealed compound heterozygous mutations of c.1332G>A in exon 13 and c.1349G>A (p.R450H) in exon 14. In Japan, neonatal mass screening is performed to detect congenital metabolic diseases. With the introduction of tandem mass screening in 2014, fatty acid metabolism disorders, including VLCAD deficiency, are being detected before the onset of symptoms. However, it is important to note that mass screening cannot detect all cases of this disease. For patients with recurrent rhabdomyolysis, it is essential to consider congenital diseases, including fatty acid metabolism disorders, as a potential diagnosis.

Preimplantation genetic testing for monogenic disorders (PGT-M) has been implemented in Japan under a novel definition of severity to reduce the chances of giving birth to a child with an inherited genetic disorder. The redefinition of disease severity is not only about changing definitions and interpretations, but also a matter of potentially expanding the number of diseases covered by PGT-M and the range of clients, which could raise serious human rights-related issues. With the rapid development of therapies for neuromuscular diseases and the possibility of the clinical course of diseases previously considered to be serious becoming progressively becoming milder in the future, the "definition of severity" classification itself, as applied to PGT-M, may become debatable. Neurologists will thus become more involved in presymptomatic diagnosis and newborn screening for the early diagnosis and treatment to enhance the efficacy of new therapies. We also need to address the technical, social, and ethical issues surrounding genetic counselling and PGT-M, and practice holistic medicine for the patients and their families.

Portable imaging in the NICU requires the assistance of a nurse, and the nurse is in close proximity to the X-ray tube, In all, 64 percent of our nurses thought that additional protective equipment was needed. Therefore, a radiation protection device was created and its usefulness was verified. A protective equipment of 0.13 mmPb with a width of 38 cm and a length of 70 cm was made and hung from the mono-tank X-ray unit of the mobile X-ray unit. The position of the nurse was set at 30 cm outward from the center of the irradiation field, and the protective effect was measured at three points: (a) the patient's height, (b) 30 cm above the patient, and (c) 60 cm above the patient. For the imaging conditions, a 2-liter plastic bottle filled with water was placed in the incubator, and measurements were taken with an SID of 100 cm, irradiated field of 20.3 cm×25.4 cm, tube voltage of 58 kV, and tube current-time product of 10 mAs, which was converted to the actual imaging condition of 1 mAs. Based on the results obtained, a questionnaire survey was conducted on nurses' thoughts for the protective equipment created for them. Only 3% reduction in height of (a) where no protective equipment is reached but (b) 50% and (c) 92%, respectively. In all, 82 percent of the nurses had a favorable impression of the new protective equipment. It is expected that the protective equipment designed to control lens dose and reduce anxiety of nurses will be useful.

A 48-year-old man underwent computed tomography for the examination of lower back pain, which incidentally detected a cardiac tumor in the right atrium. On echocardiography, the tumor was identified as a 30 mm round mass with a thin wall and iso- and hyper-echogenic contents that originated from the atrial septum. The tumor was successfully removed under cardiopulmonary bypass, and the patient was discharged in good health. The cyst was filled with old blood, and focal calcification was observed. Pathological examination revealed that the cystic wall was composed of thin-layered fibrous tissue lined with endothelial cells. Regarding a treatment, it is reported that early surgical removal is preferable to avoid embolic complications, however it is controversial. Furthermore, it needs to discuss about the difference between fetal/neonatal and adult cases.

Criss-cross heart is an extreamly rare anomaly characterized by abnormal rotation of the heart on its long axis. Almost always there are associated cardiac anomalies such as pulmonary stenosis, ventricular septal defect (VSD) and ventriculoarterial connection discord, and most cases are candidates for Fontan procedure due to hypoplasia of right ventricle or straddling atrioventricular valve. We report a case of arterial switch operation for criss-cross heart with muscular ventricular septal defect. The patient was diagnosed with criss-cross heart, double outlet right ventricle, subpulmonary VSD, muscular VSD and patent ductus arteriosus (PDA). PDA ligation and pulmonary artery banding (PAB) was performed in the neonatal period, and an arterial switch operation (ASO) was planed at 6 months of age. Preoperative angiography showed nearly normal right ventricular volume and echocardiography showed normal subvalvular structures of atrioventricular valves. ASO, intraventricular rerouting and muscular VSD closure by sandwitch technique were successfully performed.

(Objective) Pregnancy in kidney transplant recipient continues to remain challenging due to a high rate of cesarean section along with preterm delivery, and concern for worsening renal function. This study examined the prognosis and perinatal management of post-transplant pregnancies. (Patients and methods) A total of nine post-transplant recipients at Niigata University Medical and Dental Hospital between 2007 and 2021 were retrospectively examined. (Results) All pregnancies were planned. Calcineurin inhibitors and steroids were continued, and antimetabolites were changed to azathioprine. The mean age at delivery was 33±3.8 years, and the mean time from renal transplantation to delivery was 6.5±3.5 years. Five patients (55.5%) had cesarean sections, while four (44.5%) patients had normal vaginal deliveries. The mean gestational age was 35±3.0 weeks, and the mean birth weight was 2,336±565.4 g. No congenital malformation was observed. The most common reason for early delivery was worsening renal function, seen in six (66.7%) patients. The mean serum creatinine level before pregnancy was 1.11±0.23 mg/dL and then worsened to 1.59±0.37 mg/dL during pregnancy. However, it recovered to 1.14±0.40 mg/dL after delivery. One patient had antibody-mediated rejection with donor specific antibody (DSA) prior to pregnancy, and her renal graft function worsened slightly after delivery. Another patient had a de novo DSA after delivery, which was not detected before pregnancy. (Conclusions) In our hospital, pregnancy in kidney transplant recipients were safe and renal graft function after delivery was relatively stable. Patients may require adjustment of calcineurin inhibitors during pregnancy, and the appearance of DSA after delivery should be noted.

The number of reports on genetic predisposition to pediatric thrombosis is increasing. The risk of thrombosis in childhood varies according to patient age, and the contribution of genetic predisposition also differs. The term early-onset thrombophilia, which occurs until the age of 20 years in patients with genetic diagnosis, was defined. Then, the registry in Japan was established. Further, publications were reviewed comprehensively, and results revealed the genetic and clinical characteristics of patients. Less than 60% of patients presented with protein C (PC) deficiency, and over half of them had PC-gene monoallelic variants. The number of patients with protein S or antithrombin deficiency increased with age. None of them were aged between 6 and 8 years. PC-Tottori and protein S-Tokushima, which are high-frequency and low-risk variants in Japanese, contributed to the development of thrombosis. However, PC-Tottori did not affect the development of severe PC deficiency. One exceptional de novo PC-deficient variant was identified in 32 EOT families, and thrombosis developed concurrently in three pairs of mothers-newborns. Appropriate EOT screening tests targeting PC deficiency are required to prevent maternal and neonatal thromboses.

The case was a 53-year-old woman. At birth, she was diagnosed with a false Taussig-Bing anomaly with pulmonary artery stenosis and a single ventricle. However, no cardiac surgery was performed, and conservative treatment was continued by a cardiovascular surgeon even after adulthood. Because of secondary polycythemia and a history of multiple cerebral infarctions, she took anti-platelet drugs and anti-coagulants. However, she was admitted with the diagnosis of cerebral infarction for the fourth time. It was considered that the patient was at high risk of paradoxical cerebral embolism due to cardiac malformation with cyanotic congenital heart disease accompanied by coagulation abnormalities. Considering the pathophysiology, we decided to use aspirin in combination with warfarin.

Childhood hydrocephalus is a highly diverse disease caused by various factors, and most surgical treatments are performed during infancy. Despite the diversity of hydrocephalus pathologies, treatment options are limited. It is difficult for pediatric neurosurgeons to select and perform appropriate surgical procedures for neonates and infants. Treatment options for hydrocephalus are broadly divided into permanent and temporary. Permanent treatments include cerebrospinal fluid shunt and endoscopic third ventriculostomy; temporary treatment entails cerebrospinal fluid drainage using lumbar puncture and intermittent cerebrospinal fluid drainage with an Ommaya reservoir, ventricular drainage, and ventriculosubgaleal shunt. This article describes in detail Ommaya reservoir placement and ventricular drainage as representative procedures for temporarily treating hydrocephalus.

The treatment of hypoplastic left heart syndrome has improved dramatically with the development of treatment strategies due to improved understanding of hemodynamics, improved surgical methods, and the widespread use of fetal diagnosis. However, cases of early closure of the foramen ovale require emergency surgery immediately after birth, and further improvement of treatment results is needed. The right ventricular pulmonary artery shunt reported from Japan is well known worldwide and has greatly contributed to improved outcomes up to six months after the Norwood procedure. Also contributing to the improved results of the Norwood procedure is the widespread use of bilateral pulmonary artery banding to avoid palliative open heart surgery in the neonatal period. Although this method is widely used in Japan, there is still room for improvement in such areas as postoperative left pulmonary artery stenosis and aortic arch reconstruction after stenting of the ductus arteriosus. Now that the results of the Norwood procedure have stabilized, there is a need to improve treatment methods to establish a better Fontan circulation in the future.

Transposition of the great arteries( TGA) is a congenital heart disease in which the aorta originates from the right ventricle and the pulmonary artery from the left ventricle. In embryonic development, normally, the aorticopulmonary septum develops a spiral-like configuration resulting in the pulmonary trunk twisting around the ascending aorta. However, in TGA, there is lack of spiral rotation of the aorticopulmonary septum. TypeⅠ( 50%) without ventricular septal defect( VSD), typeⅡ( 25%) with VSD and left ventricular outflow tract stenosis (LVOTS), typeⅢ (25%) with VSD and LVOTS, and typeⅣ (very rare) with VSD but no LVOTS. All types present with cyanosis from the time of birth. Of these, typeⅠ is the most cyanotic, as systemic oxygen supply depends on the flow through the foramen ovale. Since the theme of this article is emergency surgery, we will discuss surgical treatment for typeⅠ, for which surgery is indicated in the early neonatal period.

A 35-years-old pregnant woman with Marfan's syndrome visited the emergent department. She had sudden severe back pain. She was at the 20th week of gestation. An emergent chest computed tomo-graphy scan showed Stanford type B acute aortic dissection. After admission, strict blood pressure control was started. According to aortic valve insufficiency and fluid retention with pregnancy, acute heart and respiratory failure was getting worse. It seemed risky for both mother and the fetus to continue pregnancy. After sincere and detailed discussion between the patient and our multidisciplinary medical team, the patient decided to continue pregnancy. An urgent Bentall operation was performed. A careful attention was paid for the fetus during and after the surgery. Strict blood pressure control was also continued. The mother and the 30-week-gestation newborn recovered uneventfully. During four years of follow-up, thoracic and thoraco-abdominal aortic replacement was performed. The patient survived all of these procedures without any complication.

The purpose of treatment hydrocephalus is to maintain intracranial pressure, as well as to create a favorable psychomotor developmental environment, particularly in pediatric cases. Various complications associated with shunt surgery require long-term care. When a shunt is performed for neonates and infants with hydrocephalus, proper management is required thereafter during whole their life. The most common complication that can occur as a result of shunt surgery is obstruction of the ventricular catheter. Ventricular catheter obstruction can be avoided by placing that the tip of the catheter is placed in an appropriate position. A further measure would include preventing the ventricular catheter from being pulled out as the skull expands. The next common complication is obstruction of the peritoneal catheter. The risk of occlusion can be reduced by making that the tip of the peritoneal catheter is open-ended as opposed to having side slits. Isolated ventricles and slit ventricle syndrome are peculiar shunt-related conditions that are difficult to treat. When shunt dysfunction occurs, hydrocephalus can progress slowly, but in many cases the patient's condition deteriorates rapidly and requires immediate medical intervention. Recently, neuroendoscopic surgery has been actively performed for cases of shunt dysfunction and prophylactic replacement of peritoneal catheters, and attempts have been made to remove the shunt device. Shunt infection is another troublesome complication in the management of hydrocephalus and has not yet been resolved. However, if all staff involved in shunt surgery have a common understanding and adopt fixed protocols related to preoperative, intraoperative, and postoperative management, the incidence of infection can be significantly reduced. Furthermore, the development of new and improved catheters may also contribute to a reduction in shunt infection. Neurosurgeons should be cognizant that a delay in the diagnosis and treatment of shunt-related complications in patients with hydrocephalus could result in death. Shunt surgery for the treatment of pediatric hydrocephalus is merely the beginning, as neurosurgeons must be responsible for management until the child reaches adulthood.

Copper is one of the essential trace elements in humans, and its deficiency causes various diseases. Zinc acetate dihydrate is administered to treat hypozincemia in preterm infants; however, zinc inhibits the gastrointestinal absorption of copper, which may cause copper deficiency. To safely treat hypozincemia in preterm infants, we retrospectively analyzed the factors reducing serum copper concentrations when zinc is administered to preterm infants with hypozincemia. Seventy preterm infants were included in the present study. Serum zinc and copper concentrations, doses, and other clinical characteristics were retrieved from electronic medical records. The administration of zinc acetate dihydrate decreased serum copper concentrations in 21 out of 70 patients. In comparisons between the two groups with and without a decrease in serum copper concentrations, significant differences were observed in postmenstrual age (34.9 and 35.9 weeks, respectively) and serum zinc concentrations (62.0 and 58.0 μg/dL, respectively) at the start of the zinc acetate dihydrate treatment. A logistic regression analysis identified postmenstrual age as a significant factor decreasing serum copper concentrations. In the ROC curve, the cut-off value for postmenstrual age for a decrease in serum copper concentrations was 34.143 weeks. The present results suggest that when zinc acetate dihydrate is administered to preterm infants with a low postmenstrual age who are at higher risk of decreased serum copper concentrations, particularly to those with a postmenstrual age <34 weeks, it is important to consider copper deficiency and periodically measure serum copper concentrations.

Midwives are responsible professionals who support the sexual and reproductive health, rights, and welfare of individuals, families, and communities. In particular, midwives work in partnership with women to provide the necessary support, care and advice needed during pregnancy, childbirth and the postpartum period. Midwives conduct normal births on her own responsibility, support breastfeeding, provide care for newborns and infants, and fully release mother-infant's latent strengths. Midwives also contribute in adopting appropriate preventative measures to promote normal birth and breastfeeding, detecting early signs of complications, and carrying out emergency measures or transferring the patient to other medical care or assistance as needed. In order to provide the best care to mother and infant, midwives should first learn the biological foundations of women's health, pregnancy, childbirth, postpartum, breastfeeding, and infant health. They must also understand the in vivo mechanisms and actions of the key hormones and neurotransmitters in play during the reproductive period. Additionally, midwives need to learn pharmaceutical treatments to complement and support biological function in cases of disorders or impairments occurring in women and infants. Midwives should also be competent in life support skills in obstetrics and neonatal cardiopulmonary resuscitation. The directors of Japanese Maternity Centers sign a contract with obstetricians that permits them to purchase and use emergency medicines. We facilitate midwifery students in their studies of medicine and pharmacology in order to train them to cope with such emergency situations. In this revision of the midwifery curriculum and the continuing education, we hope to create a new midwifery educational program focusing on personalized, client-centered pharmacology, with the ultimate objective to support and maintain the health of women, mothers, infants, child-rearing families, and communities.

We have been conducting research with the aim of generating evidence for the safety of perinatal drugs. As a result of reviewing the records of inquiries to the Drug Information Office of our hospital, we found a large discrepancy between the description of perinatal drugs in package inserts in Japan and the description of the Pregnancy Risk Category according to the U.S. Food and Drug Administration. In the Japan Environment and Children's Study (JECS), we determined the proportion of drug and supplement use among 97464 pregnant women. We clarified that prescriptions of antihypertensive drugs for pregnant women increased during the second half of pregnancy, while prescriptions of anti-epileptic and anti-anxiety drugs decreased after pregnancy using a claims database. A survey of pharmacists and pharmacy students revealed a lack of awareness of effective folic acid intake to reduce the risk of neural tube defects in infants. The percentage of pre-pregnancy folic acid supplementation among pregnant women participating in the Babies and their Parents' Longitudinal Observation in Suzuki Memorial Hospital on Intrauterine Period (BOSHI) study, the JECS, and the Tohoku Medical Megabank (TMM) Birth and Three-Generation (BirThree) cohort study was 6.3-18.0%. As a result of close examination of the records of inquiries to the Drug Information Office of our hospital, and of cases in which our lactation plan sheet was applied, it was found that there were discrepancies between the information on the drug package insert and the information on Medications & Mother's Milk, etc. in Japan. The results obtained have been clinically applied in daily practice and we are continuing our research while taking measures.

Congenital hemolytic anemia (CHA) develops not only in the neonatal period but in all age groups, from fetuses to adults. In this study, we summarized the differential diagnoses of hemolytic anemia cases with undetermined etiology in the past 5 years. In total, 319 patients with CHA were included. For cases in which autoimmune hemolytic anemia and paroxysmal nocturnal hemoglobinuria were ruled out, we performed CHA-related laboratory tests. For cases in which a definitive diagnosis of membrane and enzyme abnormalities was required, and for cases in which it was difficult to diagnose the disease type based on biochemical and cell biological tests, we used a gene panel analyzing 68 hemolytic anemia-related genes. The incidence of dehydrated hereditary stomatocytosis (DHSt) has increased since definitive diagnosis by genetic analysis became available. DHSt is now the second most frequent type of CHA. Target-captured sequencing (TCS) analysis is useful for the diagnosis of DHSt, but is a time-consuming and labor-intensive process involving the analysis of a large amount of data generated by the next-generation sequencer. In order to overcome this limitation, simpler and faster laboratory testing should be developed.

Parental age at birth has been investigated in patients diagnosed with pediatric cancer. The Japan Children's Cancer Registry1985-2007 recruited 5,510 patients with leukemia and 8,782 with other cancers. The proportion of patients born to mother and father aged >40 years showed a higher trend in leukemia than that in other cancers (odds ratio [OR] 1.41, p=0.057), especially in <12-month-old infants born to mother aged >40 years (OR 2.55, p=0.031). We then divided 27,335 patients diagnosed in 1969-2006 into every 8-year birth cohorts to compare proportions of mothers with prenatal medical irradiation. The OR of leukemia was higher than that of other cancers in 1969-1976 (1.25) or 1977-1984 (1.39), which reached statistical significance. We have also studied caregiver's exposure to anticancer drugs. In 15 pediatric patients with cancer who received cyclophosphamide (CPM), the concentration was measured using mothers and medical staff's urine. Five of 7 infants' and 2 of 8 adolescent's mothers showed increased urine CPM levels. CPM was not detected in any medical staff's samples. Maternal exposure to anticancer drugs should also be considered. Efforts of reducing the genotoxicity in both infants and mothers are crucial for pediatric cancer prevention.

Objective: A few studies have focused on pregnancy and childbirth in patients with Crohn's disease (CD) who had a history of abdominal surgery. The objective of this study is to analyze the problems of pregnant patients with CD with a history of abdominal surgery., Methods: The rates of pregnancy-related complications and adverse birth outcomes were retrospectively analyzed in 29 patients with CD (45 pregnancies) with previous intestinal surgery., Results: In this study, the following outcomes were observed:normal births occurred in 55.6% of the pregnancies, preterm births in 13.3%, and spontaneous abortions in 20.0%. The vaginal birth and cesarean section rates were 45.7% and 40.0%, respectively. The rate of low-birth weight infants was 14.3%., Conclusion: Overall, patients with CD with previous abdominal surgery can conceive and give birth. However, care needs to be taken to avoid preterm birth, spontaneous abortion, low birth weight, and cesarean delivery.

Evidence from our recent studies points to the notion that adult neurogenesis in the hippocampus may serve as a sensitive endpoint to detect developmental neurotoxicity. Adult neurogenesis is the postnatal process of continued generation of new neurons through the adult stage in the brain. Monitoring of granule cell lineages generated from the subgranular zone and γ-aminobutyric acid (GABA)-ergic interneurons in the hilus of the dentate gyrus as major players consisting of hippocampal neurogenesis is effective for detecting target cell populations of developmental neurotoxicants. Especially, reelin-expressing GABAergic interneurons are a useful marker to predict disruption of migration and correct positioning of newborn neurons following disruption of neurogenesis. Because axon terminal toxicants target granule cell lineage population showing neurite outgrowth, there may be common target mechanisms between the developmental and adult-type neurotoxicity. Because adult neurogenesis continues through the adult stage, developmental neurotoxicity could be detected in regular toxicity studies, such as in a 28-day repeated dose study. Alternatively, adult-type neurotoxicity could be detected by measuring the cellular responses in neurogenesis. Moreover, it should be stressed that there may be epigenetic toxicity mechanisms to affect the process of neurogenesis involving neuronal stem cells and interneuron subpopulations, showing continued disruption through the adult stage. These findings suggest that hippocampal neurogenesis is considered to be a critical target of neurotoxicity of both developmental and adult types.

Drug-drug interactions (DDIs) are responsible for an increase in the incidence of adverse drug reactions. Although CYP is known to be involved in metabolic processes, the DDIs among three or more drugs that involve the same CYP molecular species have not been fully investigated. In this study, we retrospectively examined the relationship between the number of drugs and potential DDIs in metabolic processes involving CYPs in patients who picked up their prescribed drugs at 11 pharmacies in the Kojima Branch of the Okayama Pharmaceutical Association. We found that 66.5% of the 924 patients had potential DDIs; more than half of the patients who took six or more drugs had potential DDIs among three or more drugs. The mean number of CYP3A4-related drugs involved in potential DDIs was 3.52±1.56 in patients who took seven drugs, suggesting the need for careful monitoring of specific symptoms and blood test results for the early detection of adverse drug reactions caused by DDIs among three or more drugs.

Massive pulmonary hemorrhage, although rare, is a potentially life-threatening complications during heart surgery. We herein present 1 such case successfully treated by selective bronchial occlusion using an Endobronchial Watanabe Spigot (EWS). The 82-year-old female underwent mitral valve replacement, tricuspid annuloplasty, and maze procedure. An hour and a half after cessation of cardiopulmonary bypass, the patient suffered a massive pulmonary hemorrhage. A subsequent bronchoscopy identified the hemorrhage site at the right middle lobe bronchus (B5b), and an EWS was then selectively deployed into this bronchus to block the hemorrhage. The following day, bronchial arterial embolization was performed, enabling the removal of the spigot on the next day. The patient's respiratory condition gradually improved, allowing for extubation on the 21st postoperative day. By preventing bleeding into neighboring bronchi, which, in turn, avoids the risk of exacerbating hypoxia, bronchial occlusion with EWSs is highly effective in managing massive pulmonary hemorrhage during heart surgery.

A man in his 40s was diagnosed with CML. He and his partner expressed their desire to have a child. We recommended planning the pregnancy after the achievement of major molecular response and completion of TKI therapy because we could not promise complete safety of the fetus, However, he and his partner insisted on starting the TKI therapy immediately and planned the pregnancy during the therapy. The patient was started on nilotinib 600mg/body. CCyR, MMR, and CMR were achieved in 3, 8, and 12 months, respectively. The patient's partner got pregnant when he had been on TKI therapy for 15 months, and she gave birth to a healthy boy. Since many patients with CMLcan live for a long time after receiving TKI therapy, the quality of life of these patients is more important. Even if the percentage of patients with CML who are under 50 years of age is approximately 30%, the safety information of TKI with respect to pregnancy is unsatisfactory. Doctors struggle to address the problems of the patient's wish of childbearing, priority of TKI therapy, and fetal risks of the treatment. Although only a few cases of pregnancy and delivery of the partners of male patients with CML treated with TKI have been reported, all cases showed healthy childbirth and normal child growth. Our experience also showed that the partner of a male patient with CML treated with TKI became pregnant and delivered a healthy baby.

Background: When corticosteroids are used for a long time in patients with bronchial asthma, a decrease in adrenal cortex function occurs. We investigated the use of salivary cortisol measurements as a simple, noninvasive method for the evaluation of the adrenal cortex function in pediatric asthmatic patients., Methods: Plasma and salivary cortisol levels were measured from 8:00 am to 10:00 am in 248 pediatric asthmatic patients aged 0-18 years that were under long-term care management at the National Hospital Organization Fukuoka National Hospital in 2011-2013. We determined the correlation between plasma and salivary cortisol levels and calculated a salivary cortisol cut-off value for screening adrenocortical function., Results: There was a significant positive correlation between salivary cortisol levels and plasma cortisol levels in all patients, patients under age 3, and patients over age 3 (r=0.759, r=0.563, r=0.827, respectively). Salivary cortisol cut-off values were 0.015μg/dL for plasma cortisol levels below 3μg/dL (sensitivity 83%, specificity 82%), and 0.045μg/dL those below 5μg/dL (sensitivity 83%, specificity 75%). 5μg/dL or less is an abnormal value, and 3μg/dL or less is considered to be adrenal insufficiency., Conclusion: Salivary cortisol levels were positively correlated with plasma cortisol levels in pediatric asthmatic patients. This is a useful method for frequently monitoring young children with adrenal dysfunction or severe asthma that are treated with high doses of inhaled corticosteroids.

Hereditary hemolytic anemia (HHA) is a group of monogenic diseases arising from the increased destruction of circulating erythrocytes. HHA is caused by germline mutations in genes encoding components of the red blood cell membrane, hemoglobin, and enzymes. Comprehensive gene analyses have identified various HHA-associated germline defects. However, early HHA diagnosis can be difficult in newborns because they present with hydrops and severe jaundice, which require urgent blood transfusions. Considering neonatal physiological hemolysis and pediatric infection, we select efficient diagnostic procedures following the exclusion of "syndromic hemolytic diseases". Clinical sequencing is performed for atypical cases, although phenotypic and laboratory tests remain essential for the verification of pathogenicity when certain variants are identified. The diagnostic gene panel can also be useful for predicting prognosis and determining treatment options. Although transfusion-dependent adult patients with HHA are rare in Japan, their management remains challenging. Clinical trials of new drugs and genetic controls are ongoing in other countries. However, the long-term management of a small group of patients with severe HHA must still be addressed in Japan. Here, we review the strategy and clinical significance of using genetic diagnostic methods for HHA in newborns.

Evidence of the molecular epidemiology of thrombophilia is growing, and the clinical management of adult thromboembolism patients has recently made significant progress. On the other hand, there is little or no evidence concerning the genetic variation, treatment, and prophylaxis of thromboembolism development in the early life stage. The clinical presentation of early-onset thrombosis/thrombophilia, which mostly occurs in newborns and adolescents, differs from that in cases of adult-onset. Recurrent purpura fulminans and/or intracranial hemorrhage/infarction leads to dangerous lifelong complications. As in the setting of cancer genomic medicine, germline variants require determination for the individualized control of early-onset thrombophilia. The genetic predisposition to thrombosis varies among ethnicities. In the Japanese population, the protein S variant (PS-Tokushima, K196E) has attracted attention as the cause of a common and low-risk prothrombotic predisposition in adults, while protein C deficiency greatly impacts the onset of pediatric thrombosis. In 2020, 3 years after the registration of idiopathic thrombosis as a designated intractable disease, genetic tests have been promulgated for health insurance portability. Disease-specific therapy for early-onset thrombophilia is crucial. Here, we review the genetic heterogeneity, prophylaxis, and treatment strategy of the rare subgroups of severe heritable thrombosis conditions in Japan.

We describe surgical treatment of a coronary artery fistula (CAF) in a neonate. A 5-day-old male neonate was diagnosed with CAF at another hospital and was transferred to our hospital. Transthoracic echocardiography revealed a right coronary artery-to-right ventricle (RV) fistula. Emergency surgery was performed to treat progressive congestive heart failure due to a significant left-to-right shunt through the large CAF. Intraoperatively, we confirmed that the large CAF drained into the inlet of the RV through multiple openings. Intracardiac CAF closure was performed with a bovine pericardial patch. The neonate showed an uneventful postoperative recovery, and postoperative echocardiography revealed a trivial residual shunt with good left ventricular function without increased pulmonary artery pressure.

Pulmonary regurgitation(PR) and right ventricular dysfunction are the major complications in a longterm period after the repair of congenital heart diseases including tetralogy of Fallot(TOF). The purpose of this study is to investigate the effectiveness of pulmonary valve replacement (PVR) after the congenital heart repair. Twenty-five patients undergoing PVR for PR with clinical symptoms in a longterm period between March 2008 and December 2016 were retrospectively reviewed. The average age at the TOF repair was 2.6±2.6 years. The average age at the PVR was 21.6±11.2 years. The mean follow-up after the PVR was 52.8±27.5 months. There was neither hospital death nor late death. All the patients underwent PVR with a bio-prosthetic valve. Nine patients had concomitant tricuspid valve repair. PVR significantly reduced right ventricular end-diastolic volume( RVEDVI)[ 123±25 vs 101± 13% of normal, p=0.002], cardio-thoracic ratio (CTR) [56.0±6.9 vs 52.6±13.0%, p=0.03], and brain natriuretic peptide (BNP) [57.6±57.0 vs 38.7±31.3 pg/dl, p=0.03]. The relatively early PVR significantly improved RVEDVI, CTR and cardiac function.

A female neonate presented with a cranial mass in the left parietal lobe region. She was born through Cesarean section, and there was no history of birth trauma or head injury. Her mother noticed the mass two weeks after birth. It increased slowly in size and turned stiff. CT showed a skull tumor with calcification. MRI findings, with no vascular abnormalities, indicated a possibility of cephalohematoma. 67 Ga scintigraphy showed no abnormal uptake in the cranial mass or any other systemic lesion. We performed an operation to examine the histology and to adjust the shape of the skull. The diagnosis from the histological examination was cephalohematoma with calcification. Cephalohematoma occurs less commonly in the case of Cesarean section and usually resolves spontaneously without any intervention. Some studies have reported birth trauma even though the baby was born through a scheduled Cesarean section. Even if there is no definite history of head trauma, it is necessary to consider cephalohematoma when we examine a cranial mass of a neonate.

We report the case of a patient with spinal immature teratoma and cerebrospinal fluid leakage from the congenital dermal sinus tract. A 0-day-old female infant presented with a subcutaneous soft mass with a dimple in the lumbosacral region at birth. Magnetic resonance imaging revealed a mixed low-intensity mass located in the extraspinal and intraspinal canal with a sinus tract. The reconstructed three-dimensional spinal computed tomography image showed spina bifida and ectopic ossification at the dorsal aspect of the sacrum. Urgent removal of the tumor and dermal sinus tract was then performed under evoked electromyography monitoring. The resected tumor was histopathologically diagnosed as immature teratoma.

To meet the fetus's calcium demand in the 3rd trimester as much as 300~500 mg/day, intestinal calcium absorption in pregnant women is upregulated, without comparable increase in bone resorption. On the contrary, to provide 210 mg/day of calcium for the neonate, bone resorption by osteoclasts and osteocytes is markedly upregulated in maternal skeleton caused by low estrogen and high PTHrP as a consequence of elevated prolactin production, without any increase in intestinal calcium absorption. Breastfeeding women lose 5~10%of trabecular bone during 3 to 6 months of lactation.

Purpose: A three-dimensional (3D) image from computed tomography (CT) angiography is a useful method for evaluation of complex anatomy such as congenital heart disease. However, 3D imaging requires high contrast enhancement for distinguishing between blood vessels and soft tissue. To improve the contrast enhancement, many are increasing the injection rate. However, one method is the use of fenestrated catheters, it allows use of a smaller gauge catheter for high-flow protocols. The purpose of this study was to compare the pressure of injection rate and CT number of a 24-gauge fenestrated catheter with an 22-gauge non-fenestrated catheter for i.v. contrast infusion during CT., Methods: Between December 2014 and March 2015, 50 newborn patients were randomly divided into two protocols; 22-gauge conventional non-fenestrated catheter (24 newborn; age range 0.25-8 months, body weight 3.6±1.2 kg) and 24-gauge new fenestrated catheter (22 newborn; age range 0.25-12 months, body weight 3.3±0.9 kg). Helical scan of the heart was performed using a 64-detector CT (LightSpeed VCT, GE Healthcare) (tube voltage 80 kV; detector configuration 64×0.625 mm, rotation time 0.4 s/rot, helical pitch 1.375, preset noise index for automatic tube current modulation 40 at 0.625 mm slice thickness)., Results: We compared the maximum pressure of injection rate, CT number of aortic enhancement, and CT number of pulmonary artery enhancement between both protocols. The median injection rate, CT number of aortic enhancement, and CT number of pulmonary artery enhancement were 0.9 (0.5-3.4) ml/s, 455.5 (398-659) HU, and 500.0 (437-701) HU in 22-gauge conventional non-fenestrated catheter and 0.9 (0.5-2.0) ml/s, 436.5 (406-632) HU, and 479.5 (445-695) HU in the 24-gauge fenestrated catheter, respectively. There are no significantly different between a 24-gauge fenestrated catheter and 22-gauge non-fenestrated catheters at injection rate and CT number. Maximum pressure of injection rate was lower with 24-gauge non-fenestrated catheters (0.33 kg/cm 2 ) than 22-gauge non-fenestrated catheters (0.55 kg/cm 2 ) (p<0.01Conclusion: A 24-gauge fenestrated catheter performs similarly to an 22-gauge non-fenestrated catheter with respect to i.v. contrast infusion and aortic enhancement levels and can be placed in most subjects whose veins are deemed insufficient for an 22-gauge catheter.

There is mounting concern about the effects of early-life exposure to chemical substances on children's health and development. We summarize the past and ongoing birth cohort studies carried out worldwide on the association between environmental exposure and children's health. Our PubMed search with the keywords 'birth cohort' revealed that the number of articles jumped from 200-300 in the 1980s to over 1,000 in the 1990s. Many of these articles reported elevated risks to children's health posed by chemical exposure owing their vulnerability. At the same time, policies implemented to reduce exposure to lead and dioxins were successful in the past few decades. Research also demonstrated that intervention to reduce exposure to certain chemicals whose exposure routes were well documented was also successful. We summarize the effects of early-life exposure to chemical substances on children's health and development. Our findings will hopefully help safeguard the environment in which future generations grow and live.

In this study, we examined the changes in the demographic characteristics of foreign residents in Japan (FRJ) and the current status of FRJ from a global health perspective. We also considered child maltreatment that occurred in FRJ families and language problems in child welfare. Japan's official statistics in the end of 2017 indicated that there were more than 2.56 million FRJ from over 190 countries. This population was diverse with heterogeneous characteristics, such as age structure, dwelling place, marital status, and childbirth. At the end of 2017, there were 219,982 FRJ children aged 0-14 of various nationalities, including Chinese, Brazilian, South Korean, North Korean, Filipino, Vietnamese, Peruvian, Nepalese, and Indian. In 2010, we conducted our first survey of child maltreatment in FRJ families, targeting 219 child protection centers across Japan. Between April 2007 and August 2010, 1,639 child maltreatment cases were reported from 56% of these centers. Details of 1,111 cases were collected and descriptive analyses were conducted. The male-to-female ratio was 0.88 and the median age was 8 years: however, the age distribution showed that females were significantly older than males (P < 0.01). The proportions of physical abuse, child neglect, emotional abuse, and sexual abuse were 38%, 33%, 21%, and 7%, respectively. Native language problems created numerous challenges and required a large amount of effort from child welfare practitioners. However, most solutions to identified problems were still at the beginning stage and some were found to be ineffective. More interdisciplinary and integrated researches are needed targeting child welfare of FRJ. An ethical framework for good counseling practices should be developed.

The incidence of pregnancy complicated with renal dysfunction has tended to increase due to aging and progress in the treatment methods. Generally, pregnancy is allowed only in women with normal renal function and in patients with mild renal insufficiency; therefore, the incidence of osteoporosis and the resulting fragile fracture is rare during pregnancy complicated with renal dysfunction. In recent years, the incidence of pregnancy in dialysis patients and in patients who have undergone kidney transplantation has been increasing due to the progress in treatment methods. Eventually, it has become possible for patients with renal dysfunction to give birth as long as they fulfill certain conditions for pregnancy; however, the rate of preterm births has remained high. The incidence of femoral neck fracture has been about 5 times more in dialysis patients than in healthy individuals; however, the prevention and treatment of osteoporosis in pregnant dialysis patients have been difficult, since many osteoporosis medications are contraindicated in pregnant women and also their pregnancy period is not long due to the higher rate of preterm births.

Objectives　Spreading awareness of shaken baby syndrome is considered to be essential in the prevention of infant deaths resulting from abuse. This study aimed to determine whether an educational video on infant crying, developed by the Ministry of Health, Labour and Welfare, was effective at increasing knowledge of infant crying and shaking among Japanese caregivers of infants aged under 1 year.Methods　We targeted caregivers who had infants aged under 1 year for intervention through health checkups and home visits in 29 municipalities across Japan from April 2013 to March 2014. The educational video on infant crying and danger of shaking and smothering was used as intervention. A questionnaire was administered to caregivers to assess their knowledge on infant crying and shaking prior to and after the intervention (N=1,444, response rate 93.8%). A sample of 1,232 caregivers was used for analysis, after excluding those who did not report the outcome of interest (i.e., knowledge on shaking or smothering) and demographics. In the analysis, pre- and post-test mean scores on crying knowledge scales and shaking knowledge scales (out of 100) were compared separately. Subgroup analysis and regression analysis were also conducted to examine whether the effect of the intervention varied by infant age, birth order, parent's sex, age, education, marital status, household income, grandparents' co-residence, postpartum depression, domestic violence during pregnancy, feelings about pregnancy, and resident area (urban/rural).Results　Scores on infant crying significantly increased by 12.4 points (95% confidence interval: 11.7-13.2), and those on shaking knowledge increased by 4.7 points (95% confidence interval: 3.9-5.6) after the caregivers had watched the educational video. Subgroup analysis confirmed that the effect of the intervention did not differ among the subgroups except shaking knowledge scores among those who were not married and those who experienced physical violence from their partner. A regression analysis on change in scores revealed that parents with higher education gained more knowledge on infant crying, and fathers and those not living with grandparents gained more knowledge on shaking than mothers.Conclusion　The educational video on infant crying was effective in increasing knowledge of infant crying and shaking, regardless of demographics of infants and parents and postnatal situation.

We experienced 2 cases of primary pulmonary vein stenosis(PVS),which developed after a bidirectional Glenn procedure was performed for complex heart defects with normal pulmonary venous return. Although the patients successfully underwent primary sutureless repair for left PVS, restenosis of the affected pulmonary veins occurred several months after surgery in both patients. Stent implantation followed by balloon angioplasty was performed for stent stenosis in 1 patient without effect. However, the patient later underwent a successful fenestrated Fontan procedure. Catheter intervention was contraindicated in the 2nd patient due to almost complete obstruction of the left pulmonary veins with upstream hypoplasia. To improve the results of PVS treatment, earlier diagnosis by quantitative lung perfusion scintigraphy, magnetic resonance imaging, and close echocardiographic observation together with earlier, aggressive treatment combining surgery and catheter interventions are recommended.

Methylxanthine is widely administered for the treatment of apnea of prematurity in many countries, and previous reports have clearly established that caffeine is effective for the treatment of apnea of prematurity. In Japan, caffeine has been available since December 2014. Thus, we compared the efficacy and safety of caffeine with that of aminophylline in our hospital. There was no significant difference between the caffeine group and aminophylline group regarding the characteristics of the study patients. The mean efficacy rate from day 1 to day 10 was 89.5% in the caffeine group, and 81.9% in the aminophylline group, although the rate of improvement in apnea episodes each day from day 1 to day 10 was not significantly different between the two groups. On the other hand, the adverse event rates in the caffeine group and the aminophylline group were 70.6% and 75.0%, respectively. No significant difference was observed in the adverse event rates between the two groups. Moreover, suspected abdominal distension due to the drug administration was more frequently observed with the aminophylline group. Our findings indicate that caffeine is as effective as aminophylline, while it is superior to aminophylline regarding its overall safety.

We evaluated 18,487 patients and 223,842 cases of donor coordination among patients enrolled in the Japan Marrow Donor Program (JMDP) from January 2004 to December 2013. For patients who underwent stem cell transplantation from a JMDP donor [unrelated bone marrow transplantation (UBMT)], the median number of coordination and days from registration to transplantation were 11 and 146, respectively. Among enrolled patients, 40% did not undergo UBMT. With the increased estimated number of human leukocyte antigen 6/6-matched donors, the probability of undergoing UBMT was higher, and in those who underwent UBMT, the duration of coordination was shorter. Regarding the reasons for the termination of coordination, those attributable to the donors varied depending on the age and sex of the donors. Male donors in their 20s had lower and higher termination rates because of health conditions and inconvenience, respectively, compared with donors of different age and female sex. Among donors who experienced coordination more than once, the donation rate was higher if the precedent coordination ended because of reasons attributable to the patient compared with the donation rate because of other reasons. Using the results of our study, strategies to achieve a more efficient and rapid coordination process are warranted.

Over the past few decades, advances in neonatal medicine have increased survival rates among very-low-birth-weight (VLBW) babies. Despite improvements in short-term outcomes, there is increasing concern about the probability of mild cognitive dysfunction in this population. Our analysis of VLBW babies born in our hospital revealed that the incidence of mild developmental disorders including autism spectrum disorder (ASD) and attention deficit hyperactive disorder (ADHD) at the age of 3 years is 7.2%, which is markedly higher than the 2.8% incidence of ASD in the general population. Because problems related to ASD or ADHD tend to become more prominent as children grow up, the ages at diagnosis of developmental disorders are generally 6 years or above. Thus, in our follow up study of VLBW babies at age 6, the incidence of these developmental disorders had risen to 30%. These patients are apparently obstinate and difficult to train, causing parental problems with child care. It is important to support these children and help them establish good relationships with their parents. Given these problems, it is necessary to follow up VLBW children in the longterm, at least until they are elementary school students.

Growth hormone (GH) therapy for short children born small for gestational age (SGA) has been approved in Japan. It is important to evaluate GH secretion ability before the initiation of GH therapy because there are some differences in dose and medical expenses between short children born SGA and GH deficiency (GHD). This study was designed to elucidate the incidence of GHD and to find a useful marker for detecting it in short SGA children. We retrospectively reviewed medical records to analyze the clinical features of short children born SGA and with GHD who had started GH therapy before the age of 6 in the University Hospital of Occupational and Environmental Health and Kyushu Rousai Hospital. Nine of 22 SGA subjects (41%) had GHD. There were no significant differences between two groups of short SGA children (GHD, non-GHD) in the median of height and serum insulin-like growth factors (IGF)-1 levels at birth or at the start of GH therapy. The probability of GHD was higher if the height standard deviation scores (SD) of the SGA children were lower than -3.2 (odds ratio, 11.6; 95% confidence interval, 1.52 - 89.1, P = 0.013). This study showed that there is an approximately 40% incidence of GHD in short SGA children needing GH treatment. We should do GH stimulation tests for short SGA children whose height SD is lower than -3 to determine the appropriate GH therapy.