Association of hyaluronan and proteoglycan link protein 1 gene with the need of home oxygen therapy in premature Japanese infants with bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD) has a lasting effect on the respiratory function of infants, imposing chronic health burdens. BPD is influenced by various prenatal, postnatal, and genetic factors. This study explored the connection between BPD and home oxygen therapy (HOT), and then we examined the association between HOT and a specific single-nucleotide polymorphism (SNP) in the hyaluronan and proteoglycan link protein 1 (HAPLN1) gene among premature Japanese infants. MATERIALS AND METHODS: Prenatal and postnatal data from 212 premature infants were collected and analyzed by four SNPs (rs975563, rs10942332, rs179851, and rs4703570) around HAPLN1 using the TaqMan polymerase chain reaction method. The clinical characteristics and genotype frequencies of HAPLN1 were assessed and compared between HOT and non-HOT groups. RESULTS: Individuals with AA/AC genotypes in the rs4703570 SNP exhibited significantly higher HOT rates at discharge than those with CC homozygotes (odds ratio, 1.20, 95% confidence interval, 1.07-1.35, p = .038). A logistic regression analysis determined that CC homozygotes in the rs4703570 SNP did not show a statistically significant independent association with HOT at discharge. CONCLUSIONS: Although our study did not reveal a correlation between HAPLN1 and the onset of BPD, we observed that individuals with CC homozygosity at the rs4703570 SNP exhibit a reduced risk of HOT.

A survey of the current status of neonatal disseminated intravascular coagulation in neonatal intensive care units in Kyushu, Japan.

BACKGROUND: Neonatal disseminated intravascular coagulation (DIC) is a rare disease with a poor outcome. However, data on the incidence, treatment, and outcome of neonatal DIC are scarce. Thus, this study investigated the status of neonatal DIC in Japan. METHODS: We sent a retrospective questionnaire-based survey regarding the status of diagnosis and treatment of neonatal DIC from January 1, 2016, to December 31, 2018, to 30 hospitals in Kyushu with a neonatal-perinatal medicine division. The data collected by the questionnaire survey included information about the patients diagnosed with neonatal DIC. RESULTS: Among the 13,582 neonates surveyed, 120 (0.9 %) were diagnosed with DIC. Of them, clinical data were available for 105 cases. There were 11 deaths (mortality rate: 10.4 %), with the most common underlying condition being infection (n = 9), followed by neonatal asphyxia and hematologic disease (both, n = 1). Compared with the survival group, the death group had more infections, as well as a higher rate of bleeding symptoms and organ dysfunction. CONCLUSIONS: Neonatal DIC associated with infectious diseases has a poor outcome. Therefore, it is necessary to formulate diagnostic and treatment guidelines for early intervention in such cases.

Early diagnosis of neonatal-onset cyclic vomiting syndrome.

Cyclic vomiting syndrome (CVS) is characterized by recurrent episodes of severe vomiting with a completely asymptomatic interictal interval. Relatively few patients develop CVS in the neonatal period, and an early diagnosis is difficult. We experienced an infant who was diagnosed with neonatal-onset CVS in early infancy. An 8-day-old girl was admitted to our neonatal intensive care unit because of frequent vomiting beginning 12 h after birth and weight loss reaching 84.2% of her birth weight. Despite extensive examinations, no abnormalities to explain the vomiting were found. She continued to vomit, and a cyclical pattern with a vomiting phase lasting for three days followed by a non-vomiting phase lasting for about one to two weeks became obvious. Based on her clinical course, the family history of migraine and the effectiveness of Phenobarbital, she was diagnosed with CVS at three months old. Although CVS is a diagnosis of exclusion, a family history of migraine can aid its early diagnosis. If the illness is suspected in the neonatal period, diagnostic treatment with Phenobarbital may be considered. The case suggests the need to include CVS in the differential diagnosis of neonates with unexplained repetitive vomiting.

Study protocol for a multicentre, open-label, single-arm phase I/II trial to evaluate the safety and efficacy of ripasudil 0.4% eye drops for retinopathy of prematurity.

INTRODUCTION: Retinopathy of prematurity (ROP) is a vascular proliferative disorder that occurs in preterm infants. Existing treatments are only indicated in severe ROP cases due to the high invasiveness and the potential risk of irreversible side effects. We previously elucidated that ripasudil, a selective inhibitor of the Rho-associated protein kinase, has the ability to inhibit abnormal retinal neovascularisation in animal models. In addition, ripasudil eye drops (Glanatec ophthalmic solution 0.4%) have been already used for the treatment of glaucoma. Since eye drop therapy is less invasive, early intervention for ROP is possible. The purpose of this phase I/II trial is to evaluate the safety and efficacy of ripasudil eye drops for preterm infants with ROP. METHODS AND ANALYSIS: This is a multicentre, open-label, single-arm phase I/II trial. To evaluate the safety and efficacy of ripasudil as much as possible, ripasudil will be administered to all enrolled preterm infants with zone I/II, stage 1, or worse ROP. The safety and efficacy of ripasudil in treated patients will be assessed in comparison to a historical control group. Because this is the first trial of ripasudil in preterm infants, a dose-escalation study (once daily for 1 week, then two times per day for 2 weeks) will be conducted in phase I. After obtaining approval from the independent data and safety monitoring board to continue the trial after the completion of phase I, phase II will be conducted. In phase II, ripasudil eye drops will be administered two times per day for 12 weeks. The primary endpoint in phase II is also safety. Efficacy and pharmacokinetics will be evaluated as secondary endpoints. ETHICS AND DISSEMINATION: This study protocol was approved by the institutional review board at each of the participating centres. Data will be presented at international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBERS: NCT04621136 and jRCT2071200047.

Measurement of the Estradiol Concentration in Cerebrospinal Fluid from Infants and Its Correlation with Serum Estradiol and Exosomal MicroRNA-126-5p.

Estradiol has an important role in the brain, such as in neuronal development and protection, but estradiol levels in the human brain have not been well investigated. In this study, we measured the estradiol concentration in the cerebrospinal fluid (CSF) of infants to reveal the relationships between the estradiol concentrations in the serum and the CSF and further determined exosomal microRNAs in serum. Estradiol in the CSF was strongly correlated with serum estradiol and moderately correlated with miR-126-5p in the serum exosomes. This report is the first to determine the estradiol concentration in CSF from infants and showed that the levels of miR-126-5p as well as serum estradiol can be candidates to predict brain estrogen status.

Vitamin K Deficiency Bleeding in Infancy.

Vitamin K is essential for the synthesis of few coagulation factors. Infants can easily develop vitamin K deficiency owing to poor placental transfer, low vitamin K content in breast milk, and poor intestinal absorption due to immature gut flora and malabsorption. Vitamin K deficiency bleeding (VKDB) in infancy is classified according to the time of presentation: early (within 24 h), classic (within 1 week after birth), and late (between 2 week and 6 months of age). VKDB in infancy, particularly late-onset VKDB, can be life-threatening. Therefore, all infants, including newborn infants, should receive vitamin K prophylaxis. Exclusive breastfeeding and cholestasis are closely associated with this deficiency and result in late-onset VKDB. Intramuscular prophylactic injections reduce the incidence of early-onset, classic, and late-onset VKDB. However, the prophylaxis strategy has recently been inclined toward oral administration because it is easier, safer, and cheaper to administer than intramuscular injection. Several epidemiological studies have shown that vitamin K oral administration is effective in the prevention of VKDB in infancy; however, the success of oral prophylaxis depends on the protocol regimen and parent compliance. Further national surveillance and studies are warranted to reveal the optimal prophylaxis regimen in term and preterm infants.

Impacts of surgical interventions on the long-term outcomes in individuals with trisomy 18.

OBJECTIVE: We aim to clarify whether surgical interventions can contribute to improve the long-term outcomes among individuals with trisomy 18. METHODS: We retrospectively studied 69 individuals with trisomy 18 admitted to 4 tertiary neonatal centers between 2003 and 2017. A cohort was divided into two groups: subjects with surgical interventions and conservative treatments. We compared the rates of survival and achieving homecare between the groups. RESULTS: Gestational age and birth weight were 37 (27-43) weeks and 1,700 (822-2,546) g, respectively. There were 68 patients with congenital heart disease and 20 patients with digestive disease. Surgical interventions including cardiac and digestive surgery were provided in 41% of individuals. There was no difference in gestational age (p=0.30), birth weight (p=0.07), gender (p=0.30), and fetal diagnosis (p=0.87) between the groups. During the median follow up duration of 51 (2-178) months, overall survival rates in 6, 12 and 60 months were 57%, 43% and 12%, respectively. Survival to hospital discharge occurred in 23 patients, and the rates of achieving homecare in 1, 6, and 12 months are 1%, 18% and 30%, respectively. There was no significant difference in survival rate (p=0.26) but in the rate of achieving home care (p=0.02) between the groups. Cox hazard analysis revealed that prenatal diagnosis (hazard ratio 0.30, 95%CI: 0.13-0.75), cardiac surgery (hazard ratio 2.40, 95%CI:,1.03-5.55), and digestive surgery (hazard ratio 1.20, 95%CI: 1.25-3.90) were related to the rate of achieving homecare. CONCLUSION: Aggressive surgical interventions contribute not to the long-term survival but to achieve homecare among individuals with trisomy 18. EVIDENCE LEVEL: Level 3 (Prognostic study, Case-Control study).

Impact of sleep duration during pregnancy on the risk of gestational diabetes in the Japan environmental and Children's study (JECS).

BACKGROUND: Gestational diabetes mellitus (GDM) has serious effects on both mother and child. Like Type 2 Diabetes Mellitus, it is increasing in prevalence world-wide. In addition to obesity, sleep duration has been named an important risk factor. Using a large cohort study, including data from 48,787 participants of the Japan Environment and Children's Study (JECS), we examined the association between sleep duration and both random blood glucose levels and GDM rates during pregnancy. METHODS: Random blood glucose levels were measured during pregnancy. GDM diagnosis was based on the results of 75 g oral glucose tolerance test. Additional anthropometric data was collected from questionnaires for statistical analysis. RESULTS: Compared to mothers averaging 7 to < 10 h sleep (reference group), women receiving < 5 h or ≥ 10 h sleep exhibited significantly elevated random blood glucose levels. This was associated with an elevated risk for positive GDM screening (< 5 h sleep: OR 1.17 (0.96-1.44) p = 0.126; ≥10 h sleep: OR 1.13 (1.03-1.25) p = 0.006). Calculating the risk for GDM, women sleeping < 5 h or ≥ 10 h exhibited elevated risks of 1.31-fold and 1.21 respectively. However, this trend was not found to be significant. CONCLUSIONS: Sleep is a critical factor in glucose metabolism, with both abnormally long and short sleep duration increasing random blood glucose levels in pregnant women. Moreover, the risk for positive GDM screening increases significantly with elevated sleep, ≥10 h per night. These findings are promising because they support the idea that sleep duration is a modifiable risk factor, and can be focused upon to improve health and pregnancy outcome.

Incidence and In-Hospital Mortality of Neonatal Disseminated Intravascular Coagulation in Japan: An Observational Study of a Nationwide Hospital Claims Database.

This study aimed to estimate the incidence and prognosis of neonatal disseminated intravascular coagulation (DIC) in Japan by analyzing data retrieved from a national administrative database. Clinically, the prognosis of DIC in neonates is poor, but there is little epidemiological data in Japan. This retrospective observational study identified patients diagnosed with neonatal DIC and who were registered in the Japanese diagnosis procedure combination (DPC) database between April 1, 2014 and March 31, 2016. The patients, who were diagnosed with neonatal DIC, included those with ICD-10 code D65 or P60 in primary and secondary diagnosis, with comorbid conditions existing at admission, and with complications occurring after admission. Of 78,073 neonates admitted to 1,474 neonatal intensive care units, 1,864 (2.4%) were diagnosed with DIC. There was no difference between sexes in incidence of DIC; the incidence of DIC was higher in extremely low birth weight infants (9.8%), and significantly higher than that in normal birth weight infants. The overall mean length of hospital stay was longer in neonates with DIC (69.5 days) than in those without DIC (32.6 days, P < 0.001). The number of deaths was 1,156 (1.5%). In-hospital mortality was significantly higher in neonates with DIC (14.1%) than in those without DIC (1.2%, P < 0.001), especially in premature babies. This nationwide study was the first report to investigate the incidence and in-hospital mortality of neonatal DIC in Japan. Neonatal DIC has a significant impact on prognosis, and its influence is greater in premature than in term infants.

The evaluation of the appropriate gentamicin use for preterm infants.

Gentamicin (GM) is used for neonates as the initial treatment for neonatal bacterial infection. An association between high trough GM levels and the elevation of the serum creatinine (sCr) level and hearing loss has been reported, although there have been no reports investigating the serial changes in the sCr level in preterm neonates treated with GM. The present study evaluated the serial changes in the sCr level and the incidence of hearing loss in preterm neonates treated with GM. This study included 56 neonates born at a gestational age of 32-36 weeks. Fifteen (group 1) and 20 (group 2) neonates were treated with 2.5 mg/kg of GM every 12 h and 4 mg/kg of GM every 36 h, respectively. Group 3 included 21 neonates without GM therapy. Serum GM levels, serial changes in the sCr levels, and the incidence of hearing loss were then compared among the three groups. The serum trough GM level in group 2 was significantly lower than that in group 1 (P < 0.001), whereas the serum peak GM levels in these groups were almost the same. The ratio of the sCr level at birth to that at the 5th day of life in group 1 was the lowest among the 3 groups. No neonates had hearing loss. GM therapy worsened the sCr level in late preterm neonates, especially those with multiple doses per day. The appropriate use of GM is needed in order to prevent the occurrence of nephrotoxicity.

Impact of High Flow Nasal Cannula Therapy on Oral Feeding in Very Low Birth Weight Infants with Chronic Lung Disease.

Previous studies on high-flow nasal cannula (HFNC) in very-low-birth-weight infants (VLBWIs) focused on comparing HFNC with nasal continuous positive airway pressure (nCPAP) to determine the usefulness of HFNC as a backup in the case of extubation failure and nasal trauma; however, the studies did not consider oral feeding. This retrospective case-control study aimed at elucidating whether HFNC could prevent the delay in feeding and achievement of full oral feeding in VLBWIs with chronic lung disease (CLD). Forty five VLBWIs were enrolled in this study: an HFNC group (n = 11) that was supported by HFNC at oral feeding initiation, and a non-HFNC group (n = 34) that could start oral feeding without HFNC. The gestational age and birth weight of the HFNC group were lower than those in the non-HFNC group. The median duration of exposure to oxygen and neonatal intensive care unit stay were comparable in both groups. The timings of oral feeding initiation and full oral feeding achievement in both groups were not significantly different: 35.3 (33.0 - 38.1) vs. 35.5 (33.7 - 42.4) weeks (P = 0.91) for the HFNC and 38.6 (34.4 - 42.3) vs. 36.7 (34.6 - 44.4) weeks postmenstrual age (P = 0.29) for the non-HFNC. Clinically significant aspiration pneumonia during the period of oral feeding was not observed in the HFNC group. Respiratory support by HFNC in VLBWIs with CLD might prevent oral feeding delay. Initiation of oral feeding of VLBWIs on HFNC might be safe and might accelerate the achievement of oral feeding milestones.

[A Field Survey of Working Conditions of Parents with Children Requiring Medical Care].

The number of children in Japan with disabilities who require medical care is increasing and is estimated to have reached about 17,000 in 2015. Their home care is a great burden on mothers, therefore it is presumed to be hard for the mothers to find outside employment. The aims of this survey are to clarify the working conditions of mothers of children with disabilities that require medical care, and to investigate effective social support for improving their working and economic status. We carried out an original questionnaire survey on parents of children with disabilities who were visiting the University Hospital of Occupational and Environmental Health, Japan or daycare facilities in Kitakyushu City. Seventy-five parents, including 73 mothers, responded. The median age of the enrolled children with disabilities was 9 years old. Thirty-two of the mothers who responded (42.7%, median age 40) were employed, but two-thirds of them were non-regular employees. Twenty-two of the mothers had experienced a loss of work because of their children's disabilities. There were no significant relationships among the working conditions, children's age, size of family and household income. Almost 89% of the mothers desired to get employment for their sense of worth and economic status, but almost 11% did not. This survey clarified that the employment rate of mothers of disabled children with special care needs was low, and that most of those who were employed had non-regular employment. It is important to support the mothers in finding employment for their mental and economic status, and special attention must be paid to the diversity of their needs.

Associations between metal concentrations in whole blood and placenta previa and placenta accreta: the Japan Environment and Children's Study (JECS).

BACKGROUND: Placenta previa and placenta accreta associate with high morbidity and mortality for both mothers and fetus. Metal exposure may have relationships with placenta previa and placenta accreta. This study analyzed the associations between maternal metal (cadmium [Cd], lead [Pb], mercury [Hg], selenium [Se], and manganese [Mn]) concentrations and placenta previa and placenta accreta. METHODS: We recruited 17,414 women with singleton pregnancies. Data from a self-administered questionnaire regarding the first trimester and medical records after delivery were analyzed. Maternal blood samples were collected to measure metal concentrations. The subjects were classified into four quartiles (Q1, Q2, Q3, and Q4) according to metal concentrations. RESULTS: The odds ratio for placenta previa was significantly higher among subjects with Q4 Cd than those with Q1 Cd. The odds ratio for placenta previa was significantly higher for subjects with Q2 Pb than those with Q1 Pb. CONCLUSION: Participants with placenta previa had higher Cd concentrations. However, this study was cross-sectional and lacked important information related to Cd concentration, such as detailed smoking habits and sources of Cd intake. In addition, the subjects in this study comprised ordinary pregnant Japanese women, and it was impossible to observe the relationship between a wide range of Cd exposure and placenta previa. Therefore, epidemiological and experimental studies are warranted to verify the relationship between Cd exposure and pregnancy abnormalities.

Pregnancy outcome of Japanese patients with glucokinase-maturity-onset diabetes of the young.

AIMS/INTRODUCTION: Glucokinase-maturity-onset diabetes of the young (GCK-MODY; also known as MODY2) is a benign hyperglycemic condition, which generally does not require medical interventions. The only known exception is increased birthweight and related perinatal complications in unaffected offspring of affected women. As previous data were obtained mostly from white Europeans, the present study analyzed the pregnancy outcomes of Japanese women with GCK-MODY to better formulate the management plan for this population. MATERIALS AND METHODS: The study participants were 34 GCK-MODY families whose members were diagnosed at Osaka City General Hospital during 2010-2017. A total of 53 pregnancies (40 from 23 affected women, 13 from 11 unaffected women) were retrospectively analyzed by chart review. RESULTS: Birthweights of unaffected offspring born to affected women were significantly greater as compared with those of affected offspring (P = 0.003). The risk of >4,000 g birthweight (16%), however, was lower as compared with that previously reported for white Europeans, and none of the offspring had complications related to large birthweight. Insulin treatment of the affected women resulted in a significant reduction in the birthweights of unaffected offspring. Perinatal complications including small-for-gestational age birthweight were found only in affected offspring born to insulin-treated women. CONCLUSIONS: In Japanese GCK-MODY families, unaffected offspring born to affected women were heavier than affected offspring. However, insulin treatment of affected women might not be advisable because of the lower risk of macrosomic birth injury, and an increased risk of perinatal complications in affected offspring.

Associations Between Metal Levels in Whole Blood and IgE Concentrations in Pregnant Women Based on Data From the Japan Environment and Children's Study.

BACKGROUND: Metal exposures could possibly affect allergic responses in pregnant women, although no studies have yet shown a clear relationship between the two, and such exposures might also affect the development of allergic diseases in children. METHODS: We investigated the relationship between metal concentrations in whole blood and immunoglobulin E (IgE; total and specific) in 14,408 pregnant women who participated in the Japan Environment and Children's Study. The subjects submitted self-administered questionnaires, and blood samples were collected from them twice, specifically, during the first trimester and again during the second/third trimester. Concentrations of the metals Cd, Pb, Hg, Se, and Mn, as well as serum total and allergen-specific IgEs for egg white, house dust-mites (HDM), Japanese cedar pollen (JCP), animal dander, and moth, were measured. Allergen-specific IgE(s) were divided based on concentrations <0.35 or ≥0.35 UA/mL, and the metal levels were divided into quartiles. RESULTS: Multivariable logistic regression analysis showed that there was a significant negative correlation between HDM- and animal dander-specific IgEs and Hg and Mn concentrations. Conversely, there was a significant positive relationship between JCP-specific IgE and Hg and Se concentrations. CONCLUSIONS: Metal exposures may be related to both increases and decreases in allergen-specific IgEs in pregnant women.

The Physiological Variation in Plasma Presepsin Levels During the Early Neonatal Period.

Neonatal sepsis continues to be a global problem with significant morbidity and mortality, because of the difficulty in predicting its onset with clinical symptoms alone. Thus, the presence of biomarkers is useful for the diagnosis of neonatal sepsis. Presepsin is a 13-kDa truncated form of soluble CD14 that is produced through proteolytic cleavage on activated monocytes. Presepsin, consisting of 64 amino acid residues, has been proposed as a reliable biomarker for the early diagnosis of sepsis in neonates. However, some biomarkers for the diagnosis of sepsis are elevated during the early neonatal period due to physiological variation, whereas such variation in presepsin levels is uncertain. The objective of this study is to investigate the physiological variation in plasma presepsin levels during the early neonatal period. This prospective study included 30 full-term healthy neonates, including 15 neonates delivered by cesarean section. Plasma presepsin levels were examined at birth and on the first day and the fifth day of life in neonates, and the levels on the 5th day of life were lower than those at any other points (P < 0.001). Moreover, there was no significant difference of plasma presepsin levels between neonates delivered vaginally and by cesarean section. The physiological variation in plasma presepsin levels was observed during the early neonatal period. Attention needs to be paid when measuring plasma presespsin levels for the screening of sepsis during the early neonatal period.

Vitamin A to prevent bronchopulmonary dysplasia in extremely low birth weight infants: a systematic review and meta-analysis.

BACKGROUND: Vitamin A (VA) supplementation reduces the risk of developing bronchopulmonary dysplasia (BPD). However, a previous meta-analysis showed that VA had minimal efficacy for preventing BPD in very low birth weight infants (VLBWIs). AIMS: To elucidate the effects of VA supplementation for BPD prevention in extremely low birth weight infants (ELBWIs). STUDY DESIGN: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We registered the protocol on PROSPERO, the international prospective registry of systematic reviews (registration number: CRD42016050887). We searched the following five databases: CINAHL, CENTRAL, EMBASE, MEDLINE, and PubMed; screened the reference lists of retrieved articles to identify randomized controlled trials (RCTs); and assessed the Cochrane Risk of Bias for each study. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. RESULTS: Four studies (total, 1,011 infants) were included. VA was administered intramuscularly in 3 studies and orally in 1 study. VA supplementation for ELBWIs had benefited oxygen dependency at the postmenstrual age of 36 weeks in survivors (pooled risk ratio, 0.88; 95% confidence intervals (CI), 0.77-0.99; 4 trials, 841 infants, moderate certainty of evidence), which is similar to the meta-analysis in VLBWIs. Length of hospital stay was reduced in the VA group (mean difference, -49.9; 95% CI, -88.78 to -11.02; 1 trial, 20 infants, low certainty of evidence). The meta-analysis showed no reduction in the risk of neonatal death, oxygen use at 28 days in survivors, duration of mechanical ventilation, intraventricular hemorrhage, retinopathy in prematurity, and necrotizing enterocolitis. CONCLUSIONS: VA supplementation for ELBWIs is potentially effective in decreasing oxygen dependency at the postmenstrual age of 36 weeks.

[Evaluation of Clinical Features and Growth Hormone Deficiency in Short Children Born Small For Gestational Age].

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.

The association between whole blood concentrations of heavy metals in pregnant women and premature births: The Japan Environment and Children's Study (JECS).

BACKGROUND: Heavy metals are widely distributed in the environment. Recent reports have demonstrated the risk of preterm birth following heavy metal exposure. Preterm births are classified as early and late, depending on the duration of pregnancy, and are associated with increased risk of congenital illnesses such as heart failure, asthma, etc. Particularly, early preterm births carry a higher risk of mortality; however, the differential effects of heavy metal exposure on early and late preterm births are unknown. OBJECTIVES: To analyze the association between maternal whole blood concentrations of heavy metals, such as cadmium (Cd), lead (Pb), mercury (Hg), selenium (Se), and manganese (Mn) that are common toxicants in Japan, and early and late preterm births. METHODS: The data of 14,847 pregnant women who were participants of the Japan Environment and Children's Study were used. Data of the self-questionnaire pertaining to the first trimester (T1), second/third trimester (T2), and medical records after delivery were analyzed. We divided preterm birth into two groups: early preterm (22 to < 34 weeks) and late preterm (34 to < 37 weeks). Maternal blood samples for measuring heavy metal concentrations were collected in T2 (pregnancy weeks: 14-39). The participants were classified into four quartiles (Q1-Q4) according to increasing heavy metal levels. RESULTS: The rate of preterm birth was 4.5%. After controlling for confounding factors, such as age, pre-pregnancy body mass index, smoking, partner's smoking, drinking habits, gravidity, parity, number of cesarean deliveries, uterine infections, household income, educational levels, and sex of infant, Cd levels were found, by multivariable logistic regression analysis, to be significantly associated with early preterm birth (p = 0.002), with odds ratio for early preterm birth of 1.91 (95% confidence interval: 1.12-3.27, P = 0.018) in subjects of Q4 compared with in subjects with term birth (≧ 37 weeks). CONCLUSION: Maternal blood Cd levels during pregnancy are positively associated with the risk of early preterm birth among Japanese women. Identification of the main source of maternal Cd exposure may contribute to the prevention of early preterm births and health maintenance of mothers and their infants in the future.

Factors associated with occupation changes after pregnancy/delivery: result from Japan Environment & Children's pilot study.

BACKGROUND: In Japan, although the number of females who continue to work after marriage has recently increased, the proportion of those working while parenting their infants is still not clearly increasing, indicating that it is still difficult for them to continue working after delivery. The present study aimed to clarify factors influencing females' continuation of work, using data obtained by continuously following up the same subjects and focusing on occupation changes, family environments, and the type of employment after pregnancy or delivery. METHODS: Based on the results of the questionnaire survey, which was conducted involving 164 participants at 4 universities, as part of the Japan Environment and Children's Pilot Study (JECS Pilot Study) led by the Ministry of Environment and the National Institute for Environmental Studies, the occupational status was compared between the detection of pregnancy (weeks 0 to 7) and 1 year after delivery. RESULTS: compared with changed their occupations significantly more frequently (OR = 5.07, 95% CI = 2.57-10.01, P < 0.001). Furthermore, on examining in detail, occupation changes were particularly marked among (OR = 12.48, 95% CI = 4.43-35.15, P < 0.001). This tendency was especially shown among < > (OR = 10.36, 95% CI = 1.59-67.38, P = 0.014) and < > (OR = 15.15, 95% CI = 2.55-90.17, P = 0.003). CONCLUSIONS: Analysis revealed that the type of employment, rather than the category of occupation, was associated with the continuation of work after pregnancy or delivery more closely, as compared with continued to work less frequently. Furthermore, on comparison of the category of occupation among , < > and < > were shown to be more likely to continue to be engaged in the same occupation after pregnancy or delivery. These differences may be related to availability of the child-care leave program and other support resources, therefore, it may be important to establish social systems that enable all females, to use these support resources if they wish, and actively work, while delivering and parenting their children.