Sex determination by ultrasonography prior to artificial breeding of the pufferfish Arothron manilensis (Tetraodontiformes, Tetraodontidae).

Artificial breeding was induced in the pufferfish Arothron manilensis following ultrasonographic sex determination. Hormonal treatment of mature male and female specimens followed the collection (and measurement) of fully developed eggs by cannulation. Fertilized eggs (0.85 ± 0.02 mm diameter) were spherical, demersal and individually adhesive. Hatching occurred 5 days after fertilization, larvae being 2.23 ± 0.15 mm in total length and 2.08 ± 0.14 mm in notochord length. The larvae had all died within 14 days of hatching. To improve artificial breeding techniques for A. manilensis, it is necessary to determine more appropriate timing for hormone injection, as well as feeding nutrient-enhanced SS type Brachionus sp. to newly hatched larvae.

A Phase I Study of TRK-250, a Novel siRNA-Based Oligonucleotide, in Patients with Idiopathic Pulmonary Fibrosis.

Purpose: TRK-250 is a novel single-stranded oligonucleotide carrying a human Transforming growth factor-beta 1-targeting siRNA motif tethered by two proline linkers. Nonclinical studies have shown that TRK-250 may have potency to prevent the progression of pulmonary fibrosis. Herein, a phase I study was conducted to investigate the safety and pharmacokinetics (PKs) of TRK-250 in patients with idiopathic pulmonary fibrosis (IPF). Method: In the phase I study, 34 IPF patients were partially randomized to receive a placebo or TRK-250 in 4 single doses of 2, 10, 30, and 60 mg or multiple rising doses of 10, 30, and 60 mg once per week for 4 weeks by oral inhalation. For both the single- and multiple-dose studies, the primary endpoint was safety, and the secondary endpoint was PKs. Result: In all IPF patients who orally inhaled TRK-250, no significant drug-related adverse events (AEs) were observed. The AEs were mild or moderate, except for one severe case with acute exacerbation. One of the more common AEs was coughing. One patient discontinued treatment before the last dose because of coughing. There were no medically important findings related to safety endpoints based on clinical laboratory data (clinical chemistry, hematology, or urinalysis), vital signs data, electrocardiogram data, physical examination findings, pulse oximetry data, spirometry data, or diffusing capacity of the lung for carbon monoxide data. All the bioanalytical results of PKs in the blood were below the lower limit of quantification. Conclusions: Both the single and multiple doses of TRK-250 were safe and well tolerated in this first study done in IPF patients. Furthermore, TRK-250 was not detected in the systemic circulation following inhalation, indicating low or virtually nonexistent systemic exposure. This study is registered at ClinicalTrials.gov with identifier number NCT03727802.

Tandem spawning and development in the African freshwater pufferfish Tetraodon schoutedeni.

To advance breeding techniques for the African freshwater pufferfish Tetraodon schoutedeni and observe tandem spawning closely, we monitored the reproduction of captive individuals. Eight spawning sessions (stable water temperature 24-25°C; daily light period 07:00-19:00) occurred between May 2016 and November 2017. After 65-150 min of tandem swimming (the male biting and clinging to the female's abdomen), 3-50 spherical, weakly adhesive eggs were spawned, being scattered onto the sandy substrate or water plants. The removal of cohabitants (potentially eating spawned eggs) and provision of small initial food items, such as small-type Brachionus spp., for larval fish were essential for successful breeding.

Seawater fish use an electrogenic boric acid transporter, Slc4a11A, for boric acid excretion by the kidney.

Boric acid is a vital micronutrient in animals; however, excess amounts are toxic to them. Little is known about whole-body boric acid homeostasis in animals. Seawater (SW) contains 0.4 mM boric acid, and since marine fish drink SW, their urinary system was used here as a model of the boric acid excretion system. We determined that the bladder urine of a euryhaline pufferfish (river pufferfish, Takifugu obscurus) acclimated to fresh water and SW contained 0.020 and 19 mM of boric acid, respectively (a 950-fold difference), indicating the presence of a powerful excretory renal system for boric acid. Slc4a11 is a potential animal homolog of the plant boron transporter BOR1; however, mammalian Slc4a11 mediates H+ (OH-) conductance but does not transport boric acid. We found that renal expression of the pufferfish paralog of Slc4a11, Slc4a11A, was markedly induced after transfer from fresh water to SW, and Slc4a11A was localized to the apical membrane of kidney tubules. When pufferfish Slc4a11A was expressed in Xenopus oocytes, exposure to media containing boric acid and a voltage clamp elicited whole-cell outward currents, a marked increase in pHi, and increased boron content. In addition, the activity of Slc4a11A was independent of extracellular Na+. These results indicate that pufferfish Slc4a11A is an electrogenic boric acid transporter that functions as a B(OH)4- uniporter, B(OH)3-OH- cotransporter, or B(OH)3/H+ exchanger. These observations suggest that Slc4a11A is involved in the kidney tubular secretion of boric acid in SW fish, probably induced by the negative membrane potential and low pH of urine.

Tetrodotoxin/Saxitoxin Accumulation Profile in the Euryhaline Marine Pufferfish Chelonodontops patoca.

Marine Takifugu pufferfish, which naturally possess tetrodotoxins (TTXs), selectively take up and accumulate TTXs, whereas freshwater Pao pufferfish, which naturally possess saxitoxins (STXs), selectively take up and accumulate STXs. To further clarify the TTXs/STXs selectivity in pufferfish, we conducted a TTX/STX administration experiment using Chelonodontops patoca, a euryhaline marine pufferfish possessing both TTXs and STXs. Forty nontoxic cultured individuals of C. patoca were divided into a seawater group (SW, acclimated/reared at 33‱ salinity; n = 20) and a brackish water group (BW, acclimated/reared at 8‱ salinity; n = 20). An aqueous TTX/STX mixture was intrarectally administered (both at 7.5 nmol/fish), and five individuals/group were analyzed after 1-48 h. Instrumental toxin analyses revealed that both TTX and STX were taken up, transferred, and retained, but more STX than TTX was retained in both groups. TTX gradually decreased and eventually became almost undetectable in the intestinal tissue, while STX was retained at ~5-10% of the dose level, and only STX showed transient transfer in the liver. The BW group showed a faster decrease/disappearance of TTX, greater STX retention in the intestine, and greater STX transient transfer to the liver. Thus, C. patoca appears to more easily accumulate STXs than TTXs, especially under hypoosmotic conditions.

Tetrodotoxin/Saxitoxins Selectivity of the Euryhaline Freshwater Pufferfish Dichotomyctere fluviatilis.

The present study evaluated differences in the tetrodotoxin (TTX)/saxitoxins (STXs) selectivity between marine and freshwater pufferfish by performing in vivo and in vitro experiments. In the in vivo experiment, artificially reared nontoxic euryhaline freshwater pufferfish Dichotomyctere fluviatilis were intrarectally administered a mixture of TTX (24 nmol/fish) and STX (20 nmol/fish). The amount of toxin in the intestine, liver, muscle, gonads, and skin was quantified at 24, 48, and 72 h. STX was detected in the intestine over a long period of time, with some (2.7-6.1% of the given dose) being absorbed into the body and temporarily located in the liver. Very little TTX was retained in the body. In the in vitro experiments, slices of intestine, liver, and skin tissue prepared from artificially reared nontoxic D. fluviatilis and the marine pufferfish Takifugu rubripes were incubated in buffer containing TTX and STXs (20 nmol/mL each) for up to 24 or 72 h, and the amount of toxin taken up in the tissue was quantified over time. In contrast to T. rubripes, the intestine, liver, and skin tissues of D. fluviatilis selectively took up only STXs. These findings indicate that the TTX/STXs selectivity differs between freshwater and marine pufferfish.

Complete mitochondrial genomes of the Southeast Asian freshwater pufferfishes, Pao abei (Roberts, 1998) and Pao suvattii (Sontirat and Soonthornsatit, 1985) (Tetraodontiformes: Tetraodontidae) and an insight into the taxonomic status of Pao species.

The complete mitochondrial genomes of the Southeast Asian freshwater pufferfishes, Pao abei and Pao suvattii, were reconstructed using the MGISEQ platform. The genomes were 16,448 bp and 16,449 bp in length, each made up of 37 mitochondrial genes (13 CDSs, 22 tRNAs, and two rRNAs) and putative control region. It is suggested that an accumulation of complete mitochondrial genome sequences can contribute to resolve the taxonomic status of Pao species.

Phylogeny and Toxin Profile of Freshwater Pufferfish (Genus Pao) Collected from 2 Different Regions in Cambodia.

The species classification of Cambodian freshwater pufferfish is incomplete and confusing, and scientific information on their toxicity and toxin profile is limited. In the present study, to accumulate information on the phylogeny and toxin profile of freshwater pufferfish, and to contribute to food safety in Cambodia, we conducted simultaneous genetic-based phylogenetic and toxin analyses using freshwater pufferfish individuals collected from Phnom Penh and Kratie (designated PNH and KTI, respectively). Phylogenetic analysis of partial sequences of three mitochondrial genes (cytochrome b, 16S rRNA, and cytochrome c oxidase subunit I) determined for each fish revealed that PNH and KTI are different species in the genus Pao (designated Pao sp. A and Pao sp. B, respectively). A partial sequence of the nuclear tributyltin-binding protein type 2 (TBT-bp2) gene differentiated the species at the amino acid level. Instrumental analysis of the toxin profile revealed that both Pao sp. A and Pao sp. B possess saxitoxins (STXs), comprising STX as the main component. In Pao sp. A, the toxin concentration in each tissue was extremely high, far exceeding the regulatory limit for STXs set by the Codex Committee, whereas in Pao sp. B, only the skin contained high toxin concentrations. The difference in the STX accumulation ability between the two species with different TBT-bp2 sequences suggests that TBT-bp2 is involved in STX accumulation in freshwater pufferfish.

Breastfeeding and risk of food allergy: A nationwide birth cohort in Japan.

BACKGROUND: Although breastfeeding has been well-established as the preferred method for infant nutrition, its prophylactic effects on food allergy remain controversial. Infantile eczema has been linked to food allergy via percutaneous sensitization; however, this relationship has not been considered in previous studies. We aimed to uncover the prophylactic effects of breastfeeding on food allergy, focusing on eczema-mediated percutaneous sensitization. METHODS: This retrospective cohort study was based on 46,616 children from the Longitudinal Survey of Newborns in the 21st Century in Japan, begun in 2001. We classified participants into three groups based on infant feeding practices (exclusive breastfeeding, partial breastfeeding including only colostrum, and formula feeding only) and used information from at least one outpatient visit for food allergy during two observation periods (age 6-18 months and age 6-66 months) as health outcomes. We performed log-binomial regression analysis adjusted for potential confounders and stratified analysis according to infantile eczema status. RESULTS: Compared with formula feeding, partial breastfeeding including only colostrum reduced the risk of food allergy only in children with infantile eczema, (RR = 0.66, 95% CI: 0.46, 0.96 for age 6-66 months), whereas exclusive breastfeeding increased this risk in those without infantile eczema (RR = 2.41, 95% CI: 1.40, 4.15, age 6-66 months). The prophylactic effects of breastfeeding on food allergy in the infantile eczema group increased with shorter breastfeeding duration. CONCLUSIONS: Our results showed that breastfeeding, especially colostrum, had prophylactic effects on food allergy only among high-risk children with infantile eczema whereas prolonged breastfeeding increased the risk of food allergy.

Correction of Humpback Deformities in Patients With Scaphoid Nonunion Using 1,2-Intercompartmental Supraretinacular Artery Pedicled Vascularized Bone Grafting With a Dorsoradial Approach.

PURPOSE: Although 1,2-intercompartmental supraretinacular artery (1,2-ICSRA)-based vascularized bone grafting (VBG) has gained popularity in the treatment of scaphoid nonunion, correcting humpback deformities with this technique remains challenging. The purpose of this retrospective study was to determine the possibility of correcting humpback deformities using a 1,2-ICSRA VBG with a dorsoradial approach. METHODS: We treated 25 patients with scaphoid nonunion using a 1,2-ICSRA VBG between January 2007 and December 2017. For those with a humpback deformity, we performed vascularized wedge grafting from the dorsoradial side, instead of inlay bone grafting from the dorsal or volar side of the scaphoid. After excluding patients with scaphoid nonunion without a humpback deformity and those followed up for less than 6 months, we reviewed the imaging results and union rate in the remaining 19 patients (18 men and 1 woman). The nonunion sites and patient distribution were as follows: proximal one-third, 2; waist, 16; and distal one-third, 1. RESULTS: The union rate at the last follow-up performed a minimum of 6 months after the intervention was 94.7%. The correction was adequate in 17 patients and inadequate in 2 patients. The lateral intrascaphoid, radiolunate, and scapholunate angles were improved. CONCLUSIONS: Humpback and dorsal intercalated segmental instability deformities can be corrected adequately using a 1,2-ICSRA VBG with a dorsoradial approach. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Association of early daycare attendance with allergic disorders in children: a longitudinal national survey in Japan.

The association between early daycare attendance and risk of allergic diseases remains inconclusive. Therefore, we examined the association among Japanese children on a long-term basis using a nationwide longitudinal survey data. We estimated the association between daycare attendance at age 6 or 18 months and allergy development using information on outpatient visits for atopic dermatitis (AD), food allergy (FA), and asthma and admission for asthma up to 12 years of age as a proxy for developing these diseases, with multilevel logistic regression. Early daycare attendance was associated with increased odds of AD at ages 2.5-3.5 years: the adjusted odds ratio (OR) was 1.34 [95% CI: 1.21, 1.47]. The association with FA was equivocal. The odds of asthma was increased before age 3.5 years and afterwards decreased: the adjusted ORs were 1.60 [1.44, 1.77] for ages 1.5-2.5 years and 0.77 [0.69, 0.87] for ages 5.5-7 years. The effect of early daycare attendance depends on the type of allergies.

Urgent intubation without neuromuscular blocking agents and the risk of tracheostomy.

Neuromuscular blocking agents play a significant role in improving the success rate for urgent intubation, although there is limited evidence about the effect on subsequent outcomes, such as the incidence of tracheostomy. In this retrospective cohort study, we aimed to examine the association between avoidance of neuromuscular blocking agents for urgent tracheal intubation and incidence of tracheostomy among patients in the intensive care unit (ICU). The setting of this study was an eight-bed ICU at a tertiary-care hospital in Okayama, Japan. We included patients who underwent urgent tracheal intubation at the emergency department or the ICU and were admitted to the ICU between April 2013 and November 2017. We extracted data on methods and medications of intubation, predictors for difficult intubation, Cormack-Lehane grade, patient demographics, primary diagnoses, reintubation. We estimated odds ratios and their 95% confidence intervals for elective tracheostomy during the ICU stay using logistic regression models. Of 411 patients, 46 patients underwent intubation without neuromuscular blocking agents and 61 patients underwent tracheostomy. After adjusting for potential confounders, patients who avoided neuromuscular blocking agents had more than double the odds of tracheostomy (odds ratio 2.59, 95% confidence interval 1.06-6.34, p value = 0.04). When stratifying the subjects by risk status for tracheostomy, the association was more pronounced in high-risk group, while we observed less significant association in the low-risk group. Avoidance of neuromuscular blocking agents for urgent intubation increases the risk of tracheostomy among emergency patients, especially those who have a higher risk for tracheostomy.

Combined effects of body mass index and unhealthy behaviors on disability in older Japanese adults: the Okayama study.

BACKGROUND: Body mass index (BMI) is a significant predictor of functional disability in older adults. However, when evaluated, the association between BMI and incident functional disability, considering behaviors only as covariates or not, may not be appropriate. The primary purpose of the study was to investigate the combined effects of BMI and unhealthy behaviors on the risk of incident functional disability. METHODS: This was a retrospective cohort study that took place in Okayama City, Japan. Data on BMI and unhealthy behaviors were obtained using the health check-up questionnaire. The certification of Long-Term Care Insurance was used to measure functional disability. Cox proportional hazard models were used; adjusted hazard ratios (HRs) with 95% confidence interval (CI) were calculated for incidence of functional disability across categories of BMI and number of unhealthy behaviors. RESULTS: The relationship between BMI and incident functional disability was U-shaped (HR = 1.18, 95% CI [1.11-1.25], among the underweight range; and 1.26 [1.19-1.34] among the obesity range), and its risk was significantly higher within the normal-to-overweight range of BMI values with co-occurring unhealthy behaviors (with normal weight range and one, 1.17 [1.01-1.21]; two, 1.29 [1.18-1.41]; and three or four unhealthy behaviors 1.38 [1.24-1.54]; as well as among overweight range and one, 1.16 [1.05-1.27]; two, 1.26 [1.15-1.38]; and three or four unhealthy behaviors, 1.47 [1.31-1.64]). In each BMI category, the risk of incident functional disability increased with increasing number of unhealthy behaviors (p < 0.05 for linear tread), with the highest risk (1.87 [1.58-2.20]) occurring in combination with at least three unhealthy behaviors with BMI ≥ 27.5, for both sexes (2.20 [1.64-2.92] in men and 1.66 [1.35-2.04] in women). CONCLUSION: It is necessary to consider the combined effects of BMI and behaviors on incident functional disability. Furthermore, interventions targeting multiple behaviors should be considered as such interventions may offer greater benefits than simple interventions.

Contrasting Toxin Selectivity between the Marine Pufferfish Takifugu pardalis and the Freshwater Pufferfish Pao suvattii.

To clarify the differences in toxin selectivity between marine and freshwater pufferfish, we conducted experiments in artificially reared nontoxic specimens of Takifugu pardalis (marine) and Pao suvattii (freshwater) using tetrodotoxin (TTX) and paralytic shellfish poison (PSP; decarbamoylsaxitoxin (dcSTX) or saxitoxin (STX)). T. pardalis specimens were administered feed homogenate containing TTX or dcSTX (dose of toxin, 55.2 nmol/fish) and P. suvattii specimens were administered feed homogenate containing TTX + STX (dose of each toxin, 19.2 nmol/fish) by oral gavage. The toxin content in the intestine, muscle, skin, liver, and gonads was quantified after 24 and 48 or 72 h. In T. pardalis, TTX administered into the intestine was absorbed into the body and transferred and retained mainly in the skin and liver, while dcSTX was hardly retained in the body, although it partly remained in the intestine. In strong contrast, in P. suvattii, little TTX remained in the body, whereas STX was absorbed into the body and was transferred and retained in the ovary and skin. The findings revealed that TTX/PSP selectivity differs between the marine species T. pardalis and the freshwater species P. suvattii. T. pardalis, which naturally harbors TTX, selectively accumulates TTX, and P. suvattii, which naturally harbors PSP, selectively accumulates PSP.

Alcohol consumption and incident dementia in older Japanese adults: The Okayama Study.

AIM: To evaluate the association between the amount and frequency of alcohol consumption and incident dementia in older Japanese adults using large sample size data over a long follow-up period. METHODS: This was a retrospective cohort study carried out in Japan. A total of 53 311 older adults were followed from 2008 to 2014. A health checkup questionnaire was used to assess the amount and frequency of alcohol consumption. The Dementia Scale of long-term care insurance was used as a measure of incident dementia. Cox proportional hazards models were used to calculate adjusted hazard ratios, with their 95% confidence intervals, for the incidence of dementia across the categories of alcohol consumption by sex. RESULTS: During a 7-year follow-up period, 14 479 participants were regarded as having incident dementia. Compared with non-drinkers, the multivariate adjusted hazard ratios for participants with alcohol consumption ≤2 units per day, occasionally (0.88, 95% CI 0.81-0.96 in men and 0.84, 95% 0.79-0.90 in women) and daily (0.79, 95% 0.73-0.85 in men and 0.87, 95% 0.78-0.97 in women) were statistically significant, and the difference between occasional and daily consumption was only statistically significant in men; however, for participants with alcohol consumption >2 units per day, occasionally (0.91, 95% 0.71-1.16 in men and 1.09, 95% 0.72-1.67 in women) and daily (0.89, 95% 0.81-1.00 in men and 1.16, 95% 0.84-1.81 in women) were not significant. CONCLUSIONS: Alcohol consumption of ≤2 units per day, occasionally or daily, could reduce the risk of incident dementia, with greater benefit for men with such daily consumption. Geriatr Gerontol Int 2019; 19: 740-746.

Physical activity and incident dementia in older Japanese adults: The Okayama study.

OBJECTIVE: To evaluate the association between regular physical activity and the risk of incident dementia in older Japanese adults. METHODS: This was a retrospective cohort study performed in Okayama City, Japan. Overall, 51 477 older Japanese adults were followed from 2008 to 2014. A health checkup questionnaire was used to assess regular physical activity. The Dementia Scale of long-term care insurance was used as a measure of incident dementia. Cox proportional hazard models were used to calculate adjusted hazard ratios, with their 95% confidence intervals, for the incidence of dementia across the categories of physical activity. RESULTS: During a 7-year follow-up, 13 816 subjects were considered as having incident dementia. Compared with participants who performed physical activity less than or equal to one time per week, the multivariate adjusted hazard ratio values (95% confidence intervals) for participants who performed physical activity greater than or equal to two times per week but not every day and those who performed physical activity every day were 0.79 (0.75-0.84) and 0.94 (0.89-0.98), respectively. The interaction of physical activity and sex was statistically significant (P < .01). In subgroup analysis, the multivariate-adjusted hazard ratio values (95% confidence intervals) remained low, at 0.76 (0.70-0.84) in males and 0.81 (0.76-0.87) in females who performed physical activity greater than or equal to two times per week but not every day; they were 0.82 (0.76-0.89) in males and 1.01 (0.95-1.07) in females who performed physical activity every day. CONCLUSIONS: Regular physical activity could reduce the risk of incident dementia in older Japanese adults, except females who performed physical activity every day.

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

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

Long-term exposure to fine particulate matter and natural-cause and cause-specific mortality in Japan.

BACKGROUND: A number of studies have linked long-term exposure to particulate matter with aerodynamic diameter <2.5 µm (PM2.5) with mortality, but most of these studies were conducted in Europe and North America. Studies in Asian countries had been conducted at relatively high exposures. We evaluated the association of long-term exposure to PM2.5 and natural-cause and cause-specific mortality in Japan, where PM2.5 levels are relatively low compared with levels in other Asian countries. METHODS: A cohort of 75,531 participants underwent basic health checkups in Okayama City in 2006 or 2007. We followed the participants until the end of 2016. Average PM2.5 levels from 2006 to 2010 were obtained and assigned to the participants by geographical location. We used the Cox proportional hazard models to estimate hazard ratios for a 5-µg/m3 increase in PM2.5 levels for natural-cause or cause-specific mortality, adjusting for potential confounders. RESULTS: PM2.5 exposure was associated with increased risk of mortality; the hazard ratios were 1.29 (95% confidence interval = 1.18, 1.41) for mortality from natural causes, 1.16 (1.02, 1.32) for cardiorespiratory mortality, and 1.63 (1.13, 2.34) for lung cancer mortality. PM2.5 exposure was more strongly associated with cardiorespiratory mortality from hypertension, pneumonia and influenza, and chronic obstructive pulmonary disease than with ischemic heart disease or cerebrovascular disease. Elderly participants and smokers tended to have higher effect estimates. CONCLUSION: Long-term exposure to PM2.5 can increase the risk of natural-cause, cardiorespiratory, and lung cancer mortality in Japan.

Population-based longitudinal study showed that children born small for gestational age faced a higher risk of hospitalisation during early childhood.

AIM: We examined the effects of being born small for gestational age (SGA) on the risk of being hospitalised for common diseases during childhood. METHODS: This Japanese nationwide, population-based longitudinal survey followed babies born before 42 weeks of gestation from 10 to 17 January and from 10 to 17 July 2001, using data from the Government's Longitudinal Survey of Babies in the 21st Century. Our study followed 41 268 children until 5.5 years of age: 39 107 full term (8.7% SGA) and 2161 preterm (15.5% SGA). We evaluated the relationship between SGA status and hospitalisation using their history of hospitalisation for common diseases and comparing full-term or preterm births. Logistic regression analysis, adjusted for potential confounders, estimated the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The full-term and preterm children who were born SGA were more likely to be hospitalised during infancy and early childhood than those born non SGA. The ORs for hospitalisation from six months to 18 months of age were 1.23 (95% CI: 1.10-1.37) for full-term and 1.67 (95% CI: 1.23-2.25) for preterm subjects. Higher risks of hospitalisation due to bronchitis, pneumonia, bronchial asthma and diarrhoea were also observed. CONCLUSION: Being born SGA was associated with all-cause and cause-specific hospitalisation in early childhood, particularly for term infants.

Associations of gestational age with child health and neurodevelopment among twins: A nationwide Japanese population-based study.

BACKGROUND: The prevalence of multiple births has recently increased. However, the association between gestational age and long-term morbidity among twins remains unclear. AIMS: To examine the association of gestational age with child health and neurological development in early childhood among twins. STUDY DESIGN: Population-based longitudinal study. SUBJECTS: We included 947 children from 479 pairs of twins with information on gestational age. OUTCOME MEASURES: Hospitalization was used as an indicator of physical health, and responses to questions about age-appropriate behaviors were used as an indicator of neurobehavioral development. We conducted binomial log-linear regression analyses, controlling for both child and maternal variables in the model. We accounted for correlations within the pairs with generalized estimating equations. RESULTS: The early term group (i.e., 37 to 38 weeks of gestation) had a lower risk of poor child health and unfavorable neurodevelopment compared with the full term group (≥39 weeks of gestation) and preterm group (<37 weeks of gestation). Compared with the early term group, the adjusted risk ratios for hospitalization for all causes during the period from 7 to 18 months of age was 2.2 (95% confidence interval: 1.3-3.8) for very preterm children (<32 weeks of gestation), 1.1 (0.8-1.6) for moderately and late preterm children (32 to 36 weeks of gestation), and 1.8 (1.0-3.2) for full term children. CONCLUSION: We observed a U-shaped association of gestational age with child health and neurodevelopment. The early term group had the lowest risk of poor outcomes among twins.