Fatality owing to pulmonary hemorrhage following pamidronate disodium administration in a neonate with osteogenesis imperfecta type 2: A case report.

We report the case of a patient with osteogenesis imperfecta (OI) who developed pulmonary hemorrhage 4 d after pamidronate disodium (PA) administration, despite a relatively stable respiratory status. Bisphosphonates are introduced to reduce osteoclast activity and are now widely used in patients with OI. Bisphosphonates are typically well-tolerated in children, and the standard of care involves cyclic intravenous administration of PA. However, in practice, there is limited experience with the use of PA for severe OI during the neonatal period, and its safety remains uncertain. This report aimed to describe the respiratory events potentially associated with PA in a neonatal patient with OI type 2, suggesting that serious life-threatening complications of pulmonary hemorrhage may occur after PA administration. Further studies are required to assess the relationship between pulmonary hemorrhage and PA administration, aiming to enhance prophylaxis measures.

Living-donor liver transplantation for methylmalonic acidemia patient with hepatocellular carcinoma: A case report and literature review.

BACKGROUND: Methylmalonic acidemia (MMA) is an autosomal recessive disorder caused by defects in propionyl-CoA (P-CoA) catabolism; of note, liver neoplasms rarely occur as a long-term complication of the disorder. Herein, we report the case of a patient with MMA and hepatocellular carcinoma (HCC) who was successfully treated with a living-donor liver transplant (LDLT) following prior kidney transplantation. CASE REPORT: A 25-year-old male patient with MMA underwent LDLT with a left lobe graft because of metabolic instability and liver neoplasms. He had presented with chronic symptoms of MMA, which had been diagnosed by genetic testing. Additionally, he had undergone living-donor kidney transplantation with his father as the donor due to end-stage kidney disease 6 years before the LDLT. He had an episode of metabolic decompensation triggered by coronavirus disease in 2019. Imaging studies revealed an intrahepatic neoplasm in the right hepatic lobe. Due to concerns about metabolic decompensation after hepatectomy, LDLT was performed using a left lobe graft obtained from the patient's mother. Pathological findings were consistent with the characteristics of well-to-moderately differentiated HCC. The postoperative course was uneventful, and the patient was discharged 48 days after the LDLT without any complications. At the 9-month follow-up, the patient's condition was satisfactory, with sufficient liver graft function and without metabolic decompensation. CONCLUSION: This case indicates that although HCC is a rare complication in patients with MMA, clinicians should be aware of hepatic malignancies during long-term follow-up.

Developments in the Management of Growth Hormone Deficiency: Clinical Utility of Somapacitan.

Growth hormone (GH) replacement therapy for growth hormone deficiency (GHD) in children and adults has for over 25 years, until recently, been administered as daily injections. This daily treatment regimen often incurs a burden to patients and caregivers, leading to high rates of non-adherence and, consequently, decreased treatment efficacy outcomes. To address this shortcoming, long-acting growth hormones (LAGHs) have been developed with the aim of reducing the burden of daily injections, thereby potentially improving treatment adherence and outcomes. Somapacitan (Sogroya®) (Novo Nordisk, Bagsværd, Denmark) is a LAGH currently approved for the treatment of adult and childhood GHD (AGHD and CGHD, respectively) in several countries. Other LAGHs, such as somatrogon (Ngenla®) (Pfizer, New York, United States) and lonapegsomatropin/TransCon GH (Skytrofa®) (Ascendis Pharma, Copenhagen, Denmark), are also currently approved and available for the treatment of CGHD in several countries. In this review, we will consider the method of protraction, pharmacokinetics (PK) and pharmacodynamics (PD), efficacy, and safety results of somapacitan in adult and pediatric trials and how these characteristics differ from those of the other aforementioned LAGHs. Additionally, the administration of somapacitan and timing of measurement of serum insulin-like growth factor-I (IGF-I) levels are summarized. Information on administration, advice on missed doses, and clinical guidelines are discussed, as well as identifying which patients are suitable for somapacitan therapy, and how to monitor and adjust dosing whilst on therapy.

Effective growth hormone replacement with once-weekly somapacitan in Japanese children with growth hormone deficiency: Results from REAL4, a phase 3 clinical trial.

OBJECTIVE: Somapacitan is a long-acting growth hormone (GH) derivative developed for the treatment of GH deficiency (GHD). This study evaluates the efficacy and tolerability of somapacitan in Japanese children with GHD after 104 weeks of treatment and after switch from daily GH. DESIGN: Subanalysis on Japanese patients from a randomised, open-labelled, controlled parallel-group phase 3 trial (REAL4, NCT03811535). PATIENTS AND MEASUREMENTS: Thirty treatment-naïve patients were randomised 2:1 to somapacitan (0.16 mg/kg/week) or daily GH (0.034 mg/kg/day) up to Week 52, after which all patients received somapacitan. Height velocity (HV; cm/year) at Weeks 52 and 104 were the primary measurements. Additional assessments included HV SD score (SDS), height SDS, bone age, insulin-like growth factor-I (IGF-I) SDS, and observer-reported outcomes. RESULTS: At Week 52, observed mean HV was similar between treatment groups (10.3 vs. 9.8 cm/year for somapacitan and daily GH, respectively). Similar HVs between groups were also observed at Week 104: 7.4 cm/year after continuous somapacitan treatment (soma/soma) and 7.9 cm/year after 1-year somapacitan treatment following switch from daily GH (switch). Other height-related endpoints supported continuous growth. IGF-I SDS increased in both groups with mean IGF-I SDS within -2 and +2 during the study. Somapacitan was well tolerated, one mild injection site reaction was reported, with no reports of injection site pain. Patient preference questionnaires showed that most patients and their caregivers (90.9%) who switched treatment at Week 52 preferred once-weekly somapacitan over daily GH treatment. CONCLUSIONS: Somapacitan showed sustained efficacy in Japanese children with GHD over 104 weeks and for 52 weeks after switching from daily GH. Somapacitan was well tolerated and preferred over daily GH.

The Population-Attributable Fractions of Small-for-Gestational-Age Births: Results from the Japan Birth Cohort Consortium.

A fetal growth restriction is related to adverse child outcomes. We investigated risk ratios and population-attributable fractions (PAF) of small-for-gestational-age (SGA) infants in the Japanese population. Among 28,838 infants from five ongoing prospective birth cohort studies under the Japan Birth Cohort Consortium, two-stage individual-participant data meta-analyses were conducted to calculate risk ratios and PAFs for SGA in advanced maternal age, pre-pregnancy underweight, and smoking and alcohol consumption during pregnancy. Risk ratio was calculated using modified Poisson analyses with robust variance and PAF was calculated in each cohort, following common analyses protocols. Then, results from each cohort study were combined by meta-analyses using random-effects models to obtain the overall estimate for the Japanese population. In this meta-analysis, an increased risk (risk ratio, [95% confidence interval of SGA]) was significantly associated with pre-pregnancy underweight (1.72 [1.42-2.09]), gestational weight gain (1.95 [1.61-2.38]), and continued smoking during pregnancy (1.59 [1.01-2.50]). PAF of underweight, inadequate gestational weight gain, and continued smoking during pregnancy was 10.0% [4.6-15.1%], 31.4% [22.1-39.6%], and 3.2% [-4.8-10.5%], respectively. In conclusion, maternal weight status was a major contributor to SGA births in Japan. Improving maternal weight status should be prioritized to prevent fetal growth restriction.

Evaluating the association between caesarean delivery and weight status in early childhood in a Japanese birth cohort study.

To examine whether the prevailing hypothesis of an association between caesarean section (CS) delivery method and increased weight status in early childhood is observed in Japanese. A total of 1277 mother-infant pairs from a prospective hospital-based mother-infant birth cohort that recruited women in their first trimester from May 2010 to November 2013 were included. We assessed the relationship between delivery method and weight status of delivered children at 1, 3 and 6 years of age. In total, 366 children (28.7%) were delivered by CS. Delivery by CS was not associated with body mass index (BMI) z-score (≥ 75 percentile) at age 1 year, (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.69-1.36), 3 years (OR 0.98, 95% CI 0.67-1.42), and 6 years (OR 0.71, 95% CI 0.45-1.12), and also showed no association with low weight status (< 25th percentile). Supplemental evaluations addressing the influence of preterm births, pre-pregnancy BMI, emergency CS, and modification by breastfeeding were consistent with the primary analyses. Our findings do not support the hypothesis that children born by CS are at risk of being overweight in childhood among the Japanese population.

Development of A Minimum Dataset for the Monitoring of Recombinant Human Growth Hormone (rhGH) Therapy Use in Children with Growth Hormone Deficiency (GHD) - A GloBE-Reg Initiative.

Introduction Although there are some recommendations in the literature on the assessments that should be performed in children on recombinant human growth hormone (rhGH) therapy, the level of consensus on these measurements is not clear. The objective of the current study was to identify the minimum dataset (MDS) that could be measured in a routine clinical setting across the world, aiming to minimise burden on clinicians and improve quality of data collection. Methods This study was undertaken by the GH Scientific Study Group (SSG) in GloBE-Reg, a new project that has developed a common registry platform that can support long-term safety and effectiveness studies of drugs. Twelve clinical experts from 7 international endocrine organisations identified by the GloBE-Reg Steering Committee, 2 patient representatives and representatives from 2 pharmaceutical companies with previous GH registry expertise collaborated to develop this recommendation. A comprehensive list of data fields routinely collected by each of the clinical and industry experts for children with GHD was compiled. Each member was asked to determine the: (1) Importance of the data field and (2) Ease of data collection. Data fields that achieved 70% consensus in terms of importance qualified for the MDS, provided <50% deemed the item difficult to collect. Results A total of 246 items were compiled and 27 removed due to redundancies, with 219 items subjected to the grading system. Of the 219 items, 111 achieved at least 70% consensus as important data to collect when monitoring children with GH deficiency (GHD) on rhGH treatment. Sixty-nine of the 219 items were deemed easy to collect. Combining the criteria of importance and ease of data collection, 63 met the criteria for the MDS. Several anomalies to the MDS rule were identified and highlighted for discussion, including whether the patients were involved in current or previous clinical trials, need for HbA1c monitoring, other past medical history, and adherence, enabling formulation of the final MDS recommendation of 43 items; 20 to be completed once, 14 every 6 months and 9 every 12 months. Conclusion In summary, this exercise performed through the GloBE-Reg initiative provides a recommendation of the minimum dataset requirement, collected through real-world data, for the monitoring of safety and effectiveness of rhGH in children with GHD, both for the current daily preparations and the newer long-acting growth hormone.

Anesthesia management protocol for liver transplantation as treatment for ornithine transcarbamylase deficiency.

BACKGROUND: Ornithine transcarbamylase deficiency is an X-linked genetic disorder that induces accumulation of ammonia in the liver and is the most common urea cycle disorder. The clinical manifestation of ornithine transcarbamylase deficiency is hyperammonemia that causes irreversible neurological damage. Liver transplantation is a curative therapy for ornithine transcarbamylase deficiency. The aim of this study is to suggest, from our previous experience, an anesthesia management protocol of liver transplantation for ornithine transcarbamylase deficiency, particularly focused on liver transplantation for cases with uncontrolled hyperammonemia. METHOD: We retrospectively reviewed our anesthesia-related experience in all cases of liver transplantation for ornithine transcarbamylase deficiency in our center. RESULTS: Twenty-nine liver transplantation cases for ornithine transcarbamylase deficiency were found between November 2005 and March 2021 in our center. Of these, 25 cases were stable through the perioperative period. However, 2 cases with carrier donor graft had hyperammonemia after liver transplantation. Another two cases had uncontrolled hyperammonemia before liver transplantation, even with continuous hemodialysis. They underwent life-saving liver transplantation. Their metabolic status stabilized after the anhepatic phase. CONCLUSION: Liver transplantation for cases with uncontrolled hyperammonemia can be performed with proper management. Second, liver transplantation with carrier donors should be avoided because of the risk of postoperative recurrence.

Effective GH Replacement With Somapacitan in Children With GHD: REAL4 2-year Results and After Switch From Daily GH.

CONTEXT: Somapacitan is a long-acting GH derivative for treatment of GH deficiency (GHD). OBJECTIVE: Evaluate the efficacy and tolerability of somapacitan in children with GHD after 2 years of treatment and after the switch from daily GH. DESIGN: A randomized, multinational, open-labelled, controlled parallel group phase 3 trial, comprising a 52-week main phase and 3-year safety extension (NCT03811535). SETTING: Eighty-five sites across 20 countries. PATIENTS: A total of 200 treatment-naïve prepubertal patients were randomized and exposed; 194 completed the 2-year period. INTERVENTIONS: Patients were randomized 2:1 to somapacitan (0.16 mg/kg/wk) or daily GH (0.034 mg/kg/d) during the first year, after which all patients received somapacitan 0.16 mg/kg/wk. MAIN OUTCOME MEASURES: Height velocity (HV; cm/year) at week 104. Additional assessments included HV SD score (SDS), height SDS, IGF-I SDS, and observer-reported outcomes. RESULTS: HV was sustained in both groups between 52 and 104 weeks. At week 104, mean (SD) for HV between weeks 52 and 104 was 8.4 (1.5) cm/year after continuous somapacitan treatment and 8.7 (1.8) cm/year after 1 year of somapacitan treatment following switch from daily GH. Secondary height-related endpoints also supported sustained growth. Mean IGF-I SDS during year 2 was similar between groups and within normal range (-2 to +2). Somapacitan was well tolerated, with no safety or tolerability issues identified. GH patient preference questionnaire results show that most patients and their caregivers (90%) who switched treatment at year 2 preferred once-weekly somapacitan over daily GH treatment. CONCLUSIONS: Somapacitan in children with GHD showed sustained efficacy and tolerability for 2 years, and after switching from daily GH. Patients/caregivers switching from daily GH expressed a preference for somapacitan. CLINICAL TRIAL REGISTRATION: NCT03811535.

The Association Between Eating Quickly and Excessive Gestational Weight Gain.

Objectives: Maintaining an appropriate gestational weight gain (GWG) is essential for a safe pregnancy and delivery. This study aimed to determine the association between the habit of eating quickly and the risk of excessive GWG. Methods: We administered a questionnaire on eating habits to 1246 pregnant Japanese women in their second to third trimesters. We categorized the participants into three groups according to their answers to the question "Do you eat quickly?" Group 1, "always" or "usually"; Group 2, "sometimes"; and Group 3, "rarely" or "never." We assessed GWG according to the "The Optimal Weight Gain Chart" (Ministry of Health, Labor and Welfare, Japan), and those who exceeded the criteria were considered "excessive." Logistic regression analysis was performed with the risk of excess GWG as the dependent variable and quick food intake as the independent variable, to obtain relevant odds ratios (ORs) and 95% confidence intervals (CIs). Model 1 was unadjusted, and Model 2 was adjusted for age, prepregnancy body mass index, energy intake, mother's educational attainment, household income, exercise habits, and childbearing experience. Results: The OR (95% CI) for Groups 2 and 3 in Model 1, compared with Group 1, was 0.80 (0.62-1.05) and 0.61 (0.43-0.88), respectively (p for trend = 0.047). In Model 2, the OR (95% CI) for Groups 2 and 3 were 0.73 (0.55-0.96) and 0.59 (0.40-0.86), respectively (p for trend = 0.003). Conclusion: These results suggest that quick food ingestion increases the risk of excessive GWG.

Association of Isolated Hypothyroxinemia and Subclinical Hypothyroidism With Birthweight: A Cohort Study in Japan.

Context: Isolated hypothyroxinemia (low maternal free thyroxine [FT4] in the absence of thyroid-stimulating hormone [TSH] elevation) and subclinical hypothyroidism (high TSH in the absence of FT4 elevation) during early pregnancy are common. However, there are limited data regarding pregnancy outcomes, particularly their association with birthweight. Objective: We assessed the association between isolated hypothyroxinemia and subclinical hypothyroidism during the first trimester and birthweight. Methods: Analyses were conducted using a database of pregnant women (n = 1105; median age, 35 years) who delivered at the National Center for Child Health and Development, a tertiary hospital in Tokyo. The primary outcomes included the rates of small for gestational age (SGA), large for gestational age (LGA), and low birth weight. Results: Of the 1105 pregnant women, 981 were classified into the euthyroidism group, 25 into the isolated hypothyroxinemia group, and 26 into the subclinical hypothyroidism group during the first trimester. The prevalence of SGA was significantly higher in isolated hypothyroxinemia and subclinical hypothyroidism groups than the euthyroidism group (28.0% and 19.2%, respectively, vs 5.7%; P < .01). The odds ratio with 95% CI for SGA was 12.51 (4.41-35.53) for isolated hypothyroxinemia and 4.44 (1.57-12.56) for subclinical hypothyroidism in a multivariable adjustment model. Isolated hypothyroxinemia and subclinical hypothyroidism were not significantly associated with LGA and low birth weight. Conclusion: Pregnant women with isolated hypothyroxinemia and subclinical hypothyroidism in the first trimester have an increased likelihood of SGA. Screening and careful perinatal checkups for isolated hypothyroxinemia and subclinical hypothyroidism may help identify pregnant women at high risk for SGA.

Comparison of physician- and self-assessed pubertal onset in Japanese children.

Introduction: Physical examinations to assess pubertal development are challenging in large epidemiological surveys. This study aimed to assess the reliability of judgment of pubertal onset in Japanese children by the original pubertal self-assessment sheet. Methods: A total of 144 children aged 10 or 12 years were recruited between March 2019 and September 2020 from the pediatric endocrine outpatient clinics of participating institutions. Agreement between the physician- and participantassessed pubertal onsets was determined using unweighted kappa (UK) and Gwet's agreement coefficient (AC1). Results: The physician's assessment of pubertal onset was in slight agreement with that of the self-assessment sheet in 10-year-old boys (UK: 0.23 and AC1: 0.14), whereas the agreement between the physician's assessment and self-assessment sheet results was good and the physician's assessment was fair (UK: 0.64 and AC1: 0.94) in 12-year-old boys. The physician's assessment of pubertal onset were in good and moderate agreement with the self-assessment sheet in 10-year-old girls (UK/AC1: 0.74/0.78, respectively). In 12-year-old girls, although it showed poor agreement with UK (0.46), there was a very good agreement with AC1 (0.88). Conclusions: Although self-assessment of breast development was in good agreement with that of the physician's assessment for determining pubertal onset in girls, large-scale epidemiological studies are difficult to conduct for adolescent boys, especially for those in the early pubertal stage.

Weekly Somapacitan in GH Deficiency: 4-Year Efficacy, Safety, and Treatment/Disease Burden Results From REAL 3.

CONTEXT: Growth hormone deficiency (GHD) in children is currently treated with daily injections of GH, which can be burdensome for patients and their parents/guardians. Somapacitan is a GH derivative in development for once-weekly treatment of GHD. OBJECTIVE: This work aimed to assess the efficacy and safety of somapacitan, and associated disease/treatment burden, after 4 years of treatment and 1 year after switching to somapacitan from daily GH. METHODS: This long-term safety extension of a multicenter, controlled phase 2 trial (NCT02616562) took place at 29 sites in 11 countries. Patients were prepubertal, GH-naive children with GHD. Fifty patients completed 4 years of treatment. Patients in the pooled group received somapacitan (0.04, 0.08, 0.16 mg/kg/week) for 1 year, followed by the highest dose (0.16 mg/kg/week) for 3 years. Patients in the switched group received daily GH 0.034 mg/kg/day for 3 years, then somapacitan 0.16 mg/kg/week for 1 year. Main outcome measures were height velocity (HV), change from baseline in HV SD score (SDS), change from baseline in height SDS, disease burden, and treatment burden for patients and parents/guardians. RESULTS: Changes from baseline in HV and HV SDS were similar and as expected in both groups. Observer-reported outcomes showed that patients and parents/guardians seem to have experienced a reduced treatment burden when switching from daily GH to somapacitan. Most parents/guardians (81.8%) strongly/very strongly preferred somapacitan over daily GH. CONCLUSIONS: Somapacitan showed similar efficacy and safety in patients who continued somapacitan treatment and those who switched from daily GH to somapacitan. Once-weekly injections may lead to a reduced treatment burden relative to once-daily injections. A plain-language summary of this work is available.

A questionnaire-based survey of medical conditions in adults with Prader-Willi syndrome in Japan: implications for transitional care.

Prader-Willi syndrome (PWS) is a multisystem disorder with increased mortality predominantly due to obesity-associated complications; therefore, the management of obesity has been centric to therapeutic strategies for PWS. Although a multidisciplinary team approach has been successful for this purpose during childhood, it is generally difficult to implement during adulthood because of the lack of a structured transitional care program. A more detailed understanding of the current medical conditions of adults with PWS is needed to establish this program; however, limited information is currently available on this issue in Japan. Accordingly, we performed a questionnaire-based survey on 425 patients with PWS. There were 162 adult patients aged 18 years or older with median body mass indexes (kg/m2) of 29.4 and 30.4 in males and females, respectively. The frequencies of type 2 diabetes mellitus (T2DM) and hypertension in adults with PWS were 40.4 and 19.4%, respectively. Growth hormone (GH) therapy during childhood correlated with lower rates of T2DM and hypertension during adulthood. Among adult patients, 54% were treated by pediatricians, whereas 44% were seen by internists with an endocrinologist/diabetologist being the most prevalent. Adult patients treated with GH during childhood showed a higher rate of being seen by pediatricians than those without, demonstrating that the multidisciplinary team approach, typically applied with GH therapy, may be continuously provided even after they reach adulthood. These results emphasize the importance of the seamless provision of the multidisciplinary team approach, which is of clinical importance for establishing an optimal transitional care program for PWS.

Somapacitan in children born small for gestational age: a multi-centre, open-label, controlled phase 2 study.

OBJECTIVE: Investigate efficacy, safety, and tolerability of 3 once-weekly somapacitan doses compared with daily growth hormone (GH) administration in short children born small for gestational age (SGA). DESIGN: Randomised, multi-centre, open-label, controlled phase 2 study comprising a 26-week main phase and a 4-year extension (NCT03878446). The study was conducted at 38 sites across 12 countries. 26-week main phase results are presented here.Sixty-two GH treatment-naïve, prepubertal short children born SGA were randomised and exposed; 61 completed the main phase. Three somapacitan doses (0.16 [n = 12], 0.20 [n = 13], 0.24 [n = 12] mg/kg/week) and 2 daily GH doses (0.035 [n = 12], 0.067 [n = 13] mg/kg/day) were administered subcutaneously. RESULTS: After 26 weeks of treatment, the estimated mean annualised height velocity (HV) was 8.9, 11.0, and 11.3 cm/year for somapacitan 0.16, 0.20, and 0.24 mg/kg/week, respectively, compared to 10.3 and 11.9 cm/year for daily GH 0.035 and 0.067 mg/kg/day. Changes from baseline in HV standard deviation score (SDS), height SDS, and insulin-like growth factor I (IGF-I) SDS showed similar dose-dependent responses. Exposure-response modelling indicated the greatest efficacy correlated with the highest somapacitan exposure. Similar safety and tolerability were demonstrated for all weekly somapacitan and daily GH doses. CONCLUSIONS: Based on the totality of data on improvements in height-based parameters combined with exposure-response analyses, somapacitan 0.24 mg/kg/week appears most efficacious, providing similar efficacy, safety, and tolerability as daily GH 0.067 mg/kg/day in short children born SGA after 26 weeks of treatment.

International Consensus Guideline on Small for Gestational Age: Etiology and Management From Infancy to Early Adulthood.

This International Consensus Guideline was developed by experts in the field of small for gestational age (SGA) of 10 pediatric endocrine societies worldwide. A consensus meeting was held and 1300 articles formed the basis for discussions. All experts voted about the strengths of the recommendations. The guideline gives new and clinically relevant insights into the etiology of short stature after SGA birth, including novel knowledge about (epi)genetic causes. Further, it presents long-term consequences of SGA birth and also reviews new treatment options, including treatment with gonadotropin-releasing hormone agonist (GnRHa) in addition to growth hormone (GH) treatment, as well as the metabolic and cardiovascular health of young adults born SGA after cessation of childhood GH treatment in comparison with appropriate control groups. To diagnose SGA, accurate anthropometry and use of national growth charts are recommended. Follow-up in early life is warranted and neurodevelopment evaluation in those at risk. Excessive postnatal weight gain should be avoided, as this is associated with an unfavorable cardiometabolic health profile in adulthood. Children born SGA with persistent short stature < -2.5 SDS at age 2 years or < -2 SDS at 3 to 4 years of age, should be referred for diagnostic workup. In case of dysmorphic features, major malformations, microcephaly, developmental delay, intellectual disability, and/or signs of skeletal dysplasia, genetic testing should be considered. Treatment with 0.033 to 0.067 mg GH/kg/day is recommended in case of persistent short stature at age of 3 to 4 years. Adding GnRHa treatment could be considered when short adult height is expected at pubertal onset. All young adults born SGA require counseling to adopt a healthy lifestyle.

Association Between Smoking and Hypertension in Pregnancy Among Japanese Women: A Meta-analysis of Birth Cohort Studies in the Japan Birth Cohort Consortium (JBiCC) and JECS.

BACKGROUND: Recent literature suggest the effect of maternal smoking on risk of hypertensive disorders in pregnancy (HDP) and preeclampsia may differ by ethnicity; however, studies on Asians are limited. METHODS: We investigated the association of maternal smoking with HDP and preeclampsia using a common analysis protocol to analyze the association in six birth cohorts participating in a Japanese consortium of birth cohorts (JBiCC). Results were compared with-published results from cohorts not included in this consortium, and, where possible, we produced a meta-analysis including these studies. RESULTS: Meta-analysis of four cohort studies including 28,219 participants produced an odds ratio (OR) of 1.24 (95% confidence interval [CI], 0.88-1.87) for the effect of smoking beyond early pregnancy compared to women who did not smoke during pregnancy. These results combined with those from the Japan Environment and Children's Study (JECS) yielded an OR of 1.19 (95% CI, 1.00-1.43, P = 0.056). Meta-analysis results for categories of smoking volume were insignificant, but when combined with JECS yielded an OR of 0.86 (95% CI, 0.65-1.12) for smoking 1-4 cigarettes, 1.25 (95% CI, 0.98-1.60) for smoking 5-9 cigarettes, and 1.27 (95% CI, 1.04-1.54) for smoking 10 or more cigarettes per day. All effects were insignificant for preeclampsia. CONCLUSION: Our results suggest that the protective effects of smoking longer and smoking more on HDP and preeclampsia repeatedly observed among Europeans and North Americans likely do not hold for the Japanese.