Maternal Prepregnancy Body Mass Index, Gestational Weight Gain, and Risk of Adverse Perinatal Outcomes in Taiwan: A Population-Based Birth Cohort Study.

Epidemiological studies have shown that maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) are associated with increased risk of perinatal outcomes. However, the evidence of such associations in Asian populations is limited. We conducted a secondary data analysis to investigate the relationships of prepregnancy BMI and GWG with the risks of adverse perinatal outcomes, including gestational diabetes (GDM), gestational hypertension (GHTN), preeclampsia, cesarean delivery, preterm birth, low birth weight (LBW), and macrosomia. We categorized prepregnancy BMI by the WHO classification and GWG by the Institute of Medicine guidelines. We performed adjusted logistic regression models to estimate the odds ratios of adverse perinatal outcomes. A total of 19,052 women were included; prepregnancy overweight and obesity were associated with a greater risk of GDM, GHTN, preeclampsia, cesarean delivery, preterm birth, and macrosomia. Women with excessive GWG had a greater risk of GHTN, preeclampsia, cesarean delivery, and macrosomia. In conclusion, regardless of the range of GWG during pregnancy, maternal prepregnancy BMI is significantly associated with the risk of adverse perinatal outcomes in Taiwan. Public health attention regarding obesity reduction before conception and prenatal counseling for optimal GWG is needed to mitigate the risk of poor perinatal outcomes.

AKR1D1 and CYP7B1 mutations in patients with inborn errors of bile acid metabolism: Possibly underdiagnosed diseases.

BACKGROUND: Inborn errors of bile acid metabolism (IEBAM) cause rare but treatable genetic disorders that can present as neonatal cholestasis or neurological diseases. Without timely primary bile acid treatment, patients may develop liver failure early in life. This study aimed to analyze the types and treatment outcomes of IEBAM in Taiwanese infants and document the allele frequency of CYP7B1 hot spot mutations in the population. METHODS: Urine samples from patients with infantile intrahepatic cholestasis and suspected IEBAM were subjected to urinary bile acid analysis by gas chromatography-mass spectrometry (GC/MS). Genetic diagnoses were made using direct sequencing or next-generation sequencing. We also tested healthy control subjects for a probable hot spot point mutation of CYP7B1. RESULTS: Among the 75 patients with infantile intrahepatic cholestasis tested during 2000 -2016, three had ∆4-3-oxosteroid 5ß-reductase deficiency with AKR1D1 mutations, and three had oxysterol-7α-hydroxylase deficiency with CYP7B1 mutation. Two patients with ∆4-3-oxosteroid 5ß-reductase deficiency were successfully treated with cholic acid. The three unrelated infants with oxysterol 7α-hydroxylase deficiencies had the same p.R112X homozygous CYP7B1 mutation. Two had mild renal or neurological involvement. Among 608 healthy control subjects, the allele frequency of the heterozygous mutation for p.R112X was 2/1216 (0.16%). The only surviving patient with oxysterol 7α-hydroxylase deficiency recovered from liver failure after chenodeoxycholic acid (CDCA) treatment beginning at 3 months of age. CONCLUSION: Distinct types of IEBAM disease were found in the Taiwanese population. Patients with early diagnosis and early treatment had a favorable outcome. IEBAM prevalence rates may be higher than expected due to the presence of heterozygous mutations in the general population.

Baseline Level of Hepatitis B Core Antibody Predicts Spontaneous Hepatitis B e Antigen (HBeAg) Seroconversion in HBeAg-Positive Children With a Normal Alanine Aminotransferase Level.

It is not clear whether baseline hepatitis B core antibody (anti-HBc) level in hepatitis B e antigen (HBeAg)-positive children with a normal alanine aminotransferase (ALT) level is predictive of spontaneous HBeAg seroconversion. We investigated the correlation between anti-HBc level and the natural course of chronic hepatitis B (CHB) virus (HBV) infection in children, particularly the ability of baseline anti-HBc level to predict spontaneous HBeAg seroconversion during long-term follow-up. HBeAg-positive children with untreated CHB and a normal ALT level were followed longitudinally. Anti-HBc level was determined by double-sandwich immunoassay. Effects of anti-HBc levels and other parameters on spontaneous HBeAg seroconversion and the natural course of CHB were assessed. A total of 182 children (106 males) with a median age at enrollment of 10.6 years (interquartile range [IQR], 10.3-15.3) were followed for a median of 19.8 years (IQR, 11.9-21.9). Spontaneous HBeAg seroconversion occurred in 85 children (46.7%) during the follow-up. A baseline anti-HBc titer of >500 IU/mL (hazard ratio [HR] = 2.81), HBV genotype B and B + C (HR = 3.46), and a baseline hepatitis B surface antigen titer of ≤4.8 log10  IU/mL (HR = 3.09) were predictive of spontaneous HBeAg seroconversion, based on multivariable survival analysis (P < 0.001). In cases remaining HBeAg positive, their anti-HBc levels increased gradually during follow-up because of ongoing inflammation. Conclusion: Baseline anti-HBc level is predictive of spontaneous HBeAg seroconversion in HBeAg-positive children with a normal ALT level. Anti-HBc level reflects anti-HBV immune response in the HBeAg-positive normal ALT phase of CHB.

Roles of Epstein-Barr virus viral load monitoring in the prediction of posttransplant lymphoproliferative disorder in pediatric liver transplantation.

BACKGROUND/PURPOSE: This study is aimed to investigate the risk factors and clinical characteristics of posttransplant lymphoproliferative disorder (PTLD) after conducting Epstein-Barr virus (EBV) viral load monitoring in pediatric liver transplant (LT) patients in Taiwan, where EBV infection is endemic. METHODS: From 2007 to 2013, pediatric LT recipients who underwent EBV viral load monitoring within 3 months after LT were recruited in this study. The impact of clinical parameters-including age at LT, sex, peak EBV viral load and immunosuppressant levels after LT-on the risk of PTLD were assessed. RESULTS: A total 39 patients underwent LT at a median age of 1.3 years (range: 0.6-14.0 years), and 5 patients developed PTLD during follow-up. Cox's proportional-hazards model identified two predictors of PTLD: peak EBV viral load within 3 months of LT >4100 copies/µg peripheral blood mononuclear cells (PBMC) DNA and peak tacrolimus level within 3 months of LT >14.8 ng/mL (Hazard ratio = 17.14 and 11.54, P = 0.02 and 0.03, respectively). Kaplan-Meier survival analysis revealed significant higher cumulative incidence rates of PTLD (27.3% and 41.8% at 0.3 and 1.2 years after LT) in subjects with peak EBV viral load >4100 copies/µg PBMC DNA within 3 months after LT. (P = 0.001, log-rank test). CONCLUSION: Close monitoring of EBV viral load within 3 months after LT is helpful to predict a high risk of PTLD. Tapering of immunosuppressants is suggested if the EBV viral load is >4100 copies/µg PBMC DNA in LT children.

Does one-man method better than two-man method for colonoscopy insertion in children.

BACKGROUND/PURPOSE: One-man method had shown several advantages over two-man method in adult colonoscopy insertion. However, whether this advantage can be extended to children is largely unknown. The aim of this study is to test the hypothesis that one-man method is the preferred method to two-man method in pediatric colonoscopy. METHODS: In this retrospective study, from July 2010 to June 2014, colonoscopy examinations in children were recruited. These colonoscopy examinations were performed by second-year pediatric GI fellows under the supervision of an experienced attending physician. Colonoscopy indicators such as cecal intubation rate (CIR), cecal intubation time (CIT), and terminal ileum (TI) intubation rate between one-man and two-man method group were recorded. The primary outcome is CIR. RESULTS: Total 72 colonoscopy examinations by one-man method and 162 examinations by two-man method were studied. Univariate logistic regression showed two patient factors: poor preparation and underweight were associated with lower CIR. (Odds ratio, OR: 0.46 and 0.40, P = 0.046 and 0.01, respectively) The CIR was higher in one-man than in two-man method group (81.9% vs 69.1%, OR = 2.03, P = 0.04). One-man method had a higher TI intubation rate than that of two-man method. (66.7% vs 44.4%, OR = 2.51, P = 0.002) The mean CIT was 27.1 ± 11.7 min in one-man method and 26.9 ± 13.3 min in two-man method. (P = 0.93) No significant difference in complications was noted. CONCLUSION: One-man method colonoscopy is safe and has higher CIR and TI intubation rate than two-man method colonoscopy in children, even performed by second-year GI fellows.