Associations of maternal periconceptional alcohol consumption with offspring prehypertension/hypertension at age 6 years: the Growing Up in Singapore Towards healthy Outcomes prospective mother-offspring cohort study.

OBJECTIVE: To evaluate the relationship of the levels of maternal alcohol consumption during the 1 year before pregnancy recognition with childhood cardiorenal, metabolic, and neurocognitive health. METHODS: In 1106 women and their children from the Growing Up in Singapore Towards healthy Outcomes mother-offspring cohort, quantity of maternal alcohol consumption in the 12 months prior to pregnancy recognition was categorized as high (≥75th percentile: 1.9 g/day), low (<1.9 g/day), and none, and frequency of alcohol consumption was categorized as high (≥2-3 times/week), low (<2-3 times/week), and none. Offspring MRI-based abdominal fat depot, kidney, and brain volumes, blood pressure, metabolic syndrome score, and cognitive intelligence scores were assessed. Child prehypertension/hypertension at age 6 years was defined using a simplified pediatric threshold of 110/70 mmHg. RESULTS: The average maternal alcohol consumption in the year prior to pregnancy recognition was 2.5 g/day, which is lower than the daily maximal limit of one standard drink (10 g) recommended for women by Singapore's Ministry of Health. After adjusting for participant characteristics, alcohol consumption at least 1.9 g/day was associated with over two-fold higher risk (risk ratio = 2.18, P = 0.013) of child prehypertension and 15% greater kidney growth between early infancy and age 6 years (P = 0.040) compared with abstinence. Alcohol consumption was not associated with metabolic and neurocognitive health at age 6-7 years. The associations with high frequency of alcohol consumption were concordant with those obtained for quantity of alcohol consumption. CONCLUSION: Maternal self-reported alcohol consumption at least 1.9 g/day prior to pregnancy recognition was associated with increased risk of child prehypertension and rapid kidney growth. Our findings highlight the potential detrimental effects of low periconceptional alcohol consumption, below national guidelines on offspring cardiorenal health.

Paternally inherited ABCC8 mutation causing diffuse congenital hyperinsulinism.

BACKGROUND: Congenital hyperinsulinism (CHI) is a rare genetic disorder characterised by inappropriate insulin secretion in the face of severe hypoglycaemia. There are two histological subtypes of CHI namely diffuse and focal. Diffuse CHI is most common due to recessive mutations in ABCC8/KCNJ11 (which encode the SUR/KIR6.2 components of the pancreatic ß-cell KATP channel) whereas focal CHI is due to a paternally inherited ABCC8/KCNJ11 mutation and somatic loss of heterozygosity for the 11p allele inside the focal lesion. Fluorine-18-l-dihydroxyphenylalanine positron emission tomography/computed tomography ((18)F-DOPA-PET/CT) is used in the pre-operative localisation of focal lesions prior to surgery. Diffuse CHI if medically unresponsive will require a near total pancreatectomy whereas focal CHI will only require a limited lesionectomy, thus curing the patient from the hypoglycaemia. AIMS: To report the first case of genetically confirmed CHI in Singapore from a heterozygous paternally inherited ABCC8 mutation. METHODS/RESULTS: A term male infant presented with severe hyperinsulinaemic hypoglycaemia (HH) after birth and failed medical treatment with diazoxide and octreotide. Genetic testing (paternally inherited mutation in ABCC8/p.D1472N) suggested focal disease, but due to the unavailability of (18)F-DOPA-PET/CT to confirm focal disease, a partial pancreatectomy was performed. Interestingly, histology of the resected pancreatic tissue showed changes typical of diffuse disease. CONCLUSION: Heterozygous paternally inherited ABCC8/KCNJ11 mutations can lead to diffuse or focal CHI. LEARNING POINTS: HH is a cause of severe hypoglycaemia in the newborn period.Paternal mutations in ABCC8/KCNJ11 can lead to diffuse or focal disease.(18)F-DOPA-PET/CT scan is the current imaging of choice for localising focal lesions.Gallium-68 tetra-aza-cyclododecane-N N'N″N-‴-tetra-acetate octreotate PET scan is not a useful imaging tool for localising focal lesions.The molecular mechanism by which a heterozygous ABCC8 mutation leads to diffuse disease is currently unclear.Focal lesions are curable by lesionectomy and so genetic studies in patients with HH must be followed by imaging using (18)F-DOPA-PET/CT scan.