Early ascending growth is associated with maternal lipoprotein profile during mid and late pregnancy and in cord blood.

INTRODUCTION: Intrauterine conditions and accelerating early growth are associated with childhood obesity. It is unknown, whether fetal programming affects the early growth and could alterations in the maternal-fetal metabolome be the mediating mechanism. Therefore, we aimed to assess the associations between maternal and cord blood metabolite profile and offspring early growth. METHODS: The RADIEL study recruited 724 women at high risk for gestational diabetes mellitus (GDM) BMI ≥ 30 kg/m2 and/or prior GDM) before or in early pregnancy. Blood samples were collected once in each trimester, and from cord. Metabolomics were analyzed by targeted nuclear magnetic resonance (NMR) technique. Following up on offsprings' first 2 years growth, we discovered 3 distinct growth profiles (ascending n = 80, intermediate n = 346, and descending n = 146) by using latent class mixed models (lcmm). RESULTS: From the cohort of mother-child dyads with available growth profile data (n = 572), we have metabolomic data from 232 mothers from 1st trimester, 271 from 2nd trimester, 277 from 3rd trimester and 345 from cord blood. We have data on 220 metabolites in each trimester and 70 from cord blood. In each trimester of pregnancy, the mothers of the ascending group showed higher levels of VLDL and LDL particles, and lower levels of HDL particles (p < 0.05). When adjusted for gestational age, birth weight, sex, delivery mode, and maternal smoking, there was an association with ascending profile and 2nd trimester total cholesterol in HDL2, 3rd trimester total cholesterol in HDL2 and in HDL, VLDL size and ratio of triglycerides to phosphoglycerides (TG/PG ratio) in cord blood (p ≤ 0.002). CONCLUSION: Ascending early growth was associated with lower maternal total cholesterol in HDL in 2nd and 3rd trimester, and higher VLDL size and more adverse TG/PG ratio in cord blood. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, http://www. CLINICALTRIALS: com , NCT01698385.

Clinical and genetic factors associated with post-operative nausea and vomiting after propofol anaesthesia.

BACKGROUND: The incidence of post-operative nausea and vomiting (PONV) remains at about 30% despite all therapeutic efforts to reduce it. The clinical risk factors guiding the prophylactic treatment are well established, but genetic factors associated with PONV remain poorly known. The aim of this study was to explore clinical and genetic factors impacting PONV by performing a genome-wide association study (GWAS) together with relevant clinical factors as covariates, and systematically attempt to replicate previously reported PONV associations. Relevant clinical factors are explored with logistic regression model. METHODS: This was an observational case control study in Helsinki University Hospital between 1 August 2006 and 31 December 2010. One thousand consenting women with elevated risk for PONV, undergoing breast cancer surgery with standardised propofol anaesthesia and antiemetics. After exclusions for clinical reasons and failed genotyping, 815 patients were included with 187 PONV cases and 628 controls. Emergence of PONV up to 7th post-operative day was recorded. PONV at 2-24 h after surgery was selected to be the primary outcome. The GWAS explored associations between PONV and 653 034 genetic variants. Replication attempts included 31 variants in 16 genes. RESULTS: The overall incidence of PONV up to 7th post-operative day was 35%, where 3% had PONV at 0-2 h and 23% at 2-24 h after surgery. Age, American Society of Anaesthesiologists status, the amount of oxycodone used in the post-anaesthesia care unit, smoking status, previous PONV, and history of motion sickness were statistically significant predictive factors in the logistic model. The receiver operating characteristic-area under the curve of 0.75 (95% CI 0.71-0.79) was calculated for the model. The GWAS identified six variants with suggestive association to PONV (p < 1 × 10-5 ). Of the previously reported variants, association with the DRD2 variant rs18004972 (TaqIA) was replicated (p = .028). CONCLUSIONS: Our GWAS approach did not identify any high-impact PONV susceptibility variants. The results provide some support for a role of dopamine D2 receptors in PONV.

Genetic risk of type 2 diabetes modifies the effects of a lifestyle intervention aimed at the prevention of gestational and postpartum diabetes.

AIMS/HYPOTHESIS: The aim of this study was to assess the interaction between genetic risk and lifestyle intervention on the occurrence of gestational diabetes mellitus (GDM) and postpartum diabetes. METHODS: The RADIEL study is an RCT aimed at prevention of GDM and postpartum diabetes through lifestyle intervention. Participants with a BMI ≥30 kg/m2 and/or prior GDM were allocated to intervention and control groups before pregnancy or in early pregnancy. The study visits took place every 3 months before pregnancy, once in each trimester, and at 6 weeks and 6 and 12 months postpartum. We calculated a polygenic risk score (PRS) based on 50 risk variants for type 2 diabetes. RESULTS: Altogether, 516 participants provided genetic and GDM data. The PRS was associated with higher glycaemic levels (fasting glucose and/or HbA1c) and a lower insulin secretion index in the second and third trimesters and at 12 months postpartum, as well as with a higher occurrence of GDM and glycaemic abnormalities at 12 months postpartum (n = 356). There was an interaction between the PRS and lifestyle intervention (p=0.016 during pregnancy and p=0.024 postpartum) when analysing participants who did not have GDM at the first study visit during pregnancy (n = 386). When analysing women in tertiles according to the PRS, the intervention was effective in reducing the age-adjusted occurrence of GDM only among those with the highest genetic risk (OR 0.37; 95% CI 0.17, 0.82). The risk of glycaemic abnormalities at 12 months postpartum was reduced in the same group after adjusting additionally for BMI, parity, smoking and education (OR 0.35; 95% CI 0.13, 0.97). CONCLUSIONS/INTERPRETATION: Genetic predisposition to diabetes modifies the response to a lifestyle intervention aimed at prevention of GDM and postpartum diabetes. This suggests that lifestyle intervention may benefit from being tailored according to genetic risk. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01698385.

Ascending Growth is Associated with Offspring Adiposity in Pregnancies Complicated with Obesity or Gestational Diabetes.

CONTEXT: Early growth is associated with childhood adiposity, but the influence of lifestyle remains unknown. OBJECTIVE: This work aimed to investigate the association of growth profiles from high-risk pregnancies with adiposity at age 5 years, taking into account lifestyle and several antenatal/postnatal exposures. METHODS: This prospective cohort study. INCLUDED: 609 children born during the Finnish Gestational Diabetes Prevention Study (RADIEL), recruiting women with body mass index (BMI) greater than or equal to 30 and/or prior gestational diabetes mellitus (GDM) (2008-2013). Altogether 332 children attended the 5-year follow-up (2014-2017). Main outcome measures included growth profiles based on ponderal index (PI = weight/height3), investigated using latent class mixed models. Adiposity was assessed with anthropometrics and body composition (InBody720). RESULTS: We identified 3 growth profiles: ascending (n = 82), intermediate (n = 351), and descending (n = 149). Children with ascending growth had a higher body fat percentage, ISO-BMI, and waist circumference (P < .05) at age 5 years. Ascending (ß 4.09; CI, 1.60-6.58) and intermediate (ß 2.27; CI, 0.50-4.03) profiles were associated with higher fat percentage, even after adjustment for age, sex, gestational age, diet, physical activity, education, and prepregnancy BMI. Similar associations existed with ISO-BMI. After adjusting for age and education, ascending growth was associated with prepregnancy BMI (odds ratio [OR] 1.06; CI, 1.01-1.12), primiparity (OR 3.07; CI, 1.68-5.62), cesarean delivery (OR 2.23; CI, 1.18-4.21), and lifestyle intervention (OR 2.56; CI, 1.44-4.57). However, meeting the intervention goals and exclusive breastfeeding for 3 months or more were associated with lower odds of ascending growth. CONCLUSION: Accelerated early growth was associated with higher adiposity in 5-year-old children from high-risk pregnancies, even when adjusted for lifestyle. Reducing cesarean deliveries and promoting breastfeeding may be beneficial for postnatal growth.