Speed Poster ESA-SRB-APEG-NZSE 2022

Does substantial preconception weight loss in women with obesity modify the epigenetic signature of the offspring? (#73)

Farrah Rodrigues 1 2 , Boris Novakovic 3 , Anna Czajko 3 , Danielle Longmore 1 4 5 , Richard Saffery 3 , Sarah Price 6 7
  1. Paediatric Endocrinology and Diabetes, Royal Children's Hospital, Melbourne, Victoria, Australia
  2. Paediatrics, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
  3. Molecular Immunity, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
  4. Inflammatory origins, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
  5. Paediatric Endocrinology and Diabetes, Joan Kirner Women's and Children's Hospital, Melbourne, Victoria, Australia
  6. Obstetric Medicine, Royal Women's Hospital, Melbourne, Victoria, Australia
  7. Endocrinology and Diabetes, Royal Melbourne Hospital, Melbourne, Victoria, Australia

One in five Australian women are obese (Body Mass Index (BMI) >30) at initial antenatal presentation(1). The Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) Follow-Up Study demonstrated the metabolic state of the mother during pregnancy, resulted in offspring with greater risk of metabolic disease in late childhood (2).

We aim to determine if substantial pre-conception weight loss in women with obesity alters the epigenome of the offspring. This would support the concept of bi-directional metabolic programming, and the importance of pre-conception weight management.

A two arm, parallel group, non-blinded randomized control trial was conducted at four hospitals in Melbourne, Australia. Women with obesity (BMI 30-55) who were planning pregnancy were randomised in to one of the two 12-week weight loss intervention - a standard lifestyle program and a Very Low Energy Diet (VLED) - followed by a 4 week weight maintenance program and 12 month observation period while trying for pregnancy. Study protocol and pregnancy outcomes have previously been published (4, 5). In a sub-group of consenting participants, buccal swabs (x2) were collected from neonates within 72 hours of delivery. DNA was extracted from these swabs and methylation analysed using the Human Genomics Facility at Erasmus MC. Methylation patterns will be analysed as discrete data according to group allocation and as a continuous variable according to preconception weight loss achieved.

Mean preconception weight loss in the standard lifestyle program and VLED was 3.2kg and 13.0kg (p<0.01) respectively. Singleton livebirth rate was 22/79 (28%) and 37/85 (44%) respectively. DNA was extracted from 29 neonates (7 from mothers randomised to the lifestyle arm and 18 from mothers allocated to the VLED arm); 4 samples were deemed unsuitable.  

At the time of writing, epigenetic results are pending. It is anticipated that results will be available and analysis complete within 3 months of abstract submission.

  1. 1. NHMRC. Clinical Practice Guidelines: Pregnancy Care: 2018.
  2. 2. Lowe WL, Lowe LP, Kuang A, Catalano PM, Nodzenski M, Talbot O, et al. Maternal glucose levels during pregnancy and childhood adiposity in the Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study. Diabetologia 2019;62: 598-610.
  3. 3. Huypens P, Sass S, Wu M, Dyckhoff D, Tschöp M, Theis F, et al. Epigenetic germline inheritance of diet-induced obesity and insulin resistance. Nat Genet 2016;48: 497-499.
  4. 4. Price S, Nankervis A, Permezel M, Prendergast L, Sumithran P, Proietto J. Health consequences for mother and baby of substantial pre-conception weight loss in obese women: study protocol for a randomized controlled trial. Trials 2018;19: 248.
  5. 5. Price SAL, Sumithran P, Nankervis AJ, Permezel M, Prendergast LA, Proietto J. Impact of preconception weight loss on fasting glucose and pregnancy outcomes in women with obesity: A randomized trial. Obesity (Silver Spring) 2021;29: 1445-1457.