Anne H Y Chu1, Mya T Tint1,2, Hsin F Chang2, Gerard Wong1, Wen Lun Yuan3, Dedreia Tull4, Brunda Nijagal4, Vinod K Narayana4, Peter J Meikle5, Kenneth T E Chang6, Rohan M Lewis7, Claudia Chi2, Fabian K P Yap8, Kok Hian Tan8, Lynette P Shek1,3, Yap-Seng Chong1,2, Peter D Gluckman1,9, Yung Seng Lee1,3, Marielle V Fortier10, Keith M Godfrey11, Johan G Eriksson1,2,12, Neerja Karnani1, Shiao-Yng Chan13,14. 1. Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore. 2. Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore, Singapore. 3. Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. 4. Metabolomics Australia, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Melbourne, VIC, Australia. 5. Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia. 6. Department of Pathology and Laboratory Medicine, KK Women's & Children's Hospital, Singapore, Singapore. 7. Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK. 8. Department of Maternal Fetal Medicine, KK Women's and Children's Hospital, Singapore, Singapore. 9. Liggins Institute, University of Auckland, Auckland, New Zealand. 10. Department of Diagnostic and Interventional Imaging, KK Women's and Children's Hospital, Singapore, Singapore. 11. MRC Lifecourse Epidemiology Unit & NIHR Southampton Biomedical Research Centre, University of Southampton & University Hospital Southampton NHS Foundation Trust, Southampton, UK. 12. Folkhalsan Research Center, Helsinki, Finland. 13. Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore. obgchan@nus.edu.sg. 14. Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore, Singapore. obgchan@nus.edu.sg.
Abstract
BACKGROUND/ OBJECTIVES: Maternal glycaemia promotes fetal adiposity. Inositol, an insulin sensitizer, has been trialled for gestational diabetes prevention. The placenta has been implicated in how maternal hyperglycaemia generates fetal pathophysiology, but no studies have examined whether placental inositol biology is altered with maternal hyperglycaemia, nor whether such alterations impact fetal physiology. We aimed to investigate whether the effects of maternal glycaemia on offspring birthweight and adiposity at birth differed across placental inositol levels. METHODS: Using longitudinal data from the Growing Up in Singapore Towards healthy Outcomes cohort, maternal fasting glucose (FPG) and 2-hour plasma glucose (2hPG) were obtained in pregnant women by a 75-g oral glucose tolerance test around 26 weeks' gestation. Relative placental inositol was quantified by liquid chromatography-mass spectrometry. Primary outcomes were birthweight (n = 884) and abdominal adipose tissue (AAT) volumes measured by neonatal MRI scanning in a subset (n = 262) of term singleton pregnancies. Multiple linear regression analyses were performed. RESULTS: Placental inositol was lower in those with higher 2hPG, no exposure to tobacco smoke antenatally, with vaginal delivery and shorter gestation. Positive associations of FPG with birthweight (adjusted β [95% CI] 164.8 g [109.1, 220.5]) and AAT (17.3 ml [11.9, 22.6] per mmol glucose) were observed, with significant interactions between inositol tertiles and FPG in relation to these outcomes (p < 0.05). Stratification by inositol tertiles showed that each mmol/L increase in FPG was associated with increased birthweight and AAT volume among cases within the lowest (birthweight = 174.2 g [81.2, 267.2], AAT = 21.0 ml [13.1, 28.8]) and middle inositol tertiles (birthweight = 202.0 g [103.8, 300.1], AAT = 19.7 ml [9.7, 29.7]). However, no significant association was found among cases within the highest tertile (birthweight = 81.0 g [-21.2, 183.2], AAT = 0.8 ml [-8.4, 10.0]). CONCLUSIONS: High placental inositol may protect the fetus from the pro-adipogenic effects of maternal glycaemia. Studies are warranted to investigate whether prenatal inositol supplementation can increase placental inositol and reduce fetal adiposity.
BACKGROUND/ OBJECTIVES: Maternal glycaemia promotes fetal adiposity. Inositol, an insulin sensitizer, has been trialled for gestational diabetes prevention. The placenta has been implicated in how maternal hyperglycaemia generates fetal pathophysiology, but no studies have examined whether placental inositol biology is altered with maternal hyperglycaemia, nor whether such alterations impact fetal physiology. We aimed to investigate whether the effects of maternal glycaemia on offspring birthweight and adiposity at birth differed across placental inositol levels. METHODS: Using longitudinal data from the Growing Up in Singapore Towards healthy Outcomes cohort, maternal fasting glucose (FPG) and 2-hour plasma glucose (2hPG) were obtained in pregnant women by a 75-g oral glucose tolerance test around 26 weeks' gestation. Relative placental inositol was quantified by liquid chromatography-mass spectrometry. Primary outcomes were birthweight (n = 884) and abdominal adipose tissue (AAT) volumes measured by neonatal MRI scanning in a subset (n = 262) of term singleton pregnancies. Multiple linear regression analyses were performed. RESULTS: Placental inositol was lower in those with higher 2hPG, no exposure to tobacco smoke antenatally, with vaginal delivery and shorter gestation. Positive associations of FPG with birthweight (adjusted β [95% CI] 164.8 g [109.1, 220.5]) and AAT (17.3 ml [11.9, 22.6] per mmol glucose) were observed, with significant interactions between inositol tertiles and FPG in relation to these outcomes (p < 0.05). Stratification by inositol tertiles showed that each mmol/L increase in FPG was associated with increased birthweight and AAT volume among cases within the lowest (birthweight = 174.2 g [81.2, 267.2], AAT = 21.0 ml [13.1, 28.8]) and middle inositol tertiles (birthweight = 202.0 g [103.8, 300.1], AAT = 19.7 ml [9.7, 29.7]). However, no significant association was found among cases within the highest tertile (birthweight = 81.0 g [-21.2, 183.2], AAT = 0.8 ml [-8.4, 10.0]). CONCLUSIONS: High placental inositol may protect the fetus from the pro-adipogenic effects of maternal glycaemia. Studies are warranted to investigate whether prenatal inositol supplementation can increase placental inositol and reduce fetal adiposity.
Authors: Reshma A Pillai; Mohammed O Islam; Preben Selvam; Neha Sharma; Anne H Y Chu; Oliver C Watkins; Keith M Godfrey; Rohan M Lewis; Shiao Y Chan Journal: J Clin Endocrinol Metab Date: 2021-01-23 Impact factor: 5.958
Authors: Oliver C Watkins; Preben Selvam; Reshma Appukuttan Pillai; Victoria K B Cracknell-Hazra; Hannah E J Yong; Neha Sharma; Amaury Cazenave-Gassiot; Anne K Bendt; Keith M Godfrey; Rohan M Lewis; Markus R Wenk; Shiao-Yng Chan Journal: Sci Rep Date: 2022-09-01 Impact factor: 4.996
Authors: Oliver C Watkins; Victoria K B Cracknell-Hazra; Reshma Appukuttan Pillai; Preben Selvam; Hannah E J Yong; Neha Sharma; Sathya Narayanan Patmanathan; Amaury Cazenave-Gassiot; Anne K Bendt; Keith M Godfrey; Rohan M Lewis; Markus R Wenk; Shiao-Yng Chan Journal: Nutrients Date: 2022-09-26 Impact factor: 6.706