Chu, A. H. Y., Tint, M. T., Chang, H. F., Wong, G., Yuan, W. L., Tull, D., … Chan, S.-Y. (2020). High placental inositol content associated with suppressed pro-adipogenic effects of maternal glycaemia in offspring: the GUSTO cohort. International Journal of Obesity, 45(1), 247–257. doi:10.1038/s41366-020-0596-5
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.
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.
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 &amp;lt; 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]).
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.
Attribution 4.0 International (CC BY 4.0)
This research / project is supported by the Singapore National Research Foundation - Translational and Clinical Research Flagship Programme
Grant Reference no. : NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014
Additional funding is provided by the Singapore Institute for Clinical Sciences (SICS), Agency for Science Technology and Research (A*STAR), and Metabolomics Australia at the University of Melbourne, a member of Bioplatforms Australia Pty Ltd. funded through the National Collaborative Research Infrastructure Strategy (NCRIS).
This is a post-peer-review, pre-copyedit version of an article published in International Journal of Obesity. The final authenticated version is available online at: http://dx.doi.org/10.1038/s41366-020-0596-5.