Impact of maternal triglyceride and novel metabolic parameters on neonatal anthropometrics in Asian mothers with normal glucose tolerance

Syahrizan, Premila,  Abqariah, Nurbazlin,  Lim Lee Ling, Sharmila, Jeya, Luqman, Siti Zawiah Omar, Yazid, Azanna , Shireene R Vethakkan 

Background and Aims: In Caucasian populations, maternal obesity and triglyceride (Tg) have been demonstrated to modulate neonatal anthropometrics via intrauterine fetal programming.(1,2,3) Less is known of these associations during pregnancy in Asians, in whom strength of/ thresholds for correlation may differ given that visceral adiposity/insulin resistance in Asians is elevated at a lower BMI.(4,5) Hence, we aimed to determine the relationship between maternal BMI/metabolic variables (including Tg) and neonatal anthropometrics in Malaysian mother-offspring pairs.

 Methods: In this prospective observational study, we recruited  women with  normal glucose tolerance (NGT) from a tertiary combined multidisciplinary antenatal clinic in Kuala Lumpur, Malaysia in the period from March 2014 to December 2016. Demographic, anthropometric and clinical data were obtained during an interview/examination using a structured questionnaire. Blood was drawn for insulin, C-peptide and Tg during the screening 75g OGTT for GDM at 14-32 weeks gestation. At birth, neonatal anthropometrics were assessed and data such as maternal weight gain during pregnancy, mode of delivery etc. extracted from records.

Results: We recruited 345 NGT mothers: 255 with BMI < 27.5 kg/m2 (Group 1), 90 with BMI ≥27.5 kg/m2(Group 2). Mean/median age  pregravid BMI ,fasting glucose and fasting Tg in the NGT mothers overall were 30.80 ± 4.43, 23.81(20.87-27.77), 4.29±0.38, and 2.00(1.60-2.50) respectively. 35.7%(123) were nulliparous and 64.3%(222) were multiparous. 70.1% were of Malay ethnicity, 18.3% of Chinese descent and 11.6% of Indian (South Asian) origin. Median BMI in the ‘lean group’(Group 1) and ‘nonlean group’(Group 2) were 22.07 (20.03-24.34) and 31.13 (29.30-33.73) respectively (p<0.001). Median Tg in the ‘lean group’ and ‘nonlean group’ were 1.90 (1.60-2.40) and 2.20 (1.75-2.60) respectively,  p=0.005* .
Mean Birth Weight(BW) in the nonlean  group was higher than that in the lean NGT group (3140.97±555.57 vs 3059.80±412.48g, p=0.148).

Seven(2.03%) offspring fulfilled criteria for macrosomia, BW ≥ 4 kg. There were 8 Large for Gestational Age(LGA) babies (2.4%) as defined by Fenton antenatal growth charts. 3(3.3%) and 5(5.7%) babies with macrosomia and LGA status were offspring of nonlean mothers. Calculated 90th centile for BW in this Asian population  was 3.63 kg. 

Fasting Tg >3.5(95th centile)(OR 6.5, 95%CI 1.057-39.981, p=0.043*) was the strongest predictor of LGA status independent of  maternal glucose, insulin sensitivity(HOMA2-%S), pregravid BMI ,and weight gain in pregnancy. Gestational wt gain >20kg (OR 5.8, 95%CI 2.1-15.7, p=0.001), and multiparity (OR 2.9, 95%CI 1.102-7.676,p=0.031) were independently predictive of BW > 3.63 kg (90th centile). Fasting glucose while significantly correlated with anthropometric measures on univariate analysis was not independently predictive of LGA status/macrosomia/neonatal adiposity upon multivariate analysis in these NGT women. 
  
Discussion:Our findings confirm that maternal hypertriglyceridemia in mid- to late-pregnancy , independently of pregravid BMI   is highly   predictive of  LGA status(augmenting risk by > 6.5-fold) and increased neonatal adiposity in Asian offspring of  NGT mothers.  Importantly,  maternal hypertriglyceridemia is more predictive than maternal obesity of increased neonatal adiposity and is therefore a potentially modifiable metabolic target in NGT pregnancy.  
 Maternal serum triglyceride  begins to increase from  10 weeks gestation and reaches levels two or three-fold that at baseline by term, secondary to physiological changes of pregnancy that increase fetal-nutrient-availability.(1)  This rise in maternal triglyceride is exacerbated in women with GDM and pregestational diabetes. .(1)

There have been only a handful of  Asian studies evaluating the impact of Tg on neonatal anthropometrics prior to this. Kitajima et al(6) studied high risk NGT mothers while Son et al evaluated mothers with GDM. Kitajima et al found that in 146 Japanese  at high risk of GDM but found to have NGT on the 75g OGTT, mid-pregnancy fasting Tg was independently predictive of BW after adjusting for plasma glucose/maternal obesity .

On the other hand Son et al(7) who studied 104 Korean women wih GDM retrospectively, found that  hypertriglyceridemia (defined as fasting Tg >3.3) was highly and independently predictive of LGA status(OR 4.43)  in addition to prepregnancy BMI and multiparity.
There is already some evidence that the correlation between maternal triglyceride  and BW is stronger in Asian-born compared with Australian and European-born mothers in a mixed population of GDM and NGT mothers in ethnically-diverse Australia.(8)

Further confirmatory studies are required in larger sample populations and the effect of  individual Asian ethnicities assessed given that not all Asians are alike. The role of maternal triglyceride in Asian mothers with GDM, above and beyond maternal glucose also remains to be elucidated. 

REFERENCES
1. Di Cianni G, Miccoli R, Volpe L, Lencioni C, Ghio A, Giovannitti MG, Cuccuru I, Pellegrini G, Chatzianagnostou K, Boldrini A, Del Prato S. Maternal triglyceride levels and newborn weight in pregnant women with normal glucoe tolerance. Diabet Med 2005; 22:21-25

2. Whyte K, Kelly H, O’Dwyer V, Gibbs M, O’Higgins A, Turner MJ. Offspring birth weight and maternal fasting lipids in women screened for gestation diabetes mellitus. Eur J Obstet Gynecol Reproductive Biology 2013; 170:67-70

3. HAPO Study Cooperative Research Group. Hyperglycaemia and Adverse Pregnancy Outcomes(HAPO) Study: associations with maternal body mass index. BJOG 2010; 117:575-584

4. Yoon, K., Lee, J., Kim, J., Cho, J. H., Choi, Y., Ko, et al (2006). Epidemic obesity and type 2 diabetes in Asia. The Lancet, 368(9548), 1681-1688. 

5. Kim, Y. G., Hahn, S., Oh, T. J., Kwak, S. H., Park, K. S., & Cho, Y. M. (2013). Differences in the glucose-lowering efficacy of dipeptidyl peptidase-4 inhibitors between Asians and non-Asians: A systematic review and meta-analysis. Diabetologia, 56(4), 696-708. 

6. Kitajima M, Oka S, Yasuhi I, Fukuda M, Rii Y, Ishimaru T. Maternal serum tiglyceride at 24-32 weeks’ gestation and newborn weight in nondiabetic women with positive diabetic screens. Obstet Gynecol 2001; 97:776-80

7. Son GH, Kwon JY, Kim YH, Park YW. Maternal serum triglycerides as predictive factors for large-for-gestational age newborns in women with gestational diabetes mellitus. Acta Obstet Gynecol Scand 2010; 89:700-704

8. Nolan CJ, Riley SF, Sheedy MT, Walstab JE, Beischer NA. Maternal serum triglyceride, glucose tolerance and neonatal birth weight ratio in pregnancy. Diabetes Care 1995; 18(12):1550-1556

Relative impact of maternal triglyceride and glucose on neonatal adiposity in Asian mothers with normal glucose tolerance