Prenatal Human Milk Oligosaccharides (HMOs) in the Context of BMI, Gestational Weight Gain, and Lipid Profile-An Association Study in Pregnant Women with Overweight or Obesity.

BACKGROUND: Human milk oligosaccharides (HMOs) are bioactive glycans first detected in human milk. Their presence in maternal blood during pregnancy suggests systemic functions. Dynamics and associations of the most abundant prenatal HMOs in relation to maternal BMI and serum lipids in a cohort of 87 pregnant women with either overweight or obesity are studied. METHODS: Serum HMOs (2'FL, 3'SL, 3'SLN, LDFT), serum lipids (total cholesterol, HDL, LDL, triglycerides), and BMI are measured at 15, 24, and 32 weeks of gestation. RESULTS: 2'FL and LDFT are negatively correlated to pre-pregnancy BMI and increase significantly slower between 15 and 24 weeks in highly obese women. Women without detectable increase of serum 2'FL (non-secretors) show a less pronounced gestational weight gain and lower BMI in the third trimester as compared to women phenotype as secretors. Higher early-pregnancy 2'FL is associated with high HDL and low triglycerides in pregnancy. On the other hand, higher 3'SL at 15 weeks is associated with higher triglycerides, LDL, and total cholesterol. CONCLUSIONS: Higher early-pregnancy 2'FL is associated with a cardioprotective lipid profile, whereas higher 3'SL is associated with an atherogenic lipid profile. Serum trajectories of 2'FL and LDFT in obese women suggest an obesity mediated delay of α-1,2-fucosylation.

The association of human milk oligosaccharides with glucose metabolism in overweight and obese pregnant women.

BACKGROUND: Human milk oligosaccharides (HMOs) were recently found in serum of normal-weight pregnant women, with concentrations increasing from early to mid- and late pregnancy. Whether HMOs have effects on maternal metabolism is unknown. OBJECTIVES: We aimed to study the presence and changes in HMOs throughout pregnancy and assess associations with maternal glucose metabolism throughout pregnancy. METHODS: The study was a prospective longitudinal cohort study including 87 overweight or obese women. Blood samples were taken at 15, 24, and 32 wk of pregnancy. In serum, 4 HMOs [2'-fucosyllactose (2'FL), lactodifucotetraose (LDFT), 3'-sialyllactose (3'SL), and 3'-sialyllactosamine (3'SLN)] were measured. In linear regression models, the associations between HMOs and (changes in) maternal metabolic parameters were assessed. RESULTS: All 4 HMOs showed a significant increase from 15 to 32 weeks of gestation. 3'SL and 3'SLN, but not 2'FL or LDFT, at 15 wk were positively associated with (changes in) fasting glucose at 24 and 32 wk. LDFT was positively associated with (changes in) insulin and HOMA-index at 24 but not 32 wk. A model to predict the development of gestational diabetes mellitus (GDM) that included fasting glucose, prepregnancy BMI, gestational weight gain, age, parity, smoking, and history of macrosomia resulted in an area under the curve (AUC) of 0.81 (95% CI: 0.70, 0.92). Adding 3'SL to this model increased the AUC to 0.91 (95% CI: 0.84, 0.97). CONCLUSIONS: The sialylated HMOs 3'SL and 3'SLN were associated with fasting glucose; LDFT was associated with fasting insulin and HOMA-index. Furthermore, 3'SL was more predictive of future GDM diagnoses than was fasting glucose in early pregnancy. Causal relations are unclear and need further investigation.