Gestational diabetes mellitus-associated changes in the breast milk metabolome alters the neonatal growth trajectory

Yue Wu; Jiaxiao Yu; Xiyao Liu; Wenling Wang; Zhi Chen; Juan Qiao; Xiaohui Liu; Huili Jin; Xin Li; Li Wen; Jing Tian; Richard Saffery; Mark D Kilby; Hongbo Qi; Chao Tong; Philip N Baker

doi:10.1016/j.clnu.2021.02.014

Gestational diabetes mellitus-associated changes in the breast milk metabolome alters the neonatal growth trajectory

Clin Nutr. 2021 Jun;40(6):4043-4054. doi: 10.1016/j.clnu.2021.02.014. Epub 2021 Feb 16.

Authors

Yue Wu¹, Jiaxiao Yu¹, Xiyao Liu¹, Wenling Wang², Zhi Chen¹, Juan Qiao¹, Xiaohui Liu³, Huili Jin¹, Xin Li¹, Li Wen¹, Jing Tian⁴, Richard Saffery⁵, Mark D Kilby⁶, Hongbo Qi⁷, Chao Tong⁸, Philip N Baker⁹

Affiliations

¹ Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, 400016, China; International Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
² Department of Obstetrics, Gansu Provincial Maternity and Child-Care Hospital, Lanzhou, Gansu, 730050, China.
³ National Protein Science Technology Center, Tsinghua University, Beijing, 100084, China.
⁴ Department of Obstetrics and Gynecology, University-Town Hospital of Chongqing Medical University, Chongqing, 401331, China.
⁵ International Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China; Cancer, Disease and Developmental Epigenetics, Murdoch Children's Research Institute, Parkville, Victoria, 3052, Australia.
⁶ College of Medical & Dental Sciences, University of Birmingham, B15 2TT, UK; Fetal Medicine Centre, Birmingham Women's & Children's Foundation Trust, Edgbaston, Birmingham, B15 2TG, UK.
⁷ Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, 400016, China; International Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China. Electronic address: qihongbo728@163.com.
⁸ Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, 400016, China; International Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China. Electronic address: chaotongcqmu@163.com.
⁹ International Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China; College of Life Sciences, University of Leicester, Leicester, LE1 7RH, UK.

PMID: 33640207
DOI: 10.1016/j.clnu.2021.02.014

Abstract

Background: Gestational diabetes mellitus (GDM) is the most common metabolic disturbance during pregnancy and leads to an altered metabolic profile of human breast milk (HBM). The association between HBM metabolites and neonatal growth in GDM pregnancies has not been thoroughly investigated.

Aims: The primary aim was to quantify differences in the HBM metabolome between normal and GDM pregnancies. The secondary aim was to identify metabolites associated with neonatal growth during the first year postpartum.

Methods: In the present study, mothers intending to exclusively breastfeed (BF) and their newborns (mother-infant pairs) were recruited at delivery (n = 129 normal pregnancies and n = 98 GDM pregnancies). HBM samples (colostrum, transition milk, and mature milk) from mothers with normal pregnancies (n = 50) and GDM pregnancies (n = 50) were subjected to metabolomic profiling via liquid chromatography tandem mass spectrometry (LC-MS/MS). Receiver operating characteristic (ROC) analysis revealed the metabolomic fingerprints of GDM-associated mature HBM. Correlations between metabolites and neonatal body weight gain (BWG) were evaluated by Spearman correlation analysis.

Results: In total, 620 metabolites were identified in each HBM sample; 253 compounds had the same variation patterns, whereas 38 compounds had significantly different pattern transitions between the GDM and normal groups. Moreover, 12, 49 and 28 metabolites exhibited significant differences in the 3 milk types between the 2 groups. Twenty-two metabolites were confirmed by ROC analysis as metabolomic fingerprints in the mature BM of GDM patients. Ten compounds were significantly negatively correlated with neonatal growth, and only 2 unsaturated lipids (eicosatrienoic acid (FA 20:3) and lysophosphatidylcholine (LysoPC) (22:6)) were positively correlated with neonatal BWG.

Conclusions: GDM is associated with alterations in the HBM metabolome. Only a small subset of compounds are associated with neonatal body weight (BW).

Trial registration: ChiCTR-ROC-17011508. Prospectively registered on 26 May 2017 (http://www.chictr.org.cn/listbycreater.aspx).

Keywords: Gestational diabetes mellitus; Human breast milk; Metabolome; Neonatal growth.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Birth Weight
Body-Weight Trajectory*
Case-Control Studies
Chromatography, Liquid
Diabetes, Gestational / metabolism*
Female
Humans
Infant Nutritional Physiological Phenomena
Infant, Newborn / growth & development*
Metabolome
Milk, Human / metabolism*
Pregnancy
ROC Curve
Statistics, Nonparametric
Tandem Mass Spectrometry
Weight Gain

Associated data

ChiCTR/ChiCTR-ROC-17011508