Metabolic Profiling of 713 Newborns and Parents in the Norwegian Mother, Father and Child Cohort Study

Abstract

Background: Lipids are important for fetal development, but the determinants of cord blood lipids have scarcely been studied. We therefore aimed to describe the associations between newborn cord blood lipid and metabolic profile, and maternal and paternal lipid and metabolic profile. Methods: This study is based on 713 mother-father-newborn trios from the Norwegian Mother, Father and Child Cohort Study (MoBa) and uses data from the Medical Birth Registry of Norway. Sixty-four cord blood metabolites detected by nuclear magnetic resonance spectroscopy were analyzed. The false discovery rate (FDR) procedure was used to correct for multiple testing. Findings: We found positive associations between maternal and newborn high-density lipoprotein (HDL) cholesterol, omega 3 and 6 fatty acids, glutamine, isoleucine, leucine, valine, phenylalanine, tyrosine, glucose, citrate, creatinine, and particle concentration of medium and small HDL (0·001 ≤ qFDR ≤ 0·049). Paternal and newborn total-, low-density lipoprotein (LDL)-, HDL3-, remnant-, esterified- and free cholesterol, phosphoglycerides, cholines, phosphatidylcholines, sphingomyelins, apolipoprotein B and A1, total fatty acids, and particle concentration of intermediate-density lipoprotein, large- and medium LDL were positively associated (0·004 ≤ qFDR ≤ 0·047). Sex differences were found for many cord blood lipids. Interpretation: Several cord blood metabolites were associated with maternal and paternal metabolites and newborn sex. This may potentially affect pregnancy- and long-term outcomes. Funding: The University of Oslo; the National Advisory Unit on Familial Hypercholesterolemia, Oslo University Hospital; the Throne Holst Foundation for Nutrition Research; the Norwegian Health Association; Eckbos Legate; the Freia Corporation Medical Fund; and the Blix Foundation for the Promotion of Medical Research, Norway. Declaration of Interests: During the past five years, MPB reports grants and personal fees from Amgen, grants and personal fees from Sanofi, personal fees from MSD, personal fees from Boehringer Ingelheim, grants and personal fees from Mills AS, and grants from Kaneka, none of which are related to the content of this manuscript. JJC reports grants or personal fees from Mills DA and Amgen, none of which are related to the content of this manuscript. SMU has received research grants and/or personal fees from Mills AS, Tine DA, and Olympic Seafood, none of which are related to the content of this manuscript. KR reports personal fees from Amgen, personal fees from Mills AS, personal fees from The Norwegian Medical Association, personal fees from The Norwegian Directorate of Health, personal fees from Sanofi, personal fees from Takeda, personal fees from Chiesi, personal fees from Bayer, and personal fees from MSD, none of which are related to the content of this manuscript. JRVL has received research grants from Amryt, which are not related to the content of this manuscript. KBH has received research grants or honoraria from Mills AS, Tine SA, Olympic Seafood, Amgen, Sanofi, and Pronova, none of which are related to the content of this manuscript. LKLO, ALB, HKB, TMM, TH, PMM, and MBV declare no conflicts of interest. Ethics Approval Statement: The current study was approved by the Regional Committees for Medical and Health Research Ethics (no. 2017/1285). The study was conducted according to the principles of the Declaration of Helsinki, and all MoBa participants gave written informed consent at the time of inclusion.