title: Maternal 25-hydroxyvitamin D is inversely correlated with foetal serotonin.
abstract: OBJECTIVE
  Maternal vitamin D deficiency during pregnancy has been linked to impaired neurocognitive development in childhood. The mechanism by which vitamin D affects childhood neurocognition is unclear but may be via interactions with serotonin, a neurotransmitter involved in foetal brain development. In this study, we aimed to explore associations between maternal and foetal vitamin D concentrations, and foetal serotonin concentrations at term.
  
  
  METHODS
  Serum 25-hydroxyvitamin D (25(OH)D, nmol/l) and serotonin (5-HT, nmol/l) concentrations were measured in maternal and umbilical cord blood from mother-infant pairs (n = 64). Association between maternal 25(OH)D, cord 25(OH)D and cord serotonin was explored using linear regression, before and after adjusting for maternal serotonin levels. We also assessed the effects of siRNA knockdown of the vitamin D receptor (VDR) and administration of 10 nm 1,25-dihydroxyvitamin D3on serotonin secretion in human umbilical vein endothelial cells (HUVECs) in vitro.
  
  
  RESULTS
  We observed an inverse relationship between both maternal and cord 25(OH)D concentrations with cord serotonin concentrations. The treatment of HUVECs with 1,25-dihydroxyvitamin D3in vitro decreased the release of serotonin (193·9 ±14·8 nmol/l vs 458·9 ± 317·5 nmol/l, control, P < 0·05). Conversely, inactivation of VDR increased serotonin release in cultured HUVECs.
  
  
  CONCLUSIONS
  These observations provide the first evidence of an inverse relationship between maternal 25(OH)D and foetal serotonin concentrations. We propose that maternal vitamin D deficiency increases foetal serotonin concentrations and thereby contributes to longer-term neurocognitive impairment in infants and children.
authors.affiliation: Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Vic., Australia.|The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Vic., Australia.
authors.forename: Padma
authors.identifier: http://orcid.org/0000-0003-2535-5134
authors.initials: P
authors.lastname: Murthi
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Vic., Australia.|Department of Obstetrics and Gynaecology, School of Clinical Sciences, Monash University, Melbourne, Vic., Australia.
authors.forename: Miranda
authors.initials: M
authors.lastname: Davies-Tuck
authors.affiliation: Department of Obstetrics and Gynaecology, University of Melbourne, Heidelberg, Vic., Australia.|Mercy Hospital for Women, Heidelberg, Vic., Australia.
authors.forename: Martha
authors.initials: M
authors.lastname: Lappas
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Vic., Australia.
authors.forename: Harmeet
authors.initials: H
authors.lastname: Singh
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Vic., Australia.|Department of Obstetrics and Gynaecology, School of Clinical Sciences, Monash University, Melbourne, Vic., Australia.
authors.forename: Joanne
authors.initials: J
authors.lastname: Mockler
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Vic., Australia.|Department of Obstetrics and Gynaecology, School of Clinical Sciences, Monash University, Melbourne, Vic., Australia.
authors.forename: Rahana
authors.initials: R
authors.lastname: Rahman
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Vic., Australia.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lim
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Vic., Australia.
authors.forename: Bryan
authors.initials: B
authors.lastname: Leaw
authors.affiliation: Monash Pathology, Monash Health, Clayton, Vic., Australia.
authors.forename: James
authors.initials: J
authors.lastname: Doery
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Vic., Australia.|Department of Obstetrics and Gynaecology, School of Clinical Sciences, Monash University, Melbourne, Vic., Australia.
authors.forename: Euan M
authors.initials: EM
authors.lastname: Wallace
authors.affiliation: Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Vic., Australia.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Ebeling
mesh_terms: D000328:Adult; D002460:Cell Line; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007231:Infant, Newborn; D008431:Maternal-Fetal Exchange; D009035:Mothers; D011247:Pregnancy; D011248:Pregnancy Complications; D012701:Serotonin / Q000097:blood*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000150:complications; D055815:Young Adult
chemical_list: D014807:Vitamin D; D012701:Serotonin; C104450:25-hydroxyvitamin D