title: The influence of sex and antenatal betamethasone exposure on vasoconstrictors and the preterm microvasculature.
abstract: OBJECTIVE
  Dysregulated vascular resistance contributes to hypotension following preterm birth with sex-specific differences in microvascular function conferring a male disadvantage. We hypothesized that glucocorticoid mediated, sex-specific differences in the endogenous catecholamine norepinephrine and endothelially derived endothelin-1 (ET-1) contribute to microvascular dysfunction in preterm neonates in the immediate newborn period.
  
  
  METHODS
  Umbilical and plasma ET-1 and normetanephrine, in 24 h urine samples, were determined at 24, 72, and 120 h of age in 24-34 week infants (n = 60). Microvascular blood flow was determined by laser Doppler flowmetry.
  
  
  RESULTS
  In infants born within 72 h of antenatal glucocorticoid exposure, normetanephrine was higher in females than males (p = 0.048). Normetanephrine was inversely correlated with both microvascular blood flow at 24 h (p = 0.025) and CRIB II (p = 0.001). While umbilical arterial ET-1 was higher in females delivered <72 h after antenatal betamethasone (p = 0.006), plasma ET-1 did not correlate with microvascular blood flow or illness severity. Only sex and normetanephrine contributed significantly to both microvascular blood flow and endothelium dependant vasodilatation.
  
  
  CONCLUSIONS
  These data support glucocorticoid mediated, sex-specific differences in mediators of vascular tone that may contribute to the impaired mechanisms compromising successful hemodynamic adaption to neonatal life and resulting in excess male morbidity and mortality.
authors.affiliation: School of Paediatrics and Reproductive Health, The Robinson Institute, University of Adelaide, Adelaide, SA 5005, Australia. michael.stark@adelaide.edu.au
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Stark
authors.forename: Nicolette A
authors.initials: NA
authors.lastname: Hodyl
authors.forename: Ian M R
authors.initials: IM
authors.lastname: Wright
authors.forename: Vicki
authors.initials: V
authors.lastname: Clifton
mesh_terms: D001623:Betamethasone / Q000494:pharmacology*; D019332:Endothelin-1 / Q000097:blood; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood / Q000652:urine; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D009647:Normetanephrine / Q000652:urine; D011247:Pregnancy; D012737:Sex Factors; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D019332:Endothelin-1; D005938:Glucocorticoids; D009647:Normetanephrine; D001623:Betamethasone