title: Fetal liver blood flow distribution: role in human developmental strategy to prioritize fat deposition versus brain development.
abstract: Among primates, human neonates have the largest brains but also the highest proportion of body fat. If placental nutrient supply is limited, the fetus faces a dilemma: should resources be allocated to brain growth, or to fat deposition for use as a potential postnatal energy reserve? We hypothesised that resolving this dilemma operates at the level of umbilical blood distribution entering the fetal liver. In 381 uncomplicated pregnancies in third trimester, we measured blood flow perfusing the fetal liver, or bypassing it via the ductus venosus to supply the brain and heart using ultrasound techniques. Across the range of fetal growth and independent of the mother's adiposity and parity, greater liver blood flow was associated with greater offspring fat mass measured by dual-energy X-ray absorptiometry, both in the infant at birth (r = 0.43, P<0.001) and at age 4 years (r = 0.16, P = 0.02). In contrast, smaller placentas less able to meet fetal demand for essential nutrients were associated with a brain-sparing flow pattern (r = 0.17, p = 0.02). This flow pattern was also associated with a higher degree of shunting through ductus venosus (P = 0.04). We propose that humans evolved a developmental strategy to prioritize nutrient allocation for prenatal fat deposition when the supply of conditionally essential nutrients requiring hepatic inter-conversion is limited, switching resource allocation to favour the brain if the supply of essential nutrients is limited. Facilitated placental transfer mechanisms for glucose and other nutrients evolved in environments less affluent than those now prevalent in developed populations, and we propose that in circumstances of maternal adiposity and nutrient excess these mechanisms now also lead to prenatal fat deposition. Prenatal developmental influences play important roles in the human propensity to deposit fat.
authors.affiliation: Institute of Developmental Sciences, University of Southampton, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Godfrey
authors.forename: Guttorm
authors.initials: G
authors.lastname: Haugen
authors.forename: Torvid
authors.initials: T
authors.lastname: Kiserud
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Inskip
authors.forename: Cyrus
authors.initials: C
authors.lastname: Cooper
authors.forename: Nicholas C W
authors.initials: NC
authors.lastname: Harvey
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Crozier
authors.forename: Sian M
authors.initials: SM
authors.lastname: Robinson
authors.forename: Lucy
authors.initials: L
authors.lastname: Davies
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hanson
mesh_terms: D000222:Adaptation, Physiological; D050154:Adiposity; D001921:Brain / Q000098:blood supply / Q000196:embryology*; D005260:Female; D005333:Fetus / Q000098:blood supply* / Q000196:embryology*; D006801:Humans; D008099:Liver / Q000098:blood supply* / Q000196:embryology*; D008297:Male; D011247:Pregnancy; D012039:Regional Blood Flow; D014471:Umbilical Veins / Q000098:blood supply / Q000502:physiology