title: Human fetal growth is constrained below optimal for perinatal survival.
abstract: OBJECTIVE
  The use of fetal growth charts assumes that the optimal size at birth is at the 50(th) birth-weight centile, but interaction between maternal constraints on fetal growth and the risks associated with small and large fetal size at birth may indicate that this assumption is not valid for perinatal mortality rates. The objective of this study was to investigate the distribution and timing (antenatal, intrapartum or neonatal) of perinatal mortality and morbidity in relation to birth weight and gestational age at delivery.
  
  
  METHODS
  Data from over 1 million births occurring at 28-43 weeks' gestation from singleton pregnancies without congenital abnormalities in the period from 2002 to 2008 were collected from The Netherlands Perinatal Registry. The distribution of perinatal mortality according to birth-weight centile and gestational age at delivery was studied.
  
  
  RESULTS
  In the 1 170 534 pregnancies studied, there were 5075 (0.43%) perinatal deaths. The highest perinatal mortality occurred in those with a birth weight below the 2.3(rd) centile (25.4/1000 births) and the lowest mortality was in those with birth weights between the 80(th) and 84(th) centiles (2.4/1000 births), according to routinely used growth charts. Antepartum deaths were lowest in those with birth weight between the 90(th) and 95(th) centiles. Data were almost identical when the analysis was restricted to infants born at ≥ 37 weeks' gestation.
  
  
  CONCLUSIONS
  From an immediate survival perspective, optimal fetal growth requires a birth weight between the 80(th) and 84(th) centiles for the population. Median birth weight in the population is, by definition, substantially lower than these centiles, implying that the majority of fetuses exhibit some form of maternal constraint on growth. This finding is consistent with adaptations that have evolved in humans in conjunction with a large head and bipedalism, to reduce the risk of obstructed delivery. These data also fit remarkably well with those on long-term adult cardiovascular and metabolic health risks, which are lowest in cases with a birth weight around the 90(th) centile.
authors.affiliation: Department of Obstetrics, University Medical Center Utrecht, Lundlaan, Utrecht, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Vasak
authors.forename: S V
authors.initials: SV
authors.lastname: Koenen
authors.forename: M P H
authors.initials: MP
authors.lastname: Koster
authors.forename: C W P M
authors.initials: CW
authors.lastname: Hukkelhoven
authors.forename: A
authors.initials: A
authors.lastname: Franx
authors.forename: M A
authors.initials: MA
authors.lastname: Hanson
authors.forename: G H A
authors.initials: GH
authors.lastname: Visser
mesh_terms: D001724:Birth Weight; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007226:Infant Mortality / Q000639:trends*; D007231:Infant, Newborn; D009426:Netherlands / Q000453:epidemiology; D054238:Perinatal Mortality / Q000639:trends*; D011247:Pregnancy; D012189:Retrospective Studies; D012307:Risk Factors
keywords: birth weight; fetal growth; maternal constraint; perinatal mortality; perinatal survival