Figure 1.
Diagrammatic representation of the fetal circulation, showing blood flow to the fetal liver and brain.
(A) Nutrient-rich blood returning from the placenta in the umbilical vein either perfuses the fetal liver or bypasses it through the shunt of the ductus venosus. (B) “Brain-sparing” is associated with cerebral vasodilation, altering the blood flow velocity waveform in the middle cerebral artery, and lowering the pulsatility index. The figure is modified from Ref 20; reproduced with permission.
Figure 2.
Brain-sparing blood flow pattern in relation to fetal sex, placental weight and liver shunting.
Measurements of middle cerebral artery pulsatility index (MCA PI) showed evidence for brain-sparing (low MCA PI) in (A) male fetuses (P = 0.03) (Bars represent mean values & SEM, n = 110 and 103, for males and females, respectively), and in (B) those with smaller placentas (P = 0.02) (Bars represent mean values & SEM, n = 49, 49, 49, and 48, respectively). (C) Greater ductus venosus liver shunting was also related to brain-sparing; MCA PI was lower in fetuses in the highest quarter of the distribution of ductus venosus liver shunting when compared with those in the lowest three-quarters of the distribution (P = 0.04) (Bars represent mean values & SEM, n = 53 and 160, respectively).
Figure 3.
Relations of fetal liver blood flow and mother's adiposity to prenatal fat deposition.
(A) Greater fetal liver blood flow at 36 weeks gestation was associated with greater neonatal body fat mass at every level of mother's pre-pregnancy adiposity. P values are for a simultaneous analysis in which both greater fetal liver blood flow and greater mother's adiposity had strong associations with greater neonatal body fat mass (Groupings are thirds of the distributions. P values are for analysis of the continuously distributed variables. Bars represent mean values & SEM, n = 15, 15 and 21 for low, 19, 13 and 18 for average, and 17, 23 and 10 for high mother's adiposity groups, respectively). (B) The effect of fetal liver blood flow on body fat mass persisted into early childhood, with greater fetal liver blood flow also being associated with body fat mass at age 4 years (Groupings are thirds of the distribution. P value is for analysis of the continuously distributed variable. Bars represent mean values & SEM, n = 61, 67 and 69, respectively).
Figure 4.
Suggested developmental strategies associated with imbalances between fetal nutrient demand and materno-placental nutrient supply.
The distribution of placental blood flow is based on nutritional status, with ductus venosus liver shunting and brain-sparing if the fetal demand for essential nutrients exceeds placental supply (A). However, when supply of conditionally essential nutrients is inadequate, the strategy is to prioritize liver blood flow, enabling hepatic nutrient interconversions and the synthesis of fatty acids required for fat deposition; in this circumstance fat deposition is prioritized as it is needed for neonatal thermoregulation and as a buffer for brain development during subsequent periods of limited nutrient supply (B). In environments less affluent than those now prevalent in developed populations, facilitated placental transfer mechanisms evolved for glucose and other nutrients to enable materno-placental nutrient supply to meet fetal nutrient demand, resulting in optimal fetal body composition (C); however, in circumstances of nutrient excess (such as maternal adiposity and impaired glucose tolerance (IGT)) these mechanisms also lead to prenatal fat deposition (D).
Table 1.
Principal findings of the study.