Fetal Liver-Sparing Cardiovascular Adaptations Linked to Mother’s Slimness and Diet

Abstract

Fetal adaptations to impaired maternoplacental nutrient supply include altered regional blood flow. Whether such responses operate within the normal range of maternal body composition or diet is unknown, but any change in fetal liver perfusion could alter hepatic development, with long-term consequences for the risk of cardiovascular and metabolic disease. In 381 low-risk pregnancies, we found that the fetuses of slimmer mothers with lower body fat stores and those eating an unbalanced diet had greater liver blood flow and shunted less blood away from the liver through the ductus venosus at 36 weeks gestation. Consequences of such "liver-sparing" may underlie the increased cardiovascular risk of people whose mothers were slimmer and had lower body fat stores in pregnancy.T he processes controlling the growth of individual fetal organs are incompletely understood, but during mammalian development, changes in blood flow to an organ affect its growth and can have major lifelong effects on organ function. The fetus uses changes in blood flow to defend itself against an insult such as reduced oxygen availability. By distributing blood pumped by the heart toward essential organs, eg, the brain ("brain-sparing"), at the expense of organs such as muscle, gut and liver, the fetus reduces nonessential growth and economizes on oxygen demand. It is not known whether similar adaptive mechanisms regulate blood flow and growth in relation to fetal nutrient supply within the normal range: if so, such mechanisms may be invoked by maternal factors such as body fat stores and diet, and might in part underlie the link between the intrauterine environment and health in adulthood. 1 Materials and MethodsTo examine the relation between maternal body fatness and diet and fetal hepatic blood flow at 36 weeks gestation, we approached a low-risk population of 410 healthy women with singleton pregnancies and no major fetal abnormality. A study of this size has 90% power to detect a correlation coefficient of 0.16 between maternal body fatness and fetal hepatic blood flow at the 5% level. The women's heights, weights, skinfold thicknesses, mid-upper arm circumferences, and diet had been measured by trained research nurses before pregnancy in the Southampton Women's Survey. 2 We used Doppler ultrasound (Acuson Sequoia) to measure blood flow in the umbilical vein and ductus venosus; the ductus venosus shunts a proportion of well-oxygenated placental blood past the fetal liver, toward the heart and head (Figure 1). We measured internal vessel diameter (late-diastole) and time-averaged maximum velocity (TAMX) (insonation angle Ͻ30°) in the intraabdominal umbilical vein (straight portion, before hepatic parenchymal branches) and at the ductus venosus inlet. Umbilical vein TAMX was obtained during a 3-to 5-second period or, if flow was pulsatile, as the mean during three heart cycles. Ductus venosus TAMX was calculated as the mean during three heart cycles. Blood flow (Q) was calculated as Qϭh ⅐ (D/2) 2 ⅐ ⅐ TAMX, where Dϭvessel diameter (mean of ...

Longitudinal Study of Umbilical and Portal Venous Blood flow to the Fetal Liver: Low Pregnancy Weight Gain is Associated With Preferential Supply to the Fetal Left Liver Lobe

“…In fetal sheep the venous blood perfusion of the liver is linked to hepatic synthesis of insulin-like growth factors and peripheral cell proliferation (4). The positive correlation between UV, LPV, PV, and total venous liver flow and BW fits with these experimental data and is in agreement with a previous study (6).…”

“…In human fetuses liver perfusion is apparently influenced by maternal body composition and diet (6). We found no overall effect of maternal prepregnancy BMI on venous liver perfusion, but analysis of the subgroup of measurements from 35 ϩ 0 wk toward term demonstrated a relationship with the DV shunt fraction, confirming a previous study (6).…”

“…In human fetuses, venous liver blood flow was shown to be modulated by maternal diet and body composition (6).…”

Early-postnatal changes in adiposity and lipids profile by transgenerational developmental programming in swine with obesity/leptin resistance

“…The development of the liver is critical for enhancing hepatic glucogenic capacity during the nutritional transition from a continuous maternal supply of nutrients via the placenta to a more intermittent supply from the milk via the intestine after birth (Shelley 1961, Dawkins 1966, Trahair & Sangild 1997 and, therefore, adequate liver development favours postnatal growth (Antipatis et al 2000). It has been described that foetuses undergoing adverse nutritional conditions have a faster liver development through a 'liver-sparing effect' (Haugen et al 2005). Therefore, our finding may be a transgenerational effect, supported by the concomitant findings of lower weights of intestine and adrenal glands.…”

The Effect of Maternal Undernutrition in Early Gestation on Gestation Length and Fetal and Postnatal Growth in Sheep

“…In studies of the Dutch Hunger Winter, maternal undernutrition during early gestation, when the nutrient demands of the conceptus are minimal, is associated with increased prevalence of cardiovascular disease (CV) disease in adulthood (2). In utero undernutrition in humans may result in CV and metabolic and growth adaptations (3)(4)(5) aimed at increasing energy supply or reducing energy expenditure but with postnatal consequences. The nature, timing, and intensity of an in utero nutritional challenge, as well as maternal age, parity, and offspring number and sex, will determine the degree of constraint (6) imposed on the fetus and are likely to dictate the strategy adopted by it to enhance immediate survival.…”