Prospective association of fetal liver blood flow at 30 weeks gestation with newborn adiposity

Abstract

Background The production of variation in adipose tissue accretion represents a key fetal adaptation to energy substrate availability during gestation. Because umbilical venous blood transports nutrient substrate from the maternal to the fetal compartment, and the fetal liver is the primary organ where nutrient inter-conversion occurs, it has been proposed that variations in the relative distribution of umbilical venous blood flow shunting either through ductus venosus or perfusing the fetal liver represents a mechanism underlying this adaptation. Objective The objective of the present study was to determine whether fetal liver blood flow assessed before the period of maximal fetal fat deposition (i.e., the third trimester of gestation) is prospectively associated with newborn adiposity. Study design A prospective study was conducted in a cohort of 62 uncomplicated singleton pregnancies. Fetal ultrasonography was performed at 30 weeks gestation for conventional fetal biometry and characterization of fetal liver blood flow (fLBF; quantified by subtracting ductus venosus flow from umbilical vein flow). Newborn body fat percentage was quantified by Dual Energy X-Ray Absorptiometry (DXA) imaging at 25.8 ± 3.3 (mean ± SEM) postnatal days. Multiple regression analysis was used to determine the proportion of variation in newborn body fat percentage explained by fLBF. Potential confounding factors included maternal age, parity, pre-pregnancy body mass index (ppBMI), gestational weight gain, gestational age at birth, infant sex, postnatal age at DXA scan, and mode of infant feeding. Results Newborn body fat percentage was 13.5 ± 2.4% (mean ± SEM). fLBF at 30 weeks gestation was significantly and positively associated with newborn total fat mass (r = 0.397, p < 0.001) and body fat percentage (r = 0.369, p = 0.004), but not with lean mass (r = 0.100, p = 0.441). After accounting for the effects of covariates, fLBF explained 13.5% of the variance in newborn fat mass. The magnitude of this association was particularly pronounced in non-overweight/non-obese mothers (ppBMI <25, n = 36), in whom fLBF explained 24.4% of the variation in newborn body fat percentage. Conclusions fLBF at the beginning of the third trimester of gestation is positively associated with newborn adiposity, particularly among non-overweight/non-obese mothers. This finding supports the role of fLBF as a putative fetal adaptation underlying variation in adipose tissue accretion.

Maternal diabetes alters the development of ductus venosus shunting in the fetus

“…In fetal lamb, occluding the DV and forcing all UV blood to perfuse the fetal liver, leads to increased liver weight, cell proliferation, and differential fetal organ growth . Up‐regulation of the UV blood distribution to the liver is believed to be an important mechanism underlying the development of macrosomia and increased fat accretion , and the present study has demonstrated this flow pattern in PGDM pregnancies. However, in macrosomia without DM, the UV flow volume accelerates during the third trimester, supporting the increased growth velocity, whereas the DV flow volume remains unchanged .…”

“…The distribution of the blood flow through the UV and DV develop differently in fetuses with normal growth, growth restriction, and macrosomia without maternal diabetes . This suggests that the umbilical supply to the liver plays a role in regulating fetal growth and fat deposition , with possible lifelong consequences . The DV shunts oxygenated UV blood to the fetal heart and brain, bypassing the liver , and increased shunting serves as a protective mechanism .…”

The impact of umbilical vein blood flow and glucose concentration on blood flow distribution to the fetal liver and systemic organs in healthy pregnancies

“…3 Several human studies in low risk populations have demonstrated a positive association between fetal liver flow and fetal variables such as growth, birth weight, 29,30 and fat deposition. 3,4 Growth restricted fetuses often display increased head-abdomen (HC/AC) ratio as well as increased DV-shunting fraction. This is assumed to ensure oxygen and nutritional supply to vital organs as the brain and heart.…”

“…6 Interestingly, Ikenoue et al found a significant correlation between fetal liver flow and newborn fat percentage, but in subclass analyses the relation was strengthened in the maternal normal-weight group and disappeared in the overweight group. 4 Body mass index (BMI) is often used as a proxy for body fat mass. In early pregnancy, BMI measures correlate better with body fat mass than BMI measures later in pregnancy.…”

“…This is supported by positive correlations between liver blood flow, growth, and fat accretion in the third trimester in human ultrasound based studies. 3,4 It has further been suggested that the fetal intrauterine nutritional environment provided by the materno-placental unit may influence fetal liver blood flow, and thus affect fetal growth and fat deposition. Haugen et al described a "liver sparing" response, where fetuses with under-or malnourished mothers tended to prioritize blood flow to the liver in gestational week 36, probably to optimize fat accumulation before birth.…”