Fetal liver blood flow distribution: role in human developmental strategy to prioritize fat deposition versus brain development

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 fa

Optimal fetal growth – a misconception?

Alterations in fetal growth trajectory, either in terms of individual organs or the fetal body, constitute part of a suite of adaptive responses that the fetus can make to a developmental challenge such as inadequate nutrition. Nonetheless, despite substantial changes in nutrition in many countries over recent centuries, mean birthweight has changed relatively little. Low birthweight is recognised as a risk factor for later noncommunicable disease, although the developmental origins of such risk are graded across the full range of fetal growth and birthweight. Many parental and environmental factors, some biological, some cultural, can influence fetal growth, and these should not be viewed as abnormal. We argue that the suggestion of establishing a universal standard for optimal fetal growth ignores the breadth of these normal fetal responses. It may influence practice adversely, through incorrect estimation of gestational age and unnecessary elective deliveries. It raises ethical as well as practical issues

Impacto de la diabetes mellitus en la circulación hepática fetal y nuevas opciones diagnósticas

While biometry and Doppler have proved useful in the management of fetal growth restriction, the same battery has been of less help in diabetic pregnancies. It is not surprising since the underlying pathophysiology is fundamentally different. Recent studies of the fetal liver, a key metabolic organ, have shown that its venous circulation reflects the impact of maternal hyperglycemia. Umbilical return from the placenta is disproportionately distributed to the fetal liver (more than in normally growing fetuses, and more than in non-diabetic macrosomia). However, what is set as a pattern at midtrimester is not followed up in the 3rd trimester when high fetal growth continues but no longer correspondingly supported by the umbilical flow to the liver (mL min−1 kg−1 is low). Thus, the status at 3rd trimester is as follows: umbilical flow does not match fetal growth, but the fetal liver still takes a major proportion of the placental return leaving less for the ductus venosus (DV). A distended DV does not help; rather it indicates reduced residual compensatory mechanisms to face hypoxic challenges. The new insights suggest taking into consideration the fetal liver when assessing risks in diabetic pregnancies at 3rd trimester. Measuring umbilical venous flow and its distribution requires high level of skills and accurate techniques, but in the left portal branch (between the DV inlet and the junction with the portal main stem), the blood velocity is regularly accessible and it reflects the skewed umbilical flow to the liver, and its consequences, in a graded manner.Si bien la biometría y el Doppler han demostrado ser útiles en el manejo de la restricción del crecimiento fetal, dichos exámenes han sido de menor ayuda en los embarazos en pacientes diabéticas. Esto no sorprende dado que la fisiopatología subyacente es fundamentalmente diferente. Estudios recientes del hígado fetal, un órgano metabólico clave, han demostrado que su circulación venosa refleja el impacto de la hiperglucemia materna. El retorno umbilical desde la placenta se distribuye de manera desproporcionada al hígado fetal (más que en los fetos de crecimiento normal y más que en la macrosomía no diabética). Sin embargo, lo que se establece como un patrón en el segundo trimestre no persiste en el tercer trimestre cuando al continuar el alto crecimiento no es apoyado proporcionalmente por el flujo umbilical al hígado (mL min−1 kg−1 es bajo). Por lo tanto, el estado en el tercer trimestre es el siguiente: el flujo umbilical no coincide con el crecimiento fetal, pero el hígado fetal sigue tomando una proporción importante del retorno placentario, dejando menos para el ductus venosos (DV). Un DV distendido no ayuda; más bien indica mecanismos compensatorios residuales reducidos para enfrentar desafíos hipóxicos. Los nuevos conocimientos sugieren tener en cuenta el hígado fetal al evaluar los riesgos en los embarazos diabéticos en el tercer trimestre. Medir el flujo venoso umbilical y su distribución requiere de un alto nivel de habilidad y técnicas precisas, pero en la rama portal izquierda (entre la entrada del DV y la unión con la vena porta), la velocidad de la sangre es habitualmente accesible y refleja el flujo umbilical sesgado al hígado, y sus consecuencias, de manera medible.publishedVersio

Birth‐weight differences at term are explained by placental dysfunction and not by maternal ethnicity

Objective To investigate the influence of ethnicity, fetal gender and placental dysfunction on birth weight (BW) in term fetuses of South Asian and Caucasian origin. Methods This was a retrospective study of 627 term pregnancies assessed at two public tertiary hospitals in Spain and Sri Lanka. All fetuses underwent biometry and Doppler examinations within 2 weeks of delivery. The influences of fetal gender and ethnicity, gestational age (GA) at delivery, cerebroplacental ratio (CPR) and maternal age, height, weight and parity on BW were evaluated by multivariable regression analysis. Results Fetuses born in Sri Lanka were smaller than those born in Spain (mean BW = 3026 ± 449 g vs 3295 ± 444 g; P < 0.001). Multivariable regression analysis demonstrated that GA at delivery, maternal weight, CPR, maternal height and fetal gender (estimates = 0.168, P < 0.001; 0.006, P < 0.001; 0.092, P = 0.003; 0.009, P = 0.002; 0.081, P = 0.01, respectively) were associated significantly with BW. Conversely, no significant association was noted for maternal ethnicity, age or parity (estimates = −0.010, P = 0.831; 0.005, P = 0.127; 0.035, P = 0.086, respectively). The findings were unchanged when the analysis was repeated using INTERGROWTH‐21st fetal weight centiles instead of BW (log odds, −0.175, P = 0.170 and 0.321, P < 0.001, respectively for ethnicity and CPR). Conclusion Fetal BW variation at term is less dependent on ethnic origin and better explained by placental dysfunction. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd

The World Health Organization Fetal Growth Charts: A Multinational Longitudinal Study of Ultrasound Biometric Measurements and Estimated Fetal Weight.

BACKGROUND: Perinatal mortality and morbidity continue to be major global health challenges strongly associated with prematurity and reduced fetal growth, an issue of further interest given the mounting evidence that fetal growth in general is linked to degrees of risk of common noncommunicable diseases in adulthood. Against this background, WHO made it a high priority to provide the present fetal growth charts for estimated fetal weight (EFW) and common ultrasound biometric measurements intended for worldwide use. METHODS AND FINDINGS: We conducted a multinational prospective observational longitudinal study of fetal growth in low-risk singleton pregnancies of women of high or middle socioeconomic status and without known environmental constraints on fetal growth. Centers in ten countries (Argentina, Brazil, Democratic Republic of the Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand) recruited participants who had reliable information on last menstrual period and gestational age confirmed by crown-rump length measured at 8-13 wk of gestation. Participants had anthropometric and nutritional assessments and seven scheduled ultrasound examinations during pregnancy. Fifty-two participants withdrew consent, and 1,387 participated in the study. At study entry, median maternal age was 28 y (interquartile range [IQR] 25-31), median height was 162 cm (IQR 157-168), median weight was 61 kg (IQR 55-68), 58% of the women were nulliparous, and median daily caloric intake was 1,840 cal (IQR 1,487-2,222). The median pregnancy duration was 39 wk (IQR 38-40) although there were significant differences between countries, the largest difference being 12 d (95% CI 8-16). The median birthweight was 3,300 g (IQR 2,980-3,615). There were differences in birthweight between countries, e.g., India had significantly smaller neonates than the other countries, even after adjusting for gestational age. Thirty-one women had a miscarriage, and three fetuses had intrauterine death. The 8,203 sets of ultrasound measurements were scrutinized for outliers and leverage points, and those measurements taken at 14 to 40 wk were selected for analysis. A total of 7,924 sets of ultrasound measurements were analyzed by quantile regression to establish longitudinal reference intervals for fetal head circumference, biparietal diameter, humerus length, abdominal circumference, femur length and its ratio with head circumference and with biparietal diameter, and EFW. There was asymmetric distribution of growth of EFW: a slightly wider distribution among the lower percentiles during early weeks shifted to a notably expanded distribution of the higher percentiles in late pregnancy. Male fetuses were larger than female fetuses as measured by EFW, but the disparity was smaller in the lower quantiles of the distribution (3.5%) and larger in the upper quantiles (4.5%). Maternal age and maternal height were associated with a positive effect on EFW, particularly in the lower tail of the distribution, of the order of 2% to 3% for each additional 10 y of age of the mother and 1% to 2% for each additional 10 cm of height. Maternal weight was associated with a small positive effect on EFW, especially in the higher tail of the distribution, of the order of 1.0% to 1.5% for each additional 10 kg of bodyweight of the mother. Parous women had heavier fetuses than nulliparous women, with the disparity being greater in the lower quantiles of the distribution, of the order of 1% to 1.5%, and diminishing in the upper quantiles. There were also significant differences in growth of EFW between countries. In spite of the multinational nature of the study, sample size is a limiting factor for generalization of the charts. CONCLUSIONS: This study provides WHO fetal growth charts for EFW and common ultrasound biometric measurements, and shows variation between different parts of the world

Fetal age assessment based on 2nd trimester ultrasound in Africa and the effect of ethnicity

<p>Abstract</p> <p>Background</p> <p>The African population is composed of a variety of ethnic groups, which differ considerably from each other. Some studies suggest that ethnic variation may influence dating. The aim of the present study was to establish reference values for fetal age assessment in Cameroon using two different ethnic groups (Fulani and Kirdi).</p> <p>Methods</p> <p>This was a prospective cross sectional study of 200 healthy pregnant women from Cameroon. The participants had regular menstrual periods and singleton uncomplicated pregnancies, and were recruited after informed consent. The head circumference (HC), outer-outer biparietal diameter (BPDoo), outer-inner biparietal diameter and femur length (FL), also called femur diaphysis length, were measured using ultrasound at 12–22 weeks of gestation. Differences in demographic factors and fetal biometry between ethnic groups were assessed by t- and Chi-square tests.</p> <p>Results</p> <p>Compared with Fulani women (N = 96), the Kirdi (N = 104) were 2 years older (p = 0.005), 3 cm taller (p = 0.001), 6 kg heavier (p < 0.0001), had a higher body mass index (BMI) (p = 0.001), but were not different with regard to parity. Ethnicity had no effect on BPDoo (p = 0.82), HC (p = 0.89) or FL (p = 00.24). Weight, height, maternal age and BMI had no effect on HC, BPDoo and FL (p = 0.2–0.58, 0.1–0.83, and 0.17–0.6, respectively).</p> <p>When comparing with relevant European charts based on similar design and statistics, we found overlapping 95% CI for BPD (Norway & UK) and a 0–4 day difference for FL and HC.</p> <p>Conclusion</p> <p>Significant ethnic differences between mothers were not reflected in fetal biometry at second trimester. The results support the recommendation that ultrasound in practical health care can be used to assess gestational age in various populations with little risk of error due to ethnic variation.</p

Heart function by M-mode and tissue Doppler in the early neonatal period in neonates with fetal growth restriction

Background: Fetal growth restricted (FGR) neonates have increased risk of circulatory compromise due to failure of normal transition of circulation after birth. Aim: Echocardiographic assessment of heart function in FGR neonates first three days after birth. Study design: Prospective observational study. Subjects: FGR- and non-FGR neonates. Outcome measures: M-mode excursions and pulsed-wave tissue Doppler velocities normalised for heart size and E/e′ of the atrioventricular plane day one, two and three after birth. Results: Compared with controls (non-FGR of comparable gestational age, n = 41), late-FGR (gestational age ≥ 32 weeks, n = 21) exhibited higher septal excursion (15.9 (0.6) vs. 14.0 (0.4) %, p = 0.021) (mean (SEM)) and left E/e′ (17.3 (1.9) vs.11.5 (1.3), p = 0.019). Relative to day three, indexes on day one were higher for left excursion (21 (6) % higher on day one, p = 0.002), right excursion (12 (5) %, p = 0.025), left e′ (15 (7) %, p = 0.049), right a′ (18 (6) %, p = 0.001), left E/e′ (25 (10) %, p = 0.015) and right E/e′ (17 (7) %, p = 0.013), whereas no index changed from day two to day three. Late-FGR had no impact on changes from day one and two to day three. No measurements differed between early-FGR (n = 7) and late-FGR. Conclusions: FGR impacted neonatal heart function the early transitional days after birth. Late-FGR hearts had increased septal contraction and reduced left diastolic function compared with controls. The dynamic changes in heart function between first three days were most evident in lateral walls, with similar pattern in late-FGR and non-FGR. Early-FGR and late-FGR exhibited similar heart function.publishedVersio