Fetal oxygen and glucose consumption in human pregnancy complicated by fetal growth restriction

In healthy pregnancy, glucose and oxygen availability are essential for fetal growth and wellbeing. However, how substrate delivery and fetal uptake are affected in human pregnancy complicated by fetal growth restriction (FGR) is still unknown. Here we show that the human FGR fetus has a strikingly reduced umbilical uptake of both oxygen and glucose. In 30 healthy term and 32 FGR human pregnancies umbilical volume flow (Qumb) and parallel umbilical vein (uv) and artery (ua) blood samples were obtained at elective Caesarean section to calculate fetal glucose and oxygen uptake as Qumb • Δ (uv-ua) differences. Umbilical blood flow was significantly lower in FGR pregnancy (-63%, P<0.001) but not when normalized for fetal body weight. FGR pregnancy had significantly lower umbilical oxygen delivery and uptake, both as absolute values (delivery: –78%; uptake: –78%) and normalized (delivery: –50%; uptake: –48%) for fetal body weight (all P<0.001). Umbilical glucose absolute delivery and uptake were significantly reduced (delivery: –68%; uptake: –72%) but only glucose uptake was decreased when normalized for fetal body weight (–30%, P<0.05). The glucose/oxygen quotient was significantly increased (+100%, P<0.05) while glucose clearance was significantly decreased (71%, P<0.001) in FGR pregnancy (both P<0.05). The human fetus in FGR pregnancy triggers compensatory mechanisms to reduce its metabolic rate, matching the proportion of substrate consumption relative to oxygen delivery as a survival strategy during complicated pregnancy.Financial support was obtained by grants from Fondazione Giorgio Pardi, by ASM (Associazione Italiana per lo Studio delle Malformazioni), and by a Grant of the Italian Ministry of University and Research PRIN 2010-2011 prot. 20102chst5_005

Relationship between in utero sonographic evaluation and subcutaneous plicometry after birth in infants with intrauterine growth restriction: an exploratory study

<p>Abstract</p> <p>Background</p> <p>Intrauterine growth restriction (IUGR) is associated with several medical complications before and after delivery. The aim of this study was to evaluate the concordance between the fetal ultrasonographic measurement of subcutaneous tissue thicknesses and the skinfold thicknesses assessment in intrauterine growth restricted newborns.</p> <p>Methods</p> <p>We designed an exploratory study. Fetal ultrasonographic measurement of subcutaneous tissue thicknesses, according to Bernstein's and Galan's method, and neonatal skinfold thicknesses were evaluated in 13 intrauterine growth restricted newborns within 4 hours before delivery and on the first day of life, respectively. Concordance between fetal and neonatal measurements was assessed using the Lin's correlation coefficient and the Bland-Altman method.</p> <p>Results</p> <p>The data obtained by the measurements of neonatal skinfold thicknesses was significantly correlated with the prenatal measurements (Lin's coefficients, arm: 0.60; subscapular: 0.72; abdomen: 0.51). Bland-Altman analysis showed moderate agreement between the fetal ultrasonographic measurement of subcutaneous tissue thicknesses and the neonatal skinfold thicknesses assessment.</p> <p>Conclusions</p> <p>The present study provides preliminary evidence that fetal sonographic measurements may represent additional indices of intrauterine growth restriction.</p

Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol

Introduction: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. Methods and analysis: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is &lt;10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. Ethics and dissemination: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. Trial registration number: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical &amp; Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200

Perinatal and Neonatal Outcomes in Fetal Growth Restriction and Small for Gestational Age

Alterations in intrauterine fetal growth increase the risk of adverse perinatal and neonatal outcomes. In this retrospective study, we analyzed data of 906 pregnancies collected in our maternal fetal medicine center, with different patterns of growth: 655 AGA (Appropriate for Gestational Age), 62 SGA (Small for Gestational Age: fetuses born with a weight less than 10&deg; centile, not diagnosed before delivery), 189 FGR (Fetal Growth Restriction, classified in early and late according to gestational week at diagnosis). For each group, we compared maternal characteristics, gestational age at delivery, and perinatal and neonatal outcomes. Risk factors for fetal growth alterations were advanced age, being primiparous, and a lower pregestational BMI. FGR fetuses were born at earlier gestational ages (32 [IQR 29&ndash;38] early-FGR and 38 [IQR 36&ndash;39] late-FGR), with blood gas values comparable to the AGA group but worse neonatal outcomes related to prematurity. Unexpected SGA fetuses born by vaginal delivery, managed as AGA, were more hyperlactacidemic (4.4 [IQR 2.7&ndash;5.5]) and hypoxemic (&minus;5.0 [IQR &minus;7.1&ndash;2.8]) at birth than both AGA and FGR. However, neonatal outcomes (accesses and days of hospitalization in NICU) were better than FGR, likely due to gestational age and birthweight similar to AGA

Plasma amino acid concentrations throughout normal pregnancy and early stages of intrauterine growth restricted pregnancy

Objectives: Assessment of maternal plasma amino acids during normal gestation and in early stages of intrauterine growth restriction (IUGR). Study design: Plasma amino acid concentrations were measured in: (1) non-pregnant women (n = 7); (2) normal pregnant women in the first (n = 13), second (n = 17) and third (n = 12) trimester; and (3) pregnant women in the first trimester with later development of IUGR (n = 8). Amino acid levels were quantified by electrochemical detection in a reversed-phase high-performance liquid chromatography (HPLC) system. Results: The levels of most essential and non-essential amino acids changed markedly in the first trimester during normal pregnancy and thereafter remained almost constant. In the first trimester of IUGR, a number of both essential and non-essential amino acids were significantly different from those observed in normal pregnancies, with values more similar to those observed in non-pregnant women. Conclusions: Levels of most maternal amino acids decrease and some increase during early gestation reflecting a metabolic adaptation that occurs in normal pregnancies. Pregnancies that later develop IUGR show a lack of these adaptations for a significant number of both essential and non-essential amino acids, suggesting a lack of adaptation