Gioia Alvino

Intrauterine growth restriction is associated with changes in polyunsaturated fatty acid fetal-maternal relationships.

Fetuses with intrauterine growth restriction (IUGR) are at increased risk of death and disease during neonatal, pediatric, and adult life. Postnatal deficits in essential fatty acids have been associated with the neural and vascular complications of premature neonates. We studied whether fetal-maternal fatty acid relationships are already impaired in utero in IUGR fetuses. Fetal (F) and maternal (M) fatty acid profiles were determined in utero in 11 normal [appropriate for gestational age (AGA)] and in 10 IUGR fetuses by fetal blood sampling (FBS) between 19 and 39 wk. Total plasma fatty acid concentrations were significantly higher in M than in F of both AGA (M: 2.03 ± 0.53 mg/mL; F: 0.64 ± 0.29 mg/mL;p < 0.001) and IUGR (M: 2.16 ± 0.59 mg/mL; F: 0.73 ± 0.17 mg/mL;p < 0.001). The F/M ratio was significantly higher for linoleic acid (AGA: 0.36 ± 0.09; IUGR: 0.52 ± 0.12;p < 0.01) and significantly lower for the long-chain polyunsaturated fatty acid docosahexaenoic acid (AGA: 1.94 ± 0.32; IUGR: 1.25 ± 0.19;p < 0.05) and arachidonic acid (AGA: 2.35 ± 0.35%; IUGR: 2.04 ± 0.3%;p < 0.05) in IUGR compared with AGA pregnancies. The differences observed in the relative amounts but not in total plasma concentrations of fatty acid fetal-maternal relationships in pregnancies associated with IUGR could be related to inadequate transplacental supply as well as to a fetal lack of the enzymes necessary for elaboration of these metabolically relevant conditionally essential fatty acids. These differences might have a role in determining the biochemical environment leading to the neural and vascular complications associated with IUGR.

Long chain fatty acids and dietary fats in fetal nutrition

Long chain polyunsaturated fatty acids are essential nutrients for a healthy diet. The different kinds consumed by the mother during gestation and lactation may influence pregnancy, fetal and also neonatal outcome. The amount of fatty acids transferred from mother to fetus depends not only on maternal metabolism but also on placental function, i.e. by the uptake, metabolism and then transfer of fatty acids to the fetus. The third trimester of gestation is characterized by an increase of long chain polyunsaturated fatty acids in the fetal circulation, in particular docosahexaenoic acid, especially to support brain growth and visual development. These mechanisms may be altered in pathological conditions, such as intrauterine growth restriction and diabetes, when maternal and fetal plasma levels of long chain polyunsaturated fatty acids undergo significant changes. The aim of this review is to describe the maternal and placental factors involved in determining fetal fatty acid availability and metabolism, focusing on the specific role of long chain polyunsaturated fatty acids in normal and pathological pregnancies.

Maternal and Fetal Fatty Acid Profile in Normal and Intrauterine Growth Restriction Pregnancies With and Without Preeclampsia

The aim of this study was to evaluate maternal and fetal lipid profile in intrauterine growth restriction (IUGR) pregnancies with and without preeclampsia (PE). Thirteen normal pregnancies studied during the third trimester (control M) and 29 at elective cesarean section (control CS) were compared with 18 pregnancies complicated by IUGR (IUGR only) and with seven pregnancies complicated by both IUGR and PE (IUGR-PE). Total plasma fatty acids, triglycerides, cholesterol, and nonesterified fatty acids (NEFA) were determined in maternal and fetal plasma. Nutritional intake was analyzed. IUGR only mothers had lower percentage of linoleic acid (LA) and higher arachidonic acid (AA) than controls, partly explained by higher AA dietary intake. Higher levels of NEFA were observed both in IUGR only and in IUGR-PE mothers whereas triglyceride levels were increased in IUGR-PE mothers only. In IUGR-PE fetuses, LA and AA were significantly decreased, whereas triglyceride and NEFA concentrations were significantly increased compared with normal fetuses. In conclusion, IUGR only is associated with altered fatty acids profile not completely accounted by dietary changes. We hypothesize that the differences observed in IUGR with PE for triglycerides and other lipids could be related to a difference in maternal phenotype.

Placental LPL Gene Expression Is Increased in Severe Intrauterine Growth-Restricted Pregnancies

Intrauterine growth restriction (IUGR) is associated with reduced placental supply of nutrients to the fetus. Lipoprotein lipase (LPL) mediates the hydrolysis of triglycerides from maternal lipoproteins to obtain fatty acids. Here, we tested the hypothesis that placental LPL gene expression level is altered in pregnancies complicated by IUGR. To this purpose, 28 IUGR fetuses were identified during pregnancy and divided in two groups: 7 M-IUGR [“mild” IUGR, with normal umbilical artery pulsatility index (PI)] and 21 S-IUGR (“severe” IUGR, with abnormal PI). Moreover, 10 out of 28 IUGR pregnancies were associated with preeclampsia. Controls were 19 normal pregnancies delivering appropriate for gestational age (AGA) fetuses. Relative real-time quantification of LPL was carried out in RNA from placental chorionic villi by the ΔΔCt method, using β-actin as normalizing gene. Placental LPL mRNA expression levels were significantly higher in IUGR than in AGA. In particular, significantly higher values were observed in S-IUGR, independent from the concomitant association with preeclampsia. No significant relationship was observed between placental LPL mRNA expression levels or gestational age. In conclusion, placental LPL mRNA gene expression is increased in severe IUGR, characterized by enhanced vascular placental resistances and alterations of placental nutrient transport.

Fetal nutrition: A review

Knowledge of fetal nutrient supply has greatly increased in the last decade due to the availability of fetal blood samples obtained under relatively steady-state conditions. These studies, together with studies utilizing stable isotope methodologies, have clarified some aspects of the supply of the major nutrients for the fetus such as glucose, amino acids and fatty acids. At the same time, the relevance of intrauterine growth has been recognized not only for the well-being of the neonate and child, but also for later health in adulthood. The major determinants of fetal nutrient availability are maternal nutrition and metabolism together with placental function and metabolism. The regulation of the rate of intrauterine growth is the result of complex interactions between genetic inheritance, endocrine environment and availability of nutrients to the fetus.

Gestational Diabetes Mellitus Upsets the Proportion of Fatty Acids in Umbilical Arterial but Not Venous Plasma

OBJECTIVE—Neonates of women with gestational diabetes mellitus (GDM) have reduced levels of arachidonic acid (AA) (20:4 n-6) and docosahexaenoic acid (DHA) (22:6 n-3). To assess whether this is the result of impaired placental transfer or endogenous fetal metabolism, fatty acids in umbilical venous and arterial plasma were analyzed in neonates of GDM women. RESEARCH DESIGN AND METHODS—Fatty acids were analyzed by gas chromatography in the plasma of 15 subjects with GDM and 30 healthy control subjects undergoing elective cesarean section and in vein and artery cord blood collected separately. RESULTS—The percentages of AA (20:4 n-6), DHA (22:6 n-3), and total n-6 or n-3 polyunsaturated fatty acids (PUFAs) as well as total PUFAs were lower in umbilical arterial but not in venous plasma of neonates of the GDM versus the control group. CONCLUSIONS—An altered handling or metabolism of long-chain PUFAs by the fetus rather than impaired placental transfer seems to be responsible for the lower proportion of those fatty acids in the plasma of neonates of GDM mothers.

Enhanced circulating retinol and non-esterified fatty acids in pregnancies complicated with intrauterine growth restriction.

IUGR (intrauterine growth restriction) increases the incidence of perinatal complications and, although several placental transport functions have been shown to be altered in pregnancies complicated by IUGR, the mechanism behind it is not well understood. The aim of the present study was to investigate factors in maternal and cord blood plasma from normal and IUGR-complicated pregnancies associated with the body weight of newborns. At the time of Caesarean section, 24 women with IUGR pregnancies were compared with a group of 30 normal controls with AGA (appropriate gestational age) fetuses who were studied at Caesarean section, which took place 5 weeks later than IUGR pregnancies, and also to a group of 25 non-delivered gestational age-matched control pregnant women (AGA-35wk). Maternal plasma retinol, gamma- and alpha-tocopherol, NEFAs (non-esterified fatty acids), and palmitic, palmitoleic, gamma-linolenic and arachidonic acids were higher in women with IUGR pregnancies than in AGA-35wk controls, whereas stearic and alpha-linolenic acids were lower. Smaller differences were found when comparing these variables for IUGR and AGA women. However, umbilical vein plasma gamma-tocopherol, cholesterol, triacylglycerols and NEFAs were higher in the IUGR group than in the AGA group, whereas arachidonic acid was lower. Maternal plasma retinol and NEFAs were the only variables negatively correlated with birthweight when multiple linear regressions were analysed. In conclusion, the increased levels of circulating retinol and NEFAs in maternal plasma are negatively associated with birth and placental weights, which may reflect an impaired placental transfer in IUGR pregnancies. As retinoids are involved in the control of gene transcription, it is proposed that a decrease in placental transfer of retinol could underlie the metabolic dysfunction of IUGR pregnancies.

OC250: Fetal oxygen uptake in normal and IUGR pregnancies

Objectives: To examine the relationship between smallness, assessed by customized standards, and the predictive value of a normal umbilical artery Doppler. Methods: A cohort was created of 7645 singleton pregnancies without congenital anomalies. Fetuses suspected antenatally of being small for gestational age were referred for assessment by umbilical artery Doppler. The associations with adverse outcome were assessed for small-for-gestational age babies who had normal and abnormal Doppler, compared with neonates who were not small for gestational age. Perinatal outcome indicators were collected, including fetal distress requiring Cesarean section and neonatal morbidity (neonatal intensive care > 14 days, neonatal seizures, intraventricular hemorrhage Grade III or more, periventricular leucomalacia, hypoxic–ischemic encephalopathy, or necrotizing enterocolitis). Results: Of the 369 small-for-gestational age fetuses which had been identified antenatally, 70 (19%) had an abnormal umbilical artery Doppler and the babies from these pregnancies had an elevated risk of fetal distress requiring Cesarean section (OR 5.89; CI, 2.64–11.84) and neonatal morbidity (OR 3.99; CI, 1.04–11.03). However the 299 fetuses (81%) with normal umbilical artery Doppler also had elevated risk of fetal distress (OR 4.49; CI, 2.96–6.66) and neonatal morbidity (OR 2.26; CI, 1.04–4.39). Because of the higher prevalence, many more instances of adverse outcome were attributable to this group than to the group with abnormal Dopper (fetal distress – population attributable risk (PAR): normal Doppler 8.6 vs. abnormal Doppler 2.7; neonatal morbidity – PAR: normal Doppler 4.0 vs. abnormal Doppler 2.2. Conclusions: Smallness for gestational age according to customized weight standards defines a group of pregnancies with significantly elevated risk of adverse perinatal outcome. Normal antenatal umbilical artery Doppler cannot be taken as an indicator of low risk in these pregnancies.

Lipid Profile in Intrauterine Growth Restriction

Reduction in the intrauterine supply of nutrients might lead to Intrauterine growth restriction alterations of the fetal growth trajectory that results in attainment of fetal own growth potential missed. IUGR is, together with premature delivery, the most relevant cause of perinatal mortality and morbidity, affecting approximately 7–15% of pregnancies. Although maternal, placental, and fetal causes may reduce the potential for fetal growth, no known causes can be detected in most cases of IUGR. These cases share a common placental phenotype, also called for many years “placental insufficiency.” In the last years many studies have described the vascular, metabolic, and endocrine changes occurring in IUGR, although the initiating factors are still to be understood. IUGR fetuses show a decreased deposition of tissue as a result of reduced uptake of nutrients from the umbilical circulation. In particular, the fetal fat component seems to be affected. Among nutrients, some fatty acids are particularly relevant for fetal nutrition and pregnancy outcome. In particular, the long chain polyunsaturated fatty acids (LCPUFA) of the n-3 and n-6 series, i.e., arachidonic acid (AA) and docosahexaenoic acid (DHA) need to be made available through the placenta since they cannot be synthesized in the fetus. They are important structural elements of cells guaranteeing the plasticity of the membranes; they are needed for the normal development of the central nervous system and retina. The biological roles of omega-3 and omega 6 FA involve eicosanoid metabolism, membrane properties, and regulation of gene expression. Significant changes in the ratios between the LCPUFA DHA and AA and their precursors ALA and LA have been reported in IUGR sampled at cordocentesis when compared to normally grown fetuses of similar gestational age. Altered availability of LCPUFA in preterm IUGR might have an important role in the increased brain damage susceptibility shown by these fetuses.

Fetal nutrition: A review: Fetal nutrition

Knowledge of fetal nutrient supply has greatly increased in the last decade due to the availability of fetal blood samples obtained under relatively steady‐state conditions. These studies, together with studies utilizing stable isotope methodologies, have clarified some aspects of the supply of the major nutrients for the fetus such as glucose, amino acids and fatty acids. At the same time, the relevance of intrauterine growth has been recognized not only for the well‐being of the neonate and child, but also for later health in adulthood. The major determinants of fetal nutrient availability are maternal nutrition and metabolism together with placental function and metabolism. The regulation of the rate of intrauterine growth is the result of complex interactions between genetic inheritance, endocrine environment and availability of nutrients to the fetus.