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.     

Lactate metabolism in normal and growth-retarded human fetuses

Lactate concentration and oxygen content were measured in 21 normal (AGA) and 34 intrauterine growth-retarded (IUGR) infants at the time of elective cesarean section. Maternal lactate and umbilical arterial and venous lactate concentrations were significantly higher in IUGR infants compared with AGA infants. However, when IUGR patients were subdivided according to pulsatility index (PI) measurements of the umbilical artery, no differences were detected between AGA and IUGR patients with PI less than 4 SD, whereas IUGR patients with PI greater than 4 SD had higher lactate concentrations in maternal arterial blood and umbilical arterial and venous blood from both other groups. There was a significant inverse linear relationship between umbilical arterial lactate concentration and umbilical venoarterial differences for both lactate concentrations and for lactate/oxygen quotients. These relationships were significantly different in IUGR fetuses with PI greater than 4 SD compared with AGA and IUGR fetuses with PI less than 4 SD. AGA and IUGR fetuses with PI less than 4 SD have arterial lactate concentrations less than 2 mM even at low oxygen concentrations (O2 content less than 2 mM, O2 saturations less than 20%). At comparable levels of oxygenation, IUGR fetuses with PI greater than 4 SD have a marked lactacidemia. The data suggest that coupling Doppler assessment of flow velocimetry with biochemical analyses of fetal blood can be useful in identifying a subset of IUGR human fetuses at risk of intrauterine hypoxia.     

Serum insulin-like growth factors and insulin-like growth factor binding proteins in the human fetus. Relationships with growth in normal subjects and in subjects with intrauterine growth retardation.

IGF-I, IGF-II, and their binding proteins (BP) were studied in sera obtained by direct puncture of umbilical cords in utero between 20 and 37 wk of gestation in 103 normal fetuses and in 16 fetuses with intrauterine growth retardation, as well as in the cord blood of 37 normal newborns of 38- to 42-wk pregnancies. In normal fetuses, IGF-I levels were approximately 50 ng/mL and IGF-II levels approximately 350 ng/mL up to the 33rd wk of pregnancy. Thereafter, both increased to reach values two to three times higher at term. Correlations were found between fetal placental lactogen levels and those of IGF-I and IGF-II, which is consistent with the hypothesis that placental lactogen is involved in the regulation of IGF synthesis in the fetus. With weight (either measured at birth or deduced from echographical data) as index of fetal size, IGF-I levels were significantly (p less than 0.001) higher in fetuses with weights above the mean for gestational age than in fetuses with weights below the mean, whereas IGF-II levels were similar in the two groups. Similarly, IGF-I (but not IGF-II) levels in fetuses with intrauterine growth retardation were significantly lower than those in normal fetuses of the same age (p less than 0.01). These findings suggest that, during the latter months of intrauterine life, IGF-I (but not IGF-II) is involved in the control of fetal size. Total fetal BP concentrations were approximately 1/3 those of adults. The fetal electrophoretic profile obtained by Western-ligand blotting bore a strong resemblance to that of subjects with growth hormone deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)     

Soluble vascular endothelial growth factor receptor-1 in intrauterine growth restricted fetuses and neonates

BACKGROUND: Angiogenesis, a critical process for growth and development is altered in intrauterine growth restriction (IUGR). Vascular endothelial growth factor (VEGF) and its receptors VEGFR-1, soluble (s) VEGFR-1 and VEGFR-2 represent a regulatory system, essential for both physiological and pathological angiogenesis. AIM: To study the implication of sVEGFR-1-a VEGF antagonist-in IUGR. STUDY DESIGN: Prospective study. METHODS: Twenty-five IUGR and 15 appropriate for gestational age (AGA) full-term fetuses and neonates with their mothers were included in the study. OUTCOME MEASURES: sVEGFR-1 levels were determined by enzyme immunoassay in the serum of: mothers (MS), umbilical cords (UC)-representing fetal state - and neonates on day 1 (N1) and 4 (N4) of life. RESULTS: MS, UC, N1 and N4 sVEGFR-1 levels in IUGR were significantly higher compared to respective AGA cases (p = 0.005, p = 0.026, p = 0.005 and p = 0.017, respectively). In IUGR and AGA groups, maternal sVEGFR-1 levels were significantly higher than fetal and neonatal levels (p in all cases < 0.001). The latter presented in both IUGR and AGA groups a significant decrease from UC to N4 (p in all cases < 0.01). MS, N1 and N4 sVEGFR-1 levels negatively correlated with the infants' customized centiles [(r = -0.489, p = 0.001), (r = -0.440, p = 0.004), (r = -0.431, p = 0.006), respectively]. CONCLUSIONS: Higher sVEGFR-1 levels in the IUGR as compared to the AGA group possibly reflect the predominance of antiangiogenic mechanisms present in IUGR. The decrease of sVEGFR-1 levels from UC to N4 may represent ex utero initiation of growth and development and therefore, prevalence of angiogenic mechanisms.     

Fetal amino acids in normal pregnancies and in pregnancies complicated by intrauterine growth retardation.

Plasma amino acid concentrations were measured in normal (AGA) and intrauterine growth retarded (IUGR) percutaneous umbilical blood sampling (PUBS) performed for prenatal diagnosis or at elective cesarean section. IUGR fetuses present significantly lower concentrations of most amino acids, with a significant reduction of the umbilical veno-arterial difference for total alpha-amino nitrogen. These findings are present early in growth retarded fetuses and may be potentially responsible for the growth retardation.     

Maternal and fetal serum insulin-like growth factor-I (IGF-I) IGF binding protein-3 (IGFBP-3), leptin levels and early postnatal growth in infants born asymmetrically small for gestational age

This study was planned to investigate the relationship between birth weight and insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3), and leptin levels in neonates with normal growth (appropriate for gestational age: AGA) and retarded growth (small for gestational age: SGA); and to evaluate these growth factors' effects in early postnatal growth. All newborns were full-term: gestational age 3,841 weeks. Of 50 neonates, 25 were SGA. IGF-I, IGFBP-3 and leptin levels were measured in maternal serum and venous cord blood at birth and at 15 days of life of neonates using specific RIAs. Maternal serum leptin concentrations were significantly higher than cord blood leptin concentrations (p < 0.001). Maternal serum IGF-I, IGFBP-3 and leptin levels did not show correlations with birth weight. In contrast, there were significantly positive correlations between birth weight and venous cord blood IGF-I, IGFBP-3 and leptin levels (p < 0.001). In the SGA group, the newborns with a slow postnatal growth pattern had lower umbilical cord serum IGF-I levels compared with newborns with a normal growth pattern. A similar result was also found in the AGA group. Similar results were not found for serum leptin and IGFBP-3. In conclusion, cord blood IGF-I, IGFBP-3 and leptin levels play an important role in the regulation of fetal and neonatal growth. It is likely that IGF-I has a more important role than the other factors in early postnatal growth.     

Steady state maternal-fetal leucine enrichments in normal and intrauterine growth-restricted pregnancies.

The aim of this study was to compare the fetal/maternal (F/M) leucine-enrichment ratio in normal (AGA) and intrauterine growth-restricted (IUGR) pregnancies at the time of fetal blood sampling (FBS). A maternal primed-constant infusion of L-[1-13C]-leucine was given in six AGA and 14 IUGR pregnancies, divided into three groups according to the pulsatility index (PI) of the umbilical artery and to fetal heart rate (FHR): group 1 (normal FHR and PI, four cases); group 2 (normal FHR and abnormal PI, five cases); and group 3 (abnormal FHR and PI, five cases). Maternal arterialized samples were taken at time zero and every 20 min for 125+/-7 min. Umbilical venous samples were obtained after 114+/-42 min of infusion. Under steady state conditions, there was a significant linear relationship between maternal leucine disposal rate and maternal leucine concentration. The comparison of fetal to maternal leucine enrichment showed a progressive dilution of the fetal enrichment relative to the mother between AGA and IUGR of group 1 (0.89 versus 0.78, p < 0.02), group 2 (0.71, p < 0.001), and group 3 (0.62, p < 0.001), and also among the three IUGR groups. The F/M leucine molar percent enrichment (MPE) ratio showed a positive correlation with the umbilical venous oxygen content and an inverse correlation with fetal lactate concentration. We conclude that the dilution in the fetal/maternal leucine-enrichment ratio correlates with the severity of growth restriction and reflects decreased transplacental leucine flux and/or increased protein breakdown within the fetoplacental compartments.     

Third trimester fetal growth and umbilical venous blood concentrations of IGF-1, IGFBP-1, and growth hormone at term.

Insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-1 (IGFBP-1) and growth hormone (GH) concentrations were measured in umbilical venous blood after delivery of 78 term newborn infants. Three groups of pregnancies were prospectively identified during the third trimester, according to fetal size and subsequent fetal growth, assessed by repeated ultrasound scans. Fetal size was considered either appropriate for gestational age (AGA) or small for gestational age (SGA), according to whether the first ultrasound measurement of abdominal circumference was equal to or above, or below the tenth centile for gestational age, respectively. Subsequent fetal growth was quantified by the change in the standard deviation score of abdominal circumference measurements between the first and last scans before delivery. Fetal growth retardation (FGR) was defined as a (negative) change in SD score of greater than -1.5. Eighteen SGA fetuses with evidence of FGR had significantly lower IGF-1 (median 0.05 (range 0.0-0.24) U/ml) at delivery than 35 SGA fetuses with normal growth (median 0.13 (range 0.0-0.94) U/ml; P < 0.05) and 25 AGA fetuses with normal growth (median 0.31 (range 0.0-0.84) U/ml; P < 0.05). The median concentration in the SGA group with normal growth was also significantly lower than that of the AGA group with normal growth. There were no significant differences in IGFBP-1 or GH concentrations between the three groups. These observations indicate that umbilical blood concentrations at birth of IGF-1, but not IGFBP-1 or GH, relate to both fetal size and fetal growth during the third trimester of pregnancies reaching term.     

Fetal and maternal non-glucose carbohydrates and polyols concentrations in normal human pregnancies at term

The objective of the present investigation was to determine fetal and maternal plasma concentrations of nonglucose carbohydrates and polyols in normal human pregnancies at term. Uncomplicated human pregnancies (n = 50) were studied at > or =37 wk gestation. Blood samples were obtained from umbilical artery, umbilical vein, and maternal peripheral blood at the time of elective cesarean section. Plasma concentrations of inositol, glycerol, erythritol, sorbitol, and mannose were determined by HPLC analysis. Differences between umbilical venous, umbilical arterial, and maternal concentration were tested by the two-tailed t test for paired samples. Correlations between umbilical and maternal concentration and between umbilical venoarterial concentration difference and umbilical arterial concentration were assessed by Pearson's correlation and multiple regression analysis. All newborns were appropriate for gestational age, and oxygenation and acid-base balance were within the normal range for all fetuses studied. For most of the polyols (inositol, sorbitol, and erythritol), the fetal concentration was significantly higher than the maternal concentration. The umbilical venoarterial concentration difference for inositol was -10.5 +/- 3.6 microM, for glycerol was 10 +/- 1.7 microM, for sorbitol was 3.8 +/- 0.5 microM (p < 0.001), and for mannose was 7.6 +/- 0.7 microM. There was a significant correlation between maternal concentration and umbilical venous concentration of mannose (UV(MAN) = 15.38 + 0.69 M(MAN); R(2) = 0.46; p < 0.001). These results indicate that in normal human pregnancies at term, inositol is produced by the fetus, sorbitol is produced by the placenta, and there is a significant umbilical uptake of mannose from the maternal circulation.     

The metabolism of free fatty acids and triacylglycerols by the fetal liver in a guinea pig model of intrauterine growth retardation.

The aim of this study was to determine whether intrauterine growth retardation (IUGR) is associated with an alteration in hepatic lipid metabolism. IUGR was induced in 25 guinea pigs by uterine artery ligation on gestational d 30. On d 62, after anesthesia, an infusion of [1-14C]-palmitic acid was given. Fetuses were exposed at 15, 30, and 45 min, and simultaneous maternal and umbilical venous blood samples were taken. Livers were divided into right lobe, right and left sublobes of the quadrate lobe, and left lobe. In control fetuses, plasma radiolipids rose in parallel with, but were about half the value of, maternal levels. In IUGR fetuses, plasma radiolipids were lower than in controls at 15 and 30 min but were comparable at 45 min. Most of the radiolipid in the maternal plasma was FFA, with only 6% incorporated into triglycerides at 45 min. In control and IUGR fetal plasmas, 36-37% of the radiolipid was triglycerides by 45 min. Radiolabel incorporation into the right lobe was less than into the left lobe and left half of the quadrate lobe in control and IUGR fetuses. Compared with controls, radiolabel incorporation in IUGR fetuses was less in some or all liver lobes at each time point. The proportion of label associated with FFA and triglycerides did not vary with time, between lobes, or between control and IUGR fetuses. The difference in uptake between lobes reflects their blood supply, implying that most FFA is extracted during the first passage of the umbilical venous blood. Growth retardation was not associated with compromised hepatic FFA metabolism.     

Intrauterine growth restriction and circulating neurotrophin levels at term

BACKGROUND: Intrauterine growth restricted (IUGR) fetuses are those with estimated weight <10th customized centile, displaying signs of chronic malnutrition and hypoxia leading to brain sparing effect. Neurotrophins, [Nerve Growth Factor (NGF), Brain Derived Neurotrophic Factor (BDNF), Neurotrophin-3 (NT-3), Neurotrophin-4 (NT-4)] are important for pre- and post-natal brain development. AIMS: To investigate circulating NGF, BDNF, NT-3 and NT-4 levels in IUGR and appropriate for gestational age (AGA) fullterm fetuses and neonates (day-1 [N1] and day-4 [N4]) and in their mothers. STUDY DESIGN: Prospective case control study. SUBJECTS: 60 mothers and their single 30 IUGR and 30 AGA fullterm fetuses and neonates. OUTCOME MEASURES: Determination, by enzyme immunoassays, of NGF, BDNF, NT-3 and NT-4 plasma levels. RESULTS: No statistically significant differences existed between IUGR and AGA maternal, fetal and neonatal levels of BDNF, NT-3 and NT-4. NGF was significantly higher in AGA than IUGR maternal (p=0.007), fetal (p=0.01), neonatal day 1 (p=0.043) and 4 (p=0.003) plasma, and positively correlated with the infants' centiles and birthweights. IUGR and AGA maternal neurotrophins were higher than the respective fetal and neonatal ones and no correlation with gender or delivery mode in both groups was observed. CONCLUSIONS: In the perinatal period, circulating levels of BDNF, NT-3 and NT-4 do not differ in IUGR and AGA pregnancies, in contrast to NGF levels, which are higher in the AGA group. NGF is the only neurotrophin correlating with customized centiles and birthweights of the infants. Neurotrophin concentrations are higher in maternal plasma and do not depend on gender.     

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??Abstract??Objective??To investigate alterations of circulating levels of the inflammatory markers— reflecting brain and adipose tissue inflammation—in the fetal growth restriction??FGR??fetuses and newborns??and explore its possible relation ship with adverse intrauterine development. Methods??Sixty parturients??hospitalized in Shengjing hospital of China Medical University??giving consecutively birth either to 30 appropriate for gestational-age??AGA?? singleton infants ??AGA group ?? or 30 FGR full-term singleton infants ??FGR group????were recruited.Plasm hs-CRP??PAI-1??S100B and leptin levels were determined by enzyme link immune assay??ELISA??in the umbilical cords blood ??UC ?? and venous blood from neonates on postnatal day 1 ??D1?? and day 4??D4??. Results??The birth weight??body length and the body mass index ??BMI?? of the FGR neonates were significantly lower compared with those of AGA group ??P < 0.05??.The leptin levels of UC in the FGR neonates were lower than that in the AGA groups??P < 0.05????and correlated positively with the birth weights and the BMI??P < 0.05??.Plasma hs-CRP levels did not differ significantly at all time points between AGA and FGR groups??P > 0.05??.hs-CRP levels in Umbilical cords blood were significantly decreased when compared with D1 hs-CRP in both AGA and FGR groups ??P < 0.05????and D1 hs-CRP was significantly increasedwhen compared with respective D4 hs-CRP??P < 0.05??.Plasma PAI-1 and S100B levels did not differ significantly at all time points between AGA and FGR groups??P > 0.05????and did not correlated with the birth weights and the BMI. Conclusion??Despite the lower birth weight??BMI and leptin levels in FGRs?? there was no difference for the levels of inflammatory markers hs-CRP and PAI-1 between IUGR and AGA fetuses/neonates.The CRP level in both studied groups fluctuated from fetus to neonate stage might attribute to parturition stress and adaptation recovery.     

Endothelin-1 and leptin as markers of intrauterine growth restriction

Objective  To explore the role of endothelin-1 (ET-1) and leptin in intrauterine growth restriction (IUGR) among preeclamptic and non-pre-eclamptic women. Methods  Forty three patients with a pregnancy complicated by IUGR, 23 cases with severe pre-eclampsia and 20 cases of non-pre-eclamptic were enrolled. Control group comprised 15 cases with uncomplicated pregnancy. Blood samples from umbilical artery and maternal venous blood were collected at the time of delivery for analysis of ET-1 and leptin levels. Mode of delivery, birth weight and Apgar score were also recorded. Results  The mean maternal and fetal ET-1 level was significantly higher in pregnancies complicated by IUGR than in control group. The mean maternal leptin level was significantly higher in pre-eclamptic patients when compared to non-preeclamptic and control groups. Mean fetal leptin level was significantly lower in patients compared to control; however, when fetal leptin corrected to fetal weight, it was insignificantly different in the both groups. E-mail: m. alhaggar@yahoo.co.uk. Conclusion  Maternal plasma ET-1 and leptin correlate with the degree of fetal growth restriction originating from deterioration of placental function. Maternal plasma leptin and ET-1 levels may reflect deterioration in fetal growth.     

Increased leptin concentration in preterm infants of pre-eclamptic mothers

AIM: To study the effect of maternal pre-eclampsia on cord plasma leptin concentrations in preterm infants. METHODS: Leptin concentration was analysed in cord plasma of 74 preterm infants, gestational age 24 to 32 weeks. Of these, 14 were born to pre-eclamptic mothers, in 10 intrauterine growth retardation (IUGR) was present, and 59 had been exposed antenatally to corticosteroids. RESULTS: The mean (SD) concentration of cord plasma leptin was 1.31 (0.88) microg/l. A significant correlation was found between leptin concentration and gestational age (r = 0.336; p = 0.0037). Leptin levels were higher in infants of pre-eclamptic mothers (p = 0.0007), in those with IUGR (p = 0.0005), and in infants exposed antenatally to corticosteroids (p = 0.02). In multiple regression analysis, leptin was associated with gestational age and maternal pre-eclampsia (both p < 0.05), but not with antenatal corticosteroids. CONCLUSIONS: Increased fetal leptin in maternal pre-eclampsia may reflect a physiological adaptation to fetal stress such as hypoxia.     

Two-dimensional and M-mode assessment of aortic growth in the normal and growth-retarded (IUGR) human fetuses

Summary This study compares human fetal aortic dimensions in 128 normal and 30 intrauterine growth-retarded (IUGR) fetuses using two-dimensional (2D) and M-mode echocardiography. We found that the fetal aortic root in the normally grown fetuses is significantly larger than the descending aorta at all gestational ages. Furthermore, IUGR fetuses had smaller descending aortic dimensions then did normally grown fetuses. When the descending aortic dimension in the IUGR fetuses was corrected for estimated fetal weight, it was found to be of comparable size to those of the normal fetuses. The difference in aortic size of growth-retarded fetuses is proportional to growth and therefore probably a secondary phenomenon.     

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 DeltaDeltaCt method, using beta-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.     

Placental lesion multiplicity: risk factor for IUGR and neonatal cranial ultrasound abnormalities

OBJECTIVE: To determine whether placental lesions are risk factors for neurologic morbidities in intrauterine growth restricted (IUGR) infants, we compared the incidence of cranial ultrasound (CUS) abnormalities and the number and type of placental lesions in IUGR cases and gestational age-matched appropriate for gestational age (AGA) controls. STUDY DESIGN: Retrospective case-control study of 94 singleton IUGR and 145 AGA infants. Medical records, CUS reports, and placental histology were reviewed. Analyses included chi2, t-test, analysis of variance and logistic regressions to identify those variables significantly associated with IUGR and those associated with CUS abnormalities. RESULTS: The incidence of CUS abnormalities was 1.7-fold higher in IUGR cases (50%) than controls (29.7%) (p<0.05). A total placental lesion score of > or =3 was associated with an increased risk for IUGR (OR 14.18, 3.41-58.99; p<0.001) and increased risk for CUS abnormality (OR 12.571, 3.33-47.416; p<0.05). In a logistic regression model only > or =2 placental lesions, IUGR and gestational age <30 weeks were significant independent predictors of CUS abnormalities. CONCLUSIONS: The severity of placental abnormalities expressed as the cumulative number of placental lesions is a significant risk factor for IUGR and perinatal brain injury. These results suggest that abnormal uteroplacental or fetoplacental blood flow may adversely affect intrauterine growth and increase the risk for brain injury.     

Prediction of chronic neonatal lung disease in very low birthweight neonates using clinical and radiological variables.

In a prospective observational study, the fatty acid content of human umbilical artery and vein wall phospholipids was determined in fetuses classified according to their change in abdominal circumference during the third trimester. Three groups were identified: appropriate for gestational age (AGA; 24 infants) and small for gestational age (SGA; 38 infants) with normal antenatal growth rate, and SGA with fetal growth retardation (22 infants). The venous linoleic acid (18:2 omega 6) content (expressed as a percentage of the total fatty acids identified) was greater in growth retarded SGA fetuses (3.5 (0.6)%) than in SGA fetuses with a normal growth rate (3.1 (0.5)%) and AGA fetuses (3.0 (0.5)%), whereas the venous contents of eicosatrienoic (20:3 omega 6) and docosahexaenoic acid (22:6 omega 3) were lower. In growth retarded SGA fetuses, the venous and arterial 20:3 omega 6 content correlated with the change in abdominal circumference. In SGA fetuses with a normal growth rate, lower contents of arterial 18:2 omega 6 and 22:6 omega 3 were associated with a smaller change in abdominal circumference and birth weight. Different metabolic derangements appear to underly normal and subnormal growth rate in SGA fetuses, suggesting that different strategies of dietary intervention may be required to aid fetal growth and reduce the sequelae of fetal growth retardation.     

Noninvasive assessment of cranial blood circulation in the fetus

The blood velocity in the common carotid artery, umbilical artery and descending aorta of 15 term fetuses with birth weights appropriate for gestational age and 20 fetuses, ultrasonically suspected of intrauterine growth retardation (IUGR), was recorded by means of a technique combining real-time linear-array ultrasonography and 2-MHz pulsed Doppler ultrasound. The waveform of the maximum blood velocity was characterized by a pulsatility index (PI) indicating peripheral vascular resistance. In the normal fetuses, the mean PI was 1.89 (+/- 0.07 SEM) in the common carotid artery, 0.93 (+/- 0.04) in the umbilical artery and 2.19 (+/- 0.06) in the descending aorta. In the IUGR fetuses, the PI was higher than in the normal fetuses in the umbilical artery (1.19 +/- 0.04; p less than 0.05) and lower in the carotid artery (1.48 +/- 0.03; p less than 0.05). The changes of the PI were even more pronounced in 10 IUGR fetuses in whom cardiotocographic signs (late decelerations) of imminent asphyxia were present. The results indicate an increase in the peripheral vascular resistance in the placental circulation and the lower body, and a decrease in the cranial vascular resistance in the growth-retarded fetuses. Furthermore, these findings suggest that in chronic and acute fetal distress, there is a redistribution of the fetal circulation favoring the brain.     

Circulating S100beta protein is increased in intrauterine growth-retarded fetuses.

To determine whether S100beta, an acidic calcium-binding protein previously demonstrated as a reliable indicator of a brain lesion, could be helpful in the detection of brain distress in intrauterine growth-retarded (IUGR) fetuses, we studied, by a case-control study, the correlation between S100B protein and the degree of fetoplacental blood flow impairment. Maternal and umbilical blood samples and placental tissue specimens were collected at delivery from IUGR pregnancies with normal (n = 10) or abnormal (n = 10) umbilical artery Doppler findings and from 40 uncomplicated pregnancies. S100beta protein levels were measured by means of a specific RIA, and flow velocimetry waveforms were recorded from uterine, umbilical, and fetal middle cerebral arteries. Overall mean S100beta proteins in umbilical plasma levels were higher (p < 0.05) in IUGR patients (121.8 +/- 70.4 fmol/mL) than in control patients (54.7 +/- 21.9 fmol/mL). IUGR fetuses with redistribution of blood flow showed the higher concentration of the protein (163.7 +/- 55.2 fmol/mL). Fetal S100beta concentrations correlated with middle cerebral artery pulsatility index (r = -0.536, p < 0.03) and with umbilical artery pulsatility index to middle cerebral artery pulsatility index ratio (r = 0.469, p < 0.03). No difference in the localization or intensity of S100beta staining in the placental tissues or cord between uncomplicated and IUGR pregnancies was found. This study provides evidence that circulating S100beta protein is increased in IUGR fetuses and correlates with cerebral hemodynamics, suggesting that it may represent an index of cerebral cell damage in the perinatal period.