Carol H Gilmour

Hemodynamic disturbances in premature infants born after chorioamnionitis: Association with cord blood cytokine concentrations

Chorioamnionitis and elevated cord blood inflammatory cytokine concentrations are associated with detectable disturbances of systemic and cerebral hemodynamics in premature newborns. Fifty-five infants (25–31 wk gestation) were enrolled. Chorioamnionitis was defined by placental histology. IL-6, IL-1β, and tumor necrosis factor-α were quantified by ELISA. Blood pressure, heart rate, cardiac output, stroke volume, fractional shortening, and middle cerebral artery blood flow velocities were measured at 3 ± 1 h after birth. Chorioamnionitis was evident in 22 placentas and was associated with increased IL-6 (p < 0.001), IL-1β (p = 0.035), and heart rate (p = 0.027); and with decreased mean and diastolic blood pressure (p = 0.026 and p = 0.019, respectively). IL-6 concentration correlated inversely with systolic, mean, and diastolic blood pressures. Right ventricular cardiac output was elevated (p = 0.028) in infants with fetal vessel inflammation. Maternal temperature ≥38.0°C and newborn immature-to-total white blood cell ratio ≥0.4 were associated with significant decreases in left ventricular fractional shortening (p = 0.001 and p = 0.005, respectively). Neither chorioamnionitis nor elevated cytokine concentrations were associated with changes in middle cerebral artery Doppler blood flow velocities. Chorioamnionitis and elevated cord blood IL-6 concentrations are associated with decreased blood pressure in premature newborns. Inflammation of the fetal vessels and nonspecific indicators of infection are associated with disturbances in cardiac function. Infants with chorioamnionitis and elevated cytokine concentrations do not manifest changes in cerebral Doppler indices within the first few postnatal hours. We speculate that cytokine-associated systemic hemodynamic disturbances in premature infants born after chorioamnionitis predispose such infants to perinatal brain injury.

Evidence of endothelial activation and endothelial activators in cord blood of infants of preeclamptic women

OBJECTIVE In preeclampsia markers of endothelial activation (e.g., increased cellular fibronectin and activities that alter in vitro endothelial function (e.g., stimulation of nitric oxide and prostacyclin generation) are increased in the maternal circulation. We tested preeclamptic infant blood for these markers and activities and correlated these findings with fetal growth. STUDY DESIGN Plasma was obtained from 17 term nulliparcus preeclamptic and normal pregnant women and their infants and from 8 additional preeclamptic mother-baby pairs from earlier gestations. Plasma cellular fibronectin and production of nitric oxide and prostacyclin by cultured endothelial cells exposed to 2% plasma were measured. RESULTS Cellular fibronectin was higher in maternal plasma of preeclamptic than nonpregnant women (6.1 +/- 0.29 vs 4.2 +/- 0.27 microgram/ml, p < 0.01), as were stimulated endothelial nitric oxide and prostacyclin production (nitric oxide 42.5 +/- 3.9 vs 26.9 +/- 2.3 nmol nitrite/microgram protein/24 hours, p < 0.05; prostacyclin 261.7 +/- 31.2 vs 151.9 +/- 18.7 pg prostaglandin F1 alpha/microgram protein/24 hours, p < 0.05). In the preeclamptic infants cellular fibronectin was also greater (3.3 +/- 0.15 vs 2.6 +/- 0.14 microgram/ml, p < 0.01), as was endothelial nitric oxide production in response to the plasma (24.4 +/- 1.1 vs 21.4 +/- 0.09 mumol/L nmol nitrite/microgram protein/24 hours, p < 0.05). Prostacyclin production was not significantly different. In preeclamptic infants across a wide gestational age there was no correlation of endothelial activation and fetal growth. CONCLUSIONS Infants of women with preeclampsia may be affected by endothelial dysfunction, as well as reduced uteroplacental perfusion.

Increased umbilical cellular fibronectin concentrations are associated with a decreased prevalence of growth restriction in preeclampsia.

Objective: Cellular fibronectin (cFN), a marker of endothelial activation, is elevated in maternal and cord blood in preeclampsia. We tested whether maternal or fetal cFN is related to fetal growth restriction in preeclampsia, in the context of gestational age at delivery. Methods: Cellular fibronectin was measured in maternal and cord blood of 29 preeclamptic women and their infants delivered at Magee-Womens Hospital at 25-41 weeks of gestation. Relationships amog maternal and cord cFN, birth weight, birth weight percentile, and ponderal index were evaluated using Pearson correlation and regression analyses controlled for gestational age. Results: Cord cFN was not significantly related to maternal cFN (r = -.34, P = .08) or gestational age (r = -.32, P = .09). The relationship of maternal cFN to each index of infant size was not significant. By contrast, higher cord cFN predicted higher birth weight, birth weight percentile, and ponderal index (P < .05). Conclusion: Elevated maternal and cord cFN concentrations have been reported in pregnancy complicated by preeclampsia. This study assessed the relationship among maternal cFN, cord cFN, and indices of fetal growth in preeclampsia. Elevated cord cFN was associated with measures of better fetal growth.

Adverse Outcome After Delivery Room Cardiovascular Resuscitation of Extremely Premature Infants. † 1167

Adverse Outcome After Delivery Room Cardiovascular Resuscitation of Extremely Premature Infants. † 1167

Maternal and Fetal Leptin Correlate with Fetal Growth in Preeclampsia.|[dagger]| 1519

Serum leptin, the product of the obesity (ob) gene, correlates with adiposity and increases fat utilization. Leptin mRNA is present in the placenta, suggesting a role for leptin in fetal growth. Maternal serum leptin, triglyceride (trig) and free fatty acids (FFA) are elevated in healthy pregnancy, and are increased further in preeclampsia (PRE). Umbilical cord leptin levels correlate with birth weight, but not with maternal leptin levels in healthy pregnancy. Preeclampsia is associated with reduced perfusion of the placenta. We hypothesized that leptin production is increased in poorly perfused placenta in PRE and by increasing maternal fat utilization increases fuel availability to the fetus promoting fetal growth. Methods: Venous blood was obtained prepartum from 14 women with PRE and 15 healthy pregnant women (CNTL). Mixed arterio-venous blood was obtained from the umbilical cord of their infants at delivery. Plasma leptin concentration was measured by human antibody RIA. Lipids were measured by standard techniques. Data were analyzed using Mann-Whitney comparison of medians and Pearson correlation. Results: Median gestational age (38.1 v 37.7 wks), birth weight (BW, 3.1 v 3.2 kg), maternal leptin (52.8 v 26.7 ng/ml), cord leptin (3.7 v 5.6 ng/ml), maternal trig (263 v 239 mg/dl) and FFA (0.84 v 0.61 mmol/L) did not differ between PRE and CNTL, while BW%ile (29.3 v 59.7%) was significantly different at p=0.05. The correlation between maternal and cord leptin was highly significant in PRE (r=0.87, p=0.000) but not in CNTL(r=-0.16). Maternal trig did not correlate with leptin in PRE (r=-0.34) or CNTL (r=0.10). Maternal FFA correlated with leptin in CNTL (r=-0.72, p=0.003) but not PRE (r=-0.16). BW correlated with both maternal leptin (r=0.71, p=0.004) and cord leptin (r=0.67, p=0.012) in PRE. Only cord leptin was related to BW in CNTL (r=0.69, p=0.005). Conclusion: These data confirm the positive relationship between cord leptin and BW. We also found highly significant correlations of maternal leptin to cord leptin and to BW in preeclampsia which are not present in healthy pregnancy. Our hypothesis that maternal leptin increased in preeclampsia to increase fuel availability for the fetus is, however, not supported by these preliminary data.

Serum Leptin Predicts Adiposity in Infancy † 1520

Early identification of infants at high risk to develop obesity may allow intervention and prevention of childhood obesity. Leptin, the translated and secreted 16 kD product of the obesity (ob) gene, reflects adiposity in adults. This peptide serves as a link between the peripheral fat stores and the hypothalamus, thereby regulating feeding behavior. The presence of leptin mRNA in the placenta and peptide in fetal and neonatal blood support a role for leptin in the determination of infant adiposity. We hypothesized that circulating leptin levels predict adiposity in infants. Methods: 12 male infants were fed a single proprietary formula to one year of age. Solids were fed no earlier than the fourth month (mon). Measurements were made at 4 and 12 mon. Adiposity was measured by anthropometry and total body electrical conductance (TOBEC, EmScan). Serum leptin levels were measured by RIA. Dietary intake was measured from 4-day records. Paired t-tests and Pearson correlations were used for statistical analyses.

Effect of Dietary Fiber on Endogenous Cholesterol Synthesis in Infants† 1521

Cholesterol (chol) content of infant diet varies with human milk providing≈150 mg/dl vs 11 mg/dl in commercial (Similac) infant formula. Endogenous chol fractional synthesis rate (FSR) is significantly lower in human milk vs formula fed infants (Pediatr Res 1994;35:135). Dietary fiber decreases chol absorption in adults. Parents often begin solids before the AAP- recommended 4-6 months (mon) of age, but metabolic effects of infant feeding practices are unknown. We conducted a pilot study to test the hypothesis that addition of dietary fiber to infant diet would result in higher chol FSR.Methods: 12 male term infants were fed SMA formula (chol 33mg/dl) to 1 yr of age. Subjects were randomized to begin barley cereal 8 Tbs/d (1.5g fiber/d) at the start of the 4th or 6th mon. Growth, dietary intake by 4-day records, serum chol and lipoproteins, & FSR were measured after 4 & 12 mon of age. FSR was measured using deuterium enrichment of erythrocyte membrane chol over a 4-day period (J Lipid Res 1991;32:1049). Nonparametric statistics were used. Results: There were no significant differences between groups for weight, intake, lipid, or FSR analyses. Median chol intake& synthesis rates are shown in the Table. Conclusion: In this pilot study of infants with moderate chol intake, earlier addition of dietary fiber resulted in a trend toward higher endogenous chol FSR that persisted beyond the dietary intervention.Speculation: Chol FSR during infancy may be responsive to early diet, which may have life-long implications for chol metabolism and cardiovascular disease risk. These pilot data may be used to design definitive studies of infant diet & cholesterol metabolism.

EARLY INTRODUCTION OF CEREAL FEEDING INCREASES ADIPOSITY OF INFANTS.|[dagger]| 695

The AAP recommends introducing cereal (C) into infant diet at 4-6 months(mos) of age. In practice, parents often begin C before 4 mos. Shifting a balanced diet to a carbohydrate-enriched diet may promote fat storage. We hypothesized that infants fed formula+cereal from 3 mos become heavier and have increased fat mass vs. controls fed formula alone.Methods: 12 male term formula fed infants were randomized to receive C beginning at 3 (n=6) or 5 (n=6) mos of age. Weight (wt, kg) and length (cm) were measured at birth, 3, 4, & 5 mos of age.%Fat was assessed by total body electrical conductance (TOBEC) at 3, 4 & 5 mos.Results:(mean ± SEM) Birth weight, GA and race did not differ by group. Both wt (p=0.002) and%fat (p=0.006) were significantly higher in the cereal group by repeated measures regression analysis (BMDP 5V).Conclusion: Early introduction of cereal to infant diet resulted in increased weight attributable to increased fat mass. Speculation: Increased adiposity in infants fed cereal early is due to replacement of protein rich formula with carbohydrate. This may be relevant to the development of obesity later in life. (Funded by NIDDK #DK46204)Table