Maternal and umbilical venous adrenomedullin and nitric oxide levels in intrauterine growth restriction.

OBJECTIVE: To verify whether adrenomedullin (AM) and nitric oxide (NO) concentrations are changed in the maternal and fetal circulation in pregnancies complicated by intrauterine growth restriction (IUGR) compared to normal pregnancies, and to determine any relationship between them. METHODS: Forty-six small for gestational age (SGA) and 34 appropriate for gestational age (AGA) infants were included in the study. Umbilical and maternal venous AM and NO concentrations were determined. RESULTS: Umbilical NO concentrations in SGA infants (mean +/- SD; 176.2 +/- 75.8 micromol/L) were significantly greater than in AGA infants (143.4 +/- 39.2 micromol/L) (p = 0.015). However, umbilical AM concentrations were similar in SGA and AGA infants with 14.2 +/- 4.4 pmol/mL and 14.5 +/- 6.2 pmol/mL, respectively (p > 0.05). There was no relationship between NO and AM levels in umbilical blood (r = 0.09, p = 0.40). No difference was found between either AM or NO levels in the maternal plasma of the two groups. CONCLUSIONS: We suggest that NO is increased in the fetoplacental circulation in SGA infants probably as a response to decreased blood flow, whereas AM is not. Additionally, increased NO in the fetoplacental circulation was found to be independent from AM secretion.     

Maternal and neonatal circulating visfatin concentrations in patients with pre-eclampsia and a small-for-gestational age neonate

Objective.?Maternal circulating visfatin concentrations are higher in patients with a small-for-gestational-age (SGA) neonate than in those who delivered an appropriate-for-gestational age (AGA) neonate or in those with pre-eclampsia. It has been proposed that enhanced transfer of visfatin from the foetal to maternal circulation may account for the high concentrations of maternal visfatin observed in patients with an SGA neonate. The aims of this study were: (1) to determine whether cord blood visfatin concentrations differ between normal neonates, SGA neonates and newborns of pre-eclamptic mothers; and (2) to assess the relationship between maternal and foetal circulating visfatin concentrations in patients with an SGA neonate and those with pre-eclampsia.

Study design.?This cross-sectional study included 88 pregnant women and their neonates, as well as 22 preterm neonates in the following groups: (1) 44 normal pregnant women at term and their AGA neonates; (2) 22 normotensive pregnant women and their SGA neonates; (3) 22 women with pre-eclampsia and their neonates; and (4) 22 preterm neonates delivered following spontaneous preterm labour without funisitis or histologic chorioamnionitis, matched for gestational age with infants of pre-eclamptic mothers. Maternal plasma and cord blood visfatin concentrations were determined by ELISA. Non-parametric statistics were used for analyses.

Results.?(1) The median visfatin concentration was lower in umbilical cord blood than in maternal circulation, in normal pregnancy, SGA and pre-eclampsia groups (p?<?0.001 for all comparisons); (2) the median cord blood visfatin concentrations did not differ significantly between term AGA or SGA neonates, infants of mothers with pre-eclampsia and their gestational-age-matched preterm AGA neonates; (3) maternal and cord blood visfatin concentrations correlated only in the normal term group (r?=?0.48, p?=?0.04).

Conclusion.?Circulating visfatin concentrations are lower in the foetal than in the maternal circulation and did not significantly differ between the study groups. Thus, it is unlikely that the foetal circulation is the source of the high maternal visfatin concentrations reported in patients with an SGA neonate.     

Serum prohepcidin levels and iron parameters in term small-for gestational age newborns

Abstract

Aim.?To understand the effect of prenatal chronic hypoxia on prohepcidin levels in term newborns.

Method.?We determined prohepcidin (Pro-Hep) levels in both term appropriate-for-gestational age (AGA) and term small-for-gestational-age (SGA) infants. Uteroplacental insufficiency had exposed all SGA infants to chronic hypoxia. Serum samples were collected from nine full-term SGA infants. Samples were analyzed for complete blood count, serum iron and ferritin concentrations, iron-binding capacity, and prohepcidin levels.

Results.?The mean serum Pro-Hep level was 156.4 ± 46.7 ng/ml for SGA infants and 482 ± 371.9 ng/ml for 16 healthy term AGA infants (historical controls); this difference was statistically significant. Statistical analyses revealed significant between-group differences for hemoglobin, hematocrit, mean corpuscular volume, red blood cell distribution width, and serum ferritin and Pro-Hep levels.

Conclusion.?This study showed that compared with AGA infants, Pro-Hep levels were lower in term SGA infants, suggesting that prenatal chronic hypoxia decreases Pro-Hep synthesis.     

Iron status at birth and at 4 weeks in term small-for-gestation infants in comparison with appropriate-for-gestation infants

Objective.?To determine body iron stores at birth in term small-for-gestational age (SGA) infants as compared to appropriate-for-gestational age (AGA) infants.

Methods.?In this prospective study, mother–infant pairs with gestation of?≥37 weeks and birth weight of at least 1.5?kg were enrolled. Asymmetric SGA infants were taken as cases and term AGA infants as controls. Maternal, cord blood, and infant blood samples at 4 weeks were obtained for measurement of various iron indices – cord serum ferritin, serum ferritin at 4 weeks, and correlation among maternal and neonatal iron indices – Hb, serum iron, ferritin, and total iron binding capacity (TIBC).

Results.?There were 50 SGA and 50 AGA mother–infant pairs. Cord serum ferritin levels were low in SGA group as compared to AGA [median (IQR): 68 (30,136) vs. 141 (63,259), p?=?0.007]. The proportion of infants with ‘low’ cord ferritin (<40?μg/l) were more in SGA [p?=?0.05]. There was no correlation among various maternal and neonatal cord iron parameters. The serum ferritin levels at 4 weeks were similar in both the groups (p?=?0.16).

Conclusions.?Term SGA infants have lesser total iron stores as compared to AGA infants at birth. Future studies can be designed to look at long-term neurodevelopmental outcome of the SGA babies with low as well as normal ferritin and also the role of early iron supplementation in term SGA neonates.     

The relationship between serum visfatin,adiponectin, and insulin sensitivity markers in neonates after birth

Aim.?The aim of this study was to assess the adiponectin and visfatin concentrations in small-for-gestational age (SGA), appropriate-for-gestational age (AGA), and large-for-gestational age (LGA) newborns and their mothers. Sixty parturients giving birth to 20 term AGA singleton infants, 20 term singleton SGA infants, and 20 term singleton LGA infants were included into the study.

Results.?Mean visfatin levels were found significantly higher in the SGA (p?<?0.001) and LGA (p?<?0.001) groups, and adiponectin levels were found significantly lower in the SGA group (p?<?0.001) when compared with the AGA group. The SGA and LGA groups had higher insulin concentrations and HOMA-IR in comparison with the AGA group. The visfatin, glucose levels, and HOMA-IR (p?<?0.001, p?<?0.001, and p: 0.002, respectively) were higher in the LGA group than SGA group.

Conclusion.?We found significantly higher insulin and visfatin levels in LGA neonates and lower adiponectin levels in SGA neonates. We concluded that the relationship between adiponectin and visfatin and insulin sensitivity (metabolic disturbances) is very complex with little evidence of correlation in SGA and LGA neonates.     

The maternal plasma soluble vascular endothelial growth factor receptor-1 concentration is elevated in SGA and the magnitude of the increase relates to Doppler abnormalities in the maternal and fetal circulation

Objectives. The soluble form of vascular endothelial growth factor receptor-1 (sVEGFR-1), an antagonist to vascular endothelial growth factor and placental growth factor, has been implicated in the pathophysiology of preeclampsia. Preeclampsia and pregnancy complicated with small for gestational age (SGA) fetuses share some pathophysiologic derangements, such as failure of physiologic transformation of the spiral arteries, endothelial cell dysfunction, and leukocyte activation. The objectives of this study were to: (1) determine whether plasma concentrations of sVEGFR-1 in mothers with SGA fetuses without preeclampsia at the time of diagnosis are different from those in patients with preeclampsia or normal pregnant women, and (2) examine the relationship between plasma concentrations of sVEGFR-1 and Doppler velocimetry in uterine and umbilical arteries in patients with preeclampsia and those with SGA.

Study design. A cross-sectional study was conducted to determine the concentrations of the soluble form of VEGFR-1 in plasma obtained from normal pregnant women (n = 135), women with SGA fetuses (n = 53), and patients with preeclampsia (n = 112). Patients with SGA fetuses and those with preeclampsia were sub-classified according to the results of uterine and umbilical artery Doppler velocimetry examinations. Plasma concentrations of sVEGFR-1 were determined by an ELISA. Since these concentrations change with gestational age, differences among various subgroups were statistically estimated with the delta value, defined as the difference between the observed and expected plasma sVEGFR-1 concentration. The expected values were derived from regression analysis of plasma sVEGFR-1 concentrations in normal pregnancy. Regression analysis and univariate and multivariate analysis were employed.

Results. (1) Mothers with SGA fetuses had a mean plasma concentration of sVEGFR-1 higher than normal pregnant women (p < 0.001), but lower than patients with preeclampsia (p < 0.001). (2) Among patients with SGA fetuses, only those with abnormal uterine artery Doppler velocimetry had a mean plasma sVEGFR-1 concentration significantly higher than normal pregnant women (p < 0.001). (3) Among mothers with SGA fetuses in whom Doppler velocimetry was performed (n = 41), those with abnormalities in both the uterine and umbilical artery velocimetry had the highest mean delta of sVEGFR-1 plasma concentration (mean ± standard deviation (SD): 0.69 ± 0.29). Conversely, patients who had normal Doppler velocimetry in both uterine and umbilical arteries had the lowest mean delta (mean ± SD: 0.09 ± 0.29) of sVEGFR-1 plasma concentrations (ANOVA; p < 0.001). (4) Among patients with preeclampsia in whom Doppler velocimetry was performed (n = 69), those with abnormalities in both the uterine and umbilical artery velocimetry had the highest mean delta sVEGFR-1 plasma concentration (mean ± SD: 1.01 ± 0.22) among all groups classified (ANOVA; p < 0.001). (5) Among patients with SGA and those with preeclampsia, there was a relationship (Chi-square for trend p < 0.001 for both) between the severity of Doppler velocimetry abnormalities and the proportion of patients who had high delta sVEGFR-1 plasma concentrations (defined as a concentration two standard deviations (2SD) above the mean delta of normal pregnant women). (6) Multiple regression analysis suggested that the diagnostic category (e.g., SGA or preeclampsia), Doppler abnormalities, and gestational age at blood sampling were associated with an increase in plasma sVEGFR-1 concentrations (p < 0.001).

Conclusions. These observations provide support for the participation of the soluble receptor of vascular endothelial growth factor in the pathophysiology of SGA with abnormal uterine artery Doppler velocimetry and preeclampsia. An excess of sVEGFR-1 is released into the maternal circulation of patients with preeclampsia and those with SGA fetuses, as abnormalities of impedance to blood flow involve uterine and umbilical circulation.     

Customized versus population-based growth curves: Prediction of low body fat percent at term corrected gestational age following preterm birth

Objective: Compare customized versus population-based growth curves for identification of small-for-gestational-age (SGA) and body fat percent (BF%) among preterm infants. Methods: Prospective cohort study of 204 preterm infants classified as SGA or appropriate-for-gestational-age (AGA) by population-based and customized growth curves. BF% was determined by air-displacement plethysmography. Differences between groups were compared using bivariable and multivariable linear and logistic regression analyses. Results: Customized curves reclassified 30% of the preterm infants as SGA. SGA infants identified by customized method only had significantly lower BF% (13.8 ± 6.0) than the AGA (16.2 ± 6.3, p = 0.02) infants and similar to the SGA infants classified by both methods (14.6 ± 6.7, p = 0.51). Customized growth curves were a significant predictor of BF% (p = 0.02), whereas population-based growth curves were not a significant independent predictor of BF% (p = 0.50) at term corrected gestational age. Conclusion: Customized growth potential improves the differentiation of SGA infants and low BF% compared with a standard population-based growth curve among a cohort of preterm infants.     

Maternal nitric oxide supplementation increases adrenomedullin concentrations in growth retarded fetuses

Nitric oxide (NO) and adrenomedullin (AM) are both involved in the regulation of fetoplacental circulation in human pregnancy. The aim of this study was to investigate the effect of maternal NO supplementation in pregnancies complicated by intrauterine growth retardation (IUGR) on maternal and fetal NO and AM concentrations and their correlation with uteroplacental and fetal blood flow. We studied 20 pregnant women with IUGR and impaired uteroplacental blood flow between 27 and 35 weeks of gestation randomly selected to receive either transdermal glyceryl trinitrate or placebo. Maternal NO metabolites (NOx) and AM concentrations did not change before and after NO treatment. AM levels were significantly higher in growth retarded fetuses whose mothers received NO donors (114.1 ± 17.6 pg/ml) than in untreated fetuses (59.8 ± 38.6 pg/ml), whereas NO treatment did not affect significantly fetal NOx levels. Fetal AM correlated with middle cerebral artery pulsatility index in untreated IUGR but not in NO treated pregnancies.     

Galanin concentrations in maternal circulation,amniotic fluid and umbilical cord blood during term labor: Relationship with maternal body mass and neonatal birth weight

Background.?Galanin is a hypothalamic regulatory peptide involved in the regulation of appetite. It is synthesized by the nervous system, anterior pituitary gland, adrenal medulla, pancreas, intestine and placenta. Placental secretion of galanin has until now only been investigated in animals. Additionally, galanin concentration has not been assessed in umbilical cord blood and amniotic fluid.

Patients and methods.?Galanin concentrations were measured in maternal circulation before term delivery, in cord blood and in amniotic fluid of 45 healthy pregnant women (gestational age 38 – 40 gestational weeks). The control group consisted of 26 normally menstruating healthy women.

Results.?Plasma galanin concentrations were found to be similar in pregnant healthy women before term delivery (20.8 ± 1.9 pg/ml) and non-pregnant women (19.0 ± 1.7 pg/ml). Galanin concentration in umbilical cord blood (26.5 ± 2.2 pg/ml) was significantly higher (p < 0.05) than in maternal circulation. Galanin concentration in amniotic fluid (20.4 ± 1.0 pg/ml) was similar to that observed in maternal plasma, but significantly (p < 0.01) lower than in umbilical cord blood. A significant correlation was found between maternal body mass index and plasma galanin concentration (τ = 0.246; p < 0.05) and between birth weight and cord blood galanin concentration (τ = 0.345; p = 0.01). There was no significant correlation between placental mass and cord blood galanin concentration (τ = 0.124; p = 0.26).

Conclusions.?Plasma galanin concentration in pregnant women before term delivery is similar to that in non-pregnant women. The fetus rather than the placenta is the source of the high galanin concentration in umbilical cord blood. The role of galanin in the regulation of newborn weight is uncertain.     

Intrapartum stress and lipid status of term infants: relation to fetal adrenal production of dehydroepiandrosterone sulphate

Objective. Evaluate the effect of acute intrapartum stress on umbilical cord plasma levels of cholesterol, triglyceride and dehydroepiandrosterone sulphate (DS) in term infants.

Methods. Umbilical cord plasma levels of cholesterol, triglyceride and DS were measured in 176 infants that delivered ≥37 weeks' gestation. Eighty-eight infants experienced acute intrapartum stress while the remaining infants were non-stressed controls who were case-matched by gestational age and delivery method.

Results. The umbilical cord plasma levels of cholesterol in the stressed infants (71.7 ± 16.1 mg/dL, mean ± SD) were similar to those of the control infants (70.9 ± 16.0 mg/dL). Triglyceride levels in stressed infants were significantly higher (p = 0.003) than those of control infants. Both stressed and control infants with increased triglyceride levels had normal DS levels; however, those with increased cholesterol levels had reduced umbilical cord plasma levels of DS. Stressed infants with increased cholesterol levels had significantly lower DS levels than control infants (p = 0.008).

Conclusions. Intrapartum stress leads to increased fetal plasma levels of triglycerides; yet, cholesterol levels are usually unaffected. Infants with increased cholesterol levels also have reduced DS levels, suggesting that the rise in cholesterol was due to a reduction in fetal adrenal utilisation of plasma cholesterol as substrate for steroid formation.     

Levels of asymmetric dimethylarginine throughout normal pregnancy and in pregnancies complicated with preeclampsia or had a small for gestational age baby

Objective: The aim of this study was to investigate maternal asymmetric dimethylarginine (ADMA) concentrations at the three trimesters of pregnancy in uncomplicated pregnancies and in women who developed preeclampsia or had small for gestational age infants (SGA) without preeclampsia. Methods: ADMA concentrations were retrospectively determined in the first, second and third trimester of pregnancy in 41 uncomplicated pregnancies, 10 pregnancies complicated with preeclampsia and 14 pregnancies that delivered a SGA baby. ADMA was measured with an ELISA kit. Results: Mean (±SD) concentrations of ADMA (µmol/L) in uncomplicated l pregnancies were: 0.51?±?0.14; 0.52?±?0.13; 0.58?±?0.16 in the three trimesters, respectively. ADMA concentrations in SGA pregnancies were significantly lower in each trimester compared to uncomplicated pregnancies: (0.40?±?0.10, p?=?0.005 1st trim; 0.42?±?0.10, p?=?0.007 2nd trim; 0.45?±?0.10, p?=?0.007 3rd trim). Although pregnancies that developed preeclampsia had higher ADMA concentration in all trimesters compared to uncomplicated pregnancies (0.58?±?0.10; 0.63?±?0.14; 0.68?±?0.11), the difference was statistically significant only in the 2nd trimester (p?=?0.02). Conclusions: Maternal serum ADMA concentration tends to increase during normal pregnancy. Pregnancies with SGA infants had significantly lower ADMA levels in all trimesters of pregnancy. ADMA concentrations in the 2nd trimester was significantly elevated in pregnancies that later developed preeclampsia.     

The creation of Adam and God-placenta

Objective. We retrospectively investigated a cohort of very low birthweight infants (VLBWI) by comparing two methods for assessment of albuminuria: nephelometry (standard) and high performance liquid chromatography (HPLC), measuring urinary immunoreactive and non-immunoreactive albumin to evaluate if the latter is more sensitive in identifying childhood onset of albuminuria and hypertension in VLBWI individuals.

Methods. Spot urine samples of a total of 109 subjects (5.3 ± 2.2 years old) who were VLBWI were investigated by HPLC and nephelometry. Twenty-eight subjects were small for gestational age (SGA) and 81 were appropriate for gestational age (AGA). Blood Pressure (BP) was also recorded.

Results. Twelve children (11%) with albuminuria 20 mg/g Cr by nephelometry versus 48 (44.5%) by HPLC (p < 0.001) were identified. The mean ± SD of values in the range of normoalbuminuria was 2.9 ± 5.81 by nephelometry versus 22.6 ± 14 for HPLC (p < 0.001). The values were not statistically different in the two birthweight categories (<1000, 1000–1499 g), in AGA versus SGA and in high BP (>90th percentile) versus normal BP children.

Conclusions. Microalbuminuria by HPLC was more marked in VLBWI than in adults and the difference between values using the two methods was significative.     

Plasma adrenomedullin levels in pregnancies with appropriate for gestational age and small for gestational age infants.

AIMS: To evaluate whether maternal and fetal plasma adrenomedullin levels in pregnancies with small for gestational age (SGA) infants are different from those in pregnancies with appropriate for gestational age (AGA) infants. METHODS: Maternal and fetal circulating adrenomedullin levels were compared between 62 pregnancies with AGA (43 delivered vaginally and 19 delivered by elective cesarean section) and 28 pregnancies with SGA (20 delivered vaginally and 8 delivered by elective cesarean section) at birth. Plasma adrenomedullin levels were measured from maternal and cord venous blood samples using a radioimmunoassay. Umbilical artery blood pH was also measured. RESULTS: There were no significant differences for maternal total adrenomedullin levels, mature adrenomedullin levels, and its ratio among the groups. There were also no significant differences for fetal total adrenomedullin levels, mature adrenomedullin levels, and its ratio among the groups. In the AGA group delivered vaginally, fetal mature/total adrenomedullin ratio (mean +/- standard error, 16.6 +/- 0.7%) was significantly higher than the maternal ratio (13.8 +/- 0.6%) (p < 0.05). In the SGA group delivered vaginally, fetal mature/total adrenomedullin ratio (18.5 +/- 1.0%) was also significantly higher than the maternal ratio (14.5 +/- 0.6%) (p < 0.05). There was no significant difference in umbilical artery blood pH among the groups. CONCLUSIONS: These results suggest that maternal and fetal plasma circulating adrenomedullin levels may play a role in maternal and fetal cardiovascular adaptation during delivery in pregnancies with both AGA and SGA infants.     

Iron status at birth and at 4 weeks in preterm-SGA infants in comparison with preterm and term-AGA infants

Objective: To determine the iron status at birth in preterm small for gestational age (SGA) in comparison with preterm appropriate for gestation (AGA) and term-AGA infants. Methods: Mother–infant pairs with gestation of < 37 weeks, both SGA, and preterm-AGA and term-AGA as control were enrolled. Maternal, cord blood and infant blood samples at 4 weeks were obtained for various iron indices – cord serum ferritin, proportion of infants with “low” serum ferritin, serum ferritin at 4 weeks and correlation among maternal and neonatal iron indices – hemoglobin,serum ferritin and total iron-binding capacity. Results: There were 50 mother–infant pairs in each group. Cord serum ferritin levels were less in preterm-SGA group as compared to preterm-AGA group (median [interquartile range]: 68 [30 113] vs. 120 [73 127], p = 0.002) and preterm-AGA had less cord ferritin than term-AGA (141 [63 259], p = 0.006). The proportion of the infants with “low” serum ferritin was more in preterm-SGA than in preterm-AGA (16 [32%] vs. 5 [10%], p = 0.01). The serum ferritin levels at follow-up were also less in preterm-SGA as compared to preterm-AGA (143.5 ± 101 vs. 235.1 ± 160, p = 0.004). Other cord blood iron indices and follow-up serum ferritin levels were similar. There was no correlation among various maternal and neonatal cord iron parameters. Conclusions: Preterm-SGA infants have lesser total iron stores as compared to gestation-matched AGA infants, which is again lesser than term infants. Future studies can be planned to look at iron status at 12 months as well as their neurodevelopmental outcome.     

The small-for-gestational-age fetus has an intact ability to develop lacticemia when exposed to hypoxia: a retrospective comparative register study

Objective: To investigate the ability of small-for-gestational-age (SGA) fetuses to develop lacticemia during hypoxia.

Methods: Umbilical cord arterial and venous pH, lactate and glucose concentrations were determined in 1777 SGA (<10th percentile) and 14,569 AGA newborns and related to acidemia (pH?p?Results: Glucose and lactate were linearly related and both variables correlated negatively with pH. Glucose was equal in SGA and AGA at a normal pH, but at severe acidemia it was lower in SGA. Glucose was higher in both groups during acidemia. Lactate was higher in SGA at both a normal and a low pH, and in both groups lactate increased progressively with the severity of acidemia.

Conclusions: In both SGA and AGA fetuses, glucose was mobilized during acidemia; lactate was higher in SGA at both a normal and low pH. Considering SGA being a proxy for fetal growth restriction, and acidemia a proxy for hypoxia, it is concluded that growth-restricted fetuses have an intact ability to develop lacticemia during hypoxia.     

Total energy intake accounts for postnatal anthropometric growth in moderately/late preterm infants

Objective: Moderately preterm (MP) (32–33 weeks) and late preterm (LP) (34–36 weeks) infants have higher risks of mortality and growth and developmental problems. We, herein present a new concept of nutritional assessment, total energy intake (TEI), which is the sum total of kilocalories administered in all nutrient forms.

Methods: Fifty-two preterm infants were classified as MP (n?=?12), LP/appropriate for gestational age (LP/AGA) (n?=?33), or LP/small for gestational age (LP/SGA) (n?=?7). All groups received nutrient therapy by the same protocol. The sum of the daily energy intake at 14 and 28 days after birth was determined.

Results: TEI was 2822.1?±?162.1?kcal/kg/28 days in the MP group, 3187.2?±?265.0?kcal/kg/28 days in the LP/AGA group and 3424.6?±?210.4?kcal/kg/28 days in the LP/SGA group. In all groups, TEI for 28 days was significantly correlated with body weight gain (r?=?0.465, p?=?0.006). TEI for 14 days after birth was inversely correlated with the body weight loss rate after birth (r?=??0.491, p?=?0.0002).

Conclusion: TEI was well correlated with anthropometric changes after birth. TEI may be used to effectively assess preterm infants’ nutritional needs.     

Serum fetuin-A/alpha2-HS-glycoprotein in human pregnancies with normal and restricted fetal growth

Objective. To investigate circulating concentrations of human fetuin-A (important fetal glycoprotein, involved in vascular pathology and bone metabolism) in mothers, fetuses and neonates from intrauterine-growth-restricted (IUGR, associated with low bone mass at birth and metabolic syndrome in adult life) and appropriate-for-gestational-age (AGA) pregnancies.

Methods. Serum fetuin-A concentrations were prospectively measured in 40 mothers, the doubly-clamped umbilical cords (representing fetal state) and their 20 IUGR and 20 AGA full-term neonates on postnatal day 1 (N1) and 4 (N4).

Results. No significant differences in fetuin-A concentrations were observed between groups, or between maternal, fetal and neonatal samples in both groups. In the AGA group, maternal fetuin-A concentrations positively correlated with fetal and N1 ones (r = 0.599, p = 0.005 and r = 0.469, p = 0.037, respectively). In the IUGR group, maternal fetuin-A concentrations positively correlated with N4 ones (r = 0.541, p = 0.014).

Conclusion. Serum fetuin-A concentrations do not differ between IUGR cases and AGA controls. Maternal and fetal fetuin-A concentrations are similar and positively correlated, indicating the likelihood of passive transplacental transfer of this substance.     

Umbilical cord asymmetric dimethylarginine levels and ultrasound assessment of carotid arteries in neonates born small for gestational age

Background: To examine asymmetric dimethylarginine (ADMA) level as an endothelial function parameter in addition to ultrasonographic evaluation of carotid arteries in babies born small for gestational age (SGA).

Methods: Twenty-six neonates born SGA and 34 appropriate for gestational age (AGA) controls were included in the study. The serum levels of ADMA were measured. Intima-media thickness (cIMT) and resistive index (cRI) of the both carotid arteries were determined by ultrasonography.

Results: The mean ADMA level was higher in SGA neonates compared to AGAs (16 267.7?±?6050 versus 12 810.2?±?3302?ng/L; p?=?0.01). The mean cIMT (0.34?±?0.02 versus 0.31?±?0.03?mm; p?=?0.001) and cRI (0.66?±?0.07 versus 0.61?±?0.04, p?=?0.003) were also higher in SGAs. Serum ADMA levels were positively correlated to the mean cIMT (r?=?0.41, p?=?0.001). Although there was a weak correlation between cIMT and mean cRI (r?=?0.26, p?=?0.04), no correlation was found between ADMA and mean cRI (r?=?0.17, p?=?0.18).

Conclusions: Neonates born SGA have elevated cord blood ADMA level in addition to thicker IMT and higher RI of carotid arteries at birth. ADMA was correlated to cIMT, suggesting that higher ADMA levels might influence vascular health in later life in these neonates.     

Placental growth hormone is increased in the maternal and fetal serum of patients with preeclampsia

Objectives. Placental growth hormone (PGH) is a pregnancy-specific protein produced by syncytiotrophoblast and extravillous cytotrophoblast. No other cells have been reported to synthesize PGH Maternal. PGH Serum concentration increases with advancing gestational age, while quickly decreasing after delivery of the placenta. The biological properties of PGH include somatogenic, lactogenic, and lipolytic functions. The purpose of this study was to determine whether the maternal serum concentrations of PGH change in women with preeclampsia (PE), women with PE who deliver a small for gestational age neonate (PE + SGA), and those with SGA alone.

Study design. This cross-sectional study included maternal serum from normal pregnant women (n = 61), patients with severe PE (n = 48), PE + SGA (n = 30), and SGA alone (n = 41). Fetal cord blood from uncomplicated pregnancies (n = 16) and PE (n = 16) was also analyzed. PGH concentrations were measured by ELISA. Non-parametric statistics were used for analysis.

Results. (1) Women with severe PE had a median serum concentration of PGH higher than normal pregnant women (PE: median 23,076 pg/mL (3473–94 256) vs. normal pregnancy: median 12 157 pg/mL (2617–34 016); p < 0.05), pregnant women who delivered an SGA neonate (SGA: median 10 206 pg/mL (1816–34 705); p < 0.05), as well as pregnant patients with PE and SGA (PE + SGA: median 11 027 pg/mL (1232–61 702); p < 0.05). (2) No significant differences were observed in the median maternal serum concentration of PGH among pregnant women with PE and SGA, SGA alone, and normal pregnancy (p > 0.05). (3) Compared to those of the control group, the median umbilical serum concentration of PGH was significantly higher in newborns of preeclamptic women (PE: median 356.1 pg/mL (72.6–20 946), normal pregnancy: median 128.5 pg/mL (21.6–255.9); p < 0.01). (4) PGH was detected in all samples of cord blood.

Conclusions. (1) PE is associated with higher median concentrations of PGH in both the maternal and fetal circulation compared to normal pregnancy. (2) Patients with PE + SGA had lower maternal serum concentrations of PGH than preeclamptic patients without SGA. (3) Contrary to previous findings, PGH was detectable in the fetal circulation. The observations reported herein are novel and suggest that PGH may play a role in the mechanisms of disease in preeclampsia and fetal growth restriction.     

Feeding tolerance of preterm infants appropriate for gestational age (AGA) as compared to those small for gestational age (SGA)

Abstract

Preterm infants are often considered too unstable to be fed enterally so they are exposed to complications related to a prolonged enteral fasting. Our study aims to compare feeding tolerance of adequate for gestational age (AGA) versus small for gestational age (SGA) infants and to evaluate which perinatal factors affect feeding tolerance (measured as time to achieve full enteral feeding, FEF). Inborn infants with a gestational age (GA) less than 32 weeks, born from January 2006 to December 2010, were eligible for this study. We enrolled 310 infants. The time to FEF was longer for SGA infants than for AGA, while a longer GA was associated to a reduced time to FEF. A beneficial effect was observed for antenatal steroids, while Apgar score below 7, the administration of inotrops or caffeine, the occurrence of sepsis or NEC and the presence of PDA were associated to a longer time to FEF. When evaluated jointly with a multivariate analysis, GA (p?<?0.0001), antenatal steroids prophylaxis (p?=?0.002), SGA (p?<?0.0001) and occurrence of NEC (p?=?0.0002) proved to have independent prognostic impact on the time to FEF. Feeding tolerance is better as GA increases, and worsen in SGA infants. Antenatal betamethasone is effective in reducing the time to FEF in both AGA and SGA.