Assessment of ten trace elements in umbilical cord blood and maternal blood: association with birth weight.

BACKGROUND: Trace elements are an essential nutritional component for humans and inadequate tissue-concentrations may have a significant effect on fetal size. OBJECTIVE: To measure ten trace elements in blood samples from mothers and their newborns, and assess their association with anthropometric characteristics at birth. The effects of other factors on fetal growth, such as biologic characteristics of the infant and mother, were analysed. METHODS: A cross-sectional study was conducted in the Hospital general, University of Valencia, Spain. Healthy pregnant women, and their full-term infants were selected (n = 54 paired samples). Infants were grouped according to birth weight: small for gestational age (SGA n = 11), appropriate (AGA n = 30), and large (LGA n = 13). Anthropometric and biologic characteristics of the infant and mother were recorded. Levels of ten essential elements: arsenic (As), barium (Ba), cobalt (Co), copper (Cu), chrome (Cr), iron (Fe), magnesium (Mg), manganese (Mn), selenium (Se) and zinc (Zn), in maternal and cord plasma samples were determined. Samples were obtained from the umbilical cord immediately after delivery and the samples of their mothers were drawn at 2-4 h after delivery. RESULTS: The analysis identified that cord blood Cu (p = 0.017) and maternal blood Ba and Mg (p = 0.027 and p = 0.002, respectively) concentrations were significantly higher among SGA infants compared to AGA and LGA infants. A multiple linear regression analysis showed that increased umbilical cord Cu concentration (adjusted ß -146.4 g, 95% CI -255 to -37.7; p = 0.009), maternal smoking during pregnancy (adjusted ß -483.8 g, 95% CI -811.7 to -155.9; p = 0.005), shorter gestational age (adjusted ß 350.1 g, 95% CI 244.5 to 455.8; p = 0.000), and female sex (adjusted ß -374 g, 95% CI -648 to -100; p = 0.009) were significantly associated with decreased birth weight. Maternal anaemia was positively associated with birth weight (adjusted ß 362 g, 95% CI 20.8 to 703.1; p = 0.038). No significant associations were found between maternal trace elements and birth weight in multivariate analysis. CONCLUSIONS: We did not observe significant associations of cord blood trace elements other than Cu and maternal trace elements with birth weight in the multivariate analyses.

DNA methylation patterns in newborns exposed to tobacco in utero.

BACKGROUND: Maternal smoking during pregnancy is a major risk factor for adverse health outcomes. The main objective of the study was to assess the impact of in utero tobacco exposure on DNA methylation in children born at term with appropriate weight at birth. METHODS: Twenty mother-newborn dyads, after uncomplicated pregnancies, in the absence of perinatal illness were included. All mothers were healthy with no cardiovascular risk factors, except for the associated risks among those mothers who smoked. Umbilical cord blood and maternal peripheral venous blood were collected and an epigenome-wide association study was performed using a 450 K epigenome-wide scan (Illumina Infinium HumanMethylation 450BeadChip) with adjustment to normalize the DNA methylation for data cell variability in whole blood. RESULTS: The maternal plasmatic cotinine levels ranged from 10.70-115.40 ng/ml in the exposed group to 0-0.59 ng/ml in the non-exposed group. After adjusting for multiple comparisons in 427102 probes, statistically significant differences for 31 CpG sites, associated to 25 genes were observed. There was a greater than expected proportion of statistically-significant loci located in CpG islands (Fisher's exact test, p = 0.029) and of those CpG islands, 90.3% exhibit higher methylation levels in the exposed group. The most striking and significant CpG site, cg05727225, is located in the chromosome 11p15.4, within the adrenomedullin gene. CONCLUSIONS: In utero tobacco exposure, even in the absence of fetal growth restriction, may alter the epigenome, contributing to global DNA hypomethylation. Therefore, DNA status can be used as a biomarker of prenatal insults. Considering the possibility to reverse epigenetic modifications, a window of opportunity exists to change the programmed chronic disease.

Associations of birth weight and postnatal weight gain with cardiometabolic risk parameters at 5 years of age.

The present prospective study assessed the impact of birth weight (BW) and postnatal weight gain on blood pressure and metabolic profile during the first 5 years of life. One hundred thirty-nine newborns (63 women) born at term after uncomplicated pregnancies and in the absence of perinatal illness were included. Subjects were divided according to size at birth in small, appropriate, and large for gestational age. After the initial evaluation on the second day of life, infants were followed up at 6 months and 2 and 5 years. Anthropometric parameters and blood pressure were measured at each visit and metabolic assessment was performed at 5 years of age. Among the BW groups, mothers did not differ in terms of age, smoking, and weight gain during pregnancy. BW was a positive determinant of systolic blood pressure at birth. Afterward, current weight was the strongest determinant, becoming significant at 2 years of age and progressively increasing in influence. At 5 years insulin, the homeostasis model assessment index and triglycerides were dependent on BW, current weight, and postnatal weight gain. In addition, BW was positively associated with high-density lipoprotein-cholesterol and inversely so to uric acid. A positive relationship among insulin, blood pressure values, and uric acid was observed even early in life. In conclusion, the acceleration of early infant weight gain may aggravate the effects of low BW. Multiple interactions between hemodynamic and metabolic parameters foreshadow the clustering of cardiometabolic risk factors later in life.

High cotinine levels are persistent during the first days of life in newborn second hand smokers.

BACKGROUND: Despite the adverse effects of maternal smoking during pregnancy on the newborn's health are well-known, in the pediatric population, a high prevalence exists that is very much affected by second hand smoke (SHS). This study aims to investigate the impact of maternal smoking habits during pregnancy on cotinine levels in newborns during the first days of life. The high association between cotinine concentration in maternal and umbilical cord blood (UCB) has been previously reported, but the levels of blood cotinine that remain in infants born to smokers is unknown. METHODS: Cotinine concentration was measured in UCB, in maternal and newborn peripheral blood. Data from UCB sample dyads of ninety mothers and from seventy-one newborns were analyzed. RESULTS: Cotinine levels were significantly different among non-smokers (9.9 ± 5.9 ng/ml), moderate (67.3 ± 7.4 ng/ml), and heavy smokers (137.7 ± 19.5 ng/ml) (p<0.0001). Significant correlations were found between maternal and UCB cotinine (r=0.748; p<0.001), and between UCB and newborn plasma cotinine at 48 h after birth (r=0.541; p<0.001). The smokers exposed their infants to cotinine with a median of 31.7 ± 8.6 ng/ml (moderate) or 59.1 ± 13.3 ng/ml (heavy smokers) until at least, 48 h after birth. Reduced birth weight and length were significantly related with UCB cotinine levels. CONCLUSIONS: A positive association between UCB and plasmatic cotinine in newborns was found. The high cotinine levels detected in newborns from smoker mothers indicates that their infants are subjected to elevated SHS from birth. These results can help to reinforce the awareness of the adverse effects of smoking during pregnancy.

Metabolomic profiling in blood from umbilical cords of low birth weight newborns.

BACKGROUND: Low birth weight has been linked to an increased risk to develop obesity, type 2 diabetes, and hypertension in adult life, although the mechanisms underlying the association are not well understood. The objective was to determine whether the metabolomic profile of plasma from umbilical cord differs between low and normal birth weight newborns. METHODS: Fifty healthy pregnant women and their infants were selected. The eligibility criteria were being born at term and having a normal pregnancy. Pairs were grouped according to their birth weight: low birth weight (LBW, birth weight < 10th percentile, n = 20) and control (control, birth weight between the 75th-90th percentiles, n = 30). Nuclear Magnetic Resonance (NMR) was used to generate metabolic fingerprints of umbilical cord plasma samples. Simultaneously, the metabolomic profiles of the mothers were analysed. The resulting data were subjected to chemometric, principal component and partial least squares discriminant analyses. RESULTS: Umbilical cord plasma from LBW and control newborns displayed a clearly differentiated metabolic profile. Seven metabolites were identified that discriminate the LBW from the control group. LBW newborns had lower levels of choline, proline, glutamine, alanine and glucose than did the control newborns, while plasma levels of phenylalanine and citrulline were higher in LBW newborns (p < 0.05). No significant differences were found between the two groups of mothers. CONCLUSIONS: Low birth weight newborns display a differential metabolomic profile than those of normal birth weight, a finding not present in the mothers. The meaning and the potential utility of the findings as biomarkers of risk need to be addressed in future studies.

Blood pressure and obesity exert independent influences on pulse wave velocity in youth.

The objective was to analyze pulse wave velocity (PWV) in normotensive, high-normal, and hypertensive youths by using aortic-derived parameters from peripheral recordings. The impact of obesity on vascular phenotypes was also analyzed. A total of 501 whites from 8 to 18 years of age were included. The subjects were divided according to BP criteria: 424 (85%) were normotensive, 56 (11%) high-normal, and 21 (4%) hypertensive. Obesity was present in 284 (56%) and overweight in 138 (28%). Pulse wave analysis using a SphygmoCor device was performed to determine central blood pressure (BP), augmentation index, and measurement of PWV. Among the BP groups, differences appeared in age, sex, and height but not in body mass index. Significant differences in peripheral and central systolic and diastolic BPs and pulse pressures were observed within groups. A graded increase in PWV was present across the BP strata without differences in augmentation index. Using a multiple regression analysis, age, BP groups, and obesity status were independently associated with PWV. Older and hypertensive subjects had the highest PWV, whereas, from normal weight status to obesity, PWV decreased. Likewise, PWV was positively related to peripheral or central systolic BP and negatively related to body mass index z score. For 1 SD of peripheral systolic BP, PWV increased 0.329 m/s, and for 1 SD of body mass index z score PWV decreased 0.129 m/s. In conclusion, PWV is increased in hypertensive and even in high-normal children and adolescents. Furthermore, obesity, the factor most frequently related to essential hypertension in adolescents, blunted the expected increment in PWV of hypertensive and high-normal subjects.

Birth weight and characteristics of endothelial and smooth muscle cell cultures from human umbilical cord vessels.

BACKGROUND: Low birth weight has been related to an increased risk for developing high blood pressure in adult life. The molecular and cellular analysis of umbilical cord artery and vein may provide information about the early vascular characteristics of an individual. We have assessed several phenotype characteristics of the four vascular cell types derived from human umbilical cords of newborns with different birth weight. Further follow-up studies could show the association of those vascular properties with infancy and adulthood blood pressure. METHODS: Endothelial and smooth muscle cell cultures were obtained from umbilical cords from two groups of newborns of birth weight less than 2.8 kg or higher than 3.5 kg. The expression of specific endothelial cell markers (von Willebrand factor, CD31, and the binding and internalization of acetylated low-density lipoprotein) and the smooth muscle cell specific alpha-actin have been evaluated. Cell culture viability, proliferation kinetic, growth fraction (expression of Ki67) and percentage of senescent cells (detection of beta-galactosidase activity at pH 6.0) have been determined. Endothelial cell projection area was determined by morphometric analysis of cell cultures after CD31 immunodetection. RESULTS: The highest variation was found in cell density at the confluence of endothelial cell cultures derived from umbilical cord arteries (66,789 +/- 5,093 cells/cm(2) vs. 45,630 +/- 11,927 cells/cm(2), p < 0.05). Morphometric analysis indicated that the projection area of the artery endothelial cells (1,161 +/- 198 and 1,544 +/- 472 microm(2), p < 0.05), but not those derived from the vein from individuals with a birth weight lower than 2.8 kg was lower than that of cells from individuals with a birth weight higher than 3.5 kg. CONCLUSION: The analysis of umbilical cord artery endothelial cells, which demonstrated differences in cell size related to birth weight, can provide hints about the cellular and molecular links between lower birth weight and increased adult high blood pressure risk.

Procedure to consistently obtain endothelial and smooth muscle cell cultures from umbilical cord vessels.

The prenatal history of an individual can be responsible to some extent for the occurrence of several diseases later in life. Thus, low birth weight has been related to an increased risk of developing hypertension or type 2 diabetes. The molecular and cellular basis of this increased risk could be found in body fluids and cell types that can be obtained just after birth. To get this unique information, a methodology was developed to consistently obtain cultures of 4 cell types, endothelial and smooth muscle cells from both the vein and the arteries present in the umbilical cord of an individual. From 21 umbilical cords processed, 82 of the 84 possible cell cultures were obtained. The cell cultures exhibit the expected cell morphology and cellular characteristics. Thus, endothelial cells express the von Willebrand factor, CD31, as well as bind and internalize acetylated low-density lipoprotein. Vascular smooth muscle cells express the distinctive alpha-actin. Cell cultures can be cryopreserved and grow healthy for several passages. No influence of birth weight of the newborn has been found in the time required to obtain a primary cell culture for any of the 4 cell types. In conclusion, the procedure developed allows one to routinely obtain actively growing vascular cell cultures that could be used to study the molecular and cellular basis of vascular diseases that emerge in adulthood.

First-year blood pressure increase steepest in low birthweight newborns.

AIM: The present research has been undertaken prospectively to study the impact of birthweight and growth pattern on blood pressure changes from birth through the first year of life. METHODS: Parents of newborns born at term (gestational age > 37 weeks) after uncomplicated pregnancies and in the absence of perinatal illness were randomly invited to allow their children to participate in the study. One hundred and forty-nine (84 male and 65 female) newborns were included in the present analysis. The newborns were divided into four groups according to birthweight: < 2500 g (n = 23); 2500-2999 g (n = 39); 3000-3500 g (n = 48); and > 3500 g (n = 39). RESULTS: At birth systolic and diastolic blood pressure were significantly lower and heart rate was significantly higher in those children with the lowest birthweight as compared to those in the other groups. During the first month of life a significant trend, inversely related to birthweight, was present for systolic as well as diastolic blood pressure. After the first month of life, at 3, 6, 9 and at 12 months, systolic and diastolic blood pressure were similar across birthweight groups. In a multiple regression analysis, birthweight was a positive independent determinant of systolic blood pressure at birth and an inverse independent determinant of the increment of systolic blood pressure during the first month of life and of the systolic blood pressure at the end of the first year. CONCLUSIONS: In summary, the present study goes further towards understanding blood pressure changes in low birthweight babies. Beginning at birth, both blood pressure values, as well as changes in blood pressure, provide information about the impact of intrauterine life on the risk of developing hypertension later in life.