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ABSTRACT: Low birth weight and accelerated infant growth are associated with cardiovascular disease in adulthood. Endothelial dysfunction is regarded as a precursor of atherosclerosis and is also related to infant growth. We aimed to examine whether an association between infant growth and endothelial function is already present during discrete periods of growth during the first 6 months of life in healthy term infants. A cohort of 104 newborns was studied in the first week after birth and reexamined at the age of 6 months. Maximum vasodilatation in response to acetylcholine (endothelium dependent) and nitroprusside (endothelium independent) was measured in the vasculature of the forearm skin, using laser Doppler flowmetry and iontophoresis. Growth was calculated as difference in Z scores for weight, length, weight-for-length, and head circumference. Multivariable multilevel linear regression was used for the analysis. Growth from 0 to 1 month (calculated as difference in weight) was the only window in the first 6 months of life that was significantly and inversely associated with endothelium-dependent vasodilatation at 6 months (b=-11.72 perfusion units per Z score, P=0.01 in multivariable analysis). Birth size was not important when considered simultaneously with infant growth. Maximum endothelium-independent vasodilatation was not associated with birth size or growth parameters. We conclude that growth in the first month of life is inversely associated with endothelium-dependent vasodilatation at the age of 6 months in healthy term infants, regardless of birth size.
Hypertension 10/2012; 60(5):1294-300. · 6.21 Impact Factor
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ABSTRACT: Objective: The fetal response to an adverse intrauterine environment – reflected in low birth weight – is thought to cause an increased risk for adult hypertension. A possible mechanism by which fetal adaptive responses contribute to hypertension is an adverse effect on endothelial function. Identifying individuals with endothelial dysfunction as early as possible may assist in understanding the inverse association between birth weight and hypertension. The present study aimed to identify determinants of endothelial vasodilatation in the first week of life.
Methods: One hundred and four term newborns were studied in the first week after birth with regard to maximum vasodilatation in response to acetylcholine (endothelium-dependent) and nitroprusside (endothelium-independent) in the vasculature of the forearm skin, by use of a laser-Doppler device and iontophoresis. Bivariable and multivariable linear regression with various familial, gestational and neonatal potential covariates were used for the analysis.
Results: In the bivariable analysis, maximum perfusion after administration of acetylcholine was positively associated with birth weight, length, head circumference and maternal education level, but negatively associated with maternal hypertension during pregnancy. In the multivariable analysis, head circumference [b = 11.9 perfusion units/z-score, P = 0.02] and hypertension during pregnancy (b = −25.3 perfusion units from nonhypertensive to hypertensive, P = 0.02) remained significantly associated. Maximum perfusion after administration of nitroprusside was not related to any of the anthropometric measures; it was, however, related to gestational age (b = −11.1 perfusion units/week, P = 0.009).
Conclusion: This study showed that body size, head circumference in particular, is positively associated with endothelial vasodilatation in newborns, whereas hypertension during pregnancy is inversely associated with endothelial vasodilatation.
Journal of Hypertension 12/2011; 30(1):124–131. · 4.02 Impact Factor
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Robbert N Touwslager,
Marij Gielen,
Antonius L Mulder,
Willem J Gerver, Luc J Zimmermann,
Tom Fowler,
Alfons J Houben,
Coen D Stehouwer,
Catherine Derom,
Robert Vlietinck,
Ruth J F Loos,
Maurice P Zeegers
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ABSTRACT: Accelerated infant growth is a possible explanation for the relation between birth weight and adult diseases.
The aim of this study was to estimate the heritability of infant growth and to examine whether the genetic contribution changes with increasing or decreasing birth weight and gestational age.
Growth (change in weight z score) was analyzed in 522 infants from the East Flanders Prospective Twin Survey for age windows of 0-1, 1-6, 6-12, and 12-24 mo. Structural equation modeling was performed to estimate the relative importance of additive genetic, shared environmental, and unique environmental sources of variance.
We showed no genetic contribution to growth in the 0-1-mo growth period. However, at later ages, the heritability of growth was high at 94% (95% CI: 90%, 96%) from 1 to 6 mo, 85% (95% CI: 80%, 89%) from 6 to 12 mo, and 86% (95% CI: 77%, 91%) in the 12-24-mo growth period. Nevertheless, in the last age window, a model without genetic factors was also statistically plausible. From 0 to 1 mo, the genetic contribution to growth was low in the average birth weight range but higher at both extremes of birth weight. The genetic contribution from 0 to 1 mo increased with increasing gestational age from 36 wk of gestation onward.
This study shows that genetic factors are not important in early infant growth (0-1 mo), whereas heritability is high after 1 mo. Because many (nutritional) interventions are aimed at influencing early postnatal growth, to target long-term health, these interventions may be most successful if implemented in the first month of postnatal growth.
American Journal of Clinical Nutrition 11/2011; 94(6):1568-74. · 6.67 Impact Factor
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ABSTRACT: The fetal response to an adverse intrauterine environment - reflected in low birth weight - is thought to cause an increased risk for adult hypertension. A possible mechanism by which fetal adaptive responses contribute to hypertension is an adverse effect on endothelial function. Identifying individuals with endothelial dysfunction as early as possible may assist in understanding the inverse association between birth weight and hypertension. The present study aimed to identify determinants of endothelial vasodilatation in the first week of life.
One hundred and four term newborns were studied in the first week after birth with regard to maximum vasodilatation in response to acetylcholine (endothelium-dependent) and nitroprusside (endothelium-independent) in the vasculature of the forearm skin, by use of a laser-Doppler device and iontophoresis. Bivariable and multivariable linear regression with various familial, gestational and neonatal potential covariates were used for the analysis.
In the bivariable analysis, maximum perfusion after administration of acetylcholine was positively associated with birth weight, length, head circumference and maternal education level, but negatively associated with maternal hypertension during pregnancy. In the multivariable analysis, head circumference [b = 11.9 perfusion units/z-score, P = 0.02] and hypertension during pregnancy (b = -25.3 perfusion units from nonhypertensive to hypertensive, P = 0.02) remained significantly associated. Maximum perfusion after administration of nitroprusside was not related to any of the anthropometric measures; it was, however, related to gestational age (b = -11.1 perfusion units/week, P = 0.009).
This study showed that body size, head circumference in particular, is positively associated with endothelial vasodilatation in newborns, whereas hypertension during pregnancy is inversely associated with endothelial vasodilatation.
Journal of hypertension 10/2011; 30(1):124-31. · 4.02 Impact Factor
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Hendrik J Niemarkt,
Ward Jennekens,
Imke A Maartens,
Tessa Wassenberg,
Marijke van Aken,
Titia Katgert,
Boris W Kramer,
Antonio W D Gavilanes, Luc J Zimmermann,
Sidarto Bambang Oetomo,
Peter Andriessen
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ABSTRACT: To analyze quantitatively multi-channel amplitude-integrated EEG (aEEG) characteristics and assess regional differences.
We investigated 40 preterm infants (postmenstrual age, PMA: range 27-37 weeks) with normal follow-up at 24 months of age, at a median postnatal age of 8 days using 4-h EEG recordings according to the international 10-20 system reduced montage. Nine (3 transverse and 6 longitudinal) channels were selected and converted to aEEG registrations. For each aEEG registration, lower margin amplitude (LMA), upper margin amplitude (UMA) and bandwidth (UMA-LMA) were calculated.
In all channels PMA and LMA showed strong positive correlations. Below 32 weeks of PMA, LMA was ≤5μV. Linear regression analysis showed a maximum LMA difference between channels of approximately 2 and 1μV at 27 and 37 weeks of PMA, respectively. The lowest are LMA values in the occipital channel and the highest values are in centro-occipital channels. In the frontal, centro-temporal and centro-occipital channels, UMA and bandwidth changed with PMA. No differences in LMA, UMA and bandwidth were found between hemispheres. Skewness of LMA values strongly correlated with PMA, positive skewness indicating an immature brain (PMA≤32 weeks) and negative skewness a maturing (PMA>32 weeks) brain.
We detected symmetric increase of aEEG characteristics, indicating symmetric brain maturation of the left and right hemispheres. Our findings demonstrate the clinical potential of computer-assisted analyses of aEEG recordings in detecting maturational features which are not readily identified visually. This may provide an objective and reproducible method for assessing brain maturation and long-term prognosis.
Early human development 09/2011; 88(4):209-16. · 2.12 Impact Factor
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ABSTRACT: Our study aimed at automated power spectral analysis of the EEG in preterm infants to identify changes of spectral measures with maturation. Weekly (10-20 montage) 4-h EEG recordings were performed in 18 preterm infants with GA <32 wk and normal neurological follow-up at 2 y, resulting in 79 recordings studied from 27(+4) to 36(+3) wk of postmenstrual age (PMA, GA + postnatal age). Automated spectral analysis was performed on 4-h EEG recordings. The frequency spectrum was divided in delta 1 (0.5-1 Hz), delta 2 (1-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), and beta (13-30 Hz) band. Absolute and relative power of each frequency band and spectral edge frequency were calculated. Maturational changes in spectral measures were observed most clearly in the centrotemporal channels. With advancing PMA, absolute powers of delta 1 to 2 and theta decreased. With advancing PMA, relative power of delta 1 decreased and relative powers of alpha and beta increased, respectively. In conclusion, with maturation, spectral analysis of the EEG showed a significant shift from the lower to the higher frequencies. Computer analysis of EEG will allow an objective and reproducible analysis for long-term prognosis and/or stratification of clinical treatment.
Pediatric Research 07/2011; 70(5):529-34. · 2.70 Impact Factor
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ABSTRACT: The preservation of nutritional status and growth is an important aim in critically ill infants, but difficult to achieve due to the metabolic stress response and inadequate nutritional intake, leading to negative protein balance. This study investigated whether increasing protein and energy intakes can promote anabolism. The primary outcome was whole body protein balance, and the secondary outcome was first pass splanchnic phenylalanine extraction (SPE(Phe)).
This was a double-blind randomised controlled trial. Infants (n=18) admitted to the paediatric intensive care unit with respiratory failure due to viral bronchiolitis were randomised to continuous enteral feeding with protein and energy enriched formula (PE-formula) (n=8; 3.1 ± 0.3 g protein/kg/24 h, 119 ± 25 kcal/kg/24 h) or standard formula (S-formula) (n=10; 1.7 ± 0.2 g protein/kg/24 h, 84 ± 15 kcal/kg/24 h; equivalent to recommended intakes for healthy infants <6 months). A combined intravenous-enteral phenylalanine stable isotope protocol was used on day 5 after admission to determine whole body protein metabolism and SPE(Phe).
Protein balance was significantly higher with PE-formula than with S-formula (PE-formula: 0.73 ± 0.5 vs S-formula: 0.02 ± 0.6 g/kg/24 h) resulting from significantly increased protein synthesis (PE-formula: 9.6 ± 4.4, S-formula: 5.2 ± 2.3 g/kg/24 h), despite significantly increased protein breakdown (PE-formula: 8.9 ± 4.3, S-formula: 5.2 ± 2.6 g/kg/24 h). SPE(Phe) was not statistically different between the two groups (PE-formula: 39.8 ± 18.3%, S-formula: 52.4 ± 13.6%).
Increasing protein and energy intakes promotes protein anabolism in critically ill infants in the first days after admission. Since this is an important target of nutritional support, increased protein and energy intakes should be preferred above standard intakes in these infants. Dutch Trial Register number: NTR 515.
Archives of Disease in Childhood 06/2011; 96(9):817-22. · 2.88 Impact Factor
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Robbert N H Touwslager,
Marij Gielen,
Catherine Derom,
Antonius L M Mulder,
Willem-Jan M Gerver, Luc J Zimmermann,
Alfons J H M Houben,
Coen D A Stehouwer,
Robert Vlietinck,
Ruth J F Loos,
Maurice P Zeegers
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ABSTRACT: To identify determinants of growth during infancy.
The sample included 424 twin pairs from the East Flanders Prospective Twin Survey. Multilevel regression analysis was performed and intrapair growth correlations were calculated. The main outcome measure was growth, measured in g/kg/d (0-1 month) or in change in weight z-score (0-6, 6-12 and 12-24 months).
Growth during infancy was associated with birth weight and gestational age. One z-score increase in birth weight resulted in -1.77 g/kg/d less growth from 0-1 month (P < .0001). The effect size decreased with age until -0.02 (P = .70) z-scores less growth from 12 to 24 months. Corresponding numbers for one z-score increase in gestational age decreased from 0.78 (P = .001) to 0.06 (P = .40). From 12 to 24 months, paternal height had a significant positive effect. The difference in growth similarity within the twin pair between monozygotic and dizygotic twins increased from non-significant from 0 to 1 month (P = .49) to a monozygotic:dizygotic ratio approximating 2:1 from 12 to 24 months (P = .002).
From 0 to 1 month, environmental factors are most important for growth, whereas genetic factors become more important over time. This is a first step in identifying age windows for future counseling and interventions on the effects of accelerated growth.
The Journal of pediatrics 12/2010; 158(4):566-572.e2. · 4.02 Impact Factor
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The Journal of pediatrics 07/2010; · 4.02 Impact Factor
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ABSTRACT: We evaluated the impact of chorioamnionitis on the intrapartal EEG delta frequency in the non-anesthetized preterm sheep. 10 mg intra-amniotic LPS or saline were given 2 or 14 days before preterm birth at gestational day 125. Lambs were delivered by Caesarean section under local anesthesia. A 5-minute EEG depicted delta activity and amplitude, and the relationship between EEG delta activity and both the white matter (WM) and cortical microglial activation and apoptosis was analyzed. EEG delta activity was increased significantly in the 14-day LPS preterm fetuses compared to both preterm control and 2-day LPS animals (p less than 0.05). No differences were seen between controls and the 2-day LPS fetuses. A direct association was demonstrated between EEG delta activity and both cortical microglial activation (r = 0,645, p = 0,024) and apoptosis (r = 0,580, p = 0,048), and between delta and WM activated microglia (r = 0,742, p = 0,006) and apoptosis (r = 0,777, p = 0,003). This study is the first to show a relationship between brain dysfunction and chorioamnionitis-related injury at birth.
Frontiers in bioscience (Scholar edition) 01/2010; 2:432-8.
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ABSTRACT: To study the association between antenatal exposure to chorioamnionitis and the neonatal response to surfactant.
Prospective observational cohort of 301 preterm infants of gestational age < or = 32.0 weeks, 146 of whom received surfactant according to standardized criteria. Fraction of inspired oxygen (FiO(2)) requirement (using analysis of variance) and time to extubation (using Kaplan-Meier and Cox regression analyses) were compared between groups based on the presence of histological chorioamnionitis (HC) with or without fetal involvement (HC-, n = 88; HC + F-, n = 25; HC + F+, n = 33) and between infants who developed bronchopulmonary dysplasia (BPD) or died (n = 57) and BPD-free survivors (n = 89). Multiple logistic regression was performed to investigate the association between HC and BPD.
Compared with HC- infants, HC + F+ infants had significantly greater FiO(2) requirement and prolonged time to extubation postsurfactant, not accounted for by differences in gestational age and birth weight. Infants with BPD/death had a strikingly similar pattern of increased FiO(2) requirement postsurfactant. Moreover, in infants who received surfactant, HC + F+ status was associated with increased risk for BPD (odds ratio [OR] = 3.40; 95% confidence interval [CI] = 1.02-11.3; P = .047) and for BPD/death (OR = 2.72; 95% CI = 1.00-7.42; P = .049).
An impaired surfactant response was observed in preterm infants with severe chorioamnionitis and may be involved in the association between chorioamnionitis, mechanical ventilation, and the development of BPD.
The Journal of pediatrics 10/2009; 156(1):10-15.e1. · 4.02 Impact Factor
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ABSTRACT: Nutritional support improves outcome in critically ill infants but is impeded by fluid restriction, gastric intolerance and feeding interruptions. Protein and energy-enriched infant formulas may help to achieve nutritional targets earlier during admission and promote anabolism.
Randomized controlled design. Infants with respiratory failure due to RSV-bronchiolitis received a protein and energy-enriched formula (PE-formula, n=8) or a standard formula (S-formula, n=10) during 5 days after admission. Primary outcome: nutrient delivery, energy and nitrogen balance and plasma amino acid concentrations. Secondary outcome: tolerance and safety.
Nutrient intakes were higher in PE fed infants and met population reference intake (PRI) on day 3-5 whilst in S-fed infants PRI was met on day 5 only. Cumulative nitrogen balance (cNB) and energy balance (cEB) were higher in PE-infants compared to S-infants (cNB: 866+/-113 vs. 296+/-71 mg/kg; cEB: 151+/-31 and 26+/-17 kcal/kg, both P<0.01). Essential amino acid levels were higher in PE-infants but within reference limits whereas below these limits in S-infants. Both formulas were well tolerated.
Early administration of a protein and energy-enriched formula in critically ill infants is well tolerated, promotes a more adequate nutrient intake and improves energy and nitrogen balance without adverse effects.
Clinical nutrition (Edinburgh, Scotland) 05/2009; 28(3):249-55. · 3.27 Impact Factor
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ABSTRACT: Because meconium directly inhibits surfactant function, we sought to determine the effect of meconium on endogenous surfactant synthesis and clearance.
We studied surfactant phosphatidylcholine kinetics with the use of stable isotopes in 11 newborn infants with meconium aspiration syndrome (MAS) who required extracorporeal membrane oxygenation (ECMO). For comparison we studied 6 neonates with persistent pulmonary hypertension (PPHN) on ECMO and 10 term neonates ventilated for non-pulmonary indications and not on ECMO. All patients received a 24-hour [U- 13C]glucose infusion as precursor for the palmitic acid in surfactant phosphatidylcholine.
In the meconium group, the maximal 13C-incorporation in phosphatidylcholine (PC) was half of that in controls (0.09 +/- 0.01 vs 0.18 +/- 0.03 atom percent excess [APE], P = .027). There was a trend toward lower surfactant synthesis in the MAS group (3.3 +/- 0.7%/day) and PPHN group (2.6 +/- 0.3%/day) compared with controls 8.0 +/- 2.4%/day, P = .058). Significantly lower PC concentrations in tracheal aspirates were found in the MAS group (4.4 +/- 2.6 mg/mL) and PPHN group (3.6 +/- 2.0 mg/mL) compared with controls (12.8 +/- 2.6 mg/mL, P = .01). Endogenously synthesized surfactant had a similar half-life in all groups, ranging from 63 to 98 hours.
We conclude that surfactant synthesis is disturbed and that surfactant PC concentrations are low in infants with MAS on ECMO.
Journal of Pediatrics 12/2006; 149(5):634-9. · 4.11 Impact Factor
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ABSTRACT: We determined incidences of underfeeding and overfeeding in children who were admitted to a multidisciplinary tertiary pediatric intensive care and evaluated the usefulness of the respiratory quotient (RQ) obtained from indirect calorimetry to assess feeding adequacy.
Children 18 y and younger who fulfilled the criteria for indirect calorimetry entered our prospective, observational study and were studied until day 14. Actual energy intake was recorded, compared with required energy intake (measured energy expenditure plus 10%), and classified as underfeeding (<90% of required), adequate feeding (90% to 110% of required), or overfeeding (>110% of required). We also evaluated the adequacy of a measured RQ lower than 0.85 to identify underfeeding, and an RQ higher than 1.0 to identify overfeeding.
Ninety-eight children underwent 195 calorimetric measurements. Underfeeding, adequate feeding, and overfeeding occurred on 21%, 10%, and 69% of days, respectively. An RQ lower than 0.85 to identify underfeeding showed low sensitivity (63%), high specificity (89%), and high negative predictive value (90%). An RQ higher than 1.0 to indicate overfeeding showed poor sensitivity (21%), but a high specificity (97%) and a high positive predictive value (93%). Food composition, notably high-carbohydrate intake, was responsible for an RQ exceeding 1.0 in the overfed group.
Children admitted to the intensive care unit receive adequate feeding on only 10% of measurement days during the first 2 wk of admission. The usefulness of RQ to monitor feeding adequacy is limited to identifying (carbohydrate) overfeeding and excluding underfeeding.
Nutrition 03/2005; 21(2):192-8. · 3.03 Impact Factor
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ABSTRACT: To determine if high frequency oscillatory ventilation (HFOV) decreases surfactant production in premature infants with respiratory distress syndrome (RDS).
We randomized 19 infants <28 weeks of gestation to either HFOV (n = 8) or conventional ventilation (CV, n = 11) at 24 hours of life. After a 24-hour continuous infusion of uniformly labeled carbon 13 glucose (U-(13)C(6)) glucose, we measured (13)C enrichment in surfactant phosphatidylcholine (PC) in tracheal aspirate samples using gas chromatography/mass spectrometry. We calculated the fractional synthetic rate (FSR) of surfactant PC from labeled glucose and its half-life of clearance (T(1/2)).
FSR did not differ between groups (4.7% +/- 2.7%/day CV vs 4.2% +/- 3.1%/day HFOV, P =.7). T(1/2) was 79 +/- 18 hours in the CV group and 76 +/- 23 hours in the HFOV group (P =.7). Neither degree of ventilatory support nor supplemental oxygen exposure correlated with surfactant metabolic indices. Three of 4 infants who died from RDS within the first month of life had a shorter T(1/2) than 14 of 15 infants who survived.
Surfactant metabolism is similar in preterm infants ventilated with HFOV and CV. Shortened surfactant half-life may characterize a subset of preterm infants with lethal RDS.
Journal of Pediatrics 06/2002; 140(6):693-8. · 4.11 Impact Factor
