Ronit Lubetzky - Academia.edu (original) (raw)

Papers by Ronit Lubetzky

Research paper thumbnail of Fatty acids composition of human milk fed to small for gestational age infants

The Journal of Maternal-Fetal & Neonatal Medicine, 2015

To test the null hypothesis that mothers of asymmetric small for gestational age (SGA) infants pr... more To test the null hypothesis that mothers of asymmetric small for gestational age (SGA) infants produce milk with fatty acids composition similar to that of lactating mothers of appropriate-for-gestational-age (AGA) infants. We obtained human milk (HM) from 2 groups of lactating volunteers that gave birth to asymmetric SGA (study group) or AGA infants (control group). Each mother was asked to contribute by manual expression at least one of 3 samples: first 72 hours after labor (colostrum), day 2-7 postpartum (transitional milk) and 14 days post partum (mature milk). After lipid extraction using Folch's cold-extraction procedure fatty acids were analyzed using gas chromatography. A total of 108 samples were obtained in 60 women. In univariate analysis, there were no significant differences in any of the fatty acids concentrations examined between groups. This remained true when timing of the sample (colostrum, transitional or mature milk) or gestational age were introduced as confounders in analysis of variance (general linear model). Fatty acid composition of human milk is not affected by whether or not the infant was fetal growth restricted. We suggest that mothers of SGA infants may be reassured about the fat quality of their milk.

Research paper thumbnail of Circadian Macronutrients Variations over the First 7 Weeks of Human Milk Feeding of Preterm Infants

Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine, Jan 29, 2015

Little is known about circadian variations of macronutrients content of expressed preterm human m... more Little is known about circadian variations of macronutrients content of expressed preterm human milk (HM). This study evaluated diurnal variations of macronutrients and energy content of preterm HM over the first 7 weeks of lactation and tested the hypothesis that values obtained during a morning sample are predictive of those obtained from an evening sample. Expressed HM was obtained from 32 mothers of preterm infants (26-33 weeks in gestational age), who routinely expressed all their milk every 3 hours from the beginning of the second to the seventh week after delivery. One aliquot was obtained from the first morning expression and the second from the evening expression. Energy and macronutrients contents were measured using an HM analyzer. Mean fat and energy contents of all samples obtained during the whole period were significantly higher in evening samples (p<0.0001). There were no significant differences between morning and evening carbohydrates and protein contents. Conce...

Research paper thumbnail of TIMP-1 inhibition of occludin degradation in Caco-2 intestinal cells: a potential protective role in necrotizing enterocolitis

Pediatric research, Jan 9, 2015

BackgroundNecrotizing enterocolitis (NEC), a common intestinal disease affecting premature infant... more BackgroundNecrotizing enterocolitis (NEC), a common intestinal disease affecting premature infants, is a major cause of morbidity and mortality. Previous reports indicate an up regulation of intestinal Matrix Metalloproteinases (MMPs) activity that may play key roles on the higher permeability of the intestinal barrier, typical to NEC. Recently, TIMP-1, a natural inhibitor of MMP's, was found to be over expressed in preterm human breast milk (HBM). Previous studies have shown that infants fed with HBM have a significant reduction in the incidence of NEC.The aim of the present study was to investigate the possible role that TIMP-1 may play on the maintenance of tight junctions and therefore the gut barrier integrity.MethodsTimp-1 treated Caco-2 intestinal cells were tested for MMP-2 enzymatic activity and cell junction integrity.ResultsTIMP-1 inhibited MMP-2 activity, induced a significant increase in the expression of occludin but not of claudin-4. TIMP-1 did not affect apoptosi...

Research paper thumbnail of Human milk fatty acids profile changes during prolonged lactation: a cross-sectional study

The Israel Medical Association journal : IMAJ, 2012

Human milk produced during prolonged lactation (> 1 year) is extraordinarily rich in fat and h... more Human milk produced during prolonged lactation (> 1 year) is extraordinarily rich in fat and has a higher energy content than human milk produced during short lactation. To estimate the fatty acid (FA) profile of human milk and to test the hypothesis that the proportion of C12 and C14 (two dietary saturated FA known to most promote hypercholesterolemia) in human milk during prolonged lactation is similar to that in short lactation. We conducted a cross-sectional study of 30 mothers of term infants lactating for more than 1 year as compared with 25 mothers of full-term infants who lactated for 2-6 months. Milk was collected by manual expression in mid-breastfeeding. The two groups did not differ in maternal height, weight, body mass index, diet, infant birth weight and gestational age, but mothers in the prolonged lactation group were significantly older. There was a significant correlation between lactation duration and C12 or C14. The percentage of all FA combined (except for C1...

Research paper thumbnail of A Reappraisal of Neonatal Blood Chemistry Reference Ranges Using the Nova M Electrodes

American Journal of Perinatology, 2001

The objective of this study is to establish new reference ranges for whole blood electrolytes, ga... more The objective of this study is to establish new reference ranges for whole blood electrolytes, gases, and selected chemistries in normal healthy newborn infants obtained from cord blood and at 2-4 hours of life based on modern analytic techniques. Healthy appropriate-for-gestational age (AGA), term infants were studied. Whole venous cord blood and blood drawn at 2-4 hours of life were analyzed for gases, sodium, potassium, chloride, ionized calcium, ionized magnesium, hemoglobin, and hematocrit. Concentrations for blood glucose and blood urea nitrogen were close to older published concentrations. Na(+), K(+), and Cl(-) were significantly different and had much narrower normal margins. New norms are included for blood gases, lactate, iCa, and iMg. We offer a range of values for often-measured blood chemistries in term, healthy infants, using modern laboratory methods. These values could serve as more up-to-date references compared with older values found in major textbooks of Neonatology.

Research paper thumbnail of Nucleated Red Blood Cells in Preterm Infants With Retinopathy of Prematurity

PEDIATRICS, 2005

The aim of this retrospective study was to examine hematologic indices of potential intrauterine ... more The aim of this retrospective study was to examine hematologic indices of potential intrauterine hypoxia, including circulating nucleated red blood cells, lymphocytes, and platelets in preterm infants who developed retinopathy of prematurity (ROP) compared with suitable controls. We hypothesized that higher neonatal absolute nucleated red blood cell (ANRBC) and lymphocyte counts and lower platelets would be found in infants who developed ROP, compared with control infants. Each of 23 infants with ROP was pair matched for gestational age and Apgar scores with a control without ROP. Criteria for exclusion in both groups included factors that may influence the ANRBCs at birth. Venous ANRBC counts were obtained within 1 hour of life. Statistical analyses used paired t tests, a paired Wilcoxon test, and backward stepwise-regression analysis. Groups did not differ in birth weight, gestational age, Apgar scores, or hematocrit, white blood cell, or platelets counts. The ANRBC counts at birth were significantly higher in infants who developed ROP than in controls. Infants who develop ROP have higher ANRBC counts at birth than matched controls. We suggest that increased fetal erythropoiesis exists in preterm infants who later on will develop ROP. If correct, our interpretation supports the theory that long-lasting fetal hypoxia and/or ischemia may play a role in the pathogenesis of ROP.

Research paper thumbnail of Effect of Music by Mozart on Energy Expenditure in Growing Preterm Infants

PEDIATRICS, 2010

The rate of weight gain in preterm infants who are exposed to music seems to improve. A potential... more The rate of weight gain in preterm infants who are exposed to music seems to improve. A potential mechanism could be increased metabolic efficiency; therefore, we conducted this study to test the hypothesis that music by Mozart reduces resting energy expenditure (REE) in growing healthy preterm infants. DESIGN. A prospective, randomized clinical trial with crossover was conducted in 20 healthy, appropriate-weight-for-gestational-age, gavage-fed preterm infants. Infants were randomly assigned to be exposed to a 30-minute period of Mozart music or no music on 2 consecutive days. Metabolic measurements were performed by indirect calorimetry. REE was similar during the first 10-minute period of both randomization groups. During the next 10-minute period, infants who were exposed to music had a significantly lower REE than when not exposed to music (P = .028). This was also true during the third 10-minute period (P = .03). Thus, on average, the effect size of music on REE is a reduction of approximately 10% to 13% from baseline, an effect obtained within 10 to 30 minutes. Exposure to Mozart music significantly lowers REE in healthy preterm infants. We speculate that this effect of music on REE might explain, in part, the improved weight gain that results from this &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Mozart effect.&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;

Research paper thumbnail of Fat and Energy Contents of Expressed Human Breast Milk in Prolonged Lactation

PEDIATRICS, 2005

To estimate fat and energy contents of human milk during prolonged lactation. Thirty-four mothers... more To estimate fat and energy contents of human milk during prolonged lactation. Thirty-four mothers, of term, healthy, growing children, who had been lactating for &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1 year (12-39 months) were recruited. Control subjects were 27 mothers, of term infants, who had been lactating for 2 to 6 months. Fat contents of the milk samples were estimated as creamatocrit (CMT) levels. Energy contents of the milk were measured with a bomb calorimeter. The groups did not differ in terms of maternal height and diet, infant birth weight, gestational age, or breastfeeding frequency. They differed significantly in terms of maternal age, maternal weight, and BMI. The mean CMT levels were 7.36 +/- 2.65% in the short-duration group and 10.65 +/- 5.07% in the long-lactation group. The mean energy contents were 3103.7 +/- 863.2 kJ/L in the short-duration group and 3683.2 +/- 1032.2 kJ/L in the long-duration group. The mean CMT levels and mean energy contents were correlated significantly with the duration of lactation (R2 = 0.22 and R2 = 0.23, respectively). In multivariate regression analysis, CMT levels (or energy contents) were not influenced by maternal age, diet, BMI, or number of daily feedings but remained significantly influenced by the duration of lactation. Human milk expressed by mothers who have been lactating for &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1 year has significantly increased fat and energy contents, compared with milk expressed by women who have been lactating for shorter periods. During prolonged lactation, the fat energy contribution of breast milk to the infant diet might be significant.

Research paper thumbnail of Postnatal Rise in Hematocrit in Infants Delivered by Cesarean Section

Research paper thumbnail of Circadian Variations in Fat Content of Expressed Breast Milk from Mothers of Preterm Infants

Journal of the American College of Nutrition, 2006

Little is known about circadian variations of the fat content in expressed human milk by mothers ... more Little is known about circadian variations of the fat content in expressed human milk by mothers of preterm infants. To test the hypothesis that the fat content of expressed preterm human milk is higher in samples expressed in the evening (i.e. after 3 daily meals) than in the morning (after a night-long fast). We collected samples of expressed human milk obtained from 39 mothers of hospitalized growing preterm infants aged 7-14 days, with a gestational age at birth ranging from 26 to 33 weeks, who routinely expressed all their milk every 3 hours, during the day time, just before bed time, and as soon as they woke up, using a commercial breast pump (Medela AG, Baar, Switzerland). One sample was obtained from the first morning expression (between 0600 and 0900) and the second from the evening expression (between 2100 and 2400). The entire quantity of expressed milk was collected, mixed and measured in a capillary tube after centrifugation at 9000 rpm for 5 minutes. Creamatocrits (CMT) were performed in duplicates. Each sample was read independently by 2 investigators who were not aware of the origin and time of sampling and the results were averaged. Results are expressed as mean +/- SD, and analyses were by paired t-test and regression analysis. CMT was significantly higher in evening than in morning samples (7.9 +/- 2.9% vs. 6.6 +/- 2.8%, P = 0.005). Neither CMT nor the morning-evening difference in CMT correlated with gestational age or birthweight. The morning CMT correlated significantly with the evening CMT (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). There are significant circadian variations in the CMT of expressed preterm human milk. We speculate that if higher caloric content of expressed human milk is needed in a specific preterm infant, evening sample, if available, should be used preferentially.

Research paper thumbnail of Nucleated red blood cells in preterm infants who have necrotizing enterocolitis

The Journal of Pediatrics, 2004

Absolute nucleated red blood cell counts for 23 preterm newborn infants who subsequently had deve... more Absolute nucleated red blood cell counts for 23 preterm newborn infants who subsequently had development of necrotizing enterocolitis were significantly higher than for 23 control infants. These infants may have been exposed to relative intrauterine hypoxemia, a possible risk factor for the development of necrotizing enterocolitis. (J Pediatr 2004;144:653-5) A n increased rate of necrotizing enterocolitis (NEC) was found in infants with fetal growth restriction, 1 neonatal polycythemia, 2,3 and neonatal asphyxia, 4,5 suggesting that perinatal ischemia of the gastrointestinal tract is a possible risk factor. Since intrauterine hypoxia may increase fetal erythropoiesis and lead to an elevation of nucleated red blood cells (NRBC) at birth, 6,7 we hypothesized that higher NRBC counts would be found in infants who had subsequent development of NEC than in control infants.

Research paper thumbnail of MMP-2 and MMP-9 and Their Tissue Inhibitor in Preterm Human Milk

Journal of Pediatric Gastroenterology and Nutrition, 2010

Matrix metalloproteinases (MMPs) are a group of endopeptidases that play a key role in the degrad... more Matrix metalloproteinases (MMPs) are a group of endopeptidases that play a key role in the degradation of the extracellular matrix. The natural inhibitors of MMPs are the tissue inhibitors of metalloproteinases (TIMPs). It has been shown that several MMPs may be major factors in tissue destruction and remodeling in necrotizing enterocolitis. We designed the present prospective observational study to determine whether specific MMPs activity and expression of their inhibitors are similar in the milk fed to preterm and term infants. We compared specific matrix metalloproteinases (MMP-2 and MMP-9) and 1 MMP inhibitor (TIMP-1) activities or expression in human milk (HM) fed to 18 preterm infants and 13 full-term infants, obtained at 72 hours and 1 and 2 weeks postpartum. MMP-2 and MMP-9 activities were similar in both groups and did not vary over time. TIMP-1 was significantly higher in preterm HM. TIMP-1 expression increased significantly over time exclusively in the preterm group. There are differences in the expression of TIMP-1 between colostrum and mature milk in preterm HM and differences in the expression of TIMP-1 between preterm and term milk.

Research paper thumbnail of Energy expenditure in human milk versus formula fed preterm infants

Clinical Nutrition, 2003

We compared energy expenditure (EE) of preterm infants fed their mother&amp;amp;amp;amp;amp;a... more We compared energy expenditure (EE) of preterm infants fed their mother&amp;amp;amp;amp;amp;amp;amp;amp;#39;s milk versus preterm infant formula. Study design A prospective, randomized crossover study of 13 healthy, appropriate weight for gestational age, gavage-fed, preterm infants. Before the study and according to our feeding protocol, infants uniformly received alternate feeds of human milk and formula. Each infant was randomly assigned to 24 hours of formula feeding followed by 24 hours of breast milk or the reverse. Infants were studied asleep, at the end of each 24-hour period. EE was measured by indirect calorimetry 1 hour before feeding, 20 minutes during feeding, and 1 hour after feeding in a servo-controlled convective incubator. Energy content of human milk was analyzed by bomb calorimetry. EE was significantly lower in breast milk-fed infants during prefeeding (52+/-6 vs 57+/-10 kcal/kg per 24 hours) (P&amp;amp;amp;amp;amp;amp;amp;amp;lt;.05), per feeding (55+/-6 vs 60+/-10 kcal/kg per 24 hours) (P&amp;amp;amp;amp;amp;amp;amp;amp;lt;.05), and at the postfeeding measurement (60+/-7 vs 65+/-7 kcal/kg per 24 hours) (P=.059). After correction of the results for the actual measured energy intake, all statistical differences reached the &amp;amp;amp;amp;amp;amp;amp;amp;lt;.05 level. Preterm infants have lower EE when they are fed breast milk than when they are fed preterm infant formula.

Research paper thumbnail of Parathyroid Hormone-Related Protein in Preterm Human Milk

Breastfeeding Medicine, 2010

Parathyroid hormone-related protein (PTHrP) has the ability to activate parathyroid hormone recep... more Parathyroid hormone-related protein (PTHrP) has the ability to activate parathyroid hormone receptors and cause hypercalcemia. High concentrations of PTHrP are found in human breastmilk of mothers of term-infants. It is not known whether PTHrP is excreted in preterm human milk. This study tested the hypothesis that PTHrP concentrations in milk obtained from mothers of preterm infants are similar to those found in milk from mothers of term infants. We collected samples of expressed human milk obtained from 27 mothers of preterm infants (27-34 weeks&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; gestation) and from 16 mothers of full-term infants. Samples were collected within the first 72 hours postpartum (colostrum) and again at 1 and 2 weeks postpartum. PTHrP concentrations in these samples were measured by two-site immunoradiometric assay. PTHrP concentrations were significantly higher in samples obtained after 1 week postpartum than in samples obtained during the first 72 hours of life in breastmilk obtained from mothers of both term and preterm infants (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). PTHrP concentrations were similar in colostrum and after 1 week in term and preterm milk. PTHrP concentrations after 2 weeks of lactation were significantly higher in samples obtained from mothers of term infants (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.006). Human milk expressed by mothers of preterm infants contains amounts of PTHrP similar to those measured in milk expressed by mothers of term infants.

Research paper thumbnail of Consistent Circadian Variations in Creamatocrit over The First 7 Weeks of Lactation: A Longitudinal Study

Breastfeeding Medicine, 2007

Objective: The objective of this study was to test the hypothesis that fat content of expressed h... more Objective: The objective of this study was to test the hypothesis that fat content of expressed human milk from mothers of preterm infants is higher in samples expressed in the evening than in the morning during the first 7 weeks of lactation.

Research paper thumbnail of Changes in Serum Parathyroid Hormone–Related Protein in Breastfed Preterm Infants

Breastfeeding Medicine, 2012

Parathyroid hormone-related protein (PTHrP) has the ability to activate parathyroid hormone recep... more Parathyroid hormone-related protein (PTHrP) has the ability to activate parathyroid hormone receptors and cause hypercalcemia. In a previous study we have demonstrated high concentrations of PTHrP in both term and preterm human milk (HM). PTHrP intestinal absorption and its influence upon calcium homeostasis of the preterm infant have not been studied yet. This study assessed the correlation between PTHrP concentrations in preterm HM and PTHrP in maternal and neonatal serum. We collected samples of expressed HM obtained from 16 mothers of preterm infants (25-34 weeks of gestation) and drew blood samples from both mothers and infants on postpartum days 2 and 10. PTHrP concentrations were measured by two-site immunoradiometric assay. Blood calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP) concentrations were also measured. Neither maternal nor neonatal PTHrP serum concentrations varied significantly after 10 days of breastfeeding. There was a correlation between PTHrP concentrations in maternal serum and HM concentrations (R² = 0.24, p = 0.04), but not between HM and neonatal serum concentrations or between PTHrP concentrations in HM and preterm serum concentrations of Ca, P, and ALP. Despite high concentrations of PTHrP in preterm HM, serum concentrations of PTHrP of breastfed preterm infants did not increase over time. There was no correlation between PTHrP concentrations in HM and neonatal serum Ca concentration.

Research paper thumbnail of MODE OF DELIVERY AND NEONATAL HEMATOCRIT

American Journal of Perinatology, 2000

The objective of this paper is to test the hypothesis that the 2-h hematocrit (HCT) is lower in i... more The objective of this paper is to test the hypothesis that the 2-h hematocrit (HCT) is lower in infants born by cesarean section (CS) than in infants born vaginally and that the postnatal rise of HCT is lower in infants born by CS than in infants delivered vaginally. We prospectively studied 31 infants delivered by elective CS, 21 infants delivered by CS because of arrest of descent and 30 vaginally delivered (VD) infants. All pregnancies were term, uncomplicated in nonsmoking mothers. Apgar scores were &gt; 7 at 1 and 5 min. In all infants umbilical cord was clamped early. Umbilical vein and 2-h peripheral venous micro-HCT were measured by centrifugation. Cord-blood HCT, 2-h HCT, and rise in HCT were similar in the two CS groups and significantly lower than in the VD group. In multiple regression, gestational age, Apgar score, or the presence or not of labor did not influence cord-blood HCT, 2-h HCT, or the rise in HCT. Infants born by CS have lower HCT than infants born vaginally. Prediction of 2-h HCT from cord-blood HCT must take into account the mode of delivery.

Research paper thumbnail of Indomethacin-Induced Early Patent Ductus Arteriosus Closure Cannot Be Predicted by a Decrease in Pulse Pressure

American Journal of Perinatology, 2004

Wide pulse pressure is considered to be a sign of patent ductus arteriosus (PDA). We tested the h... more Wide pulse pressure is considered to be a sign of patent ductus arteriosus (PDA). We tested the hypothesis that, following indomethacin therapy, PDA closure is associated with a significant decrease in pulse pressure. Thirty-two ventilated preterm infants were echocardiographically diagnosed within the first 24 hours of life with PDA. Systolic, diastolic, and mean arterial blood pressures were measured prior to indomethacin treatment and after echocardiographically confirmed PDA closure. Following PDA closure, systolic and diastolic blood pressures and mean arterial pressure increased significantly without a significant change of pulse pressure (17 +/- 7 to 20 +/- 12 torr). We conclude that in preterm infants with PDA, systolic, diastolic, and mean arterial blood pressures increase significantly within first few days of life. Pulse pressure does not appear to be affected by early PDA closure. We speculate that high pulmonary resistance in the first days of life prevents significant diastolic aortic runoff and leaves pulse pressure unaffected by PDA, as well as by its closure.

Research paper thumbnail of The effect of olfactory stimulation on energy expenditure in growing preterm infants

Acta Paediatrica, 2012

Aim: To test the hypothesis that olfactory stimulation in growing healthy preterm infants leads t... more Aim: To test the hypothesis that olfactory stimulation in growing healthy preterm infants leads to an increase in resting energy expenditure (REE).

Research paper thumbnail of Trends in neonatology and pediatrics publications over the past 12 years

Acta Paediatrica, 2007

Objective: To test the hypothesis that the number of publications in Neonatology and Pediatrics i... more Objective: To test the hypothesis that the number of publications in Neonatology and Pediatrics increases over time, and to verify whether the categories of publications all follow the same pattern over time. Design and setting: We evaluated all Medline articles during 1994-2005. Search was limited to humans, English and to 'newborn' or 'all-child'. We used regression analysis to determine the effect of year-of-publication upon the number-of-publications of each type. Results: Medline reported 36,141 publications in Neonatology and 169,823 in Pediatrics during the evaluation period. There was a significant linear increase in the number of publications in Neonatology and Pediatrics. There was a steady increase over time in Neonatology and in Pediatrics in meta-analyses, reviews and editorials. There was a steady decrease over time in letters in Neonatology, but no significant change in letters in Pediatrics. While there was no significant change in clinical trials (CTs), randomized control trials (RCTs) in Neonatology, there was a significant increase in CTs and RCTs in Pediatrics.

Research paper thumbnail of Fatty acids composition of human milk fed to small for gestational age infants

The Journal of Maternal-Fetal & Neonatal Medicine, 2015

To test the null hypothesis that mothers of asymmetric small for gestational age (SGA) infants pr... more To test the null hypothesis that mothers of asymmetric small for gestational age (SGA) infants produce milk with fatty acids composition similar to that of lactating mothers of appropriate-for-gestational-age (AGA) infants. We obtained human milk (HM) from 2 groups of lactating volunteers that gave birth to asymmetric SGA (study group) or AGA infants (control group). Each mother was asked to contribute by manual expression at least one of 3 samples: first 72 hours after labor (colostrum), day 2-7 postpartum (transitional milk) and 14 days post partum (mature milk). After lipid extraction using Folch&amp;amp;#39;s cold-extraction procedure fatty acids were analyzed using gas chromatography. A total of 108 samples were obtained in 60 women. In univariate analysis, there were no significant differences in any of the fatty acids concentrations examined between groups. This remained true when timing of the sample (colostrum, transitional or mature milk) or gestational age were introduced as confounders in analysis of variance (general linear model). Fatty acid composition of human milk is not affected by whether or not the infant was fetal growth restricted. We suggest that mothers of SGA infants may be reassured about the fat quality of their milk.

Research paper thumbnail of Circadian Macronutrients Variations over the First 7 Weeks of Human Milk Feeding of Preterm Infants

Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine, Jan 29, 2015

Little is known about circadian variations of macronutrients content of expressed preterm human m... more Little is known about circadian variations of macronutrients content of expressed preterm human milk (HM). This study evaluated diurnal variations of macronutrients and energy content of preterm HM over the first 7 weeks of lactation and tested the hypothesis that values obtained during a morning sample are predictive of those obtained from an evening sample. Expressed HM was obtained from 32 mothers of preterm infants (26-33 weeks in gestational age), who routinely expressed all their milk every 3 hours from the beginning of the second to the seventh week after delivery. One aliquot was obtained from the first morning expression and the second from the evening expression. Energy and macronutrients contents were measured using an HM analyzer. Mean fat and energy contents of all samples obtained during the whole period were significantly higher in evening samples (p<0.0001). There were no significant differences between morning and evening carbohydrates and protein contents. Conce...

Research paper thumbnail of TIMP-1 inhibition of occludin degradation in Caco-2 intestinal cells: a potential protective role in necrotizing enterocolitis

Pediatric research, Jan 9, 2015

BackgroundNecrotizing enterocolitis (NEC), a common intestinal disease affecting premature infant... more BackgroundNecrotizing enterocolitis (NEC), a common intestinal disease affecting premature infants, is a major cause of morbidity and mortality. Previous reports indicate an up regulation of intestinal Matrix Metalloproteinases (MMPs) activity that may play key roles on the higher permeability of the intestinal barrier, typical to NEC. Recently, TIMP-1, a natural inhibitor of MMP's, was found to be over expressed in preterm human breast milk (HBM). Previous studies have shown that infants fed with HBM have a significant reduction in the incidence of NEC.The aim of the present study was to investigate the possible role that TIMP-1 may play on the maintenance of tight junctions and therefore the gut barrier integrity.MethodsTimp-1 treated Caco-2 intestinal cells were tested for MMP-2 enzymatic activity and cell junction integrity.ResultsTIMP-1 inhibited MMP-2 activity, induced a significant increase in the expression of occludin but not of claudin-4. TIMP-1 did not affect apoptosi...

Research paper thumbnail of Human milk fatty acids profile changes during prolonged lactation: a cross-sectional study

The Israel Medical Association journal : IMAJ, 2012

Human milk produced during prolonged lactation (> 1 year) is extraordinarily rich in fat and h... more Human milk produced during prolonged lactation (> 1 year) is extraordinarily rich in fat and has a higher energy content than human milk produced during short lactation. To estimate the fatty acid (FA) profile of human milk and to test the hypothesis that the proportion of C12 and C14 (two dietary saturated FA known to most promote hypercholesterolemia) in human milk during prolonged lactation is similar to that in short lactation. We conducted a cross-sectional study of 30 mothers of term infants lactating for more than 1 year as compared with 25 mothers of full-term infants who lactated for 2-6 months. Milk was collected by manual expression in mid-breastfeeding. The two groups did not differ in maternal height, weight, body mass index, diet, infant birth weight and gestational age, but mothers in the prolonged lactation group were significantly older. There was a significant correlation between lactation duration and C12 or C14. The percentage of all FA combined (except for C1...

Research paper thumbnail of A Reappraisal of Neonatal Blood Chemistry Reference Ranges Using the Nova M Electrodes

American Journal of Perinatology, 2001

The objective of this study is to establish new reference ranges for whole blood electrolytes, ga... more The objective of this study is to establish new reference ranges for whole blood electrolytes, gases, and selected chemistries in normal healthy newborn infants obtained from cord blood and at 2-4 hours of life based on modern analytic techniques. Healthy appropriate-for-gestational age (AGA), term infants were studied. Whole venous cord blood and blood drawn at 2-4 hours of life were analyzed for gases, sodium, potassium, chloride, ionized calcium, ionized magnesium, hemoglobin, and hematocrit. Concentrations for blood glucose and blood urea nitrogen were close to older published concentrations. Na(+), K(+), and Cl(-) were significantly different and had much narrower normal margins. New norms are included for blood gases, lactate, iCa, and iMg. We offer a range of values for often-measured blood chemistries in term, healthy infants, using modern laboratory methods. These values could serve as more up-to-date references compared with older values found in major textbooks of Neonatology.

Research paper thumbnail of Nucleated Red Blood Cells in Preterm Infants With Retinopathy of Prematurity

PEDIATRICS, 2005

The aim of this retrospective study was to examine hematologic indices of potential intrauterine ... more The aim of this retrospective study was to examine hematologic indices of potential intrauterine hypoxia, including circulating nucleated red blood cells, lymphocytes, and platelets in preterm infants who developed retinopathy of prematurity (ROP) compared with suitable controls. We hypothesized that higher neonatal absolute nucleated red blood cell (ANRBC) and lymphocyte counts and lower platelets would be found in infants who developed ROP, compared with control infants. Each of 23 infants with ROP was pair matched for gestational age and Apgar scores with a control without ROP. Criteria for exclusion in both groups included factors that may influence the ANRBCs at birth. Venous ANRBC counts were obtained within 1 hour of life. Statistical analyses used paired t tests, a paired Wilcoxon test, and backward stepwise-regression analysis. Groups did not differ in birth weight, gestational age, Apgar scores, or hematocrit, white blood cell, or platelets counts. The ANRBC counts at birth were significantly higher in infants who developed ROP than in controls. Infants who develop ROP have higher ANRBC counts at birth than matched controls. We suggest that increased fetal erythropoiesis exists in preterm infants who later on will develop ROP. If correct, our interpretation supports the theory that long-lasting fetal hypoxia and/or ischemia may play a role in the pathogenesis of ROP.

Research paper thumbnail of Effect of Music by Mozart on Energy Expenditure in Growing Preterm Infants

PEDIATRICS, 2010

The rate of weight gain in preterm infants who are exposed to music seems to improve. A potential... more The rate of weight gain in preterm infants who are exposed to music seems to improve. A potential mechanism could be increased metabolic efficiency; therefore, we conducted this study to test the hypothesis that music by Mozart reduces resting energy expenditure (REE) in growing healthy preterm infants. DESIGN. A prospective, randomized clinical trial with crossover was conducted in 20 healthy, appropriate-weight-for-gestational-age, gavage-fed preterm infants. Infants were randomly assigned to be exposed to a 30-minute period of Mozart music or no music on 2 consecutive days. Metabolic measurements were performed by indirect calorimetry. REE was similar during the first 10-minute period of both randomization groups. During the next 10-minute period, infants who were exposed to music had a significantly lower REE than when not exposed to music (P = .028). This was also true during the third 10-minute period (P = .03). Thus, on average, the effect size of music on REE is a reduction of approximately 10% to 13% from baseline, an effect obtained within 10 to 30 minutes. Exposure to Mozart music significantly lowers REE in healthy preterm infants. We speculate that this effect of music on REE might explain, in part, the improved weight gain that results from this &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Mozart effect.&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;

Research paper thumbnail of Fat and Energy Contents of Expressed Human Breast Milk in Prolonged Lactation

PEDIATRICS, 2005

To estimate fat and energy contents of human milk during prolonged lactation. Thirty-four mothers... more To estimate fat and energy contents of human milk during prolonged lactation. Thirty-four mothers, of term, healthy, growing children, who had been lactating for &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1 year (12-39 months) were recruited. Control subjects were 27 mothers, of term infants, who had been lactating for 2 to 6 months. Fat contents of the milk samples were estimated as creamatocrit (CMT) levels. Energy contents of the milk were measured with a bomb calorimeter. The groups did not differ in terms of maternal height and diet, infant birth weight, gestational age, or breastfeeding frequency. They differed significantly in terms of maternal age, maternal weight, and BMI. The mean CMT levels were 7.36 +/- 2.65% in the short-duration group and 10.65 +/- 5.07% in the long-lactation group. The mean energy contents were 3103.7 +/- 863.2 kJ/L in the short-duration group and 3683.2 +/- 1032.2 kJ/L in the long-duration group. The mean CMT levels and mean energy contents were correlated significantly with the duration of lactation (R2 = 0.22 and R2 = 0.23, respectively). In multivariate regression analysis, CMT levels (or energy contents) were not influenced by maternal age, diet, BMI, or number of daily feedings but remained significantly influenced by the duration of lactation. Human milk expressed by mothers who have been lactating for &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1 year has significantly increased fat and energy contents, compared with milk expressed by women who have been lactating for shorter periods. During prolonged lactation, the fat energy contribution of breast milk to the infant diet might be significant.

Research paper thumbnail of Postnatal Rise in Hematocrit in Infants Delivered by Cesarean Section

Research paper thumbnail of Circadian Variations in Fat Content of Expressed Breast Milk from Mothers of Preterm Infants

Journal of the American College of Nutrition, 2006

Little is known about circadian variations of the fat content in expressed human milk by mothers ... more Little is known about circadian variations of the fat content in expressed human milk by mothers of preterm infants. To test the hypothesis that the fat content of expressed preterm human milk is higher in samples expressed in the evening (i.e. after 3 daily meals) than in the morning (after a night-long fast). We collected samples of expressed human milk obtained from 39 mothers of hospitalized growing preterm infants aged 7-14 days, with a gestational age at birth ranging from 26 to 33 weeks, who routinely expressed all their milk every 3 hours, during the day time, just before bed time, and as soon as they woke up, using a commercial breast pump (Medela AG, Baar, Switzerland). One sample was obtained from the first morning expression (between 0600 and 0900) and the second from the evening expression (between 2100 and 2400). The entire quantity of expressed milk was collected, mixed and measured in a capillary tube after centrifugation at 9000 rpm for 5 minutes. Creamatocrits (CMT) were performed in duplicates. Each sample was read independently by 2 investigators who were not aware of the origin and time of sampling and the results were averaged. Results are expressed as mean +/- SD, and analyses were by paired t-test and regression analysis. CMT was significantly higher in evening than in morning samples (7.9 +/- 2.9% vs. 6.6 +/- 2.8%, P = 0.005). Neither CMT nor the morning-evening difference in CMT correlated with gestational age or birthweight. The morning CMT correlated significantly with the evening CMT (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). There are significant circadian variations in the CMT of expressed preterm human milk. We speculate that if higher caloric content of expressed human milk is needed in a specific preterm infant, evening sample, if available, should be used preferentially.

Research paper thumbnail of Nucleated red blood cells in preterm infants who have necrotizing enterocolitis

The Journal of Pediatrics, 2004

Absolute nucleated red blood cell counts for 23 preterm newborn infants who subsequently had deve... more Absolute nucleated red blood cell counts for 23 preterm newborn infants who subsequently had development of necrotizing enterocolitis were significantly higher than for 23 control infants. These infants may have been exposed to relative intrauterine hypoxemia, a possible risk factor for the development of necrotizing enterocolitis. (J Pediatr 2004;144:653-5) A n increased rate of necrotizing enterocolitis (NEC) was found in infants with fetal growth restriction, 1 neonatal polycythemia, 2,3 and neonatal asphyxia, 4,5 suggesting that perinatal ischemia of the gastrointestinal tract is a possible risk factor. Since intrauterine hypoxia may increase fetal erythropoiesis and lead to an elevation of nucleated red blood cells (NRBC) at birth, 6,7 we hypothesized that higher NRBC counts would be found in infants who had subsequent development of NEC than in control infants.

Research paper thumbnail of MMP-2 and MMP-9 and Their Tissue Inhibitor in Preterm Human Milk

Journal of Pediatric Gastroenterology and Nutrition, 2010

Matrix metalloproteinases (MMPs) are a group of endopeptidases that play a key role in the degrad... more Matrix metalloproteinases (MMPs) are a group of endopeptidases that play a key role in the degradation of the extracellular matrix. The natural inhibitors of MMPs are the tissue inhibitors of metalloproteinases (TIMPs). It has been shown that several MMPs may be major factors in tissue destruction and remodeling in necrotizing enterocolitis. We designed the present prospective observational study to determine whether specific MMPs activity and expression of their inhibitors are similar in the milk fed to preterm and term infants. We compared specific matrix metalloproteinases (MMP-2 and MMP-9) and 1 MMP inhibitor (TIMP-1) activities or expression in human milk (HM) fed to 18 preterm infants and 13 full-term infants, obtained at 72 hours and 1 and 2 weeks postpartum. MMP-2 and MMP-9 activities were similar in both groups and did not vary over time. TIMP-1 was significantly higher in preterm HM. TIMP-1 expression increased significantly over time exclusively in the preterm group. There are differences in the expression of TIMP-1 between colostrum and mature milk in preterm HM and differences in the expression of TIMP-1 between preterm and term milk.

Research paper thumbnail of Energy expenditure in human milk versus formula fed preterm infants

Clinical Nutrition, 2003

We compared energy expenditure (EE) of preterm infants fed their mother&amp;amp;amp;amp;amp;a... more We compared energy expenditure (EE) of preterm infants fed their mother&amp;amp;amp;amp;amp;amp;amp;amp;#39;s milk versus preterm infant formula. Study design A prospective, randomized crossover study of 13 healthy, appropriate weight for gestational age, gavage-fed, preterm infants. Before the study and according to our feeding protocol, infants uniformly received alternate feeds of human milk and formula. Each infant was randomly assigned to 24 hours of formula feeding followed by 24 hours of breast milk or the reverse. Infants were studied asleep, at the end of each 24-hour period. EE was measured by indirect calorimetry 1 hour before feeding, 20 minutes during feeding, and 1 hour after feeding in a servo-controlled convective incubator. Energy content of human milk was analyzed by bomb calorimetry. EE was significantly lower in breast milk-fed infants during prefeeding (52+/-6 vs 57+/-10 kcal/kg per 24 hours) (P&amp;amp;amp;amp;amp;amp;amp;amp;lt;.05), per feeding (55+/-6 vs 60+/-10 kcal/kg per 24 hours) (P&amp;amp;amp;amp;amp;amp;amp;amp;lt;.05), and at the postfeeding measurement (60+/-7 vs 65+/-7 kcal/kg per 24 hours) (P=.059). After correction of the results for the actual measured energy intake, all statistical differences reached the &amp;amp;amp;amp;amp;amp;amp;amp;lt;.05 level. Preterm infants have lower EE when they are fed breast milk than when they are fed preterm infant formula.

Research paper thumbnail of Parathyroid Hormone-Related Protein in Preterm Human Milk

Breastfeeding Medicine, 2010

Parathyroid hormone-related protein (PTHrP) has the ability to activate parathyroid hormone recep... more Parathyroid hormone-related protein (PTHrP) has the ability to activate parathyroid hormone receptors and cause hypercalcemia. High concentrations of PTHrP are found in human breastmilk of mothers of term-infants. It is not known whether PTHrP is excreted in preterm human milk. This study tested the hypothesis that PTHrP concentrations in milk obtained from mothers of preterm infants are similar to those found in milk from mothers of term infants. We collected samples of expressed human milk obtained from 27 mothers of preterm infants (27-34 weeks&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; gestation) and from 16 mothers of full-term infants. Samples were collected within the first 72 hours postpartum (colostrum) and again at 1 and 2 weeks postpartum. PTHrP concentrations in these samples were measured by two-site immunoradiometric assay. PTHrP concentrations were significantly higher in samples obtained after 1 week postpartum than in samples obtained during the first 72 hours of life in breastmilk obtained from mothers of both term and preterm infants (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). PTHrP concentrations were similar in colostrum and after 1 week in term and preterm milk. PTHrP concentrations after 2 weeks of lactation were significantly higher in samples obtained from mothers of term infants (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.006). Human milk expressed by mothers of preterm infants contains amounts of PTHrP similar to those measured in milk expressed by mothers of term infants.

Research paper thumbnail of Consistent Circadian Variations in Creamatocrit over The First 7 Weeks of Lactation: A Longitudinal Study

Breastfeeding Medicine, 2007

Objective: The objective of this study was to test the hypothesis that fat content of expressed h... more Objective: The objective of this study was to test the hypothesis that fat content of expressed human milk from mothers of preterm infants is higher in samples expressed in the evening than in the morning during the first 7 weeks of lactation.

Research paper thumbnail of Changes in Serum Parathyroid Hormone–Related Protein in Breastfed Preterm Infants

Breastfeeding Medicine, 2012

Parathyroid hormone-related protein (PTHrP) has the ability to activate parathyroid hormone recep... more Parathyroid hormone-related protein (PTHrP) has the ability to activate parathyroid hormone receptors and cause hypercalcemia. In a previous study we have demonstrated high concentrations of PTHrP in both term and preterm human milk (HM). PTHrP intestinal absorption and its influence upon calcium homeostasis of the preterm infant have not been studied yet. This study assessed the correlation between PTHrP concentrations in preterm HM and PTHrP in maternal and neonatal serum. We collected samples of expressed HM obtained from 16 mothers of preterm infants (25-34 weeks of gestation) and drew blood samples from both mothers and infants on postpartum days 2 and 10. PTHrP concentrations were measured by two-site immunoradiometric assay. Blood calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP) concentrations were also measured. Neither maternal nor neonatal PTHrP serum concentrations varied significantly after 10 days of breastfeeding. There was a correlation between PTHrP concentrations in maternal serum and HM concentrations (R² = 0.24, p = 0.04), but not between HM and neonatal serum concentrations or between PTHrP concentrations in HM and preterm serum concentrations of Ca, P, and ALP. Despite high concentrations of PTHrP in preterm HM, serum concentrations of PTHrP of breastfed preterm infants did not increase over time. There was no correlation between PTHrP concentrations in HM and neonatal serum Ca concentration.

Research paper thumbnail of MODE OF DELIVERY AND NEONATAL HEMATOCRIT

American Journal of Perinatology, 2000

The objective of this paper is to test the hypothesis that the 2-h hematocrit (HCT) is lower in i... more The objective of this paper is to test the hypothesis that the 2-h hematocrit (HCT) is lower in infants born by cesarean section (CS) than in infants born vaginally and that the postnatal rise of HCT is lower in infants born by CS than in infants delivered vaginally. We prospectively studied 31 infants delivered by elective CS, 21 infants delivered by CS because of arrest of descent and 30 vaginally delivered (VD) infants. All pregnancies were term, uncomplicated in nonsmoking mothers. Apgar scores were &gt; 7 at 1 and 5 min. In all infants umbilical cord was clamped early. Umbilical vein and 2-h peripheral venous micro-HCT were measured by centrifugation. Cord-blood HCT, 2-h HCT, and rise in HCT were similar in the two CS groups and significantly lower than in the VD group. In multiple regression, gestational age, Apgar score, or the presence or not of labor did not influence cord-blood HCT, 2-h HCT, or the rise in HCT. Infants born by CS have lower HCT than infants born vaginally. Prediction of 2-h HCT from cord-blood HCT must take into account the mode of delivery.

Research paper thumbnail of Indomethacin-Induced Early Patent Ductus Arteriosus Closure Cannot Be Predicted by a Decrease in Pulse Pressure

American Journal of Perinatology, 2004

Wide pulse pressure is considered to be a sign of patent ductus arteriosus (PDA). We tested the h... more Wide pulse pressure is considered to be a sign of patent ductus arteriosus (PDA). We tested the hypothesis that, following indomethacin therapy, PDA closure is associated with a significant decrease in pulse pressure. Thirty-two ventilated preterm infants were echocardiographically diagnosed within the first 24 hours of life with PDA. Systolic, diastolic, and mean arterial blood pressures were measured prior to indomethacin treatment and after echocardiographically confirmed PDA closure. Following PDA closure, systolic and diastolic blood pressures and mean arterial pressure increased significantly without a significant change of pulse pressure (17 +/- 7 to 20 +/- 12 torr). We conclude that in preterm infants with PDA, systolic, diastolic, and mean arterial blood pressures increase significantly within first few days of life. Pulse pressure does not appear to be affected by early PDA closure. We speculate that high pulmonary resistance in the first days of life prevents significant diastolic aortic runoff and leaves pulse pressure unaffected by PDA, as well as by its closure.

Research paper thumbnail of The effect of olfactory stimulation on energy expenditure in growing preterm infants

Acta Paediatrica, 2012

Aim: To test the hypothesis that olfactory stimulation in growing healthy preterm infants leads t... more Aim: To test the hypothesis that olfactory stimulation in growing healthy preterm infants leads to an increase in resting energy expenditure (REE).

Research paper thumbnail of Trends in neonatology and pediatrics publications over the past 12 years

Acta Paediatrica, 2007

Objective: To test the hypothesis that the number of publications in Neonatology and Pediatrics i... more Objective: To test the hypothesis that the number of publications in Neonatology and Pediatrics increases over time, and to verify whether the categories of publications all follow the same pattern over time. Design and setting: We evaluated all Medline articles during 1994-2005. Search was limited to humans, English and to 'newborn' or 'all-child'. We used regression analysis to determine the effect of year-of-publication upon the number-of-publications of each type. Results: Medline reported 36,141 publications in Neonatology and 169,823 in Pediatrics during the evaluation period. There was a significant linear increase in the number of publications in Neonatology and Pediatrics. There was a steady increase over time in Neonatology and in Pediatrics in meta-analyses, reviews and editorials. There was a steady decrease over time in letters in Neonatology, but no significant change in letters in Pediatrics. While there was no significant change in clinical trials (CTs), randomized control trials (RCTs) in Neonatology, there was a significant increase in CTs and RCTs in Pediatrics.