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Early dropout and treatment adherence are main challenges in the treatment of children with obesity. The aim of this study was to identify factors associated with attrition and adherence to weight loss intervention program. We retrospectively reviewed the medical records of all the children who entered the program for pediatric weight loss over 5 years and retrieved demographic and clinical characteristics. Attrition and adherence were documented. Ninety-two of the 248 enrolled children (52% women, mean age 11.1 ± 3.9 years, mean body mass index 31.1 ± 7 kg/m2) dropped out (37%). Dropping out correlated with male sex, low parental education, and self-referral to the clinic ( P < .05 for all). Adherence correlated with older age and the mother’s healthy lifestyle ( P < .05 for all). Sex, parental education, and referral source may predict treatment attrition. Early recognition of children at risk of attrition may help to facilitate better care of those children.

Background Non-alcoholic fatty liver disease (NAFLD) can range from simple steatosis to steatohepatitis with or without fibrosis. The predictors for liver fibrosis and the effect of nutritional intervention on hepatic fibrosis in pediatric population are not well established. We aimed to investigate the predictors for liver fibrosis and the effects of short-term nutritional intervention on steatosis and fibrosis among obese adolescents with NAFLD. Methods Cross-sectional study among obese adolescents. Sociodemographic and clinical data were collected. Liver fibrosis was estimated by Shearwave elastography. All participants were recommended to consume a low carbohydrate diet and were followed biweekly. Blood tests and elastography were performed upon admission and repeated after 3 months. Results Fifty-seven pediatric patients were recruited (35 males, mean age 13.5±2.9 years, mean body mass index [BMI] 38.8±9.7). Liver fibrosis was diagnosed in 34 (60%) subjects, which was moderate/severe (F≥2) in 24 (70%). A higher BMI Z score and moderate/severe steatosis correlated with moderate/severe fibrosis (P < 0.05). Seventeen patients completed 3 months of follow-up and displayed a decrease in BMI Z score (from BMI Z score 2.6±0.5 before intervention to 2.4±0.5 after intervention), with a significant decrease in liver fibrosis (P = 0.001). Conclusion Pediatric patients with high BMIs and severe liver steatosis are at risk for severe liver fibrosis. Nutritional intervention with minimal weight loss may improves hepatic fibrosis among the pediatric population. Trial registration TRN NCT04561804 (9/17/2020)

OBJECTIVE The etiology of anemia in premature neonates is multifactorial and may involve anemia of inflammation mediated by hepcidin. Hepcidin expression is suppressed by vitamin D. We aimed to investigate the interrelationship between hepcidin, anemia, and vitamin D status in preterm infants. STUDY DESIGN Preterm infants aged 1 to 5 weeks were prospectively recruited at the neonatal intensive care unit of the Dana Dwek Children Hospital. Blood counts and serum levels of hepcidin, ferritin, iron, 25-hydroxyvitamin D [25(OH)D] and C-reactive protein (CRP) were measured and compared between anemic and nonanemic preterm infants. RESULTS Forty-seven preterm infants (mean ± standard deviation gestational age at birth 32.8 ± 1.1 weeks, 66% males) were recruited. In total, 36% of the preterm infants were vitamin D deficient [25(OH)D

Background The effect of biologic therapy on the incidence of inflammatory bowel disease (IBD)-related hospitalizations is controversial. The high efficacy of biologic agents is weighted against potential therapy-related adverse events, however, there are no data on the effect of biologic therapy on the indications for hospitalization in IBD. We aimed to evaluate the impact of biologic therapy on the indications and rate of hospitalization in pediatric IBD. Methods This retrospective cohort study included all children ( Results Included were 218 hospitalizations of 100 children, of whom 65 (65%) had Crohn’s disease and 35 (35%) had ulcerative colitis. The indications for hospitalization were IBD exacerbations or complications in 194 (89%) and therapy-related adverse events in 24 (11%). The patients of 56 (25.7%) hospitalizations were receiving biologic therapy. In a multivariate analysis, no correlation between therapy and indication for hospitalization was found (p = 0.829). Among children under biologic therapy, a decrease in the rate of hospitalizations from 1.09 (0.11–3.33) to 0.27 (0–0.47) per year was observed for patients that were hospitalized during 2016–2019 (p = 0.043). Conclusion Biologic therapy did not influence the indication for hospitalization, but were associated with a decrease in the rate of hospitalization during 2016–2019 in pediatric IBD.

The clinical applicability and yield of brain magnetic resonance imaging (MRI) in the setting of an inpatient pediatric department has not been investigated. The authors performed a retrospective chart review of nontraumatic/nonneurosurgical children who underwent brain MRI during their hospitalization in a general pediatric department over a 5-year period. Of the 331 children who underwent brain MRI, 148 (45%) had abnormal findings. High-risk headaches and focal seizures were significantly correlated with findings on brain MRI. Diagnostic and therapeutic yields were most significant in acute demyelinating events, acute cerebrovascular disorders, high-risk headaches when supported by neurologic and ophthalmologic findings, focal seizures with evidence of multifocal epileptic activity on an electroencephalogram and ophthalmic complaints when accompanied by cranial nerve palsy and optic nerve impairment. Since the contributions of a brain MRI in hospitalized children is pivotal in specific clinical situations, a judicious decision-making process should be done before its scheduling, in order to optimize clinical care.

Background Previous studies have suggested seasonal variation in macronutrient content of milk produced from animals. The influence of seasonal variation upon human milk macronutrient content has not been elucidated. This study aimed to compare the macronutrient content of HM produced by lactating mothers during the winter and the summer seasons. Methods We compiled previously generated data on macronutrient content of colostrum milk samples collected from lactating mothers of healthy term infants. The mothers were recruited during their postpartum stay at the Lis Maternity Hospital of the Tel Aviv Medical Center. Macronutrient content was measured by mid-infrared spectroscopy. Results The carbohydrate content of the colostrum was significantly higher in the summer season than in the winter season (5.9 ± 1.3 vs 5.4 ± 1.4 g/100 ml, p value

Background:Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants found in human tissues. PCBs can be transferred through the placenta and may disrupt the maternal thyroid homeostasis, and affect fetal thyroid hormone production. Several studies have shown that intrauterine exposure to PCBs might be associated with abnormal levels of thyroid hormones in mothers and their offspring.Objectives:To examine the associations between environmental exposure to PCBs and thyroid hormone levels in mothers and newborns.Methods:The EHF-Assaf-Harofeh-Ichilov cohort includes 263 mothers-newborns dyads. A total of 157 mother-newborn dyads had both PCBs and thyroid function measures. Regression models were used to estimate associations between maternal PCB exposure and maternal and newborn thyroid function, controlling for possible confounders.Results:Four PCBs congeners were analyzed: PCBs 118, 138, 153, and 180. ∑PCBs median (IQR) level was 14.65 (2.83–68.14) ng/g lipids. The median maternal thyroid-stimulating hormone (TSH) level was 2.66 (0.70–8.23) μIU/ml, the median maternal free thyroxine (FT4) level was 12.44 (11.27–13.53) μg/dL, the median maternal thyroid peroxidase antibodies (TPO Ab) level was 9.6 (7.36–12.51) IU/mL. Newborns' median total thyroxine (T4) level was 14.8 (7.6–24.9) μg/dL. No association was found between exposure to different congeners or to ∑PCBs and maternal TSH, FT4, thyroglobulin autoantibodies (Tg Ab), TPO Ab and newborn total T4 levels. In multivariable analysis a 1% change in ∑PCBs level was significantly associated with a 0.57% change in maternal TSH levels in women with body mass index (BMI) < 19. The same association was observed for each of the studied PCB congeners. Maternal TPO Ab levels statistically significantly increased by 0.53 and 0.46% for 1% increase in PCB 118 and 153 congeners, respectively. In women with BMI > 25, the association between the PCBs levels and maternal TSH levels was in the opposite direction. No association was found in women with normal BMI (19–24.9).Conclusions:Background exposure to environmentally relevant concentrations of some PCBs can alter thyroid hormone homeostasis in pregnant women and might be associated with abnormal TSH levels and TPO-Ab in women with low BMI. However, these findings require further investigation.

Background: Many obese children have at least one obese parent, and some of them have one parent who had undergone bariatric surgery (“bariatric families”). The perceptions and attitudes towards child obesity of parents in bariatric families vs. non-bariatric families have not been explored. We assessed how parents who underwent bariatric surgery for obesity perceived their child’s obesity compared to those perceptions of obese parents who did not undergo bariatric surgery.Methods: We conducted a cross-sectional survey by interviewing families in which one or both parents underwent bariatric surgery (bariatric group) and comparing their responses to those of families in which one or both parents had been treated conservatively for obesity (control group). The children of both groups were attending the Obesity Clinic of our children’s hospital. Results: Thirty-six children (median age 10.6 years, 18 in each group, matched for age and sex) were recruited. More parents in the bariatric group replied that weight plays an important role in determining self-image (pppppConclusion: Families in which one or both parents underwent bariatric surgery for obesity revealed different perceptions of their child’s obesity and different opinions about interventions for treating it compared to families with no bariatric surgery.

Hepcidin is a master regulator of iron metabolism. Recently, it has been shown that vitamin D suppresses hepcidin expression. Our hypothesis was that hepcidin levels inversely correlate with vitamin D levels in anemic children during acute infection. A prospective study was performed on 90 patients (45 females, 45 males, mean age 7.3 ± 5 years) who were admitted to the pediatric ward. Sixty-two patients had infectious disease (32 with coexisting anemia, 30 without anemia), and 28 patients were hospitalized for noninfectious causes. Blood samples for IL-6, hepcidin, iron status parameters, and 25-hydroxyvitamin D (25-OHD) were obtained within 72 h after admission. Serum concentrations of IL-6 and hepcidin were significantly higher and 25-OHD, iron, and transferrin were significantly lower in anemic children with infectious disease compared with controls. Children with a serum 25-OHD level 20 ng/ml (OR: 6.1, CI: 1.15–32.76). Correlation analyses found positive associations between hepcidin levels and ferritin (R2 = 0.47, P

Aim This study described outcomes following treatment for lactose intolerance, which is common in children. Methods The medical records of children aged 6-18 years who underwent lactose hydrogen breath testing at Dana-Dwek Children's Hospital, Tel Aviv, Israel, from August 2012 to August 2014 were analysed. We compared 154 children with gastrointestinal symptoms and positive lactose hydrogen breath tests to 49 children with negative test results. Results Of the 154 children in the study group, 89 (57.8%) were advised to follow a lactose-restricted diet, 32 (20.8%) were advised to avoid lactose completely, 18 (11.7%) were instructed to use substitute enzymes, and 15 (9.7%) did not receive specific recommendations. Only 11 patients (7.1%) received recommendations to add calcium-rich foods or calcium supplements to their diet. Lactose reintroduction was attempted in 119 of 154 patients (77.3%), and 65 of 154 (42.2%) experienced clinical relapses. At the final follow-up of 3.3 years, 62.3% of the study children were still observing a restricted diet. Older children and those who were symptomatic during lactose hydrogen breath testing were more likely to be on a prolonged restricted diet. Conclusion Our long-term follow-up of lactose-intolerant children showed that only a third were able to achieve a regular diet.

Helicobacter pylori, one of the most common bacterial pathogens in humans, is generally acquired during childhood. The inverse correlation between H. pylori colonization and obesity that was found in adults has not been investigated in depth in children. Our aim was to assess the correlation between overweight and obesity and H. pylori colonization in a pediatric population.H. pylori colonization in 70 symptomatic children was determined after antral biopsies during esophagogastroduodenoscopy. Data on anthropometric measurements, sociodemographic characteristics, and medical history were recorded.The participants' mean age was 12.41 ± 3.16 years, 58% were females, and 24% were obese or overweight (BMI85th percentile). The H. pylori colonization rate was 31%. There were no significant differences between the H. pylori-infected and H. pylori-noninfected groups in terms of age, gender, or clinical and sociodemographic characteristics. Nevertheless, the prevalence of overweight and obesity was significantly lower in children with H. pylori colonization compared to children with normal histology (31% in the noninfected group compared to 11% in the infected group, p = 0.04). The mean fat percentage was 24.3 ± 8.8 and 19.4 ± 6.9, respectively (p = 0.02).The findings of this prospective study are in agreement with previous studies and demonstrate an inverse relationship between H. pylori colonization and overweight or obesity among symptomatic children. A larger prospective, multiethnic investigation is warranted to more definitively determine the extent of this association.

This study is a systematic review of the macronutrient and energy composition of preterm human milk to enable the practicing neonatologist to make informed nutritional decisions in preterm infants. Meta-analyses were conducted in all the studies that reported total energy, true protein, fat, and lactose. Protein content decreased massively (by one-half) and significantly from day 1 to 3 at week 10 to 12. There was a significant linear increase in fat, lactose, and energy content during the same timeframe. Theoretic calculations on energy and macronutrient intake of preterm infants must be made according to a lactation time-specific manner.

There is evidence that multinutrient fortification of human milk increases in-hospital growth of preterm infants, but fortification has not been shown to improve long-term growth and neurodevelopmental outcome. We aimed to ascertain whether randomized controlled trials have determined the effect of early versus late introduction of fortifiers on growth and/or other outcomes, and have compared the efficacy/adverse effects of human milk-based versus cow milk-based fortifiers. We conclude that there is little evidence that early introduction of human milk fortification affects important outcomes, and limited evidence that a bovine fortifier places the infant at a higher risk of NEC.

Inflammatory bowel disease (IBD) exacerbations may lead to prolonged and complicated hospitalizations. The characteristics of exacerbation-related hospitalizations and predictors for poor outcome of pediatric patients hospitalized due to IBD have not been thoroughly described. All children who were hospitalized due to IBD exacerbation in a tertiary referral center between 2004 and 2017 were enrolled. Data on demographic and disease characteristics before and during hospitalization were retrospectively reviewed, as was the course of hospitalization, including laboratory findings, diagnostic work-up, and management. Poor outcomes were defined as prolonged hospitalization (≥ 7 days) and/or the need for surgery during hospitalization. There were 181 hospitalizations of 78 IBD children with a median (IQR) age of 14.8 (11.8-16.2) years. They included 53 (67.9%) with Crohn's disease and 25 (32.1%) with ulcerative colitis. In a multivariate analysis, severe disease activity at hospitalization (odds ratio [OR] = 3.33, P = 0.013), lower weight percentile (OR = 0.98, P = 0.009), treatment with antibiotics (OR = 5.03, P = 0.001), blood transfusion (OR = 8.03, P = 0.003), undergoing endoscopy (OR = 2.73, P = 0.027), and imaging studies during hospitalization (OR = 3.61, P = 0.001) predicted prolonged hospitalization. Surgical intervention was performed in 16 patients (8.8%), due to penetrating (OR = 7.73, P = 0.019) and stricturing disease (OR = 12.38, P < 0.001).Conclusion: We identified predictors for poor outcomes of children hospitalized due to IBD. Among the variables that can be measured at the beginning of the admission, severe disease activity was the most significant predictor recognition of these predictors that may contribute to modification of patient management.What is Known:• Inflammatory bowel disease (IBD) patients may require hospitalization due to disease exacerbation or treatment-related complications.• Hospitalizations of IBD patients constitute a heavy emotional burden on patients and families.What is New:• Lower weight percentile, severe disease activity, and a lower albumin level were predictors for prolonged hospitalization in children with IBD.• Recognition of these predictors may contribute to modification of patient management.

Human colostrums and transition milk were collected from women under the age of 37 years and women aged 37 years and older. Transition milk of the younger group had lower fat content and 10-fold higher concentrations of omega 6 FA, eicosadecanoic, and arachdonic acids. Gestational age affected the colostrum concentration of total fat and omega 3 and omega 6 FA composition only in the older group. We concluded that age may be a factor in the FA composition of human milk. This should be taken into account when planning diets for pregnant women of different ages.

Objective: To assess the intracranial pressure in pediatric acute disseminated encephalomyelitis using spinal tap opening pressure on lumbar puncture, which is routinely performed as part of suspected acute disseminated encephalomyelitis workup. Compared to other cerebrospinal fluid parameters such as cell count, protein concentration, and presence of oligoclonal bands, cerebrospinal fluid opening pressure is infrequently recorded. Methods: A retrospective chart review of demographic, clinical, and laboratory data of children diagnosed with acute disseminated encephalomyelitis admitted to a tertiary referral hospital between 2005 and 2016. Results: Of the 36 children diagnosed with acute disseminated encephalomyelitis, 24 had the cerebrospinal fluid opening pressure documented in their records. The mean cerebrospinal fluid opening pressure was 27.6±12.6 cmH2O, range 9-55 cmH2O (95% confidence interval 21.9-33.6). Cerebrospinal fluid opening pressure in the acute disseminated encephalomyelitis group was statistically significantly higher ( P = .0013, 95% confidence interval 4.2-15.0) than the accepted upper limit in this age group (18 cmH2O). In 10 of 24 patients (42%), the opening pressure was above 28 cmH2O. Conclusions: Increased opening pressure was the most frequent cerebrospinal fluid abnormal finding in our cohort, which suggests a potential role of increased intracranial pressure in the acute disseminated encephalomyelitis pathophysiological disease mechanism. In certain cases, the opening pressure value could have monitoring and therapeutic implications, and therefore its measurement is highlighted by this study.

To test the null hypothesis that human milk (HM) macronutrients (fat, lactose, protein) and caloric content in women with gestational diabetes mellitus (GDM) is similar to that of women without GDM. Sixty-two lactating mothers (31 GDM, 31 no-GDM) were studied after confirmation by 100-g oral glucose tolerance test. Each mother contributed three manually expressed HM samples (within 72 h after labor (colostrum), after 7 days (transitional) and at 14 days (mature)). Analysis was done by infrared transmission spectroscopy. Non-GDM and GDM groups did not differ by maternal age, pre-pregnancy weight, height, diet, pregnancy weight gain, gestational age, and infant birth weight. Macronutrients content in colostrum and transitional milk did not differ between groups. Fat and energy contents in mature HM were higher in non-GDM samples than in GDM samples (p = 0.07 and p

AIM Nutritional deficiencies associated with coeliac disease include iron, folic acid and fat-soluble vitamins. This study compared the prevalence and degree of vitamin A deficiency among newly diagnosed coeliac disease patients to controls in a developed country. METHODS This prospective cohort study included all children evaluated by gastroscopy at Dana-Dwek Children's Hospital, Israel, between September 2014 and February 2017. Vitamin A, haemoglobin, C-reactive protein (CRP), ferritin, tissue transglutaminase, immunoglobulin A and vitamin D levels were measured. RESULTS Of the 113 children (69% females), 47 were diagnosed with coeliac disease whereas the others were the controls (mean age of 8.2 ± 3.8 years and 12.4 ± 3.5 years, respectively). There was no group difference in vitamin A, vitamin D or CRP levels. Among coeliac children, two had true vitamin A deficiency compared with three controls, while 18 coeliac children had subclinical vitamin A deficiency compared with 25 controls (p > 0.05). CONCLUSION Paediatric coeliac disease was not associated with increased prevalence of vitamin A deficiency. Children evaluated for gastrointestinal complaints in a developed country were found to have an unexpectedly high prevalence of subclinical vitamin A deficiency. Further prevalence and causality assessments of vitamin A deficiency in developed countries are needed.

There is a paucity of studies on the impact of maternal body mass index (BMI) on macronutrient content of human milk colostrum (HMC). The objective of this study was to compare macronutrient content of HMC in healthy women of term infants in relation to their BMI. We hypothesized that mother habitus influences human milk colostrum content. Colostrum was collected from 109 healthy mothers of hospitalized healthy term infants divided into four prepregnancy BMI groups: 12 underweight, 59 normal weight, 20 overweight, and 18 obese women between 24 and 72 h after birth. Macronutrient content was measured using mid-infrared spectroscopy. There were no significant differences in macronutrients between the BMI groups. We performed four separate stepwise backward multiple regression analyses taking into account fat, carbohydrate, protein or energy content as dependent variables and maternal BMI, parity, gestational age, infant gender, maternal age, maternal education, mode of delivery and time postdelivery. In these analyses, fat, carbohydrate and energy content were not related to maternal BMI, while protein content was significantly and positively correlated with BMI (P=0.008) and negatively correlated with gestational age (P=0.004) and time postdelivery (P

IntroductionPolybrominated Diphenyl Ethers (PBDEs) are non-biodegradable flame retardants, accumulated in biological systems and acting as endocrine disruptors. Breast feeding is a major route of exposure in infancy. Taken together with the critical development of this age and the potential adverse effects of PBDEs, it is important to monitor these contaminants in breastmilk.ObjectiveTo evaluate the exposure of infants to PBDEsMethods343 families were recruited during 2013–2016 in Assaf Harofeh and Ichilov to create the AHI-EHF cohort. Maternal blood and urine, cord blood, breast milk and meconium were collected. Participants filled out questionnaires about socio-demographic status, medical history, exposures and life habits. Colostrum samples were collected from women at the maternity department. PBDEs in colostrum and Infant formulas levels were analyzed using GC-MSResults and discussionOut of 183 serum samples, only 11(6%) detectable levels of PBDEs. PBDEs were found in all colostrum samples. The average concentration of total PBDEs in breastmilk was 714ng/L. PBDEs levels were also measured in three infant formulas. Unlike breastmilk, infant formulas had of only 3 congeners and levels were relatively low. The average concentration of total PBDEs in infant formulas was 153ng/L. PBDEs, were found to be negatively correlated to anno-penile index (API) which serve as a marker for endocrine disruption.ConclusionsPBDEs levels in breast milk are higher than levels in some European countries, but lower than in North America. PBDEs might have negative influence on AGD in boys. Maternal exposure to PBDEs and the significance of it should be further investigated.Disclosure(s)Nothing to disclose

Aim: To test the hypothesis that olfactory stimulation in growing healthy preterm infants leads to an increase in resting energy expenditure (REE). Design: A prospective, randomized clinical trial with crossover was conducted in 20 healthy, appropriate weights for gestational age, gavage-fed preterm infants. Infants were studied while asleep and cared for in a skin servo-controlled convective incubator. Using a pipette, 15 drops of saturated solution of vanillin (Aldrich, Fallavier, France) were dripped to a cloth diaper that was placed on the opposite side of the incubator. REE was measured by indirect calorimetry (DeltaTrac II, Helsinki, Finland) exactly 1 h after feeding. Each infant was studied twice by randomization: after a period of 20 min of vanillin odour or after 20 min without vanillin odour. Results: We found no statistically significant difference in REE of preterm infants when exposed to vanillin odour (74.5 ± 10.1 kcal ⁄kg ⁄day) in comparison with their REE when not exposed to vanillin odour (79.0 ± 11.3 kcal ⁄kg ⁄day). Conclusions: Vanillin odour does not significantly influence REE in metabolically and thermally stable preterm infants.

Long-term storage of human milk (HM) requires freezing at low temperatures, the consequences of which upon macronutrients are unclear. To test the null hypothesis that HM freezing and storage for a range of 1 to 10 weeks at −80 °C does not affect HM fat, protein, lactose and energy contents. Samples of HM were obtained from 20 mothers (60 samples) of preterm infants (25 to 35 weeks gestation), who routinely expressed their milk, every 3 h, using an electric pump, from the second to the seventh week after delivery. All samples were frozen at −80 °C for 8 to 83 days (43.8 days average). After thawing and homogenization, energy and macronutrient contents were measured using an HM analyzer. Fat, carbohydrates and energy contents were significantly lower in thawed HM than in fresh HM (fat, fresh vs thawed: 3.72±1.17 vs 3.36±1.19 g/100 ml, P

OBJECTIVE: 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.RESULTS: 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 ∼10% to 13% from baseline, an effect obtained within 10 to 30 minutes.CONCLUSIONS: 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 “Mozart effect.”

Little is known about the effect of maternal handedness and preferential side of breastfeeding upon macronutrients concentration in human milk (HM). We aimed to compare macronutrients content of HM from both breasts, taking into account the self-reported preferential feeding ('dominant') breast, breast size and handedness (right versus left). We tested the null hypothesis that macronutrients content of HM is not affected by breast dominancy, breast size or maternal handedness. Fifty-seven lactating mothers were recruited. HM macronutrients were measured after mid manual expression using infrared transmission spectroscopy. Out of the 57 mothers recruited, 12 were excluded from the analyses because they brought in insufficient samples. Among the 22 who reported a size difference, 16 (73%) had a larger left breast (P

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.

Objective. To estimate fat and energy contents of human milk during prolonged lactation. Methods. Thirty-four mothers, of term, healthy, growing children, who had been lactating for >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 esti- mated as creamatocrit (CMT) levels. Energy contents of the milk were measured with a bomb calorimeter. Results. The groups did not differ in terms of mater- nal 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 (R 2 0.22 and R 2 0.23, respec- tively). 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. Conclusions. Human milk expressed by mothers who have been lactating for >1 year has significantly in- creased fat and energy contents, compared with milk expressed by women who have been lactating for shorter periods. During prolonged lactation, the fat energy con- tribution of breast milk to the infant diet might be significant. Pediatrics 2005;116:e432-e435. URL: www. pediatrics.org/cgi/doi/10.1542/peds.2005-0313; breast milk, breastfeeding, lactation, energy intake.

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.

We investigated whether the presence or absence of physiologic labor may affect the neonatal nucleated red blood cell (RBC) count. We compared absolute nucleated RBC counts taken at approximately 6 hours of life in term infants born by elective cesarean delivery without trial of labor ( n = 32) and in vaginally delivered infants ( n = 28). Venous blood samples were analyzed and differential cell counts were performed manually; absolute nucleated RBC were counted and expressed as an absolute number. There were no significant differences between groups in birth weight, gestational age, maternal age, gravidity, parity, maternal analgesia during labor, 1- and 5-minute Apgar scores, and infant sex. There was a significantly higher hematocrit and RBC count in the vaginally delivered group as compared with the cesarean group. The absolute nucleated RBC, corrected leukocyte and lymphocyte, and platelet counts were strikingly similar in both groups. We conclude that labor does not affect the neonatal nucleated RBC count. This finding supports the speculation that physiologic labor does not induce a fetal hypoxemia severe or prolonged enough to produce hematological evidence of increased erythropoiesis.

Little is known about the composition of human milk (HM) expressed by mothers of asymmetrically growth-restricted infants. To test the null hypothesis that lactating mothers of small-for-gestational-age (SGA) infants produce milk with fat content similar to that of lactating mothers of infants whose growth is appropriate for gestational age (AGA). Fifty-six lactating mothers of newborns (26 SGA and 30 AGA) were recruited within the first 3 days of delivery. Creamatocrit (CMT) levels in HM were measured at 72 h, 7 days and 14 days postdelivery in capillary tubes after centrifugation at 9000 r.p.m. for 5 min. The groups did not differ in terms of maternal age, body mass index, gestational age (GA), pregnancy weight gain and parity. They differed significantly in terms of infant’s birth weight by design. The mean CMT levels at the three time points were similar for the two groups. This remained true when timing of the sample (colostrum, transitional, mature milk) was introduced as a confounder in the analysis of variance (general linear model). Fat content of HM is not affected by fetal growth status. We suggest that mothers of SGA infants may be reassured that their milk contains adequate amount of fat that is appropriate for the growth of their infants.

Necrotizing enterocolitis (NEC), a common intestinal disease affecting premature infants, is a major cause of morbidity and mortality. Previous reports indicate an upregulation 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.Timp-1-treated Caco-2 intestinal cells were tested for MMP-2 enzymatic activity and cell junction integrity.TIMP-1 inhibited MMP-2 activity, which induced a significant increase in the expression of occludin but not of claudin-4. TIMP-1 did not affect apoptosis.One of the putative mechanisms associated with HBM protection against NEC is mediated by TIMP-1, which downregulates MMP-2 activity, inhibits the degradation of occluding, and preserves tight junctions and gut barrier integrity.

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.

Background and Aims: 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. Methods: 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. Results: 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. Conclusions: 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.

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 > 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.

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. Conclusions: The field of neonatology has not had a significant yearly increase of original studies, but has seen an increase of reviews, meta-analyses and editorials. This contrasts with Pediatrics, which shows a similar increase in reviews, meta-analyses and editorials, but also an increase in the number of CTs and RCTs and guidelines.

To study whether Johan Sebastian Bach music has a lowering effect on resting energy expenditure (REE) similar to that of Wolfgang Amadeus Mozart music. Prospective, randomized clinical trial with cross-over in 12 healthy, appropriate weights for gestational age (GA), gavage fed, metabolically stable, preterm infants. Infants were randomized to a 30-min period of either Mozart or Bach music or no music over 3 consecutive days. REE was measured every minute by indirect calorimetry. Three REE measurements were performed in each of 12 infants at age 20±15.8 days. Mean GA was 30.17±2.44 weeks and mean birthweight was 1246±239 g. REE was similar during the first 10-min of all three randomization periods. During the next 10-min period, infants exposed to music by Mozart had a trend toward lower REE than when not exposed to music. This trend became significant during the third 10-min period. In contrast, music by Bach or no music did not affect significantly REE during the whole study. On average, the effect size of Mozart music upon REE was a reduction of 7.7% from baseline. Mozart music significantly lowers REE in preterm infants, whereas Bach music has no similar effect. We speculate that ‘Mozart effect’ must be taken into account when incorporating music in the therapy of preterm infants, as not all types of music may have similar effects upon REE and growth.

Aim : To assess the conclusiveness of the Cochrane Neonatal Reviews (CNRs). We tested the hypotheses that: 1) the majority of the reviews is inconclusive; 2) the majority of reviews recognizes the need for further studies; 3) the ability to reach a conclusion is dependent upon both the number of studies and the number of patients. We also aimed to determine whether the conclusiveness of the CNRs was affected by time. Methods : We selected CNRs available in the Cochrane Library in June 2004. The number of randomized clinical trials (RCTs) found, number of RCTs included for analysis, number of patients enrolled, the stated need for further studies, and the conclusiveness of CNRs were recorded. Results: Out of 170 CNRs, 67.7% were conclusive. The average number of articles was similar, but the total number of patients enrolled was three times higher in the conclusive CNRs. The percentage of articles included in conclusive studies was significantly higher than in inconclusive ones. The vast majority of CNRs recognized the need for further studies. The number of studies included correlated significantly with the total number of patients included. The percentage of conclusive CNRs correlated negatively with year of publication. Conclusion: The majority of CNRs is conclusive, but emphasizes the need for further studies. The ability of a CNR to reach a conclusion is affected by the cumulative sample size and by the number of studies performed. The probability of a newer review to be conclusive is lower than that of an older review.

Objective. 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.Methods. 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.Results. 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.Conclusions. 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.

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.

We compared energy expenditure (EE) of preterm infants fed their mother'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.05), per feeding (55+/-6 vs 60+/-10 kcal/kg per 24 hours) (P.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.05 level.Preterm infants have lower EE when they are fed breast milk than when they are fed preterm infant formula.

Background:Parathyroid hormone-related protein (PTHrP) has the ability to activate parathyroid hormone receptors and cause hypercalcaemia. In a previous study we demonstrated high levels of PTHrP in both term and preterm human milk (HM) (Breastfeeding Medicine, 2009). PTHrP intestinal absorption and its influence upon calcium homeostasis of the preterm infant (PTI) has not been studied yet. Objective: To assess the correlation between PTHrP level in preterm HM and PTHrP in maternal and neonatal serum. Design/Methods: We collected samples of expressed HM obtained from 16 mothers of preterm infants (25-34 weeks' gestation). In addition, blood samples from both mothers and infants were drawn. All samples were collected at days 2 and 10 postpartum. PTHrP levels were measured by twosite immunoradiometric assay. Blood calcium (Ca), Phosphorus (P) and alkaline phosphatase (ALP) levels were also measured. Results: Both maternal and neonatal PTHrP serum levles did not vary after 10 days of breastfeeding. No correlation was found between PTHrP level in HM and serum PTHrP, Ca, P and ALP of the breastfed PTI. Conclusions: Despite high levels of PTHrP in preterm HM, serum levels of PTHrP of the breast fed PTI do not increase over time. We found no correlation between PTHrP in HM and neonatal Ca serum concentration. We speculate that PTHrP intestinal absorption in the PTI is not significant.

In Reply .— We are thankful to Larnkjaer et al for their interest in our article1 and for their thoughtful comments. When we ran our Medline search while writing our article, using the key words “lactation” or “breast milk” and “duration,” we were not able to retrieve their important communication. …