Anemia, Hepcidin, and Vitamin D in Healthy Preterm Infants: A Pilot Study.

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 < 20 ng/mL] and 15% were anemic. Hepcidin levels were significantly higher in anemic premature infants than in the nonanemic group (55.3 ± 23.9 ng/mL vs. 30.1 ± 16.3 ng/mL, respectively, p < 0.05). No differences were found in iron, ferritin, 25(OH)D, and CRP levels between anemic and nonanemic premature newborn infants. A positive correlation was found between hepcidin and ferritin (R 2 = 0.247, p = 0.02) and a negative correlation was found between 25(OH)D and CRP (R 2 = 0.1, p = 0.04). No significant correlations were found between 25(OH)D and hepcidin, iron, ferritin, or CRP. CONCLUSION: Anemia of prematurity was associated with high hepcidin serum levels. The exact mechanisms leading to anemia and the role of vitamin D warrant further investigation. KEY POINTS: · Hepcidin levels were significantly higher in anemic premature infants.. · A positive correlation was found between hepcidin and ferritin.. · Negative correlation was found between 25(OH)D and CRP..

Maternal Exposure to Polychlorinated Biphenyls and Asthma, Allergic Rhinitis and Atopic Dermatitis in the Offspring: The Environmental Health Fund Birth Cohort.

Background: Polychlorinated biphenyls (PCBs) are persistent organic pollutants banned for use worldwide. Due to their biodegradation resistance, they accumulate along the food chain and in the environment. Maternal exposure to PCBs may affect the fetus and the infant. PCBs are immunotoxic and may damage the developing immune system. PCBs are associated with elevated IgE antibodies in cord blood and are considered to be predictive of atopic reactions. Several studies on the association between prenatal exposure to PCBs and atopic reactions were previously published, albeit with conflicting results. Objectives: To examine the association between maternal PCBs levels and atopic reactions in their offspring. Methods: During the years 2013-2015, a prospective birth cohort was recruited at the delivery rooms of Shamir Medical Center (Assaf Harofeh) and "Dana Dwek" Children's Hospital. Four PCBs congeners were investigated: PCBs 118, 138, 153, and 180. In 2019, when children reached the age of 4-6 years, mothers were interviewed using the ISAAC questionnaire to assess symptoms of atopic reactions, including asthma, allergic rhinitis, and atopic dermatitis. Results: One hundred and fifty mother-child dyads were analyzed. No significant differences were found in the median serum PCBs concentrations of each studied congener or total PCBs for asthma, allergic rhinitis, atopic dermatitis diagnosis, or parent-reported symptoms. No association was found between exposure to total PCBs and the risk for asthma symptoms or diagnosis, adjusted to maternal age and family member with atopic condition: aOR = 0.94, 95%CI: (0.88; 0.99). No association was observed between each studied PCB congener and asthma symptoms or diagnosis. The same results were found also for other studied outcomes-allergic rhinitis and atopic dermatitis. Conclusion: Our study joins a series of previous studies that attempt to shed light on environmental exposures in utero as influencing factors for atopic conditions in children. Our results reflect the complexity of the pathophysiology of these phenomena. No relationship between maternal serum PCBs levels was demonstrated for asthma, allergic rhinitis, or atopic dermatitis. However, additional multi-participant studies, with longer, spanning into later pediatric age follow up are needed.

Neonatal morbidity among African refugee women in Israel: a case-control study.

OBJECTIVES: Reports on neonatal morbidity (NM) among refugees in developed countries remain inconsistent. We aimed to compare NM among infants of African refugees in Israel to the native population based on a large population sample. DESIGN: A case-control study. SETTING: A tertiary hospital in Israel. PARTICIPANTS: Data on hospital-based live births of refugee women and their newborns who were born in 2014 and 2017 were retrieved from medical records. Perinatal and neonatal data were compared between the refugee group and the native residents matched for gestational age and year of birth as well as within the refugee group. PRIMARY OUTCOME: Prevalence of NM among African refugees in Israel. RESULTS: Newborns delivered by 357 refugee women (mean age 30.2 years) and 357 controls (mean age 32.2 years) were analysed. Both groups were similar for the newborns' weight and gestational age. There were no significant differences in NM between the groups. A within-refugee comparison conducted between 2014 and 2017 yielded significant differences in birth weight (3051.4 vs 3373.6 gr, p<0.001, 95% CI (198.3 to 446.2), d=0.56), the number of twin deliveries (10 vs 4, p=0.002, Φ=0.173), the number of neonates evaluated as small for gestational age (15 vs 10, p=0.003, Φ=0.167) and the use of human milk (71% vs 93%, p<0.001, Φ=-0.298). CONCLUSIONS: We conclude that NM among neonates born to refugee mothers was not higher than that of neonates born to native Israeli mothers. We suggest that successful implementation of health policies for refugees has improved their accessibility to mother-child health services.

Maternal and Newborn Thyroid Hormone, and the Association With Polychlorinated Biphenyls (PCBs) Burden: The EHF (Environmental Health Fund) Birth Cohort.

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.

Twin versus singleton pregnancy in women ≥ 45 years of age: comparison of maternal and neonatal outcomes.

Objectives: The aim of the study is to compare the effect of very advanced maternal age (≥45 years) on maternal and neonatal outcomes of twin and singleton pregnancies.Materials and methods: This retrospective cohort study included women ≥ 45 years of age who gave birth to twins. Each was randomly matched to two women ≥ 45 years of age who gave birth to singletons within 7 days of the study subject. Data on maternal age, gravidity, parity, background medical information, body mass index at conception, number of fetuses, mode of conception (either spontaneous or assisted reproductive technology [ART]), mode of delivery, and gestational age at delivery were extracted from a real-time computerized database.Results: The data of 75 twin pregnancies of women aged ≥ 45 years were compared with those of 150 singleton pregnancies matched for maternal age. There were significantly more cases of hypertensive complications among the twin pregnancies compared to the singleton pregnancies (41.33 versus 14.00%, respectively, OR = 3.33, 95% CI = 2.26-8.30, p = .000) and more cases of preeclamptic toxemia (29.33 versus 12.00%, respectively, OR = 3.04, 95% CI = 1.51-6.13, p = .001). The duration of twin pregnancies was much shorter compared to singleton pregnancies, with a higher incidence of deliveries prior to 37 weeks' gestation (56.00 versus 8.00%, respectively, OR = 14.64, 95% CI = 6.94-30.85, p = .000), and deliveries prior to 34 weeks' gestation (22.67 versus 2.00%, respectively, OR = 14.36, 95% CI = 4.06-50.86, p = .000). More infants of twin pregnancies had a low birth weight (68.00 versus 10.00%, respectively, OR = 19.13, 95% CI = 10.14-36.06, p = .000), and many had a very low birth weight (10.67 versus 0.67%, respectively, OR = 17.79, 95% CI = 2.33-135.97, p = .000). The infants of twin pregnancies also included more cases of intubation (10.00 versus 0.00%, respectively, p = .000), more cases of hypoglycemia (12.67 versus 5.33%, respectively, OR = 2.57, 95% CI = 1.09-6.08, p = .026), and were admitted much more often to the neonatal intensive care unit (36.00 versus 8.00%, respectively, OR = 6.47, p = .00, CI = 3.29-12.74).Conclusions: Women ≥ 45 years of age with twin pregnancies and their neonates sustain more severe adverse outcome compared to matched pairs of singleton pregnancies. It is recommended that a single embryo transfer should be offered in preference to multiple embryos when those women are undergoing ART.

[THE EFFECT OF MUSIC IN PRETERM ON RESTING ENERGY EXPENDITURE - A PROSPECTOVE RANDOMIZED CLINICAL TRIAL].

BACKGROUND: We have recently showed that Wolfgang Amadeus Mozart's music significantly lowers resting energy expenditure (REE) in preterm infants. Whether or not this effect is specific to Mozart is unknown. OBJECTIVES: To study whether familiar ("ethnic") music has the same effect on REE in preterm infants as music by Mozart. METHODS: A prospective, randomized clinical trial with cross-over was conducted in 9 healthy, appropriate weights for gestational age, gavage fed, preterm infants. Infants were randomized to be exposed to a 30-minute period of Mozart music or "ethnic" music or no music over 3 consecutive days. Metabolic measurements were performed by indirect calorimetry. RESULTS: A total of 27 REE measurements were performed. On average REE was lower in preterm infants who were exposed to "ethnic" music compared to preterm infants who were exposed to music by Mozart (p=0.388). REE was lower in preterm infants who didn't listen to music at all compared to Mozart (p=0.014) or to "ethnic" (p=0.134). CONCLUSIONS: Exposure to music by Mozart significantly elevated REE in healthy preterm infants compared to preterm infants who didn't listen to music at all. Nevertheless a trend of lower REE was demonstrated when preterm infants listened to "ethnic" music compared to Mozart. DISCUSSION: We were unable to demonstrate a significant decrease in REE by exposure of preterm infants to Mozart- or "familiar" music. At this time point we cannot recommend music therapy for preterm infants in order to lower the REE. We speculate that a larger study sample might show a definite effect.

A silent outbreak of vancomycin-resistant Enterococcus faecium in a neonatal intensive care unit.

OBJECTIVE: To describe the containment of a widespread silent outbreak of vancomycin-resistant Enterococcus faecium (VRE-fm) in the Tel-Aviv Medical Center (TASMC) neonatal intensive care unit (NICU). METHODS: Setting - an NICU, participants - 49 cases of VRE-fm-colonized neonatal inpatients. RESULTS: A newborn was transferred from the TASMC NICU to another hospital and screened positive for VRE-fm upon arrival. All TASMC NICU patients were then immediately screened for VRE and 21/38 newborns were identified as VRE carriers. Interventional measures were strictly enforced. By the end of the outbreak, 49 cases of VRE carriage had been identified. There were no VRE clinical infections. The source of the outbreak was not identified. CONCLUSION: Our study highlights the importance of screening implementation in a NICU setting since this outbreak could have been prevented by active screening of all out-born transfer patients and by having adopted mandatory screening into the NICU's routine procedures. Screening for multi-drug resistant organisms upon admission of all transferred patients to the NICU has been implemented.

Associations between intrauterine exposure to polychlorinated biphenyls on neonatal ano-genital distance.

Polychlorinated Biphenyls (PCBs) are widespread environmental contaminants. PCBs have endocrine disrupting properties which raises concerns regarding their effect on the developing fetus. This study aimed to examine the association between prenatal exposure to PCBs and anogenital distance (AGD) in newborns. Serum concentrations of PCB congeners -118, -138, -153 and -180 were measured in 175 pregnant women presenting to the delivery room. AGD was measured in their newborns. Regression models were used to estimate associations between maternal PCB exposure and infant anogenital measurements, controlling for possible confounding variables. Mean maternal serum concentrations were 2.95 ± 2.18 ng/g, 4.62 ± 3.54 ng/g, 7.67 ± 6.42 ng/g and 5.10 ± 3.91 ng/g for congeners -118, -138, -153 and -180, respectively. Higher maternal concentrations of PCBs were associated with reduced AGD measures in male infants. Higher maternal concentrations of PCB-138 and PCB-153 were associated with reduced ano-scrotal distances and higher maternal concentrations of all four PCB congeners were associated with reduced ano-penile distances. No significant associations were found between any PCB congener and any AGD measure in female newborns. This study demonstrates that intrauterine exposure to PCBs may be associated with reduced AGD in male newborns. More research is needed to reveal the implications for adult reproductive health.

Vitamin D Status among Israeli Medical Residents.

BACKGROUND: Israel is a country with a sunny climate; however, vitamin D deficiency and insufficiency are common findings in certain populations whose exposure to sunlight is limited. Medical residency is known for long indoor working hours, thus theoretically limiting the opportunities for sun exposure. OBJECTIVES: To evaluate whether the vitamin D status among residents in a single medical center in Tel Aviv is below the normal range. METHODS: Forty-six residents (28 females, 18 males, average age 33.9 ± 2.8 years) in three residency programs (internal medicine, general surgery/obstetrics and gynecology, pediatrics) were recruited. Demographic data, personal lifestyle, physical activity details and sun exposure duration were obtained by a questionnaire. Serum levels for 25(OH)D were analyzed by a radioimmunoassay. RESULTS: The mean serum 25(OH)D concentration was 29.8 ± 5.8 ng/ml. According to Institute of Medicine definitions, none of the residents were vitamin D deficient and only two residents (4%) were vitamin D insufficient (15 ng/ml each). The level of 25(OH)D was similar among the various medical specialties. The 25(OH)D levels correlated with the duration of sun exposure and the number of offspring (regression analysis: R2 = 9.2%, P < 0.04 and R2 = 8.9%, P < 0.04, respectively), but not with nutritional data, blood chemistry, or extent of physical activity. CONCLUSIONS: Most of the residents maintained normal or near normal 25(OH)D levels, indicating that the residency program itself did not pose a significant risk for vitamin D deficiency.

Pulmonary hemorrhage due to Coxsackievirus B infection-A call to raise suspicion of this important complication as an end-stage of enterovirus sepsis in preterm twin neonates.

BACKGROUND: Prematurity is an important risk factor for the fulminate form of neonatal enteroviral infection. Pulmonary hemorrhage is a morbid complication that should be anticipated and managed aggressively due to its fatal outcome. OBJECTIVE: To emphasize the significance of pulmonary hemorrhage as a complication of severe enterovirus infection in preterm neonates. STUDY DESIGN: This report is a description of the clinical history, medical management and clinical outcomes of two pairs of preterm twin newborns (30 weeks and 36 weeks) with fulminant infection due to Coxsackievirus B (CBV) infection. RESULTS: Maternal fever was reported in both deliveries and it was a factor in the decision for urgent cesarean section of the 30-week twins. Three of the four infants failed to survive. Their clinical course involved multiple organ system failure complicated with profound disseminated intravascular coagulopathy and pulmonary hemorrhage. Pulmonary bleeding leading to hypovolemic shock and respiratory failure was the direct cause of death in two cases. CONCLUSIONS: This small series of preterm neonates with the diagnosis of CBV sepsis highlights the importance of correct diagnosis of maternal enterovirus infection in order to extend pregnancy and allow the fetus time to passively acquire protective antibodies. This report emphasizes the morbid complication of pulmonary hemorrhage as a result of enterovirus infection that should be anticipated and managed aggressively due to its potentially fatal outcome. Moreover, evaluation and observation of the asymptomatic twin is recommended in order to detect early signs of infection and deterioration in that sibling as well.

Circadian Macronutrients Variations over the First 7 Weeks of Human Milk Feeding of Preterm Infants.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. Concentrations of protein, carbohydrates, and fat from morning samples were predictive of evening concentrations to different extents (R(2) = 0.720, R(2) = 0.663, and R(2) = 0.20, respectively; p < 0.02). The predictability of evening values by morning values was not influenced by the week of lactation at sampling or by individual patients. In repeated-measures analysis of variance performed on 11 patients who completed the whole 7-week period, over time, there was a significant decrease in fat, energy, and protein contents, whereas carbohydrates content remained unchanged. Day-night differences remained significant only for fat content. CONCLUSIONS: Circadian variations in fat and energy concentrations of HM are consistent over the first 7 weeks of lactation. There are no consistent circadian variations in HM protein and carbohydrates. Over a given day, there are little variations in protein and carbohydrates content, but fat concentrations are more variable, and evening values are less well predicted by morning sample analysis than values for protein or carbohydrates.

Higher Fat Content in Breastmilk Expressed Manually: A Randomized Trial.

OBJECTIVE: This study aimed to evaluate the effect of milk expression method (manual expression versus electric pump) on the composition of breastmilk. STUDY DESIGN: Data on 21 mothers of 21 newborns 48-72 hours postdelivery were collected and analyzed. The women were randomly assigned to express breastmilk manually followed by pump, or in reverse order. The fat, carbohydrate, and protein contents of the milk samples were analyzed using a human milk analyzer (Miris AB, Uppsala, Sweden). RESULTS: The fat and energy contents of milk obtained through manual expression were higher than those obtained by pump (p=0.024 and p=0.04, respectively, by the Wilcoxon signed rank test). There were no significant differences in protein or carbohydrate content of milk obtained by either method of expression. The difference in fat content between milk obtained by the two methods was not correlated with mother's age, delivery method, gestational age at delivery, parity, or the interval between delivery and the time the sampled milk was obtained. CONCLUSIONS: Manually expressed human milk had higher fat content than milk expressed by electric pump. We speculate that this difference is due to the presence of hindmilk in the manually expressed milk because the technique of massaging the breast during manual expression is more likely than the pump to eject hindmilk, which has been shown to have higher fat content than foremilk.

Secular trends in impact factor of breastfeeding research publications over a 20-year period.

OBJECTIVE: The aim of the current study was to determine whether secular changes have occurred in the breastfeeding literature, in terms of number and type of yearly published articles and impact factor of journals publishing these articles. RESEARCH DESIGN AND SETTING: In order to evaluate all Medline articles related to breastfeeding, we used the Internet URL www.ncbi.nlm.nih.gov/entrez and searched for articles recorded from January 1, 1992 through December 31, 2011 using as a key word "breast milk," "breast feeding," or "human milk." We specifically studied randomized controlled trials (RCTs), clinical trials, case reports, meta-analyses, letters to the editor, reviews, systematic reviews, practice guidelines, and editorials. RESULTS: There was a linear increase over the years in all articles recorded, from approximately 1,100/year in 1992 to 2,100/year in 2011 (i.e., an approximately 1.9-fold increase [R(2)=0.995, p=0.001]). Concomitant with the yearly increase in the number of published RCTs per year, there was a linear increase in the number of journals publishing articles on breastfeeding per year (from approximately 20 in 1992 to >60 in 2011 [R(2)=0.811, p<0.001]) but an overall decrease in the average impact factor every year (R(2)=0.202, p=0.047). However, the ratio of high-quality articles selected (RCTs+meta-analyses+systematic reviews+CR)/low-quality articles (reviews+editorials+letters to the editor+case reports) increased significantly over time in favor of the former. CONCLUSIONS: There was a linear increase in the number of publications related to the field of breastfeeding and human milk, and the ratio of high-quality/low-quality articles improved over time, indicating a relative and absolute increase in the number of articles usually considered as being of high quality. There was a significant increase in the number of journals publishing breastfeeding-related articles, with a significant decrease of average impact factor of those journals.

Emergency use of intravenous phytonadione (vitamin K1) for treatment of severe bleeding in a child with chronic cholestasis.

We present a 5-year-old boy with multiple hematomas associated with chronic cholestasis. A week before admission he suffered minor trauma at day care. The next day he complained of trunk and limb pain and orthopedic consultation, including leg x-rays, revealed no abnormalities. Over the next 5 days multiple hematomas developed over his body and increased in size. In the Emergency Department he was in pain and looked sick but alert. He had fever and tachycardia, with normal blood pressure and respiratory status and physical examination showed several hematomas on the legs, which increased in size during observation in the Emergency Department over 2 hours. Blood work revealed multiple coagulation abnormalities, and International Normalized Ratio was 12. Intravenous phytonadione (vitamin K1) was immediately administered with normalization of coagulation abnormalities within 1 hour and the hematomas stopped growing in size. In addition to missing follow-up with the Pediatric Gastroenterology Department, social service agency inquiry found he had not taken his medications for several months. With severe abnormal bleeding and hepatic disease, intravenous vitamin K1 may be lifesaving, even before obtaining confirmatory blood work, fresh-frozen plasma, or blood transfusion.

Anemia of acute infection in hospitalized children-no evidence of hemolysis.

The objective of the study is to examine the assumption that a process of hemolysis plays a role in anemia of acute infection in children. The study was comprised of febrile pediatric patients, who had a positive blood or urine culture. Complete blood count measures were compared between hospitalization and prehospitalization or posthospitalization values. Children admitted to the hospital for elective surgical procedures served as controls. Blood parameters of hemolysis were investigated in some of the patients. Of the 70 patients studied, 49 (70%) were diagnosed with pyelonephritis and 21 (30%) had bacteremia. Mean (+/-SD) hemoglobin (Hgb) on hospital admission was 10.9+/-1.27 g/L as compared with 12.1+/-1.03 g/L of the controls, P<0.0001. Compared with normal-for-age Hgb values as a standard, 42 (60%) cases were identified as anemic. Compared with hospitalization values, Hgb and hematocrit (Hct) were significantly higher in prehospitalization or posthospitalization, whereas WBC values were significantly lower. All parameters of hemolysis, namely reticulocytes, bilirubin, lactate dehydrogenase (LDH), and haptoglobin, were normal. Bacteremia and pyelonephritis are accompanied by a significant drop in Hgb level. There is no evidence of hemolytic anemia in these patients.