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To evaluate risk factors and impact of delivery room cardiopulmonary resuscitation (DR-CPR) on very low birth weight (VLBW) preterm infants.A national, population-based, observational study evaluating risk factors and short-term neonatal outcomes associated with DR-CPR among VLBW, extremely preterm infants (EPIs, 24 to 27 weeks' gestation) and very preterm infants (VPI, 28 to 31 weeks' gestation) born in 1995 to 2010.Among 17 564 VLBW infants, 636 (3.6%) required DR-CPR. In the group of 6478 EPI, 412 (6.4%) received DR-CPR compared with 224 of 11 086 infants (2.0%) in the VPI group. EPI who underwent DR-CPR had higher odds ratios (ORs (95% confidence interval)) for mortality compared to EPI not requiring DR-CPR (OR 3.32 (2.58, 4.29)), grades 3 to 4 intraventricular hemorrhage (IVH) (OR 1.59 (1.20, 2.10)) and periventricular leukomalacia (OR 1.81 (1.17, 2.82)). DR-CPR among VPI was associated with higher ORs for mortality (OR 4.99 (3.59, 6.94)), early sepsis (OR 2.07 (1.05, 4.09)), grades 3 to 4 IVH (OR 3.74 (2.55, 5.50)) and grades 3 to 4 retinopathy of prematurity (ROP) (OR 2.53 (1.18, 5.41)) compared to VPI not requiring DR-CPR. Only 11% of infants in the EPI DR-CPR group had favorable outcomes compared with 44% in the VPI DR-CPR group. Significantly higher ORs for mortality, IVH and ROP were found in the VPI compared to the EPI group.Preterm VLBW infants requiring DR-CPR were at increased risk of adverse outcomes compared to those not requiring CPR. This effect was more pronounced in the VPI group.

We aimed to compare the effect of 12-week feeding of commercially available infant formulas with different percentages of palmitic acid at sn-2 (beta-palmitate) on anthropometric measures and bone strength of term infants. It was hypothesized that feeding infants with high beta-palmitate (HBP) formula will enhance their bone speed of sound (SOS). Eighty-three infants appropriate for gestational age participated in the study; of these, 58 were formula-fed and 25 breast-fed infants, serving as a reference group. The formula-fed infants were randomly assigned to receive HBP formula (43 % of the palmitic acid is esterified to the middle position of the glycerol backbone, study group; n = 30) or regular formula with low-beta palmitate (LBP, 14 % of the palmitic acid is esterified to the middle position of the glycerol backbone, n = 28). Sixty-six infants completed the 12-week study. Anthropometric and quantitative ultrasound measurements of bone SOS for assessment of bone strength were performed at randomization and at 6 and 12 weeks postnatal age. At randomization, gestational age, birth weight, and bone SOS were comparable between the three groups. At 12 weeks postnatal age, the mean bone SOS of the HBP group was significantly higher than that of the LBP group (2,896 ± 133 vs. 2,825 ± 79 m/s respectively, P = 0.049) and comparable with that of the breast-fed group (2,875 ± 85 m/s). We concluded that infants consuming HBP formula had changes in bone SOS that were comparable to those of infants consuming breast milk and favorable compared to infants consuming LBP formula.

To reassess iron supplementation practice safety in very low birth weight (VLBW) preterm infants receiving restrictive red blood cell transfusions during initial hospitalization.Iron status, including hemoglobin (Hb), serum iron, ferritin, and soluble transferrin receptor (sTfR) levels and reticulocyte count of transfused (n=236) and non-transfused (n=166) preterm infants at ≤24 h and 2, 4 and 8 weeks were recorded. As per protocol, a restrictive blood transfusion policy and supplementation of 5 mg kg(-1) per day of iron polymaltose complex from 4 weeks and 25 mg(-1) per day of vitamin E from 2 weeks were imposed for all infants. Normative reference cord-blood ferritin value of preterm infants was used for comparison. Vitamin E levels and incidence of morbidities associated with prematurity were recorded.At ≤24 h, the characteristics and iron status of both groups were similar. At 2, 4 and 8 weeks, the transfused group had significantly higher Hb, iron and ferritin levels; sTfR levels were lower at 4 and 8 weeks (all indices, P0.05). At 8 weeks, the median ferritin levels of our transfused group were lower than that of normative reference cord-blood value (115 (50th percentile) vs 79 (43 to 107) μg l(-1), respectively). Vitamin E levels and the incidence of morbidities associated with prematurity of the transfused and non-transfused groups were not different (both indices, P0.18).Adding iron supplementation to preterm infants receiving restrictive blood transfusions has shown to be a judicious and safe practice in terms of iron status for VLBW preterm infants.

Continuous epidural anaesthesia attenuates perioperative stress and avoids the need for systemic opioids. In addition, it may prevent the need for postoperative mechanical ventilation. The aim of the study was to prospectively follow the perioperative course of young infants treated with continuous thoracic/lumbar epidural anaesthesia for major surgery. Data were collected prospectively from 44 epidural anaesthetics in 40 infants (18 premature or former premature) weighing 1,400–4,300 g who underwent major abdominal surgery (33 cases), thoracic surgery (5), or both (1), or ano-rectal surgery (5) at our centre. Epidural placement was achieved easily in all cases, with high quality analgesia for 24–96 h. Tracheal extubation was delayed after 4 anaesthetics due to muscle relaxant overdose (n = 1), surgeon’s request (n = 2), and systemic opioid administration before epidural anaesthesia was considered (n = 1). Intraoperative complications included haemodynamic instability (n = 1) and vascular catheter placement (n = 5). Postoperative complications included meningitis (n = 1), insertion site erythema (n = 7), apnoea (n = 6; 4 premature and 2 full-term infants) and tracheal re-intubation (n = 6). Continuous epidural analgesia is effective in low-weight infants undergoing major surgery. The trachea may be extubated immediately after surgery. Attention should be paid to the unique anatomical, physiological, and pharmacological aspects. The patients should be monitored carefully for pain, respiratory failure, and meningitis (an extremely rare complication).

On the basis of preliminary data, this larger bi-institutional continuation trial evaluating the efficacy and safety of early iron supplementation in preterm infants calls attention to the levels of vitamin E, a marker of antioxidant activity, during iron treatment. A total of 116 preterm infants were randomly assigned to receive at 2 or 4 weeks of age ( N = 62, N = 54, respectively) 5 mg/kg/d of nonionic iron polymaltose complex concomitantly with a daily dose of 25 IU vitamin E (as dl-alpha-tocopherol acetate) from 2 weeks of age. Vitamin E (alpha-tocopherol) levels, iron, ferritin, hemoglobin concentration, and reticulocyte count were recorded from 2 to 8 weeks of age. The morbidities of prematurity associated with free radicals formation were also documented. A gradual increase of alpha-tocopherol levels within physiological range (0.8 to 3.5 mg/dL) was found in the 2-week and 4-week groups during the study period with no difference among the groups ( P > 0.05 for all comparisons). At 8 weeks of age, iron and ferritin levels, hemoglobin concentration, and reticulocyte count were higher in the 2-week group. No correlation was observed between timing of both iron and vitamin E supplement and hemolysis or morbidities associated with prematurity. Thus, treatment of iron with vitamin E supplement at 2 weeks of age is, in our experience, an efficacious and safe treatment for improving anemia in preterm infants.

The purpose of this study was to examine the efficacy and safety of early nonionic iron supplementation in preterm infants. Infants with gestational age < or = 32 weeks who were fed enriched human milk were assigned concurrently to receive 5 mg/kg/d enteral iron polymaltose complex (IPC) at 2 or 4 weeks of age. The levels of hemoglobin, reticulocytes, serum iron, ferritin, and soluble transferrin receptor were recorded at 2, 4, and 8 weeks of age. The incidence of morbidities associated with prematurity and the need for red blood cell transfusions (RBCTs) were recorded. The 2-week group (n = 32) had a better iron status than the 4-week group (n = 36) at 4 weeks and at 8 weeks of age. The incidence of morbidities associated with prematurity was not different among the groups ( P = 0.26). RBCT was required in one infants of the 2-week group and in 10 infants in the 4-week group ( P = 0.045). The number needed to treat to prevent one RBCT was five. Supplementation of 5 mg/kg/d enteral IPC to preterm infants fed enriched human milk as early as 2 weeks of age was more beneficial to iron status than at 4 weeks of age, and was associated with decreased need for RBCTs and no increase in the incidence of morbidities associated with prematurity.

Objectives In 2002 there was an increase in the incidence of Bacillus species sepsis in our NICU that was almost completely resolved in 2003–2004 after the NICU was relocated. Our aims were to identify the source, the risk factors, and to characterize the clinical features of these infections. Methods The epidemiological investigation commenced during the outbreak and thereafter. The patient's data were collected retrospectively and a case control study was used to analyze the risk factors. Results There were eight cases of Bacillus species sepsis: five during 2002, two in 2003, and one in 2004. All infants recovered and salvaging percutaneous central venous catheter (PCVC) was successful in 4/6 of the cases. A case control study identified necrotizing enterocolitis (NEC) and PCVC as risk factors in univariate analysis but only NEC in multivariate analysis. No focal source of Bacillus bacteria was identified, but a high load of bacteria was found in the NICU's air before it was relocated. Conclusion The risk factors for Bacillus species sepsis in our NICU were NEC and PCVC. The clinical course was milder than previously described, and PCVC was successfully salvaged in most cases. The increase in the incidence could be related to the construction work connected with NICU's relocation.

To assess whether elevated levels of estriol (E3) in pregnancy are a factor in the fetal environment associated with undescended testes, we carried out a two-part study: case-control followed by a retrospective cohort study on cryptorchid boys born in the Sapir Medical Center (Kfar Saba, Israel). We found significantly lower pregnancy urinary E3 levels in cryptorchid newborns as compared to controls; however, subgroup comparison yielded significantly higher pregnancy unconjugated E3 levels in the infants who underwent orchiopexy as compared to those who did not.

Amphotericin B is the primary antifungal agent used for candida sepsis in neonates. Breakthrough candidemia was not reported in neonates during either amphotericin B or liposomal amphotericin B (AmBisome) treatment. We describe a case of a premature infant with congenital cutaneous candida infection, who had two episodes of breakthrough infection, from Candida albicans and Candida parapsilosis, while he was treated with amphotericin B and AmBisome, respectively. We discuss the pathogenesis of breakthrough infections, and the relevance of antifungal resistance and sensitivities testing.

Background: Few studies demonstrated that serum amyloid A (SAA), a non-specific acute-phase reactant, could be used as a reliable early marker for the diagnosis of late-onset sepsis (LOS). Objectives: To evaluate the diagnostic value and the dynamics of SAA levels during the course of LOS and to compare it to those of other inflammatory markers. Methods: Levels of SAA, C-reactive protein (CRP) and IL-6 together with clinical variables, biochemical parameters and cultures retrieved from all preterm infants suspected of LOS were checked at the first suspicion of sepsis and after 8, 24, 48 and 72 h. Results were compared to healthy, matched infants. Results: One hundred and sixteen infants were included in the study, 38 in the sepsis and 78 in the non-sepsis group. High levels of SAA were observed at sepsis onset, with a gradual decline thereafter, while CRP levels increased only at 24 h after sepsis onset. In the sepsis group, levels of SAA returned faster to baseline than CRP levels. Receiver-operating characteristic analysis values revealed that SAA at 10 µg/ml had the highest sensitivity at 0, 8 and 24 h after sepsis onset (95, 100 and 97%, respectively) and a negative predictive value (97, 100 and 98%, respectively). Conclusions: SAA is an accurate acute-phase protein during LOS in preterm infants. Quick and reliable SAA kits can make this marker a useful tool in LOS in preterm infants.

Objective We examined the effect of intrauterine growth restriction on mortality and morbidity in the Israel cohort of very low birth weight premature infants. Methods The study population included 2764 singleton very low birth weight infants without congenital malformations born from 24 to 31 weeks of gestation during 1995 to 1999. Four hundred six (15%) were born small for gestational age (SGA). The effect of SGA on death, bronchopulmonary dysplasia, and retinopathy of prematurity was assessed using multiple logistic regression analysis. Results After adjustment for perinatal risk factors, SGA infants had a 4.52-fold risk for death (95% CI, 3.24-6.33), a 3.42-fold risk for bronchopulmonary dysplasia (95% CI, 2.29-5.13), and a 2.06-fold risk for grade 3 to 4 retinopathy of prematurity (95% CI, 1.15-3.66). Conclusions SGA premature infants had an increased risk for death, and major morbidity among survivors was increased.

OBJECTIVE: To assess the effect of daily movements on weight gain, serum leptin, and insulin-like growth factor I (IGF-I) in premature infants. STUDY DESIGN: Twenty very-low-birth-weight premature infants were matched and randomized to a daily movement (n=10) and control groups (n=10). Daily movement consisted of passive range of motion with gentle compression of both the upper and lower extremities 5 days per week for 4 weeks. RESULTS: Daily movements led to a significant increase in weight gain (784±51 vs 608±26 g in movements and controls, respectively, p

In a previous study, we found that increased sodium concentrations in the drinking water led to an increase in mean arterial pressure (MAP) and systolic blood pressure (SBP) in fourth- and fifth-grade school children. Milk powder formulae have a low content of sodium, almost identical to that of breast milk. However, the final sodium concentration in the milk formula depends upon the concentration of sodium in the diluting water, which varies remarkably.To evaluate changes in blood pressure during the first 2 months of life in neonates receiving low-sodium mineral water (LSMW), high-sodium tap water (HSTW), or breast milk.A randomized, prospective study in a teaching hospital.Fifty-eight Jewish term infants maintained on milk formula were randomly assigned to two groups. Group 1 consisted of 25 infants whose formula was diluted with LSMW (Eden Spring Mineral Water) having a sodium concentration of 32 mg/l (1.4 mmol/l). Group 2 contained 33 infants whose formula was diluted with HSTW having a sodium concentration of 196 mg/l (8.5 mmol/l). Fifteen breastfed babies served as the control group (group 3). Weekly weight, height, head circumference, heart rate, and systolic (SBP), diastolic (DBP) and mean (MAP) blood pressures were recorded for each infant for 8 consecutive weeks after birth. After 8 weeks, group 1 reverted to a diet similar to that of group 2. At 6 months of age (week 24), a follow-up blood pressure measurement was performed in 11, 20 and seven infants in groups 1, 2 and 3, respectively. Blood pressure was measured during sleep. Urinary sodium : creatinine ratio was determined monthly during the initial 2 months.Increases in weight and height were equal in all groups. Heart rate did not differ between groups during the entire study period. From the age of 6 weeks until week 8, MAP, SBP and DBP were found to be significantly greater in the group 2 (HSTW). In parallel, the urinary sodium : creatinine ratio was significantly greater in this group. At week 24, blood pressure values in group 1 increased towards those of group 2.Diluting milk formula with tap water containing a high concentration of sodium will result in the infant being fed a high-salt diet. To equilibrate with breast milk, formula should be diluted with low-salt water. Blood pressure in the neonate is increased by a high sodium intake via drinking water.

We assessed the effect of a four weeks exercise training intervention on bone turnover markers in premature infants. Twenty-four very low birth weight premature infants were matched for gestational age, birth weight, gender, as well as for corrected age and weight at initiation of the study. Then the subjects were randomly divided into an exercise (n = 12) and a control group (n = 12). Exercise consisted of passive range of motion exercise with gentle compression of both the upper and lower extremities lasting 5 - 10 minutes each day, 5 days per week for 4 weeks. This protocol has been shown to increase bone mineral density in premature infants. Bone formation was assessed by measurements of circulating bone specific alkaline phosphatase (BSAP) and the C-terminal procollagen peptide (PICP). Bone resorption was determined by serum measurements of C- terminal cross-links telopeptide of type-I collagen (ICTP). Training led to a significant (P < 0.05) increase in weight gain (767 +/- 49 versus 586 +/- 24 gr in trained and control premature infants, respectively); and to a significant increase in BSAP (37.2 +/- 14.6 versus 4.1 +/- 8.4 % in trained and control premature infants, respectively). PICP increased also following exercise (34.6 +/- 18.9 versus 5.4 +/- 9.1 % in trained and control subjects, respectively), however, this increase was not statistically significant. Exercise led to a significant decrease in ICTP (-24.7 +/- 3.1 versus -5.5 +/- 5.4 % in trained and control subjects, respectively). A relatively brief exercise intervention was associated with a biochemical evidence of bone formation in very low birth weight premature infants.

We describe two newborn sisters who presented in the third trimester with diminished fetal movements and skin edema, but with no other signs of hydrops fetalis. Within hours of birth, both developed profound lactic acidemia, followed by multi-organ failure. In muscle mitochondria, the activity of all enzymatic complexes that contain mitochondrial DNA (mtDNA)-encoded subunits was markedly decreased. Southern blot analysis revealed a profound reduction in the mtDNA/nuclear DNA ratio, implying mtDNA depletion. The prenatal identification of skin edema in two patients with mtDNA depletion, and its absence in a healthy sibling, suggest that skin edema should be regarded as a novel manifestation of mtDNA depletion. This finding shows that mtDNA depletion can present prenatally and, consequently, may aid the clinician in making a diagnosis, prenatally, of this genetic defect.

The aim of this national population-based study was to identify perinatal and neonatal factors associated with active intensive treatment (AIT) of infants born at the periviable period of 22 to 24 weeks of gestation.Data from the Israel national very low-birth weight infant database on 2207 infants born alive in 1995 to 2010 at gestational age (GA) 22 to 24 weeks were evaluated. AIT was defined as endotracheal intubation in the delivery room or mechanical ventilation in the neonatal intensive care unit. Multivariable logistic regression analyses were used to identify the independent effect of demographic and perinatal factors on AIT for each gestational week.Of the 2207 infants born at 22 to 24 weeks GA, 1643 (74.4%) received AIT and 564 (25.6%) received comfort care. AIT increased from 25.5% at 22 weeks to 62.7 and 93.5% at 23 and 24 weeks GA, respectively, reflecting a 4.66 (95% confidence interval (CI) 3.32 to 6.54)- and 29.8 (95% CI 19.9 to 44.6)-fold odds for AIT at 23 and 24 weeks GA, respectively, compared with 22-week GA infants. Perinatal treatments associated with AIT included maternal tocolytic therapy (odds ratio (OR) 1.51, 95% CI 1.04 to 2.20), prenatal steroid therapy, both partial (OR 3.30, 95% CI 2.14 to 5.10) and complete (OR 3.17, 95% CI 1.91 to 5.26) and cesarean delivery (OR 2.68, 95% CI 1.88 to 3.83). Each unit increase in birth weight z-score was associated with an OR of 1.58 (95% CI 1.30 to 1.92) for AIT. At 22 weeks GA, maternal tocolytic treatment was associated with higher odds of AIT. In the 23 and 24-week GA infants, maternal infertility treatment, antenatal steroids, cesarean delivery and higher-birth weight z-scores were significantly associated with AIT. Among 23-week GA infants, AIT decreased significantly in the period 2006 to 2010 compared with 1995 to 2000 (OR 0.51, 95% CI 0.34 to 0.77).An active approach in obstetric management of pregnancies appears to impact the neonatologists' decision to undertake AIT treatment in infants born at the border of viability. The higher odds for AIT associated with obstetric interventions might contribute to the reported beneficial effect of antenatal steroids and cesarean delivery on the survival of infants born at the border of viability.

We measured bone speed of sound in premature infants by quantitative ultrasound. A total of 44 neonates participated in the study including 29 premature infants (median birth weight 1264 g, range 578–2420 g; median gestational age 31 weeks, range 24–36 weeks) and 15 full-term infants (median birth weight 3360 g, range 2700–3730 g; median gestational age 40 weeks, range 37–41 weeks). The left tibial speed of sound (SOS) was measured by quantitative ultrasound. Bone SOS was successfully measured in all infants. We found a significant correlation between tibial SOS and gestational age (r=0.78, P

Currently, preterm labour is treated with tocolytic agents and prenatal steroids until the 34th week of gestation only. Our objective in this study was to assess this practice. Seven-year records of all preterm infants born in our institution at 34--36 weeks of gestation, were evaluated retrospectively. All babies, born in singleton well-dated pregnancies, without maternal, medical or obstetric complications, and by normal vaginal delivery, were included. Their length of hospital stay and perinatal complications were compared across gestational age groups of 34, 35 and 36 weeks. Of the 207 babies included, statistically significant reductions in the rates of respiratory distress syndrome (15.0% vs. 3.2%), nosocomial sepsis (5.0% vs. 0%) and apnoea of prematurity (11.7% vs. 2.2%), and consequently, in length of hospital stay (16 +/- 2.7 vs. 4 +/- 0.3 days) occurred between 34 and 36 weeks of gestation. The severity of respiratory distress syndrome also declined significantly. The changes were most noticeable after 35 weeks of gestation, and it was concluded that neonatal complications are still prevalent at 34 and 35 weeks. Therefore, we propose that labour should not be induced at 34 and 35 weeks of gestation and that tocolytic agents and maternal prenatal steroids may be considered in preterm labour during this period.

Meconium periorchitis (MP) is a rare disorder caused by fetal meconium peritonitis with subsequent spillage of meconium into the scrotal sac. The condition is seldom diagnosed correctly during fetal life and the ultrasonographic diagnoses reported vary from no diagnosis to hematoma or hydrocele. It is usually diagnosed clinically during the first year of life when a scrotal mass is an incidental finding. Here, we describe two cases of MP that were diagnosed during routine intrauterine ultrasound examination for fetal growth assessment, and confirmed after birth. One infant underwent a surgical excision of the scrotal mass, confirming the histological diagnosis of meconium periorchitis. The other was managed conservatively. Neither had cystic fibrosis. Thus, we believe that a diagnosis of MP should be considered when prenatal ultrasonographic findings are suspicious for the problem. The awareness of the ultrasonographer and the neonatologist are important for immediate postnatal management, as congenital scrotal masses may have other etiologies.

Music therapy has been recommended as an adjuvant therapy for both preterm infants and mothers during their stay in the neonatal intensive care unit (NICU), and has been shown to have beneficial effects.To study the usefulness of combining live harp music therapy and kangaroo care (KC) on short-term physiological and behavioral parameters of preterm infants and their mothers in the NICU setting.Included in this study were stable infants born between 32 and 37 weeks of gestation, with normal hearing. Mother-infant dyads were randomly assigned to KC and live harp music therapy or to KC alone. Using repeated measures, neonatal and maternal heart rate, oxygen saturation and respiratory rate were recorded along with neonatal behavioral state and maternal anxiety state. Maternal age, ethnicity, education, and love of music were documented.Fifty-two mother-infant dyads were tested. Compared with KC alone, KC and live harp music therapy had a significantly beneficial effect on maternal anxiety score (46.8 +/- 10 vs. 27.7 +/- 7.1, respectively, P0.01). Infants' physiological responses and behavior did not differ significantly. No correlation was found between mothers' age, ethnicity, years of education and affinity for music, and anxiety scores (P = 0.2 to 0.5 for all four variables).KC combined with live harp music therapy is more beneficial in reducing maternal anxiety than KC alone. This combined therapy had no apparent effect on the tested infants' physiological responses or behavioral state.

The umbilical venous hematocrit at birth (Hct 1) and the peripheral venous hematocrit at 2 h of life (Hct 2) were determined in 78 healthy full-term and 14 healthy preterm newborn infants. Hct 1 was 51.6 +/- 4.1% in full-term infants and 50.8 +/- 4% in preterm infants. Hct 2 was 60.9 +/- 2 and 58.6 +/- 6.1% in full-term and preterm infants, respectively. Significant differences between Hct 1 and Hct 2 were found in both groups of infants (p less than 0.01). The blood viscosity increased significantly in both groups from birth to 2 h of life. Neonatal polycythemia (Hct higher than 70% at 2 h of life) was detected in only 3 full-term infants (3.8%). They received partial exchange transfusion. There was a positive linear correlation of Hct 1 with Hct 2 in full-term newborns (r = 0.71, p less than 0.001) and preterm infants (r = 0.57, p less than 0.02). No infants with Hct 1 equal to or below 50% had Hct 2 higher than 65%. None with Hct 1 between 51 and 54% had Hct 2 higher than 70%. Neither Hct 1 nor Hct 2 correlated with birth weight, gestational age, total blood solutes, or reticulocyte counts at birth in either group. An inverse linear correlation was found between blood pH at birth and Hct 2 in preterm newborn infants (r = 0.66, p less than 0.02).

Coxsackievirus group B can cause a severe systemic disease in the perinatal period. Severe manifestations like meningitis, encephalitis, hepatitis, and myocarditis have been previously reported. A case of a twin neonate infected by coxsackievirus group B is described, who developed progressive extensive hepatic calcifications demonstrated by ultrasound and computed tomography with follow-up. Hepatic calcifications in coxsackievirus infection have not been previously reported.

To initiate a longitudinal pilot study comparing the effect of nutrient-enriched post-discharge formula (PDF) with standard term formula (TF) on bone strength of very low birth weight (VLBW) infants in the first six months post-term.Two matched groups of VLBW infants were randomly assigned to enriched PDF (n=10) or TF (n=10) at corrected age of 40 weeks. Anthropometric measurements of growth and measurements of bone speed of sound (SOS) indicating bone strength and bone turnover markers (bone-specific alkaline phosphatase and cross-linked carboxy terminal telopeptide of type I collagen) were taken at term and at three and six months corrected age.The anthropometric measurements of infants fed PDF and TF were comparable at three and six months corrected age. Bone SOS of the PDF group increased from 2760+/-113 m/s at term to 2877+/-90 m/s and 3032+/-60 m/s at three and six months corrected age, respectively (P0.001). Likewise, bone SOS of the TF group increased from 2695+/-116 m/s at term to 2846+/-72 and 2978+/-83 m/s at three and six months, respectively (P0.001). No statistically significant difference was found between the groups in terms of growth and bone SOS measurements. The levels of both bone turnover markers decreased significantly during the study period (P0.001 for both groups).Feeding with PDF after term had no short-term beneficial effect on bone strength and bone turn-over of VLBW infants.

To evaluate the accuracy of serum amyloid A (SAA), an acute phase protein in the detection of neonatal early-onset sepsis, by means of a fast automated SAA kit. Full-term infants

Background:Music stimulation has been shown to provide significant benefits to preterm infants. We hypothesized that live music therapy was more beneficial than recorded music and might improve physiological and behavioral parameters of stable preterm infants in the neonatal intensive care unit. Methods:Thirty-one stable infants randomly received live music, recorded music, and no music therapy over 3 consecutive days. A control of the environment noise level was imposed. Each therapy was delivered for 30 minutes. Inclusion criteria were postconceptional age ≥ 32 weeks, weight ≥ 1,500 g, hearing confirmed by distortion product otoacoustic emissions (DPOAEs), and no active illness or documentation of hyperresponsiveness to the music. Heart rate, respiratory rate, oxygen saturation, and a behavioral assessment were recorded, every 5 minutes, before, during, and after therapy, allowing 30 minutes for each interval. The infant's state was given a numerical score as follows: 1, deep sleep; 2, light sleep; 3, drowsy; 4, quiet awake or alert; 5, actively awake and aroused; 6, highly aroused, upset, or crying; and 7, prolonged respiratory pause > 8 seconds. The volume range of both music therapies was from 55 to 70 dB. Parents and medical personnel completed a brief questionnaire indicating the effect of the three therapies. Results:Live music therapy had no significant effect on physiological and behavioral parameters during the 30-minute therapy; however, at the 30-minute interval after the therapy ended, it significantly reduced heart rate (150 ± 3.3 beats/min before therapy vs 127 ± 6.5 beats/min after therapy) and improved the behavioral score (3.1 ± 0.8 before therapy vs 1.3 ± 0.6 after therapy, p

Studies have previously demonstrated that brief (4 weeks) passive range-of-motion exercise is beneficial for bone development in very low birth weight (VLBW) preterm infants. However, the optimal duration of exercise for bone development in preterm infants is yet unknown. The aim of the present study was to examine the effect of 8 weeks of assisted exercise on bone strength and metabolism in VLBW premature infants. Sixteen infants (mean +/- standard error of the mean birth weight 1,009 +/- 55 g and gestational age 27.3 +/- 0.3 weeks) were randomly assigned into exercise (n = 8) and control (n = 8) groups. The intervention started at the first week of life and involved 8 weeks of daily passive extension and flexion range-of-motion exercise of the upper and lower extremities. Biochemical markers of bone turnover were measured at enrollment and after 8 weeks. Bone strength was measured weekly by quantitative ultrasound measurement of tibial bone speed of sound (SOS). Bone SOS decreased significantly in the control group (-108.1 +/- 33.7 m/second, P < 0.0001) during the study period, while remaining stable in the exercise group (11.3 +/- 22.8 m/second). The main beneficial effect of exercise occurred in the first 4 weeks of the intervention. There were no significant differences in the bone turnover marker changes between the groups. There is a significant postnatal decrease in bone SOS in VLBW preterm infants. Eight weeks of assisted range-of-motion exercise attenuates the decrease in bone strength and may decrease the risk of osteopenia in premature infants.

Objective: Bone strength in infants of mothers with gestational diabetes mellitus (IGDM) was reported to be either decreased or unaltered. However, no report using quantitative ultrasound measurement of speed of sound (QUS-SOS) for bone strength assessment has been published. The aim of the present study was to assess bone strength by QUS-SOS measurements in IGDM in comparison to healthy matched full-term infants. Design: Nineteen IGDM and 18 healthy controls participated in the study. Postnatal tibial bone SOS was measured by Sunlight Omnisense. Results: Mean birth weight (BW) of IGDM (3,587.6 ′ 148.6 g) was higher compared to the control infants (3,311.1 ′ 74.5 g), but this difference was not statistically significant. Mean bone SOS was significantly lower in IGDM (2,976.7 ′ 27.2 m/sec) compared to the control infants (3,093.3 ′ 23.6 m/sec; p

Hemoglobin Taybe is an unstable alpha-chain hemoglobin variant caused by a deletion of a threonine residue at codon 38 or 39 of the alpha-1 globin chain. We describe preterm infant triplets born with hydrops fetalis and anemia who were found by DNA analysis to be homozygous for hemoglobin Taybe. All three infants developed intrauterine hemolytic anemia, which subsequently led to hydrops fetalis. To the best of our knowledge, this is the first description of hydrops fetalis associated with this hemoglobinopathy. We suggest that hemoglobin Taybe be considered in the differential diagnosis of hydrops fetalis and that known affected fetuses be carefully followed both antenatally and postnatally.

Late-onset sepsis (occurring after the first three days of life) is a serious complication in preterm infants. In order to assess the possible prognostic virtues of the acute phase inflammatory response in the disease, we compared the inflammatory response of preterm infants who died within 72 hours (h) (fulminant sepsis) to infants who recovered from the disease (non-fulminant sepsis).Of 42 preterm infants that were evaluated: 10 had fulminant sepsis and 32 non-fulminant sepsis. Acute phase inflammatory response markers-C-reactive protein (CRP), serum amyloid A (SAA), interleukin (IL)-6 levels and white blood cell (WBC) counts were measured at the first suspicion of LOS and after 8, 24 and 48 h.Small for gestational age (SGA) infants who were treated with fewer days of antibiotics characterized the fulminant sepsis group. The initial high levels of inflammatory markers were similar in both groups, but as early as 8 h after onset significantly lower levels of SAA, CRP and WBC counts were documented in the fulminant sepsis group. The inflammatory response remained low at 24 and 48 h in the fulminant sepsis group, while in the survivors, significantly increased inflammatory markers were measured. Decreases in the levels of the inflammatory markers preceded episodes of metabolic acidosis and arterial hypotension that were more common in the fulminant sepsis group. Infant mortality correlated inversely with SAA levels at 8 h and with CRP and WBC counts at 24 h after onset.SAA, CRP and WBC counts can be used as prognostic markers in LOS in preterm infants, with SAA being the earliest prognostic marker.

OBJECTIVE To determine the association between changes in bone turnover markers and bone strength of very low birth weight infants during the first eight postnatal weeks. STUDY DESIGN Twelve very low birth weight premature infants [mean gestational age: 28.4 +/- 0.6 weeks, mean birth weight: 1131 +/- 62 grams] participated in the study. Bone strength was evaluated weekly by quantitative ultrasound measurements of tibial bone speed of sound (SOS, Sunlight Omnisense). Bone specific alkaline phosphatase (BSAP), a marker of bone formation, and carboxy terminal cross-links telopeptide of type-I collagen (ICTP), a marker of bone resorption, were collected at the ages of one, four and eight weeks. RESULTS BSAP increased significantly (from 119.9 +/- 16.2 U/L to 132.1 +/- 11.9 U/L and 152.1 +/- 15.7 U/L at one, four and eight weeks of life, respectively, p

Objective. To evaluate the effect of early range-of-motion intervention on bone strength and bone turnover in very low birth weight infants. Methods. Twenty-four infants (mean birth weight: 1135 ± 247 g; mean gestational age: 28.5 ± 2.3 weeks) were matched for gestational age and birth weight and then randomly assigned into exercise (n = 12) and control (n = 12) groups. Exercise protocol started at the first week of life and involved daily extension and flexion range of motion against passive resistance of the upper and lower extremities (5 minutes per day, 5 days per week, 4 weeks). Growth parameters, bone strength, and biochemical markers of bone homeostasis were measured at enrollment and after 4 weeks. Bone strength was determined using quantitative ultrasound measurement of bone speed of sound (SOS) at the middle left tibial shaft. Results. Bone SOS decreased significantly in the control group during the study period (from 2892 ± 30 m/sec to 2799 ± 26), whereas bone SOS of the exercise group remained stable (2825 ± 32 m/sec and 2827 ± 26 m/sec at baseline and 4 weeks, respectively). This significant difference in bone SOS was not expressed in the biochemical markers of bone homeostasis. Conclusions. There is a significant postnatal decrease in the bone SOS of very low birth weight infants. A brief range-of-motion exercise attenuates the decrease in bone strength and may decrease the risk of osteopenia.

Neonatal sepsis is very common in preterm infants, and severe morbidity during the neonatal period is a major cause of osteopenia of prematurity. We examined the effect of neonatal sepsis on bone turnover markers in premature infants. Twenty-four premature infants participated in the study. Ten of the premature infants developed sepsis during their hospitalization in the neonatal intensive care unit (mean gestational age [GA] 27.3 +/- 0.4 weeks; mean birth weight [BW] 898 +/- 82 g). Fourteen infants who did not develop sepsis served as controls (GA: 26.8 +/- 0.8 weeks, BW: 892 +/- 66 g). Blood samples for bone turnover markers were collected during the initial sepsis workup, and at the end of the first week of treatment, and were compared to the corresponding weekly changes in bone markers in the controls. In addition, samples were collected at the end of the 10th week of life to determine long-term effects of sepsis on bone turnover. Bone osteoblastic activity was assessed by measurements of circulating osteocalcin, bone-specific alkaline phosphatase (BSAP) and the C-terminal procollagen peptide (PICP) levels. Bone resorption was assessed by measurements of circulating carboxy terminal cross-links telopeptide of type I collagen (ICTP). There were no significant differences in the weekly changes of all bone turnover markers in premature infants who developed or did not develop sepsis. No significant differences were found in bone turnover markers at the age of 10 weeks between the groups. Neonatal sepsis in premature infants was not associated with biochemical evidence of reduced bone turnover.

OBJECTIVE: Determination of bone strength of lower extremities in very low birth weight (VLBW) premature infants with central nervous system pathology resulting in reduced unilateral spontaneous leg movements. STUDY DESIGN: Quantitative ultrasound (QUS) measurements of speed of sound (SOS) of the tibiae of both legs in three VLBW premature infants with brain insult and unilateral reduced spontaneous activity. Results were compared to QUS measurements of both legs in healthy premature infants. Measurements were performed by the same investigator who was blinded to the clinical course of the participants. RESULTS: Reduced spontaneous activity of one leg due to brain pathology resulted in decreased tibial SOS in the affected side. There was no difference in bone SOS between the legs of the healthy controls. CONCLUSION: Spontaneous movements (mainly antigravity flexion and extension) are important for bone structure and mineralization in VLBW premature infants. QUS may become an important diagnostic modality for the evaluation, treatment, and follow-up of bone strength and osteopenia in this unique population.

In order to evaluate serum amyloid A as an early diagnostic marker of late-onset sepsis, seventy-nine preterm infants with clinically suspected sepsis and 40 healthy matched controls were assayed for serum amyloid A. In parallel, clinical and biochemical variables that are used to evaluate neonatal sepsis were compared. Forty-two episodes were diagnosed as sepsis. Serum amyloid A levels were elevated in the sepsis group (187.6 +/- 78.3 micrograms/ml), compared with infants who had no sepsis (10.2 +/- 8.3 micrograms/ml) and the control group (6.9 +/- 3.3 micrograms/ml), and were significantly higher in gram-negative compared to gram-positive sepsis (221.8 +/- 84.4 micrograms/ml vs. 48.5 +/- 22.2 micrograms/ml). Analysis of the data suggests serum amyloid A has the highest sensitivity (100%), specificity (93%) and positive predictive value (96%) for sepsis among the clinical and biochemical parameters that were tested. In conclusion, serum amyloid A seems to be a reliable early marker for the diagnosis of late-onset sepsis in preterm infants.

We describe a patient diagnosed with lethal perinatal hypophosphatasia with a unique clinical presentation of convulsions that responded to vitamin B6. Genomic DNA sequence analysis of the tissue-nonspecific alkaline phosphatase (TNSALP) gene revealed two missense mutations: a G-to-A transition resulting in a Glu to Lys at codon 274 (E274K), and a G-to-C transversion resulting in a Gly to Arg at codon 309 (G309R). The first mutation was maternally transmitted and was previously characterized as a moderate one, whereas the latter was paternally transmitted and has not been previously reported. Phenotype/genotype correlation indicates that G309R is a deleterious mutation that can lead to seizures and a lethal outcome, as was demonstrated in our patient.

We describe three unrelated cases of Wiedemann-Beckwith syndrome (WBS). Two of them were diagnosed postnatally while the third was detected during pregnancy that resulted in elective termination. Amniotic karyotypes were normal in all. PCR amplification of polymorphic loci mapping to 11p15.5 region documented partial trisomy of 11p15.5 due to paternal translocation in one, and segmental and mosaic segmental unipaternal disomy (UPD) in the second and third cases, respectively. Based on findings documented in these cases and the literature, we tabulated the anomalies that might be detected prenatally by ultrasound and that may suggest the syndrome. Constant findings included fetal overgrowth, polyhydramios, enlarged placenta, and specifically a distended abdomen. As most described signs developed after 22 weeks of gestation, a careful follow-up should be carried on until late stages of pregnancy. An amniotic karyotype might not detect subtle chromosomal rearrangements. We therefore recommend utilizing PCR of polymorphic loci on 11p15.5, in addition to conventional cytogenetic analysis of the fetus and both parents to detect possible maternal deletions or inversions, paternal duplications, and UPD that may account for the largest subset of sporadic WBS reaching 25% of cases. An early diagnosis of WBS is important for counseling the parents concerning potential risk for developing embryonic tumors, selection of the mode of delivery due to potential adrenal cysts that might bleed during labor, and prevention of neonatal hypoglycemia.

We report a case of Dubin-Johnson Syndrome in a neonate presenting with severe direct hyperbilirubinemia, which failed to respond to phenobarbital treatment. Ursodeoxycholic Acid added to therapy was well tolerated, and resulted in declining bilirubin concentration. We suggest ursodeoxycholic acid in treatment for Dubin-Johnson Syndrome with severe direct hyperbilirubinemia presenting in the neonatal age.

Acinetobacter is one of the organisms responsible for nosocomial infections in intensive care, neurosurgery, burn and hemodialysis units. There are only a few reports on Acinetobacter infections in neonatal intensive care units. Over a 31 month period, nine cases of Acinetobacter sepsis occurred in our unit, with four deaths. There was a cluster of four cases within 3 days. In this study the English literature on this pathogen is reviewed and it is suggested that Acinetobacter should be added to the list of organisms causing severe nosocomial infection in neonatal intensive care units.

We determined the levels of circulating bone turnover markers in preterm infants during the first weeks of life. Twenty premature infants (mean gestational age 27+/-2.2 weeks, mean birth weight 894+/-231 g) hospitalized in the neonatal intensive care unit (NICU) at the Meir General Hospital, Israel, participated in the study. Measurements of bone turnover markers were performed at birth, and every week thereafter for an average follow-up of 11.2+/-0.7 weeks. Bone osteoblastic activity was assessed by measurements of circulating osteocalcin, bone-specific alkaline phosphatase (BSAP) and the C-terminal procollagen peptide (PICP) levels. Bone resorption was assessed by measurements of serum levels of the carboxy-terminal cross-links telopeptide of type I collagen (ICTP). All three markers of osteoblastic activity increased markedly and significantly during the first three weeks of life, and then continued to increase gradually until week 10 (p

Reported herein are the cases of three infants who were born with serious intrathoracic injuries, apparently sustained at the time of the mother's involvement in a motor vehicle accident. The accidents occurred at 26th, 29th and 36th weeks of pregnancy and resulted in minimal injuries to the mothers themselves. The infants were born four weeks, three hours and two days later, respectively. Their injuries were manifested (singly) by hemothorax, pneumothorax and contusion of lung, the latter in a setting of multi-organ trauma. We suggest that chest x-ray, in addition to brain ultrasound, be routinely included in the evaluation of neonates whose mothers were involved in a motor vehicle accident during pregnancy, not excluding cases wherein the mother's injuries were negligible or inapparent and regardless of the time elapsed between accident and delivery.

Acute renal failure was diagnosed within 6 days of birth in a full-term neonate. The mother was known to have a monoclonal gammopathy, immunoglobulin G (IgG) lambda, discovered a year before pregnancy on being investigated for hematuria and proteinuria. Her renal function was intact. Maternal renal biopsy performed at the time showed a focal proliferative glomerulonephritis with nonfibrillary homogeneous mesangial and intramembranous electron-dense deposits. Immunoperoxidase staining was positive for IgG and lambda and kappa light chains along the glomerular and tubular basement membranes. Pregnancy was uneventful. Protein electrophoresis and immunofixation of the infant girl's serum and urine samples showed the presence of a paraprotein electrophoretically identical to that found in the mother. Exchange transfusion resulted in a rapid improvement of renal function in parallel to the disappearance of the monoclonal component.

Vascular trauma from accidental or iatrogenic causes is becoming more common in children. In early infancy, the most common arterial injuries are caused by diagnostic or interventional cardiac catheterizations. Doppler arterial pressure measurements and the computed ankle-brachial pressure index (ABI) are the most helpful diagnostic modalities in the assessment and follow-up of the ischemic extremity. Because normative ABI data in small children are not available, an ABI of 0.9 or less (based on data obtained from an adult population), is used to indicate limb ischemia in young infants. The purpose of this study was to define the normal values of ABI in newborns and infants.Three hundred and fifty patients were divided into two groups: group 1 (n = 200; male-to-female ratio, 1:1) were full-term (gestational age 40 +/- 1.3 weeks, surface area 0.22 +/- 0.02 m2) healthy newborns following uneventful pregnancy and delivery. Group 2 (n = 150) were healthy patients aged 2 weeks to 2.5 years admitted for elective hernia repair. All the patients underwent a complete physical examination, which excluded any cardiovascular pathology. The systolic blood pressure (BP) was measured bilaterally over the brachial, tibialis posterior, and dorsalis pedis arteries. All BP data were obtained in the supine position, using an ultrasonic Doppler flow detector, an appropriately-sized pneumatic cuff and a sphygmomanometer. The chosen cuff size was long enough to completely encircle the circumference and wide enough to cover 75% of the length of the upper arm. The same cuff was applied around the ankle above the malleoli. BP values were expressed as mean +/- SD in mm Hg. If there was a difference between the BP in the two arms, the higher pressure was used for calculation of the ABI.The BP measurements in newborns (group 1) were left brachial, 98 +/- 11; right brachial, 90 +/- 10 (P.001), left and right tibialis posterior and left and right dorsalis pedis were 83, 81, 84, and 82 mm Hg, respectively. The mean computed ABI was 0.88 +/- 0.11. Fifty eight percent of the newborns had an ABI less than 0.9 (lower limit of normal in adults). The ABI values in patients belonging to group 2 increased with age and surface area. The mean ABI was 1.0, 1.1, and more than 1.1 in patients aged, 1, 1.5, and 2 years with surface areas of 0.4, 0.5 and 0.6 m2, respectively (P.001 compared with group 1).The normative ABI in newborns and infants is significantly lower than in older children and reaches normal (adult) values during the second year of life. These data may be used as a reference when assessing lower extremity ischemia caused by trauma in young patients.

We describe a preterm neonate with documented group B Streptococcus sepsis and associated metabolic acidosis whose lactic acidemia was refractory to conventional sodium bicarbonate therapy but responded well to dichloroacetate treatment.

A huge pericardial effusion was diagnosed during fetal ultrasound examination performed in the 42nd week of pregnancy on a healthy 25-year-old woman. Immediately after the birth, a two-dimensional echocardiogram confirmed this finding in the infant, and an intrapericardial kidney-shaped solid mass measuring 45 × 56 × 15 mm, completely surrounded by pericardial effusion, was visualized to the left part of the heart. The heart was normal. No signs of cardiac tamponade were seen. At the age of two days, the mass was surgically resected and the pericardial fluid evacuated. Microscopic examination revealed that the mass was formed totally of normal lung tissue surrounded by normal pleura. To the best of our knowledge, this is the first case of intrapericardial extralobar sequestration consisting of an accessory lung with completely normal lung tissue. EPS = extralobar pulmonary sequestration

A total of 95 preterm infants, delivered consecutively in a perinatal center, over a 9-month period, were studied serially with real-time ultrasound for detection of subependymal/intraventricular hemorrhage (SEH/IVH); all infants were less than or equal to 32-week gestation and/or less than or equal to 1500 gm birthweight. Detailed statistical analysis was carried out to determine the influence of perinatal factors on the occurrence of SEH/IVH. The incidence of SEH/IVH was 34%; severe hemorrhage (Grade III-IV) occurred in only 13%. Gestational age was an important factor associated with SEH/IVH. Thus, the incidence in infants less than or equal to 29-weeks gestation was 45%, whereas in infants greater than 29-weeks gestation age, it was 19% (p less than 0.01). The overall incidence of SEH/IVH in the group which was less than or equal to 29-weeks gestation and delivered by cesarean section was 53%, whereas in those infants delivered vaginally it was 47%. In infants whose gestational age was less than or equal to 29-weeks, the incidence of hemorrhage was 47% if delivered vaginally and presenting as a vertex and 31% if delivered by cesarean section. In infants greater than 29-weeks gestation, the incidence of SEH/IVH was 42% in those delivered by the vaginal vertex route, 5% if presentation was vertex and delivered by cesarean section (p less than 0.05). In infants greater than 29-weeks gestation, cesarean section in vertex presentation decreased the incidence of SEH/IVH when compared with vaginal vertex delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Periventricular leukomalacia is an ischemic lesion in periventricular white matter of premature infants. Hemorrhage into the ischemic area occurs in up to 25% of cases. We report two cases in which the diagnosis of periventricular leukomalacia was made during life with real-time ultrasound scanning. In one case, serial scans demonstrated the evolution of echodense regions, observed in the first 3 days of life, to cystic echolucent areas at 4 weeks. In the second case, periventricular echodense areas did not precede the occurrence of cystic echolucent lesions. This may reflect a more chronic ischemic cerebral insult (consistent with recurrent apnea and bradycardia) rather than a presumed acute episode of cerebral ischemia (with or without secondary hemorrhage) sustained by the first case. Real-time ultrasound scanning is a simple, non-invasive technique with which to document the evolution of periventricular leukomalacia, and thus to define the clinical neurological correlates in the neonatal period.