High Beta-palmitate formula and bone strength in term infants: a randomized, double-blind, controlled trial.

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.

Combining kangaroo care and live harp music therapy in the neonatal intensive care unit setting.

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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, P < 0.01). 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). CONCLUSIONS: 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.

Continuous lumbar/thoracic epidural analgesia in low-weight paediatric surgical patients: practical aspects and pitfalls.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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).

Vitamin E levels during early iron supplementation in preterm infants.

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.

Enriched post-discharge formula versus term formula for bone strength in very low birth weight infants: a longitudinal pilot study.

AIM: 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. METHODS: 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. RESULTS: 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 (P<0.001). 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 (P<0.001). 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 (P<0.001 for both groups). CONCLUSION: Feeding with PDF after term had no short-term beneficial effect on bone strength and bone turn-over of VLBW infants.

The efficacy and safety of early supplementation of iron polymaltose complex 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.

Live music is beneficial to preterm infants in the neonatal intensive care unit environment.

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 > or = 32 weeks, weight > or = 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 < 0.001). Recorded music and no music therapies had no significant effect on any of the tested parameters during all intervals. Both medical personnel and parents preferred live music therapy to recorded music and no music therapies; however, parents considered live music therapy significantly more effective than the other therapies. CONCLUSIONS: Compared with recorded music or no music therapy, live music therapy is associated with a reduced heart rate and a deeper sleep at 30 minutes after therapy in stable preterm infants. Both recorded and no music therapies had no significant effect on the tested physiological and behavioral parameters.

Bacillus species sepsis in the neonatal intensive care unit.

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.

High maternal estriol level in pregnancy as a predictor of surgical intervention for undescended testis.

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.

Breakthrough candida Infection in a preterm infant with congenital cutaneous Candida albicans infection.

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.

Serum amyloid A protein is a useful inflammatory marker during late-onset sepsis in preterm infants.

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 mug/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.

Bone speed of sound in infants of mothers with gestational diabetes mellitus.

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 <0.003). There was a significant negative correlation between bone SOS and BW in all the study participants (r = -0.32, p <0.025). No significant difference in BW and bone SOS was noted between infants with postnatal hypoglycemia and normoglycemia. There was no correlation between maternal HbA1c during pregnancy and neonatal bone SOS. CONCLUSIONS: Bone strength was significantly decreased in IGDM compared to healthy controls. Neonates with higher BW had lower bone SOS. Since mechanical strain is a potent stimulation for bone formation and strength, it is suggested that the reduced bone strength in IGDM may also be the result of reduced intrauterine fetal mobility due to maternal gestational diabetes mellitus.

Hydrops fetalis associated with homozygosity for hemoglobin Taybe (alpha 38/39 THR deletion) in newborn triplets.

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.

The prognostic virtue of inflammatory markers during late-onset sepsis in preterm infants.

AIM: 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). METHODS: 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. RESULTS: 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. CONCLUSION: SAA, CRP and WBC counts can be used as prognostic markers in LOS in preterm infants, with SAA being the earliest prognostic marker.

Bone turnover markers and bone strength during the first weeks of life in very low birth weight premature infants.

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<0.05). ICTP decreased significantly during the study period (from 122.3 +/- 8.7 ng/ml to 96.0 +/- 4.8 ng/ml and 92.3 +/- 5.4 ng/ml at one, four and eight weeks of life, respectively; p<0.05). There was a significant decrease in bone SOS (from 2886 +/- 29 m/sec to 2792 +/- 30 m/sec and 2753 +/- 30 m/sec at birth, four weeks and eight weeks of life, respectively; p<0.02). There was no correlation between the levels of bone markers and bone SOS. CONCLUSION: In VLBW premature infants, there is a significant decrease in bone strength concomitant with biochemical evidence for new bone formation (increase in BSAP and a decrease in ICTP) during the first eight postnatal weeks. Changes in the biochemical markers could not predict the changes in bone strength.

Excess mortality and morbidity among small-for-gestational-age premature infants: a population-based study.

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.

Early physical activity intervention prevents decrease of bone strength in very low birth weight infants.

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.

Urinary tract infection in very low birth weight preterm infants.

BACKGROUND: The prevalence of urinary tract infection (UTI) in preterm neonates ranges between 4 and 25%. The need for a radiologic investigation has not yet been established in very low birth weight premature newborns (<1500 g birth weight). PATIENTS AND METHODS: For an 11-year period (1990 to 2001), medical records of 62 very low birth weight premature infants admitted to a Level III neonatal intensive care unit and who developed UTI were reviewed retrospectively. Results of renal ultrasound and voiding cystourethrograms were compared between extremely low birth weight infants (birth weight, <1000 g) (Group A, Patient 34) and premature infants with birth weight between 1001 and 1500 g (Group B, Patient 28). RESULTS: UTI was more common in Group A (12.2%) than in Group B (5.7%) infants. Renal ultrasound detected mild renal pelvic dilatation (unilateral or bilateral) in 9 infants in Group A (26%) and in 1 infant in Group B (3.5%). Voiding cystourethrograms were performed in 26 of 34 (76%) infants in Group A and in 17 of the 28 (61%) premature infants in Group B. Vesicourethral reflux (VUR) was observed in 6 infants, 2 in group A (7.7%) and 4 in Group B (23%). CONCLUSIONS: We found that the rate of VUR was lower in very low birth weight premature newborns than that reported in the medical literature among term newborns who developed UTI. VUR was less frequent in extremely low birth weight infants who developed UTI than in infants weighing 1001 to 1500 g.