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Objective: To evaluate the yield of work-up in intrauterine growth restriction (IUGR) pregnancies and their outcomes., Materials and Methods: Retrospective data regarding prenatal work-up (serology, genetic testing and imaging), and neonatal outcomes of 198 IUGR pregnancies (estimated fetal weight <10th percentile) were analyzed., Results: IUGR was isolated in 72 cases. Work-up performed in 158 (80%) cases was positive in 4 (2.5%). No abnormalities were detected in prenatal genetic testing. Echocardiogram performed in 27 cases was abnormal in 3 (11.1%). Serological testing performed in 150 pregnancies (75.8%) detected 1 case (0.7%) of cytomegalovirus (CMV) infection. Thirteen neonates (6.5%) were diagnosed with significant health problems. A positive work-up and significant postnatal health problems were not correlated with IUGR severity, symmetry or additional concurrent findings., Conclusion: The yield of IUGR work-up is not clear and is probably highest for fetal echocardiography. The rate of significant adverse outcomes after birth is increased in IUGR pregnancies.

Aim: To evaluate the possible association between major neonatal morbidities and poor head growth from birth to discharge home in very-low-birthweight (VLBW) infants born preterm., Method: Population-based observational study comprising 12 992 infants (6340 male, 6652 female) of 24 to 32 weeks' gestation, and birthweight ≤1500g. Severe head growth failure (HGF) was defined as a decrease in head circumference z-score >2 z-scores, and moderate HGF as a decrease of 1 to 2 z-scores. Multinomial logistic regression analysis was applied to determine morbidities associated with HGF., Results: Severe HGF occurred in 4.5% and moderate HGF in 20.9% of infants. Each unit increase in head circumference z-score at birth was associated with increased odds for severe and moderate HGF (odds ratios [OR] 5.29, 95% confidence intervals [CI] 4.67-6.00, and OR 2.38, 95% CI 2.23-2.54 respectively). Both severe and moderate HGF were associated with respiratory distress syndrome (OR 2.03, 95% CI 1.58-2.62, and OR 1.66, 95% CI 1.48-1.85 respectively); bronchopulmonary dysplasia (OR 3.38, 95% CI 2.33-4.91, and OR 1.87, 95% CI 1.52-2.30 respectively); necrotizing enterocolitis (OR 2.89, 95% CI 2.04-4.09, and OR 1.72, 95% CI 1.38-2.16 respectively), and sepsis (OR 2.06, 95% CI 1.69-2.50, and OR 1.38, 95% CI 1.24-1.53 respectively)., Interpretation: Major neonatal morbidities were associated with HGF in VLBW infants born preterm. Identification of whether this is a direct effect of these morbidities or mediated through nutritional or growth factors may enable interventions to improve postnatal head growth of infants born preterm., (© 2016 Mac Keith Press.)

We aimed to assess whether a twice daily assisted exercise interventional program will have a greater effect on bone strength compared to a once daily intervention or no intervention in very low birth weight (VLBW) preterm infants. Thirty-four very VLBW preterm infants (mean BW 1217 ± 55 g and mean gestational age 28.6 ± 1.1 weeks) were randomly assigned into one of three study groups: twice daily interventions (n = 13), a once daily intervention (n = 11), and no intervention (control, n = 10). The intervention was initiated at a mean of 8 ± 2.4 days of life and continued for 4 weeks. It included passive extension and flexion range-of-motion exercise of the upper and lower extremities. Bone strength was measured at enrollment and after 2 and 4 weeks using quantitative ultrasound of tibial bone speed of sound (SOS, Sunlight Omnisense™). At enrollment, the mean bone SOS was comparable between the twice daily interventions, once daily intervention and control groups (2918 ± 78, 2943 ± 119, and 2910 ± 48 m/s, respectively). As expected, the bone SOS declined in all groups during the study period (-23.6 ± 24, -68.8 ± 28, and -115.8 ± 30 m/s, respectively, p < 0.05), with a significantly attenuated decrease in bone strength in the twice daily intervention group (p = 0.03). A twice daily intervention program of assisted range-of-motion exercise attenuates the decrease in bone strength and may decrease the risk of osteopenia and future fractures in VLBW preterm infants.

Background: Pregnancy-induced hypertension (PIH) has been associated with a decreased risk of infant mortality in small for gestational age (SGA) preterm infants., Objective: To evaluate the influence of PIH on mortality and major neonatal morbidities in singleton preterm SGA infants, in the presence and absence of acute pregnancy complications., Methods: Population-based observational study of singleton SGA infants, born at 24 to 32 weeks gestation in the period 1995-2010 (n = 2139). Multivariable logistic regression analyses were used to assess the independent effect of PIH on mortality and neonatal morbidities. Acute pregnancy complications comprised premature labor, premature rupture of membranes >6 h, antepartum hemorrhage and clinical chorioamnionitis., Results: In the absence of pregnancy complications, the odds ratio (95% confidence interval) for mortality (0.77; 0.50-1.16), survival without severe neurological morbidity (1.14; 0.79-1.65) and survival without bronchopulmonary dysplasia (BPD) (0.85; 0.59-1.21) were similar in the PIH versus no-PIH groups. In the presence of pregnancy complications, mortality (0.76; 0.40-1.44), survival without severe neurological morbidity (1.16; 0.64-2.12) and survival without BPD (1.04; 0.58-1.86) were also similar in the PIH versus no-PIH groups., Conclusions: PIH was not associated with improved outcome in preterm SGA infants, both in the presence and absence of acute pregnancy complications.

Background: Beta-palmitate (sn-2 palmitate) mimics human milk fat, enabling easier digestion.Therefore, we hypothesized that infants consuming high beta-palmitate formula would have more frequent, softer stools and reduced crying compared to infants consuming low beta-palmitate formula., Methods: Formula-fed infants were randomly assigned to receive either (1) formula with high beta-palmitate (HBP, n = 21) or (2) regular formula with a standard vegetable oil mix (LBP, n = 21). A matched group of breastfed infants served as a reference (BF, n = 21). Crying and stool characteristics data were recorded by the parents for 3 days before the 6- and 12-week visits., Results: We found no significant differences in the stool frequency or consistency between the two formula groups. The percentage of crying infants in the LBP group was significantly higher than that in the HBP and BF groups during the evening at 6 weeks (88.2% vs. 56.3% and 55.6%, p < 0.05) and during the afternoon at 12 weeks (91.7% vs. 50.0% and 40%, p < 0.05). The infants fed HBP had significantly shorter crying durations when compared with infants fed LBP formula (14.90 ± 3.85 vs.63.96 ± 21.76 min/day, respectively; p = 0.047)., Conclusions: Our study indicates that consumption of a high beta-palmitate formula affects infant crying patterns during the first weeks of life. Comparable to breastfeeding, it reduced crying duration and frequency, primarily during the afternoon and evening hours, thereby improving the well-being of formula-fed infants and their parents., Trial Registration: NCT00874068.Registration date March 31, 2009.

Objective: To examine the effect of initiating very early feeding on time-to-reach full feeding in stable, small for gestational age (SGA) preterm infants., Method: Preterm infants with gestational age below 37 weeks and birth weight below the 10(th) percentile were randomly allocated to a very early (within 24 hours of birth) feeding regimen or delayed (after 24 hours of birth) feeding. All infants had in utero evidence of absent or reverse diastolic flow. Infants unable to start early feeding were excluded. Time-to-reach full feeding, feeding progression, and related morbidity were compared. Electrogastrography (EGG) was used to measure pre- and postprandial gastric motility on the second and seventh day after feeding initiation., Results: Sixty infants were included in the study, 30 in each group. Infants included in the very early feeding regimen achieved full enteral feeding sooner than controls (98±80-157 vs. 172±123-261 hours of age, respectively; p= 0.004) and were discharged home earlier (p=0.04). No necrotizing enterocolitis (NEC) was documented in both study groups. Gastric motility was improved at day seven after feeding initiation in both study groups, with no difference between groups., Conclusions: Stable SGA preterm infants on a very early feeding regimen achieved full enteral feeding and were discharged home significantly earlier than those on a delayed regimen, with no excess morbidity., (Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

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.

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.

Premature infants born with IUGR are at a several-fold increased risk for mortality and major neonatal morbidities, including RDS, BPD, ROP, and NEC. These severe complications of prematurity are intensified by the effect of suboptimal fetal growth. The possible pathophysiologic processes initiated in utero and continuing after birth have been discussed. Recently reported data suggest that IUGR is a risk factor in programming for the later development of cardiovascular diseases, hypertension, and diabetes mellitus in adult life. Experimental research related to the pathophysiology and etiology of these conditions may enable appropriate intervention directed at reducing the excess risk associated with the short- and long-term mortality and morbidity among premature SGA 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 <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.

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: 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.

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.