Anetoderma is a skin disorder characterized by focal loss of elastic tissue in the mid dermis, resulting in localized areas of macular depressions or pouchlike herniations of skin. An iatrogenic form of anetoderma has been rarely described in extremely premature infants and has been related to the placement of monitoring devices on the patient skin. Because of the increasing survival of extremely premature infants, it is easy to foresee that the prevalence of anetoderma of prematurity will increase in the next future. Although it is a benign lesion, it persists over time and can lead to significant aesthetic damage with need for surgical correction. Sometimes the diagnosis can be difficult, especially when the atrophic lesions become evident after discharge. Here, we report on a premature infant born at 24 weeks of gestation, who developed multiple anetodermic patches of skin on the trunk at the sites where electrocardiographic electrodes were previously applied. The knowledge of the disease can encourage a more careful management of the skin of extremely premature babies and aid the physicians to diagnose the disease when anetoderma patches are first encountered later in childhood.
Pre-term infants who develop bronchopulmonary dysplasia (BPD) are at risk of postnatal growth failure. It has been reported that energy expenditure is higher in infants with BPD than in those without BPD. The aim of the study was to evaluate whether increasing the enteral energy intake of pre-term infants with BPD can improve post-natal growth.
This prospective, non-randomised interventional cohort study was designed to assess growth in 57 preterm infants with BPD (gestational age <32 weeks, birth weight <1500 g, and persistent oxygen dependency for up to 28 days of life) fed individually tailored fortified breast milk and/or preterm formula, and a historical control group of 73 pre-term infants with BPD fed breast milk fortified in accordance with the instructions of the manufacturer and/or pre-term formula. Between-group differences in the continuous variables were analysed using Student’s t test or the Mann-Whitney test; the discrete variables were compared using the chi-squared test. Linear regression analysis was used to investigate the independent contribution of enteral energy intake to weight gain velocity.
The duration of parenteral nutrition was similar in the historical and intervention groups (43.7 ± 30.9 vs 39.6 ± 17.4 days). After the withdrawal of parenteral nutrition, enteral energy intake was higher in the infants in the intervention group with mild or moderate BPD (131 ± 6.3 vs 111 ± 4.6 kcal/kg/day; p < 0.0001) and in those with severe BPD (126 ± 5.3 vs 105 ± 5.1 kcal/kg/day; p < 0.0001), whereas enteral protein intake was similar (3.2 ± 0.27 vs 3.1 ± 0.23 g/kg/day).
Weight gain velocity was greater in the infants in the intervention group with mild or moderate BPD (14.7 ± 1.38 vs 11.5 ± 2 g/kg/day, p < 0.0001) and in those with severe BPD (11.9 ± 2.9 vs 8.9 ± 2.3 g/kg/day; p < 0.007). The percentage of infants with post-natal growth retardation at 36 weeks of gestational age was higher in the historical group (75.3 vs 47.4; p = 0.02).
On the basis of the above findings, it seems that improved nutritional management promotes post-natal ponderal growth in pre-term infants with BPD.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2431-14-235) contains supplementary material, which is available to authorized users.
Pre-term infants; Bronchopulmonary dysplasia; Growth; Nutrition
Identifying single nucleotide polymorphisms (SNPs) in the genes involved in sepsis may help to clarify the pathophysiology of neonatal sepsis. The aim of this study was to evaluate the relationships between sepsis in pre-term neonates and genes potentially involved in the response to invasion by infectious agents. The study involved 101 pre-term neonates born between June 2008 and May 2012 with a diagnosis of microbiologically confirmed sepsis, 98 pre-term neonates with clinical sepsis and 100 randomly selected, otherwise healthy pre-term neonates born during the study period. During the study, 47 SNPs in 18 candidate genes were genotyped on Guthrie cards using an ABI PRISM 7900 HT Fast real-time and MAssARRAY for nucleic acids instruments. Genotypes CT and TT of rs1143643 (the IL1β gene) and genotype GG of rs2664349GG (the MMP-16 gene) were associated with a significantly increased overall risk of developing sepsis (p = 0.03, p = 0.05 and p = 0.03), whereas genotypes AG of rs4358188 (the BPI gene) and CT of rs1799946 (the DEFβ1 gene) were associated with a significantly reduced risk of developing sepsis (p = 0.05 for both). Among the patients with bacteriologically confirmed sepsis, only genotype GG of rs2664349 (the MMP-16 gene) showed a significant association with an increased risk (p = 0.02). Genotypes GG of rs2569190 (the CD14 gene) and AT of rs4073 (the IL8 gene) were associated with a significantly increased risk of developing severe sepsis (p = 0.05 and p = 0.01). Genotype AG of rs1800629 (the LTA gene) and genotypes CC and CT of rs1341023 (the BPI gene) were associated with a significantly increased risk of developing Gram-negative sepsis (p = 0.04, p = 0.04 and p = 0.03). These results show that genetic variability seems to play a role in sepsis in pre-term neonates by influencing susceptibility to and the severity of the disease, as well as the risk of having disease due to specific pathogens.
Preterm infants are at risk for adverse neurodevelopment. Furthermore, nutrition may play a key role in supporting neurodevelopment. The aim of this study was to evaluate whether a nutrient-enriched formula fed to preterm infants after hospital discharge could improve their neurodevelopment at 24 months (term-corrected age).
We conducted an observer-blinded, single-center, randomized controlled trial in infants admitted to the Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Italy between 2009 and 2011. Inclusion criteria were gestational age < 32 weeks and/or birth weight < 1500 g, and being fed human milk for < 20% of the total milk intake. Exclusion criteria were congenital malformations or conditions that could interfere with growth or body composition. Included infants were randomized to receive a standard full-term formula or a nutrient-enriched formula up until 6 months of corrected age, using two computer-generated randomization lists; one appropriate for gestational age (AGA) and one for small for gestational age (SGA) infants. We assessed neurodevelopment at 24 months of corrected age using the Griffiths Mental Development Scale and related subscales (locomotor, personal-social, hearing and speech, hand and eye coordination, and performance).
Of the 207 randomized infants, 181 completed the study. 52 AGA and 35 SGA infants were fed a nutrient-enriched formula, whereas 56 AGA and 38 SGA infants were fed a standard full-term formula. The general quotient at 24 months of corrected age was not significantly different between infants randomized to receive a nutrient-enriched formula compared with a standard term formula up until 6 months of corrected age (AGA infants: 93.8 ± 12.6 vs. 92.4 ± 10.4, respectively; SGA infants: 96.1 ± 9.9 vs. 98.2 ± 9, respectively). The scores of related subscales were also similar among groups.
This study found that feeding preterm infants a nutrient-enriched formula after discharge does not affect neurodevelopment at 24 months of corrected age, in either AGA or SGA infants, free from major comorbidities.
Current Controlled Trials (http://www.controlled-trials.com/ISRCTN30189842) London, UK.
Preterm infants; Neurodevelopment; Nutrient-enriched formula; Post discharge nutrition
Severe hypertriglyceridemia (sHTG) (plasma triglyceride level > 10 mmol/L) due to lipoprotein lipase (LPL) deficiency is a known risk factor for acute pancreatitis. A 23-day-old male with sHTG was admitted to the Neonatal Intensive Care Unit for plasmapheresis being at high risk for acute pancreatitis. Given the potential hazard of an extracorporeal technique in a very young infant, we decided to perform an exchange transfusion (ET), a procedure widely used by neonatologists and less invasive than plasmapheresis. ET led to a dramatic reduction in plasma triglyceride level, from 93.2 to 3.8 mmol/L at the end of the procedure, without adverse events. The subsequent administration of a special formula low in fat and high in medium-chain triglycerides was effective in keeping fasting plasma triglyceride level below 5.6 mmol/L during the first 5 months of life. The sequence of LPL gene revealed that the patient was apparently homozygous for a novel nucleotide deletion (c.840delG) in exon 6 leading to a premature termination codon (p.N281Mfs*23). However, family studies revealed that while the patient’s mother was heterozygous for this mutation, the father was heterozygous for a novel deletion eliminating the whole LPL gene. The patient therefore turned out to be a compound heterozygous for two LPL gene mutations predicted to abolish LPL activity. This is the first case of sHTG treated with ET in a neonate reported in the literature. ET appears to be a safe procedure, alternative to plasmapheresis, to prevent acute pancreatitis in young infants with sHTG due to LPL deficiency.
Activated lymphocytes release nano-sized vesicles (exosomes) containing microRNAs that can be monitored in the bloodstream. We asked whether elicitation of immune responses is followed by release of lymphocyte-specific microRNAs. We found that, upon activation in vitro, human and mouse lymphocytes down-modulate intracellular miR-150 and accumulate it in exosomes. In vivo, miR-150 levels increased significantly in serum of humans immunized with flu vaccines and in mice immunized with ovalbumin, and this increase correlated with elevation of antibody titers. Immunization of immune-deficient mice, lacking MHCII, resulted neither in antibody production nor in elevation of circulating miR-150. This study provides proof of concept that serum microRNAs can be detected, with minimally invasive procedure, as biomarkers of vaccination and more in general of adaptive immune responses. Furthermore, the prompt reduction of intracellular level of miR-150, a key regulator of mRNAs critical for lymphocyte differentiation and functions, linked to its release in the external milieu suggests that the selective extracellular disposal of microRNAs can be a rapid way to regulate gene expression during lymphocyte activation.
Whole-body deep hypothermia (DH) could be a new therapeutic strategy for asphyxiated newborn. This retrospective study describes how DH modified the heart rate and arterial blood pressure if compared to mild hypothermia (MH). Fourteen in DH and 17 in MH were cooled within the first six hours of life and for the following 72 hours. Hypothermia criteria were gestational age ≥36 weeks; birth weight ≥1800 g; clinical signs of moderate/severe hypoxic-ischemic encephalopathy. Rewarming was obtained in the following 6–12 hours (0.5°C/h) after cooling. Heart rates were the same between the two groups; there was statistically significant difference at the beginning of hypothermia and during rewarming. Three babies in the DH group and 2 in the MH group showed HR < 80 bpm and QTc > 520 ms. Infant submitted to deep hypothermia had not bradycardia or Qtc elongation before cooling and after rewarming. Blood pressure was significantly lower in DH compared to MH during the cooling, and peculiar was the hypotension during rewarming in DH group. Conclusion. The deeper hypothermia is a safe and feasible, only if it is performed by a well-trained team. DH should only be associated with a clinical trial and prospective randomized trials to validate its use.
Some studies have suggested that the early sustained lung inflation (SLI) procedure is effective in decreasing the need for mechanical ventilation (MV) and improving respiratory outcome in preterm infants. We planned the present randomized controlled trial to confirm or refute these findings.
In this study, 276 infants born at 25+0 to 28+6 weeks’ gestation at high risk of respiratory distress syndrome (RDS) will be randomized to receive the SLI maneuver (25 cmH2O for 15 seconds) followed by nasal continuous positive airway pressure (NCPAP) or NCPAP alone in the delivery room. SLI and NCPAP will be delivered using a neonatal mask and a T-piece ventilator.
The primary endpoint is the need for MV in the first 72 hours of life. The secondary endpoints include the need and duration of respiratory support (NCPAP, MV and surfactant), and the occurrence of bronchopulmonary dysplasia (BPD).
Trial registration number:
Sustained lung inflation; Preterm infants, Resuscitation; Delivery room; Mechanical ventilation
Prevention of postnatal growth restriction of very preterm infants still represents a challenge for neonatologists. As standard feeding regimens have proven to be inadequate. Improved feeding strategies are needed to promote growth. Aim of the present study was to evaluate whether a set of nutritional strategies could limit the postnatal growth restriction of a cohort of preterm infants.
We performed a prospective non randomized interventional cohort study. Growth and body composition were assessed in 102 very low birth weight infants after the introduction of a set of nutritional practice changes. 69 very low birth weight infants who had received nutrition according to the standard nutritional feeding strategy served as a historical control group. Weight was assessed daily, length and head circumference weekly. Body composition at term corrected age was assessed using an air displacement plethysmography system. The cumulative parenteral energy and protein intakes during the first 7 days of life were higher in the intervention group than in the historical group (530±81 vs 300±93 kcal/kg, p<0.001 and 21±2.9 vs 15±3.2 g/kg, p<0.01). During weaning from parenteral nutrition, the intervention group received higher parental/enteral energy and protein intakes than the historical control group (1380±58 vs 1090±70 kcal/kg; 52.6±7 vs 42.3±10 g/kg, p<0.01). Enteral energy (kcal/kg/d) and protein (g/kg/d) intakes in the intervention group were higher than in the historical group (130±11 vs 100±13; 3.5±0.5 vs 2.2±0.6, p<0.01). The negative changes in z score from birth to discharge for weight and head circumference were significantly lower in the intervention group as compared to the historical group. No difference in fat mass percentage between the intervention and the historical groups was found.
The optimization and the individualization of nutritional intervention promote postnatal growth of preterm infants without any effect on percentage of fat mass.
Human milk is the optimal nutrition for infants. When breastfeeding is not possible, supplementation of infant formula with long chain polyunsaturated fatty acids appears to promote neurodevelopmental outcome and visual function. Plant oils, that are the only source of fat in most of infant formulas, do not contain specific fatty acids that are present in human and cow milk and do not encounter milk fat triglyceride structure. Experimental data suggest that a mix of dairy lipids and plant oils can potentiate endogenous synthesis of n-3 long chain polyunsaturated fatty acids. This trial aims to determine the effect of an infant formula supplemented with a mixture of dairy lipids and plant oils on the erythrocyte membrane omega-3 fatty acid profile in full-term infants (primary outcome). Erythrocyte membrane long chain polyunsaturated fatty acids and fatty acids content, the plasma lipid profile and the insulin-growth factor 1 level, the gastrointestinal tolerance, the changes throughout the study in blood fatty acids content, in growth and body composition are evaluated as secondary outcomes.
In a double-blind controlled randomized trial, 75 healthy full-term infants are randomly allocated to receive for four months a formula supplemented with a mixture of dairy lipids and plant oils or a formula containing only plant oils or a formula containing plant oils supplemented with arachidonic acid and docosahexaenoic acid. Twenty-five breast-fed infants constitute the reference group. Erythrocyte membrane omega-3 fatty acid profile, long chain polyunsaturated fatty acids and the other fatty acids content, the plasma lipid profile and the insulin-growth factor 1 level are measured after four months of intervention. Gastrointestinal tolerance, the changes in blood fatty acids content, in growth and body composition, assessed by means of an air displacement plethysmography system, are also evaluated throughout the study.
The achievement of an appropriate long chain polyunsaturated fatty acids status represents an important goal in neonatal nutrition. Gaining further insight in the effects of the supplementation of a formula with dairy lipids and plant oils in healthy full-term infants could help to produce a formula whose fat content, composition and structure is more similar to human milk.
ClinicalTrials.gov Identifier NCT01611649
Full-term infants; Formula supplementation; Dairy lipids; Erythrocyte membrane omega-3 fatty acid profile
Preterm small for gestational age (SGA) infants may be at risk for increased adiposity, especially when experiencing rapid postnatal weight gain. Data on the dynamic features of body weight and fat mass (FM) gain that occurs early in life is scarce. We investigated the postnatal weight and FM gain during the first five months after term in a cohort of preterm infants.
Changes in growth parameters and FM were prospectively monitored in 195 infants with birth weight ≤1500 g. The infants were categorized as born adequate for gestational age (AGA) without growth retardation at term (GR−), born AGA with growth retardation at term (GR+), born SGA. Weight and FM were assessed by an air displacement plethysmography system. At five months, weight z-score was comparable between the AGA (GR+) and the AGA (GR−), whereas the SGA showed a significantly lower weight.The mean weight (g) differences (95% CI) between SGA and AGA (GR−) and between SGA and AGA (GR+) infants at 5 months were −613 (−1215; −12) and −573 (−1227; −79), respectively. At term, the AGA (GR+) and the SGA groups showed a significantly lower FM than the AGA (GR−) group. In the first three months, change in FM was comparable between the AGA (GR+) and the SGA groups and significantly higher than that of the AGA (GR−) group.The mean difference (95% CI) in FM change between SGA and AGA (GR−) and between AGA (GR+) and AGA (GR−) from term to 3 months were 38.6 (12; 65); and 37.7 (10; 65). At three months, the FM was similar in all groups.
Our data suggests that fetal growth pattern influences the potential to rapidly correct anthropometry whereas the restoration of fat stores takes place irrespective of birth weight. The metabolic consequences of these findings need to be elucidated.
Despite new therapeutic approaches have improved the prognosis of newborns with retinopathy of prematurity (ROP), an unfavourable structural and functional outcome still remains high. There is high pressure to develop new drugs to prevent and treat ROP. There is increasing enthusiasm for anti-VEGF drugs, but angiogenic inhibitors selective for abnormal blood vessels would be considered as an optimal treatment.
In an animal experimental model of proliferative retinopathy, we have recently demonstrated that the pharmacological blockade of beta-adrenoreceptors improves retinal neovascularization and blood retinal barrier breakdown consequent to hypoxia. The purpose of this study is to evaluate the propranolol administration in preterm newborns suffering from a precocious phase of ROP in terms of safety and efficacy in counteracting the progression of retinopathy.
Preterm newborns (gestational age at birth lower than 32 weeks) with stage 2 ROP (zone II-III without plus) will be randomized, according to their gestational age, to receive propranolol added to standard treatment (treatment adopted by the ETROP Cooperative Group) or standard treatment alone. Propranolol will be administered until retinal vascularization will be completely developed, but not more than 90 days. Forty-four participants will be recruited into the study. To evaluate the safety of propranolol administration, cardiac and respiratory parameters will be continuously monitored. Blood samplings will be performed to check renal, liver and metabolic balance. To evaluate the efficacy of propranolol, the progression of the disease, the number of laser treatments or vitrectomies, the incidence of retinal detachment or blindness, will be evaluated by serial ophthalmologic examinations. Visual function will be evaluated by means of behavioural standardized tests.
This pilot study is the first research that explores the possible therapeutic role of beta blockers in ROP. The objective of this research is highly ambitious: to find a treatment simple, inexpensive, well tolerated and with few adverse effects, able to counteract one of the major complications of the prematurity. Any favourable results of this research could open new perspectives and original scenarios about the treatment or the prevention of this and other proliferative retinopathies.
Current Controlled Trials ISRCTN18523491; ClinicalTrials.gov Identifier NCT01079715; EudraCT Number 2010-018737-21
The prevalence of genetic arrhythmogenic diseases is unknown. For the long QT syndrome (LQTS), figures ranging from 1:20,000 to 1:5,000 were published but none was based on actual data. Our objective was to define the prevalence of LQTS.
Methods and Results:
In 18 maternity hospitals an ECG was performed in 44,596 infants 15-25 days old (43,080 Caucasians). In infants with a QTc >450 ms the ECG was repeated within 1-2 weeks. Genetic analysis, by screening 7 LQTS genes, was performed in 28/31 (90%) and in 14/28 (50%) of infants with, respectively, a QTc >470 ms or between 461 and 470 ms. A QTc of 451-460, of 461-470, and >470 ms was observed in 184 (0.41%), in 28 (0.06%), and in 31 (0.07%) infants. Among genotyped infants, disease-causing mutations were found in 12/28 (43%) with a QTc >470 ms and in 4/14 (29%) with a QTc of 461-470 ms. One genotype-negative infant (QTc 482 ms) was diagnosed affected by LQTS on clinical grounds. Among family members of genotype-positive infants, 51% were found to carry disease-causing mutations. In total, 17/43,080 Caucasian infants were affected by LQTS demonstrating a prevalence of at least 1:2,534 apparently healthy live-births (95% C.I. 1:1,583- 1:4,350).
This study provides the first data-based estimate of the prevalence of LQTS among Caucasians. Based on the non-genotyped infants with QTc between 451 and 470 ms we advance the hypothesis that this prevalence might be close to 1:2,000. ECG-guided molecular screening can identify most infants affected by LQTS and unmask affected relatives, thus allowing effective preventive measures.
arrhythmia; death, sudden; electrocardiography; genetics; long-QT syndrome
Intrauterine growth restriction (IUGR) is associated with several medical complications before and after delivery. The aim of this study was to evaluate the concordance between the fetal ultrasonographic measurement of subcutaneous tissue thicknesses and the skinfold thicknesses assessment in intrauterine growth restricted newborns.
We designed an exploratory study. Fetal ultrasonographic measurement of subcutaneous tissue thicknesses, according to Bernstein's and Galan's method, and neonatal skinfold thicknesses were evaluated in 13 intrauterine growth restricted newborns within 4 hours before delivery and on the first day of life, respectively. Concordance between fetal and neonatal measurements was assessed using the Lin's correlation coefficient and the Bland-Altman method.
The data obtained by the measurements of neonatal skinfold thicknesses was significantly correlated with the prenatal measurements (Lin's coefficients, arm: 0.60; subscapular: 0.72; abdomen: 0.51). Bland-Altman analysis showed moderate agreement between the fetal ultrasonographic measurement of subcutaneous tissue thicknesses and the neonatal skinfold thicknesses assessment.
The present study provides preliminary evidence that fetal sonographic measurements may represent additional indices of intrauterine growth restriction.
evaluation of thyroid function in neonates born from mothers affected by autoimmune thyroiditis in order to define if a precise follow-up is necessary for these children. The influence of maternal thyroid peroxidase antibody (TPOAb) and L-thyroxine therapy during pregnancy on neonatal thyroid function was also investigated.
129 neonates were tested for thyroid function by measurement of free thyroxine (FT4) and thyroid stimulating hormone (TSH) in 3th day, 15th day and at one month of life. TPOAb were measured in all patients; periodical control of thyroid function were performed until 6 months of life if Ab were positive. Data concerning etiology of maternal hypothyroidism and maternal replacement therapy with L-thyroxine during pregnancy were retrospectively collected.
28% neonates showed at least a mild increase of TSH value at the different determinations. In the majority of them, a spontaneous completely normalisation of TSH value was observed within the first month life. L-thyroxine replacement therapy was started in 3 neonates. TPOAb titer and maternal L-thyroxine replacement therapy were not related to alteration of thyroid hormone function in our study population.
transient mild elevation of serum TSH above the normal reference value for age is frequently observed in the first month of life in infants born from mothers affected by autoimmune thyroiditis. Persistent hyperthyrotropinemia requiring replacement therapy is observed in 2.2% of these neonates. According to our experience, follow-up is recommended in these newborns; the most accurate and not invasive way to carefully monitor these infants after neonatal screening for CH seems to be serum-testing TSH between 2ndand 4th week of life.
Many congenitally cytomegalovirus-infected (cCMV) neonates are at risk for severe consequences, even if they are asymptomatic at birth. The assessment of the viral load in neonatal blood could help in identifying the babies at risk of sequelae.
In the present study, we elaborated the results obtained on blood samples collected in the first two weeks of life from 22 symptomatic and 48 asymptomatic newborns with cCMV diagnosed through urine testing. We evaluated the performances of two quantitative methods (pp65 antigenemia test and plasma Real-time PCR) and the semi-quantitative results of dried blood sample (DBS) test in the aim of identifying a valid method for measuring viral load.
Plasma qPCR and DBS tests were positive in 100% of cases, antigenemia in 81%. Only the latter test gave quantitatively different results in symptomatic versus asymptomatic children. qPCR values of 103 copies/ml were found in 52% of newborn. "Strong" DBS test positivity cases had higher median values of both pp65 positive PBL and DNA copies/ml than cases with a "weak" positivity.
As expected antigenemia test was less sensitive than molecular tests and DBS test performed better on samples with higher rates of pp65 positive PBL and higher numbers of DNA copies/ml. The prognostic significance of the results of these tests will be evaluated on completion of the ongoing collection of follow-up data of these children.