Josep Figueras-Aloy

The effects of varying protein and energy intakes on the growth and body composition of very low birth weight infants

ObjectiveTo determine the effects of high dietary protein and energy intake on the growth and body composition of very low birth weight (VLBW) infants.Study designThirty-eight VLBW infants whose weights were appropriate for their gestational ages were assessed for when they could tolerate oral intake for all their nutritional needs. Thirty-two infants were included in a longitudinal, randomized clinical trial over an approximate 28-day period. One control diet (standard preterm formula, group A, n = 8, 3.7 g/kg/d of protein and 129 kcal/kg/d) and two high-energy and high-protein diets (group B, n = 12, 4.2 g/kg/d and 150 kcal/kg/d; group C, n = 12, 4.7 g/kg/d and 150 kcal/kg/d) were compared. Differences among groups in anthropometry and body composition (measured with bioelectrical impedance analysis) were determined. An enriched breast milk group (n = 6) served as a descriptive reference group.ResultsGroups B and C displayed greater weight gains and higher increases in fat-free mass than group A.ConclusionAn intake of 150 kcal/kg/d of energy and 4.2 g/kg/d of protein increases fat-free mass accretion in VLBW infants.

Efficacy of three treatment schedules in severe meconium aspiration syndrome

Aim: To compare three different schedules in severe meconium aspiration syndrome (MAS) treatment: standard, bronchoalveolar lavage (BAL) with diluted surfactant, and diluted surfactant BAL plus a single early dexamethasone dose. Methods: Twenty‐four full‐term newborns with severe MAS (needing mechanical ventilation and with oxygenation index ± 15) were divided into three groups: group I (historical control group; n= 6) treated with standard therapy; group II (n= 7) treated in the first hours of life with one BAL using diluted surfactant (beractant 5 mg/mL) in a volume of 15 mL/kg in four aliquots; and group III (n = 11) treated with one diluted surfactant BAL and a previous single dose of intravenous dexamethasone (0.5 mg/kg) Results: At 12h, groups II and III showed a significant improvement in oxygenation index (OI) compared with group I (14.7% and 27.0% vs – 19.6% respectively; p= 0.012). Group III also showed a significantly lower OI than group I at 24 h (63.6% vs – 27.9%) and at 48 h (87.1% vs 49.6%). Group III, in comparison to group I, showed a lower FiO2 requirement at 12 h (0.66 vs 1), at 24 h (0.4 vs 0.87) and at 48 h (0.35 vs 0.67), and a decrease in the number of days of inhaled nitric oxide administration, mechanical ventilation, oxygen therapy and hospitalisation period. All patients from groups II and III survived and none developed pneumothorax or respiratory infections.

Erythropoietin and prematurity - where do we stand?

Abstract Erythropoietin (EPO) treatment for anemia of prematurity is still controversial. Large multicentric trials demonstrate that administration of EPO+Fe cannot prevent early transfusions, particularly in very low birth weight newborns and in infants with severe neonatal diseases, but may have some beneficial effect to prevent late transfusions. Current treatment of anemia of prematurity should be multifactorial trying to minimize all causes that reduce erthrocytic mass (phlebotomies, use of noninvasive procedures) and promoting all factors that increase it (placental transfusion, adequate nutrition support). To evaluate the real impact of EPO treatment it is mandatory to follow similar transfusion protocols for preterm infants in all the studies. The aim of EPO+Fe administration should be to avoid new late transfusions in very low birth weight preterm infants or to prevent the first transfusion after the second week of life in less immature premature with the objective of reducing the number of donors rather than the number of transfusions. We have limited the use of EPO+Fe to infants <30 weeks gestational age and birth weight ≤1250 g as well as to infants weighing 1250–1500 g with initial severe disease. The comparison of outcomes before (28 months period with EPO+Fe treatment to all premature ≤32 weeks gestational age) and after 20 months of implementation of the new protocol showed a significant decrease in EPO+Fe treatment candidates (40.3% vs. 85.9%, P<0.001) without changes in the percentage of transfusions in both periods. Therefore if EPO treatment is to be given it should be limited to preterm infants with a birth weight <1000 g or those of 1000–1250 g associated with risk factors for blood transfusion. It should be started at 3–7 days of life at doses of 250 U/kg subcutaneously, three times a week, for 4–6 weeks depending on gestational age with oral iron 2–12 mg/kg/day to keep ferritin levels greater than 100 ng/mL.

Monitoring the postnatal growth of preterm infants: A paradigm change

There is no evidence that preterm postnatal growth should mimic that of healthy fetuses. It is seldom achieved and creates extrauterine growth–restricted or overfat infants. There is no consensus regarding how the growth of preterm infants should be monitored or what constitutes their ideal pattern of growth, especially after term-corrected age. The concept that the growth of preterm infants should match that of healthy fetuses is not substantiated by data and, in practice, is seldom attained, particularly for very preterm infants. Hence, by hospital discharge, many preterm infants are classified as postnatal growth–restricted. In a recent systematic review, 61 longitudinal reference charts were identified, most with considerable limitations in the quality of gestational age estimation, anthropometric measures, feeding regimens, and how morbidities were described. We suggest that the correct comparator for assessing the growth of preterm infants, especially those who are moderately or late preterm, is a cohort of preterm newborns (not fetuses or term infants) with an uncomplicated intrauterine life and low neonatal and infant morbidity. Such growth monitoring should be comprehensive, as recommended for term infants, and should include assessments of postnatal length, head circumference, weight/length ratio, and, if possible, fat and fat-free mass. Preterm postnatal growth standards meeting these criteria are now available and may be used to assess preterm infants until 64 weeks’ postmenstrual age (6 months’ corrected age), the time at which they overlap, without the need for any adjustment, with the World Health Organization Child Growth Standards for term newborns. Despite remaining nutritional gaps, 90% of preterm newborns (ie, moderate to late preterm infants) can be monitored by using the International Fetal and Newborn Growth Consortium for the 21st Century Preterm Postnatal Growth Standards from birth until life at home.

Anaemia of prematurity: treatment with erythropoietin

Anemia of prematurity is a hyporegenerative anemia usually appearing after the second week, reaching highest intensity in the second month of life. Its normocytic and normochromic with low reticulocyte count. It has been attributed to EPO deficiency. The low EPO levels detected in premature infants and the proper response to synthetic erythropoietin suggested that EPO administration in premature of < or =32 weeks gestational age could be of benefit trying to maintain or increase the hematocrit levels. Protocols of EPO administration to premature babies should always be considered as EPO+Fe, keeping ferritin levels over 100 ng/ml. Failures to EPO+Fe treatment in very small premature babies, measured as no decrease in the need of blood transfusions, may be due to the amount of blood looses that should be restricted.

Trends in survival among extremely-low-birth-weight infants (less than 1000 g) without significant bronchopulmonary dysplasia

ObjectiveThe aim of this study was to analyze the evolution from 1997 to 2009 of survival without significant (moderate and severe) bronchopulmonary dysplasia (SWsBPD) in extremely-low-birth-weight (ELBW) infants and to determine the influence of changes in resuscitation, nutrition and mechanical ventilation on the survival rate.Study designIn this study, 415 premature infants with birth weights below 1000 g (ELBW) were divided into three chronological subgroups: 1997 to 2000 (n = 65), 2001 to 2005 (n = 178) and 2006 to 2009 (n = 172).Between 1997 and 2000, respiratory resuscitation in the delivery room was performed via a bag and mask (Ambu®, Ballerup, Sweden) with 40-50% oxygen. If this procedure was not effective, oral endotracheal intubation was always performed. Pulse oximetry was never used. Starting on January 1, 2001, a change in the delivery room respiratory policy was established for ELBW infants. Oxygenation and heart rate were monitored using a pulse oximeter (Nellcor®) attached to the newborn’s right hand. If resuscitation was required, ventilation was performed using a face mask, and intermittent positive pressure was controlled via a ventilator (Babylog2, Drägger). In 2001, a policy of aggressive nutrition was also initiated with the early provision of parenteral amino acids. We used standardized parenteral nutrition to feed ELBW infants during the first 12–24 hours of life. Lipids were given on the first day. The glucose concentration administered was increased by 1 mg/kg/minute each day until levels reached 8 mg/kg/minute. Enteral nutrition was started with trophic feeding of milk. In 2006, volume guarantee treatment was instituted and administered together with synchronized intermittent mandatory ventilation (SIMV + VG). The complications of prematurity were treated similarly throughout the study period. Patent ductus arteriosus was only treated when hemodynamically significant. Surgical closure of the patent ductus arteriosus was performed when two courses of indomethacin or ibuprofen were not sufficient to close it.Mild BPD were defined by a supplemental oxygen requirement at 28 days of life and moderate BPD if breathing room air or a need for <30% oxygen at 36 weeks postmenstrual age or discharge from the NICU, whichever came first. Severe BPD was defined by a supplemental oxygen requirement at 28 days of life and a need for greater than or equal to 30% oxygen use and/or positive pressure support (IPPV or nCPAP) at 36 weeks postmenstrual age or discharge, whichever came first. Moderate and severe BPD have been considered together as “significant BPD”. The goal of pulse oximetry was to maintain a hemoglobin saturation of between 88% and 93%. Patients were considered to not need oxygen supplementation when it could be permanently withdrawn. The distribution of the variables was not normal based on a Kolmogorov-Smirnov test (p < 0.05 in all cases). Therefore, quantitative variables were expressed as the median and interquartile range (IQR; 25th-75th percentile). Statistical analysis of the data was performed using nonparametric techniques (Kruskal-Wallis test and Mann–Whitney U test). A chi-square analysis was used to analyze qualitative variables. Potential confounding variables were those possibly related to BPD in survivors (p between 0.05 and 0.3 in univariate analysis). Logistic regression analysis was performed with variables related to BPD in survivors (p < 0.05) and potential confounding variables. The forward stepwise method adjusted for confounding factors was used to select the variables, and the enter method using selected variables was used to obtain the odds ratios.Results and conclusionThere was an increase in the rate of SWsBPD (1997 to 2000: 58.5%; 2001 to 2005: 74.2%; and 2006 to 2009: 75.0%; p = 0.032). In survivors, the occurrence of significant BPD decreased after 2001 (9.5% vs. 2.3%; p = 0.013). The factors associated with improved SWsBPD were delivery by caesarean section, a reduced endotracheal intubation rate and a reduced duration of mechanical ventilation.While the mortality of ELBW infants has not changed since 2001, the frequency of SWsBPD has significantly increased (75.0%) in association with increased caesarean sections and reductions in the endotracheal intubation rate, as well as the duration of mechanical ventilation.

Nonimmune hydrops fetalis due to congenital xerocytosis.

Hereditary xerocytosis is a rare hemolytic anemia in which erythrocytes are dehydrated due to a loss of potassium and water through their cell wall membrane. In adults, this condition leads to a mild-to-moderate hemolysis. We report a case of hydrops fetalis secondary to hereditary xerocytosis. Management with intrauterine erythrocyte and albumin transfusions resulted in a favorable postnatal course.

Can cerebellar and brainstem apparent diffusion coefficient (ADC) values predict neuromotor outcome in term neonates with hypoxic-ischemic encephalopathy (HIE) treated with hypothermia?

Background and purpose To determine the apparent diffusion coefficient (ADC) in specific infratentorial brain structures during the first week of life and its relation with neuromotor outcome for Hypoxic-ischemic encephalopathy (HIE) in term neonates with and without whole-body hypothermia (TH). Materials and methods We retrospectively evaluated 45 MRI studies performed in the first week of life of term neonates born between 2010 and 2013 at Boston Childrens Hospital. Selected cases were classified into three groups: 1) HIE neonates who underwent TH, 2) HIE normothermics (TN), and 3) controls. The neuromotor outcome was categorized as normal, abnormal and death. The ADCmean was calculated for six infratentorial brain regions. Results A total of 45 infants were included: 28 HIE TH treated, 8 HIE TN, and 9 controls. The mean gestational age was 39 weeks; 57.8% were male; 11.1% were non-survivors. The median age at MRI was 3 days (interquartile range, 1–4 days). A statistically significant relationship was shown between motor outcome or death and the ADCmean in the vermis (P = 0.002), cerebellar left hemisphere (P = 0.002), midbrain (P = 0.009), pons (P = 0.014) and medulla (P = 0.005). In patients treated with TH, the ADC mean remained significantly lower than that in the controls only in the hemispheres (P = 0.01). In comparison with abnormal motor outcome, ADCmean was lowest in the left hemisphere (P = 0.003), vermis (P = 0.003), pons (P = 0.0036) and medulla (P = 0.008) in case of death. Conclusion ADCmean values during the first week of life in the left hemisphere, vermis, pons and medulla are related to motor outcome or death in infants with HIE either with or without hypothermic therapy. Therefore, this objective tool can be assessed prospectively to determine if it can be used to establish prognosis in the first week of life, particularly in severe cases of HIE.

Learning and memory disabilities in IUGR babies: Functional and molecular analysis in a rat model

Intrauterine growth restriction (IUGR) is the failure of the fetus to achieve its inherent growth potential, and it has frequently been associated with neurodevelopmental problems in childhood. Neurological disorders are mostly associated with IUGR babies with an abnormally high cephalization index (CI) and a brain sparing effect. However, a similar correlation has never been demonstrated in an animal model. The aim of this study was to determine the correlations between CI, functional deficits in learning and memory and alterations in synaptic proteins in a rat model of IUGR.

Vertically transmitted cytomegalovirus infection in newborn preterm infants.

Abstract Objective: To determine the epidemiology of congenital and acquired cytomegalovirus (CMV) infections in preterm infants and to analyze the efficacy of breast milk freezing in decreasing the vertical transmission rate of CMV. Study design: During 2013 and 2014, preterm newborns who weighed ≤1500 g and were admitted to 22 Spanish neonatal units were included and screened for CMV infection according to the Spanish Neonatology Society recommendations. Each hospital treated the breast milk according to its own protocols. Results: Among the 1236 preterm neonates included, 10 had a congenital infection (0.8%) and 49 had an acquired infection (4.0%) (82% demonstrated positive PCR-CMV in breast milk). The neonates who received only frozen milk presented less frequently with acquired infection (1.2%) than those fed fresh milk (5.5%) (RR=0.22; 95% CI 0.05–0.90; P=0.017). The newborns who received bank milk followed by frozen or fresh breast milk more frequently had an acquired infection (2.1% or 2.2%, respectively) than those fed only frozen breast milk. Conclusions: The incidence of congenital CMV infection in our sample is low, as described in the literature. To reduce acquired CMV infection, freezing breast milk might be an advisable procedure for preterm neonates born from seropositive mothers, either from the beginning of lactation or after a period of bank milk administration.