Publications by authors named "Elisa Ballardini"

14 Publications

  • Page 1 of 1

ATP1A2- and ATP1A3-associated early profound epileptic encephalopathy and polymicrogyria.

Brain 2021 Apr 21. Epub 2021 Apr 21.

Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories, Meyer Children's Hospital, University of Florence, Florence, Italy.

Constitutional heterozygous mutations of ATP1A2 and ATP1A3, encoding for two distinct isoforms of the Na+/K+-ATPase (NKA) alpha-subunit, have been associated with familial hemiplegic migraine (ATP1A2), alternating hemiplegia of childhood (ATP1A2/A3), rapid-onset dystonia-parkinsonism, cerebellar ataxia-areflexia-progressive optic atrophy, and relapsing encephalopathy with cerebellar ataxia (all ATP1A3). A few reports have described single individuals with heterozygous mutations of ATP1A2/A3 associated with severe childhood epilepsies. Early lethal hydrops fetalis, arthrogryposis, microcephaly, and polymicrogyria have been associated with homozygous truncating mutations in ATP1A2. We investigated the genetic causes of developmental and epileptic encephalopathies variably associated with malformations of cortical development in a large cohort and identified 22 patients with de novo or inherited heterozygous ATP1A2/A3 mutations. We characterized clinical, neuroimaging and neuropathological findings, performed in silico and in vitro assays of the mutations' effects on the NKA-pump function, and studied genotype-phenotype correlations. Twenty-two patients harboured 19 distinct heterozygous mutations of ATP1A2 (six patients, five mutations) and ATP1A3 (16 patients, 14 mutations, including a mosaic individual). Polymicrogyria occurred in 10 (45%) patients, showing a mainly bilateral perisylvian pattern. Most patients manifested early, often neonatal, onset seizures with a multifocal or migrating pattern. A distinctive, 'profound' phenotype, featuring polymicrogyria or progressive brain atrophy and epilepsy, resulted in early lethality in seven patients (32%). In silico evaluation predicted all mutations to be detrimental. We tested 14 mutations in transfected COS-1 cells and demonstrated impaired NKA-pump activity, consistent with severe loss of function. Genotype-phenotype analysis suggested a link between the most severe phenotypes and lack of COS-1 cell survival, and also revealed a wide continuum of severity distributed across mutations that variably impair NKA-pump activity. We performed neuropathological analysis of the whole brain in two individuals with polymicrogyria respectively related to a heterozygous ATP1A3 mutation and a homozygous ATP1A2 mutation and found close similarities with findings suggesting a mainly neural pathogenesis, compounded by vascular and leptomeningeal abnormalities. Combining our report with other studies, we estimate that ∼5% of mutations in ATP1A2 and 12% in ATP1A3 can be associated with the severe and novel phenotypes that we describe here. Notably, a few of these mutations were associated with more than one phenotype. These findings assign novel, 'profound' and early lethal phenotypes of developmental and epileptic encephalopathies and polymicrogyria to the phenotypic spectrum associated with heterozygous ATP1A2/A3 mutations and indicate that severely impaired NKA pump function can disrupt brain morphogenesis.
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April 2021

Hypospadias prevalence in the Emilia Romagna Region registry: Increasing or methodology?

J Pediatr Urol 2020 Aug 20;16(4):448.e1-448.e7. Epub 2020 Jun 20.

IMER Registry (Emilia Romagna Registry of Birth Defects), Centre for Clinical and Epidemiological Research, University of Ferrara.

Introduction: Hypospadias is one of the most common congenital anomalies in male infants, defined as incomplete development of the urethra. Despite the wealth of literature, there are conflicting data on the values and trends of prevalence, due to multifactorial origin but often also to methodological differences between studies. The aim of this study was to analyse prevalence, trends and risk factors of hypospadias in the Emilia Romagna Region, Italy.

Material And Methods: The Emilia-Romagna Registry (IMER) is a population-based congenital anomaly database covering the first year of life, active since 1978. IMER uses multi-source ascertainment, including hospital discharge records (SDO) from 2009, through a validated algorithm. From 2014, IMER changed the algorithm, and included all hypospadias identified in SDO, and not only those confirmed by surgery. All cases identified in the IMER database, coded 7526.01-7526.09 or Q54.0-Q54.9 in 2010-2016, were analysed.

Result And Discussion: A total of 604 hypospadias cases were registered among 267,285 births; 526 were isolated, giving a prevalence of 2 per 1000. An increase from 1.6 in 2010 to 2.9 in 2016 was seen. The comparison between consecutive years was not significant neither from 2010 to 2013 nor in the period 2014-2016. There was instead a significant difference between the two periods, suggesting that the ascertainment change in 2014 is probably responsible for the increase. In the last three years analysed, isolated hypospadias prevalence is 2.5 per 1000. In the study period, mother's age over 39 years, multiple birth, preterm birth, small for gestational age, Caucasian compared with Asiatic or Africans were statistically associated with higher hypospadias prevalence. There was no association neither between hypospadias and paternal age nor maternal body mass index or assisted reproductive technology.

Conclusion: Whilst hypospadias prevalence trend is debated in the literature, in IMER it seems to be stable, with methodological changes affecting the trends. Risk factors potentially involved in developing hypospadias are environment and population characteristics, so understanding and monitoring hypospadias prevalence remains important.
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August 2020

Neuroprem: the Neuro-developmental outcome of very low birth weight infants in an Italian region.

Ital J Pediatr 2020 Feb 22;46(1):26. Epub 2020 Feb 22.

Neonatal Intensive Care Unit, University Hospital of Modena, Via del Pozzo 71, 41100, Modena, Italy.

Introduction: The survival of preterm babies has increased worldwide, but the risk of neuro-developmental disabilities remains high, which is of concern to both the public and professionals. The early identification of children at risk of neuro-developmental disabilities may increase access to intervention, potentially influencing the outcome.

Aims: Neuroprem is an area-based prospective cohort study on the neuro-developmental outcome of very low birth weight (VLBW) infants that aims to define severe functional disability at 2 years of age.

Methods: Surviving VLBW infants from an Italian network of 7 neonatal intensive care units (NICUs) were assessed for 24 months through the Griffiths Mental Developmental Scales (GMDS-R) or the Bayley Scales of Infant and Toddler Development (BSDI III) and neuro-functional evaluation according to the International Classification of Disability and Health (ICF-CY). The primary outcome measure was severe functional disability at 2 years of age, defined as cerebral palsy, a BSDI III cognitive composite score < 2 standard deviation (SD) or a GMDS-R global quotients score < 2 SD, bilateral blindness or deafness.

Results: Among 211 surviving VLBW infants, 153 completed follow-up at 24 months (72.5%). Thirteen patients (8.5%) developed a severe functional disability, of whom 7 presented with cerebral palsy (overall rate of 4.5%). Patients with cerebral palsy were all classified with ICF-CY scores of 3 or 4. BSDI III composite scores and GMDS-R subscales were significantly correlated with ICF-CY scores (p < 0.01).

Conclusion: Neuroprem represents an Italian network of NICUs aiming to work together to ensure preterm neuro-developmental assessment. This study updates information on VLBW outcomes in an Italian region, showing a rate of cerebral palsy and major developmental disabilities in line with or even lower than those of similar international studies. Therefore, Neuroprem provides encouraging data on VLBW neurological outcomes and supports the implementation of a preterm follow-up programme from a national network perspective.
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February 2020

Prevalence and characteristics of positional plagiocephaly in healthy full-term infants at 8-12 weeks of life.

Eur J Pediatr 2018 Oct 20;177(10):1547-1554. Epub 2018 Jul 20.

Department of Medical Sciences, Pediatric Section, Neonatal Intensive Care Unit, University of Ferrara, Via Aldo Moro, 8-44124 Cona, Ferrara, Italy.

Positional plagiocephaly (PP) denotes flattening of the skull that occurs frequently in healthy infants. Aim of this study was to estimate the prevalence of positional plagiocephaly and to identify the risk factors in a cohort of healthy infants in order to help prevention of PP. In a prospective design, all healthy full-term infants, ranging from 8 to 12 weeks of age, who presented at the public immunization clinic in Ferrara, were eligible for the study. After obtaining informed consent, we interviewed the parents and examined the infants using the Argenta's assessment tool. Of 283 infants examined, 107 (37.8%) were found to have PP at 8-12 weeks of age. In 64.5%, PP was on the right side, 50.5% were male and 15% presented also with brachycephaly. Risk factors significantly associated were lower head circumference, advanced maternal age, Italian compared to African, and supine sleep position, in particular for infants born at 37 weeks, preference for one side of the head. In logistic regression, risk factors significantly associated were lower birth weight, advanced maternal age, and supine sleep position.

Conclusions: Positional plagiocephaly is a common issue faced by pediatricians; our results reinforce the need of improving prevention both of sudden infant death and positional plagiocephaly, through uniform messages provided prenatally and postnatally by different health professionals. "What is Known:" •The incidence of positional plagiocephaly varies due to population studied and measuring methods. •Different factors are considered in the literature as being associated to positional plagiocephaly (infant factors, obstetric factors, infant care practices, sociodemographic factors). "What is New:" •This is one of the few European studies quantifying positional plagiocephaly prevalence in a population of unselected healthy infants. •In this study, positional plagiocephaly is confirmed as a common issue, related to some factor (as supine sleep position and positional head prevalence) that should be addressed in pre and postnatal counseling. •The prone sleepers rate in our population highlight the need to improve parental awareness regarding SIDS prevention, in particular in borderline gestational age.
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October 2018

Prevalence and associated factors for agenesis of corpus callosum in Emilia Romagna (1981-2015).

Eur J Med Genet 2018 Sep 12;61(9):524-530. Epub 2018 Jun 12.

IMER Registry (Emilia Romagna Registry of Birth Defects), Center for Clinical and Epidemiological Research, University of Ferrara, Italy.

Agenesis and hypoplasia of the corpus callosum (ACC and HCC) are heterogeneous group with a large variation in published prevalence based on few population based studies. The aim of this work is to describe prevalence, associated factors and other malformations present in cases with either agenesis or hypoplasia of the corpus callosum, using a population-based database of all malformations diagnosed in Emilia-Romagna, Italy, (the Emilia-Romagna Registry on Congenital Malformations, IMER). This registry links and integrates hospital discharge records, birth certificates with cases reported by referral clinicians to identify all structural malformations diagnosed within one year of life regarding live birth, fetal death or termination of pregnancy due to fetal malformations (TOPFA). During the study period (1981-2015) the number of cases with ACC or HCC was 255, in a reference population of 1,023,784 live births, giving an overall prevalence of 2.49 per 10,000 (1.47 per 10,000 only live birth). After 1996, with the inclusion of TOPFA in IMER registry, the overall prevalence rate increase significantly from 1.42 to 3.03 cases per 10,000 birth (p-value<0.001). Prenatal diagnosis was made in 192 cases (75.3%), at a median gestational age of 20.7 [IQR: 19.71-22.71]. Termination of pregnancy occurred in 105 of the 255 cases (41,2%). Where a prenatal diagnosis was available, 55% of cases ended in TOPFA (105/192), with higher prevalence of cases associated to central nervous system malformations and multiple birth defects, and median gestational age at diagnosis significantly less than in live birth cases (20.3 vs 29 weeks). Agenesis/hypoplasia ratio was 5.7 (217/38). The most frequently associated malformations were musculoskeletal. Trisomies were the most frequent chromosomal anomalies, in particularly trisomy18 and 13 (respectively 9/32 and 4/32 cases). Our study showed an increased risk for male infants (RR of 1.68, RR 95% CI 1.19-2.37). No differences were detected analyzing maternal age and ethnicity, and the increased risk associated to preterm birth disappeared when compared with other malformed infants. This is one of the few population based studies dealing with prevalence of agenesis and hypoplasia of corpus callosum. Prevalence is still debated, but this study adds comprehensive data, in particular inclusion of TOPFA cases. Early prenatal diagnosis, not always possible, could be crucial for decision making regarding continuation of pregnancy.
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September 2018

Expanding the clinical spectrum of recessive truncating mutations of to a Bohring-Opitz-like phenotype.

J Med Genet 2017 12 26;54(12):830-835. Epub 2017 Oct 26.

Inserm UMR 1231 GAD Team, Genetics of Developmental Anomalies, Université de Bourgogne-Franche Comté, Dijon, France.

Background: Bohring-Opitz syndrome (BOS) is a rare genetic disorder characterised by a recognisable craniofacial appearance and a typical 'BOS' posture. BOS is caused by sporadic mutations of. However, several typical patients with BOS have no molecular diagnosis, suggesting clinical and genetic heterogeneity.

Objectives: To expand the phenotypical spectrum of autosomal recessive variants of , reported as causing Crisponi syndrome/cold-induced sweating syndrome type 1 (CS/CISS1)-like syndrome.

Methods: We performed whole-exome sequencing in two families with a suspected recessive mode of inheritance. We used the Matchmaker Exchange initiative to identify additional patients.

Results: Here, we report six patients with microcephaly, facial dysmorphism, including exophthalmos, nevus flammeus of the glabella and joint contractures with a suspected BOS posture in five out of six patients. We identified autosomal recessive truncating mutations in the gene. encodes a BTB-kelch protein implicated in the cell cycle and in protein degradation by the ubiquitin-proteasome pathway. Recently, biallelic mutations in the gene were reported in four families and associated with CS/CISS1, characterised by clinical features overlapping with our patients.

Conclusion: We have expanded the clinical spectrum of autosomal recessive variants by describing a syndrome with features overlapping CS/CISS1 and BOS.
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December 2017

Universal Head Ultrasound Screening in Full-term Neonates: A Retrospective Analysis of 6771 Infants.

Pediatr Neurol 2017 Jun 30;71:14-17. Epub 2017 Mar 30.

Neonatal Intensive Care Unit, Department of Reproduction and Growth, University Hospital of Ferrara, Ferrara, Italy.

Background: Full-term neonates may have asymptomatic cranial injuries at birth and head ultrasound screening could be useful for early diagnosis. The aim of this study was to assess the prevalence and type of intracranial abnormalities and the usefulness of head ultrasound screening in these infants.

Methods: Head ultrasound screening was performed on all full-term neonates (gestational age between 37 and 42 weeks), born at Sant'Anna University Hospital of Ferrara, Italy, from June 1, 2008 through May 31, 2013. Ultrasound findings were categorized into three groups: normal, minor, and major anomalies.

Results: All full-term neonates (6771) born at our hospital underwent head ultrasound screening. One hundred fourteen of 6771 (1.7%) presented ultrasound abnormalities, whereas 6657 were normal or exhibited insignificant findings. In 101 of 114 (88.6%), abnormalities were minor, and only 13 infants had major abnormalities (0.19% of all full-term newborns). All neonates with major abnormalities presented with either microcephaly or abnormal neurological evaluations. Only one individual with major abnormalities was detected exclusively by ultrasound.

Conclusions: The number of significant anomalies detected by head ultrasound screening in asymptomatic full-term neonates born during the study period was low. Therefore, there is no indication for routine general head ultrasound screening in these patients. However, even if low, in neonates who have neurological abnormalities, risk factors or suspected brain malformations, head ultrasound screening may play an important role in the early diagnosis of intracranial anomalies.
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June 2017

Corrigendum to "Two Mutations in Surfactant Protein C Gene Associated with Neonatal Respiratory Distress".

Case Rep Pediatr 2015 19;2015:592053. Epub 2015 Oct 19.

Neonatal Intensive Care Unit and Neonatology, University Hospital S. Anna, Ferrara, Italy.

[This corrects the article DOI: 10.1155/2015/591783.].
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November 2015

Two mutations in surfactant protein C gene associated with neonatal respiratory distress.

Case Rep Pediatr 2015 27;2015:591783. Epub 2015 Apr 27.

Neonatal Intensive Care Unit and Neonatology, University Hospital S. Anna, Ferrara, Italy.

Multiple mutations of surfactant genes causing surfactant dysfunction have been described. Surfactant protein C (SP-C) deficiency is associated with variable clinical manifestations ranging from neonatal respiratory distress syndrome to lethal lung disease. We present an extremely low birth weight male infant with an unusual course of respiratory distress syndrome associated with two mutations in the SFTPC gene: C43-7G>A and 12T>A. He required mechanical ventilation for 26 days and was treated with 5 subsequent doses of surfactant with temporary and short-term efficacy. He was discharged at 37 weeks of postconceptional age without any respiratory support. During the first 16 months of life he developed five respiratory infections that did not require hospitalization. Conclusion. This mild course in our patient with two mutations is peculiar because the outcome in patients with a single SFTPC mutation is usually poor.
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May 2015

Universal cranial ultrasound screening in preterm infants with gestational age 33-36 weeks. A retrospective analysis of 724 newborns.

Pediatr Neurol 2014 Dec 29;51(6):790-4. Epub 2014 Aug 29.

Paediatric Unit, Department of Medical Sciences, University Hospital of Ferrara, Ferrara, Italy.

Background: Cranial ultrasonography is a useful tool to detect intracranial lesions in premature neonates at risk. Our primary aim was to determine the number of patients with abnormal cranial ultrasonography. Secondary aims were to evaluate the usefulness of universal cranial ultrasonography screening in moderately preterm infants.

Methods: All infants born from 2007 to 2012 at the University Hospital of Ferrara (Italy), with gestational age of 33-36 weeks, were included in the study. Cranial ultrasonography findings were retrospectively classified into nonsignificant and significant.

Results: All the 724 babies born were screened. Intracranial lesions were in 13% of neonates (3.7% at 36 weeks to 27.1% at 33 weeks of gestational age). Babies born at 33-34 weeks of gestational age were four times more likely to have an abnormal cranial ultrasonography than those at 35-36 weeks. Statistical analysis revealed no association between cranial ultrasonography abnormalities and being small for gestational age or mode of delivery. A significant association was present between the presence of head circumference less than the third percentile, the need for ventilation or surfactant, low Apgar index at fifth minute, and neurological abnormalities. The presence of at least one considered risk factor increases the probability of cranial ultrasonography abnormalities twice in infants born at 33-34 weeks and 15 times in born at 35-36 weeks.

Conclusions: A considerable number of infants born between 33 and 36 weeks have cranial ultrasonography abnormalities. We suggest that screening should be performed or at least that a uniform protocol should be developed for the early detection of all significant cranial ultrasonography abnormalities.
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December 2014

Use of ketamine in a newborn with refractory status epilepticus: a case report.

Pediatr Neurol 2014 Jul 15;51(1):154-6. Epub 2014 Mar 15.

Department of Medical Sciences, Neonatology and NICU, S. Anna University Hospital, Ferrara, Italy.

Background: Brain malformations represent a major cause of refractory seizures. Standardized protocols to treat status epilepticus of newborn are not available in the literature.

Patient: We present a case report of use of ketamine administered to a late preterm with Pierre Robin sequence, lissencephaly, polymicrogyria, and severe epilepsy.

Results: The infusion of ketamine permitted resolution of status epilepticus, cardiorespiratory stabilization, and improved parental care for 15 days. No significant side effects were noted.

Conclusion: In the literature there are few studies regarding the use of ketamine for refractory status epilepticus, and only in nine of these described the use of, ketamine in children (2 months-18 years). This is the first report to document the effective use of ketamine in the newborn with status epilepticus.
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July 2014

Prophylactic use of a probiotic in the prevention of colic, regurgitation, and functional constipation: a randomized clinical trial.

JAMA Pediatr 2014 Mar;168(3):228-33

Department of Pediatrics, Aldo Moro University of Bari, Bari, Italy.

Importance: Infantile colic, gastroesophageal reflux, and constipation are the most common functional gastrointestinal disorders that lead to referral to a pediatrician during the first 6 months of life and are often responsible for hospitalization, feeding changes, use of drugs, parental anxiety, and loss of parental working days with relevant social consequences.

Objective: To investigate whether oral supplementation with Lactobacillus reuteri DSM 17938 during the first 3 months of life can reduce the onset of colic, gastroesophageal reflux, and constipation in term newborns and thereby reduce the socioeconomic impact of these conditions.

Design: A prospective, multicenter, double-masked, placebo-controlled randomized clinical trial was performed on term newborns (age <1 week) born at 9 different neonatal units in Italy between September 1, 2010, and October 30, 2012.

Setting: Parents were asked to record in a structured diary the number of episodes of regurgitation, duration of inconsolable crying (minutes per day), number of evacuations per day, number of visits to pediatricians, feeding changes, hospitalizations, visits to a pediatric emergency department for a perceived health emergency, pharmacologic interventions, and loss of parental working days.

Participants: In total, 589 infants were randomly allocated to receive L reuteri DSM 17938 or placebo daily for 90 days.

Interventions: Prophylactic use of probiotic.

Main Outcomes And Measures: Reduction of daily crying time, regurgitation, and constipation during the first 3 months of life. Cost-benefit analysis of the probiotic supplementation.

Results: At 3 months of age, the mean duration of crying time (38 vs 71 minutes; P < .01), the mean number of regurgitations per day (2.9 vs 4.6; P < .01), and the mean number of evacuations per day (4.2 vs 3.6; P < .01) for the L reuteri DSM 17938 and placebo groups, respectively, were significantly different. The use of L reuteri DSM 17938 resulted in an estimated mean savings per patient of €88 (US $118.71) for the family and an additional €104 (US $140.30) for the community.

Conclusions And Relevance: Prophylactic use of L reuteri DSM 17938 during the first 3 months of life reduced the onset of functional gastrointestinal disorders and reduced private and public costs for the management of this condition.

Trial Registration: Identifier: NCT01235884.
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March 2014

Universal neonatal screening for sickle cell disease and other haemoglobinopathies in Ferrara, Italy.

Blood Transfus 2013 Apr 12;11(2):245-9. Epub 2012 Sep 12.

Department of Clinical and Experimental Medicine, Paediatric Section, University Hospital S. Anna, Ferrara, Italy.

Background: Sickle cell disease is the commonest haemoglobinopathy in Africa, the Middle East and India. In recent years, its incidence has increased dramatically also in Europe and North America because of the high rate of migration of people from endemic areas. From January 2009 to January 2010 the number of foreign residents in the province of Ferrara (Italy) increased by 12.2%: most of the immigrants were from countries at high risk of sickle cell disease. Since neonatal screening and prophylactic penicillin in early childhood could reduce mortality by 10 years of age to less than 2%, the aim of this study was to establish a neonatal screening programme for haemoglobinopathies in Ferrara.

Materials And Methods: First we assessed how many pregnant women underwent haemoglobin analysis by high performance liquid chromatography before or during pregnancy and how many of them were carriers of haemoglobinopathies. Subsequently, we verified the feasibility of neonatal screening for sickle cell disease and other haemoglobinopathies, analysing cord blood by high performance liquid chromatography. Neonates found to be positive were managed by a multidisciplinary team to implement all the appropriate prophylactic and therapeutic measures.

Results: We found that 59% of women who delivered at the University Hospital of Ferrara, from 2007 to 2009, had undergone high performance liquid chromatography. Of the 41% who were not tested, many were from areas in which sickle cell disease is common. Between September 26th 2010 and January 31st 2012, 1992 neonatal tests were performed and 24 carriers of haemoglobinopathies were identified (16 with HbS, 4 with HbC, 2 with HbE, 1 with HbD Punjab and 1 with HbD-Ouled Rabah); 42.6% of the mothers of these 1,992 neonates had not undergone high performance liquid chromatography during pregnancy.

Discussion: Currently prevention of haemoglobinopathies in Italy is provided during the pre-conception period but only to patients with abnormal blood counts. Neonatal screening is useful and cost-effective to ensure early diagnosis and appropriate treatment for infants with sickle cell disease or other haemoglobinopathies.
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April 2013

Different pre-term formulas for different pre-term infants.

Early Hum Dev 2010 Jul 12;86 Suppl 1:27-31. Epub 2010 Feb 12.

Neonatal Intensive Care Unit, Department of Clinical and Experimental Medicine, University of Ferrara, via Savonarola 9, Ferrara, Italy.

Optimal nutrition is one of the most important aspects in the care of pre-term infants, especially for the gestationally youngest ones. These infants should receive a supply of nutrients that can sustain growth similar to that of a third trimester normal foetus. Traditional pre-term formulas do not ensure an optimal protein supply except when fed at high volumes, with an excess of fat and carbohydrates. Formulas with a protein content of 2-2.5 g 100ml(-1) and a protein/energy (P:E) ratio of less than 3g 100 kcal(-1) are not the best choice for the very low birth weight (VLBW) infants. We have tested a new formulation designed for the nutrition of the VLBW infants that is characterised by a protein content of 2.9 g 100ml(-1) and a P:E ratio of 3.5 g 100 kcal(-1). The milk formula was well tolerated and associated with better weight gain compared with fortified breast milk (18.1 vs. 15.2 g kg(-1)day(-1); p=0.0015). These results were obtained with a noticeably lower fluid supply (157 vs. 177 ml kg day(-1); p<0.0001) and lower energy intake (130 vs. 151 kcal kg(-1)day(-1); p<0.0001). Infant length and head circumference did not differ significantly between groups. Currently, the use of a formula with a P:E ratio of 3.5 g 100 kcal(-1) appears to be safe and to represent the best choice available for the gestationally youngest infants.
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July 2010