RESUMO
Birth asphyxia is a cause of neonatal death or adverse neurological sequelae. Biomarkers can be useful to clinicians in order to optimize intensive care management and communication of prognosis to parents. During perinatal adverse events, increased cortisol secretion is due to hypothalamo-pituitary-adrenal axis activation. We aimed to investigate if cortisol variations during therapeutic hypothermia are associated with neurodevelopmental outcome. We compared 18 cases (neonates with birth asphyxia) with 18 controls (healthy term newborns) and confirmed increased serum cortisol concentrations following the peri-partum adverse event. Among cases, we stratified patients according to neurological outcome at 18 months (group A - good; group B - adverse) and found that after 24 h of therapeutic hypothermia serum cortisol concentration was significantly lower in group A vs group B (28.7 ng/mL vs 344 ng/mL, *p = 0.01). In group B serum, cortisol concentration decreased more gradually during therapeutic hypothermia. We conclude that monitoring serum cortisol concentration during neonatal therapeutic hypothermia can add information to clinical evaluation of neonates with birth asphyxia; cortisol values after the first 24 h of hypothermia can be a biomarker associated with neurodevelopmental outcome at 18 months of age.
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Asfixia Neonatal/terapia , Desenvolvimento Infantil , Hidrocortisona/sangue , Hipotermia Induzida , Sistema Nervoso/crescimento & desenvolvimento , Fatores Etários , Asfixia Neonatal/sangue , Asfixia Neonatal/diagnóstico , Asfixia Neonatal/fisiopatologia , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Valor Preditivo dos Testes , Fatores de Tempo , Resultado do TratamentoRESUMO
Oxidative stress (OS) is defined as an imbalance between pro- and antioxidant factors that can lead to cellular and tissue damage. Under condition of gestational diabetes, OS is exacerbated and can cause vascular dysfunction in the placenta, leading to fetal and perinatal complications. We investigated the oxidative status of diabetic pregnant women and of their babies. A group of those diabetic women received lutein, and another group did not receive anything. In order to verify a possible antioxidant function of lutein, we compared the OS values of the two groups. OS appeared lower in treated gravidas than in untreated ones; however, there was not a statistically significant difference between the two groups. As far as newborns are concerned, there was a significant difference of OS values between babies born to mothers treated with lutein and newborns to mothers untreated at 2 h of life. However, at 48 h, there was not a significant difference between the two groups. In conclusion, lutein administration during pregnancy significantly reduced neonatal OS at birth. Further studies are necessary to evaluate the effects of combined administration to mother and infants.
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Antioxidantes/administração & dosagem , Diabetes Gestacional/tratamento farmacológico , Recém-Nascido/metabolismo , Luteína/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Estudos de Casos e Controles , Diabetes Gestacional/metabolismo , Feminino , Humanos , Peróxido de Hidrogênio/metabolismo , Masculino , Gravidez , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Newborns can experience adverse effects as a consequence of maternal or in utero exposure, altered growth of the fetus, or placental dysfunctions. Accurate characterization of gestational age allows monitoring of fetal growth, identification of deviations from the normal growth trajectory, and classification of babies as adapted, small, or large for gestational age (AGA, SGA, or LGA). The aim of this work was to evaluate nuclear and oxidative damage in umbilical cord-blood cells of newborns (sampled at birth), by applying the γH2AX assay and the fluorescent probe BODIPY581/591 C11, to detect DNA DSB and cell membrane oxidation, respectively. No statistically significant differences were observed in the proportion of oxidized cord-blood cells among the groups of newborns, although the LGA group showed the highest value. With regard to genome damage, elevated levels of γH2AX foci were detected in the cell nuclei from LGA newborns as compared to AGA or SGA babies, whose values did not differ from each other. Considering that the observed DNA damage, although still repairable, can represent a risk factor for obesity, metabolic diseases, or other pathologies, monitoring genome and cell integrity at birth can provide useful information for prevention of diseases later in life.
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Recém-Nascido Pequeno para a Idade Gestacional , Placenta , Peso ao Nascer , Células Sanguíneas , Feminino , Humanos , Lactente , Recém-Nascido , Fosforilação , GravidezRESUMO
Permanent neonatal diabetes mellitus (PNDM) is a rare disorder usually presenting within 6 months of birth. Although several genes have been linked to this disorder, in almost half the cases documented in Italy, the genetic cause remains unknown. Because the Akita mouse bearing a mutation in the Ins2 gene exhibits PNDM associated with pancreatic beta cell apoptosis, we sequenced the human insulin gene in PNDM subjects with unidentified mutations. We discovered 7 heterozygous mutations in 10 unrelated probands. In 8 of these patients, insulin secretion was detectable at diabetes onset, but rapidly declined over time. When these mutant proinsulins were expressed in HEK293 cells, we observed defects in insulin protein folding and secretion. In these experiments, expression of the mutant proinsulins was also associated with increased Grp78 protein expression and XBP1 mRNA splicing, 2 markers of endoplasmic reticulum stress, and with increased apoptosis. Similarly transfected INS-1E insulinoma cells had diminished viability compared with those expressing WT proinsulin. In conclusion, we find that mutations in the insulin gene that promote proinsulin misfolding may cause PNDM.
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Proteínas de Ligação a DNA/biossíntese , Diabetes Mellitus/genética , Proteínas de Choque Térmico/biossíntese , Insulina/genética , Insulina/fisiologia , Chaperonas Moleculares/biossíntese , Mutação , Proteínas Nucleares/biossíntese , Proinsulina/biossíntese , Sequência de Aminoácidos , Análise Mutacional de DNA , Chaperona BiP do Retículo Endoplasmático , Feminino , Heterozigoto , Humanos , Lactente , Masculino , Dados de Sequência Molecular , Linhagem , Fatores de Transcrição de Fator Regulador X , Fatores de Transcrição , Proteína 1 de Ligação a X-BoxRESUMO
AIM: Early intervention programmes based on the manipulation of the extra-uterine environment have been used in preterm infants with the aim of improving development and functional outcome. Infant massage, among them, has proved effective for weight gain and reduced length of stay in the neonatal intensive care unit. We have recently shown that infant massage accelerates brain maturation of low-risk preterm infants without brain abnormalities as measured by global parameters of electroencephalography (EEG) activity. In the present study we further analyse the same cohort of preterm infants, testing the hypothesis that massage determines changes in EEG spectral activity, a highly sensitive index of brain maturation. METHOD: Infants were randomly allocated to a massage or comparison group. Intervention consisted of standard care only (comparison group) or standard care plus infant massage (massage group). Massage was started at around 10 days after birth and was provided for 12 days during a 2-week period. EEG was performed at around 1 and 4 weeks, i.e. before and after intervention. Spectral EEG analysis was performed on 80 seconds of active sleep, applying the fast Fourier transform on the signal obtained from eight monopolar derivations. RESULTS: The modification in global EEG spectral power between the two assessments was significantly different for the two groups, especially for the delta band activity; the spectral power did not change in massaged infants although, not surprisingly, it decreased significantly in the comparison group, as shown by previous studies. INTERPRETATION: We propose that massage intervention affects the maturation of brain electrical activity and favours a process more similar to that observed in utero in term infants.
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Encéfalo/fisiologia , Desenvolvimento Infantil/fisiologia , Eletroencefalografia/métodos , Recém-Nascido Prematuro/fisiologia , Massagem/métodos , Encéfalo/crescimento & desenvolvimento , Análise de Fourier , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro/crescimento & desenvolvimentoRESUMO
INTRODUCTION: Placental anatomopathologic lesions are usually associated with pregnancy complications and neonatal impaired outcome. PATIENTS AND METHODS: We included in our study 122 patients with gestational age of 26-35 weeks. From the analysis of three pathological aspects (chorioamnionitis, funisitis and chronic hypoxia), a score was assigned to each lesion depending on the severity of the alteration, to establish a correlation with an impaired neonatal outcome in preterm newborns. RESULTS: We found a correlation between chronic hypoxia and preeclampsia, intrauterine growth restriction and/or small-for-gestational age status at birth. Our results also showed the strong association of fetal placental inflammatory status (chorioamnionitis and funisitis) with premature rupture of membranes, very low birth weight, birth at/before 32 gestational weeks, late-onset sepsis, patent duct arteriosus, intraventricular haemorrhage (IVH) and retinopathy of prematurity (ROP). CONCLUSIONS: We confirm that placental lesions are associated with impaired pregnancy and neonatal outcome. During pregnancy it may be useful to identify some markers of inflammatory status and chronic hypoxia for an early diagnosis and a detailed monitoring of pregnancy course. Placental pathological analysis is very important to predict the risk of developing serious complications of preterm birth as ROP and IVH.
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Corioamnionite/patologia , Hipóxia/complicações , Hemorragias Intracranianas/etiologia , Placenta/patologia , Retinopatia da Prematuridade/etiologia , Feminino , Retardo do Crescimento Fetal/etiologia , Ruptura Prematura de Membranas Fetais/etiologia , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Recém-Nascido de muito Baixo Peso , Masculino , Pré-Eclâmpsia/etiologia , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Sepse/complicaçõesRESUMO
BACKGROUND AND AIM: Maternal diet and early nutrition of newborns may affect the phenotype later in adulthood. Susceptibility of epigenetic mechanisms to the nutritional environment is a critical element in neonatal development. Epigenetic mechanisms could be considered as a bridge between environmental stimuli and long lasting phenotype. IC2, a key region on 11p15, is involved in the control of growth and regulates CDKN1C, PHLDA2 and KCNQ1, growth inhibitor genes. Our aim was to investigate the relationship between epigenetic markers, nutrition and postnatal growth. METHODS: We enrolled 37 newborns (gestational age at birth was <34 weeks) admitted to Neonatal Intensive Care Unit at University Hospital of Pisa. RESULTS: We observed a relationship between reduced protein and lipid intake and IC2 hypermethylation (p = .003 and p = .001 respectively) and we also investigated the correlation between growth pattern and IC2 methylation. CONCLUSION: The reduced growth, in part related to a reduced intake of nutrients (lipids and proteins), might be due to IC2 hypermethylation, causing an increased expression of growth inhibitor genes. IC2 hypermethylation could be a marker of reduced infants' growth and may guides us to nutritional interventional strategies for a precocious prevention of extrauterine growth restriction (EUGR).
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Recém-Nascido Prematuro , Estado Nutricional , Adulto , Epigênese Genética , Idade Gestacional , Humanos , Recém-Nascido , Unidades de Terapia Intensiva NeonatalRESUMO
Environmental enrichment (EE) was shown recently to accelerate brain development in rodents. Increased levels of maternal care, and particularly tactile stimulation through licking and grooming, may represent a key component in the early phases of EE. We hypothesized that enriching the environment in terms of body massage may thus accelerate brain development in infants. We explored the effects of body massage in preterm infants and found that massage accelerates the maturation of electroencephalographic activity and of visual function, in particular visual acuity. In massaged infants, we found higher levels of blood IGF-1. Massage accelerated the maturation of visual function also in rat pups and increased the level of IGF-1 in the cortex. Antagonizing IGF-1 action by means of systemic injections of the IGF-1 antagonist JB1 blocked the effects of massage in rat pups. These results demonstrate that massage has an influence on brain development and in particular on visual development and suggest that its effects are mediated by specific endogenous factors such as IGF-1.
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Encéfalo/crescimento & desenvolvimento , Desenvolvimento Infantil/fisiologia , Massagem/métodos , Visão Ocular/fisiologia , Análise de Variância , Animais , Animais Recém-Nascidos , Comportamento Animal , Glicemia/metabolismo , Peso Corporal/fisiologia , Eletroencefalografia/métodos , Meio Ambiente , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Potenciais Evocados Visuais/fisiologia , Movimentos Oculares , Seguimentos , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Movimentos da Cabeça , Humanos , Hidrocortisona/sangue , Lactente , Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Estimulação Física/métodos , Radioimunoensaio/métodos , Ratos , Estatísticas não Paramétricas , Hormônios Tireóideos/sangue , Estudos em Gêmeos como Assunto , Vias Visuais/crescimento & desenvolvimentoRESUMO
AIM: The aim of this study was to explore the predictive value of quantitative assessment of hand movements in 3-month-old infants after neonatal stroke. METHOD: Thirteen infants born at term (five females, eight males; mean gestational age 39.4wks, SD 1.19, range 37-41wks; mean birthweight 3240g, SD 203, range 2900-3570g) with neonatal arterial ischaemic cerebral infarction, and 13 healthy infants (mean gestational age 39.1wks, range 37-41wks, SD 1.26; mean birthweight 3190g, SD 259, range 2680-3490g) were enrolled in the study. The absolute frequency and the asymmetry of global hand opening and closing, wrist segmental movements, and independent digit movements were assessed from videotapes recorded at around 12 weeks. Neurological outcome was assessed when the infants were at least 18 months old using Touwen's neurological examination. RESULTS: Five of the 13 infants with neonatal stroke had normal neurological development, and eight had hemiplegia. Asymmetry of wrist segmental movements and the absolute frequency of independent digit movements were significantly different between infants with and without hemiplegia (p=0.006 and p=0.008, respectively). No differences were found in global hand movements. INTERPRETATION: We propose that the observed abnormalities of hand movements are the result of two different mechanisms: direct disruption of the corticospinal projection to the spinal cord, and altered modulation of the central pattern generators of general movements.
Assuntos
Isquemia Encefálica/epidemiologia , Isquemia Encefálica/fisiopatologia , Encéfalo/irrigação sanguínea , Encéfalo/fisiopatologia , Mãos/fisiopatologia , Hemiplegia/diagnóstico , Hemiplegia/epidemiologia , Transtornos dos Movimentos/epidemiologia , Transtornos dos Movimentos/fisiopatologia , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Masculino , Transtornos dos Movimentos/diagnóstico , Valor Preditivo dos Testes , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
Early nutritional compromise after preterm birth is shown to affect long-term neurodevelopment, however, there has been a lack of early functional measures of nutritional effects. Recent progress in computational electroencephalography (EEG) analysis has provided means to measure the early maturation of cortical activity. Our study aimed to explore whether computational metrics of early sequential EEG recordings could reflect early nutritional care measured by energy and macronutrient intake in the first week of life. A higher energy or macronutrient intake was assumed to associate with improved development of the cortical activity. We analyzed multichannel EEG recorded at 32 weeks (32.4 ± 0.7) and 36 weeks (36.6 ± 0.9) of postmenstrual age in a cohort of 28 preterm infants born before 32 weeks of postmenstrual age (range: 24.3-32 weeks). We computed several quantitative EEG measures from epochs of quiet sleep (QS): (i) spectral power; (ii) continuity; (iii) interhemispheric synchrony, as well as (iv) the recently developed estimate of maturational age. Parenteral nutritional intake from day 1 to day 7 was monitored and clinical factors collected. Lower calories and carbohydrates were found to correlate with a higher reduction of spectral amplitude in the delta band. Lower protein amount associated with higher discontinuity. Both higher proteins and lipids intake correlated with a more developmental increase in interhemispheric synchrony as well as with better progress in the estimate of EEG maturational age (EMA). Our study shows that early nutritional balance after preterm birth may influence subsequent maturation of brain activity in a way that can be observed with several intuitively reasoned and transparent computational EEG metrics. Such measures could become early functional biomarkers that hold promise for benchmarking in the future development of therapeutic interventions.
RESUMO
Increasing evidence suggests that early-life events can predispose the newborn to a variety of health issues in later life. In adverse pre- and perinatal conditions, oxidative stress appears to play an important role in the development of future pathological outcomes. From a molecular point of view, oxidative stress can result in genome damage and changes in DNA methylation that can in turn prime pathogenic mechanisms. Interestingly, both alterations have been related to a reciprocal regulation of oxidative stress. The aim of this review is to give a brief overview of the complex relationship linking oxidative stress to DNA damage and methylation and to go through the different sources of exposure that a neonate can encounter in utero or shortly after birth. In this context, the setup of methodologies to monitor the extent of oxidative stress, genomic damage and instability or the presence of altered methylation patterns contributes to the understanding on how the complex events occurring in early life can lead to either a healthy status or a pathological condition.
Assuntos
Dano ao DNA , Metilação de DNA , Estresse Oxidativo , Exposição Ambiental/efeitos adversos , Epigênese Genética , Feminino , Humanos , Recém-Nascido , Doenças Metabólicas/genética , Doenças Metabólicas/metabolismo , Gravidez , Complicações na Gravidez/genética , Complicações na Gravidez/metabolismo , Nascimento PrematuroRESUMO
An increased awareness on neonatal pain-associated complications has led to the development of pain scales adequate to assess the level of pain experienced by newborns such as the ABC score. A commonly used analgesic procedure is to administer a 33% oral dextrose solution to newborns prior to the painful intervention. Although this procedure is very successful, not in all subjects it reaches complete efficacy. A possible explanation for the different response to the treatment could be genetic variability. We have investigated the genetic variability of the OPRM1 gene in 1077 newborns in relation to non-pharmacologic pain relief treatment. We observed that the procedure was successful in 966 individuals and there was no association between the genotypes and the analgesic efficacy when comparing individuals that had an ABC score = 0 and ABC score >0. However, considering only the individuals with ABC score>0, we found that the homozygous carriers of the G allele of the missense variant SNP rs1799971 (A118G) showed an interesting association with higher ABC score. We also observed that individuals fed with formula milk were more likely to not respond to the analgesic treatment compared to those that had been breastfed.
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Genótipo , Doenças do Recém-Nascido , Manejo da Dor , Dor , Receptores Opioides mu , Feminino , Humanos , Recém-Nascido , Doenças do Recém-Nascido/genética , Doenças do Recém-Nascido/fisiopatologia , Doenças do Recém-Nascido/terapia , Masculino , Dor/genética , Dor/fisiopatologia , Polimorfismo de Nucleotídeo ÚnicoRESUMO
During pregnancy, drug addiction represents one of the most dangerous situations. Each drug can badly affect the fetal development and, when the pregnancy is over, the negative influence continues in the newborn which is exposed to many risks, in particular the withdrawal syndrome. Since it is difficult to predict the newborn's outcome only on the basis of the kind of drug assumed by the mother during pregnancy, we propose the idea of a score based on the placenta's state of health. The aim of the study is to correlate the placental score to the withdrawal symptoms graveness. Our retrospective study includes 35 newborns exposed in uterus to illegal and legal drugs. We used the Finnegan's scoring system to quantify withdrawal symptoms and the placental score, based on the anatomopathological analysis, to assess the placenta's health. The newborns included in our study have been divided into two groups depending on the result of the placental score (< or =2 or > or =3). We found a significant statistical difference between the newborns whose placental score was low (< or =2) and those whose score was high (> or =3): the second group showed severe withdrawal symptoms for a longer time during the hospital stay (p = 0.014).
Assuntos
Troca Materno-Fetal , Síndrome de Abstinência Neonatal/etiologia , Placenta/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Adulto , Analgésicos Opioides/efeitos adversos , Cannabis/efeitos adversos , Cocaína/efeitos adversos , Etanol/efeitos adversos , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Prontuários Médicos , Metadona/efeitos adversos , Valor Preditivo dos Testes , Gravidez , Nascimento Prematuro , Estudos Retrospectivos , Transtornos Relacionados ao Uso de Substâncias , Fatores de Tempo , Nicotiana/efeitos adversosRESUMO
OBJECTIVE: The aim of this study is to establish the serum level distribution of cortisol and ACTH in VLBW preterm newborns and determine which neonates are ideal candidates for the stimulation test for adrenal insufficiency. METHODS: Plasma cortisol and ACTH levels were evaluated in 416 VLBW newborns on days 1, 7, and 30 of life. Gender, gestational age, weight, type of delivery, RDS prophylaxis, and perinatal morbidities were considered as potential variability factors. RESULTS: Cortisol and ACTH levels significantly decreased between 1, 7, and 30 days. Significantly higher cortisol levels were found at lower gestational ages and in infants born by vaginal delivery, whereas lower levels were observed in those born after maternal corticosteroid treatment. The distribution of cortisol and ACTH levels in healthy infants born by cesarian section is presented. CONCLUSION: Even if high or low levels were not frequently linked to illness, the presented distribution data may indicate that the newborns are ideal candidates for the stimulation test.
Assuntos
Hormônio Adrenocorticotrópico/sangue , Hidrocortisona/sangue , Recém-Nascido Prematuro/sangue , Recém-Nascido de muito Baixo Peso/sangue , Feminino , Humanos , Lactente Extremamente Prematuro/sangue , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/sangue , Masculino , Valores de ReferênciaRESUMO
Among neonatal epileptic syndromes, benign familial neonatal seizures (BFNS) are often due to autosomal-dominant mutations of the KCNQ2 gene. Seizures are usually characterized by asymmetric tonic posturing with apnea with onset in the first 7 days of life; they may even occur more than 10 times per day or evolve into status epilepticus. The delivery course of our patient was uneventful and family history was negative; on the second day of life the baby became pale, rigid, and apnoic during breastfeeding and appeared jittery and irritable when stimulated or examined. At age 3 days, she experienced clusters of generalized tonic seizures with pallor, desaturation, bradycardia, and partial response to intravenous phenobarbital; during her 4th and 5th days of life, three episodes of tonic seizures were noticed. At age 6 days, the patient experienced about 10 episodes of tonic seizures involving both sides of the body, which gradually responded to intravenous phenytoin. Electroencephalograms revealed abnormalities but brain MRI was normal. The patient is seizure-free since postnatal day 21; she is now 12 months old with cognitive development within normal limits at Bayley III Scale and mild motor delay. The patient is on maintenance therapy with phenobarbital since she was 7 months old. A de novo heterozygous mutation (c.853C>T/p.P285S) in the KCNQ2 gene was identified. We therefore describe a case of de novo KCNQ2-related neonatal convulsions with necessity of multiple anticonvulsants for the control of seizures, mutation occurring in the pore channel of the voltage-gated potassium channel subfamily Q member 2 associated with a likely benign course; furthermore, the same mutation of the KCNQ2 gene and a similar one (c.854C>A/p.P285H) have already been described in association with Ohtahara syndrome. Probably acquired environmental, perinatal and genetic risk factors are very important in determining the different phenotype; we hope that the rapid progress of analysis tools in molecular diagnosis can also be used in the search of an individualized therapeutic approach for these patients.
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Background/Aims: IntraUterine (IUGR) and ExtraUterine Growth Restriction (EUGR) may induce reprogramming mechanisms, finalized to survive before and after birth. Nutritional factors and other environmental signals could regulate gene expression through epigenetic modification, but the molecular mechanisms involved are not yet well understood. Epigenetic mechanisms could be considered as a bridge between environmental stimuli and long lasting phenotype, acquired during the intrauterine life and the first weeks of life. Our aim was to investigate the relationship between growth patterns, nutritional determinants, and epigenetic pathways. Methods: We enrolled 38 newborns admitted to Neonatal Intensive Care Unit (NICU) at University Hospital of Pisa. Gestational age at birth was <34 weeks and post-menstrual age (PMA) was 36-42 weeks at discharge. We excluded infants with malformations or clinical syndromes. EUGR was defined as the reduction in weight z score between birth and discharge >1 SD. We also evaluated DNA methylation of Imprinting Centre 1 (IC1) at birth and at discharge. Results: We observed a decrease in SD of weight and head circumference mainly during the first weeks of life. We found a correlation between EUGR for weight and for head circumference and an increased IC1 methylation (p = 0.018 and p = 0.0028, respectively). We observed a relationship between reduced protein and lipid intake and IC1 hypermethylation (p = 0.009 and p = 0.043, respectively). Conclusion: IC1 hypermethylation could be a reprogramming mechanism to promote a catch-up growth, by means of an increased Insulin-like growth factor 2 (IGF2) expression, that may have potential effects on metabolic homeostasis later in life.
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BACKGROUND: Newborn hearing screening has to be considered the first step of a program for the identification, diagnosis, treatment and habilitation/rehabilitation of children with hearing impairment. MAIN PART: In Tuscany Region of Italy, the universal newborn hearing screening is mandatory since november 2007. The first guidelines for the execution of the screening have been released in June 2008; then many other Italian regions partially or totally adopted these guidelines. On the basis of the experience from 2008 and according to the recent evidences in the scientific literature, a new screening protocol was released in Tuscany region. The new protocol is an evolution of the previous one. Some issues reported in the previous protocol and in the Joint Committee on Infant Hearing statement published in 2007 were revised, such as the risk factors for auditory neuropathy and for late onset, progressive or acquired hearing loss. The new updated guidelines were submitted to the Sanitary Regional Council and then they have been approved in August 2016. The updated screening protocol is mainly aimed to identify newborns with a congenital moderate-to-profound hearing loss, but it also provides indications for the audiological follow-up of children with risk's factor for progressive or late onset hearing loss; further it provides indications for the audiological surveillance of children at risk for acquired hearing impairment. Then, in the new guidelines the role of the family paediatrician in the newborn hearing screening and audiological follow-up and surveillance is underscored. Finally the new guidelines provide indications for the treatment with hearing aids and cochlear implant, in accordance with the recent Italian Health Technology Assessment (HTA) guidelines. CONCLUSIONS: In the paper we report the modality of execution of the universal newborn hearing screening in the Tuscany Region, according to the recently updated protocol. The main features of the protocol and the critical issues are discussed.
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Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/epidemiologia , Triagem Neonatal/normas , Feminino , Perda Auditiva Neurossensorial/congênito , Humanos , Recém-Nascido , Itália/epidemiologia , Masculino , Triagem Neonatal/métodos , Guias de Prática Clínica como Assunto , Prevalência , Medição de Risco , Fatores SexuaisRESUMO
We report the case of 2 sisters (46,XX) born from consanguineous Moroccan parents. Both sisters had normal female genitalia, but within 2 weeks after birth, they presented with a severe salt-wasting crisis. Hormonal investigations suggested the diagnosis of congenital adrenal hyperplasia, which was confirmed by subsequent molecular analysis to be caused by 3ß-hydroxysteroid dehydrogenase type 2 deficiency. Here, we discuss the main features like onset, possible complications, genetics, and replacement therapy of this rare disease.
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Hiperplasia Suprarrenal Congênita/patologia , Genitália Feminina/patologia , Irmãos , Glândulas Suprarrenais/diagnóstico por imagem , Glândulas Suprarrenais/patologia , Hiperplasia Suprarrenal Congênita/diagnóstico por imagem , Feminino , Humanos , Recém-Nascido , Masculino , Marrocos , LinhagemRESUMO
Sotos syndrome (SoS) is characterized by overgrowth of prenatal onset, learning disability, and characteristic facial appearance; it is usually due to haploinsufficiency of NSD1 gene at chromosome 5q35. An Italian child was born at 37 weeks of gestation (weight 2,910 g, 25th-50th centiles; length 50 cm, 75th centile; head circumference 36 cm, 97th centile) showing cryptorchidism on the right side, hypertelorism, dolichocephaly, broad and prominent forehead, and narrow jaw; the pregnancy was worsened by maternal preeclampsia and gestational diabetes, and his mother had a previous history of four early miscarriages. The patient showed neonatal jaundice, hypotonia, feeding difficulties, frequent vomiting, and gastroesophageal reflux. After the age of 6 months, his weight, length, and head circumference were above the 97th centile; psychomotor development was delayed. At the age of 9 years, the patient showed also joint laxity and scoliosis. DNA sequence analysis of NSD1 gene detected a novel heterozygous mutation (c.521T>A, p.Val174Asp) in exon 2. The same mutant allele was also found in the mother and in the maternal grandfather of the proband; both the mother and the maternal grandfather of the proband showed isolated overgrowth with height above the 97th centile in absence of other features of SoS. At present 23 familial cases of SoS have been described (two cases with mutation in exon 2 of NSD1 gene); no familial cases of SoS with mutation of NSD1 gene and isolated overgrowth have been reported. Probably, point mutations of NSD1 gene, and particularly mutations between exon 20 and exon 23, are not likely to affect reproductive fitness. Epigenetic mechanisms and intrauterine environment may influence phenotypes, therefore genetic tests are not useful to predict the phenotype but they are indispensable for the diagnosis of SoS. This is the first Italian familial case of SoS with genetic confirmation and the third report in which a missense mutation of NSD1 gene is found in three generations of the same family.
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It is well established that somatic genomic changes can influence phenotypes in cancer, but the role of adaptive changes in developmental disorders is less well understood. Here we have used next-generation sequencing approaches to identify de novo heterozygous mutations in sterile α motif domain-containing protein 9 (SAMD9, located on chromosome 7q21.2) in 8 children with a multisystem disorder termed MIRAGE syndrome that is characterized by intrauterine growth restriction (IUGR) with gonadal, adrenal, and bone marrow failure, predisposition to infections, and high mortality. These mutations result in gain of function of the growth repressor product SAMD9. Progressive loss of mutated SAMD9 through the development of monosomy 7 (-7), deletions of 7q (7q-), and secondary somatic loss-of-function (nonsense and frameshift) mutations in SAMD9 rescued the growth-restricting effects of mutant SAMD9 proteins in bone marrow and was associated with increased length of survival. However, 2 patients with -7 and 7q- developed myelodysplastic syndrome, most likely due to haploinsufficiency of related 7q21.2 genes. Taken together, these findings provide strong evidence that progressive somatic changes can occur in specific tissues and can subsequently modify disease phenotype and influence survival. Such tissue-specific adaptability may be a more common mechanism modifying the expression of human genetic conditions than is currently recognized.