Perinatal stress and methylation of the NR3C1 gene in newborns: systematic review.

Adverse experiences in the perinatal period have been associated with the methylation of the human glucocorticoid receptor gene (NR3C1) and long-term diseases. We conducted a systematic review on the association between adversities in the perinatal period and DNA methylation in the 1 F region of the NR3C1 gene in newborns. We explored the MEDLINE, Web of Science, Scopus, Scielo, and Lilacs databases without time or language limitations. Two independent reviewers performed the selection of articles and data extraction. A third participated in the methodological quality assessment and consensus meetings at all stages. Finally, ten studies were selected. Methodological quality was considered moderate in six and low in four. Methylation changes were reported in 41 of the 47 CpG sites of exon 1 F. Six studies addressed maternal conditions during pregnancy: two reported methylation changes at the same sites (CpG 10, 13, 20, 21 and 47), and four at one or more sites from CpG 35 to 39. Four studies addressed neonatal parameters and morbidities: methylation changes at the same sites 4, 8, 10, 16, 25, and 35 were reported in two. Hypermethylation associated with stressful conditions prevailed. Hypomethylation was more often associated with protective conditions (maternal-foetal attachment during pregnancy, breast milk intake, higher birth weight or Apgar). In conclusion, methylation changes in several sites of the 1 F region of the NR3C1 gene in newborns and very young infants were associated with perinatal stress, but more robust and comparable results are needed to corroborate site-specific associations.

NR3C1 gene methylation and cortisol levels in preterm and healthy full-term infants in the first 3 months of life.

Aim: To describe NR3C1 exon-1F methylation and cortisol levels in newborns. Materials & methods: Preterm ≤1500 g and full-term infants were included. Samples were collected at birth and at days 5, 30 and 90 (or at discharge). Results: 46 preterm and 49 full-term infants were included. Methylation was stable over time in full-term infants (p = 0.3116) but decreased in preterm infants (p = 0.0241). Preterm infants had higher cortisol levels on the fifth day, while full-term infants showed increasing levels (p = 0.0177) over time. Conclusion: Hypermethylated sites in NR3C1 at birth and higher cortisol levels on day 5 suggest that prematurity, reflecting prenatal stress, affects the epigenome. Methylation decrease over time in preterm infants suggests that postnatal factors may modify the epigenome, but their role needs to be clarified.

We investigated the methylation of a gene, NR3C1 exon-1F, and cortisol levels in newborns. DNA methylation is a biochemical process that can modify gene activity. In the case of this gene, higher methylation might be associated with higher cortisol levels. We studied 46 preterm infants (born weighing 1500 g or less) and 49 full-term infants. Our results revealed that the preterm infants had hypermethylation at birth and higher cortisol levels on day 5, but decreasing methylation and stable cortisol levels over time. Meanwhile, methylation remained stable and cortisol levels increased in full-term babies with time. These unexpected results suggest that prematurity can be associated with prenatal epigenetic changes in the NR3C1 gene, but postnatal factors may induce further modifications. More research is needed to understand these findings better.

[Risk factors for respiratory morbidity at 12 to 36 months in very low birth weight premature infants previously admitted to a public neonatal intensive care unit]. / Fatores associados à morbidade respiratória entre 12 e 36 meses de vida de crianças nascidas de muito baixo peso oriundas de uma UTI neonatal pública.

The aim of this paper was to estimate respiratory morbidity and its determinants for premature infants aged 12 to 36 months. The population comprised 84 infants from a cohort of very low birth weight premature infants. The outcome was the respiratory morbidity incidence rate. The relationship between the independent variables and respiratory morbidity was estimated using a Poisson regression model. From 12 to 24 months of age, 56.3% of children had experienced at least one episode of respiratory disease. >From 24 to 36 months, 38.1% of children were affected. Variables significantly associated with respiratory morbidity were bronchopulmonary dysplasia (RR = 1.9; 95%CI: 1.2-2.9), abnormal lung compliance (RR = 1.6; 95%CI: 1.1-2.3), neonatal pneumonia (RR = 2.8; 95%CI: 1.9-4.0), patent ductus arteriosus (RR = 1.6; 95%CI: 1.1-2.5), and respiratory morbidity in the first year of life (RR = 1.7; 95%CI: 1.2-2.5). The incidence of respiratory morbidity remains high in this group of high-risk infants, which calls for regular follow-up and effective interventions to prevent respiratory disease and to improve the quality of life of these children and their families.

Predictive factors for neuromotor abnormalities at the corrected age of 12 months in very low birth weight premature infants.

BACKGROUND: The increase in survival of premature newborns has sparked growing interest in the prediction of their long-term neurodevelopment. OBJECTIVE: To estimate the incidence of neuromotor abnormalities at the corrected age of 12 months and to identify the predictive factors associated with altered neuromotor development in very low birth weight premature infants. METHOD: Cohort study. The sample included 100 premature infants. The outcome was neuromotor development at 12 months classified by Bayley Scale (PDI) and neurological assessment (tonus, reflexes, posture). A multivariate logistic regression model was constructed. Neonatal variables and neuromotor abnormalities up to 6 months of corrected age were selected by bivariate analysis. RESULTS: Mean birth weight was 1126g (SD: 240). Abnormal neuromotor development was presented in 60 children at 12 months corrected age. CONCLUSION: According to the model, patients with a diagnosis including bronchopulmonary dysplasia, hypertonia of lower extremities, truncal hypotonia showed a 94.0% probability of neuromotor involvement at 12 months.

Fatores associados à morbidade respiratória entre 12 e 36 meses de vida de crianças nascidas de muito baixo peso oriundas de uma UTI neonatal pública / Risk factors for respiratory morbidity at 12 to 36 months in very low birth weight premature infants previously admitted to a public neonatal intensive care unit

O objetivo do estudo foi estimar a morbidade respiratória entre 12 e 36 meses em crianças prematuras e identificar os fatores associados. A população compreendeu 84 crianças de uma coorte de prematuros de muito baixo peso. O desfecho foi a taxa de incidência de morbidade respiratória. A associação entre as variáveis independentes e morbidade respiratória foi verificada por modelo linear generalizado. Entre 12 e 24 meses, 56,3 por cento das crianças apresentaram morbidade respiratória. Entre 24 e 36 meses, 38,1 por cento das crianças foram acometidas. As variáveis associadas à morbidade respiratória foram: displasia broncopulmonar (RT = 1,9; IC95 por cento: 1,2-2,9), complacência pulmonar alterada (RT = 1,6; IC95 por cento: 1,1-2,2), pneumonia neonatal (RT = 2,8; IC95 por cento: 2,0-4,0), persistência do canal arterial (RT = 1,6; IC95 por cento: 1,1-2,4) e morbidade respiratória no primeiro ano de vida (RT = 1,8; IC95 por cento: 1,3-2,6). A incidência de morbidade respiratória entre 12 e 36 meses se manteve elevada neste grupo de crianças de alto risco, o que reforça a necessidade de acompanhamento e de intervenções efetivas na prevenção do adoecimento e na melhora da qualidade de vida destas crianças e suas famílias.

The aim of this paper was to estimate respiratory morbidity and its determinants for premature infants aged 12 to 36 months. The population comprised 84 infants from a cohort of very low birth weight premature infants. The outcome was the respiratory morbidity incidence rate. The relationship between the independent variables and respiratory morbidity was estimated using a Poisson regression model. From 12 to 24 months of age, 56.3 percent of children had experienced at least one episode of respiratory disease. >From 24 to 36 months, 38.1 percent of children were affected. Variables significantly associated with respiratory morbidity were bronchopulmonary dysplasia (RR = 1.9; 95 percentCI: 1.2-2.9), abnormal lung compliance (RR = 1.6; 95 percentCI: 1.1-2.3), neonatal pneumonia (RR = 2.8; 95 percentCI: 1.9-4.0), patent ductus arteriosus (RR = 1.6; 95 percentCI: 1.1-2.5), and respiratory morbidity in the first year of life (RR = 1.7; 95 percentCI: 1.2-2.5). The incidence of respiratory morbidity remains high in this group of high-risk infants, which calls for regular follow-up and effective interventions to prevent respiratory disease and to improve the quality of life of these children and their families.

Predictive factors for neuromotor abnormalities at the corrected age of 12 months in very low birth weight premature infants / Fatores preditivos para anormalidades neuromotoras aos 12 meses de idade corrigida em prematuros de muito baixo peso

BACKGROUND: The increase in survival of premature newborns has sparked growing interest in the prediction of their long-term neurodevelopment. OBJECTIVE: To estimate the incidence of neuromotor abnormalities at the corrected age of 12 months and to identify the predictive factors associated with altered neuromotor development in very low birth weight premature infants. METHOD: Cohort study. The sample included 100 premature infants. The outcome was neuromotor development at 12 months classified by Bayley Scale (PDI) and neurological assessment (tonus, reflexes, posture). A multivariate logistic regression model was constructed. Neonatal variables and neuromotor abnormalities up to 6 months of corrected age were selected by bivariate analysis. RESULTS: Mean birth weight was 1126g (SD: 240). Abnormal neuromotor development was presented in 60 children at 12 months corrected age. CONCLUSION: According to the model, patients with a diagnosis including bronchopulmonary dysplasia, hypertonia of lower extremities, truncal hypotonia showed a 94.0 percent probability of neuromotor involvement at 12 months.

INTRODUÇÃO: O aumento na sobrevida de recém-nascidos prematuros tem suscitado interesse crescente na predição do seu neurodesenvolvimento a longo prazo. OBJETIVO: Estimar a incidência de anormalidades neuromotoras aos 12 meses de idade corrigida e identificar os fatores associados ao desenvolvimento neuromotor alterado em prematuros de muito baixo peso. MÉTODO: Estudo de coorte. A amostra incluiu 100 crianças prematuras.O desfecho foi o desenvolvimento neuromotor aos 12 meses. Modelo de regressão logística multivariado foi construído. Variáveis neonatais e anormalidades neuromotoras até os 6 meses de idade corrigida foram selecionadas por análise bivariada. RESULTADOS: O peso de nascimento médio foi 1126g (DP:240). Aos 12 meses 60 por cento das crianças apresentaram desenvolvimento neuromotor alterado. CONCLUSÃO: De acordo com o modelo, pacientes com diagnóstico incluindo displasia broncopulmonar, hipertonia de membros inferiores e hipotonia de tronco tinham 94 por cento de probabilidade de comprometimento neuromotor aos 12 meses.

Morbidade respiratória em prematuros de muito baixo peso durante a infância / Respiratory Morbidade in prematures of very low weight during infancy

O objetivo deste estudo foi avaliar a incidência de morbidade respiratória em 84 crianças de uma coorte de prematuros, com peso ao nascer inferior a 1500g e verificar fatores associados à morbidade respiratória entre 12 e 36 meses de idade. Morbidade respiratória foi definida como presença de internação por problema respiratório e/ou pneumonia e/ou sibilos. O modelo adotado no estudo foi de uma coorte não concorrente. A associação entre as variáveis sócio-demográficas, maternas, neonatais e pós-neonatais com a morbidade respiratória na idade entre 12 e 36 meses foi verificada através do modelo linear generalizado com distribuição de Poisson e função de ligação logarítmica. Os resultados foram expressos como razões de taxas com intervalo de confiança.A população estudada foi composta por 42 crianças do sexo masculino. A idade gestacional média foi de 28,6 semanas e peso médio ao nascimento de 1097g. Na idade entre 12 e 24 meses, observamos que 45 das 80 crianças acompanhadas no período apresentaram morbidade respiratória, enquanto entre 24 e 36 meses 24das 63 crianças que compareceram às consultas no ambulatório de seguimento foram acometidas. No período entre 12 e 24 meses, 8,8 por cento das crianças necessitaram ser internadas, 26,3 por cento delas apresentaram pneumonia e 45 por cento sibilos. Entre 24 e 36 meses, 9,5 por cento das crianças foram internadas, 20,6 por cento tiveram diagnóstico de pneumonia e 28,6 por cento apresentaram sibilos. Os resultados foram obtidos através da razão de taxas ajustadas para o número de consultas das crianças no ambulatório. Após foi realizado o ajuste do modelo para número de consultas, idade gestacional, tempo de amamentação e sexo. As variáveis que mostraram associação com morbidade respiratória entre 12 e 36 meses de vida foram: displasia broncopulmonar, complacência pulmonar alterada, pneumonia neonatal, persistência do canal arterial e morbidade respiratória no primeiro ano de vida. A variável uso de ventilação mec...