Conservative management of newborns with 35 weeks or more of gestational age at risk for early-onset sepsis: a Brazilian cohort study

Abstract Objective: To evaluate the conservative management of newborns born at ≥35 weeks of gestational age, at risk for early-onset neonatal sepsis (EOS). Methods: Retrospective, analytic cohort study (2016 to 2019), including newborns ≥35 weeks of gestational at risk of EOS, asymptomatic at birth, managed conservatively in full rooming-in: serial physical examination and clinical observation for at least 48 h. They were classified into three groups, according to the clinical course: asymptomatic (group A), symptomatic for other reasons (group B), and with sepsis (group C). Risk factors, clinical signs and differential diagnoses of sepsis, length of stay, and discharge conditions were evaluated. Results: The authors evaluated 769 asymptomatic newborns at risk of EOS. (mean birth weight 2999 ± 485 g and gestational age 37.6 ± 1.7 weeks, respectively) corresponding to 12.2% of rooming-in admissions. The most prevalent risk factors were colonization by Group B Streptococcus (29%), prolonged rupture membrane duration (21.9%) and preterm labor (21.4%). Most of all of them (53.9%) remained asymptomatic (group A). Group B corresponded for 45.3%, and the most common clinical signs were hypothermia (24.5%), tremors (8.7%) and vomiting (8%). Environmental dysthermia (50.7%), prematurity (20.0%), and feeding intolerance (15.7%) were common in Group B. Laboratory tests were performed in 3.5%. Five patients (one confirmed) comprised group C (0.8/1,000 live births). There were no deaths. The median length of stay was 64 h (IQR 50-93). Conclusion: The rate of clinical/confirmed EOS was low. Most of the symptomatic patients only needed clinical evaluation to rule out sepsis. Management was shown to be safe.

Conservative management of newborns with 35 weeks or more of gestational age at risk for early-onset sepsis: a Brazilian cohort study.

OBJECTIVE: To evaluate the conservative management of newborns born at ≥35 weeks of gestational age, at risk for early-onset neonatal sepsis (EOS). METHODS: Retrospective, analytic cohort study (2016 to 2019), including newborns ≥35 weeks of gestational at risk of EOS, asymptomatic at birth, managed conservatively in full rooming-in: serial physical examination and clinical observation for at least 48 h. They were classified into three groups, according to the clinical course: asymptomatic (group A), symptomatic for other reasons (group B), and with sepsis (group C). Risk factors, clinical signs and differential diagnoses of sepsis, length of stay, and discharge conditions were evaluated. RESULTS: The authors evaluated 769 asymptomatic newborns at risk of EOS. (mean birth weight 2999 ± 485 g and gestational age 37.6 ± 1.7 weeks, respectively) corresponding to 12.2% of rooming-in admissions. The most prevalent risk factors were colonization by Group B Streptococcus (29%), prolonged rupture membrane duration (21.9%) and preterm labor (21.4%). Most of all of them (53.9%) remained asymptomatic (group A). Group B corresponded for 45.3%, and the most common clinical signs were hypothermia (24.5%), tremors (8.7%) and vomiting (8%). Environmental dysthermia (50.7%), prematurity (20.0%), and feeding intolerance (15.7%) were common in Group B. Laboratory tests were performed in 3.5%. Five patients (one confirmed) comprised group C (0.8/1,000 live births). There were no deaths. The median length of stay was 64 h (IQR 50-93). CONCLUSION: The rate of clinical/confirmed EOS was low. Most of the symptomatic patients only needed clinical evaluation to rule out sepsis. Management was shown to be safe.

Acute liver failure in a term neonate after repeated paracetamol administration.

OBJECTIVE: Severe hepatotoxicity caused by paracetamol is rare in neonates. We report a case of paracetamol-induced acute liver failure in a term neonate. CASE DESCRIPTION: A 26-day-old boy was admitted with intestinal bleeding, shock signs, slight liver enlargement, coagulopathy, metabolic acidosis (pH=7.21; bicarbonate: 7.1 mEq/L), hypoglycemia (18 mg/dL), increased serum aminotransferase activity (AST=4,039 IU/L; ALT=1,087 IU/L) and hyperbilirubinemia (total: 9.57 mg/dL; direct: 6.18 mg/dL) after receiving oral paracetamol (10 mg/kg/dose every 4 hours) for three consecutive days (total dose around 180 mg/kg; serum concentration 36-48 hours after the last dose of 77 µg/ mL). Apart from supportive measures, the patient was successfully treated with intravenous N-acetylcysteine infusion during 11 consecutive days, and was discharged on day 34. The follow-up revealed full recovery of clinical and of laboratory findings of hepatic function. COMMENTS: The paracetamol pharmacokinetics and pharmacodynamics in neonates and infants differ substantially from those in older children and adults. Despite the reduced rates of metabolism by the P-450 CYP2E1 enzyme system and the increased ability to synthesize glutathione--which provides greater resistance after overdoses--, it is possible to produce hepatotoxic metabolites (N-acetyl-p-benzoquinone) that cause hepatocellular damage, if glutathione sources are depleted. Paracetamol clearance is reduced and the half-life of elimination is prolonged. Therefore, a particular dosing regimen should be followed due to the toxicity risk of cumulative doses. This report highlights the risk for severe hepatotoxicity in neonates after paracetamol multiple doses for more than two to three days.

Acute liver failure in a term neonate after repeated paracetamol administration / Falencia hepatica aguda en neonato a termino despues de la ingestion de dosis repetidas de paracetamol / Falencia hepatica aguda em neonato de termo apos ingestao de doses repetidas de paracetamol

Objective: Severe hepatotoxicity caused by paracetamol is rare in neonates. We report a case of paracetamol-induced acute liver failure in a term neonate. Case description: A 26-day-old boy was admitted with intestinal bleeding, shock signs, slight liver enlargement, coagulopathy, metabolic acidosis (pH=7.21; bicarbonate: 7.1mEq/L), hypoglycemia (18mg/dL), increased serum aminotransferase activity (AST=4,039IU/L; ALT=1,087IU/L) and hyperbilirubinemia (total: 9.57mg/dL; direct: 6.18mg/dL) after receiving oral paracetamol (10mg/kg/dose every 4 hours) for three consecutive days (total dose around 180mg/kg; serum concentration 36-48 hours after the last dose of 77µg/ mL). Apart from supportive measures, the patient was successfully treated with intravenous N-acetylcysteine infusion during 11 consecutive days, and was discharged on day 34. The follow-up revealed full recovery of clinical and of laboratory findings of hepatic function. Comments: The paracetamol pharmacokinetics and pharmacodynamics in neonates and infants differ substantially from those in older children and adults. Despite the reduced rates of metabolism by the P-450 CYP2E1 enzyme system and the increased ability to synthesize glutathione - which provides greater resistance after overdoses -, it is possible to produce hepatotoxic metabolites (N-acetyl-p-benzoquinone) that cause hepatocellular damage, if glutathione sources are depleted. Paracetamol clearance is reduced and the half-life of elimination is prolonged. Therefore, a particular dosing regimen should be followed due to the toxicity risk of cumulative doses. This report highlights the risk for severe hepatotoxicity in neonates after paracetamol multiple doses for more than two to three days. .

Objetivo: La hepatotoxicidad grave inducida por el paracetamol es muy rara en neonatos. Se relata el caso de un neonato a término que desarrolló falencia hepática aguda después del uso de paracetamol. Descripción del caso: Niño, 26 días, admitido con sangrado intestinal, señales de choque, discreta hepatomegalia, coagulopatía, acidosis metabólica (pH=7,21; bicarbonato: 7,1mEq/L), hipoglucemia (18mg/dL), aumento de las aminotransferasas séricas (AST=4.039UI/L; ALT=1.087UI/L) e hiperbilirrubinemia (total: 9,75mg/dL; directa: 6,18mg/dL), después del uso de paracetamol por vía oral (10mg/kg/dosis a cada cuatro horas) durante tres días consecutivos (dosis alrededor de 180mg/kg; nivel sérico de 36-48 horas después de la última dosis de 77µg/mL). Además de las medidas de soporte, el paciente fue tratado con N-acetilcisteína (infusión intravenosa continua por 11 días consecutivos), recibiendo alta después de 34 días de internación. El seguimiento mostró recuperación clínica y de los parámetros laboratoriales de la función hepática. Comentarios : La farmacocinética y la farmacodinámica del paracetamol en neonatos y lactantes jóvenes (menores de un año) difieren substancialmente de niños más grandes y adultos. A pesar de que las tasas de metabolismo del sistema enzimático P-450 CYP2E1 están reducidas y la capacidad de generar glutatión, aumentada - confiriendo más protección después de superdosis -, existe la posibilidad de producción de metabólitos hepatotóxicos (N-acetil-pbenzoquinoneimina) que determinan lisis celular, caso se agoten las reservas de glutatión. La depuración es reducida y la media vida de la eliminación, alargada, recomendándose posología distinta por el riesgo de toxicidad ...

Objetivo: A hepatoxicidade grave induzida pelo paracetamol é muito rara em neonatos. Relata-se o caso de um neonato de termo que desenvolveu falência hepática aguda após o uso de paracetamol. Descrição do caso: Menino, 26 dias, admitido com sangramento intestinal, sinais de choque, discreta hepatomegalia, coagulopatia, acidose metabólica (pH=7,21; bicarbonato: 7,1mEq/L), hipoglicemia (18mg/dL), aumento das aminotransferases séricas (AST=4.039UI/L; ALT=1.087UI/L) e hiperbilirrubinemia (total: 9,57mg/dL; direta: 6,18mg/dL), após uso de paracetamol via oral (10mg/kg/dose a cada quatro horas) por três dias consecutivos (dose total ao redor de 180mg/kg; nível sérico de 36-48 horas após a última dose de 77µg/mL). Além das medidas de suporte, o paciente foi tratado com N-acetilcisteína (infusão intravenosa contínua por 11 dias consecutivos), recebendo alta após 34 dias de internação. O seguimento mostrou recuperação clínica e dos parâmetros laboratoriais da função hepática. Comentários: A farmacocinética e a farmacodinâmica do paracetamol em neonatos e lactentes jovens (menores de um ano) diferem substancialmente de crianças maiores e adultos. Apesar de as taxas de metabolismo do sistema enzimático P-450 CYP2E1 estarem diminuídas e a capacidade de gerar glutationa, aumentadas - conferindo maior proteção após superdosagens -, existe a possibilidade de produção de metabólitos hepatotóxicos (N-acetil-p-benzoquinoneimina) que determinam lise celular, caso se esgotem as reservas de glutationa. A depuração é diminuída e a meia-vida de eliminação é prolongada, recomendando-se posologia distinta pelo risco de toxicidade de doses cumulativas. O presente relato destaca o risco de hepatotoxicidade grave ...