Early neurodevelopmental outcomes of extreme preterm infants exposed to paracetamol: a retrospective cohort study.

BACKGROUND: Paracetamol is commonly used for analgesia and patent ductus arteriosus (PDA) treatment in preterm infants. We aimed to evaluate early neurodevelopmental outcomes of extreme preterm infants exposed to paracetamol during their neonatal admission. METHODS: This retrospective cohort study included surviving infants born at <29 weeks gestation, or with a birth weight of <1000 grams. Neurodevelopmental outcomes studied were early cerebral palsy (CP) or high risk of CP diagnosis, Hammersmith Infant Neurological Examination (HINE) score and Prechtl General Movement Assessment (GMA) at 3-4 months corrected age. RESULTS: Two hundred and forty-two infants were included, of which 123 were exposed to paracetamol. After adjusting for birth weight, sex and chronic lung disease, there were no significant associations between paracetamol exposure and early CP or high risk of CP diagnosis (aOR 1.46, 95% CI 0.61, 3.5), abnormal or absent GMA (aOR 0.82, 95% CI 0.37, 1.79) or HINE score (adjusted ß -0.19, 95% CI -2.39, 2.01). Subgroup analysis stratifying paracetamol exposure into <180 mg/kg or ≥180 mg/kg cumulative dose found that neither had significant effects on outcomes. CONCLUSIONS: In this cohort of extreme preterm infants, no significant association was found between exposure to paracetamol during the neonatal admission and adverse early neurodevelopment. IMPACT: Paracetamol is commonly used in the neonatal period for analgesia and patent ductus arteriosus treatment in preterm infants, although prenatal paracetamol use has been associated with adverse neurodevelopmental outcomes. Exposure to paracetamol during the neonatal admission was not associated with adverse early neurodevelopment at 3-4 months corrected age in this cohort of extreme preterm infants. The findings from this observational study is consistent with the small body of literature supporting the lack of association between neonatal paracetamol exposure and adverse neurodevelopmental outcomes in preterm infants.

Assessing the Utility of Neonatal Screening Assessments in Early Diagnosis of Cerebral Palsy in Preterm Infants.

Background: Early diagnosis of cerebral palsy (CP) in high-risk infants is possible at 3−4 months' corrected age (CA) using standardised assessments. Aim: To assess the utility of neonatal screening assessments­writhing general movements (GMs) and the Hammersmith Neonatal Neurological Examination (HNNE)­to predict CP/high-risk status at 3−4 months' CA in extremely preterm infants. Methods: Retrospective cohort study of high-risk preterm infants (born < 29 weeks' gestation and/or birth weight < 1000 g) attending an Early Neurodevelopment Clinic. Data from neonatal assessments were compared with CP/high-risk diagnosis at 3−4 months' CA, fidgety GMs, and Hammersmith Infant Neurological Examinations (HINE) using logistic regression, linear regression, and Spearman rank correlation. Results: Two hundred and two preterm infants (median gestation age at birth 27.3 (IQR 25.4−28.3) weeks, mean birth weight 870.3 (SD 248.4) grams) were included. A total of 26 (12.8%) infants received early CP/high-risk diagnoses at 3−4 months' CA. A lower gestational age (GA) (OR = 0.78; p = 0.029, 95% CI [0.26, 0.97]) and abnormal writhing GMs (OR 1.56; p = 0.019, 95% CI [1.07, 2.27]) were predictive of CP/high-risk diagnosis. Although after adjustment for sex, GA, birth weight, and growth restriction, GA (aOR = 0.67; p = 0.068, 95% CI [0.44, 1.03]) and writhing GMs (aOR = 1.44; p = 0.087, 95% CI [0.95, 2.20]) were not significant, a strong trend still persisted. The HNNE scores significantly correlated with both the HINE evaluation (rs = 0.43, p < 0.001, 95% CI [0.31, 0.56]) and fidgety GMs (rs = −0.10, p = 0.012, 95% CI [−0.32, −0.04]). Linear regression confirmed the HNNE was highly predictive of the HINE (correlation coefficient 0.82; p < 0.001, 95% CI [0.48, 1.15]). Writhing GMs did not significantly correlate with either fidgety GMs (p = 0.723, 95% CI [−0.12, 0.17]) or the HINE (p = 0.173, 95% CI [−0.24, 0.04]). Conclusions: Abnormal writhing GMs in the neonatal period were non-significantly associated with early CP/high-risk diagnoses in extremely preterm infants in a multivariate analysis. Additionally, the HNNE significantly correlated with both fidgety GMs and the HINE.

Early detection of cerebral palsy in high-risk infants: Translation of evidence into practice in an Australian hospital.

AIM: The early diagnosis of cerebral palsy (CP) allows children timely access to early intervention. In 2018, Monash Children's Hospital established an Early Neurodevelopment Clinic based upon evidence-based guidelines for the early diagnosis of CP in high-risk infants. In this study, we aimed to characterise the infants presenting to the clinic and determine the rate of CP diagnosis. METHODS: This study analysed data from infants attending the Early Neurodevelopment Clinic between May 2019 and April 2020. Infants at high-risk for CP attended the clinic at 3 months corrected age. Neuroimaging reports were reviewed, and a Prechtl's General Movement Assessment and Hammersmith Infant Neurological Examination were performed. Infants were diagnosed as having typical development, delayed development, high-risk of CP or CP at the time of clinic attendance and referred on to the appropriate pathway. RESULTS: Ninety-six high-risk infants attended the clinic over the 1 year study period. Sixty-eight (71%) infants were extremely preterm or extremely low birthweight, and 28 (29%) were infants at born at older gestation with evidence of moderate to severe brain injury. Nine (9.6%) infants received a CP diagnosis and 12 (12.5%) were considered high-risk of CP. All infants with CP or high-risk of CP were referred to the Victorian Paediatric Rehabilitation Service. CONCLUSIONS: It is feasible to implement the early CP diagnosis guidelines into a high-risk infant follow-up clinic. Implementation of the guidelines allows for early diagnosis of CP and appropriate referral of high-risk infants.