Marie-Noëlle Simard

Neurodevelopmental Outcomes Following Bevacizumab Injections for Retinopathy of Prematurity

BACKGROUND AND OBJECTIVE: Bevacizumab intravitreal injection, a vascular endothelial growth factor inhibitor, is used to treat retinopathy of prematurity (ROP). However, concerns have been raised regarding its systemic absorption and effect on developing tissues including brain. This study compared neurodevelopment at 18 months’ corrected age in preterm infants of <29 weeks’ gestation treated with bevacizumab versus laser ablation. METHODS: Data from the Canadian Neonatal Network and the Canadian Neonatal Follow-Up Network databases were retrospectively reviewed. Infants born at <29 weeks’ in 2010–2011 with treated ROP were studied. Neurodevelopmental outcome at 18 months was assessed by using neurologic examination and the Bayley Scales of Infant and Toddler Development Third Edition. Regression analyses were performed. RESULTS: Of 125 treated infants, 27 received bevacizumab and 98 laser. The bevacizumab group, compared with laser, obtained a median Bayley Scales of Infant and Toddler Development Third Edition motor composite score of 81 (interquartile range, 70–91) versus 88 (79–97), a language composite score of 79 (65–97) versus 89 (74–97), and a cognitive score of 90 (80–100) versus 90 (85–100). Difference was detected on the motor score only (P = .02). Odds of severe neurodevelopmental disabilities (Bayley scores <70, severe cerebral palsy, hearing aids, or bilateral blindness) was 3.1 times higher (95% confidence interval: 1.2–8.4) in infants treated with bevacizumab versus laser after adjusting for gestational age, gender, maternal education, Score for Neonatal Acute Physiology-II score, bronchopulmonary dysplasia, sepsis, and severe brain injury. CONCLUSIONS: Preterm infants treated with bevacizumab versus laser had higher odds of severe neurodevelopmental disabilities. Further investigation on the long-term safety of antivascular endothelial growth factor treatment of ROP is needed.

Concurrent validity of ages and stages questionnaires in preterm infants.

BACKGROUND: Although preterm infants born at 29 to 36 gestational weeks (GW) are at risk for developmental delay, they do not always benefit from systematic follow-up. Primary care physicians are then responsible for their developmental surveillance and need effective screening tests. This study aimed to determine whether the Ages and Stages Questionnaires (ASQ) at 12 and 24 months’ corrected age (CA) identify developmental delay in preterm infants. METHODS: With a cross-sectional design involving 2 observations at 12 and 24 months’ CA, 124 and 112 preterm infants were assessed. Infants were born between May 2004 and April 2006 at 29 to 36 GW. The ASQ and the Bayley Scales of Infant Development were used. Concurrent validity was calculated by using κ coefficient, sensitivity, and specificity. RESULTS: At 12 months’ CA, the ASQ did not perform well in identifying infants with mental delay (κ = 0.08–0.19; sensitivity = 0.20–0.60; specificity = 0.68–0.88). Agreement (κ = 0.28–0.44) and specificity (0.90–0.97) were better for the psychomotor scale, but the sensitivity remained insufficient (0.25–0.52). At 24 months, the ASQ had good sensitivity (0.75–0.92) and specificity (0.55–0.78) for detecting mental delays (κ = 0.45). Results remained unsatisfactory for detecting motor delays (sensitivity = 0.31–0.50; specificity = 0.73–0.92). CONCLUSIONS: Preterm infants with developmental delays at 12 months’ CA are not adequately identified with the ASQ. At 24 months’ CA, the ASQ identifies mental delays but not psychomotor delays. Additional measures should be used to increase yield of detecting at-risk preterm infants.

Stability of neurocranial signs in the first two years of life in infants at risk.

BACKGROUND Acknowledgement of low-severity/high-prevalence disabilities in infants born preterm singles out the need to identify early markers of brain impairments which could predict these late emergent disabilities. The neurological status as assessed by the Amiel-Tison Neurological Assessments (ATNA) has been proposed as one such potential marker. However, the stability of the ATNA has never been formally assessed. AIM This study aimed to assess the stability of the ATNA. STUDY DESIGN A total of 89 infants born preterm with a gestational age ranging from 29 0/7 to 37 0/7 weeks inclusively and a birth weight below 2500 g were followed during their first two years of life (term age, 4, 8, 12 and 24 months corrected age) in a clinical context. RESULTS Of these, 62 children (69.7%) were classified in the same category on the five assessments while 14 (15.7%) had only one divergent result and 13 (14.6%) had two divergent results over the follow-up. The neurological status throughout the assessments remains stable according to Cochrans Q. CONCLUSION As the neurological status identified by the ATNA remained stable throughout repeated measurements in a regular clinical context and has been shown to correlate with later developmental performances, it should be included as a criterion to target children at risk and used during follow-up.

The Predictive Value of Head Circumference Growth during the First Year of Life on Early Child Traits

Atypical head circumference (HC) growth has been associated with neurodevelopmental disorders. However, whether it is associated with specific aspects of development in early childhood in the general population is unknown. The objective of this study was to assess the predictive value of HC growth as an early biomarker of behavioral traits. We examined longitudinal associations between HC growth from 0 to 12 months and temperament, cognitive, and motor development at 24 months. A subsample of healthy children (N = 756) was drawn from the 3D (Design, Develop, Discover) cohort study. Early HC growth was modeled with latent growth curve analysis. Greater postnatal HC growth predicted lower temperamental effortful control and lower surgency/extraversion in boys. HC growth did not predict cognitive or fine motor scores, but did predict greater gross motor skills in boys. No significant effect of HC growth was found in girls. This study is the first to demonstrate an association between postnatal HC growth and specific aspects of child development in a healthy population. Results suggest HC growth overshadows brain mechanisms involved in behavioral traits in early infancy. Whether links are maintained throughout development and the mechanisms involved correspond to traits found in atypical populations remains to be studied.

Validity of the language development survey in infants born preterm.

BACKGROUND Preterm infants are at greater risk of language delay. Early identification of language delay is essential to improve functional outcome in these children. AIM To examine the concurrent validity of Rescorlas Language Development Survey and the Bayley Scales of Infant and Toddler Development (Bayley-III) at 18months corrected age in preterm infants. STUDY DESIGN Test accuracy study. PARTICIPANTS 189 preterm infants born <29weeks were assessed at 18months. OUTCOME MEASURES The Language Development Survey, a parent-reported screening instrument, was administered in French concurrently with the Language Scales of the Bayley-III. Receiver-Operating-Characteristics curves were used to determine optimal cut-off score on the Language Development Survey to identify Bayley-III score <85. Sensitivity, specificity, positive and negative predictive values, and κ coefficient were calculated. RESULTS Using Rescorlas original cut-off scores of ≤10 words for boys and ≤24 for girls, sensitivity was 76% and 88% for boys and girls, respectively, and specificity was 73% and 52% for boys and girls, respectively, in identifying language delay as per the Bayley-III. The optimal threshold was ≤10 words for both boys and girls. In girls, lowering the cut-off score decreased sensitivity (79%), but improved specificity (82%), thus lowering the number of false-positives. CONCLUSION Our findings support using the Language Development Survey as an expressive language screener in preterm infants.