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.

Objectives To compare cognitive, language, behavioural and educational outcomes of preterm children to term controls, and to evaluate the impact of neonatal brain injury, indomethacin and environmental risk factors on intellectual function at 12 years. Methods 375 children born in 1989−1992 with birth weight 600−1250g enrolled in the Indomethacin Intraventricular Hemorrhage (IVH) Prevention Trial and 111 term controls were evaluated at 12 years of age. Neuropsychometric testing, neurological exam, and interviews on educational needs were completed. Severe brain injury was defined as the presence of grade 3−4 IVH, periventricular leukomalacia or severe ventriculomegaly on cranial ultrasound. Results On the Wechsler Scales of Intelligence for Children, the preterm cohort obtained a mean full scale IQ of 87.9 ± 18.3, verbal IQ of 90.8 ± 18.9, and performance IQ of 86.8 ±17.9. Preterm children obtained scores 6−14 points lower than term controls on all psychometric tests after adjustment for socio-demographic factors. On the Clinical Evaluation of Language Fundamentals (test of basic language skills), 22−24% of preterm children scored in the abnormal ranges (<70) as opposed to 2−4% of controls. Preterm children with and without brain injury required more school services (76% and 44% vs. 16%), and support in reading (44% and 28% vs. 9%), writing (44% and 20% vs. 4%), and mathematics (47% and 30% vs. 6%) compared to controls. Preterm children also displayed more behaviour problems than their term counterparts. Severe neonatal brain injury was the strongest predictor of poor intelligence (mean difference −22.1; CI −28.1, −16.2). Antenatal steroids, higher maternal education, and 2-parent family were associated with better cognition, whereas minority status incurred a disadvantage. Indomethacin did not affect intellectual function among preterm children. Conclusion Preterm children born in the early 1990s, especially those with severe brain injury, demonstrate serious deficits in their neuropsychological profile, which translates into increased use of school services at 12 years.

Most preterm survivors are free of sNDI. The risk factors, including site, associated with neurodevelopmental status suggest opportunities for improving outcomes.

Even after exclusion of preterm subjects with significant disabilities, adolescents born preterm in the early 1990s were at increased risk of deficits in executive function and memory.

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Significant catch-up in receptive vocabulary is observed by the age of 16 years among very preterm children compared to term peers. The absence of neurosensory impairment and residing in a favorable socioeconomic milieu are associated with the most optimal developmental trajectories.

Objectives-To examine whether indomethacin, gender, neonatal and sociodemographic factors predict patterns of receptive language development from 3-12 years of age in preterm children.Methods-355 children born in 1989-1992 with birth weight 600-1250g were evaluated at 3, 4.5, 6, 8 and 12 years with the Peabody Picture Vocabulary Test -Revised (PPVT-R) as a measure of receptive language. Hierarchical growth-curve modeling was used to explore differences in language trajectories.Results-From 3 to 12 years corrected ages, preterm children displayed catch-up gains on the PPVT-R. Preterm children started with an average standard score of 84.1 at 3 years and gained 1.2 points per year across the age period studied. Growth-curve analyses on PPVT-R raw scores revealed an indomethacin-by-gender effect on initial scores at 3 years with preterm boys randomized to indomethacin scoring, on average, 4.2 points higher than placebo control boys. However, velocity of receptive vocabulary development from 3-12 years did not differ by treatment groups. Children with grade 3-4 intraventricular hemorrhage, periventricular leukomalacia or grade 2 and above ventriculomegaly demonstrated slower gains in skills over time than those who did not suffer severe brain injury. Significant differences in language trajectories were predicted by maternal education and minority status. Higher initial scores and faster language development were observed among children whose mothers had higher education levels and who had not identified themselves as a minority ethnic group. Conclusion-Although indomethacin incurs an initial benefit in preterm boys, this pharmacologic intervention did not alter the developmental trajectory of PPVT-R scores in our study subjects. Severe brain injury leads to long-term sequelae on language development, whereas a socioeconomically advantaged environment supports better language development among preterm children. KeywordsVery low birth weight; preterm birth; language development; preschool outcome; middle childhood development; indomethacin; intraventricular hemorrhage (3,5,6,9,10) One of the main goals of neonatal interventions is to reduce the rates of both neonatal morbidities and neurodevelopmental impairment. Prophylactic indomethacin decreases the incidence and severity of intraventricular hemorrhage (IVH).(11,12) Furthermore, exposure to indomethacin is associated with reduction in white matter injury on cerebral magnetic resonance imaging (MRI) in extremely preterm infants. (13) As part of the Multicenter Randomized Indomethacin IVH Prevention Trial, preterm children were longitudinally followed from birth to 12 years. A previous study on this cohort showed an increase in median Peabody Picture Vocabulary Test -Revised (PPVT-R) standard scores from 3 to 8 years. (8) Among preterm children with no early brain injury, standard scores were 89, 92, 97, and 99 at 3, 4.5, 6, and 8 years corrected age, respectively. Another report of this cohort also indicated that preterm boys assigned to indomethacin perfo...

Preterm birth incurs a higher risk for adult cardiovascular diseases, including hypertension. Because preterm birth may impact nephrogenesis, study objectives were to assess renal size and function of adults born preterm versus full term and to examine their relationship with blood pressure (BP; 24-hour ambulatory BP monitoring) and circulating renin-Ang (angiotensin) system peptides. The study included 92 young adults born (1987–1997) preterm (≤29 weeks of gestation) and term (n=92) matched for age, sex, and race. Young adults born preterm had smaller kidneys (80±17 versus 90±18 cm 3 /m 2 ; P <0.001), higher urine albumin-to-creatinine ratio (0.70; interquartile range, 0.47–1.14 versus 0.58, interquartile range 0.42 to 0.78 mg/mmol, P =0.007), higher 24-hour systolic (121±9 versus 116±8 mm Hg; P =0.001) and diastolic (69±5 versus 66±6 mm Hg; P =0.004) BP, but similar estimated glomerular filtration rate. BP was inversely correlated with kidney size in preterm participants. Plasma Ang I was higher in preterm versus term participants (36.3; interquartile range, 13.2–62.3 versus 19.4; interquartile range, 9.9–28.1 pg/mL; P <0.001). There was no group difference in renin, Ang II, Ang (1–7), and alamandine. In the preterm, but not in the term group, higher BP was significantly associated with higher renin and alamandine and lower birth weight and gestational age with smaller adult kidney size. Young adults born preterm have smaller kidneys, higher urine albumin-to-creatinine ratio, higher BP, and higher circulating Ang I levels compared with term controls. Preterm young adults with smaller kidneys have higher BP. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT03261609.