Letters to the Editor

Follow-up of preterm children: important to document dropouts

We assessed the feasibility of obtaining parent-collected General Movement Assessment videos using the Baby Moves app. Among 261 participants from 4 Chicago NICUs, 70% submitted videos. Families living in higher areas of childhood opportunity used the app more than those from areas of lower opportunity.

Preterm delivery is a risk factor for suboptimal neurodevelopment. Pregnancies conceived after medically assisted reproduction—which includes in vitro fertilization, with or without intracytoplasmic insemination, and induction of ovulation followed by intrauterine insemination or timed intercourse—have a higher risk of preterm delivery. Few studies have evaluated the outcome at >2 years of age of such preterm-born children.

To evaluate neurodevelopmental outcome at 5½ years of age of children born preterm according to the mode of conception (spontaneous vs medically assisted reproduction).

A total of 4349 children born between 24 and 34 weeks of gestation who survived to 5½ years of age in the 2011 French prospective national cohort study “EPIPAGE-2” were included: 814 in the medically assisted reproduction group (433 by in vitro fertilization, with or without intracytoplasmic insemination, and 381 by induction of ovulation) and 3535 in the spontaneously conceived group. The studied neurodevelopmental outcomes were sensory (hearing and vision) impairments, cerebral palsy, cognition, and developmental coordination disorders. Multivariate analyses were performed with generalized estimating equation models adjusted for gestational age, antenatal steroids, and social characteristics. All analyses were performed following multiple imputation. Sensitivity analyses were performed with the populations of singletons and cases with complete data.

No differences in cerebral palsy (adjusted odds ratio, 1.00; 95% confidence interval, 0.67–1.49), neurodevelopmental impairment (adjusted odds ratio, 1.09; 95% confidence interval, 0.82–1.45), or developmental coordination disorders (adjusted odds ratio, 0.75; 95% confidence interval, 0.50–1.12) were found between children born following medically assisted reproduction and children born following spontaneous conception after adjustment for sociodemographic factors. For proportions of children with an intelligence quotient below 1 and 2 standard deviations, there were no differences between those born after medically assisted reproduction and those born after spontaneous pregnancy (respectively, adjusted odds ratio, 0.99; 95% confidence interval, 0.80–1.23 and adjusted odds ratio, 1.14; 95% confidence interval, 0.83–1.56). In subgroup analyses, no differences were observed between children born following induction of ovulation or in vitro fertilization and those conceived spontaneously. Sensitivity analyses were consistent with the main results.

In this cohort of preterm-born children, there was no evidence of an impact of the mode of conception on neurodevelopmental outcomes at 5½ years of age.

Intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors is increasingly used to treat retinopathy of prematurity (ROP) in the absence of evidence about long-term efficacy or safety. In this prespecified interim analysis of the RAINBOW extension study, we aimed to prospectively assess outcomes at age 2 years.

RAINBOW was an open-label, randomised trial that compared intravitreal ranibizumab (at 0·1 mg and 0·2 mg doses) with laser therapy for the treatment of ROP in very low birthweight infants (<1500 g). Families of the 201 infants that completed the RAINBOW core study were approached for consent to enter the extension study, which evaluates treatment outcomes prospectively through to 5 years of age. At age 20–28 months corrected for prematurity, participants had ophthalmic, development, and health assessments. The primary outcome was the absence of structural ocular abnormalities; secondary outcomes included vision-related quality of life (reported by parents using the Children's Visual Function Questionnaire), development (assessed with the Mullen Scales of Early Learning), motor function, and health status. Investigator-determined ocular and non-ocular serious and other adverse events were recorded. This study is registered with ClinicalTrials.gov, NCT02640664.

Between June 16, 2016, and Jan 22, 2018, 180 infants were enrolled in the RAINBOW extension study, and 153 (85%) were evaluated at 20–28 months of age. No child developed new ocular structural abnormalities. Structural abnormalities were present in one (2%) of 56 infants in the ranibizumab 0·2 mg group, one (2%) of 51 infants in the 0·1 mg group, and four (9%) of 44 infants in the laser therapy group. The odds ratio of no structural abnormality was 5·68 (95% CI 0·60–54·0; p=0·10) for ranibizumab 0·2 mg versus laser therapy, 4·82 (0·52–45·0; p=0·14) for ranibizumab 0·1 mg versus laser therapy, and 1·21 (0·07–20; p=0·90) for ranibizumab 0·2 mg vs 0·1 mg. High myopia (–5 dioptres or worse) was less frequent after 0·2 mg ranibizumab (five [5%] of 110 eyes) than with laser therapy (16 [20%] of 82; odds ratio 0·19, 95% CI 0·05–0·69; p=0·012). Composite vision-related quality of life scores seemed higher among the ranibizumab 0·2 mg group (mean 84, 95% CI 80–88) compared with laser therapy (77, 72–83; p=0·063). Mullen Scales T-scores for visual reception, receptive and expressive language were distributed similarly between the three trial groups and there were similar proportions of infants with motor and hearing problems among treatment groups. The proportion of infants with respiratory symptoms and Z scores of standing height, weight, and head circumference were similarly distributed in the treatment groups. There were no adverse events considered by the investigator to be related to the study intervention.

2-year outcomes following ranibizumab 0·2 mg for the treatment of ROP confirm the ocular outcomes of the original RAINBOW trial and show reduced high myopia, with possibly better vision-related quality of life. This treatment did not appear to affect non-ocular infant development.

Novartis Pharma AG.

To examine changes in referral rates of very low birthweight (birthweight <1500 g) infants to high-risk infant follow-up in California and identify factors associated with referral before and after implementation of a statewide initiative in 2013 to address disparities in referral.

We included very low birthweight infants born 2010-2016 in the population-based California Perinatal Quality Care Collaborative who survived to discharge home. We used multivariable logistic regression to examine factors associated with referral and derive risk-adjusted referral rates by neonatal intensive care unit (NICU) and region.

Referral rate improved from 83.0% (preinitiative period) to 94.9% (postinitiative period); yielding an OR of 1.48 (95% CI, 1.26-1.72) for referral in the postinitiative period after adjustment for year. Referral rates improved the most (≥15%) for infants born at ≥33 weeks of gestation, with a birthweight of 1251-1500 g, and born in intermediate and lower volume NICUs. After the initiative, Hispanic ethnicity, small for gestational age status, congenital anomalies, and major morbidities were no longer associated with a decreased odds of referral. Lower birthweight, outborn status, and higher NICU volume were no longer associated with increased odds of referral. African American race was associated with lower odds of referral, and higher NICU level with a higher odds of referral during both time periods. Referral improved in many previously poor-performing NICUs and regions.

High-risk infant follow-up referral of very low birthweight infants improved substantially across all sociodemographic, perinatal, and clinical variables after the statewide initiative, although disparities remain. Our results demonstrate the benefit of a targeted initiative in California, which may be applicable to other quality collaboratives.