S.P. Verloove-Vanhorick

The relation between neonatal thyroxine levels and neurodevelopmental outcome at age 5 and 9 years in a national cohort of very preterm and/or very low birth weight infants

Transient neonatal hypothyroxinemia is very common in preterm infants. The literature on the effect of this hypothyroxinemia is, however, controversial, and large or long-term follow-up studies are not available. In a nationwide prospective follow-up study on very preterm and (or) very low birth weight infants (n = 717), we studied the relationship between thyroxine levels in the 1st wk of life and neurodevelopmental outcome at 5 y of age and school performance at 9 y of age. Thyroxine concentrations from filter paper eluates were determined in 717 infants: 32% had levels of more than 3 SD below the mean (<60 nmol/L). The percentage of infants with such low levels increased with decreasing gestational age. At the age of 5 y, 96% of survivors(n = 640) were available for extensive neurodevelopmental examination: 85 (13.3%) had a disability and 92 (14.3%) a handicap. At the age of 9 y, 83% of survivors (n = 552) answered a questionnaire on school performance: 300 (54.3%) were in mainstream education in a grade appropriate for age, 151 (27%) were in mainstream education with grade retention, and 101 (18.3%) were in special education. Both neurologic dysfunction at age 5 y and school failure at age 9 y were significantly related to lower neonatal thyroxine levels even after adjustment for other perinatal factors (odds ratio, 1.3). Whether this relationship is causal should be investigated. If a causal relationship exists, substitution therapy may at least partially prevent neurologic dysfunction and learning disabilities, both common sequelae of very preterm birth.

Functional outcomes and participation in young adulthood for very preterm and very low birth weight infants: the Dutch Project on Preterm and Small for Gestational Age Infants at 19 years of age.

OBJECTIVE. Young adults who were born very preterm or with a very low birth weight remain at risk for physical and neurodevelopmental problems and lower academic achievement scores. Data, however, are scarce, hospital based, mostly done in small populations, and need additional confirmation. METHODS. Infants who were born at <32 weeks of gestation and/or with a birth weight of <1500 g in the Netherlands in 1983 (Project on Preterm and Small for Gestational Age Infants) were reexamined at age 19. Outcomes were adjusted for nonrespondents using multiple imputation and categorized into none, mild, moderate, or severe problems. RESULTS. Of 959 surviving young adults, 74% were assessed and/or completed the questionnaires. Moderate or severe problems were present in 4.3% for cognition, 1.8% for hearing, 1.9% for vision, and 8.1% for neuromotor functioning. Using the Health Utility Index and the London Handicap Scale, we found 2.0% and 4.5%, respectively, of the young adults to have ≥3 affected areas in activities and participation. Special education or lesser level was completed by 24%, and 7.6% neither had a paid job nor followed any education. Overall, 31.7% had ≥1 moderate or severe problems in the assessed areas. CONCLUSIONS. A total of 12.6% of young adults who were born very preterm and/or with a very low birth weight had moderate or severe problems in cognitive or neurosensory functioning. Compared with the general Dutch population, twice as many young adults who were born very preterm and/or with a very low birth weight were poorly educated, and 3 times as many were neither employed nor in school at age 19.

Nonresponse bias in a follow-up study of 19-year-old adolescents born as preterm infants

Objective. To assess the effect of demographic and neonatal risk factors and outcome at the last available assessment on the probability of full responders, postal responders (those who only responded to the mailed questionnaire), or nonresponders in a follow-up study of 19-year-old adolescents who were born as preterm infants. Design. The 19-year follow-up program was part of a large ongoing collaborative study in the Netherlands on the long-term effect of prematurity and dysmaturity on various medical, psychological, and social parameters. In the original cohort, 1338 infants (94%) with a gestational age of <32 weeks and/or a birth weight of <1500 g were enrolled. Neonatal mortality was 23% (n = 312), and another 67 children had died between the ages of 28 days and 19 years, leaving 959 survivors (72% of the original cohort) for follow-up at the present assessment. To study the effect of nonresponse, we divided the 959 survivors into 3 groups: full responders (596 [62.1%]), postal responders (109 [11.4%]), and nonresponders (254 [26.5%]). In the 3 groups we compared demographic and neonatal data, as well as outcome at the last available assessment. Results. The odds ratios (ORs) for male versus female for the probabilities of nonresponse and postal response were statistically significant: 2.7 (95% CI: 1.9–3.9) and 1.6 (95% CI: 1.0–2.5), respectively. The same holds for the ORs for non-Dutch versus Dutch and low versus high maternal education for nonresponse: 2.0 (95% CI: 1.3–3.2) and 3.7 (95% CI: 2.0–6.7), respectively. Special education and severe handicap showed a statistically significant influence on nonresponse (OR: 1.6; 95% CI: 1.1–2.4 and OR: 2.6; 95% CI: 1.3–5.2) and postal response (OR: 2.0; 95% CI: 1.2–3.3 and OR: 4.4; 95% CI: 2.0–9.9), respectively. At the age of 19 years, primary school and special education were found significantly more frequent in the postal responders than in the full-response group (20% and 21% vs 6% and 12%). The full responders, on the other hand, were higher educated than were the postal responders. Conclusions. In this follow-up study at the age of 19 years, boys, non-Dutch adolescents, and low maternal education were overrepresented in the nonresponse and postal-response groups. Nonresponse decreased the proportion of infants with adverse outcome in assessed children. To be able to present reliable results for the total group of survivors in long-term follow-up studies, the nonresponse bias needs to be quantified. Therefore, it is evident that more research using statistical methods such as imputation of missing data is needed.

Development and evaluation of a follow up assessment of preterm infants at 5 years of age

Background: Long term follow up shows a high frequency of developmental disturbances in preterm survivors of neonatal intensive care formerly considered non-disabled. Aims: To develop and validate an assessment tool that can help paediatricians to identify before 6 years of age which survivors have developmental disturbances that may interfere with normal education and normal life. Methods: A total of 431 very premature infants, mean gestational age 30.2 weeks, mean birth weight 1276 g, were studied at age 5 years. Children with severe handicaps were excluded. The percentage of children with a correctly identified developmental disturbance in the domains cognition, speech and language development, neuromotor development, and behaviour were determined. Results: The follow up instrument classified 67% as optimal and 33% as at risk or abnormal. Of the children classified as at risk or abnormal, 60% had not been identified at earlier follow up assessments. The combined set of standardised tests identified a further 30% with mild motor, cognitive, or behavioural disturbances. The paediatrician’s assessment had a specificity of 88% (95% CI 83–93%), a sensitivity of 48% (95% CI 42–58%), a positive predictive value of 85% (95% CI 78–91%), and a negative predictive value of 55% (95% CI 49–61%). Conclusions: Even after standardised and thorough assessment, paediatricians may overlook impairments for cognitive, motor, and behavioural development. Long term follow up studies that do not include detailed standardised tests for multiple domains, especially fine motor domain, may underestimate developmental problems.

Measuring health status using the Health Utilities Index: Agreement between raters and between modalities of administration

The aim of this study was to evaluate interrater and intermodality agreement in assessing health status using the Health Utilities Index. A random sample from a Dutch cohort of 14-year-old Very Low Birth Weight children and their parents were invited to participate in a face-to-face (n = 150) or telephone (n = 150) interview. All 300 participants were also sent a questionnaire by mail. Response rate was 68%. Interrater and intermodality agreement were high for the physical HUI3 attributes and poor for the psychological attributes. Children and parents reported more dysfunction in the psychological attributes when interviewed than when completing the mailed questionnaire. High agreement on the physical attributes may have resulted from the fact that hardly any dysfunction was reported in these attributes, and poor agreement in the psychological attributes may have been a result of the fact that in these attributes much more dysfunction was reported. In measuring childrens health status using the HUI3, the results and their interpretation vary with the source of information and the modality of administration. For maximum comparability between studies, written self-report questionnaires seem the preferred option.

Breech delivery in very preterm and very low birthweight infants in the Netherlands

Objective To study the relation between various perinatal factors and the sequelae of very preterm birth, applying logistic regression analysis.

The viability of the preterm infant

Viability is the capability of the liveborn infant to survive without major handicaps. Although opinions differ in the Netherlands as to the justification of starting treatment in infants of less than 26 weeks gestation, our preliminary results indicate that mortality and major-handicap rate do not differ in infants of less than 26 weeks compared to infants of 26 and 27 weeks. However, we should encourage preventive perinatal medicine in order to reduce the alarming high rate of major handicaps in all extremely preterm infants.

SCHOOLPERFORMANCE IN VERY PRETERM CHILDREN: A report from the Collaborative Project On Preterm and Small for gestational ago (POPS) infants in the Netherlands

A virtually complete birthcohort of infants <32 weeks and/or <1500 g (n=1338) was followed-up until 9 years ol age. In 88% of survivors (n=813) data on schoolperfxsormance were available.Of the children in mainstream education 38% had remedial teaching (27% at appropnate level, 60% bolow level). The need for remedial teaching was not different for children who were not handicapped at 5 years of age. Logistic regression for non-handicapped children with any schoolfailure as dependent factor showed significantly higher ORs for SGA (1.8) boys (1.9) low or middle SES (5.4 and 2.1) mild or severe developmental delay (5 years) (1.7 and 13.0) and low schoolresults at 5 years (3.6). When special education was the dependent factor higher ORs were found for boys (2.0) twins (1.9) low and middle SES (7.1 and 3.0) severe montal delay (10.1) mild speech delay (3.3) high inattention and hyporactivityscore (2.9) and low schoolresults at 5 years (2.8). Porinatal factors (gestational age, birthweight and neonatal illness) were not significant.