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OBJECTIVE: Previous studies have demonstrated an increased risk for attention-deficit/hyperactivity disorder (ADHD) in follow-up studies of preterm survivors from NICUs. In this study we analyzed the effect of moderate as well as extreme preterm birth on the risk for ADHD in school age, taking into account genetic, perinatal, and socioeconomic confounders. METHODS: Register study in a Swedish national cohort of 1 180 616 children born between 1987 and 2000, followed up for ADHD medication in 2006 at the age of 6 to 19 years. Logistic regression was used to test hypotheses. A within-mother-between-pregnancy design was used to estimate the importance of genetic confounding in a subpopulation of offspring (N = 34 334) of mothers who had given birth to preterm (<= 34 weeks) as well as term infants. RESULTS: There was a stepwise increase in odds ratios for ADHD medication with increasing degree of immaturity at birth; from 2.1 (1.4-2.7) for 23 to 28 weeks' gestation, to 1.6 (1.4-1.7) for 29 to 32 weeks', 1.4 (1.2-1.7) for 33 to 34 weeks', 1.3 (1.1-1.4) for 35 to 36 weeks', and 1.1 (1.1-1.2) for 37 to 38 weeks' gestation compared with infants born at 39 to 41 weeks' gestation in the fully adjusted model. The odds ratios for the within-mother-between-pregnancy analysis were very similar. Low maternal education increased the effect of moderate, but not extreme, preterm birth on the risk for ADHD. CONCLUSION: Preterm and early term birth increases the risk of ADHD by degree of immaturity. This main effect is not explained by genetic, perinatal, or socioeconomic confounding, but socioeconomic context modifies the risk of ADHD in moderately preterm births.

OBJECTIVE: Preterm birth is associated with respiratory morbidity later in life, including asthma. Previous studies have mainly focused on asthma in early childhood in children born extremely preterm. In this study, we examined the risk of asthma in a national cohort of schoolchildren grouped according to degree of immaturity expressed as completed gestational weeks at birth. METHODS: This was a register study in a Swedish national cohort of 1 100 826 children 6 to 19 years old. Retrieval of at least 1 prescription of inhaled corticosteroids (ICS) during 2006 was used as the main indicator for asthma. Logistic regression was used to test hypotheses, with adjustment for multiple socioeconomic and perinatal indicators. RESULTS: Degree of immaturity, expressed as completed gestational weeks at birth, had an inverse dose-response relationship with ICS use. Compared with children born between 39 and 41 weeks' gestation, the odds ratio for ICS use increased with the degree of prematurity, from 1.10 (95% confidence interval: 1.08–1.13) for children born in weeks 37 to 38, to 2.28 (95% confidence interval: 1.96–2.64) for children born in weeks 23 to 28, after adjustment for confounders. The increase in ICS use with decreasing gestational age at delivery was similar in boys and girls, and declined with older age. CONCLUSION: Preterm birth increased the risk of ICS use in these 6- to 19-year-olds by degree of immaturity, from extremely preterm to early term birth.

The World Health Organization defines preterm birth as birth before 37 complete weeks. The proportion of very preterm children with severe neurological disabilities has become smaller, but bulks of data indicate that, for many of the children born preterm, persistent subtle difficulties are evident in school age. Most studies have focused on the situation for infants born before 33 complete weeks. However, moderately preterm (gestational week 33–36) are much more common, and hence important from a public health perspective. In this thesis, long-term consequences of all degrees of preterm birth in school age and young adulthood have been studied. Swedish national registers have been used as data sources. The outcomes for preterm individuals have been compared with the outcomes for infants born at term (here defined as 39–41 gestational weeks). The objective was to investigate the impact of preterm birth on social adjustment, mental health and asthma. Also, the interplay between preterm birth and socioeconomic characteristics of the childhood household has been analysed. One cohort of over half a million individuals born 1973– 79 and another cohort of over a million individuals born 1987–2000 have been used for these purposes. The risk for inhaled corticosteroid medication (our main indicator for asthma) in 6–19 year-olds born 1987–2000 increased with the degree of prematurity. For prematurely born children, compared with children with similar socioeconomic backgrounds born at term, the risk increased from 10 % in 37–38 weeks of gestation at birth, to more than a doubled risk for 23–28 weeks of gestation. For individuals born 1987–2000, there was a stepwise increase in odds ratios for Attention- Deficit/Hyperactivity Disorder medication (our indicator for ADHD) at 6–19 years of age, with increasing degree of immaturity at birth from more than a doubled risk for infants born after 23–28 weeks of gestation, to a 20 % increased risk for 37–38 weeks of gestation compared

OBJECTIVE: The aim was to study the impact of a range of gestational ages (GAs) on cognitive competence in late adolescence and how this effect is modified by contextual social adversity in childhood. METHODS: This was a register study based on a national cohort of 119664 men born in Sweden from 1973 to 1976. Data on GA and other perinatal factors were obtained from the Medical Birth Register, and information on cognitive test scores was extracted from military conscription at the ages of 18 to 19 years. Test scores were analyzed as z scores on a 9-point stanine scale, whereby each unit is equivalent to 0.5 SD. Socioeconomic indicators of the childhood household were obtained from the Population and Housing Census of 1990. The data were analyzed by multivariate linear regression. RESULTS: The mean cognitive test scores decreased in a stepwise manner with GA. In unadjusted analysis, the test scores were 0.63 stanine unit lower in men who were born after 24 to 32 gestational weeks than in those who were born at term. The difference in global scores between the lowest and highest category of socioeconomic status was 1.57. Adjusting the analysis for the childhood socioeconomic indicators decreased the effect of GA on cognitive test scores by 26% to 33%. There was also a multiplicative interaction effect of social adversity and moderately preterm birth on cognitive test scores. CONCLUSIONS: This study confirms previous claims of an incremental association of cognitive competence with GA. Socioeconomic indicators in childhood modified this effect at all levels of preterm birth.

OBJECTIVE: Increasing numbers of infants born preterm survive into adulthood. Previous studies have reported increased levels of neurologic and cognitive disabilities in these children. In this study, we analyzed the effect of having been born preterm on psychiatric morbidity. METHODS: A Swedish national cohort of 545628 individuals born in 1973-1979 was followed up in the national registers during 1987-2002. Multivariate Cox analysis of proportional hazards was used to estimate the hazard ratios of hospital admissions for psychiatric disorders and alcohol/illicit drug abuse. RESULTS: There was a stepwise increase in psychiatric hospital admissions with an increasing degree of preterm birth. A total of 5.2% of children born at 24 to 28 weeks' gestation and 3.5% born at 29 to 32 weeks' gestation had been hospitalized because of a psychiatric disorder. The hazard ratios for psychiatric disorders were 1.68 in the group of very preterm children (gestational weeks 24-32), 1.21 in the moderately preterm group (gestational weeks 33-36), and 1.08 in the early term group (gestational weeks 37-38) after adjustment for socioeconomic confounders. Moderately preterm and early term birth accounted for 85% of the risk attributed to preterm/early term birth. The effect of preterm birth was greater in households with low socioeconomic status. CONCLUSION: Preterm birth carries some risk for psychiatric disorders requiring hospitalization in adolescence and young adulthood (ages 8-29 years). Even if this risk increases with degree of preterm birth, most subjects are moderately preterm, a group in need of more attention in research and secondary prevention.

OBJECTIVE: Increasing numbers of infants born preterm survive into adulthood. In this study, we analyzed the effect of having been born preterm on disability and vocational success in young adults. METHODS: A Swedish national cohort of 522,310 infants born in 1973-1979 were followed up for disabilities and income in national registers in 2002 at the age of 23 to 29. Hypotheses were tested in multivariate analysis with logistic regression models on the log scale for dichotomized outcomes and linear regression for continuous variables. RESULTS: There was a stepwise increase in disability in young adulthood with increasing degree of preterm birth. A total of 13.2% of children born at 24 to 28 weeks' gestation and 5.6% born at 29 to 32 weeks' gestation received economic assistance from society because of handicap or persistent illness, which is equivalent to nearly 4 [corrected] times the risk of those born at term after adjustment for socioeconomic and perinatal confounders. Moderate (33-36 weeks' gestation) and marginal (37-38 weeks' gestation) preterm birth also carried significantly increased risks for disability and were responsible for 74% of the total disability associated with preterm birth. Preterm birth was associated with a lower chance of completing a university education and a lower net salary in a stepwise manner. The total economic gain for Swedish society, in terms of taxes and decreased costs for benefits, if all long-term effects of preterm birth could have been prevented in the birth cohorts in this study, would have amounted to 65 million euros in 2002 alone. CONCLUSIONS: The majority of adults who were born very preterm lived an independent and self-supportive life. Moderately preterm birth carries a considerable risk for long-term impairment. There are strong economic incentives for secondary prevention of disability associated with preterm birth.