Five-year neurodevelopmental assessment of extremely preterm or extremely low birthweight infants: Association with school performance.

AIM: We investigated the associations between motor performance and IQ at 5 years of age and school difficulties and grade point averages (GPAs) at 18 years of age. Additionally, the accuracy of preschool IQ in predicting school difficulties was examined. METHODS: A nationwide follow-up study of children born in 1994-1995 who were <28 weeks of gestation or had a birthweight <1000 g. The Danish personal identification number was used to merge data from a national cohort study with population-based registries. Logistic regression analyses examined the associations between motor performance/IQ and school difficulties. Linear regression analyses and the area under the receiver operator curve (AUC) were used to examine the relationship between IQ and GPAs. RESULTS: The study population comprised 248 children, 37% were classified with school difficulties. Motor performance and IQ were associated with school difficulties. The odds of having school difficulties increased as IQ decreased, and the same pattern was observed for GPAs. IQ predicted school difficulties, with an AUC of 0.80 (confidence interval: 0.74-0.86). CONCLUSION: Preschool motor performance and IQ were associated with school difficulties. Additionally, IQ was linked to GPAs. As a screening tool, the predictive ability of preschool IQ for academic difficulties was moderate/high in this cohort.

The ASQ did not predict low IQ scores when children born VPT were six years.

AIM: There is a need for methods that can provide valid assessment tools in a follow-up programme without great financial costs. This study assessed the accuracy of the 60-month Ages and Stages Questionnaire as a screening tool to predict a low intelligence quotient score at 6 years in children born very preterm. METHODS: Totally, 54 children participated in a six-year follow-up study, which included an intelligence quotient test at 6 years of age and a 60-month Ages and Stages Questionnaire at four and a half or 5 years of age at respond. We used the receiver operating characteristic curve and evaluated the optimal cut-off score to predict a low intelligence quotient score. RESULTS: At four and a half years, the optimal cut-off value for predicting a low intelligence quotient score was 242, with a sensitivity of 67% and a specificity of 59%. At 5 years, only one child had a low intelligence quotient score, and the analysis was not performed. CONCLUSION: Our results did not support the use of the 60-month Ages and Stages Questionnaire as a valuable screening tool to predict a low intelligence quotient score in children born very preterm at 6 years of age.

Cerebral oximetry monitoring versus usual care for extremely preterm infants: a study protocol for the 2-year follow-up of the SafeBoosC-III randomised clinical trial.

BACKGROUND: In the SafeBoosC-III trial, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth did not reduce the incidence of death or severe brain injury in extremely preterm infants at 36 weeks' postmenstrual age, as compared with usual care. Despite an association between severe brain injury diagnosed in the neonatal period and later neurodevelopmental disability, this relationship is not always strong. The objective of the SafeBoosC-III follow-up study is to assess mortality, neurodevelopmental disability, or any harm in trial participants at 2 years of corrected age. One important challenge is the lack of funding for local costs for a trial-specific assessment. METHODS: Of the 1601 infants randomised in the SafeBoosC-III trial, 1276 infants were alive at 36 weeks' postmenstrual age and will potentially be available for the 2-year follow-up. Inclusion criteria will be enrollment in a neonatal intensive care unit taking part in the follow-up study and parental consent if required by local regulations. We aim to collect data from routine follow-up programmes between the ages of 18 and 30 months of corrected age. If no routine follow-up has been conducted, we will collect informal assessments from other health care records from the age of at least 12 months. A local co-investigator blinded to group allocation will classify outcomes based on these records. We will supplement this with parental questionnaires including the Parent Report of Children's Abilities-Revised. There will be two co-primary outcomes: the composite of death or moderate or severe neurodevelopmental disability and mean Bayley-III/IV cognitive score. We will use a 3-tier model for prioritisation, based on the quality of data. This approach has been chosen to minimise loss to follow-up assuming that little data is better than no data at all. DISCUSSION: Follow-up at the age of 2 years is important for intervention trials in the newborn period as only time can show real benefits and harms later in childhood. To decrease the risk of generalisation and data-driven biased conclusions, we present a detailed description of the methodology for the SafeBoosC-III follow-up study. As funding is limited, a pragmatic approach is necessary. TRIAL REGISTRATION: ClinicalTrials.gov NCT05134116 . Registered on 24 November 2021.

Switch from intravenous-to-oral antibiotics in neonatal probable and proven early-onset infection: a prospective population-based real-life multicentre cohort study.

OBJECTIVE: To evaluate the implementation of switch from intravenous-to-oral antibiotic therapy with amoxicillin in neonates with early-onset infection (EOI). DESIGN, SETTING AND PATIENTS: A population-based multicentre cohort study. All term-born neonates with EOI were prospectively included between 1 December 2018 to 30 November 2020. INTERVENTION: Intravenous-to-oral switch antibiotic therapy in clinically stable neonates. MAIN OUTCOME MEASURES: The primary outcome was readmission due to infection. Secondary outcomes were days of hospitalisation and antibiotic use in the pre-implementation versus post implementation period. RESULTS: During 2 years, 835 neonates commenced antibiotics for EOI (1.5% (95% CI 1.4% to 1.6%)) of all term live births). Of those, 554 (66%) underwent a full course of treatment. There were 23 episodes of culture-proven infection (0.42 per 1000 term live births (95% CI 0.27 to 0.63)). A total of 478 of 531 (90%) neonates with probable infection underwent switch therapy. None was readmitted due to infection. The median duration of hospitalisation was 3.0 days (IQR 2.5-3.5) and 7.4 days (IQR 7.0-7.5) in the switch and intravenous therapy groups, respectively. According to antibiotic surveillance data, 1.2% underwent a full course of treatment following implementation of oral switch therapy (2019-2020), compared with 1.2% before (2017-2018). CONCLUSION: In clinical practice, switch therapy was safe and used in 9 of 10 neonates with probable EOI. Knowledge of the safety of antibiotic de-escalation is important as home-based oral therapy ameliorates the treatment burden for neonates, caregivers and healthcare systems. Despite the ease of oral administration, implementation of switch therapy did not increase the overall use of antibiotics.

Exclusive breastfeeding: Relation to gestational age, birth weight, and early neonatal ward admission. A nationwide cohort study of children born after 35 weeks of gestation.

OBJECTIVES: Prematurity, being small for gestational age and early neonatal ward admission are the major neonatal conditions that may interfere with breastfeeding supportive practices in infants born at gestational age ≥35+0 weeks. We aimed to investigate the associations between gestational age, small for gestational age, early neonatal ward admission and exclusive breastfeeding at one and four months. METHODS: A register-based cohort-study of all Danish singletons with gestational age ≥35+0 weeks born in 2014-2015. In Denmark, health visitors routinely conduct free home visits throughout infants' first year and thereby report breastfeeding data to The Danish National Child Health Register. These data were linked with data from other national registers. Logistic regression models estimated the odds ratio for exclusive breastfeeding at one and four months, adjusted for confounding variables. RESULTS: The study population comprised 106,670 infants. Compared to gestational age 40 weeks, the adjusted odds ratio for exclusive breastfeeding at one month showed a decreasing tendency from gestational age ≥42 (n = 2,282) (1.07; 95% confidence interval (CI) 0.97-1.17) to 36 weeks (n = 2,062) (0.80; 95% CI 0.73-0.88). Small for gestational age (n = 2,342) was associated with decreased adjusted odds ratio for exclusive breastfeeding at one month (0.84; 95% CI 0.77-0.92). Neonatal ward admission was associated with increased adjusted odds ratio for exclusive breastfeeding at one month among late preterm infants (gestational age 35-36 weeks; n = 3,139) (1.31; 95% CI 1.12-1.54), as opposed to among early term (gestational age 37-38 weeks; n = 19,171) (0.84; 95% CI 0.77-0.92) and term infants (gestational age >38 weeks; n = 84,360) (0.89; 95% CI 0.83-0.94). The associations seemed to persist at four months. CONCLUSIONS: Decreasing gestational age and small for gestational age were associated with decreased exclusive breastfeeding rates. Neonatal ward admission was associated with increased exclusive breastfeeding rates among late preterm infants, whereas the opposite was observed among early term and term infants.

Heavy prenatal alcohol exposure and obstetric and birth outcomes: a Danish nationwide cohort study from 1996 to 2018.

BACKGROUND: Heavy alcohol use during pregnancy can harm the fetus, but the relation to most obstetric outcomes remains unclear. We therefore aimed to describe maternal characteristics and estimate the association between heavy prenatal alcohol exposure and 22 adverse obstetric and birth outcomes. METHODS: We carried out a Danish nationwide register-based historical cohort study, including all singleton births from Jan 1, 1996, to Dec 31, 2018. Births of women who had emigrated to Denmark were excluded from the study due to missing data and women who migrated within 1 year before or during pregnancy were also excluded due to loss to follow-up. Data were extracted from the Danish Medical Birth Register, the Danish National Patient Registry, the Danish National Prescription Registry, the Danish Civil Registration System, and the Population Education Register. Logistic regression models were used to estimate crude and adjusted odds ratios (ORs) of obstetric and birth outcomes. Heavy alcohol use was defined by hospital contacts for alcohol-attributable diagnoses given to the mother, her infant, or both, or maternal redeemed prescriptions for drugs to treat alcohol dependence within 1 year before or during pregnancy. FINDINGS: Of 1 191 295 included births, 4823 (0·40%) were defined as heavily alcohol-exposed and 1 186 472 were categorised as a reference group with no identified heavy prenatal alcohol exposure. Heavy-alcohol-exposed births more often had mothers with psychiatric diagnoses (49·8% vs 9·6%), substance use (22·0% vs 0·4%), tobacco use (64·3% vs 15·8%), and low educational level (64·1% vs 17·6%) than did the reference group. For heavy-alcohol-exposed births, significantly increased adjusted ORs were found for small for gestational age (OR 2·20 [95% CI 1·97-2·45]), preterm birth (OR 1·32 [1·19-1·46]), haemorrhage in late pregnancy (OR 1·25 [1·05-1·49]), and preterm prelabour rupture of membranes (OR 1·18 [1·00-1·39]). Decreased adjusted ORs were found for postpartum haemorrhage (500-999 mL; OR 0·80 [95% CI 0·69-0·93]), gestational diabetes (OR 0·81 [0·67-0·99]), planned caesarean section (OR 0·82 [0·72-0·94]), pre-eclampsia and eclampsia (OR 0·83 [0·71-0·96]), and abnormalities of forces of labour (OR 0·92 [0·86-0·99]). INTERPRETATION: Heavy prenatal alcohol exposure is associated with adverse obstetric and birth outcomes and high proportions of maternal low educational level, psychiatric disease, and lifestyle risk behaviours. These findings highlight a need for holistic public health programmes and policy attention on improving pre-conceptional care and antenatal care. FUNDING: The Obel Family Foundation, The Health Foundation, TrygFonden, Aase and Ejnar Danielsens Foundation, The North Denmark Region Health Science and Research Foundation, Holms Memorial Foundation, Dagmar Marshalls Foundation, the A.P. Møller Foundation, King Christian X Foundation, Torben and Alice Frimodts Foundation, the Axel and Eva Kastrup-Nielsens Foundation, the A.V. Lykfeldts Foundation.

Heavy prenatal alcohol exposure and overall morbidities: a Danish nationwide cohort study from 1996 to 2018.

BACKGROUND: Heavy prenatal alcohol exposure is harmful and can lead to fetal alcohol spectrum disorders. A systematic review and meta-analysis identified 428 comorbidities in individuals with fetal alcohol spectrum disorders, and reported pooled prevalence estimates. We aimed to investigate overall risk of morbidities in heavy prenatal alcohol-exposed children by estimating risk of the identified comorbidities, and previously unidentified diseases and health-related problems. METHODS: Our Danish nationwide register-based cohort study included all singleton births. Individuals were followed up to age 18 years, between 1996 and 2018. Stillbirths and children of immigrants were not included in the study, and births of women who migrated within 1 year before or during pregnancy were also excluded due to loss to follow-up. Data on health and education were extracted from the Danish Medical Birth Register, the Danish National Patient Registry, the Danish National Prescription Registry, the Danish Civil Registration System, and the Population Education Register. We estimated crude and standardised risk differences of hospital diagnoses. Heavy prenatal alcohol exposure was defined by hospital contacts with alcohol-attributable diagnoses given to the mother or her child, or by maternal redeemed prescriptions for drugs to treat alcohol dependence 1 year before or during pregnancy. FINDINGS: Of 1 407 689 identified singleton births, 219 186 were excluded for reasons including they were born to immigrants, lost to follow-up, or were stillbirths. Of the remaining 1 188 503 children, 4799 (0·4%) had heavy prenatal alcohol exposure and 1 183 704 (99·6%) were classified as non-alcohol-exposed births. 578 179 (48·6%) babies were female and 610 324 (51·4%) were male. We found 234 of 428 previously identified comorbidities in individuals with fetal alcohol spectrum disorder, of which 29 conditions had a standardised risk difference of at least 0·5%, predominantly related to brain function, behavioural disorders, infections, and neonatal conditions. The four highest standardised risk differences were found for low birthweight (4·70% [95% CI 3·70-5·71]), small for gestational age (4·63% [3·72-5·55]), delayed milestone (3·81% [2·99-4·64]), and other preterm infants (2·69% [1·71-3·68]). Of previously unidentified diseases and health-related problems, 32 of 719 had a standardised risk difference of at least 1·0%, mainly related to brain function, some injuries, substance-related conditions, and childhood adversities. INTERPRETATION: Heavy prenatal alcohol exposure is associated with an overall increased risk of child morbidities and previously unrecognised alcohol-related health problems. Prenatal alcohol exposure is a key public health issue with a potential negative impact on child and adolescent health. This study urges for renewed efforts and substantiates the profound degree to which pre-conceptional care is mandatory. FUNDING: The Obel Family Foundation, The Health Foundation, TrygFonden, Aase and Ejnar Danielsens Foundation, The North Denmark Region Health Science and Research Foundation, Holms Memorial Foundation, Dagmar Marshalls Foundation, the A.P. Møller Foundation, King Christian X Foundation, Torben and Alice Frimodts Foundation, the Axel and Eva Kastrup-Nielsens Foundation, and the A.V. Lykfeldts Foundation.

Hydrops fetalis.

Congenital hydrops fetalis describes an abnormal accumulation of fluid in two or more compartments in a fetus. The disease is categorized based on the aetiology: immune- and non-immune hydrops fetalis. Today, the non-immune form is the most common. Once born, the child is initially handled symptomatically and will often need intensive care and treatment. Even though approximately one in five cases is still idiopathic, genetic diagnostic tools have become increasingly important in the diagnostic process. The prognosis depends on the aetiology and the gestational age when diagnosed and at birth, as argued in this review.

[Herpes simplex virus infection in newborns].

Neonatal herpes simplex disease (HSV) is a rare but life-threatening infection associated with high rates of morbidity and mortality. Recent studies indicate that the incidence rate has continued to rise over the past decades, while the mortality remains unchanged. Early clinical suspicion of HSV and parenteral antiviral treatment of acute disease is essential for the prognosis. The subsequent use of suppressive therapy with oral acyclovir has further enhanced the long-term prognosis. This review presents evidence of risk factors, clinical presentation, prevention, and management of HSV in newborns.

[Treatment and follow-up of preterm infants in Denmark].

This review summarises the treatment of preterm infants in Denmark, which is dependent on the collaboration between several medical specialities. The problems of the preterm infants are related to the degree of prematurity, and the treatment should counter these issues, reduce complications related to prematurity and ensure growth and development. Developmental problems are the most common sequelae. There seems to be a dose-effect association between the whole spectrum of gestational age and developmental problems with the highest risk among the extremely preterm children. However, even in this group, most of the children will develop normally.

[An update on unconjugated neonatal hyperbilirubinaemia in Denmark].

Approximately 60% of term newborn infants are jaundiced during the first week of life, which is caused by unconjugated bilirubin. Bilirubin encephalopathy is seen with severe hyperbilirubinaemia, when unbound bilirubin crosses the blood-brain barrier. The chronic form is called kernicterus spectrum disorder. To avoid this devastating condition, the treatment of choice for neonatal hyperbilirubinaemia is phototherapy, which is most efficient with LED light of 478-nm wavelength. In this review, we argue, that a systematic approach to hyperbilirubinaemic infants as well as surveillance of extreme neonatal hyperbilirubinaemia is highly important.

The increased purchase of asthma medication for individuals born preterm seems to wane with age: A register-based longitudinal national cohort study.

INTRODUCTION: Preterm birth is associated with increased risk of respiratory symptoms in childhood, often treated with asthma medication. We designed a follow-up study to previous research and investigated whether the association of gestational age with purchasing asthma medication diminishes in adulthood. METHODS: We conducted a register-based study of a national cohort of all infants born in Denmark in 1980-2009 evaluating longitudinal data on individually prescribed asthma medication (both inhaled ß-2 receptor agonist and different controller treatment over 2-year periods) available from 1995-2011. We analyzed the effect of gestational age considering age, birth year, and perinatal variables using logistic regression with a Generalized Estimating Equations model. All data were unambiguously linked through the Civil Registration System. RESULTS: We included 1,819,743 individuals in our study population. We found an inverse dose-response relationship between gestational age and asthma medication in earlier age-groups with a gradual decrease in odds ratios with increasing age and loss of statistical significance in early adulthood (18-31 years). For our oldest generations, there was a significant effect of gestational age (p-value = 0.04), which became insignificant when adjusting for confounding and mediating factors (p = 0.44). There were significant interactions between gestational age and age (p<0.0001) and gestational age and birth year, but these were most important during childhood (0-11 years) and for our youngest generations (born after 1995). CONCLUSION: The strong association between gestational age and purchase of prescription asthma medication weakens with age into early adulthood, in consistence with the results from our previous study. The risk for purchasing medication to treat asthma-like symptoms was higher in more recent birth years, but the effect of gestational age was small beyond 11 years of age. Gestational age per se did not seem to be significant for the development of asthma-like symptoms: most of its effect could be explained by other perinatal factors.

Low gestational age at birth and difficulties in school-A matter of 'dose'.

OBJECTIVES: Several studies suggest a relationship between gestational age at birth and risk of school difficulties. Our study aimed to investigate the association between the entire range of gestational ages and significant school difficulties measured as 1) More than nine hours per week special educational support and 2) Failing to complete compulsory school. METHODS: A population-based register study including all children attending the Danish compulsory school in 2015/2016 and all live-born infants born in Denmark from 1992 to 1997. Data were collected and linked using multiple registers held by Statistic Denmark. Multiple logistic regression analyses were used to estimate the association between gestational age and significant school difficulties, adjusted for explanatory variables. RESULTS: For measurement 1) "Special educational support" 615,789 children entered the analyses after exclusion of those with missing neonatal data. The risk of special educational support increased gradually across the entire range of gestation from 40 to ≤24 weeks: The adjusted odds ratio was 1.07 (95% confidence interval 1.03-1.12) at 39 weeks of gestational and 6.18 (95% confidence interval 5.17-7.39) at gestational ages < 28 weeks. For measurement 2) "Failing to complete compulsory school" the cohort consisted of 374,798 children after exclusion of those who died, had emigrated and/or had missing neonatal data. The risk of failing to complete compulsory school increased across the entire range of gestational ages: The adjusted odds ratio was 1.07 (95% confidence interval 1.04-1.10) at 39 weeks of gestation and 2.99 (95% confidence interval 2.41-3.71) at gestational ages < 28 weeks. In both sets of analyses GA = 40 weeks was used as reference. CONCLUSIONS: We confirm a clear association between the degree of prematurity and significant school difficulties across the entire range of gestational ages from ≤ 24 to 40 weeks.

[Diagnosis of seizures in the neonatal period].

Seizures in the neonatal period are practically always a symptom of an underlying illness. Quick diagnosis and treatment can be crucial to the outcome. A few aetiological factors account for most of the seizures. However, a significant number is caused by rare conditions such as metabolic or genetic disorders, and arriving at the right diagnosis can be challenging. Previous studies indicate, that a standardized algorithm clearly improves the diagnostic success. This article presents an overview of aetiological factors and an algorithm for a standardized work-up.

Perinatal Risk Factors for Feeding and Eating Disorders in Children Aged 0 to 3 Years.

OBJECTIVE: To describe the incidence, age at diagnosis, and associations between perinatal risk factors of feeding and eating disorders (FED) diagnosed at hospital in children aged 0 to 3 years. METHODS: A nationwide cohort of 901 227 children was followed until 48 months of age in the national registers from 1997 to 2010. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) for FED diagnosis according to the International Classification of Diseases and associations with perinatal risk factors. RESULTS: A total of 1365 children (53% girls) were diagnosed with FED at hospital, corresponding to a cumulative incidence of 1.6 per 1000 live births. High risk of FED was seen in children born before gestational week 28 (HR, 3.52; 95% confidence interval [CI], 2.15-5.78). HRs were 3.74 for children small for gestational age ≤3 SD (95% CI, 2.71-5.17) and 4.71 in those with congenital malformations (95% CI, 3.86-5.74). Increased risk of FED was associated with female gender (HR, 1.2; 95% CI, 1.08-1.34), maternal smoking in pregnancy (HR, 1.24; 95% CI, 1.08-1.42), immigrant status (HR, 2.24; 95% CI, 1.92-2.61), and being the firstborn (HR, 1.33; 95% CI, 1.19-1.50). CONCLUSIONS: FED in referred children aged 0 to 3 years are associated with perinatal adversities, female gender, maternal smoking in pregnancy, being firstborn, and having immigrant parents. The results suggest complex causal mechanisms of FED and underscore the need for a multidisciplinary approach in the clinical management of young children with persistent problems of feeding, eating, and weight faltering.

Head circumference growth among extremely preterm infants in Denmark has improved during the past two decades.

INTRODUCTION: Treatment of extremely preterm and low birth weight infants is still evolving and improving. In this study, we evaluated if growth has improved from birth to two years of corrected age (CA) among extremely low birth weight (BW) and preterm born infants in Denmark. METHODS: This was an observational study with comparison of head circumference (HC), weight and length growth in two Danish cohorts of extremely preterm (gestational age (GA) < 28 weeks) and extremely low birth weight (ELBW with a BW < 1,000 g) infants (A: 1994-1995 and B: 2004-2008). RESULTS: Infants in cohort A (n = 198) and B (n = 64) had a median GA and BW of 27 + 2 weeks and 948 g in A, and 27 + 3 weeks and 934 g in B. At discharge, infants in B compared with A had increased more in HC (p = 0.000), length (p = 0.008) and weight (p = 0.000). At two years CA, HC was still significantly larger in cohort B than A (p = 0.03), while no significant difference was recorded for length or weight. CONCLUSION: Growth during hospitalisation seems to have improved among extremely preterm and low birth weight infants from 1994-1995 to 2004-2008. This may be a result of improved nutrition in combination with improved intensive care during hospitalisation. FUNDING: Collection of data in the 2004-2008 cohort was supported by the Institute of Regional Health Services Research, the Egmont Foundation and the University of Southern Denmark. Collection of data from birth to two years of age in the 1994-1995 cohort was without financial support. TRIAL REGISTRATION: For the 1994-1995 study, all eight regional Research Ethics Committees in Denmark at that time approved the study. The 2004-2008 study was approved by the Danish National Committee on Biomedical Research Ethics, and handling of data and registrations were approved by the Danish Data Protection Agency.

[Flow cytometry: a fast method to detect foetomaternal haemorrhage]. / Neonatal anæmi på grund af føtomaternel blødning diagnosticeret ved flowcytometri.

The passage of foetal blood into maternal circulation is termed a foetomaternal haemorrhage (FMH). Most cases are clinically insignificant. However, in some cases a large FMH causes serious anaemia in the newborn child. Flow cytometry is a precise and fast method to analyse maternal blood for FMH and can be used both antenatally and postnatally. The clinician should consider using the analysis in cases of unexplained anaemia. We describe a case with severe FMH.

Prematurity and prescription asthma medication from childhood to young adulthood: a Danish national cohort study.

INTRODUCTION: Preterm birth is associated with increased risk of asthma-like symptoms and purchase of prescription asthma medication in childhood. We investigated whether this association persists into adulthood and whether it is affected by accounting for neonatal respiratory morbidity (acute respiratory disease and bronchopulmonary dysplasia). METHODS: A national cohort of all infants born in Denmark in the period 1980-2009 was included in this register study. Data on purchase of asthma medication (combination of inhaled ß-2 agonists and other drugs for obstructive airway disease) in 2010-2011 were obtained from the Danish National Prescription Registry. Associations between gestational age (GA), neonatal respiratory morbidity and a cross-sectional evaluation of asthma medication purchase were explored by multivariate logistic regressions. RESULTS: A full dataset was obtained on 1,790,241 individuals, 84.6% of all infants born in the period. Odds-ratios (95% CI) for the association between GA and purchase of asthma medication during infancy were: 3.86 (2.46-6.04) in GA 23-27 weeks, 2.37 (1.84-3.04) in GA 28-31 weeks and 1.59 (1.43-1.77) in GA 32-36 weeks compared to term infants with GA 37-42 weeks. Associations weakened in older age groups and became insignificant in young adults born extremely and very preterm with odds-ratios: 1.41 (0.63-3.19) and 1.15 (0.83-1.60) in GA 23-27 and 28-31 respectively. When adjusting for neonatal respiratory morbidity, the associations weakened but persisted both in childhood and adolescence. CONCLUSION: There was a strong dose-response association between gestational age and the purchase of prescription asthma medication in infancy and childhood. This association weakened during adolescence and was mostly non-significant in young adulthood. The increased risk of prescription asthma medication purchase in ex-preterm children could only partly be explained by neonatal respiratory morbidity.