Preterm birth and prescriptions for cardiovascular, antiseizure, antibiotics and antiasthmatic medication in children up to 10 years of age: a population-based data linkage cohort study across six European regions

Abstract

Objectives: Preterm children are exposed to many medications in neonatal intensive care units, but little is known about the effect of prematurity on medication use throughout infancy and childhood. We examined prescriptions of cardiovascular medication (CVM), antiseizure medication (ASM), antiasthmatic medication and antibiotics issued/dispensed in the first 10 years of life for very and moderately preterm children compared with term.

Design: Population-based data linkage cohort study linking information from birth records to prescription records.

Setting: Six registries from five countries in the EUROlinkCAT study.

Participants: The study population included 1 722 912 children, of whom 10 820 (0.6%) were very preterm (<32 weeks gestational age (GA)), 92 814 (5.4%) were moderately preterm (32-36 weeks GA), 1 606 643 (93.3%) were born at term (≥37 weeks GA) and 0.7% had missing GA. Children with major or minor congenital anomalies were excluded (including patent ductus arteriosus).

Main outcome measures: Relative risk (RR) of receiving a prescription for CVM, ASM, antiasthmatic and antibiotics.

Results: Very preterm children had a higher RR of receiving a prescription for CVM and ASM than preterm children. For all preterm children, the RR of having a CVM prescription was 3.58 (95% CI 2.06 to 6.23); 2.06 (95% CI 1.73 to 2.41) for ASM; 1.13 (95% CI 0.99 to 1.29) for antiasthmatics and 0.96 (95% CI 0.93 to 0.99) for antibiotics in the first year of life. Increased prescription of CVM, ASM and antiasthmatics persisted for all 10 years of follow-up. Although the RR was highest for CVM and ASM, in absolute numbers more children received prescriptions for antibiotics (42.34%, 95% CI 38.81% to 45.91%) and antiasthmatics (28.40%, 95% CI 16.07% to 42.649%) than for CVM (0.18%, 95% CI 0.12% to 0.25%) and ASM (0.16%, 95% CI 0.13% to 0.20%) in the first year of life.

Conclusion: Preterm children had a higher risk of being prescribed/dispensed CVM, ASM and antiasthmatics up to age 10. This study highlights a need for further research into morbidity beyond age 10.

Keywords: Congenital heart disease; NEONATOLOGY; Public health.

Figure 1

Relative risk (RR) of receiving a prescription for all preterm (<37 GA) vs term (+37 GA) children for their first 10 years of life. Data plotted are the RR and error bars indicated 95% CIs. Each point on the graph indicates a child year, that is, from age 0 until the day before turning 1 year are termed <1 and from one till the day before turning 2 is termed <2, etc. The dotted line indicates an RR of 1 which is that of term children. Data are shown for (A) cardiovascular medication (CVM); (B) antiseizure medication (ASM); (C) antiasthmatic medication and (D) antibiotics. The highest RR is observed for CVM in the first year of life. For CVM, ASM and antiasthmatics the RR remains elevated compared with term children for all 10 years included in the analysis. Centres with data on <1000 children <37 GA were excluded from the analysis; for the two first years of life data were included from all six regions, for ages 2 years to <6 years five regions, ages 6 to <8 years 4 regions and 8 to <10 years three regions. GA, gestational age.

Figure 2

Relative risk (RR) of receiving a prescription for very preterm (<32 GA, blue line) and preterm (32–36 GA, red line) vs term children in their 10 years of life. Data are pooled into three age categories; <1 years; 1–4 years and 5–9 years. Error bars indicated 95% CIs. The dotted line indicate an RR of 1 which is that of term children. Please note the logarithmic scale of the y-axis. Data are shown for (A) cardiovascular medication (CVM); (B) antiseizure medication (ASM); (C) antiasthmatic medication; (D) antibiotics. An increased relative risk of prescription is observed for CVM, ASM and antiasthmatic medication for the three age groups, but not for antibiotics. Centres with data on <1000 children <37 GA were excluded from the analysis; for the two first years of life data was included from all six regions, for ages 2 to <6 years five regions, ages 6 to <8 years 4 regions and 8 to <10 years three regions. GA, gestational age.

Figure 3

Relative risk (RR) of receiving a prescription for all preterm (<37 GA) vs term (+37GA) children in the first year of life. Error bars indicate 95% CIs. Data are shown for all of the six regions individually (black) and the total (red) for (A) cardiovascular medication (CVM); (B) antiseizure medication (ASM); (C) antiasthmatic medication and (D) antibiotics. Please note the logarithmic scale of the x-axis in the upper panel, while in the lower panel the scale is linear but the x-axis values varies between graphs. GA, gestational age.