Acute Respiratory Tract Infections and Vitamin D: Neonatal vitamin D levels and acute respiratory tract infections in the first year of life

Abstract

Background There is growing interest in vitamin D as an immune modulator and the role of vitamin D in respiratory illnesses is increasingly being recognised. Respiratory tract infections are a prevalent cause of hospital admission in the preschool-aged population; particularly in the first year of life. In order to try to reduce the ARI disease burden, it is necessary to understand the contribution of different risk factors acting at different phases of a child’s life. One risk factor that is of particular interest for this thesis is vitamin D status at birth. Aim My aim was to investigate the association between 25-hydroxyvitamin D (25[OH]D) status at birth and hospital admission with an acute respiratory tract infection in the first year of life. Two validation studies were also undertaken that allowed us to develop a dried blood spot liquid chromatography tandem mass spectrometry assay in a NZ laboratory and determine whether the developed assay was robust enough to measure 25(OH)D concentrations on dried blood spot samples stored for more than 5 years. Methods I performed a case-control study nested within Growing Up in New Zealand; a longitudinal study that is following 6853 children since their birth in 2009-2010. All the Growing Up in New Zealand cohort children hospitalised due to acute respiratory tract infections (ARI) in their first year of life were identified from linkage to the national collection of hospital events (the national minimum dataset (NMDS)). As part of the National Newborn Screening programme, 4 drops of blood were collected onto absorbent cards called dried blood spot cards (DBS). The DBS samples of respiratory cases (children in the cohort admitted with an ARI) and controls (cohort children matched with date of birth ± 7 days and not hospitalised with an ARI) were tested for 25(OH)D concentration. Data collected during the antenatal period, birth and during infancy (9 months and immunisation register) were used to identify predictors of ARI in the first year of life. The dried blood spot 25(OH)D concentrations were categorised as deficient (<50 nmol/L) or sufficient (≥50nmol/L) and the independence of association of vitamin D deficiency at birth as a risk factor for ARI hospitalisation was determined using conditional regression models. Results Three-hundred and eighty-four (6%) of the cohort children were hospitalised with an ARI in their first year of life. After adjustment for factors acting across the life course, the odds of ARI hospital admission were increased for children who were vitamin D deficient at birth (OR= 2.04 95% CI 1.52-2.74). Other factors independently associated with the risk of ARI in the first year of life and listed in their proximity to the child were: male gender (OR=1.62 95% CI 1.12 - 2.35), Pacific (OR=3.42 95% CI 1.98 - 5.91) or Maori ethnicity (OR=2.08 95% CI 1.31 - 3.32), being a second or subsequent child (OR=1.63 95% CI 1.09 - 2.44) or living in areas of medium (OR=2.38 95% CI 1.38 - 4.09) -to-high deprivation (OR=3.10 95% CI 1.87 - 5.12); having a mother with no partner during pregnancy (OR=2.80 95% CI 1.24 - 6.33), or who took no iron, folic acid supplements either during the first 3 months of pregnancy (OR=1.70 95% CI 1.13 - 2.56) or since the first 3 months of pregnancy (OR=1.78 95% CI 1.24 - 2.55), or who took no multivitamin supplements during pregnancy or 3 months pre-pregnancy (OR=1.95 95% CI 1.60 - 4.52), who spent on average <1 hour/day outdoors during pregnancy (OR=2.11 95% CI 1.13 - 3.92); or having a birthweight <2500g (OR=2.59 95% CI 1.70 - 3.91) or gestational age <37 weeks (OR=1.77 95% CI 0.87 - 3.63), living with >3 people/bedroom (OR=1.84 95% CI 1.08 - 3.17) , living in a damp house (OR=1.54 95% CI 0.83 - 2.89), sleeping in rooms with heavy condensation (OR=1.80 95% CI 1.10 - 2.97), did not receive immunisations on time (OR=1.43 95% CI 0.89 - 2.27), and who spent on average <1 hour/day outdoors during infancy (OR=1.68 95% CI 1.09 - 2.77). Conclusion Children who are born with vitamin D deficiency (25(OH)D<50 nmol/L) are twice as likely as children who are vitamin D sufficient at birth to be hospitalised with an ARI during infancy. Prevention of vitamin D deficiency during pregnancy and infancy has the potential to reduce the burden of severe ARI during infancy.