Prenatal vitamin D supplementation mitigates inflammation-related alveolar remodeling in neonatal mice.

The development of chronic lung disease in the neonate, also known as bronchopulmonary dysplasia (BPD), is the most common long-term complication in prematurely born infants. In BPD, the disease-characteristic inflammatory response culminates in nonreversible remodeling of the developing gas exchange area, provoked by the impact of postnatal treatments such as mechanical ventilation (MV) and oxygen treatment. To evaluate the potential of prenatal treatment regimens to modulate this inflammatory response and thereby impact the vulnerability of the lung toward postnatal injury, we designed a multilayered preclinical mouse model. After administration of either prenatal vitamin D-enriched (VitD+; 1,500 IU/g food) or -deprived (VitD-; <10 IU/kg) food during gestation in C57B6 mice (the onset of mating until birth), neonatal mice were exposed to hyperoxia (FiO2 = 0.4) with or without MV for 8 h at days 5-7 of life, whereas controls spontaneously breathed room air. Prenatal vitamin D supplementation resulted in a decreased number of monocytes/macrophages in the neonatal lung undergoing postnatal injury together with reduced TGF-ß pathway activation. In consequence, neonatal mice that received a VitD+ diet during gestation demonstrated less extracellular matrix (ECM) remodeling upon lung injury, reflected by the reduction of pulmonary α-smooth muscle actin-positive fibroblasts, decreased collagen and elastin deposition, and lower amounts of interstitial tissue in the lung periphery. In conclusion, our findings support strategies that attempt to prevent vitamin D insufficiency during pregnancy as they could impact lung health in the offspring by mitigating inflammatory changes in neonatal lung injury and ameliorating subsequent remodeling of the developing gas exchange area.NEW & NOTEWORTHY Vitamin D-enriched diet during gestation resulted in reduced lung inflammation and matrix remodeling in neonatal mice exposed to clinically relevant, postnatal injury. The results underscore the need to monitor the subclinical effects of vitamin D insufficiency that impact health in the offspring when other risk factors come into play.

Association of polymorphisms in the human surfactant protein-D (SFTPD) gene and postnatal pulmonary adaptation in the preterm infant.

BACKGROUND: Surfactant protein-D (SP-D) is a member of the collagenous subfamily of calcium-dependent lectins (collectins). Associations between single nucleotide polymorphisms (SNPs) of the human gene coding surfactant protein-D (SFTPD) and infectious pulmonary diseases have been established by several groups. As the outcome of very preterm infants is mainly determined by pulmonary morbidity, the aim of the present study was to investigate the potential association between sequence variations within the SFTPD gene and pulmonary morbidity in preterm infants below 32 weeks of gestational age (GA). MATERIALS AND RESULTS: Four validated SNPs were genotyped with sequence-specific probes (TaqMan 7000) in 284 newborn infants below 32 weeks of GA. An association between the SNP rs1923537 and the development of respiratory distress syndrome (RDS) in the study population was found with a lower prevalence of RDS in infants having homozygous a minor allele genotype (odds ratio = 1.733, 95% confidence interval 1.139-2.636, adjusted p = 0.0408). Consecutively, the indicated polymorphism was found to be associated with a lower number of repetitive surfactant doses, and with a lower prevalence for the requirement of oxygen supplementation on day 28, as well as the use of diuretics. CONCLUSION: The finding of an association of a variant of the SFTPD gene, that has previously been shown to be associated with increased SP-D serum levels in adult patients with acute respiratory failure, i.e. RDS in preterm infants, may provide a basis for the initial risk assessment of RDS and modification of surfactant treatment strategies. A role for SP-D in neonatal pulmonary adaptation has to be postulated.