An altered inflammatory activity due to functionally relevant polymorphisms of the innate immune system may influence pathways leading to labour and, therefore, impact on the frequency of preterm birth. We examined five polymorphisms of the innate immune system in a large cohort of preterm very-low-birth-weight (VLBW, n = 909) and term-born infants (n = 491) and their mothers (n = 747). The primary outcome was preterm versus term birth. Frequencies of polymorphisms in mothers of term-born infants versus mothers of VLBW infants and term infants versus preterm VLBW infants (singletons) are given. Homozygous CD14-159T: 18.5 versus 21.8% (mothers) and 19.6 versus 21.2% (infants). Homozygous interleukin IL-6-174G: 28.8 versus 38% (P = 0.018, mothers) and 30 versus 32.7% (infants). Homozygous or heterozygous nuclear oligomerization domain NOD2-3020insC: 6.9 versus 6.1% (mothers) and 5.7 versus 5.1% (infants). Heterozygous or homozygous toll-like-receptor TLR2-Arg753Gln: 6.9 versus 6.1% (mothers) and 5.7 versus 5.1% (infants). Homozygous or heterozygous TLR4-896G: 8.1 versus 11.5% (mothers) and 11.6 versus 10.5% (infants). Although the homozygous maternal IL-6-174G genotype was found to be independently associated with preterm delivery in multivariate regression analysis, the incidence of intrauterine infection was not significantly increased in mothers of preterm VLBW-infants, carrying this or other polymorphisms of the innate immune system. The overall influence of the investigated polymorphisms on the development of preterm delivery seems moderate, since only the maternal IL6-174G genotype was associated with preterm birth and none of the polymorphisms were associated with intrauterine infection as the cause of preterm birth.

Interleukin 18 (IL-18) is an important cytokine and involved in the pathogenesis and genetics of many diseases. The authors studied two different populations of preterm infants to test whether polymorphisms within IL-18 are in association with prematurity itself or with typical pulmonary disease or measurements seen in preterm infants, such as bronchopulmonary dysplasia, pneumothoraces and application of surfactant, inhalation or mechanical ventilation. Whereas the first population of 228 preterm infants showed strong association of IL-18 with preterm birth (p<0.001), this was not confirmed in the second population of 346 preterm infants. In addition, no association with any lung condition of prematurity was observed. The authors conclude that IL-18 does not play an important role in the genetics of preterm birth nor in the development of bronchopulmonary dysplasia and other lung complications in preterm infants. Caution must be taken in the interpretation of the results of genetic association studies performed in one population.