Cytokine response level in patients with influenza A (H1N1) in pregnant women and the incidence of newborn pathology

Background: The physiological course of pregnancy is largely determined by immunological processes, the violation of which in the perinatal period can cause various congenital pathologies. The course of influenza during pregnancy largely depends on the level of physiological adjustment of the immune response. It is known that in severe cases of influenza A (H1N1), excessive production of a number of pro-inflammatory cytokines, the “cytokine storm”, is observed, with the development of endothelial necrosis.

Aim: To determine the nature of the cytokine response to influenza A (H1N1) against the background of pregnancy and to clarify its relationship with the development of intrauterine neonatal pathology.

Materials and methods: A total of 94 pregnant women were treated at the special clinical infectious diseases hospital of the Ministry of Health of the Krasnodar Region for influenza A (H1N1) during the epidemic recovery from December 2015 to February 2016. The diagnosis of influenza is confirmed by the isolation of RNA of influenza A (H1N1) virus by PCR in a nasopharyngeal scraping. Influenza occurred in the first trimester in 20 (21.3%), in the second trimester in 36 (38.3%) and in the third trimester in 38 (40.4%) women. The outcomes of pregnancy were traced, and a retrospective analysis of 91 neonatal observation cards in the maternity hospital was conducted. The comparison groups were as follows: 25 women with physiological pregnancy, 16 pregnant women with chronic placental insufficiency and intrauterine infection, and a control group of 20 healthy, non-pregnant women of reproductive age. The levels of IL-2, IL-4, IL-10, IFN-α, and IFN-γ cytokines in blood serum were studied using the enzyme immunoassay with Vector-Best reagent kits (Novosibirsk) at a sensitivity of 1 pg/ml. The study of cytokine status was conducted at the height of the flu on the first day of admission to the hospital.

Results: In pregnant women with influenza compared with physiological pregnancy, there are considerable decreases in the levels of IL-4 and IL-10, whereas IFN-α and IFN-γ do not change significantly but have a wide range of indicators. Against the background of altered immunoreactivity in pregnancy, the immunosuppressive effects of the influenza virus, in blocking the production of type I interferons, exert a more pronounced negative effect. In pregnant women with influenza and those with chronic placental insufficiency combined with intrauterine infection, unidirectional changes in the levels of IL-4 and IL-10 against physiological pregnancy were detected. The level of IFN-α in chronic placental insufficiency combined with intrauterine infection was significantly higher than the figures reported by other groups. The level of IFN-γ in chronic fetoplacental insufficiency and intrauterine infection was reduced. A significant increase in the IFN-γ/IL4 coefficient was associated with the development of intrauterine infection of the fetus. The level of IFN-α was maximally reduced in women with influenza in the first trimester of pregnancy, whose newborns subsequently had developmental defects in the cardiovascular system. A decrease in the level of IFN-α may reflect the onset of failure of the compensatory mechanisms of immunological regulation of pregnancy.

Conclusion: Determination of the level of interleukins in the acute period of influenza in pregnant women makes it possible to assess the threat of development of the pathology of newborns. The determination of the levels of IL-4, IFN-γ, and IFN-α is of diagnostic value. A high risk of intrauterine infection can be predicted with an increase in the IFN-γ/IL-4 coefficient. Prognostically unfavorable for the development of newborn malformations is a decrease in the level of IFN-α in the development of influenza in women who are in early gestation.