Very preterm birth : etiological aspects and short and long term outcomes

Very preterm birth, occurring before 32 completed weeks of gestation, is an often unexplained pregnancy complication affecting approximately 1 to 2 percent of all births. This thesis includes four studies regarding the etiology, and short and long term outcomes of very preterm birth, using Swedish population-based data. The aims were to investigate if viral infections during pregnancy increase the risk of very preterm delivery, to study the role of level of care for infant mortality in very preterm infants, and to explore long-term health in adults born very preterm, with regard to high blood pressure and type 2 diabetes.

Among pregnant women in Stockholm, we identified 269 cases of very preterm birth and 301 controls with term delivery, with archived blood sampled for the Rubella serology screening in early pregnancy. Serum was investigated for presence of viral genetic material. Any viremia was detected in 10 cases and in 5 controls, corresponding to an adjusted odds ratio (95 percent confidence interval) of 2.21 (0.71-6.84). Although risk estimates were consistently elevated for any viremia and for Parvovirus B19, none were significant on a 5 percent level. Whether viral infections during pregnancy increase the risk of very preterm birth needs to be investigated in larger studies.

During 1992-98, 2,253 liveborn singleton infants were born very preterm in Swedish general and university hospitals. Infant mortality rates increased by decreasing gestational age, from 5 percent at 31 weeks to 56 percent at 24 weeks. Very preterm birth at a general hospital was associated with an increased risk of infant mortality, but the risk increase was confined to extremely preterm infants born at 24 to 27 weeks, having an adjusted odds ratio for infant mortality of 2.00 (1.15-3.49).

Among 329,495 young men born in Sweden 1973-81 and conscripted for military service, gestational age at birth was inversely related to high systolic blood pressure at conscription (>=140 mm Hg). Adjusted odds ratios among men born very and extremely preterm (29-32 weeks and 24-28 weeks, respectively) were 1.45 (1.28-1.64) and 1.88 (1.33-2.68), respectively. The association was not confounded by familial (common genetic and shared environmental) factors. In addition, being born small for gestational age was not a risk factor of high systolic blood pressure among men born at 24 to 32 gestational weeks, but increased the risk among men born moderately preterm (33-36 weeks) and at term (>=37 weeks).

In a cohort of 18,230 Swedish twins, rates of type 2 diabetes increased with decreasing gestational age and with decreasing birth weight. In cohort analyses there was no association between preterm birth and type 2 diabetes, whereas risk of type 2 diabetes increased with decreasing birth weight. However, in co-twin case-control analyses, an increased risk of type 2 diabetes with lower birth weight was found within dizygotic but not within monozygotic twin pairs. Odds ratios per 500 grams decrease in birth weight were 1.38 (1.02-1.85) and 1.02 (0.63-1.64), respectively, indicating genetic confounding of the association between low birth weight and type 2 diabetes.

List of scientific papers

I. Johansson S, Buchmayer S, Harlid S, Iliadou A, Sjöholm M, Grillner L, Norman M, Sparén P, Dillner J, Cnattingius S (2008). "Infection with Parvovirus B19 and Herpes viruses in early pregnancy and risk of second trimester miscarriage or very preterm birth." Paediatric Perinatal Epidemiology. [Submitted]

II. Johansson S, Montgomery SM, Ekbom A, Olausson PO, Granath F, Norman M, Cnattingius S (2004). "Preterm delivery, level of care, and infant death in sweden: a population-based study." Pediatrics 113(5): 1230-5.
https://pubmed.ncbi.nlm.nih.gov/15121934

III. Johansson S, Iliadou A, Bergvall N, Tuvemo T, Norman M, Cnattingius S (2005). "Risk of high blood pressure among young men increases with the degree of immaturity at birth." Circulation 112(22): 3430-6.
https://pubmed.ncbi.nlm.nih.gov/16301344

IV. Johansson S, Iliadou A, Bergvall N, dé Fairé U, Kramer M S, Pawitan Y, Pedersen N L, Norman M, Lichtenstein P, Cnattingius S (2008). "Genetic factors contribute to the association between low birth weight and type 2 diabetes - a large cohort study of Swedish twins" Epidemiology.
https://pubmed.ncbi.nlm.nih.gov/18714437