Infections and infectious related morbidity during pregnancy : Short and long-term effects

Abstract: The aim of this thesis was to elucidate the association between infections during pregnancy and risks of miscarriage, preterm delivery and later development of autism. We identified 60 755 women with singleton births between 1973 and 2000 in the counties of Uppsala and Gävleborg who had a Pap smear taken during pregnancy. Risk of adverse pregnancy outcome with respect to signs of infection on Pap smear was calculated in logistic regression models. Presence of Coccobacilli on Pap smear slightly increased the risk of delivery of an SGA infant and presence of Trichomonas increased the risk of moderately preterm delivery (32-36 weeks). When the analyses was restricted to Pap smears taken within four weeks before delivery we found that presence of Coccobacilli was associated with a fourfold increase in risk of very preterm delivery (<31 weeks). Among pregnant women in Stockholm County, we identified 235 cases with second trimester miscarriage, 269 cases with very preterm delivery and 301 controls with term delivery for which we had archived blood samples for Rubella serology screening in early pregnancy. Blood samples were analyzed for Parvovirus B19 and Herpes viruses. Viremia was found in 11 (4.7%) women with second trimester miscarriage and 10 (3.7%) women with very preterm birth, compared to 5 (1.7%) women who delivered at term, corresponding to adjusted odds ratios (95 percent confidence interval) of 3.32 (0.93-11.8) and 2.21 (0.71-6.84), respectively. A cohort of all primiparous women with live singleton births from 1987 through 2000 in Sweden (n= 601 883) was linked to the Swedish Hospital Discharge Register to obtain information on previous pregnancy losses. The risk of extremely preterm delivery (< 27 weeks), very preterm delivery (28-31 weeks), and moderately preterm delivery (32-36 weeks) associated with previous pregnancy loss was estimated in logistic regression models. Previous spontaneous abortions and previous missed abortions were associated with increased risks of preterm delivery, and the risks increased with severity of preterm delivery. Previous pregnancy losses were also foremost associated with increased risks of preterm PROM and preterm labor in deliveries before 32 weeks of gestation. Among children born in Sweden between 1987 and 2002 we identified 1216 children diagnosed with autism and 6080 matched controls. Risks of autism associated with maternal and pregnancy characteristics (including maternal prenatal infections and other infectious related diagnoses) or neonatal complications were estimated using logistic regression models. To study the mediating effect of perinatal factors on the association between gestational age and autism we adjusted the models for maternal and pregnancy characteristics as well as neonatal complications in a stepwise manner. Infectious-related exposures were not associated with increased risk of autism. Compared with children born at term, the unadjusted odds ratios of autism (95 percent confidence intervals) among very (<31 weeks) and moderately (32 to 36 weeks) preterm born children were 2.03 (1.13 to 3.64) and 1.52 (1.16 to 1.99), respectively. When we controlled for maternal and birth characteristics, corresponding risks were reduced to 1.48 (0.77 to 2.84) and 1.33 (0.98 to 1.81). After also controlling for neonatal complications, the risks of autism related to very and moderate preterm were further reduced. The reductions in risks of autism related to preterm birth were primarily attributed to preeclampsia, small-for-gestational age birth, congenital malformations, low Apgar score (0 to 6) at five minutes and neonatal brain injury.