Maternal Risk Factors for Congenital Cerebral Palsy
- Author(s): Streja, Elani
- Advisor(s): Olsen, Jorn
- et al.
Congenital Cerebral Palsy (CP) is the most common physical disability in children. In spite of major advances in medical technology, the etiology of CP is still not well understood. There is growing evidence that brain damage leading to CP development occurs during pregnancy and that maternal phenotype contributes to this intrauterine environment. We hypothesized that maternal factors such as infections, smoking, comorbidities and genetics can increase the risk of CP in children. Additionally, we hypothesized the relationship between birth weight and placenta weight is a proxy for placenta insufficiency, which may be an important factor in the pathology leading to CP. The aim of this dissertation is to examine the associations between these maternal factors and CP in the child.
We carried out studies using both Danish national registries and the Danish National Birth Cohort. Diagnoses of CP in the child were ascertained using the Danish National Cerebral Palsy Register. Cox proportional hazard ratios were calculated to estimate risk of CP or risk of cardiovascular disease. For studies on placental disorders, placenta weight, and birth weight, we identified 1,874,653 singleton births occurring between January 1st 1973 and December 31st 2003, of which 2,547 had CP. We found the risk of CP decreased with increasing continuous placenta weight (/100g) (aHR 0.68; 95% CI: 0.64-0.71). However, adjustment for continuous birth weight (kg) reversed this association (aHR 1.15; 95% CI: 1.07-1.22). Associations with CP were additionally found for vaginal bleeding, diabetes in pregnancy and hypertensive disorders in pregnancy, but associations were no longer significant after adjustment for both birth weight (kg) and placenta weight (/100g). The association between placenta abruption and CP risk remained significant after adjustment for both placenta weight and birth weight. After stratification on several birth weight groups, continuous placenta weight was not significantly associated with CP.
For the study on cardiovascular risk in parents of children with CP, we used the children in Study 1, and identified the mothers of 1,021,955 singleton firstborns, of whom 2,508 had CP. After adjustment for demographic confounders, child being born small for gestational age and maternal hypertensive disorder during pregnancy, the "all cardiovascular disease" endpoint was significantly associated with CP (aHR 1.32; 95% CI: 1.04-1.68). However, after additional adjustment for preterm birth the association was no longer significant (aHR 1.11; 95% CI: 0.87-1.42). In cardiovascular subtypes, however, cerebrovascular disease and thrombosis did remain significant in adjusted models including preterm birth (aHR 2.08; 95% CI: 1.11-3.91 and aHR 3.23; 95% CI: 1.19-8.78 respectively). For fathers, the adjusted hazard ratios were much lower and did not reach the level of significance for any of the endpoints.
In the study of self reported maternal infections, maternal smoking and CP risk we included 81,066 singletons who were born between August 1996 and June 2003 in the Danish National Birth Cohort. Self-reported vaginal infections were associated with an increased risk of overall CP and spastic CP (aHR: 1.52; 95% CI: 1.04-2.24 and aHR: 1.73; 95% CI: 1.16-2.60). In particular untreated vaginal infections were associated with an increased risk of spastic CP (aHR: 1.95; 95% CI: 1.16-3.26). Fever was associated with the risk of CP (aHR: 1.53; 95% CI: 1.06-2.21). Smoking 10 or more cigarettes per day during pregnancy was also associated with spastic CP (aHR: 1.80; 95% CI: 1.10-2.94). There were interactions on a multiplicative scale for the outcome spastic CP between untreated vaginal infections and either smoking 10 or more cigarettes per day or preterm delivery. Urinary tract infections were not associated with having a child with CP.
In conclusion, maternal factors may affect the intratuterine environment and play a role in the etiology of CP.