Risk of cerebral palsy in relation to parental chronic diseases: Mother or father, does it matter?

Abstract

Introduction Cerebral palsy (CP) is the most common cause of physical disability of childhood affecting approximately 2 per 1000 live born. Lifetime disability burden is high and assessing modifiable risk factors are important. An antenatal origin is likely in most cases. Some maternal chronic diseases have previously been associated with increased risk of CP in offspring, with inflammation and genetics postulated as possible causal pathways. The aim of this study was to investigate associations between maternal and paternal chronic diseases and risk of CP in offspring. Additionally, we aimed to explore the importance of the maternal chronic diseases being present during pregnancy. Methods We used information on children born during 1990–2013 registered in the Medical Birth Registry of Norway. Information on CP status was retrieved from the Norwegian Insurance Scheme and the Norwegian Patient Registry. By record linkage between the birth registry and patient registry, we were able to extract information on maternal and paternal diagnosis unrelated to time of pregnancy. We constructed 870,212 mother–children-pairs including 2190 CP cases (2.5 per 1000) and 719,179 father–children-pairs including 1736 CP cases (2.4 per 1000). In additional analyses, we used information on maternal diagnosis registered in the birth registry as present before or during pregnancy as the exposure [1.3 million children and 3356 CP cases (2.6 per 100)]. We used log binominal regression models to estimate the risk of CP by parental disease status. Results The majority of the maternal diseases from the patient registry were positively associated with CP in children. Type 2 diabetes was associated with a 2.5-fold excess risk [relative risk (RR) 2.5, 95% confidence interval (CI) 1.9–3.3], type 1 diabetes with a 2.2-fold excess risk (RR: 2.2, 95% CI: 1.7–3.0) and gestational diabetes with a 1.8 fold (RR: 1.8, 95% CI: 1.4–2.4) excess risk. Markedly increased risk was also seen for chronic hypertension (RR: 1.8, 95% CI: 1.4–2.4), lupus (RR: 1.7, 95% CI: 0.8–3.7), chronic kidney disease (RR: 1.5, 95% CI: 1.0–2.1), Crohn's disease (RR: 1.5, 95% CI: 0.9–2.4) and hypothyreosis (RR: 1.4, 95% CI: 1.0–2.0). For many of the diseases present before or during pregnancy retrieved from the birth registry, the association were even stronger, including diabetes type 2 (RR: 3.5, 95% CI: 2.0–6.2), lupus (RR: 2.9, 95% CI: 0.9–8.9), Crohn's disease (RR: 2.3, 95% CI: 1.2–4.4) and rheumatoid arthritis (RR: 2.0, 95% CI: 1.3–2.9). Paternal diseases did not imply the same excess risks as maternal diseases. Except for psoriasis (RR: 1.6, 95% CI: 1.2–2) the risks were lower than for mothers. Conclusions We found positive associations between maternal, but not paternal chronic diseases and CP in children. Some associations were stronger when the disease was present during pregnancy. Our results do not add strength to the hypotheses of a common genetic pathway for chronic diseases in parents and CP in offspring. However, our findings may indicate that intrauterine environment is important with chronic inflammation as a possible causal pathway.