Maternal and infant factors associated with infancy-onset hydrocephalus in Washington State.

Objective: Hydrocephalus, a complex condition characterized by progressive accumulation of cerebrospinal fluid within the ventricular system of the brain, affects ∼ 6 in 10,000 infants and is heterogeneous in nature. Previous investigations of risk factors have not considered etiologic heterogeneity.

Methods: We conducted a case-control study of 1748 children with hydrocephalus identified through birth certificate check boxes and ICD-9 codes of linked hospital discharge records through the first year of life. Control infants were identified from birth records (N = 19,700), frequency matched to cases by year of birth. Three mutually exclusive, nonexhaustive subgroups were identified: hydrocephalus associated with a neural tube defect (n = 332); prenatal-onset hydrocephalus (n = 402); and hydrocephalus associated with intracranial hemorrhage (n = 446). Within each group, we examined associations with maternal age, race/ethnicity, parity, diabetes and hypertension, and infant sex and gestation. We used logistic regression to calculate odds ratios and 95% confidence intervals.

Results: Asian ethnicity was independently associated with an inverse risk of all subtypes of hydrocephalus (hydrocephalus associated with a neural tube defect: odds ratio, 0.44; 95% confidence interval, 0.23 to 0.84; prenatal-onset hydrocephalus: odds ratio, 0.47; 95% confidence interval, 0.27 to 0.83; hydrocephalus associated with intracranial hemorrhage: odds ratio, 0.59; 95% confidence interval, 0.33 to 1.07) compared with whites. Pre-existing diabetes was associated to varying degrees with all three subtypes (hydrocephalus associated with a neural tube defect: odds ratio, 1.94; 95% confidence interval, 0.61 to 6.17; prenatal-onset hydrocephalus: odds ratio, 5.20; 95% confidence interval, 2.60 to 10.40; hydrocephalus associated with intracranial hemorrhage: odds ratio, 5.26; 95% confidence intervals, 2.85 to 9.69). Hypertension had a positive association with hydrocephalus associated with intracranial hemorrhage (odds ratio, 1.91; 95% confidence interval, 1.46 to 2.52) but an inverse association with hydrocephalus associated with a neural tube defect (odds ratio, 0.59; 95% confidence interval, 0.36 to 0.98). Gestation ≤ 30 weeks was associated with all three subgroups, most notably hydrocephalus associated with intracranial hemorrhage (odds ratio, 443.56; 95% confidence intervals, 326.34 to 602.87); nearly two-thirds (64%) of hydrocephalus associated with intracranial hemorrhage infants were born ≤ 30 weeks. Male gender was independently associated only with hydrocephalus associated with intracranial hemorrhage (odds ratio, 1.82; 95% confidence interval, 1.40 to 2.39). No associations were observed with advanced or young maternal age or with parity.

Conclusions: The different risk profiles seen among these three subgroups support the biologically heterogeneous nature of infantile hydrocephalus. Future research should take specific etiologic subtypes into account.