Maternal hypertension and intrapartum fever increase the risk for ischemic stroke in infants, a large retrospective analysis suggests.

Gestational diabetes, a known risk factor for maternal hypertension and neonatal hypoglycemia, does not increase stroke risk.

“Additional research is needed to determine the mechanism underlying these associations and to develop effective preventive methods for high-risk infants,” Dr. Joshua R. Mann reported at the meeting.

Dr. Joshua Mann

Approximately 2-4 children per 10,000 births experience ischemic stroke in the first 28 days of life. Roughly 60% of infants present immediately, typically with neonatal seizures. In the remaining 40%, stroke is recognized later in childhood during evaluation for abnormal neurologic or cognitive development.

There were 43 cases of ischemic stroke before 30 days of life and 118 additional cases diagnosed from day 30 through 364 days in the retrospective analysis of 226,117 children (199,934 full-term births) born from 2000 through 2007 and enrolled in the South Carolina Medicaid program.

Of these, 37 cases and 96 cases, respectively, had confirmed ischemic strokes, defined as more than one ICD-9 code for ischemic stroke or a single diagnosis of ischemic stroke plus a neurocognitive condition that could be indicative of stroke.

Compared with infants without stroke, maternal hypertension was significantly more common for infants with ischemic stroke before 30 days (32.5% vs. 14%; P value = .0004) and before 365 days (28% vs. 14%; P less than .0001), reported Dr. Mann of family and preventive medicine at the University of South Carolina, Columbia.

Fever at delivery was significantly more common in mothers of infants with stroke prior to 365 days (4.9% vs. 1.2%; P less than .0001), but not in those with stroke before 30 days (4.6% vs. 1.2%; P = .09).

Maternal diabetes was not significant at either time point.

In a logistic regression analysis that adjusted for a broad range of demographic and other confounding risk factors, infants born to mothers with hypertension had more than twice the risk of any stroke, defined as one or more diagnoses indicating ischemic stroke, before 30 days (odds ratio 2.31; P = .0071), or a confirmed ischemic stroke (OR 2.75; P = .0021), he said.

Maternal fever at delivery more than tripled the risk of any ischemic stroke (OR 3.36; P = .048) and quadrupled the risk of confirmed ischemic stroke (OR 4.02; P = .025), he reported in a poster presentation.

Maternal diabetes did not significantly increase the odds of any stroke (OR 0.35; P = .08) or confirmed stroke (OR 0.40; P = .13).

Although it was not the primary goal of the study, the investigators also found multiple child characteristics to be associated with increased odds of any stroke prior to 365 days. The significant covariates were birth trauma (OR 5.99), birth asphyxia (OR 11.42), sickle cell disease (OR 3.58), sickle cell trait (OR 2.45), congenital infection (OR 5.39), neonatal infection (OR 6.06), meningitis (OR 6.05), encephalitis (OR 3.99) and child thrombophilia, which had a staggering odds ratio of 157.99.

There was also evidence of synergy between maternal hypertension and the presence of at least one other risk factor for stroke diagnosed before 365 days.

A recent study among 44 children indicated that the timing of the stroke has a bearing on outcomes. Children who had a stroke between 1 and 6 years had better neuropsychological outcomes than did children who had a stroke before age 1 or after age 6 (Child Neuropsychol. 2011 Dec. 6 [doi:10.1080/09297049.2011.639756]).