Intrauterine drug exposure as a risk factor for cerebral palsy

Abstract

Aim: To determine whether infants with intrauterine drug exposure (IUDE) are similarly at risk for cerebral palsy (CP) as other high-risk populations, whether CP classification differs based on IUDE status, and describe the association of CP with specific substances among exposed infants.

Method: This was a retrospective analysis of infants in a high-risk follow-up program (n=5578) between January 2014 and February 2018 with a history of IUDE or who received a CP diagnosis. CP rates were compared using two-sample z-tests. CP classification was assessed using Fisher's exact, Cochran-Armitage, and Wilcoxon rank-sum tests. Models for CP risk were assessed using multivariable logistic regression.

Results: Among all infants with IUDE (n=1086), 53.8% were male with a mean (SD) birth gestational age of 36.8 (3.6) weeks. Among unexposed infants with CP (n=259), 54.4% were male with a mean (SD) birth gestational age of 29.9 (5.7) weeks. Opioids were the most common exposure (93.7%) of all infants with IUDE. The CP rate in the IUDE (5.2%) and unexposed (5.7%) high-risk populations were not significantly different (p=0.168), nor were there differences in CP typology, topography, or severity between exposed (n=57) and unexposed (n=259) infants (all p>0.05). In patients with IUDE and after controlling for established CP risk factors, the observed odds of CP varied among substances.

Interpretation: We suggest that IUDE should be considered a 'newborn-detectable risk' in the guidelines for the early detection of CP.

Figure 1:

Rates of intrauterine drug exposure (IUDE) and cerebral palsy (CP) in infants cared for in the high-risk follow-up program. A total of 5578 patients were evaluated in the neonatal intensive care unit (NICU) follow-up program at our institution between January 2014 and February 2018. A total of 1086 patients (19.5%) had documented IUDE; 316 patients (5.7%) were diagnosed with CP. All CP diagnoses were confirmed at 2 years of age or more as meeting the established criteria.^, NOWS, neonatal opioid withdrawal syndrome.

Figure 2:

Association between specific substance exposure and cerebral palsy (CP) adjusting for newborn-detectable risks. For each substance exposure, adjusted (gray shapes) and unadjusted (black shapes) odds ratios and 95% confidence intervals are displayed. Specific substance exposures are described by exposure to ‘at least’ that substance, that is, either exposure to only that substance or exposure to that substance along with additional exposures. The adjusted model includes specific substance exposure, newborn-detectable risk for CP (preterm birth, congenital anomalies/genetic conditions, intrauterine growth restriction, neonatal encephalopathy, neonatal seizures) and the interaction term. Stimulants included amphetamines, methamphetamines, and cocaine. Due to the limited number of infants with benzodiazepine exposure and CP risk factors, the adjusted model did not provide stable estimates. Table S3 (online supporting information) has the corresponding values.