Association between prenatal methamphetamine exposure and intracranial haemorrhage in neonates and infants: nationwide cohort study.

Abstract

Central nervous system stimulants like methamphetamines and cocaine are known to increase the risk of intracranial haemorrhage (ICH) in adults. However, the effects of prenatal methamphetamine exposure on neonatal cerebrovascular outcomes remain underexplored despite its growing prevalence. To assess whether prenatal methamphetamine exposure increases offspring ICH risk versus unexposed pregnancies, and to compare findings with 3,4-methylenedioxymethamphetamine (MDMA)/opioid exposures, including stratification by gestational age. This nationwide, population-based cohort study in Taiwan included pregnancies resulting in live births between 2004 and 2018, and followed offspring through 31 December 2019 to examine the association between prenatal exposure to methamphetamines, MDMA or opioids and incident ICH in offspring. The cohort included 53 455 pairs of pregnant women and their first offspring, with 10 691 exposed to illicit drugs and 42 764 matched controls. Cox proportional hazards models estimated adjusted hazard ratios (aHRs), accounting for maternal age, comorbidities, socioeconomic status and other confounders. Prenatal methamphetamine exposure was associated with a higher risk of ICH in offspring compared with unexposed controls (0.4 <i>v</i>. 0.2%, aHR = 1.72, 95% CI 1.06-2.79). This elevated risk persisted among those exclusively exposed to methamphetamines (aHR = 1.82, 95% CI 1.04-3.29). No statistically significant association was observed for MDMA (0.2 <i>v</i>. 0.2%; aHR = 1.58, 95% CI 0.64-3.93; <i>p</i> = 0.324) or illicit opioids (0.4 <i>v</i>. 0.2%; aHR = 1.43, 95% CI 0.81-2.53; <i>p</i> = 0.214). Stratified analyses showed methamphetamine exposure increased ICH risk among full-term infants (aHR = 4.30, 95% CI 2.08-8.88), with no statistically significant association observed in preterm infants (aHR = 1.00, 95% CI 0.52-1.93). Prenatal methamphetamine exposure was associated with a higher risk of offspring ICH, particularly among full-term infants. These findings support the importance of efforts to reduce methamphetamine use during pregnancy.