Maternal Medication Use and Neuroblastoma in Offspring

Abstract

The association between a mother's use of specific medications during pregnancy and lactation and neuroblastoma in her offspring was evaluated in a case-control study. Newly diagnosed cases of neuroblastoma (n=504) in the United States and Canada were identified between 1992 and 1994 at 139 hospitals affiliated with the Pediatric Oncology Group or the Children's Cancer Group clinical trial programs. One age-matched control was sampled from the community of each case by means of random digit dialing. Exposure information was ascertained retrospectively from mothers in a structured telephone interview. Odds ratios were estimated using conditional logistic regression, with adjustment for maternal sociodemographic factors. The results did not support an association between neuroblastoma and maternal exposure to diuretic agents, antiinfective agents, estrogens, progestins, sedatives, anticonvulsant drugs, or drugs that may form N-nitroso derivatives. Mothers of cases were more likely to report using medications containing opioid agonists while they were pregnant or nursing than were mothers of controls (odds ratio=2.4, 95% confidence interval: 1.3, 4.3). Specifically, more mothers of cases reported using medications containing codeine while pregnant or nursing than did mothers of controls (odds ratio=3.4, 95% confidence interval: 1.4, 8.4). This preliminary finding may be due to bias, confounding, or chance, and additional studies are needed for confirmation.

The effects of codeine on pregnancy outcome: Results from a large population-based cohort study

“…In this study, codeine use during pregnancy was not found to be associated with infant survival rate, congenital malformation rate, or other adverse pregnancy outcomes, except for Cesarean delivery and excessive postpartum hemorrhage. Unlike previous studies [4,5,7,8] and other medical literature sources that rely either on data regardng opioid analgesic use in general or a few case studies [9,13], we found no increased risk of congenital malformations or neonatal respiratory depression. Associations of codeine use during pregnancy and neonatal abstinence syndrome were unfortunately not feasible to evaluate, as neonatal abstinence syndrome scores were not routinely applied.…”

“…One casecontrol study of 504 children with neuroblastoma found an association with in utero exposure to codeine [odds ratio (OR) 3.4, 95% confidence interval (CI) 1. 4-8.4] [4]. Another of 599 infants found that mothers who gave birth to infants with cleft palate or cleft lip with or without cleft palate used opioid analgesics (mainly codeine) much more frequently than the control group; the largest difference was seen for codeine use during the first trimester (8.6% compared with 2.1% of infants in the control group; P< 0.01) [5].…”

Overview and recent advances in the treatment of neuroblastoma

“…The underlying etiology of most neuroblastoma tumors remains unknown, and although environmental factors have been suggested as possible causes, direct linkage has not been clearly established [11][12][13]. The vast majority of neuroblastoma tumors occur in isolation in families, suggesting that the rates of oncogenic germline mutations in patients with neuroblastoma are low.…”

Perinatal characteristics and risk of neuroblastoma

“…Studies have examined prenatal exposure to maternal tobacco, [4][5][6][7][8] alcohol, 4,5,7,9,10 maternal hair dye 5,11 and drug-use. 5,7,[12][13][14][15] Other commonly examined exposures include those pertaining to sociodemographics, reproductive and pregnancy history, labor and delivery, and infant characteristics. 6,8,9,12,[16][17][18][19][20][21] To gain further understanding of whether perinatal exposures are involved in the etiology of NB, we evaluated associations between factors recorded in birth records and NB in a populationbased case-cohort study in Minnesota using prospectively collected exposure information.…”