Phenobarbital and its Sodium Salt - IARC Monographs on the ...

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<strong>IARC</strong> MONOGRAPHS VOLUME 79
the type nor duration of the exposure of mothers or children to barbiturates was
described.]
In a population-based study in the USA (Kramer et al., 1987), 181 children with
newly diagnosed, histologically confirmed neuroblastomas were identified from either
the files of the Greater Delaware Valley Pediatric Tumour Registry or the Children’s
Hospital of Philadelphia for the period 1970–79. Of the 139 children eligible for study,
18 could not be traced <strong>and</strong> 17 refused, leaving 104 for inclusion (response rate, 75%).
One population control per case was selected by r<strong>and</strong>om-digit dialling <strong>and</strong> matched to
the case by area of residence, race <strong>and</strong> date of birth (plus or minus 3 years). The
response rate of those eligible <strong>and</strong> invited was 57%. Interviews, conducted over the
telephone with mothers of study subjects, included questions on health history <strong>and</strong>
exposure to alcohol, drugs <strong>and</strong> other treatments. Three case mothers <strong>and</strong> no control
mothers reported use of phenobarbital at some time during pregnancy. When use of
phenobarbital was combined with use during pregnancy of other ‘neurally active
drugs’, defined by the authors to include other barbiturates, amphetamines, narcotics,
tranquillizers, diet pills <strong>and</strong> muscle relaxants, there was a statistically significant,
positive association with neuroblastoma in the children, with an odds ratio for the
matched pairs of 2.8 (90% CI, 1.3–6.0).
Goldhaber et al. (1990) identified 304 children aged 0–19 years, notified with
malignant intracranial or spinal cord tumours between 1960 <strong>and</strong> 1983, from a computerized
information system on patients discharged from hospitals run by a prepaid
medical care programme in northern California (USA) <strong>and</strong> the files of the Cancer
Registry of the San Francisco Bay Area. The 237 that were included were those for
which the diagnosis had been confirmed in a medical record review <strong>and</strong> whose family
had belonged to the programme for at least 6 months. For each study child, two control
children were selected from the membership list <strong>and</strong> matched to the case on year of
birth, sex <strong>and</strong> initial date of membership of the health care programme. The medical
charts of the mothers, from the respective birth departments (inside or outside the
medical care programme), were reviewed for information on barbiturate use during
pregnancy, <strong>and</strong> the available medical charts on the children after birth were reviewed.
Fifty-five cases (23%) <strong>and</strong> 72 (15%) controls had a history of childhood exposure to
barbiturates, yielding an odds ratio of 1.8 (1.2–2.7). In a subgroup of 86 women for
whom prenatal records were available, there was no difference between cases <strong>and</strong>
controls with regard to exposure to barbiturates, 19 (22%) case mothers <strong>and</strong> 39 (23%)
control mothers having taken barbiturates during pregnancy, yielding a matched-pair
odds ratio of 1.0 (95% CI, 0.5–1.9). <strong>Phenobarbital</strong>, alone or in combination, was the
predominant barbiturate used. Gastrointestinal disorder was the most common
indication for barbiturate use for the mothers of both cases (38%) <strong>and</strong> controls (29%).
Epilepsy in the child was associated with an odds ratio for brain cancer of 5.1 (1.8–14).
Adjustment for epilepsy in a conditional logistic regression model reduced the odds
ratio for brain cancer associated with barbiturate use from 1.8 to 1.4 (0.9–2.2).