Doi:10.1016/s0140-6736(99)02423-x

Research letters
Congenital anomalies after prenatal ecstasy exposure P R McElhatton, D N Bateman, C Evans, K R Pughe, S H L Prospective follow-up of 136 babies exposed to ecstasy in utero 74 pregnant women reported taking ecstasy only and 62 indicated that the drug may be associated with a significantly took ecstasy with other drugs of abuse (ecstasy and increased risk of congenital defects (15·4% [95% CI 8·2–25·4]).
amphetamine 37 women; ecstasy and cocaine 20; ecstasy and Cardiovascular anomalies (26 per 1000 livebirths [3·0–90·0]) and cannabis 16; ecstasy and alcohol 13; ecstasy and LSD nine; musculoskeletal anomalies (38 per 1000 [8·0–109·0]) were ecstasy and other drugs of abuse 13). Acute toxicity from ecstasy was reported in only two of the mothers. The maternal The illicit use of ecstasy (methylenedioxymethamphetamine) age at the time of exposure was obtained for 82 (60%) women: has increased during the past decade and there is growing 26 women were aged 16–20 years; 31 21–25 years, 20 26–31 concern about its potential toxicity.1 There are few data on the effects of ecstasy exposure in human pregnancy,2 – 4 and no 127 women (71 exposed to ecstasy alone and 56 exposed to published teratological studies in animals. Whereas ecstasy and other drugs of abuse) were exposed in the first amphetamines and related compounds have been associated trimester, two in the first and second trimesters, two in the with an increased risk of structural malformations of the heart second trimester, and one in the third trimester. Four women and great vessels in various species, studies on the were exposed to several drugs of abuse throughout pregnancy.
teratogenicity of amphetamines in human pregnancy have 11 pregnancies resulted in miscarriage, 48 women had produced conflicting results on both the overall risk of elective terminations (one after prenatal diagnosis of malformations and the risk of any specific birth defect.5 malformations). No necropsy data were available on any of the The UK National Teratology Information Service (NTIS) other aborted fetuses. The rate of miscarriage was 8%, within collected prospective follow-up data on the outcome of 136 the expected range; but the rate of elective terminations was pregnancies (one pair of twins), in which exposure to ecstasy 35%; higher than the UK a v e r a g e .
occurred between January, 1989, and June, 1998. Within this There were 78 liveborn infants; 66 were normal. 12 had period there were 302 enquiries involving ecstasy. 31 (10%) of congenital anomalies (15·4% [95% CI 8·2–25·4]), which is these pregnancies are not yet completed and 135 (45%) were significantly higher than the expected incidence of 2–3% (table).
lost to follow-up because the enquiring health professional (in Eight infants were born prematurely between 25 and 36 most cases the patient’s general practitioner) could no longer weeks of gestation (including one pair of twins born at 25 identify the patient, or the patient did not return to the surgery.
weeks of gestation). There were two cases of fetal distress In each case the enquirer was asked to provide information among those born prematurely that were thought not to be on drug exposure, both prescribed and non-prescribed, at the related to ecstasy. One neonatal death occurred in an infant time of the enquiry, together with the mother’s expected date without apparent abnormalities at birth who was born to a of delivery. Follow-up was done by contacting the enquirer, mother who had taken ecstasy, heroin, and methadone after the expected date of delivery. Where necessary, throughout pregnancy. No necropsy data are available.
information was then sought from other clinical specialists.
No adverse effects were observed in the sex ratio.
Birthweights were within the expected range for term infants (>37 weeks), with only three infants weighing less than 2·5 kg.
There were three female infants with talipes (rate of 38 per 1000 [95% CI 8–109] v s expected rate of 1 per 1000).
Idiopathic talipes equinovarus has a male predominance of The spontaneous incidence of congenital heart disease (CHD) is 5–10 per 1000 livebirths. Of infants with CHD, Absent upper limbs, left scapula, clavicles, andhypoplasticity of the first rib pair; pregnancy 24–34% have ventricular septal defects, 7% atrial septal defects, and 3% atrial and ventricular septal defects. In this Ecstasy, amphetamine and gamma hydroxybutyric acid case series there were two infants with CHD (one with Ventricular septal defect (possibly atrio and ventricular septal defects, one with ventricular septal defects or ventricular), bilateral hydronephrosis, and bilateral possible atrial and ventricular septal defects) among the 78 livebirths (26 per 1000 [95% CI 3·0–90·0]). We are aware of one other case of CHD after exposure to ecstasy.3 , 4 A l t h o u g h this small case series has insufficient statistical power to confirm a causal relation with any particular congenital One of twins born at 25 weeks, intrauterine growth anomaly, we consider that these initial data are important.
We thank the patients, the Drug Information pharmacists, healthcare personnel who provided the data on exposure and pregnancy outcome, and Henry JA. Ecstasy and the dance of death. B M J 1992; 305: 5 – 6 .
McElhatton PR, Bateman DN, Evans C, Pughe KR, Worsley AJ. Doesprenatal exposure to ecstasy cause congenital malformations?: a Malformations reported after exposure of fetus to ecstasy and prospective follow-up of 92 pregnancies. Br J Clin Pharmacol 1998; 4 5 :
THE LANCET • Vol 354 • October 23, 1999 Rost van Tonningen M, Garbis H, Reuvers M. Ecstasy exposure during Among patients with anogenital SCC, risks of SCCs pregnancy. Teratology 1998; 5 8 : 3 3 .
at other anogenital sites were high (209 observed, relative risk van Tonningen–van Driel M M, Garbis Berkvens JM, Reuvers L o d e w i j k s 3·6 [95% CI 3·1–4·1]; table 2). The risk of tonsillar SCC was WB. Zwangerschapsuitkomst na ecstacygebruik: 43 gevallen gevolgd similarly increased. All three cases of tonsillar SCC after anal door de Teratologie Informatie Service van het RIVM. Ned Tijdschr
Geneeskd 1999; 1 4 3 : 2 7 – 3 1 .
S C C were in men (relative risk 12·0 [2·4–35·1).
Schardein JL. Chemically induced birth defects, 2nd edn. New York, Other oral SCC also occurred in excess, though the relative risk (2·3 [1·7–3·0]) was significantly lower than that for National Teratology Information Service, Regional Drug and tonsillar SCC (p=0·013, one-sided). Among patients with Therapeutics Centre, Wolfson Unit, Newcastle upon Tyne NE2 4HH, HPV-unrelated cancers, relative risks were close to 1·0, although slightly low for cervical SCC.
S H L T h o m a s M D); and Scottish Poisons Information Bureau, Royal This study suggests a strong link between tonsillar and Edinburgh NHS Trust, Edinburgh, EH3 9YW, UK (D N Bateman M D) anogenital SCC. HPV may be a common aetiological factor.
Correspondence to: Dr P R M c E l h a t t o n Tobacco, a major risk factor for oral cancers, is also linked aetiologically to anogenital SCC and may have contributed tothe association. However, the finding that the relative risk wassignificantly higher for tonsillar SCC than for other oral SCCsupports a role for HPV in the aetiology of tonsillar SCC.
Although based on small numbers, the highest relative risk fortonsillar SCC was in patients with anal SCC, a cancer common among homosexual men. All three tonsillar cancers after anal SCC were in unmarried or divorced men.
Unprotected orogenital sex with an infected partner may result in transmission of HPV to the oral cavity. There are no specific Patients with human papillomavirus (HPV)-associated anogenital published data on sexual behaviours of patients with tonsillar cancers had a 4·3-fold increased risk of tonsillar squamous-cell cancer, but one study suggested an association between active carcinoma. These cancer types also have histopathological and oral sex and risk of oral cancer positive for HPV-16 DNA, of molecular biological similarities. Thus HPV may be aetiologically which tonsillar SCC was the most common type.3 The role of important in tonsillar carcinogenesis.
the immune system in tonsillar carcinogenesis is unknown.
Similarities between mucosal linings at anogenital and oral Other HPV-associated cancers occur in excess among patients sites make plausible a role for human papillomaviruses (HPV) with HIV infection and AIDS and among patients with in oral carcinogenesis. HPV are found in most anogenital transplantation-related immunosuppression. Tonsillar SCC squamous-cell carcinomas (SCC), but usually in less than has been reported in young transplant patients.4 20% of oral cancers. Tonsillar SCC, however, is more likely increasing incidence of tonsillar SCC in young US men, but than other oral cancers to be HPV positive.1 We studied not women (unpublished) may reflect an association with patients with HPV-associated anogenital SCC to test the hypothesis that these patients are at increased risk of tonsillar The tonsillar crypt epithelium, believed to favour the capture and processing of antigens, may facilitate viral access to basal Using Surveillance, Epidemiology, and End Results data mucosal cells. This idea accords with the suggestion that HPV- from 1973 to 1994, we identified 72 066 individuals whose associated tonsillar SCCs originate from the crypts, whereas first cancer was an HPV-associated anogenital SCC (or HPV-unrelated SCC emerge from the tonsillar surface.5 cervical SCC in situ) and 422 023 with invasive HPV- This study was supported partly by the Danish Medical Research Council.
unrelated first cancers of the colon, stomach, or breast Paz IB, Cook N, Odom-Maryon T, Xie Y, Wilczynski SP. Human ( t a b l e 1). Person-years were counted from 1 month after the papillomavirus (HPV) in head and neck cancer: an association of HPV initial diagnosis until a diagnosis of one of the studied 16 with squamous cell carcinoma of Waldeyer’s tonsillar ring. C a n c e r
1997; 7 9 : 5 9 5 – 6 0 4 .
i n v a s i v e SCC (tonsillar, other oral, cervical, vulvar/vaginal, Brownlee KA. Statistical theory and methodology in science and o r anal), death, or Jan 1, 1995, whichever came first.
engineering. New York: Wiley, 1967: 183–85.
Population incidence rates for these SCC were calculated Schwartz SM, Daling JR, Doody DR, et al. Oral cancer risk in relation f o r strata of sex, race, and 5-year age and calendar periods.
to sexual history and evidence of human papillomavirus infection.
The expected number of a particular SCC was calculated J Natl Cancer Inst 1998; 9 0 : 1 6 2 6 – 3 6 .
a s the sum of stratum-specific products of person-years Swoboda A, Fabrizii V. Tonsillar carcinoma in a renal graft recipient
treated with cyclosporine A. Clin Nephrol 1993; 3 9 : 2 7 2 – 7 4 .
a n d population incidence. Ratios of observed-to-expected Wilczynski SP, Lin BT, Xie Y, Paz IB. Detection of human SCC served as measures of relative risk. We compared relative papillomavirus DNA and oncoprotein overexpression are associated with risks of tonsillar SCC and of other oral SCC after anogenital distinct morphological patterns of tonsillar squamous cell carcinoma. A m J Pathol 1998; 1 5 2 : 1 4 5 – 5 6 .
HPV-associated anogenital SCCCervical SCC C209–C218 + 80503–80763, 80943, 81203–80243 ICD-O2=International Classification of Diseases for Oncology, 2nd edn, 1990.
*Proportions of women were 66%, 53%, and 39% among patients with initial anal SCC, colon cancer, and stomach cancer, respectively.
Table 1: Cohorts of patients followed up for tonsillar SCC, other oral SCC, and anogenital SCC after initial HPV-associated and HPV-unrelated cancers, SEER 1973–94 THE LANCET • Vol 354 • October 23, 1999

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