Congenital anomalies after prenatal ecstasy exposure
Volume 354, Number 9188; 23 October 1999
The Lancet, Research Letters
Prospective follow-up of 136 babies exposed to ecstasy in utero indicated that the drug may be associated with a significantly increased risk of congenital defects (15=B74% [95% CI 8=B72-25=B74]). Cardiovascular anomalies (26 per 1000 livebirths [3=B70-90=B70]) and musculoskeletal anomalies (38 per 1000 [8=B70-109=B70]) were predominant.
The illicit use of ecstasy (methylenedioxymethamphetamine) has increased during the past decade and there is growing concern about its potential toxicity.1 There are few data on the effects of ecstasy exposure in human pregnancy,2-4 and no published teratological studies in animals. Whereas amphetamines and related compounds have been associated with an increased risk of structural malformations of the heart and great vessels in various species, studies on the teratogenicity of amphetamines in human pregnancy have produced conflicting results on both the overall risk of malformations and the risk of any specific birth defect.5
The UK National Teratology Information Service (NTIS) collected prospective follow-up data on the outcome of 136 pregnancies (one pair of twins), in which exposure to ecstasy occurred between January, 1989, and June, 1998. Within this period there were 302 enquiries involving ecstasy. 31 (10%) of these pregnancies are not yet completed and 135 (45%) were lost to follow-up because the enquiring health professional (in most cases the patient's general practitioner) could no longer identify the patient, or the patient did not return to the surgery.
In each case the enquirer was asked to provide information on drug exposure, both prescribed and non-prescribed, at the time of the enquiry, together with the mother's expected date of delivery. Follow-up was done by contacting the enquirer, after the expected date of delivery. Where necessary, information was then sought from other clinical specialists.
74 pregnant women reported taking ecstasy only and 62 took ecstasy with other drugs of abuse (ecstasy and amphetamine 37 women; ecstasy and cocaine 20; ecstasy and cannabis 16; ecstasy and alcohol 13; ecstasy and LSD nine; ecstasy and other drugs of abuse 13). Acute toxicity from ecstasy was reported in only two of the mothers. The maternal age at the time of exposure was obtained for 82 (60%) women: 26 women were aged 16-20 years; 31 21-25 years, 20 26-31 years, and five 31-36 years.
127 women (71 exposed to ecstasy alone and 56 exposed to ecstasy and other drugs of abuse) were exposed in the first trimester, two in the first and second trimesters, two in the second trimester, and one in the third trimester. Four women were exposed to several drugs of abuse throughout pregnancy. 11 pregnancies resulted in miscarriage, 48 women had elective terminations (one after prenatal diagnosis of malformations). No necropsy data were available on any of the other aborted fetuses. The rate of miscarriage was 8%, within the expected range; but the rate of elective terminations was 35%; higher than the UK average.
There were 78 liveborn infants; 66 were normal. 12 had congenital anomalies (15=B74% [95% CI 8=B72-25=B74]), which is significantly higher than the expected incidence of 2-3% (table).
Eight infants were born prematurely between 25 and 36 weeks of gestation (including one pair of twins born at 25 weeks of gestation). There were two cases of fetal distress among those born prematurely that were thought not to be related to ecstasy. One neonatal death occurred in an infant without apparent abnormalities at birth who was born to a mother who had taken ecstasy, heroin, and methadone throughout pregnancy. No necropsy data are available.
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=B75 kg.
There were three female infants with talipes (rate of 38 per 1000 [95% CI 8-109] vs expected rate of 1 per 1000). Idiopathic talipes equinovarus has a male predominance of three to one in the UK.
The spontaneous incidence of congenital heart disease (CHD) is 5-10 per 1000 livebirths. Of infants with CHD, 24-34% have ventricular septal defects, 7% atrial septal defects, and 3% atrial and ventricular septal defects. In this case series there were two infants with CHD (one with ventricular septal defects, one with ventricular septal defects or possible atrial and ventricular septal defects) among the 78 livebirths (26 per 1000 [95% CI 3=B70-90=B70]). We are aware of one other case of CHD after exposure to ecstasy.3,4 Although this small case series has insufficient statistical power to confirm a causal relation with any particular congenital 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 G Masters for statistical advice.
National Teratology Information Service, Regional Drug and Therapeutics
Centre, Wolfson Unit, Newcastle upon Tyne NE2 4HH, UK (P R McElhatton PhD, C
Evans BSc, K R Pughe BSc, S H L Thomas MD); and Scottish Poisons Information
Bureau, Royal Edinburgh NHS Trust, Edinburgh, EH3 9YW, UK (D N Bateman MD)
The illicit use of ecstasy (methylenedioxymethamphetamine) has increased during the past decade and there is growing concern about its potential toxicity.1 There are few data on the effects of ecstasy exposure in human pregnancy,2-4 and no published teratological studies in animals. Whereas amphetamines and related compounds have been associated with an increased risk of structural malformations of the heart and great vessels in various species, studies on the teratogenicity of amphetamines in human pregnancy have produced conflicting results on both the overall risk of malformations and the risk of any specific birth defect.5
| Drug Exposure | Anomalies |
| Ecstasy | |
| 4 weeks | Left 4th toe underlying the 3rd toe |
| 6-12 weeks | Right-sided plagiocephaly |
| 4-5 weeks | Unilateral talipes |
| First trimester | Unilateral talipes |
| 6 and 9 weeks | Bilateral talipes |
| First trimester | Pyloric stenosis |
| First trimester | Absent upper limbs, left scapula, clavicles, and hypoplasticity of the first rib pair; pregnancy terminated at 22 weeks. |
| Ecstasy, amphetamine and gamma hydroxybutyric acid | |
| 0-7 weeks | Ventricular septal defect (possibly atrio and ventricular), bilateral hydronephrosis, and bilateral clinodactyly |
| Ecstasy and alcohol | |
| 6 weeks | Venticular septal defect |
| Ecstasy and amphetamine | |
| 0-12 weeks | One of twins born at 25 weeks, intrauterine growth retardation hydrocephalus, ambiguous sex |
| Ecstasy and alcohol | |
| 17 weeks | Ptosis of the left eye |
| First trimester | Pigmentation of the right thigh |
| Ecstasy and amphetamine | |
| First trimester | Clicking hips |
| Malformations reported after exposure of fetus to ecstasy and other drugs of abuse | |
The UK National Teratology Information Service (NTIS) collected prospective follow-up data on the outcome of 136 pregnancies (one pair of twins), in which exposure to ecstasy occurred between January, 1989, and June, 1998. Within this period there were 302 enquiries involving ecstasy. 31 (10%) of these pregnancies are not yet completed and 135 (45%) were lost to follow-up because the enquiring health professional (in most cases the patient's general practitioner) could no longer identify the patient, or the patient did not return to the surgery.
In each case the enquirer was asked to provide information on drug exposure, both prescribed and non-prescribed, at the time of the enquiry, together with the mother's expected date of delivery. Follow-up was done by contacting the enquirer, after the expected date of delivery. Where necessary, information was then sought from other clinical specialists.
74 pregnant women reported taking ecstasy only and 62 took ecstasy with other drugs of abuse (ecstasy and amphetamine 37 women; ecstasy and cocaine 20; ecstasy and cannabis 16; ecstasy and alcohol 13; ecstasy and LSD nine; ecstasy and other drugs of abuse 13). Acute toxicity from ecstasy was reported in only two of the mothers. The maternal age at the time of exposure was obtained for 82 (60%) women: 26 women were aged 16-20 years; 31 21-25 years, 20 26-31 years, and five 31-36 years.
127 women (71 exposed to ecstasy alone and 56 exposed to ecstasy and other drugs of abuse) were exposed in the first trimester, two in the first and second trimesters, two in the second trimester, and one in the third trimester. Four women were exposed to several drugs of abuse throughout pregnancy. 11 pregnancies resulted in miscarriage, 48 women had elective terminations (one after prenatal diagnosis of malformations). No necropsy data were available on any of the other aborted fetuses. The rate of miscarriage was 8%, within the expected range; but the rate of elective terminations was 35%; higher than the UK average.
There were 78 liveborn infants; 66 were normal. 12 had congenital anomalies (15=B74% [95% CI 8=B72-25=B74]), which is significantly higher than the expected incidence of 2-3% (table).
Eight infants were born prematurely between 25 and 36 weeks of gestation (including one pair of twins born at 25 weeks of gestation). There were two cases of fetal distress among those born prematurely that were thought not to be related to ecstasy. One neonatal death occurred in an infant without apparent abnormalities at birth who was born to a mother who had taken ecstasy, heroin, and methadone throughout pregnancy. No necropsy data are available.
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=B75 kg.
There were three female infants with talipes (rate of 38 per 1000 [95% CI 8-109] vs expected rate of 1 per 1000). Idiopathic talipes equinovarus has a male predominance of three to one in the UK.
The spontaneous incidence of congenital heart disease (CHD) is 5-10 per 1000 livebirths. Of infants with CHD, 24-34% have ventricular septal defects, 7% atrial septal defects, and 3% atrial and ventricular septal defects. In this case series there were two infants with CHD (one with ventricular septal defects, one with ventricular septal defects or possible atrial and ventricular septal defects) among the 78 livebirths (26 per 1000 [95% CI 3=B70-90=B70]). We are aware of one other case of CHD after exposure to ecstasy.3,4 Although this small case series has insufficient statistical power to confirm a causal relation with any particular congenital 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 G Masters for statistical advice.
- Henry JA. Ecstasy and the dance of death. BMJ 1992; 305: 5-6.
- McElhatton PR, Bateman DN, Evans C, Pughe KR, Worsley AJ. Does prenatal exposure to ecstasy cause congenital malformations?: a prospective follow-up of 92 pregnancies. Br J Clin Pharmacol 1998; 45: 184.
- Rost van Tonningen M, Garbis H, Reuvers M. Ecstasy exposure during pregnancy. Teratology 1998; 58: 33.
- van Tonningen-van Driel M M, Garbis Berkvens JM, Reuvers Lodewijks WB. Zwangerschapsuitkomst na ecstacygebruik: 43 gevallen gevolgd door de Teratologie Informatie Service van het RIVM. Ned Tijdschr Geneeskd 1999; 143: 27-31.
- Schardein JL. Chemically induced birth defects, 2nd edn. New York, Marcel Dekker, 1993.
National Teratology Information Service, Regional Drug and Therapeutics
Centre, Wolfson Unit, Newcastle upon Tyne NE2 4HH, UK (P R McElhatton PhD, C
Evans BSc, K R Pughe BSc, S H L Thomas MD); and Scottish Poisons Information
Bureau, Royal Edinburgh NHS Trust, Edinburgh, EH3 9YW, UK (D N Bateman MD)