CONGENITAL ANOMALIES AFTER PRENATAL ECSTASY EXPOSURE

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 (15B74% [95% CI 8B72-25B74]). Cardiovascular
anomalies (26 per 1000 livebirths [3B70-90B70]) and musculoskeletal
anomalies (38 per 1000 [8B70-109B70]) were predominant.

The illicit use of ecstasy (methylenedioxymethamphetamine) has increased
during the past decade and there is growing concern about its potential
toxicity.[ref 1] There are few data on the effects of ecstasy exposure in
human pregnancy,[refs 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.[ref 5]

[table]

Malformations Reported After Exposure Of Fetus To Ecstasy And Other Drugs
Of Abuse

Drug Exposure:

ECSTASY

Anomalies:

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

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
(15B74% [95% CI 8B72-25B74]), 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 2B75 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 3B70-90B70]). We are aware of one other case of CHD after
exposure to ecstasy.[refs 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.

REFERENCES:

1 Henry JA. Ecstasy and the dance of death. BMJ 1992; 305: 5-6.

2 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.

3 Rost van Tonningen M, Garbis H, Reuvers M. Ecstasy exposure during
pregnancy. Teratology 1998; 58: 33.

4 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.

5 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)

Correspondence to:

Dr P R McElhatton (e-mail: Patricia.McElhatton@ncl.ac.uk)