METHYLPHENIDATE

Fetal Risk Summary

Methylphenidate is a mild central nervous system stimulant used in the treatment of attention deficit disorders and in narcolepsy. Reproductive testing with methylphenidate in mice found no teratogenicity (1).

The Collaborative Perinatal Project monitored 3,082 mother-child pairs with exposure to sympathomimetic drugs, 11 of which were exposed to methylphenidate (2). No evidence for an increased malformation rate was found.

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 13 newborns had been exposed to methylphenidate during the 1st trimester (F. Rosa, personal communication, FDA, 1993). One (7.7%) major birth defect was observed (one expected), a cardiovascular defect (none expected).

A report of an infant with microtia following in utero exposure to methylphenidate from the 3rd to the 6th week of pregnancy appeared in a 1962 publication (3). No other details of the case were provided, other than the fact that the mother did not take antinausea medication and she had no virus infection during gestation.

A 1975 report described a male infant, delivered at 30 weeks' gestation, with multiple congenital limb malformations who had been exposed during the first 7 weeks of pregnancy to haloperidol (15 mg/day), methylphenidate (30 mg/day), and phenytoin (300 mg/day) (4). The mother had also taken tetracycline and a decongestant for a cold during the 1st trimester. The infant died at 2 hours of age of a subdural hemorrhage. Limb malformations included a thumb and two fingers on each hand, syndactyly of the two fingers on the right hand, deformed radius and missing ulna in the left forearm, four toes on the right foot, shortened right tibia, and incomplete development of the right midfoot ossification centers (4). A defect of the aortic valve (bicuspid with a notch in one of the valve leaflets) was also found (4). The chromosomal analysis was normal and the mother had no family history of limb malformations.

A study published in 1993 examined the effects on the fetus and newborn of IV pentazocine and methylphenidate abuse during pregnancy (5). During a 2-year (1987–1988) period, 39 infants (38 pregnancies, 1 set of twins) were identified in the study population as being subjected to the drug abuse during gestation, a minimum incidence of 5 cases per 1,000 live births. Many of the mothers had used cigarettes (34%), alcohol (71%), or abused other drugs (26%). The median duration of IV pentazocine and methylphenidate abuse was 3 years (range 1–9 years), with a median frequency of 14 injections/week (range 1–70 injections/week). Among the infants, 8 were delivered prematurely, 12 were growth retarded, and 11 had withdrawal symptoms after birth. Four of the infants had birth defects, including twins with fetal alcohol syndrome, one with a ventricular septal defect, and one case of polydactyly. Of the 21 infants that had formal developmental testing, 17 had normal development and 4 had low-normal developmental quotients (5).

Breast Feeding Summary

No reports describing the use of methylphenidate during lactation have been located. Because of its relatively low molecular weight (about 270), passage into milk should be expected. The effects of this predicted exposure on a nursing infant are unknown.

References

1. Takano K, Tanimura T, Nishimura H. Effects of some psychoactive drugs administered to pregnant mice upon the development of their offspring. Congenital Anom 1963;3:2. As cited in Schardein JL. Chemically Induced Birth Defects. 2nd ed. New York, NY: Marcel Dekker, 1993:223.
2. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA: Publishing Sciences Group, 1977:346–7.
3. Smithells RW. Thalidomide and malformations in Liverpool. Lancet 1962;1:1270–3.
4. Kopelman AE, McCullar FW, Heggeness L. Limb malformations following maternal use of haloperidol. JAMA 1975;231:62–4.
5. Debooy VD, Seshia MMK, Tenenbein M, Casiro OG. Intravenous pentazocine and methylphenidate abuse during pregnancy. Maternal lifestyle and infant outcome. AJDC 1993;147:1062–5.