Lewis B.Holmes, MD, MassGeneral Hospital for Children, 175 Cambridge Street, Boston, MA 02114holmes.lewis@mgh.harvard.edu
E. J. Baldwin, C. R. Smith, E. Habecker, L. Glassman, S. L. Wong, and D. F. Wyszynski
Submitted July 14, 2008
We welcome the comments of Drs. Hunt, Craig and Morrow who examined the frequency of oral clefts in infants exposed during pregnancy to lamotrigine (LTG) as monotherapy. More information is needed to answer these concerns.
Since our findings were published in abstract form [4], we have been contacted about case reports of LTG-exposed infants with cleft lip and/or cleft palate and large databases of infants with oral clefts who had been exposed to LTG as monotherapy. We have urged each clinician to publish their findings. We also hope that large datasets of LTG-exposed pregnancies without any oral clefts will be published. From this larger experience, clinicians will be better able to establish an estimate of the absolute risk of cleft palate or cleft lip and palate in LTG-exposed pregnancies.
In addition, the LTG-exposed infants with oral clefts should be carefully examined for signs of a syndromic type of oral cleft. Do they have the mid-face and digit hypoplasia that has been identified in 15% of the infants exposed to the anticonvulsant drugs, phenytoin and Phenobarbital? [5]
Exposure to many anticonvulsant drugs during pregnancy has been shown to cause problems with specific aspects of learning or communication or deficits in IQ. The risks are different for each drug. Studies of cognitive function in LTG-exposed children are needed to determine whether any deficits are a risk. If LTG-exposed infants have digit and mid-face hypoplasia, that physical effect of fetal exposure could be a marker of associated cognitive dysfunction. [6] Pregnancy registries focus on the identification of anomalies at birth. More information is needed on the prevalence at birth of isolated cleft lip, cleft palate and cleft lip and palate in unexposed infants.
Pregnancy registries rely on the referral of eligible pregnant women by their neurologists, obstetricians, nurses and other counselors. In order for our findings in the LTG-exposed pregnancies to be based on a much larger sample, we urge all health care providers in the U.S. and Canada to encourage their pregnant patients to enroll in the Registry by calling (toll-free) 1-888-233-2334.
References
4. Holmes LB, Wyszynski DF, Baldwin EJ, Habecker E, Glassman LH, Smith CR. Increased risk for non-syndromic cleft palate among infants exposed to lamotrigine during pregnancy. Birth Def Res Part A: Clinic Molec Teratol 2006;76:318.
5. Holmes LB, Harvey EA, Coull BA, et al. The teratogenicity of anticonvulsant drugs. N Engl J Med 2001;344:1132-1138.
6. Holmes LB, Coull BA, Dorfman J, Rosenberger PB. The correlation of deficits in IQ with midface and digit hypoplasia in children exposed in utero to anticonvulsant drugs. J Pediatr 2005;146:118-122.
Disclosure: Each of the authors received salary support from funds provided since 1997 by the six sponsors of the Registry. At the time this manuscript was written, the sponsors were Abbott, Eisai, GlaxoSmithKline, Novartis, Ortho-McNeil, and Pfizer.
We welcome the comments of Drs. Hunt, Craig and Morrow who examined the frequency of oral clefts in infants exposed during pregnancy to lamotrigine (LTG) as monotherapy. More information is needed to answer these concerns.
Since our findings were published in abstract form [4], we have been contacted about case reports of LTG-exposed infants with cleft lip and/or cleft palate and large databases of infants with oral clefts who had been exposed to LTG as monotherapy. We have urged each clinician to publish their findings. We also hope that large datasets of LTG-exposed pregnancies without any oral clefts will be published. From this larger experience, clinicians will be better able to establish an estimate of the absolute risk of cleft palate or cleft lip and palate in LTG-exposed pregnancies.
In addition, the LTG-exposed infants with oral clefts should be carefully examined for signs of a syndromic type of oral cleft. Do they have the mid-face and digit hypoplasia that has been identified in 15% of the infants exposed to the anticonvulsant drugs, phenytoin and Phenobarbital? [5]
Exposure to many anticonvulsant drugs during pregnancy has been shown to cause problems with specific aspects of learning or communication or deficits in IQ. The risks are different for each drug. Studies of cognitive function in LTG-exposed children are needed to determine whether any deficits are a risk. If LTG-exposed infants have digit and mid-face hypoplasia, that physical effect of fetal exposure could be a marker of associated cognitive dysfunction. [6] Pregnancy registries focus on the identification of anomalies at birth. More information is needed on the prevalence at birth of isolated cleft lip, cleft palate and cleft lip and palate in unexposed infants.
Pregnancy registries rely on the referral of eligible pregnant women by their neurologists, obstetricians, nurses and other counselors. In order for our findings in the LTG-exposed pregnancies to be based on a much larger sample, we urge all health care providers in the U.S. and Canada to encourage their pregnant patients to enroll in the Registry by calling (toll-free) 1-888-233-2334.
References
4. Holmes LB, Wyszynski DF, Baldwin EJ, Habecker E, Glassman LH, Smith CR. Increased risk for non-syndromic cleft palate among infants exposed to lamotrigine during pregnancy. Birth Def Res Part A: Clinic Molec Teratol 2006;76:318.
5. Holmes LB, Harvey EA, Coull BA, et al. The teratogenicity of anticonvulsant drugs. N Engl J Med 2001;344:1132-1138.
6. Holmes LB, Coull BA, Dorfman J, Rosenberger PB. The correlation of deficits in IQ with midface and digit hypoplasia in children exposed in utero to anticonvulsant drugs. J Pediatr 2005;146:118-122.
Disclosure: Each of the authors received salary support from funds provided since 1997 by the six sponsors of the Registry. At the time this manuscript was written, the sponsors were Abbott, Eisai, GlaxoSmithKline, Novartis, Ortho-McNeil, and Pfizer.