Prenatal Exposure to Misoprostol and Associated Congenital Malformations
Published
Jul 15, 2016
Almetrics
Dimensions
Google Scholar
##plugins.themes.bootstrap3.article.details##
Abstract
Misoprostol is a prostaglandin E1 analogue
with abortive properties and limited efficacy,
with multiple descriptions of association to congenital
defects in newborn infants exposed in
utero. We introduce five cases of newborn with
congenital defects collected through project
ECLAMC-Colombia and one case assessed by
consultation to genetics service at Hospital Universitario
San Ignacio with antecedent of exposition
in utero to misoprostol. The more frequent
defects associated to exposition to misoprostol
are clubfoot, cranial nerve affection, terminal
transverse limb defects. The teratogenic effects
of this drug haven’t been clarified, meanwhile all
related cases must be reported in order to increase
evidence related to its teratogenicity
Keywords
misoprostol, teratogens, Moebius syndrome, congenital abnormalities, abortion inducedmisoprostol, teratógenos, síndrome de Moebius, anomalías congénitas.
References
1. Lee OY, Kang DH, Lee DH, Chung IK,
Jang JY, Kim JI, et al. A comparative
study of DA-9601 and misoprostol for
prevention of NSAID-associated gastroduodenal
injury in patients undergoing
chronic NSAID treatment. Arch Pharm
Res. 2014;37(10):1308-16.
2. Madaan M, Agrawal S, Puri M, Nigam
A, Kaur H, Trivedi SS. Is low dose vaginal
misoprostol better than dinoprostone
gel for induction of labor: a randomized
controlled trial. J Clin Diagn Res.
2014;8(9):OC31-4.
3. Gatter M, Cleland K, Nucatola DL.
Efficacy and safety of medical abortion
using mifepristone and buccal misoprostol
through 63 days. Contraception.
2015;91(4):269-73.
4. Wiebe ER. Methotrexate with or without
misoprostol to terminate pregnancies with
no gestational sac visible by ultrasound.
Int J Gynaecol Obstet. 2009;107(1):64-5.
5. Schonhofar PS. Brazil: misuse of misoprostol
as an abortifacient may induce
malformations. Lancet. 1991;337
(8756):1534-5.
6. Kim SK, Shin SJ, Yoo Y, Kim NH, Kim
DS, Zhang D, et al. Oral toxicity of isotretinoin,
misoprostol, methotrexate,
mifepristone and levonorgestrel as pregnancy
category X medications in female
mice. Exp Ther Med. 2015M9(3):853-9.
7. Cavieres MF. [Developmental toxicity of
misoprostol: an update]. Rev Med Chil.
2011;139(4):516-23.
8. Cohen J, Ortiz O, Llaguno SE, Goodyear
L, Billings D, Martinez I. Reaching women
with instructions on misoprostol
use in a Latin American country. Reprod
Health Matters. 2005;13(26):84-92.
9. Lara D, Abuabara K, Grossman D, Díaz-
Olavarrieta C. Pharmacy provision of medical
abortifacients in a Latin American
city. Contraception. 2006;74(5):394-9.
10. Poletta FA, Gili JA, Castilla EE. Latin
American Collaborative Study of Congenital
Malformations (ECLAMC): a
model for health collaborative studies.
Public Health Genomics. 2014;17(2):61-
7.
11. Rodríguez MI, Mendoza WS, Guerra-Palacio
C, Guzman NA, Tolosa JE. Medical
abortion and manual vacuum aspiration
for legal abortion protect women’s health
and reduce costs to the health system:
findings from Colombia. Reprod Health
Matters. 2015;22(44 Suppl 1):125-33.
12. Prada E, Singh S, Villarreal C. Health
consequences of unsafe abortion in Colombia,
1989-2008. Int J Gynaecol Obstet.
2012;118 Suppl 2:S92-8.
13. Hofmeyr GJ, Milos D, Nikodem VC, de
Jager M. Limb reduction anomaly after
failed misoprostol abortion. S Afr Med J.
1998;88(5):566-7.
14. Coelho KE, Sarmento MF, Veiga CM,
Speck-Martins CE, Safatle HP, Castro
CV, et al. Misoprostol embryotoxicity:
clinical evaluation of fifteen patients
with arthrogryposis. Am J Med Genet.
2000;95(4):297-301.
15. Isaza C, Saldarriaga W, Pachajoa H. Uso
inadecuado de misoprostol: ¿un problema
de salud pública? Colomb Med.
2008;39(S2):61-5.
16. Ramírez J. VACTERL association and
Moebius syndrome in a newborn girl
prenatally exposed to misoprostol. IATREIA.
2014;27(2):216-20.
17. Isaza C, Saldarriaga W, Ortiz E, et al.
Riesgos del misoprostol cuando falla
como abortivo en el primer trimestre. Salud
UIS. 2006;38:66-70.
18. Gonzalez CH, Marques-Dias MJ, Kim
CA, Sugayama SM, Da Paz JA, Huson
SM, et al. Congenital abnormalities in
Brazilian children associated with misoprostol
misuse in first trimester of pregnancy.
Lancet. 1998;351(9116):1624-7.
19. Kulier R, Kapp N, Gülmezoglu AM,
Hofmeyr GJ, Cheng L, Campana A.
Medical methods for first trimester
abortion. Cochrane Database Syst Rev.
2011(11):CD002855.
20. Vauzelle C, Beghin D, Cournot MP, Elefant
E. Birth defects after exposure to
misoprostol in the first trimester of pregnancy:
prospective follow-up study. Reprod
Toxicol. 2013;36:98-103.
21. de Elizalde P. [Teratogenic effect of misoprostol:
a prospective study in Argentina].
Arch Argent Pediatr. 2011;109(6):558;
author reply 559.
22. Kozma C, Ramasethu J. Methotrexate
and misoprostol teratogenicity:
further expansion of the clinical manifestations.
Am J Med Genet A.
2011;155A(7):1723-8.
23. Escumalha M, Gouveia C, Cunha M, Vale
F, Machado MC. Neonatal morbidity and
outcome of live born premature babies
after attempted illegal abortion with misoprostol.
Pediatr Nurs. 2005;31(3):228-
31.
24. Billings DL, Walker D, Mainero del Paso
G, Clark KA, Dayananda I. Pharmacy
worker practices related to use of misoprostol
for abortion in one Mexican state.
Contraception. 2009;79(6):445-51.
25. Voigt F, Goecke TW, Najjari L, Pecks U,
Maass N, Rath W. Off-label use of misoprostol
for labor induction in Germany:
a national survey. Eur J Obstet Gynecol
Reprod Biol. 2015;187:85-9.
26. Maternowska MC, Mashu A, Moyo P,
Withers M, Chipato T. Perceptions of misoprostol
among providers and women
seeking post-abortion care in Zimbabwe.
Reprod Health Matters. 2015;22(44
Suppl 1):16-25.
27. Tamang A, Puri M, Lama K, Shrestha
P. Pharmacy workers in Nepal can provide
the correct information about using
mifepristone and misoprostol to women
seeking medication to induce abortion.
Reprod Health Matters. 2015;22(44
Suppl 1):104-15.
28. Resolución 5926/2014, por el cual se sustituye
el anexo 01 de la Resolución 5521
de 2013 del “Listado General de Medicamentos
POS 2014” al encontrarse imprecisiones
en algunos ítems del listado
general. Ministerio de Salud y Protección
Social (2014).
29. República de Colombia, Corte Constitucional
Colombiana. Sentencia C-355/06.
2006.
Jang JY, Kim JI, et al. A comparative
study of DA-9601 and misoprostol for
prevention of NSAID-associated gastroduodenal
injury in patients undergoing
chronic NSAID treatment. Arch Pharm
Res. 2014;37(10):1308-16.
2. Madaan M, Agrawal S, Puri M, Nigam
A, Kaur H, Trivedi SS. Is low dose vaginal
misoprostol better than dinoprostone
gel for induction of labor: a randomized
controlled trial. J Clin Diagn Res.
2014;8(9):OC31-4.
3. Gatter M, Cleland K, Nucatola DL.
Efficacy and safety of medical abortion
using mifepristone and buccal misoprostol
through 63 days. Contraception.
2015;91(4):269-73.
4. Wiebe ER. Methotrexate with or without
misoprostol to terminate pregnancies with
no gestational sac visible by ultrasound.
Int J Gynaecol Obstet. 2009;107(1):64-5.
5. Schonhofar PS. Brazil: misuse of misoprostol
as an abortifacient may induce
malformations. Lancet. 1991;337
(8756):1534-5.
6. Kim SK, Shin SJ, Yoo Y, Kim NH, Kim
DS, Zhang D, et al. Oral toxicity of isotretinoin,
misoprostol, methotrexate,
mifepristone and levonorgestrel as pregnancy
category X medications in female
mice. Exp Ther Med. 2015M9(3):853-9.
7. Cavieres MF. [Developmental toxicity of
misoprostol: an update]. Rev Med Chil.
2011;139(4):516-23.
8. Cohen J, Ortiz O, Llaguno SE, Goodyear
L, Billings D, Martinez I. Reaching women
with instructions on misoprostol
use in a Latin American country. Reprod
Health Matters. 2005;13(26):84-92.
9. Lara D, Abuabara K, Grossman D, Díaz-
Olavarrieta C. Pharmacy provision of medical
abortifacients in a Latin American
city. Contraception. 2006;74(5):394-9.
10. Poletta FA, Gili JA, Castilla EE. Latin
American Collaborative Study of Congenital
Malformations (ECLAMC): a
model for health collaborative studies.
Public Health Genomics. 2014;17(2):61-
7.
11. Rodríguez MI, Mendoza WS, Guerra-Palacio
C, Guzman NA, Tolosa JE. Medical
abortion and manual vacuum aspiration
for legal abortion protect women’s health
and reduce costs to the health system:
findings from Colombia. Reprod Health
Matters. 2015;22(44 Suppl 1):125-33.
12. Prada E, Singh S, Villarreal C. Health
consequences of unsafe abortion in Colombia,
1989-2008. Int J Gynaecol Obstet.
2012;118 Suppl 2:S92-8.
13. Hofmeyr GJ, Milos D, Nikodem VC, de
Jager M. Limb reduction anomaly after
failed misoprostol abortion. S Afr Med J.
1998;88(5):566-7.
14. Coelho KE, Sarmento MF, Veiga CM,
Speck-Martins CE, Safatle HP, Castro
CV, et al. Misoprostol embryotoxicity:
clinical evaluation of fifteen patients
with arthrogryposis. Am J Med Genet.
2000;95(4):297-301.
15. Isaza C, Saldarriaga W, Pachajoa H. Uso
inadecuado de misoprostol: ¿un problema
de salud pública? Colomb Med.
2008;39(S2):61-5.
16. Ramírez J. VACTERL association and
Moebius syndrome in a newborn girl
prenatally exposed to misoprostol. IATREIA.
2014;27(2):216-20.
17. Isaza C, Saldarriaga W, Ortiz E, et al.
Riesgos del misoprostol cuando falla
como abortivo en el primer trimestre. Salud
UIS. 2006;38:66-70.
18. Gonzalez CH, Marques-Dias MJ, Kim
CA, Sugayama SM, Da Paz JA, Huson
SM, et al. Congenital abnormalities in
Brazilian children associated with misoprostol
misuse in first trimester of pregnancy.
Lancet. 1998;351(9116):1624-7.
19. Kulier R, Kapp N, Gülmezoglu AM,
Hofmeyr GJ, Cheng L, Campana A.
Medical methods for first trimester
abortion. Cochrane Database Syst Rev.
2011(11):CD002855.
20. Vauzelle C, Beghin D, Cournot MP, Elefant
E. Birth defects after exposure to
misoprostol in the first trimester of pregnancy:
prospective follow-up study. Reprod
Toxicol. 2013;36:98-103.
21. de Elizalde P. [Teratogenic effect of misoprostol:
a prospective study in Argentina].
Arch Argent Pediatr. 2011;109(6):558;
author reply 559.
22. Kozma C, Ramasethu J. Methotrexate
and misoprostol teratogenicity:
further expansion of the clinical manifestations.
Am J Med Genet A.
2011;155A(7):1723-8.
23. Escumalha M, Gouveia C, Cunha M, Vale
F, Machado MC. Neonatal morbidity and
outcome of live born premature babies
after attempted illegal abortion with misoprostol.
Pediatr Nurs. 2005;31(3):228-
31.
24. Billings DL, Walker D, Mainero del Paso
G, Clark KA, Dayananda I. Pharmacy
worker practices related to use of misoprostol
for abortion in one Mexican state.
Contraception. 2009;79(6):445-51.
25. Voigt F, Goecke TW, Najjari L, Pecks U,
Maass N, Rath W. Off-label use of misoprostol
for labor induction in Germany:
a national survey. Eur J Obstet Gynecol
Reprod Biol. 2015;187:85-9.
26. Maternowska MC, Mashu A, Moyo P,
Withers M, Chipato T. Perceptions of misoprostol
among providers and women
seeking post-abortion care in Zimbabwe.
Reprod Health Matters. 2015;22(44
Suppl 1):16-25.
27. Tamang A, Puri M, Lama K, Shrestha
P. Pharmacy workers in Nepal can provide
the correct information about using
mifepristone and misoprostol to women
seeking medication to induce abortion.
Reprod Health Matters. 2015;22(44
Suppl 1):104-15.
28. Resolución 5926/2014, por el cual se sustituye
el anexo 01 de la Resolución 5521
de 2013 del “Listado General de Medicamentos
POS 2014” al encontrarse imprecisiones
en algunos ítems del listado
general. Ministerio de Salud y Protección
Social (2014).
29. República de Colombia, Corte Constitucional
Colombiana. Sentencia C-355/06.
2006.
How to Cite
García Robles, R., Suárez Obando, F., López, M. C., & Zarante Montoya, I. (2016). Prenatal Exposure to Misoprostol and Associated Congenital Malformations. Universitas Medica, 57(2), 226–235. https://doi.org/10.11144/Javeriana.umed57-2.epmm
Issue
Section
Case Reports