misoprostol and Abnormalities--Drug-Induced

Although genetic defects are the leading cause of central nervous system malformations including in the posterior fossa, specific malformative patterns should alert the clinician to consider rather a teratogenic etiology. We discuss the imaging features of 2 mid-hindbrain malformations consecutive to the intake of isotretinoin (Roaccuatane®; case 1) and misoprostol (Cytotec®; case 2) during pregnancy and review the pertinent literature. We correlate the morphological appearance of the mid-hindbrain malformation, as seen on high-resolution magnetic resonance imaging to possible drug-induced pathogenetical mechanisms. The recognition of characteristic imaging patterns enables diagnosis of and/or confirmation of suspected drug-induced hindbrain malformations. This has important medicolegal implications and also clinical significance to avoid unsuccessful and misleading genetic testing.

Topics: Abnormalities, Drug-Induced; Dermatologic Agents; Female; Humans; Imaging, Three-Dimensional; Infant; Isotretinoin; Magnetic Resonance Imaging; Male; Misoprostol; Oxytocics; Pregnancy; Prenatal Exposure Delayed Effects; Rhombencephalon

Misoprostol, a synthetic analog of prostaglandin E1, is currently used in Chile and other countries as an antiulcer medication, mainly for the prevention of non-steroidal anti-inflammatory-induced gastric ulcers. Due to its uterotonic properties, it is also indicated in obstetrics for induction of labor and termination of pregnancy. In this last case, misoprostol is either used alone or in combination with other oxytocic drugs such as methotrexate or mifepristone. The use of misoprostol as an abortifacient agent is considered to be safe since it rarely causes serious side effects. However up to 15 % of misoprostol-induced-abortions may not be successful, even under medical supervision, leading to in utero exposure to the drug and to the induction of a series of birth defects including limb and joints defects and Moebius syndrome. Reports from the nineties failed to show a strong epidemiological association between in utero drug exposure and induction of defects, a situation that has changed now that the number of cases reported has increased. Since the practice of abortion is illegal in Chile, many women turn to off-medical procedures to interrupt their pregnancy and use misoprostol as an easy and cheap alternative, readily available in the INTERNET. The lack of medical supervision in these cases may lead to situations that favor the induction of congenital defects. Here, we present an updated review of scientific data, to evaluate the risk of birth defects in babies exposed to the drug during pregnancy termination failed attempts.

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Abortion, Induced; Female; Humans; Infant, Newborn; Misoprostol; Pregnancy; Treatment Failure

Thalidomide is a very potent teratogen capable of causing severe systemic malformations if the fetus is exposed during the sensitive period. Although structural anomalies of the eye can occur from thalidomide exposure, the most frequent eye complication is secondary to damage to the cranial nuclei in the brain stem, resulting in aberrant neurologic connections causing a condition of abnormal ocular movement, Duane syndrome. A less frequent anomalous neurologic complication is tearing when eating (paradoxical gustolacrimal tearing or "crocodile tears") or lack of emotional tearing. The involvement of the 6th and 7th cranial nerves, often seen together in the thalidomide-affected individual, is also characteristic of Möbius syndrome/sequence. This syndrome usually occurs sporadically, but characteristic findings of this condition have also been observed in South American children who were born after an unsuccessful attempt to induce abortion with the prostaglandin drug misoprostol (Cytotec). Aberrant tearing also occurs in some individuals with Möbius syndrome. Autism spectrum disorder (ASD), an unexpected associated finding in a Swedish thalidomide study, is now also noted in Möbius studies, in patients both with and without exposure to misoprostol.

Topics: Abnormalities, Drug-Induced; Adult; Autistic Disorder; Child; Child, Preschool; Cranial Nerves; Embryonic Development; Eye Abnormalities; Female; Humans; Infant; Lacrimal Apparatus Diseases; Misoprostol; Mobius Syndrome; Pregnancy; Teratogens; Thalidomide

Misoprostol is prostaglandin E1 analogous and marketed for prevention and treatment of peptic ulcer disease. However, it has been used widely in obstetrics and gynecology practice because of its effectiveness, low cost, stability in light and hot climate conditions, and ease of administration compared with its licensed counterparts--dinoprostone and gemeprost. A large number of studies have shown that misoprostol is effective in first and second trimester abortion, late pregnancy labor induction, and third stage of labor management (misoprostol has not been approved by the U.S. Food and Drug Administration for these indications). Because misoprostol is not registered for such use, it has not undergone the extensive testing for appropriate dosage and safety required for registration. Serious complications such as teratogenesis after failed abortions and uterine rupture during second trimester abortions and third trimester labor induction have been reported as the result of increasingly wide use of misoprostol in obstetric and gynecology practice. There is an urgent need to evaluate all the available data and organize a large randomized trial to determine the safety of its use in obstetric and gynecology practice.. Obstetricians & Gynecologists, Family Physicians.. After completion of this article, the reader will be able to identify the various uses of misoprostol, to describe the potential complications of misoprostol use and its teratogenic effects, to compare the various routes of administration, and to define the appropriate dose.

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Abortion, Induced; Administration, Intravaginal; Administration, Oral; Female; Humans; Infant, Newborn; Labor, Induced; Misoprostol; Pregnancy; Pregnancy Trimesters; Uterine Rupture

We report a fetus from an elective termination at 17 weeks gestation following maternal ingestion of 1200 micrograms of misoprostol at 7 weeks of gestation. The fetus had abscence of the middle and distal phalanges of fingers 1, 3, 4 and 5 with tethering by thin strands of tissue on one hand, a below-knee amputation of one leg and omphalocele. There was absence of amnion on the chorionic surface of the placenta, a pathologic feature of early amnion rupture. The association in this case of the phenotypic features of the amniotic band syndrome suggests that the teratogenicity of misoprostol at 9 to 12 weeks gestation can overlap that of other acute insults at that time, such as chorionic villus sampling, dilatation and curettage and abdominal trauma in the first trimester.

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Adult; Female; Hernia, Umbilical; Humans; Limb Deformities, Congenital; Misoprostol; Pregnancy; Pregnancy Trimester, First; Ultrasonography, Prenatal

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Adult; Female; Humans; Hypoventilation; Infant, Newborn; Misoprostol; Mobius Syndrome; Pregnancy; Risk Factors; Sleep Apnea, Central; Treatment Failure; Withholding Treatment

Misoprostol is a well known abortifacient. It can cause teratogenicity like Mobius sequence and terminal transverse limb defects. We report a rare case of proximal focal femoral deficiency with fibular hemimelia in a woman who had attempted abortion with self-administered misoprostol and later continued the pregnancy. Though the absolute risk of congenital malformations with its use is low ∼1%, this should be clearly communicated to the women requesting abortion to help them make fully informed reproductive health decisions.

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Abortion, Induced; Adult; Ectromelia; Female; Fetal Death; Fetus; Fibula; Humans; Male; Misoprostol; Pregnancy

To report the prospective follow-up of pregnancies exposed to misoprostol during the first trimester and analyse the teratogenic risk depending on the indication for use.. Prospective observational study of 265 women exposed to misoprostol during the first 12 weeks of pregnancy and followed until the delivery. Women were included if they or their physician had contacted a French pharmacovigilance centre before 22 weeks of gestation (WG) to obtain information on the risk of misoprostol exposure, and if there had been misoprostol exposure before 13 WG. Data were collected at the time of the first contact, and the pregnancy outcome was recorded at follow-up. Women were prospectively enrolled from January 1988 to December 2013.. The main indication for misoprostol was voluntary abortion (60.9%). Ten major malformations (5.5%) (95% CI 2.65-9.82%) were reported and five of them were consistent with the pattern of malformations attributed to misoprostol: Möbius sequence, hydrocephalus, terminal transverse limb reduction associated with a clubfoot, syndactyly, and complete posterior encephalocele. The rate of malformations was higher, but not significantly, in women exposed to misoprostol for voluntary abortion (7.9%) compared with women exposed to misoprostol for other or unknown indications (3.2%).. Our results confirmed a specific pattern of malformations due to misoprostol use in early pregnancy, even with low dose of misoprostol. Despite the small number of cases, we observed a higher proportion of major malformations in fetuses born to women who continued their pregnancy after a failed voluntary abortion with misoprostol. Further studies should be conducted to evaluate other potential factors, such as combination treatment with mifepristone and the socio-environmental characteristics in this group of women.

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Adult; Anti-Ulcer Agents; Female; Follow-Up Studies; France; Humans; Hydrocephalus; Infant, Newborn; Maternal-Fetal Exchange; Misoprostol; Mobius Syndrome; Pharmacovigilance; Pregnancy; Pregnancy Trimester, First; Prospective Studies; Risk; Teratogens; Young Adult

Topics: Abnormalities, Drug-Induced; Abortifacient Agents; Abortion, Therapeutic; Female; Humans; Misoprostol

Misoprostol is a synthetic analogue of prostaglandin E1. It is used in gynaecology because of its properties of myometrium smooth muscle cells contraction and its effects on the cervix. Misoprostol oral bioavailability is low and several authors have assessed whether the administration by other routes increased its pharmacodynamic effects. This paper summarizes the pharmacokinetic studies after other routes of administration: vaginal, sublingual, buccal or rectal. It also provides an update on its adverse effects and teratogenic effects.

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Abortion, Induced; Administration, Buccal; Administration, Intravaginal; Administration, Rectal; Administration, Sublingual; Cervical Ripening; Cervix Uteri; Female; Humans; Misoprostol; Oxytocics; Pregnancy; Uterine Contraction; Uterus

Misoprostol during the first trimester of pregnancy is associated with a specific malformative pattern (Moebius sequence and limb defects) whose incidence remains unknown. Data originate mostly from illegal use for abortion and are mainly retrospective. The present prospective controlled study analyses outcomes of first trimester misoprostol exposures after medical prescriptions. Malformation rate was higher among 236 pregnancies exposed before 12 gestational weeks (4%) than in 255 controls (1.8%), although not statistically significant (OR=2.2 [95% CI=0.6-7.7]). Three malformations (2%) in the exposed group were consistent with the misoprostol malformative pattern. This is the largest prospective study on first trimester misoprostol exposure and the first one relying on prescriptions. A trend toward a doubling of the overall rate of malformations was observed and for the first time an estimation of the incidence of misoprostol specific spectrum is proposed (2%). Brainstem injuries including severe trismus might be added to this specific pattern.

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Adult; Brain Stem; Drug Prescriptions; Female; Follow-Up Studies; France; Humans; Incidence; Limb Deformities, Congenital; Misoprostol; Mobius Syndrome; Practice Patterns, Physicians'; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, First; Prenatal Exposure Delayed Effects; Prospective Studies; Teratogens

Misoprostol is commonly used in Argentina to attempt abortion, although a certain proportion of pregnancies is not interrupted. On the other hand, various reports showed an association between misoprostol and congenital anomalies.. To estimate the risk of major congenital anomalies in children prenatally exposed to misoprostol, and to know their way of consumption during pregnancy.. A cohort study compared the frequency of abortion and major congenital abnormalities in offspring of pregnant women exposed to misoprostol (94) and an unexposed group of pregnant women (401), both groups consulting to a teratology information service.. Among women exposed to misoprostol only the 8.2% purchased it on prescription, 81.5% heard about its abortifacient effect by friends, neighbors or relatives, the average dose was 1.439 μg which was used both orally and vaginally by the 77.2%; the mean gestational age was 48.5 days and 35.2% used an additional abortive agent. Women exposed to misoprostol had a significantly higher frequency of abortions (exposed: 17/94= 18.1%, unexposed, 29/401= 7.2%, RR= 2.27, 95%: 1,30-3,98), and offspring with major congenital abnormalities (exposed: 5/77= 6.49%, unexposed: 8/372= 2.15%, RR= 3.02, 95%:1,02-8.98). The five malformed children prenatally exposed to misoprostol showed: 1) encephalocele and transverse limb defects; 2) porencephaly, 3) pulmonary adenomatous cystic malformation, 4) occipital encephalocele and, 5) intestinal malrotation.. The study found a significant association between prenatal exposure to misoprostol and the occurrence of major congenital anomalies.

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Adult; Argentina; Female; Humans; Misoprostol; Pregnancy; Prospective Studies

We describe a boy who was exposed to misoprostol and methotrexate in the first trimester of gestation as a result of a failed medical abortion. He presented with severe growth retardation, skull defects, proptotic eyes, cleft palate, and severe micrognathia. There were bilateral defects of the upper and lower extremities, missing and hypoplastic ribs, and undescended testicles. He had clinical features of pulmonary hypoplasia with severe persistent pulmonary hypertension and remained ventilator-dependent until he expired. An autopsy revealed brain anomalies consistent with arrhinencephaly. Methotrexate is frequently used in conjunction with misoprostol to induce medical abortion, an off-label use as abortifacient. Both of these medications are well-established teratogens and have an X classification during pregnancy. Data from eight patients who were exposed to both medications in the first trimester indicate a significant teratogenic risk to the developing fetus. Reported anomalies include growth retardation, absence or hypoplasia of the frontal bones, craniosynostosis, large fontanelle, ocular hypertelorism, short palpebral fissures, wide nasal bridge, malformed and low-set ears, and micrognathia. Skeletal anomalies are frequent consisting of syndactyly, mesomelic shortening of the forearms, missing ribs, dislocated hips, and talipes equinovarus. The findings in our case are consistent with the pattern of abnormalities that have been reported in the literature. In addition, our patient had severe pulmonary hypoplasia and arrhinencephaly, anomalies that have not been described previously. This case adds to the documentation of the teratogenic effects of methotrexate and misoprostol on the developing fetus.

Topics: Abnormalities, Drug-Induced; Abortifacient Agents; Fatal Outcome; Humans; Infant; Infant, Newborn; Male; Methotrexate; Misoprostol; Phenotype; Teratogens

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Female; Humans; Misoprostol; Pregnancy

Approximately 15% of misoprostol-induced-abortions may not be successful, leading to in utero exposure to the drug and to the induction of a series of defects including central nervous system, limb and visceral defects. A common proposal is that the drug causes disruption of the fetal vasculature leading to embryonic or fetal hypoxia.. To evaluate the teratogenicity of misoprostol using the rat post-implantation embryo culture.. Rat embryos were collected at the beginning of organogenesis and cultured in rat serum containing misoprostol at concentrations of 200, 2,000 or 20,000 pg/ml. Functionality, morphology and morphometry parameters were evaluated.. Misoprostol induced a dose-dependent embryotoxic effect causing a decrease in embryo viability and function (poor vascular development and survival) and morphometry (alterations in branchial arches, heart and cephalic portions of the neural tube, among others).. All the manifestations observed are indicative of the ability of misoprostol to directly induce developmental retardation and alterations.

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Animals; Embryo, Mammalian; Female; Misoprostol; Mutagenicity Tests; Pregnancy; Rats; Rats, Sprague-Dawley

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Female; Humans; Misoprostol; Pregnancy

failed attempted abortions with the use of misoprostol (Cytotec(R)) without medical indication have been associated with the occurrence of congenital malformations. The objective of the present study was to identify, in newborns with malformations and in normal controls, the frequency of exposure to misoprostol and the spectrum of associated malformations.. this was a case-control study involving a daily survey at four public maternities in Fortaleza (CE) for the identification of newborns with malformations and paired controls (1:1) during the period from July to November 2005. The sample comprised 252 parturients interviewed by a trained team by means of a structured questionnaire based on the Latin American Collaborative Study of Congenital Malformations (Estudo Colaborativo Latino-Americano de Malformações Congênitas, ECLAMC). The questionnaire was used to obtain sociodemographic data and a family history of malformations, as well as to identify diverse forms of exposure during pregnancy, including misoprostol. Bivariate analysis and the chi-square test were used to compare cases and controls regarding their characteristics and factors associated with malformation, and the Odds Ratio was calculated to determine the chance of the Case Group to present malformations as compared to the Control Group after exposure to misoprostol.. there were no significant differences between groups regarding most of the risk factors for malformations investigated. Attempted abortion was reported by 6.8% of the mothers, with a higher exposure to misoprostol during pregnancy resulting in a greater proportion of malformed newborns, Odds Ratio (OR)=3.65 (95%CI=0.74-17.91). The spectrum of congenital defects encountered with exposure to misoprostol included defects of the central nervous, musculoskeletal, urogenital and cardiovascular systems, in agreement with literature data.. the findings of this study suggest that fetuses exposed to misoprostol tend to be at higher risk of developing congenital malformations in comparison to non-exposed fetuses. Other studies should be encouraged for a better identification of the damage caused by the improper use of misoprostol, especially in countries where the control of medication is inadequate.

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Case-Control Studies; Female; Humans; Infant, Newborn; Male; Misoprostol; Pregnancy; Risk Assessment

To report on a unique medical situation after self-obtained use of misoprostol in a country where abortion is illegal.. A 29-year-old woman was seen at 12 weeks' gestation with a history of use of 10,800 microg of misoprostol orally and vaginally over the preceding six weeks. She had experienced mild-to-moderate pelvic pain but no vaginal bleeding. Because the pregnancy was intrauterine and viable, surgical termination could not be carried out. The risks of fetal congenital anomalies due to in utero exposure to misoprostol were discussed with the patient. A detailed ultrasonography at 16 weeks' gestation revealed no anomaly. Vaginal delivery at 38 weeks' gestation resulted in the birth of a baby without discernible congenital anomalies.. In countries where abortion is illegal, women should be informed about the risks associated with unsupervised self-induced abortion with misoprostol.

Topics: Abnormalities, Drug-Induced; Abortion, Criminal; Abortion, Induced; Administration, Intravaginal; Administration, Oral; Adult; Female; Humans; Misoprostol; Pregnancy; Risk Factors; Saudi Arabia; Ultrasonography

This study evaluated the association between use of misoprostol and other drugs to induce menstruation, and congenital anomalies. A sample of 4,856 pregnant women 20 years and older were enrolled consecutively in prenatal services in the Unified National Health System, in six Brazilian State capitals. Data on socio-demographics and use of medicines were obtained using an interview from the 21st to 28th week of pregnancy. Other data, including information on delivery and diagnosis of congenital anomalies by the attending neonatal physician were obtained from patient charts. Potential confounders were adjusted by logistic regression. Use of drugs to induce menstruation was reported by 707 women (14.6%), of whom 120 (17%) reported use of misoprostol. After adjusting for the study center, a positive association was observed between misoprostol and congenital anomalies (OR = 2.64; 95% CI: 1.03-6.75); a positive association was also observed for sex hormones (OR = 2.24; 95% CI: 1.06-4.74). The results suggest that the use of misoprostol or sex hormones during pregnancy increases the risk of congenital anomalies.

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Adult; Brazil; Female; Gonadal Steroid Hormones; Humans; Infant, Newborn; Middle Aged; Misoprostol; Pregnancy; Prenatal Exposure Delayed Effects; Risk Factors; Socioeconomic Factors; Young Adult

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Abortion, Induced; Female; Humans; Misoprostol; Pregnancy

To report a case of a child born with Möbius syndrome following exposure in utero to mifepristone and misoprostol for elective abortion.. In the seventh week of pregnancy, a woman was administered mifepristone 600 mg and, 2 days later, misoprostol 400 mug for abortion. One month later, despite significant metrorrhagia, an ultrasound examination showed ongoing gestation. At 33 weeks and 3 days of gestation, the woman gave birth to a male with left facial palsy, microretrognathia, and axial hypotonia related to Möbius syndrome.. Möbius syndrome is characterized by unilateral or bilateral palsy of the abducens (VI) and facial (VII) cranial nerves. Other cranial nerves (eg, the hypoglossal [XII]), craniofacial or orofacial anomalies, and limb malformations are often associated. The etiology of the Möbius syndrome remains largely unknown and probably involves multiple factors. The most likely etiological hypothesis is disruption of the developing vascular system, with transient ischemia (particularly in the vertebral arteries) and fetal hypoxia. A teratogenic cause of Möbius syndrome has been suggested. The critical period for the development of Möbius syndrome following teratogen exposure appears to be 5-8 weeks of gestation. To date, mifepristone alone does not appear to have induced Möbius syndrome. In contrast, oral or vaginal misoprostol administration can lead to a significant increase in Doppler-measured uterine artery resistance and may induce uterine contractions. If these occur during the critical embryonic period, they may cause flexion in the areas of the sixth and seventh cranial nerves and decreased blood flow.. Ineffective use of mifepristone and misoprostol in the first trimester of pregnancy may be associated with a risk of Möbius syndrome, primarily due to misoprostol activity. Women with ongoing pregnancy after failed abortion with misoprostol administration should be informed of this risk.

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Abortifacient Agents, Steroidal; Abortion, Induced; Adult; Female; Humans; Infant, Newborn; Male; Mifepristone; Misoprostol; Mobius Syndrome; Pregnancy; Pregnancy Trimester, First

Poland syndrome has been attributed to a process of vascular disruption, and exposure to misoprostol at 6-8 weeks of gestation has been shown to produce defects attributed to vascular disruption. Herein we report the first case of a patient with Poland syndrome associated with an aberrant subclavian artery and vascular abnormalities of the retina, whose mother used misoprostol during pregnancy.. A White boy of 1 year and 7 months of age, whose mother used misoprostol during the second month of pregnancy, presented with bilateral epicanthal folds, aplasia of the sternocostal head of the pectoralis major muscle with a hypoplastic nipple on the right side, and asymmetry between the upper limbs. The results of an angiotomographic study showed the presence of an aberrant right subclavian artery. Ultrasonographic evaluation showed turbulence and a high peak in the diastolic velocity in both carotid arteries, suggesting stenosis. Ophthalmologic assessment disclosed an intense bilateral tortuosity of the retinal blood vessels, with arterialnarrowing and rarefaction of the retinal pigment epithelium.. This case suggests that the mechanism of vascular disruption of misoprostol could be related to the aberrant subclavian artery and the observed Poland syndrome. His retinal findings are different from those in cases described thus far in the literature, and this pattern of anomaly has never been associated with a gestational exposure to misoprostol. The possibility of a relationship of the aberrant right subclavian artery and the pattern of blood flow verified in the carotid arteries with the eye fundus abnormalities could be causally related or simply coincidental.

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Female; Humans; Infant; Male; Misoprostol; Poland Syndrome; Pregnancy; Retinal Diseases; Retinal Vessels; Subclavian Artery

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Animals; Autistic Disorder; Brain Stem; Databases, Factual; Databases, Nucleic Acid; Facial Expression; Female; Genes, Homeobox; Humans; Male; Mice; Misoprostol; Mobius Syndrome; Placental Circulation; Pregnancy

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Adult; Brazil; Cohort Studies; Female; Fetal Death; Humans; Misoprostol; Pregnancy

To review the association of autism spectrum disorder (ASD) in individuals manifesting thalidomide embryopathy and Möbius sequence and compare them with three new studies in which ASD was also associated with ocular and systemic malformations: (1) a Swedish study of individuals with CHARGE association (Coloboma, Heart, choanal Atresia, developmental or growth Retardation, Genital anomaly, and Ear involvement); (2) a Swedish study of Goldenhar syndrome; and (3) Brazilian Möbius syndrome (sequence) study.. In the Swedish CHARGE study, 31 patients met the inclusion criteria (3+ or 4 of the common characteristics of the CHARGE syndrome). The same team of investigators also evaluated 20 Swedish patients with Goldenhar syndrome. In the Brazilian Möbius study, 28 children with a diagnosis of Möbius sequence were studied; some children had a history of exposure during their mother's pregnancy to the abortifacient drug misoprostol in an unsuccessful abortion attempt.. In the CHARGE study, five patients had the more severe autism disorder and five had autistic-like condition. In the Goldenhar study, two had autism disorder and one had autistic-like condition. In the Brazilian Möbius study, the systemic findings of the misoprostol-exposed and misoprostol-unexposed patients were almost undistinguishable, and ASD was present in both groups (autism disorder in five and autistic-like condition in three).. Autism spectrum disorder has been reported in two conditions with known early pregnancy exposure to the teratogenic agents thalidomide and misoprostol. In the Brazilian Möbius study, autism also occurred in both the misoprostol-exposed and misoprostol-unexposed groups. Autism also was present in patients with both CHARGE association and Goldenhar syndrome.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Adolescent; Autistic Disorder; Child; Child, Preschool; Eye Abnormalities; Female; Goldenhar Syndrome; Humans; Male; Misoprostol; Mobius Syndrome; Severity of Illness Index; Teratogens; Thalidomide

Misoprostol exposure in the first trimester of pregnancy has been related to congenital malformations, particularly the Möbius sequence and terminal transverse limb defects.. Neuropathological findings of three patients with Möbius sequence related to misoprostol are reported. No previous pathological studies have shown these abnormalities to be associated with misoprostol exposure in utero. The brain stem was cut serially, from the rostral mesencephalum to the caudal aspect of the medulla, and all fragments were stained with hematoxylin-eosin and cresyl violet. Old ischemic-anoxic foci of gliosis, with necrosis and calcification, dorsally situated, were present from the pons to the medulla, involving some cranial nerve nuclei (especially the IV, VII, and XII) that were partially or completely depopulated of neural cells.. The findings suggest a circulatory mechanism to the Möbius sequence, with vascular disruption involving the territory of the subclavian artery, occurring in a critical period of embryonic life between six to eight weeks postconception. These cases add further evidence of the role of misoprostol as a teratogen.

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Abortion, Induced; Child, Preschool; Fatal Outcome; Female; Gestational Age; Humans; Infant; Infant, Newborn; Male; Misoprostol; Mobius Syndrome; Pregnancy

Fetal aminopterin/methotrexate syndrome was described nearly 50 years ago when these agents were first used as abortifacients. Physicians essentially stopped using these agents when the associated anomalies were recognized. Over the last several years the use of methotrexate with or without misoprostol for management of ectopic pregnancy and medical terminations of pregnancy has increased.. A 23-year-old female sought a termination at eight weeks gestation. She was given methotrexate followed by misoprostol.. The medical termination was unsuccessful. The patient elected to continue the pregnancy secondary to financial considerations. She presented at 39 weeks without intervening prenatal care. She was diagnosed with severe preeclampsia. At delivery the infant was hypotonic and growth restricted with multiple anomalies.. Physicians are increasingly using methotrexate with or without misoprostol for treatment of ectopic pregnancies and medical terminations. Clinicians need to be aware of the characteristic teratologic effects of these two agents.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Abortifacient Agents, Nonsteroidal; Abortion, Incomplete; Abortion, Induced; Adult; Female; Growth Disorders; Humans; Infant; Methotrexate; Misoprostol; Pregnancy

I prescribed misoprostol to one of my patients with a peptic ulcer. When she found out she was pregnant while on the drug, both she and, admittedly, I were very scared to learn that the drug is teratogenic in that it causes Möbius syndrome. How great is the risk?. Very small. Although women who use misoprostol during the first trimester have a 30-fold higher risk of having babies with Möbius syndrome, the malformation is so rare that, even if you see 1000 women who took misoprostol during embryogenesis, you might not see a single child with the syndrome. It is crucial to explain the size of the risk; otherwise women tend to believe the risk is huge even when, in fact, it is hardly measurable.

Topics: Abnormalities, Drug-Induced; Anti-Ulcer Agents; Female; Humans; Infant, Newborn; Misoprostol; Mobius Syndrome; Peptic Ulcer; Pregnancy; Pregnancy Complications; Risk

To verify if any of the 15 congenital defects already reported in association with misoprostol can be found within an epidemiological registry of congenital defects.. Case-control study including case-sick and case-health controls.. Comparison of misoprostol exposure for each specific defect, using the exposure for the rest of defects as a reference group.. Four thousand six hundred seventy-three consecutive newborn infants with malformations of unknown aetiology, in the Latin American Collaborative Study of Congenital Malformation.. There was no difference in exposure rate between the malformed (34/4,673) and nonmalformed (23/4,980) newborns. Four of the five more frequently cited defects in the literature were found to be in excess: constriction ring, terminal transverse-limb defects, hydrocephalus, and arthrogryposis. Equinovarus feet had a normal frequency in our study. Thirteen different defects not described in the literature were seen in our misoprostol exposed cases, but only holoprosencephaly and bladder exstrophy significantly exceeded the expected number.. The confirmation from an epidemiological registry of an association for four of the five more commonly observed congenital defects among misoprostol exposed children described in the literature seems indicative of a real teratogenic effect. The defects are of vascular disruption type. However, additional attempts to achieve abortion could not be excluded as a concurrent contribution.

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Case-Control Studies; Female; Humans; Infant, Newborn; Latin America; Misoprostol; Pregnancy

We report on clinical evaluations of Brazilian patients with misoprostol-induced arthrogryposis. All 15 patients had growth retardation, underdeveloped bones, short feet with equinovarus, rigidity of several joints with skin dimples and webs, decreased movement of legs stemming from neurologic impairment, bilateral symmetrical hypoplasia or atrophy of limb muscles, and absent tendon reflexes. Of the 15 patients, five had upper limb deformities in addition to lower limb involvement, and one had spinal cord disruption leading secondarily to segmental sensory loss and neurogenic bladder and bowel. Electroneuromyography of five patients indicated that the abnormalities were of neurogenic origin and suggestive of anterior horn cell defects. All of their mothers took 400-4,800 mcg of misoprostol orally or vaginally at 8 to 12 weeks of pregnancy. Our observations support a previously stated caution with regard to the embryotoxicity of misoprostol.

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Administration, Intravaginal; Administration, Oral; Adolescent; Adult; Arthrogryposis; Child; Child, Preschool; Embryo, Mammalian; Female; Fetal Growth Retardation; Humans; Infant; Infant, Newborn; Limb Deformities, Congenital; Male; Misoprostol; Pregnancy

Prenatal exposure to misoprostol has been associated with Moebius and limb defects. Vascular disruption has been proposed as the mechanism for these teratogenic effects. The present study is a multicenter, case-control study that was designed to compare the frequency of prenatal misoprostol use between mothers of Brazilian children diagnosed with vascular disruption defects and matched control mothers of children diagnosed with other types of defects. A total of 93 cases and 279 controls were recruited in eight participating centers. Prenatal exposure was identified in 32 infants diagnosed with vascular disruption defects (34.4%) compared with only 12 (4.3%) in the control group (P<0.0000001). Our data suggest that prenatal exposure to misoprostol is associated to the occurrence of vascular disruption defects in the newborns.

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Administration, Oral; Adult; Case-Control Studies; Female; Fetus; Humans; Limb Deformities, Congenital; Misoprostol; Mobius Syndrome; Odds Ratio; Pregnancy; Prenatal Exposure Delayed Effects

Misoprostol is commonly used to induce abortion in Brazil, and in other countries in South and Central America where abortions are illegal. However, misoprostol is not very effective in inducing abortions, and exposure to the drug in utero can cause abnormalities in the fetus. We aimed to define the common phenotypical effects of exposure to the drug.. We studied 42 infants from São Paulo, Brazil, who were exposed to misoprostol during the first 3 months of gestation, and then born with congenital abnormalities. We interviewed each of the infants' mothers to find out about misoprostol exposure and dosage. Each infant was physically examined by a geneticist or a neuropaediatrician.. 17 of the infants had equinovarus with cranial-nerve defects. Ten children had equinovarus as part of more extensive arthrogryposis. The most distinctive phenotypes were arthrogryposis confined to the legs (five cases) and terminal transverse-limb defects (nine cases) with or without Mobius sequence. The most common dose of misoprostol taken was 800 microg (range 200-16000 microg).. Deformities attributed to vascular disruption were found in these children. We suggest that the uterine contractions induced by misoprostol cause vascular disruption in the fetus, including brain-stem ischaemia. Information on the effects of taking misoprostol during pregnancy should be made more widely available, to dissuade women from misusing the drug.. In Brazil and other South and Central American countries where abortion is illegal, misoprostol is widely available and commonly used to induce abortion. However, misoprostol is not very effective as an abortifacient agent and can cause fetal abnormalities. The present study reviewed the cases of 42 infants from Sao Paulo, Brazil, who were exposed to misoprostol during the first trimester of pregnancy and then born with a congenital abnormality. 17 children had equinovarus with cranial nerve deficiencies and 10 had equinovarus as part of a more extensive arthrogryposis. The most distinctive phenotypes were arthrogryposis confined to the legs (5 cases) and terminal transverse limb defects (9 cases). Congenital hydrocephalus was present in 8 children. The most commonly taken dose of misoprostol was 800 mcg (range, 200-16,000 mcg). Greater awareness of the widespread use of misoprostol to induce abortion should lead to public health interventions to prevent teratogenic effects.

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Abortion, Criminal; Arthrogryposis; Brazil; Clubfoot; Cranial Nerves; Female; Humans; Infant, Newborn; Male; Misoprostol; Pregnancy; Self Administration

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Abortion, Induced; Adult; Female; Humans; Leg; Misoprostol; Pregnancy; Treatment Failure

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Abortifacient Agents, Steroidal; Abortion, Induced; Alprostadil; Female; Humans; Mifepristone; Misoprostol; Pregnancy; Prostaglandins E, Synthetic; Risk Factors; Treatment Failure

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Female; Humans; Misoprostol; Pregnancy; Risk Factors; Teratogens

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Anti-Ulcer Agents; Female; Humans; Misoprostol; Oxytocics

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Abortion, Induced; Female; Humans; Methotrexate; Misoprostol; Pregnancy

Topics: Abnormalities, Drug-Induced; Animals; Cranial Nerves; Female; Humans; Limb Deformities, Congenital; Misoprostol; Paralysis; Rats; Syndrome; Uterine Contraction

Topics: Abnormalities, Drug-Induced; Abortion, Induced; Female; Humans; Misoprostol; Pregnancy

Misoprostol (MSP) is a synthetic prostaglandin E1 methyl analogue indicated for the prevention of gastric ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs). Because of its abortifacient properties, MSP has been extensively misused for abortion induction in Brazil. Since abortion induction with MSP very often fails and pregnancy continues to term, there has been increasing concern regarding the potential teratogenicity of this PGE1 analogue in humans. The objective of the present study was to evaluate the embryotoxicity of MSP in mice. A single dose of MSP (20 or 30 mg/kg body weight) was administered to Han:NMRI mice (ca 60 days old) by gavage on day 10 of pregnancy. The number of treated mice was as follows: control, 19; MSP 20 mg/kg, 10; MSP 30 mg/kg, 28. Cesarean sections were performed on day 18 of pregnancy and the number of resorptions and implantation sites were recorded. Fetuses were weighed, examined for external malformations, fixed, cleared and stained with Alizarin Red S for skeleton evaluation. No evidence of embryotoxicity was found at the lower dose tested. A slight and reversible deficit in pregnancy weight gain (day 10-11: control, 1.3 +/- 0.3 g; MSP 20 mg/kg, -0.9 +/- 0.9 g; MSP 30 mg/kg, -1.7 +/- 0.6 g) was the only sign of maternal toxicity noted in both groups of mice treated with misoprostol.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Abnormalities, Drug-Induced; Animals; Anti-Ulcer Agents; Body Weight; Embryonic and Fetal Development; Female; Humans; Infant, Newborn; Mice; Mice, Inbred Strains; Misoprostol; Pregnancy; Weight Gain

In Brazil, many women are using the synthetic prostaglandin misoprostol to induce abortion. Since abortion is illegal in Brazil, they take misoprostol without any medical supervision. It was introduced in Brazil in 1986 as a treatment for gastric ulcers. Its brand name is Cytotec. The prescription drug is widely available on the black market, where the price for 4 200-mg tablets begins at US$100. Use of the drug with failure to abort may be linked to birth defects. A geneticist and a neuropediatrician at the Children's Institute of the Sao Paulo Hospital das Clinicas are studying 9 children with congenital or neurological abnormalities. Physicians in other parts of Brazil are following another 30 children with the same circumstances. A physician in Porto Alegre is following 40 women who took misoprostol but did not abort. As of mid 1994, she had found 3 cases of congenital abnormalities. The Brazilian Society for Clinical Genetics is overseeing an epidemiologic study in 10 major maternity hospitals where researchers will examine all neonates and ask all mothers about the possible use of misoprostol. Staff at the genetics outpatient clinics of 6 leading hospitals are about to conduct a related study among mothers. Both of these studies run the risk of low reporting, since mothers may be disinclined to admit to criminal use of misoprostol. Almost 50% of all women who want pregnancy termination in Brazil use misoprostol. The abortion fails in about 33% of these cases. The evidence suggests an 8-10% risk of abnormalities among women who use misoprostol and experience abortion failure. Ministry of Health sources unofficially appreciate that misoprostol use is reducing the number of women hospitalized with infections caused by abortion attempts with sharp instruments, which in turn has reduced maternal mortality.

Topics: Abnormalities, Drug-Induced; Brazil; Female; Humans; Infant, Newborn; Misoprostol; Pregnancy

Topics: Abnormalities, Drug-Induced; Female; Humans; Infant, Newborn; Latin America; Male; Misoprostol; Neonatal Screening

Misoprostol, a synthetic analog of prostaglandin, has been widely used in Brazil as an abortifacient. Abortion is illegal in Brazil. An uncertain number of these abortion attempts are unsuccessful and the pregnancy continues. We report on 7 patients whose mothers attempted to abort using this drug in the first trimester of gestation without success. The 7 patients presented with limb defects and in 4 of them a diagnosis of Möbius sequence was made.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Abortion, Criminal; Brazil; Cranial Nerve Diseases; Ectromelia; Facial Paralysis; Female; Foot Deformities, Congenital; Hand Deformities, Congenital; Humans; Infant, Newborn; Male; Misoprostol; Pregnancy; Syndrome

Topics: Abnormalities, Drug-Induced; Female; Humans; Misoprostol; Pregnancy

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Alprostadil; Female; Humans; Misoprostol; Pregnancy; Skull

Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Brazil; Female; Humans; Misoprostol; Pregnancy