acenocoumarol and Abnormalities--Drug-Induced

Vitamin K antagonists (VKA) are known to act as teratogens; however, there is still uncertainty about the relative risk for birth defects and the most sensitive period. In a multi-centre (n = 12), observational, prospective study we compared 666 pregnant women exposed to phenprocoumon (n = 280), acenocoumarol (n = 226), fluindione (n = 99), warfarin (n = 63) and phenindione (n = 2) to a non-exposed control group (n = 1,094). Data were collected by institutes collaborating in the European Network of Teratology Information Services (ENTIS) during individual risk counselling between 1988 and 2004. Main outcome measures were coumarin embryopathy and other birth defects, miscarriage rate, birth-weight, and prematurity. The rate of major birth defects after 1st trimester exposure was significantly increased (OR 3.86, 95% CI 1.86-8.00). However, there were only two coumarin embryopathies (0.6%; both phenprocoumon). Prematurity was more frequent (16.0% vs. 7.6%, OR 2.61, 95% CI 1.76-3.86), mean gestational age at delivery (37.9 vs.39.4, p<0.001), and mean birth weight of term infants (3,166 g vs. 3,411 g; p < 0.001) were lower compared to the controls. Using the methodology of survival analysis, miscarriage rate reached 42% vs. 14% (hazard ratio 3.36; 95% CI 2.28-4.93). In conclusion, use of VKA during pregnancy increases the risk of structural defects and other adverse pregnancy outcomes. The risk for coumarin embryopathy is, however, very small, in particular when therapy during the 1(st) trimester did not take place later than week 8 after the 1(st) day of the last menstrual period. Therefore, elective termination of a wanted pregnancy is not recommended if (inadvertent) exposure took place in early pregnancy. Close follow-up by the obstetrician including level II ultrasound should be recommended in any case of VKA exposure during pregnancy.

Topics: Abnormalities, Drug-Induced; Abortion, Induced; Abortion, Spontaneous; Acenocoumarol; Adverse Drug Reaction Reporting Systems; Anticoagulants; Birth Weight; Female; Fetal Diseases; Gestational Age; Humans; Phenindione; Phenprocoumon; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, First; Premature Birth; Prospective Studies; Vitamin K; Warfarin

Topics: Abnormalities, Drug-Induced; Acenocoumarol; Administration, Oral; Adult; Aged; Anticoagulants; Diet; Duty to Warn; Female; Humans; Middle Aged; Patient Compliance; Patient Education as Topic; Pregnancy; Surveys and Questionnaires; Vegetables

We report a case of warfarin embryopathy. This disease affects more than 6% of fetuses exposed in utero to a vitamin K antagonist.. A child whose mother was treated with acenocoumarol because of a mechanical heart valve presented with signs of warfarin embryopathy. He showed chondrodysplasia punctata with telebrachydactyly, facial dysmorphism with nasal hypoplasia, a cataract, and a bilateral pyeloureteral junction syndrome.. Characteristics of this drug induced embryopathy are reminded, while bearing in mind the conflict of interests between the mother and the fetus. The mechanisms of this embryopathy are debated in light of the recent knowledge concerning fetal metabolism of vitamin K.

Topics: Abnormalities, Drug-Induced; Acenocoumarol; Adult; Age Factors; Anticoagulants; Child, Preschool; Chondrodysplasia Punctata; Female; Fetus; Follow-Up Studies; Heart Valve Prosthesis; Humans; Infant; Male; Pregnancy; Pregnancy Complications, Cardiovascular; Prenatal Exposure Delayed Effects; Time Factors; Warfarin

Topics: Abnormalities, Drug-Induced; Acenocoumarol; Anticoagulants; Embryonic Structures; Female; Follow-Up Studies; Humans; Infant, Newborn; Pregnancy; Prenatal Exposure Delayed Effects

In an attempt to identify the best treatment for pregnant women with cardiac-valve prostheses who are receiving oral anticoagulants, we studied 72 pregnancies prospectively. In 23 pregnancies (Group I), the coumarin derivative acenocoumarol was discontinued and the patients received 5,000 U of subcutaneous heparin every 12 hours from the 6th to the 12th week of gestation, in 12 pregnancies (Group II), heparin was not substituted for the coumarin derivative until after the 7th week, and in 37 pregnancies, detected after the first trimester (Group III), the coumarin derivative was given throughout gestation. In most patients heparin was again substituted for the oral anticoagulant after the 38th week. Three mothers had thrombosis of a tilting-disk mitral prosthesis (two cases were fatal) during heparin treatment. No differences were found in the rates of spontaneous abortion in the three groups. Coumarin embryopathy occurred in 25 percent and 29.6 percent of the pregnancies in Groups II and III, respectively. We conclude that in the second and third trimesters of pregnancy, coumarin derivatives provide effective protection against thromboembolism while causing few fetopathic effects, but that these agents are contraindicated from the 6th to the 12th weeks of gestation. Low-dose heparin does not protect against prosthetic-valve thrombosis, and the possibility that a larger dose might be more effective requires further exploration.

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Acenocoumarol; Adolescent; Adult; Coumarins; Drug Administration Schedule; Female; Fetal Death; Fetus; Heart Valve Prosthesis; Heparin; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Trimester, First; Thromboembolism

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Acenocoumarol; Female; Heart Valve Diseases; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Risk

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Acenocoumarol; Female; Fetal Diseases; Humans; Infant; Maternal-Fetal Exchange; Pregnancy; Risk

Topics: 4-Hydroxycoumarins; Abnormalities, Drug-Induced; Acenocoumarol; Adult; Chondrodysplasia Punctata; Female; Humans; Phenprocoumon; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Third

The ability of most anticoagulants (except heparin) to cross the placenta and the consequent hemorrhage in the fetus has been recognized for some time (3). A teratogenic effect specifically attributed to warfarin sodium is a more recent finding (7, 9, 10). The following is a case report of a newborn with clinical and roentgenographic features similar to the cases reported previously.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Acenocoumarol; Adult; Chondrodysplasia Punctata; Female; Humans; Infant, Newborn; Maternal-Fetal Exchange; Pregnancy