A 27-yr-old woman who had been taking warfarin for 10 yr after mitral valve replacement became pregnant. After knowing her pregnancy, she received heparinization for nine weeks instead of warfarin, and took oral anticoagulant again. At 24 weeks of gestation, fetal ultrasound and MRI showed a left subdural hematoma, and the pregnancy was terminated. Subdural hematoma was demonstrated on autopsy. Fatal bleeding of the fetus is a rare complication of maternal warfarin medication, occurring mostly in the second or third trimester. There is no alternative regimen available, so that regular monitoring by fetal ultrasound and strict control of warfarin dose with regular measurement of prothrombin time are the best way to prevent intrauterine fetal death due to bleeding.
Adult ; Anticoagulants/*adverse effects ; Ductus Arteriosus, Patent/surgery ; Female ; Fetal Diseases/*chemically induced ; Heart Valve Diseases/therapy ; Hematoma/chemically induced ; Heparin/adverse effects ; Human ; Intracranial Hemorrhages/*chemically induced ; Maternal Exposure ; Pregnancy ; Pregnancy Complications, Hematologic ; Prothrombin Time ; Warfarin/*adverse effects

OBJECTIVE: To investigate the relationship between homocysteine (HCY) and congenital heart defects, and to observe the toxic effect of different doses of HCY on embryonic heart development in mammalian. METHODS: A total of 30 SD pregnant rats were randomly divided into 3 groups: a high dose group [200 mg/(kg.d)], a low dose group [(100 mg/(kg.d)] and a control group (equal volume of physiologic saline, n=10 in each group). The HCY or vehicle was given intraperitoneally from 7 to 20 days after uterineincision delivery. The contents of HCY in serum were analyzed by high performance liquid chromatogram electrochem before the pregnancy and 20 days after the pregnancy. The structure changes of the newborn rats heart were observed by stereoscope. The ultrastructure changes of cadiomyocyte were observed through transmission electron microscope. RESULTS: Comparing with the control, serum HCY in rats 20 days after pregnancy was significantly increased in the high or low dose group [(30.47 ± 1.12), (20.90 ± 1.08)vs(10.98 ± 0.77)μmol/L, P<0.01)], indicating that the hyperhomocysteinemia animal model was successfully established. The incidence rate of congenital heart defects in neonatal was significantly increased in the high or low dose group(14.13%, 9.57% vs 0.76%, P<0.01). The number of apoptotic cells were significantly increased in the high dose group. CONCLUSION Hyperhomocysteinemia may exert toxic effect on embryonic heart development in pregnancy rats, which led to congenital heart defects in the newborn rats. Hyperhomocysteinemia induced cardiomyocyte apoptosis may, at least partially, contribute to the heart defects.
Animals ; Apoptosis ; drug effects ; Female ; Fetal Diseases ; chemically induced ; Heart Defects, Congenital ; chemically induced ; pathology ; Hyperhomocysteinemia ; complications ; Myocytes, Cardiac ; pathology ; Pregnancy ; Pregnancy Complications ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Animals ; Caffeine/adverse effects* ; Central Nervous System Stimulants/adverse effects* ; Dose-Response Relationship, Drug ; Female ; Fetal Growth Retardation/chemically induced* ; Immune System Diseases/chemically induced* ; Male ; Organ Size/drug effects* ; Pregnancy ; Pregnancy Complications/immunology* ; Rats ; Spleen/growth & development*

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a highly toxic halogenated aromatic hydrocarbon, is a teratogen to induce cleft palate when exposed during the pregnancy. There are inter-strain differences in the sensitivity to cleft palate induced by TCDD and other chemicals including polychlorinated terphenyls (PCTs). The C57BL/6 mouse and the ddY mouse had been shown to be different in the induction of cleft palate following the treatment of PCTs, which attempts us to evaluate the TCDD-induced cleft palate in two mouse strains to understand the mechanism through which TCDD and PCTs induce cleft palate. This study evaluated the induction of cleft palate in the fetuses of ddY and C57BL/6 mice after subcutaneous treatment of TCDD on gestation day (GD) 10.5-14.5 or oral treatment on GD 8.5-13.5. Our results clearly showed that ddY mice, a susceptible strain to PCTs-induced cleft palate, are resistant to the induction of cleft palate by TCDD comparably to the high susceptibility of C57BL/6 mice, suggesting a different teratological mechanism between TCDD and PCTs. In addition, at the low doses, our study supported the concept of "window effect" of TCDD on around GD 12 for the induction of cleft palate in C57BL/6 and ddY mice.
Administration, Oral ; Animals ; Cleft Palate/chemically induced/genetics/pathology/*veterinary ; Female ; Fetal Diseases/chemically induced/mortality/veterinary ; Incidence ; Injections, Subcutaneous ; Male ; Mice ; *Mice, Inbred C57BL ; Polychloroterphenyl Compounds/toxicity ; Pregnancy ; Rodent Diseases/*chemically induced/genetics/pathology ; Teratogens/*toxicity ; Tetrachlorodibenzodioxin/administration & dosage/*toxicity