vitamin-k-semiquinone-radical and Premature-Birth

Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease during pregnancy, characterized by otherwise unexplained pruritus in late second and third trimester of pregnancy and elevated bile acids and/or transaminases. ICP is associated with an increased risk of adverse perinatal outcomes for the fetus and the later development of hepatobiliary disease for the mother. Bile acids should be monitored throughout pregnancy since fetal risk is increased at serum bile acids >40 µmol/l. Management of ICP consists of treatment with ursodeoxycholic acid, which reduces pruritus. Early elective delivery is common practice but should be performed on an individualized basis as long as strong evidence supporting this practice is lacking. Mothers should be followed-up for normalization of liver function tests 6-12 weeks after delivery. Future research in large-scale studies is needed to address the impact of ursodeoxycholic acid and early elective delivery on fetal outcome.

Topics: Antifibrinolytic Agents; Bile Acids and Salts; Cholagogues and Choleretics; Cholestasis, Intrahepatic; Female; Fetal Death; Histamine Antagonists; Humans; Labor, Induced; Nucleic Acid Synthesis Inhibitors; Pregnancy; Pregnancy Complications; Premature Birth; Pruritus; Rifampin; Ursodeoxycholic Acid; Vitamin K

Vitamin K is the most common 'drug' administered to babies born in the western world. For many decades vitamin K prophylaxis has been a routine treatment at birth for preterm infants. Despite universal use in preterm infants, very little work has been done to date to refine vitamin K dosage in this population or to assess vitamin K status after prophylaxis. Current regimens of prophylaxis used for preterm infants vary widely in terms of dose, route of administration, and formulation used.

Topics: Chemoprevention; Humans; Infant Formula; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Nutrition Policy; Premature Birth; Vitamin K; Vitamin K Deficiency

The purpose of this study was to investigate first trimester anticoagulant exposure and risks of adverse pregnancy-related and fetal outcomes.. Using Danish nationwide registries, we identified all pregnant women with preconception venous thromboembolism, 2000-2017, and linked data on exposure to low-molecular-weight heparin (LMWH), vitamin K antagonist (VKA), or non-VKA oral anticoagulant (NOAC) during pregnancy. We assessed pregnancy-related and fetal outcomes associated with first trimester anticoagulant exposure.. Among 4490 pregnancies in women with preconception venous thromboembolism (mean age 31 years, 40% nulliparous) during the first trimester, 63.1% were unexposed, 25.9% were exposed to LMWH, 10.4% VKA, and 0.6% NOAC. Adverse outcomes were lowest in unexposed and LMWH exposed. Compared with unexposed, VKA was associated with higher risks of preterm (adjusted odds ratio [OR] 2.26; 95% confidence interval [CI], 1.70-2.99) and very preterm birth (adjusted OR 3.78; 95% CI, 1.91-7.49), shorter mean gestational age was associated with VKA (-7.5 days; 95% CI, -9.1 to -5.9 days) or NOAC (-2.3 days; 95% CI, -8.4-3.8), and lower mean birthweight with VKA (-55 g; 95% CI, -103.1 to -8.5) or NOAC (-190 g; 95% CI, -364.1 to -16.4). Adjusted ORs for small-for-gestational-age infants were 1.07 (95% CI, 0.77-1.50) with VKA, and 3.29 (95% CI, 1.26-7.95) with NOAC. Mean 5-minute Apgar score (9.8) and congenital defect prevalence (8.4%-10%) varied little across exposure groups.. Fetal risk was lowest in unexposed and LMWH-exposed pregnancies, supporting the recommendation of LMWH during pregnancy. NOAC safety during pregnancy is unclear due to the rarity of NOAC exposure.

Topics: Adult; Anticoagulants; Cohort Studies; Female; Heparin, Low-Molecular-Weight; Humans; Infant, Newborn; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, First; Premature Birth; Venous Thromboembolism; Vitamin K

The aim of this observational cohort study was to specify the risk of the vitamin K antagonist (VKA) phenprocoumon during first trimester of pregnancy, in particular to estimate the risk of birth defects and spontaneous fetal loss. Four hundred eight pregnancies with phenprocoumon exposure were compared to 1,642 pregnancies neither exposed to VKA nor to other major teratogens or fetotoxicants. There was no typical warfarin embryopathy in our exposed cohort. However, the overall rate of major birth defects was significantly increased (7.4 % vs 2.3 %; adjusted odds ratio [OR

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Abortion, Therapeutic; Adult; Anticoagulants; Birth Weight; Blood Coagulation; Drug Administration Schedule; Drug Substitution; Female; Humans; Infant, Newborn; Logistic Models; Odds Ratio; Phenprocoumon; Pregnancy; Pregnancy Trimester, First; Premature Birth; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vitamin K; Young Adult

Topics: Humans; Infant Formula; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Premature; Premature Birth; Vitamin K

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: Antifibrinolytic Agents; Blood Coagulation; Child; Female; Heparin Antagonists; Humans; Infant; Infant, Newborn; Infant, Premature; Pregnancy; Premature Birth; Vitamin K

Topics: Female; Humans; Infant; Pregnancy; Premature Birth; Vitamin A; Vitamin K; Vitamins