The use of antenatal vitamin K in the prevention of early neonatal intraventricular hemorrhage. Maternal administration of vitamin K does not improve the coagulation profile of preterm infants. Maternally administered antenatal vitamin K1: effect on neonatal prothrombin activity, partial thromboplastin time, and intraventricular hemorrhage. Maternal antenatal administration of vitamin K1 results in increasing the activities of vitamin K-dependent coagulation factors in umbilical blood and in decreasing the incidence rate of periventricular-intraventricular hemorrhage in premature infants. Antenatal vitamin K therapy of the low-birth-weight infant. Maternal-fetal transport of vitamin K1 and its effects on coagulation in premature infants.
To establish the effect of antenatal vitamin K on the incidence and severity of intraventricular hemorrhage, 92 patients destined to deliver infants less than 32 weeks' gestation were, in a prospective fashion, randomly assigned to two groups. Group I received 10 mg of vitamin K1 intramuscularly every 5 days until delivery. Group II received no antenatal vitamin K1 therapy. There were 100 neonates less than 1500 gm, equally divided between groups I and II with respect to gestational age, birth weight, race, sex, presentation, route of delivery, duration of labor, Apgar scores, and arterial umbilical cord acid-base balance. The antenatal use of vitamin K resulted in significant reduction in the prothrombin time (12.7 versus 15.2 seconds) and partial thromboplastin time (42.6 versus 58.9 seconds; p less than 0.05). Furthermore, group I experienced a lower incidence of total (16% versus 36%) and severe (0% versus 11%) grades of intraventricular hemorrhage (p less than 0.05). This study suggests that the antenatal use of vitamin K may result in a reduction and severity of intraventricular hemorrhage in the neonate less than 1500 gm. The effect of maternal administration of vitamin K1 on cord blood prothrombin time, activated partial thromboplastin time, activity of factors II, VII, and X, and antigen levels of factors II and X in infants less than 35 weeks' gestation was evaluated. Pregnant women in preterm labor were randomly assigned to receive 10 mg of vitamin K1 intramuscularly or no injection. If delivery did not occur in 4 days, the dose of vitamin K1 was repeated. Women who continued their pregnancy 4 days beyond the second dose received 20 mg of vitamin K1 orally daily until the end of the 34th week of gestation. The birth weights of infants ranged from 370 to 2550 g and gestational age ranged from 22 to 34 weeks. The prothrombin time, activated partial thromboplastin time, factors II, VII, and X activity, and factors II and X antigen levels were not statistically different in either group of infants. Intraventricular hemorrhage occurred in 25 of 51 control infants and 25 of 47 vitamin K-treated infants. More control infants had grade III intraventricular hemorrhage on day 1 (P = .032), but on day 3 and 14 of life, the severity of intraventricular hemorrhage was comparable in both groups. Infants in whom an intraventricular hemorrhage developed were significantly smaller, younger, and more critically ill than infants without intraventricular hemorrhage. Administration of vitamin K1 to pregnant women at less than 35 weeks' gestation does not improve the hemostatic defects nor does it reduce the incidence or severity of intraventricular hemorrhage in their infants. Infants weighing 1500 g or less at birth are susceptible to intraventricular hemorrhage. This may be due in part to low concentrations of vitamin K-dependent clotting factors. Women in labor between 24-34 weeks' gestation were selected, according to their hospital registration number, to receive 10 mg vitamin K1 intramuscularly at least four hours before delivery. Control women received no vitamin K. The study included only infants born of mothers who were in hospital more than four hours before delivery, who weighed 1500 g or less at birth, and were less than 34 weeks' gestation. Twenty vitamin K1 and 33 control infants qualified for the study. Infants in both groups received routine postnatal vitamin K1. On admission, the infant's prothrombin activity and partial thromboplastin time (PTT) were measured. A head ultrasound was done between days 2 and 4 of life. Results demonstrated significantly improved prothrombin activity, a nonsignificant trend toward improved PTT, and a significantly decreased frequency of intraventricular hemorrhage in infants whose mothers had received vitamin K1. The effect of antenatal vitamin K1 on prothrombin activity and PTT appeared to be more pronounced in female infants. Infants less than 35 weeks' gestation age are susceptible to periventricular-intraventricular hemorrhage (PIVH). This may be partially attributable to low concentrations of vitamin K-dependent coagulation factors. The purposes of this study were: (1) to determine the umbilical blood activity levels of vitamin K-dependent coagulation factors II, VII, IX and X; (2) to investigate the change in activities of these factors in premature infants' umbilical blood after prenatal administration of vitamin K1 to the mothers; and (3) to study the prophylactic effects on PIVH after maternal antenatal supplemental vitamin K1.
                Pregnant women in preterm labor at less than 35 weeks of gestation were randomly selected to receive antenatal vitamin K1 10 mg per day injection intramuscularly or intravenously for 2-7 days (vitamin K1 group, n = 40), or no such treatment (control group, n = 50). At the same period, cord blood samples were collected from thirty full-term neonates to compare the factor levels with those of premature infants. Intracranial ultrasound was performed by the same sonographer to determine the presence and severity of PIVH.
                The activities of vitamin K-dependent coagulation factors in umbilical blood in the control group were: factor II 25.64+/-9.49%, factor VII 59.00+/-17.66%, factor IX 24.67+/-8.88%, and factor X 30.16+/-5.02%. In full-term infants, the respective values were: factor II 36.70+/-4.88%, factor VII 64.54+/-10.62%, factor IX 30.18+/-5.69%, and factor X 34.32+/-12.63%. In vitamin K1 group these factors were: factor II 36.35+/-6.88%, factor VII 69.59+/-16.55%, factor IX 25.71+/-10.88%, and factor X 39.26+/-8.02%. The data suggest the absence of vitamin K-dependent coagulation factors in preterm infants, and antenatal supplement of vitamin K1 may increase the cord blood activity of factor II, VII and factor X (P < 0.001). In addition, the overall rates of PIVH in the vitamin K1 group and in controls were 32.4 and 52.0%, respectively (P = 0.036), and the frequency of severe PIVH was 5.0 and 20.0%, respectively (P = 0.038).
                Administration of vitamin K1 to pregnant women at less than 35 weeks' gestation age may result in improved coagulation and may reduce the incidence as well as the severity degree of PIVH. The purpose of our study was to determine whether maternal vitamin K1 administered antenatally improved global coagulation parameters and the levels of specific vitamin K-dependent proteins in low-birth-weight infants.
                Thirty-three preterm mothers admitted in labor were assigned in a prospective, blinded fashion to receive either intramuscular vitamin K1 (17) or placebo (16). At delivery cord blood samples were tested for prothrombin time, activated partial thromboplastin time, factor II and protein C activity, and antigen levels. Statistical analysis was by Student t test.
                No statistically significant differences could be demonstrated with regard to group mean values for global tests (prothrombin time, activated partial thromboplastin time) or specific vitamin K-dependent protein levels (factor II, protein C) in newborns whose mothers received antenatal vitamin K compared with those who did not.
                These results would suggest that antenatal vitamin K1 therapy to mothers < 32 weeks' gestation has no significant effect on the level of vitamin K-dependent factors in the fetus. We conducted a prospective study to determine (1) the maternal-fetal vitamin K1 transport in premature infants after vitamin K1 was given to the mothers antenatally and (2) the vitamin K1 effects on blood coagulation in the babies. Women in labor at less than or equal to 34 weeks of gestation were randomly selected to receive antenatal vitamin K1, 5 mg given intramuscularly (vitamin K1 group), or no vitamin K1 (control group). Eight infants, including one set of twins, were in the vitamin K1 group and six in the control group. Vitamin K1 concentrations were higher in the vitamin K1 group than in the control group (p = 0.06). Activated partial thromboplastin time was prolonged, and factor II coagulation activity and factor II antigen were proportionately decreased in cord plasma in both groups. The average ratio of factor II coagulation activity to antigen was not decreased in either group. Protein induced by vitamin K absence-II (PIVKA-II) was not detectable in any cord plasma sample in either group. These findings support previous reports that the decreased vitamin K-dependent coagulation activity in premature infants is the result of reduced synthesis of precursor proteins, rather than the result of vitamin K deficiency, and suggest that additional vitamin K1 is not likely to improve coagulation activity. Among those infants who underwent cranial ultrasonography, all four in the vitamin K1 group and one of five in the control group had mild intraventricular hemorrhage. Studies of a larger number of patients are necessary before it can be established that maternal antenatal administration of vitamin K1 results in improvement of coagulation and the prevention of intraventricular hemorrhage in premature infants.
Vitamin K administered to women prior to very preterm birth has not been shown to significantly prevent PVH in preterm infants or improve neurodevelopmental outcomes in childhood.