{'fraction_non_alphanumeric': 0.02323943661971831, 'fraction_numerical': 0.0032863849765258214, 'mean_word_length': 5.27540500736377, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Prenatal Vitamin K for Low Birth Weight Infants

Periventricular/intraventricular hemorrhage (PIVH) continues to be a major complication in the low and very tow birth weight infant (1). Its pathogenesis is undoubtedly multifactorial. It includes bleeding from fragile small vessels in the germinal matrix layer and choroid plexus due to lack of fully developed connective tissue support; loss of cerebral blood flow autoregulation in response to distress states; direct damage to these vessels by hypoxia; and the immaturity of the fetal coagulation system, particularly of the vitamin K dependant factors that are gestational age dependent. In premature, healthy infants Andrew et al have shown that the vitamin K dependant coagulation factors (II, VII, IX, X, protein C and protein S) are between 25-70% of adult values (2). Whether this is due to differences in the rate of synthesis, secretion or turnover of these proteins, any pharmacologic intervention that could result in increase synthesis of these proteins antenatally could theoretically reduce the incidence of PIVH. Two questions arise if such an approach were to be recommended as standard policy. First, does maternally administered vitamin K, increase the fetal vitamin K, concentration, and, second, could the fetal liver respond to this intervention. Addressing the issue of placental transfer of vitamin K, from mother to fetus, Shearer et al used high performance liquid chromatography to show that vitamin K, was not detected in most fetal cord samples (3). In mothers given vitamin K, however, low but detectable levels could now be measured in four of six infants. Mandelbrot et al measured levels of vitamin K, during the second trimester and at birth and also found a marked maternal/fetal gradient, it being fourteen fold at the second trimester point and eighteen fold at birth (4). In those mothers given oral supplementation of vitamin K" cord levels rose thirty and sixty fold respectivaly, indicating placental transfer. The findings of Kazzi et al were similar, even greater levels being found in cord blood if mothers had received both intramuscular and oral supplementation (5). The results of these studies readily demonstrate that maternally administered vitamin K, given to the mother does cross the placenta, abeit slowly and to a limited degree. Does antenatal supplementation then improve the coagulation parameters in the preterm infant? Since PIVH is multifactorial, this question must be addressed on its own merit lest benefit be assigned to this intervention inappropriately. What evidence supports the premise that vitamin K given to women in preterm labor improves the coagulation profile of low birth weight infants? Pomerance and coworkers noted an improved prothrombin activity in infants whose mothers had received vitamin K, (6). Morales et al suggested antenatal vitamin K, reduced significantly the prothrombin time and the activated partial thromboplastin time (7). This improvement in these global coagulation tests was not confirmed in subsequent studies, nor was there any statistical difference between treated and untreated groups in the plasma levels of specific vitamin K-dependent coagulation factors. Mandlebrot, et al demonstrated that despite vitamin K, supplementation and documented increases in fetal vitamin K, levels, total or coagulation prothrombin activity did not increase (9). Subsequently Kazzi et al in a similar design study found no statistical change in prothrombin time, activated partial thromboplastin time, factors II, VII, X, or the antigen levels of these proteins in groups of infants or mothers receiving vitamin K or those not so treated (8). Our results confirm and extend those of Kazzi et ai, in that we could find no statistical difference in the coagulation parameters of low birth weight infants of those mothers supplemented with vitamin K compared to those not antenatally treated (9). Our study included factor II activity and antigen, protein C activity and antigen. In addition no evidence for increased levels of des-gamma carboxy prothrombin could be found in either group using either commercial thromboplastin preparation or ecarin, a snake venom enzyme. The results of these various studies suggest that