Journal of Perinatology (2014) 34, 636–639 © 2014 Nature America, Inc. All rights reserved 0743-8346/14 www.nature.com/jp PERINATAL/NEONATAL CASE PRESENTATION Early vitamin K deficiency bleeding in a neonate associated with maternal Crohn’s disease A Ohishi, S Nakashima, T Ogata and S Iijima We report herein a case of early vitamin K deficiency bleeding (VKDB) in a neonate associated with maternal Crohn’s disease. A female neonate was born at 37 weeks’ gestation and weighed 2778 g. She developed broad purpura on her back on day 1. Laboratory data showed anemia, prolonged coagulation time and elevated protein induced by vitamin K absence or antagonist-II. Early VKDB has not been reported in a neonate born from mother with active Crohn’s disease. It is essential to give vitamin K selectively as soon as possible after birth to prevent early VKDB in neonates. Journal of Perinatology (2014) 34, 636–639; doi:10.1038/jp.2014.64 INTRODUCTION hospital; third: one month of age) (Table 1).8 There were no It is well known that neonatal vitamin K deficiency bleeding particular descriptions on the record of nurse until next morning, (VKDB) can be prevented through the administration of vitamin K. but the neonate could not take oral vitamin K syrup because of Early VKDB is known in association with maternal medications feeling of sickness. such as antiepileptic drugs,1,2 but is not well known in relation to Broad purpura and some petechiae on the neonate’s back were maternal Crohn’s disease. Early VKDB has not been reported in a discovered at the first clinical examination by a pediatrician at neonate born from mother with active Crohn’s disease. On the about 24 h after birth (Figure 1a). The neonate cried vigorously, other hand, in adults, vitamin K deficiency due to Crohn’s disease but her skin was slightly pale. Her blood pressure was 69/36 (mean has been reported in association with osteoporosis,3–5 but is not 46) mm Hg, and her heart rate was 170 beats per minute. Her well known in association with bleeding in neonates. blood examination done before blood transfusion and vitamin K Here, we report a case of early neonatal VKDB that was infusion showed severe anemia and disorder of clotting function associated with maternal Crohn’s disease. In high-risk neonates (Table 2a). Biochemical examination revealed no abnormalities such as infant with prematurity or delivered from complicated (Table 2b). The neonate received an infusion of vitamin K (2 mg) and mother, selective administration of vitamin K parenterally as soon − as possible after birth is very important for preventing early VKDB. transfusion of frozen fresh plasma (15 ml kg 1) and packed red blood cells (15 ml kg − 1) two times after which her clotting function and anemia improved. Laboratory results made improve- CASE ments at 24 h after initiation of treatment in the neonatal A female neonate was born at 37 weeks’ gestation by scheduled intensive care unit (Table 2a). Toward evening, the purpura on cesarean section because of breech presentation. Her mother was her back had enlarged and swollen (Figure 1b). She started enteral feedings on day 3, received phototherapy from days 3 to 10 with 34 years old, gravida 1, para 1. The mother began suffering from − Crohn’s disease at age 17 years, and had undergone massive total bilirubin 17.3 and 21.0 mg dl 1, respectively, and was enterectomy (broad range ileum, ascending colon and sigmoid discharged on day 18. Head and abdominal computed tomo- colon) because of ileo-sigmoid colon fistula and stenosis at age 27 graphy performed on day 11 and head magnetic resonance years. The mother had received mesalazine for Crohn’s disease imaging performed on day 15 revealed no intracranial hemor- and took a low-residue diet, although mild diarrhea had continued rhage, ischemic changes in the brain or abdominal hemorrhage. since enterectomy. IOIBD (International Organization For the Also, absence of clinical presentations such as irritability, convul- Study of Inflammatory Bowel Disease) assessment score6 was 4 sion, bloody stool and abdominal distension, denied the at age 17 years, 0 at the mother’s first pregnancy and 1 at present possibility of intracranial, interperitoneal and gastrointestinal pregnancy. The mother’s first delivery at age 31 was normal. In hemorrhages. present pregnancy, she had received ritodrine because of Close investigation of the blood clotting function and threatened premature delivery since 29 weeks’ gestation. The fibrinolytic function were conducted (Table 2b). Elevated PIVKA present neonate’s birth weight was 2778 g, with Apgar scores of (protein induced by vitamin K absence or antagonist)-II1,9,10 over − 8 and 9 at 1 and 5 min, respectively. The neonate was brought 8000 mAU ml 1, decreasing PIVKA-II with vitamin K administra- to the newborn nursery. tion, and low vitamin K-dependent clotting and fibrinolytic factors A common practice of neonatal vitamin K prophylaxis in Japan indicated a status of vitamin K deficiency. The neonate was given is to give oral vitamin K three times (first: after birth by vitamin K intravenously on day 4 and orally once per week up to establishing oral feeding; second: on discharge from maternity 2 months of age from then on and she did not need to Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan. Correspondence: Dr A Ohishi, Department of Pediatrics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan. E-mail: [email protected] Received 19 July 2013; revised 6 March 2014; accepted 6 March 2014 Crohn’s disease and neonatal vitamin K deficiency A Ohishi et al 637 Table 1. Recommendations for prophylactic administration of vitamin K for newborn (2011 modified version)7,8 by the Japan Pediatric Society I. Recommendation for all full-term neonates without any complications. 1. After birth: give 1 ml of vitamin K2 syrup (2 mg of vitamin K2) once orally, after checking that the infant has established oral feedings several times. 2. One week of age (on discharge from the maternity hospital): give 1 ml of vitamin K2 syrup once orally. 3. One month of age (at the time of routine health checkup): give 1 ml of vitamin K2 syrup once orally. Administrations after 1 month can be omitted if the infant is fed with milk. As an alternative method, vitamin K2 syrup can be given once orally per week until 3 months of age. Mothers should be encouraged to consume a vitamin K-rich diet that includes green and yellow vegetables or natto (fermented soybeans). Infants born at a maternity center and at home with an obstetric nurse should also be given vitamin K. II. Recommendation for premature infants and infants with complications. 1. Orally administered infants: give vitamin K same as full-term newborn. 2. Infants unable to receive oral administration: give vitamin K2 0.5–1.0 mg through the venous circulation. 3. Mothers receiving drugs with vitamin K inhibitory effects or mothers complicated by malabsorption diseases such as celiac Figure 1. (a) Broad purpura on neonate’s back discovered at – sprue: give vitamin K2 0.5 1.0 mg through the venous approximately 24 h after birth. (b) The purpura on her back had circulation. (Parenteral administration of vitamin K for over enlarged and swollen toward evening. 1 week before delivery also can be considered.) Parenterally fed expectant mothers should be administered vitamin K as needed. maternal medication, such as anticoagulants or anticonvulsants, 1,2 III. Therapeutic administration. which results in vitamin K deficiency in the neonate. 1. With suspicion of vitamin K deficiency bleeding: give vitamin In Japan, since 1988, physicians have followed the recommen- – K2 0.5 1.0 mg through the venous circulation as soon as possible dation that oral vitamin K2 should be given three times after blood sampling. (Intramuscular injection should be avoided.) (Table 1).7,8,12 Consequently, the frequency of late VKDB in Japan 2. Severe cases and extremely low birth weight infants: concurrent has significantly decreased from 18 (1978 to 1980) to 1.9 (1999 to use of fresh frozen plasma and factor IX preparation should be 2004) per 100 000 births.12 Oral vitamin K prophylaxis similar to considered. that in Japan is administered in the France, Germany, Denmark and many other European countries, while using vitamin K1 in countries except Japan.1,12 be supplemented with vitamin K thereafter. There were no risk However, oral administration with this guideline has a limitation factors for vitamin K deficiency other than Crohn’s disease, such as in the prevention of early VKDB because this condition often maternal medication (warfarin or antiepileptic drugs), poor oral occurs before the first oral vitamin K administration. In fact, the feeding, total parenteral nutrition or extreme fattiness. We neonate in the present case developed purpura and petechiae investigated the mother’s clotting function with serum obtained before she was given the first vitamin K dose. We conducted a before the cesarean section at 33 weeks’ gestation (Table 3). These small survey in the newborn nurseries of two obstetric clinics and results indicated that the mother’s clotting function was slightly at our university hospital, which follows the Japanese vitamin K lower than the usual values for pregnant women.11 The mother’s recommendation,7,8 and discovered that full-term neonates with- C-reactive protein at 31 and 34 weeks’ gestation was 1.99 and out any complications (n = 148) were given the first vitamin K at 4.35 mg dl − 1, respectively; this suggested the probable presence approximately 18.2 ± 6.0 h after birth.