Perinatal/Neonatal Case Presentation

Early vitamin K deficiency bleeding in a neonate associated with maternal Crohn’s disease


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.


It is well known that neonatal vitamin K deficiency bleeding (VKDB) can be prevented through the administration of vitamin K. Early VKDB is known in association with maternal medications such as antiepileptic drugs,1,2 but is not well known in relation to maternal Crohn’s disease. Early VKDB has not been reported in a neonate born from mother with active Crohn’s disease. On the other hand, in adults, vitamin K deficiency due to Crohn’s disease has been reported in association with osteoporosis,3, 4, 5 but is not well known in association with bleeding in neonates.

Here, we report a case of early neonatal VKDB that was associated with maternal Crohn’s disease. In high-risk neonates such as infant with prematurity or delivered from complicated mother, selective administration of vitamin K parenterally as soon as possible after birth is very important for preventing early VKDB.


A female neonate was born at 37 weeks’ gestation by scheduled cesarean section because of breech presentation. Her mother was 34 years old, gravida 1, para 1. The mother began suffering from Crohn’s disease at age 17 years, and had undergone massive enterectomy (broad range ileum, ascending colon and sigmoid colon) because of ileo-sigmoid colon fistula and stenosis at age 27 years. The mother had received mesalazine for Crohn’s disease and took a low-residue diet, although mild diarrhea had continued since enterectomy. IOIBD (International Organization For the Study of Inflammatory Bowel Disease) assessment score6 was 4 at age 17 years, 0 at the mother’s first pregnancy and 1 at present pregnancy. The mother’s first delivery at age 31 was normal. In present pregnancy, she had received ritodrine because of threatened premature delivery since 29 weeks’ gestation. The present neonate’s birth weight was 2778 g, with Apgar scores of 8 and 9 at 1 and 5 min, respectively. The neonate was brought to the newborn nursery.

A common practice of neonatal vitamin K prophylaxis in Japan is to give oral vitamin K three times (first: after birth by establishing oral feeding; second: on discharge from maternity hospital; third: one month of age) (Table 1).8 There were no particular descriptions on the record of nurse until next morning, but the neonate could not take oral vitamin K syrup because of feeling of sickness.

Table 1 Recommendations for prophylactic administration of vitamin K for newborn (2011 modified version)7,8 by the Japan Pediatric Society

Broad purpura and some petechiae on the neonate’s back were discovered at the first clinical examination by a pediatrician at about 24 h after birth (Figure 1a). The neonate cried vigorously, but her skin was slightly pale. Her blood pressure was 69/36 (mean 46) mm Hg, and her heart rate was 170 beats per minute. Her blood examination done before blood transfusion and vitamin K infusion showed severe anemia and disorder of clotting function (Table 2a). Biochemical examination revealed no abnormalities (Table 2b).

Figure 1

(a) Broad purpura on neonate’s back discovered at approximately 24 h after birth. (b) The purpura on her back had enlarged and swollen toward evening.

Table 2a Infant’s laboratory data (timeline)
Table 2b Infant’s coagulation status (on admission)

The neonate received an infusion of vitamin K (2 mg) and 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 improvements at 24 h after initiation of treatment in the neonatal intensive care unit (Table 2a). Toward evening, the purpura on her back had enlarged and swollen (Figure 1b). She started enteral feedings on day 3, received phototherapy from days 3 to 10 with total bilirubin 17.3 and 21.0 mg dl−1, respectively, and was discharged on day 18. Head and abdominal computed tomography performed on day 11 and head magnetic resonance imaging performed on day 15 revealed no intracranial hemorrhage, ischemic changes in the brain or abdominal hemorrhage. Also, absence of clinical presentations such as irritability, convulsion, bloody stool and abdominal distension, denied the possibility of intracranial, interperitoneal and gastrointestinal hemorrhages.

Close investigation of the blood clotting function and fibrinolytic function were conducted (Table 2b). Elevated PIVKA (protein induced by vitamin K absence or antagonist)-II1,9,10 over 8000 mAU ml−1, decreasing PIVKA-II with vitamin K administration, and low vitamin K-dependent clotting and fibrinolytic factors indicated a status of vitamin K deficiency. The neonate was given vitamin K intravenously on day 4 and orally once per week up to 2 months of age from then on and she did not need to be supplemented with vitamin K thereafter. There were no risk factors for vitamin K deficiency other than Crohn’s disease, such as maternal medication (warfarin or antiepileptic drugs), poor oral feeding, total parenteral nutrition or extreme fattiness. We investigated the mother’s clotting function with serum obtained before the cesarean section at 33 weeks’ gestation (Table 3). These results indicated that the mother’s clotting function was slightly lower than the usual values for pregnant women.11 The mother’s C-reactive protein at 31 and 34 weeks’ gestation was 1.99 and 4.35 mg dl−1, respectively; this suggested the probable presence of inflammation or activation of her Crohn’s disease. The hemoglobin of the cord blood at birth was 13.7 g dl−1, and the mother’s hemoglobin F was negative, which indicates that there was no fetomaternal transfusion. We possibly thought that early VKDB was due to severe maternal vitamin K deficiency secondary to vitamin K malabsorption from Crohn’s disease.

Table 3 Mother’s laboratory data (33 weeks gestation)


VKDB in neonates is classified into three types: early, classical and late.1,2 Classical VKDB develops mainly as gastrointestinal hemorrhage from day 2 to 7, and late VKDB develops as mainly intracranial hemorrhage from 2 weeks to 6 months. The underlying reasons for these hemorrhages are mostly maternal nutritional and cholestatic conditions. Compared with classical and late VKDB, early neonatal VKDB causes mainly internal hemorrhage within 24 h after birth. The etiology of early VKDB is maternal medication, such as anticoagulants or anticonvulsants, which results in vitamin K deficiency in the neonate.1,2

In Japan, since 1988, physicians have followed the recommendation that oral vitamin K2 should be given three times (Table 1).7,8,12 Consequently, the frequency of late VKDB in Japan has significantly decreased from 18 (1978 to 1980) to 1.9 (1999 to 2004) per 100 000 births.12 Oral vitamin K prophylaxis similar to 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

However, oral administration with this guideline has a limitation in the prevention of early VKDB because this condition often occurs before the first oral vitamin K administration. In fact, the neonate in the present case developed purpura and petechiae before she was given the first vitamin K dose. We conducted a small survey in the newborn nurseries of two obstetric clinics and at our university hospital, which follows the Japanese vitamin K recommendation,7,8 and discovered that full-term neonates without any complications (n=148) were given the first vitamin K at approximately 18.2±6.0 h after birth. It would be better to describe clear time restriction until administering vitamin K orally in the Japanese guideline.

Although there have been some descriptions of neonates with complications or risk factors for early VKDB,1 there are no concrete guidelines for determining which neonates require prompt prophylaxis. There are some methods to note vitamin K deficiency mother and neonate who need vitamin K administration: (1) screening the mother’s clotting function and administering vitamin K to the neonate immediately after birth parenterally, (2) screening the mother’s clotting function and administering vitamin K to the mother at least 1 week before delivery,13 (3) checking the neonate’s PIVKA-II level after birth and administering vitamin K to the neonate. Screening the mother’s clotting function can be misleading, in that some cases have occurred in which the neonate experienced VKDB despite the mother’s normal prenatal clotting function.2,14 Investigation of the neonate’s PIVKA-II level is ideal,15,16 but requires substantial time to obtain the laboratory results.

We think that the mother’s more severe vitamin K deficiency raised by disease activity and diet possibly led the present neonate to VKDB in contrast to the fact that the mother’s first child did not develop VKDB. Vitamin K deficiency with inflammatory bowel disease is well known in internal medicine and orthopedics because vitamin K and D deficiency lead to osteoporosis.3,4,14 The degree of vitamin K and D deficiency has been reported to be well correlated with inflammatory bowel disease.3 It has been reported that 46% patients with Crohn’s disease have vitamin K deficiency.5 In the present case, the mother’s Crohn’s disease was possibly more active and that her nutrition could have been poorer at delivery of this neonate than at the delivery of her first child, because her C-reactive protein was slightly higher (2.41 vs less than 1 mg dl−1) and her serum albumin was slightly lower (2.6 to 2.9 vs 3.1 to 3.3 mg dl−1).17,18 In addition, her diarrhea was more severe and she could not take enough meal because of gastric distress and abdominal fullness at the current delivery. On the other hand, in order for vitamin K to be absorbed in the gastric tract, it needs to be ingested simultaneously with bile acid and fat. The mother’s vitamin K deficiency at her current hospital admission was considered to be influenced by her fat-restricted diet for Crohn’s disease. We regarded that the mother’s disease activity and diet at the time of hospitalization have led to her vitamin K malabsorption and vitamin K deficiency. As fetal vitamin K is supplied from the mother, it is possible that maternal vitamin K deficiency led to fetal vitamin K deficiency.14,19

From a practical standpoint, high-risk neonates are selected for vitamin K prophylaxis preliminarily according to the mother’s medical information. In cases of expectant mothers with inadequate oral intake, total parenteral hyperalimentation, inflammatory bowel disease, history of enterectomy or prolonged coagulation time, it is encouraged to investigate both the mother’s and neonate’s vitamin K status and to actively administer vitamin K to both as needed.


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Correspondence to A Ohishi.

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Ohishi, A., Nakashima, S., Ogata, T. et al. Early vitamin K deficiency bleeding in a neonate associated with maternal Crohn’s disease. J Perinatol 34, 636–639 (2014).

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