Life-Threatening Intracranial Bleeding in a Newborn with Congenital Cytomegalovirus Infection: Late-Onset Neonatal Hemorrhagic Disease

The authors present a case of a 36-day-old infant with intracranial and intramuscular hemorrhage due to vitamin K deficiency bleeding, who received intramuscular vitamin K prophylaxis at birth. In this case, laboratory tests showed anemia, liver dysfunction with cholestasis, and coagulopathy, consistent with vitamin K deficiency abnormality. Serological analyses showed that cytomegalovirus immunoglobulin (Ig)M and IgG avidity were both positive. The infant was treated successfully with intravenous ganciclovir and blood products. This case suggests that it is imperative to meticulously investigate the etiology in neonates with late-onset hemorrhagic disease of the newborn. Cholestatic liver disease caused by congenital cytomegalovirus infection should be in mind in term infants who presented with late-onset hemorrhagic disease.     

Intra-cranial hemorrhage in infants due to vitamin K deficiency - report of 2 cases

OBJECTIVE: Drive attention to the late form of the hemorrhagic disease of the newborn, secondary to vitamin K deficiency, as a cause of intracranial hemorrhage in young infants.METHODS: The authors describe and analyze two cases of late hemorrhagic disease of the newborn, secondary to vitamin K deficiency, producing intracranially hemorrhage during the second month of age. The most important publications on this subject are reviewed.RESULTS: Both infants had not received prophylaxis with vitamin K at birth. They were both being fed exclusively on breast milk. They developed intracranial hemorrhage, and the clotting defect was rapidly corrected with intramuscular vitamin K. At 3 and 4 years of age, one of them has showed normal psychomotor development, and the other has showed moderate developmental delay with microcephaly.CONCLUSION: Late hemorrhagic disease of the newborn must be considered in young infants, between 2 and 12 weeks of age, with intracranial hemorrhage, especially those fed exclusively on breast milk who did not receive vitamin K at birth. It may produce neurodevelopmental delay. The clotting defect is rapidly corrected with intramuscular vitamin K. This condition is preventable. The prophylaxis is recommended with 1 mg of intramuscular vitamin K to all newborns, at birth, even without risk factors.     

Cerebral hemorrhage associated with vitamin K deficiency in congenital tuberculosis treated with isoniazid and rifampin

We report a male infant with congenital tuberculosis who developed cerebral hemorrhage associated with vitamin K deficiency during treatment with isoniazid and rifampin. Despite an absence of risk factors for vitamin K deficiency, the severe hemorrhagic disorder occurred at 4 months of age. We speculate that vitamin K deficiency in the present case may have resulted from a synergic effect of antituberculosis agents and immaturity of vitamin K metabolism and/or its absorption.     

Late onset haemorrhagic disease in premature infants who received intravenous vitamin K1

Abstract: The clinical details are reported of two premature infants who developed late onset haemorrhagic disease after receiving their initial doses of vitamin K₁ prophylaxis intravenously. Both reported infants had received two doses of intravenous vitamin K₁, 0.1 mg, in the 1st week of life, and a further oral dose, 1.0 mg, at 4 weeks. Bleeding due to vitamin K deficiency occurred on days 74 and 84, respectively. Vitamin K deficiency bleeding is rare in low birthweight infants, probably because it has been routine practice to give such infants intramuscular vitamin K₁. One of the reported infants had cytomegalovirus hepatitis, the other did not have liver disease. These findings could be explained if intramuscular vitamin K₁ were to have a longer duration of effect than intravenous vitamin K₁. This may be because intramuscular vitamin K₁ acts as a depot preparation. The findings suggest that intravenous vitamin K₁ is less effective than intramuscular for long-term prophylaxis against late onset haemorrhagic disease. Intravenous vitamin K₁ should not be used for long-term prophylaxis in the prevention of late onset haemorrhagic disease.     

Alpha1-antitrypsin deficiency with fatal intracranial hemorrhage in a newborn.

A 4-week-old boy had a fatal intracranial hemorrhage resulting from vitamin K deficiency. The infant had received no vitamin K prophylaxis and was exclusively breastfed. At autopsy, examination of the liver showed cholestasis and fibrosis. DNA was isolated from a blood spot on a Gutherie sample card obtained from the infant for routine metabolic screening. This DNA was used for alpha1-antitrypsin genotyping studies. Genotyping studies identified homozygosity for the point mutation 9989G-->A, confirming a diagnosis of alpha1-antitrypsin deficiency (ZZ phenotype), and resulted in appropriate screening of siblings born after this child's death. Alpha1-antitrypsin deficiency should be considered in the differential diagnosis of infants with late hemorrhagic disease of the newborn. Use of blood from the metabolic screening card as a source of DNA allowed confirmation of this diagnosis after the infant's death.     

Vitamin K status of lactating mothers and their infants

Vitamin K deficiency remains a world-wide problem in the newborn. Vitamin K traverses the placenta from mother to infant very poorly and is present only in very low concentrations in human milk. Thus, it is not surprising that the newborn infant has undetectable vitamin K serum levels with abnormal amounts of the coagulation proteins and undercarboxylated prothrombin. Hemorrhagic disease of the newborn, secondary to vitamin K deficiency, remains largely a disease of breastfed infants. Lactating mothers easily achieve the recommended dietary allowance for vitamin K (1 microg kg(-1) d(-1)) and the breast milk concentration is readily increased by increasing maternal vitamin K intake. Breastfed infants do not receive the recommended vitamin K intake via human milk. To prevent vitamin K deficiency in the newborn, intramuscular or oral vitamin K prophylaxis is necessary.     

Vitamin K status of lactating mothers and their infants

Vitamin K deficiency remains a world-wide problem in the newborn. Vitamin K traverses the placenta from mother to infant very poorly and is present only in very low concentrations in human milk. Thus, it is not surprising that the newborn infant has undetectable vitamin K serum levels with abnormal amounts of the coagulation proteins and undercarboxylated prothrombin. Hemorrhagic disease of the newborn, secondary to vitamin K deficiency, remains largely a disease of breastfed infants. Lactating mothers easily achieve the recommended dietary allowance for vitamin K (1 μg kg⁻¹ d⁻¹) and the breast milk concentration is readily increased by increasing maternal vitamin K intake. Breastfed infants do not receive the recommended vitamin K intake via human milk. To prevent vitamin K deficiency in the newborn, intramuscular or oral vitamin K prophylaxis is necessary.     

Vitamin K deficiency in newborns: a case report in alpha-1-antitrypsin deficiency and a review of factors predisposing to hemorrhage

A 4-week-old, breast-fed female infant appeared healthy until signs and symptoms of CNS deterioration suddenly occurred. At presentation the infant was found to have a left-sided parietal intracerebral hematoma, markedly prolonged prothrombin time, and partial thromboplastin time, normal platelet count, and jaundice with a total and direct serum bilirubin level of 5.4 mg/dL and 2.6 mg/dL, respectively. Vitamin K1 and fresh frozen plasma returned the prothrombin time and partial thromboplastin time to normal values within 18 hours, suggesting that the infant had severe vitamin K deficiency complicated by intracerebral hemorrhage. Evaluation of the infant's direct hyperbilirubinemia led to the diagnosis of homozygous (pi-type ZZ [PiZZ] ) alpha-1-antitrypsin deficiency. The clinical circumstances predisposing to vitamin K deficiency in newborns and infants are discussed. Based on our observations in this case, we suggest that cholestatic liver disease should be suspected when unexplained vitamin K deficiency occurs in early infancy. The role of vitamin K in hemostasis and the laboratory diagnosis of vitamin K deficiency are discussed as they apply to the evaluation of hemorrhage in newborns and infants.     

Hemorrhagic disease of the newborn despite vitamin K prophylaxis at birth

Late hemorrhagic disease of the newborn (HDN) presents 0.5-6 months after birth with mucocutaneous and intracranial bleeding. We describe here two cases of late HDN in infants who received vitamin K. The first case is a previously healthy breastfed male who received one dose of oral vitamin K at birth and developed an intracranial hemorrhage 5 weeks later. He was treated with intravenous vitamin K and recombinant factor VIIa prior to emergent craniectomy. An unrelated infant presented at 5 months of age with diarrhea and easy bruising despite IM vitamin K at birth. These cases illustrate the morbidity associated with late HDN.     

Hemothorax due to hemorrhagic disease of the newborn

A three day old male, term infant with hemothorax due to hemorrhagic disease of the newborn was treated successfully with vitamin K and thoracocentesis. Exclusive breast feeding and absence of vitamin K prophylaxis were important diagnostic clues, although hemothorax as a sole manifestation of hemorrhagic disease of the newborn is rare. This case highlighted the good prognosis of an uncommon complication when prompt diagnosis and appropriate treatment are instituted. The importance of vitamin K prophylaxis to all newborns is emphasized.     

Mother-infant prothrombin precursor status at birth

Previous work from this laboratory has suggested there is a risk of hemorrhagic disease of the newborn (HDNB) in approximately one-third of term neonates, presumably as a result of vitamin K deficiency. Using the same assay for PIVKA (protein induced by vitamin K absence, prothrombin precursor), we studied 46 normal mother-infant pairs at term to investigate the relationship between neonatal and maternal PIVKA status. PIVKA was found in 13 infants (28%) and in seven mothers (15%). Maternal PIVKA status correlated with infant status (p less than 0.03). These data suggest that fetal vitamin K deficiency and risk of HDNB may be a consequence of maternal deficiency of the vitamin.     

Back to the basics: hemorrhage after vaccination: a case report

A 50-day-old girl with swelling and ecchymosis of right hand dorsum after DTP vaccination on ipsilateral deltoid area was referred to the pediatric infectious disease outpatient unit with a presumed diagnosis of gangrenous cellulites. Physical examination and laboratory evaluation revealed intramuscular bleeding as a result of vitamin K deficiency. We would like to emphasize the importance of both vitamin K prophylaxis in the newborn to prevent hemorrhagic disease of the newborn and of the education of persons administering vaccines about this very basic aspect of pediatrics for early recognition.     

Yellow is pale: The complications and challenges of late diagnosis of extrahepatic biliary atresia

Extrahepatic biliary atresia classically presents in the neonatal period with jaundice and pale stools. The lack of bile pigment in stool can be unrecognised, delaying diagnosis and surgical treatment. Vitamin K is given at birth to reduce the risk of haemorrhagic disease of the newborn, but this may be inadequate to prevent the development of coagulopathy secondary to fat soluble vitamin malabsorption. We present the case of a 3 month old infant who presented with an intracerebral haemorrhage and coagulopathy thought to be secondary to fat malabsorption resulting from delayed diagnosis of extrahepatic biliary atresia. This was despite the perinatal administration of intramuscular vitamin K. His parents did not recognise the stool pallor as being abnormal. This case illustrates the importance of educating parents on the significance of pale stools, and also the risk of coagulopathy in extrahepatic biliary atresia despite perinatal intramuscular vitamin K.     

Late hemorragic disease of the newborn: case report

OBJECTIVE: In this study the authors review this subject, and call attention for the late hemorrhagic disease of the newborn, due to the severity and higher risk of mortality and neurological sequelae.METHODS: In this article, four cases of children, age raging from 12 to 21 days, with late hemorrhagic disease associated with vitamin K deficiency were reported. RESULTS: All newborns had multiple hemorrhagic manifestations of the disease. The systems more affected were digestive tract, urinary system, umbilical cord, respiratory system and nervous system.CONCLUSION: Three forms of hemorrhagic disease of newborn have been related with vitamin K deficiency. However, late vitamin K deficiency bleeding is not common and may not be diagnosed by pediatrician. This form of disease can be prevented by vitamin K prophylaxis administration after birth.     

Acute anemia caused by hemoperitoneum disclosing hemorrhagic disease of the newborn

A neonate who was not given prophylactic vitamin K injection was admitted with acute anemia and hemoperitoneum. The evolution was favorable with medical treatment only. Vitamin K deficiency appears to be the main cause of this hemorrhagic disease. There is a controversy on this subject, as hepatic deficiency seems to be involved in certain cases.     

Late vitamin K deficiency bleeding in an infant with choledochal cyst

Infantile choledochal cyst (CC) usually presents as jaundice, vomiting, acholic stools, and hepatomegaly, and it can resemble biliary atresia. Although bleeding tendency is a rare clinical presentation of CC, it can be the first symptom, especially in infants less than 12 months of age. We report a case of a two-month-old infant with choledochal cyst presenting as late vitamin K deficiency bleeding (VKDB). Early recognition of diseases predisposing to VKDB and immediate investigation and treatment of warning bleeds help to prevent the worst consequences. Late VKDB is often the presenting feature of a serious underlying disease that may be recognized early. The sudden onset of bleeding tendency in infants with congenital liver or biliary tract disease may suggest not only biliary atresia but also, although extremely rare, CC. Early vitamin K administration leads to rapid normalization of hemostatic parameters, which enables major liver surgery.     

Vitamin B12 deficiency in a breast fed infant.

We report the case of a 5 month old breast fed infant who presented with a history of vomiting, pallor, and failure to thrive. Investigations showed severe nutritional vitamin B12 deficiency with a megaloblastic pancytopenia. This deficiency was due to low vitamin B12 concentrations in the maternal breast milk, and subsequent investigations showed maternal pernicious anaemia. Treatment of the infant with vitamin B12 resulted in a rapid clinical and haematological improvement. This case represents an unusual presentation of pernicious anaemia.     

Prevention of vitamin K deficiency bleeding with oral mixed micellar phylloquinone: results of a 6-year surveillance in Switzerland

In 1995, a new form of vitamin K prophylaxis with two oral doses of 2 mg mixed micellar phylloquinone (Konakion MM) on the 1st and 4th day of life was introduced in Switzerland. It was hoped that this new galenic preparation of phylloquinone would protect infants with insufficient or absent bile acid excretion from late vitamin K deficiency bleeding (VKDB). Subsequently, the occurrence of VKDB was monitored prospectively between July 1, 1995 and June 30, 2001 with the help of the Swiss Paediatric Surveillance Unit (SPSU). Over a period of 6 years (475,000 deliveries), there were no cases of early (<24 h of age), one case of classical (2–7 days of life), and 18 cases of late (1–12 weeks) VKDB fulfilling standard case definitions. In 13/18 patients with late VKDB there was pre-existing liver disease and in 4/18 patients, parents had refused prophylaxis. The incidence of late VKDB for infants with completed Konakion MM prophylaxis was 2.31/100,000 (95% CI: 1.16–4.14) and for the entire population 3.79/100,000 (95% CI: 2.24–5.98). There was only one case of late VKDB after complete prophylaxis in an infant without underlying liver disease. Conclusion: two oral doses of 2 mg of a mixed micellar vitamin K preparation failed to abolish VKDB. The recommendations for vitamin K prophylaxis in Switzerland have therefore been changed to include a third dose at 4 weeks of age. Starting on January 1, 2004, the incidence of vitamin K deficiency bleeding will again be monitored prospectively by the Swiss Paediatric Surveillance Unit.Abbreviations CI confidence interval - SPSU Swiss Paediatric Surveillance Unit - VKDB vitamin K deficiency bleeding     

Developmental regression as an early manifestation of vitamin B12 deficiency

Loss of previously attained developmental milestones in an infant is often associated with central nervous system tumor, neuromuscular disease, or an inborn metabolic error. An infant with developmental regression and involuntary movements who was found to be vitamin B12 deficient on the basis of unrecognized maternal vitamin B12 deficiency is described. The infant had a dramatic neurologic recovery after receiving vitamin B12. The case and a review of similar cases is presented.     

Intracranial Hemorrhage in a Previously Healthy Infant

We describe a 5-week-old infant who presented in cardiac arrest and was later found to have intracranial hemorrhage due to late vitamin K deficiency bleeding. The infant had not received vitamin K prophylaxis following a home birth. Because of worsening direct hyperbilirubinemia and transaminitis, she was subsequently found to have biliary atresia. This case allows us to review the differential diagnosis of intracranial hemorrhage in infants and underscores the importance of considering whether infants presenting with any source of bleeding had received vitamin K prophylaxis. As refusal of vitamin K prophylaxis has increased in the United States over the last decade, pediatricians now play an increasingly vital role in promoting strong adherence to universal prophylaxis for newborns in their practice.