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Brief Reports Indian Pediatrics 2003; 40:243-248 |
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Intracranial Hemorrheage in Late Hemorrhagic Disease of the Newborn |
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Hemorrhagic disease of the newborn (HDN) is one of the most common causes of acquired haemostatic disorder in early infancy(1). It is categorized as early, classical or late depending on the time of onset. Late HDN usually occurs between 2-8 weeks but can occur anytime in the first year. Incidence of Late-HDN in the eastern world is 25-80/100,000 births which is higher than that in the western world (4-25/100,000 births)(2). Newborns have only 20-50% of adult coagulation activity. Lack of vitamin K administration at birth, exclusive breast feeding, chronic diarrhea and prolonged use of antibiotics make them more prone to vitamin K deficiency bleeding(1). Almost 2/3rd of the babies with late HDN present with serious intracranial bleeds leading to high morbidity and subsequent mortality. Routine vitamin K prophylaxis at birth brought down the incidence of late HDN from 7/100,000 to 1.1/100,000 live births in Netherlands(3). There is no standard recommendation to routinely administer vitamin K to all neonates in developing countries where exclusive breast-feeding is promoted. While the exact incidence of HDN is possible only in an elaborate population based study, the morbidity and mortality can be indirectly gauged from referral centers considering the alarming nature of clinical manifestations necessitating admission in most cases. There are few case reports available on this aspect from the region. The present hospital based study was carried out to assess the clinical profile, risk factors and outcome of patients with late HDN. Subjects and Methods All infants above the age of 7 days admitted in pediatric ward of Dayanand Medical College and Hospital, Ludhiana (a 1200 bedded referral institution catering to adjoining districts of Punjab), with vitamin K deficiency bleeding from Jan 1998 to Dec 2001 were evaluated. A neonate fulfilling the following criteria(4,5) was defined as having late HDN: (i) bleeding in an infant after 7 days of life, (ii) no thrombocytopenia (platelet counts >1.5 lac/cumm), (iii) normal peripheral blood smear examination, (iv) prolonged prothrombin time index (PTI) (INR >1.8), and rapid correction of PTI or cessation of bleeding after vitamin K administration. Protein induced in vitamin K absence (PIVKA) and serum fibrinogen levels were not available and were not considered essential in the case definition. Vitamin K 2 mg intravenous was given to all the patients and investigations were repeated after 24 hours. Infants fulfilling the criteria were evaluated with regard to following aspects: place of birth, vitamin K administration, feeding history, history of prolonged diarrhea, use of antibiotics, clinical signs, investigations with particular reference to CT scan head where indicated, and outcome. Infants with presence of icterus, significant hepatomegaly and/or derangement of liver enzymes and failure of PT to return to normal after a single dose of vitamin K were considered to have liver disease and were excluded. Results Forty two infants fulfilled the criteria of late HDN; 37(86%) were males and 5 females. Majority of the babies i.e. 32 (76%) were in the age group 1-3 months, and out of these 28 were between 4-8 weeks. There were 6 babies less than 4 weeks of age and 4 each were between 8-12 weeks and 12-16 weeks respectively. All babies were born at term. Thirty eight babies were born by normal vaginal delivery and four by cesarean section, indication being nonprogression of labour. The place of delivery was home in 20 (47%) while 22 were born in private nursing homes. Vitamin K was not given to any of the infants at birth. All the babies were on exclusive breastfeeding. Two babies had prolonged diarrhea (duration >14 days). One baby had received antibiotics for a week just prior to bleeding. The clinical manifestations are shown in Table I.
Majority of the infants (76.1%) presented with neurological features in
the form of excessive cry, lethargy, bulging anterior fontanel and/or
convulsions. Of these 2 cases had minor skin bleeds which were not noted
by the parents. Only 35.7% patients had visible bleeding as the
presenting feature; of these 6 cases also had clinical signs of
neurological involvement. Nearly 2/3rd of the patients had pallor on
examination. Table I__ Clinical Profile of Patients with Late-HDN (n = 42)
* 6 patients also had an evidence of ICH. ** 24 patients presented with isolated ICH. + In combination of various features. Hemoglobin levels of <5g/dL, 5-10g/dL and >10g/dL were seen in 12%, 76% and 12% babies respectively. Mean platelet count was 3.5 lac/cumm(ranging from 1.8 to 8.27 lac/cumm). PTI was significantly prolonged in all cases; in 58% no clot was detected over 120 sec. PTI returned to normal after vitamin K therapy in all the cases. Seventeen patients were given packed RBCs because of severe anemia. No patient was given fresh frozen plasma. Although CT scan head was clinically indicated in 30 (72%) cases, it could be done in 28. All the scans revealed large intracranial hemorrhage. The majority of the patients showed hemorrhage at more than one site (75%). The hemorrhage was intracerebral in 67% cases followed by subdural (SDH) and subarachnoid (SAH) in 57% and 46% cases respectively as shown in Table II. Table II__Types of intracranial hemorrhages in the patients of Late-HDN (n = 28)
* Commonest combination.
All patients with intracranial bleed were managed in the pediatric intensive care unit. Seven infants needed ventilatory support, out of whom 5 patients were discharged and 2 patients left against medical advice. Two were operated for large subdural hematoma, and were later discharged. Three patients (5%) expired. One of these had evidence of fresh bleed in the tentorium cerebelli with herniation and died within 24 hours of admission. Other had massive intra-ventricular, subdural and subarachnoid bleed with hypoxic changes. Discussion The low concentration of vitamin K in human breast milk and the predisposition to vitamin K deficiency bleeding following exclusive breast feeding is emerging as a matter of concern especially in developing countries where exclusive breast feeding is vigorously advocated to promote optimal health in the infant. In developed countries HDN is now a rare life threatening disease due to the widespread use of effective prophylaxis with vitamin K at birth(1,6). Most reports of late HDN have been in babies born at home(7,8). In the present study however, 53% deliveries were conducted in nursing homes, where the practice of routine vitamin K administration does not exist. An incidence of 2.2% of the total admissions in infants in the pediatrics department excluding early neo-natal life indicates that late-HDN is not an insignificant problem. Since visible hemorr-hage is an alarming manifestation and clinical features of ICH are unlikely to be ignored by the parents, it may seem that the incidence of hospitalization reflects the actual incidence. Two thirds of babies (66.6%) were in the age group of 4-8 weeks. Vitamin K (menaquinones) is absent in newborn liver, but gradually accumulates after birth. This, together with low concentration of vitamin K in human breast milk (1.5 µg/dL)as compared to 6 µg/dL in cow’s milk) may explain the peak frequency of late HDN at this age(1,9). In the present study ICH was the presenting feature in 71% of cases. The remaining had skin hemorrhage and rectal bleeding. Subdural hemorrhage has been the commonest type of ICH reported, followed by subarachnoid hemorrhage(8). In other studies ICH was found to be subdural, subarachnoid, intracerebral in 100, 80, 30% respectively(10). In the present study, most of the patients i.e., 75% had hemorrhages at multiple sites, which is not frequently described. The common manifestations of late HDN reported are evidence of intracranial hemorr-hage, deep ecchymosis, bleeding from GI tract and/or bleeding from mucus membrane, skin punctures or surgical incisions(11,12). ICH has been seen in 50-80% of affected babies in various studies and causes death or severe handicap in 50-70% of these babies(2). An overall mortality of 14% to 50%(2,11,13) has been reported. The low mortality of 5% in this study may be because most patients with ICH were managed in pediatric intensive care unit. Almost all of the infants of late HDN in studies received breast feeding and did not receive vitamin K prophylaxis at birth(10,12,14). In the present study also, all the babies were on breast milk exclusively and had not received vitamin K at birth. One infant had diarrhea. Gastroenteritis causing vitamin K deficiency has been reported(15). Late HDN may mimic findings of nonaccidental head injury and may lead to mistaken diagnosis of child abuse(16). Occasionally, baby may present with respiratory distress due to thymic hemorrhage or hemothorax(17,18). Babies may rarely present with secondary hydrocephalus(19). In the present study vitamin K was not administered at birth in any case. A few case reports are available of late HDN in babies even after receiving injection vitamin K(20). An epidemiological study from Germany by von Kries(21) showed a failure rate (occurrence of late HDN) of 0.25 per 100,000 infants after IM administration compared with 1.4 per 10,000 in countries where oral vitamin K is given. There are reports of preterm babies who had received intravenous injections of vitamin K at birth presenting with late HDN(22); this is because IM route has longer duration of effect than IV as a result of depot preparations. Intravenous route is less effective for long-term prophylaxis for preventing HDN(22). Oral route is economical, effective, practical and more acceptable to the parent(23). But many studies have shown that oral Vitamin K is less effective in preventing late HDN(4,6). It may be difficult to organize vitamin K injection to all newborn babies especially those born at home, which form the bulk of total deliveries in a country like India. However, it is clear that concept of vitamin K administration at birth is not familiar to health care providers; more than 50% of babies admitted in this series were delivered at nursing homes and yet did not receive vitamin K. Although there was initial reservation, it has been shown now that vitamin K administration does not increase the risk of leukemia(1,24,25). The occurrence of a significant hemorrhage like ICH leading to death or life-long neurological deficit is enough justification for routine administration of vitamin K at birth. Contributors: PA was the chief investigator and was responsible for identification of cases and data collection. She will act as guaranter for this article. DS was responsible for analysis and interpretation of data and guided preparation of the manuscript. HS and BKJ participated in data collection and conducted literature search and were responsible for critical review of the patients. Funding: None. Competing interests: None stated.
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