Neonatal Cholestasis Presenting With Seizures Associated With Vitamin K Deficiency: A Case Report

Abstract

Neonatal Cholestasis is one of the rare yet important causes of Vitamin K deficiency bleeding (VKDB) in infants. VKDB may present as Gastro Intestinal (GI) bleeding and in severe cases as Intracranial hemorrhage. We report a case of a 42 days old, previously healthy, male infant presenting with seizures and GI bleeding. Laboratory investigations revealed direct hyperbilirubinemia and markedly elevated PT/INR. These findings were consistent with neonatal cholestasis and Vitamin K deficiency. Cranial and Abdominal Ultrasonography were normal. The seizure was managed with Vit K and Fresh Frozen Plasma following which his coagulation profile and clinical status improved. Although intracranial hemorrhage could not be confirmed radiologically, this case highlights the importance of considering vitamin K deficiency and underlying hepatobiliary pathology in infants presenting with bleeding manifestations and seizures. Early recognition and treatment are essential to prevent life-threatening complications.

Introduction

Cholestatic jaundice has an incidence of about 1 in every 2,500 to 5,000 term infants. ¹ The most commonly observed causes of cholestasis in infant include BA, genetic and metabolic diseases. ² A major complication of cholestasis is malabsorption of fat-soluble vitamins especially Vitamin K resulting from impaired bile flow.

Cholestasis is a major risk factor for Vitamin K deficiency bleeding (VKDB), however it is infrequently diagnosed when seizures and GI Bleeding occur as the initial presentation. Neurological manifestations like seizures may occur secondary to intracranial hemorrhage, metabolic disturbances, infections or hypoglycemia. ² Yet, Cholestasis is not always considered early in the diagnostic evaluation.

Presentation with gastrointestinal bleeding and seizures as the first manifestation of cholestasis, in the absence of cholestatic features, is rarely reported. We report a case of neonatal cholestasis presenting with seizures and gastrointestinal bleeding, likely related to vitamin K deficiency.

Case Report

A 42 days old, previously healthy, full-term baby boy presented with repeated seizure and passing blood in stool for 1 day. It was reported that prior to the presentation he had been crying during defecation and had vomited several times, though the vomit was neither bilious nor projectile. He had no other significant history.

The infant developed seizure episodes characterized by uprolling of the eyes (upward gaze deviation) accompanied by rigid movements of the upper limbs, suggestive of a tonic seizure. Each episode lasted for a short duration and was associated with decreased responsiveness during the event.

He was born at term via cesarean section due to a prior C-section history, cried immediately at birth, and had an unremarkable prenatal, perinatal, and postnatal course. He had been exclusively breastfeeding. He had been immunized as per national immunization protocol. The history regarding vitamin K prophylaxis at birth could not be confirmed and this represents a limitation, as absence of prophylaxis is a known risk factor for late vitamin K deficiency bleeding.

Examination and Investigations

On examination, his vital signs were appropriate for his age. On physical examination, there was a bulging anterior fontanelle. Liver was palpable 2 cm below right costal margin and spleen was not palpable.

Result for initial investigations carried out are given below in Table 1.

Table 1.

Investigations

Parameter	Result	Reference range	Interpretation
Prothrombin Time (PT)	> 60 seconds	11 – 16 seconds	Markedly prolonged
INR	4.16	0.8 – 1.2	Markedly elevated
Total Bilirubin	6 mg/dL	< 1.2 mg/dL	Elevated
Direct Bilirubin	2.3 mg/dL	< 1 mg/dL	Elevated (cholestasis)
TSH	12.1 µIU/mL	0.4 – 4.2 µIU/mL	Mildly elevated; clinical significance was uncertain
Other routine tests	Within normal limits	—	Normal
Cranial Ultrasound	Normal	—	No hemorrhage detected
Abdominal Ultrasound	Normal	—	No structural abnormality

Investigations for the Serum TORCH profile were performed which is shown in Table 2.

Table 2.

TORCH Panel

TORCH panel	Result	Unit	Reference
Toxoplasma IgG	19.43	IU/mL	<8
Toxoplasma IgM	0.23	RATIO	<0.8
Rubella IgG	9.17	IU/ml	<8
Rubella IgM	0.16	RATIO	<0.8
Cytomegalovirus IgG	37.62	RU/ml	<16
Cytomegalovirus IgM	1	RATIO	<0.8
HSV IgG	72.51	RU/ml	<16
HSV IgM	0.24	RATIO	<0.80

Here, the table shows IgG to be positive in Toxoplasma, Rubella, Cytomegalovirus and Herpes Simplex Virus indicating past infection with TORCH while IgM is equivocal in Cytomegalovirus which is indicative of possible infection however in absence of blood or urine PCR testing a definitive diagnosis could not be established. Serological testing was available, however, molecular diagnostic facilities (PCR) were not accessible at our center.

Treatment

Based on direct hyperbilirubinemia, a diagnosis of neonatal cholestasis of undetermined etiology was considered. Further evaluation (including metabolic, genetic, and endocrine causes) could not be completed due to resource limitations.

The infant received Intravenous vitamin K (1 mg) and Fresh frozen plasma (10 mL/kg). Seizure was managed with Inj. Leviteracetam 20mg/kg IV single dose. Following treatment PT improved to 14 seconds, INR normalized to 1.0 and clinical improvement was noted with cessation of bleeding and seizures. The child was also started on fat-soluble vitamin supplementation (A, D, E, and K).

Follow Up

On follow-up at 2 weeks and 1 month with Liver Function Test and Coagulation profile the infant remained clinically stable with no recurrence of seizures or bleeding, and showed continued improvement with normal investigation reports.

Discussion

We have reported a case of an infant with Cholestasis presenting atypically as seizure and GI bleeding as the initial manifestations. Such presentations may be diagnostically challenging since the classical symptoms of cholestasis like jaundice, pale stools or dark urine may be missed. This case points to the significance of considering hepatobiliary pathology as a probable diagnosis in an infant with seizure taking into account its risk of Vitamin K deficiency Bleeding Disorders (VKBD).

In cholestatic diseases, impaired bile acid secretion results in fat malabsorption and deficiency of fat-soluble vitamins (A, D, E, and K), leading to complications such as rickets, xerophthalmia, and bleeding. This is rationale for fat-soluble vitamin supplementation in neonatal cholestasis. Infants are prone to develop vitamin K deficiency due to poor placental transfer, low vitamin K content in breast milk, and poor intestinal absorption due to malabsorption.^3,4 In the presented case, the normalization of PT/INR following Vitamin K administration is highly suggestive of Vitamin K induced coagulopathy.

Seizures in infants may arise from hemorrhagic, metabolic, or infectious causes, including vitamin K deficiency–related intracranial bleeding. ⁵ However, seizures occurring as a result of hemorrhagic complications of Vitamin K deficiency may remain unrecognized especially in infants with Cholestasis. Although vitamin K deficiency can lead to intracranial hemorrhage, intracranial bleeding was not confirmed in this case, as cranial ultrasonography was normal and advanced imaging (CT/MRI) was not performed. Therefore, attributing seizures definitively to intracranial hemorrhage is not possible, and alternative causes cannot be excluded.

Vitamin K Deficiency Bleeding can manifest as Intracranial bleeding and Gastrointestinal bleeding as seen in our case. The presence of a bulging anterior fontanelle suspecting Intracranial bleeding and fresh blood in stool is suggestive of bleeding manifestations. In a 5-year prospective study by Alzuhairy et al. involving 47 children diagnosed with late vitamin K deficiency, the most common bleeding sites at presentation were skin and GI tract (40%), followed by an intracranial hemorrhage (ICH) (32%). ⁶

Cholestatic hyperbilirubinemia is characterized by serum conjugated bilirubin greater than 1.0 mg/dL (if the total bilirubin is <5.0 mg/dL) or greater than 20% of the total serum bilirubin (if the total serum bilirubin is >5.0 mg/dL). ² The major etiologies are BA (25%–40%); genetic and metabolic diseases, including α1-antitrypsin (A1AT) deficiency (10%–20%), Alagille syndrome (ALGS; 2%–14%), cystic fibrosis (CF); progressive familial intrahepatic cholestasis (PFIC); hypopituitarism (5%); inspissated bile syndrome; idiopathic neonatal hepatitis (INH) or transient neonatal cholestasis (TNC); and PN-associated cholestasis (PNAC) in preterm infants and those with intestinal failure. ²

Infants with cholestasis usually have jaundice and scleral icterus. ² Sometimes, these features may be overlooked and the infant might present in later stages following complications of Vitamin K deficiency. The reported case had presented with GI bleeding and seizure as their first presentation however the investigations showed direct hyperbilirubinemia prompting our diagnosis to Neonatal Cholestasis.

Infectious etiology like CMV is a major cause of neonatal cholestasis. In a comparative study on Serum IgM and PCR for CMV infection conducted by Albanna et al. it was found that PCR is more sensitive (100%) and specific (100%) than CMV IgM ELISA whose sensitivity and specificity being 63.2% and 85% respectively. ⁷ In this case, the results for serum CMV IgM were equivocal. However, due to lack of availability of urine and blood polymerase chain reaction testing, the definitive diagnosis of CMV couldn’t be established.

The etiological evaluation of cholestasis was limited. While infectious causes (e.g., CMV) and biliary atresia were considered, comprehensive evaluation including metabolic, genetic, and endocrine causes could not be performed due to resource constraints.

Abdominal ultrasonography is an essential initial investigation in infants with cholestasis; however, some infants with biliary atresia may have entirely normal hepatobiliary ultrasound findings. ² Cranial ultrasonography is the first-line imaging modality for infants presenting with seizures to evaluate for intracranial hemorrhage (ICH). In a study by Sheikh et al., cranial ultrasound detected ICH in 43.7% of suspected cases, with MRI confirmation in 37.9%, supporting its reliability in identifying and excluding ICH. ⁸ Due to non-invasive nature and convenience of bedside use in infants, cranial ultrasound remains a widely utilized workup in routine clinical practice. In our case, cranial ultrasonography was normal though the presence of bulging anterior fontanelle makes a suspicion for minimal intracranial hemorrhage which could have been missed by imaging.

Cranial ultrasonography is a useful first-line modality for detecting intracranial hemorrhage in infants due to its accessibility and non-invasive nature. However, it may miss small or early hemorrhages. In this case, while the bulging fontanelle raised suspicion, the absence of imaging confirmation limits diagnostic certainty.

In the present case, there were clinical and biochemical findings of cholestasis, but the definite etiology for cholestasis could not be evaluated. Though, infectious etiology like cytomegalovirus was considered, confirmatory tests with blood and urine PCR for cytomegalovirus was not available. Similarly tests for metabolic and genetic investigations could not be done due to limited availability of resources. Hence, this case was managed as cholestasis of undetermined etiology and there was improvement in patient.

Management of infants with cholestasis should focus on ensuring adequate nutrition supporting the normal growth. Malnutrition is commonly seen in these infants as a result of impaired absorption of fats and other essential nutrients. Supplementation with fat-soluble vitamins (A, D, E, and K) is recommended, except in infants who are receiving sufficient parenteral nutrition.

The use of fresh frozen plasma (FFP) in this case was aimed at rapid correction of coagulopathy in the setting of active bleeding. However, vitamin K remains the definitive treatment for vitamin K deficiency, and FFP is generally reserved for significant bleeding or severe coagulopathy.

Limitations

The absence of advanced neuroimaging (CT or MRI) limits the ability to definitively confirm or exclude intracranial hemorrhage as the cause of seizures. Additionally, the etiological evaluation of cholestasis was incomplete, as comprehensive metabolic, genetic, and endocrine investigations could not be performed. Although infectious causes such as cytomegalovirus were considered, confirmatory polymerase chain reaction (PCR) testing was not available. Furthermore, the history of vitamin K prophylaxis at birth could not be confirmed, which limits the ability to fully assess the risk factors for vitamin K deficiency bleeding. These constraints reflect real-world challenges in resource-limited settings, where diagnostic evaluation is often guided by clinical judgment and availability of investigations.

Conclusion

Manifestations of vitamin K deficiency bleeding require prompt evaluation, particularly of the hepatobiliary system, since vitamin K deficiency often results from fat malabsorption. This condition can lead to life-threatening complications, including intracranial hemorrhage and seizures. Seizures should be managed with careful attention to airway, breathing, and circulation. In addition, cholestasis should be managed with a focus on the infant’s nutrition, growth, and vitamin supplementation and treatment of underlying cause to ensure optimal outcomes. The sustained clinical improvement on follow-up further supports the effectiveness of timely intervention.