What tests should be ordered for a newborn with low birth weight, microcephaly, hepatosplenomegaly, and a 'blueberry muffin' rash to investigate a possible intrauterine infection?

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Diagnostic Testing for Suspected Congenital TORCH Infection

Order TORCH serologic testing (IgM and IgG antibodies for Toxoplasmosis, Rubella, Cytomegalovirus, and Herpes simplex virus) along with CMV PCR from urine or saliva, as this clinical presentation of low birth weight, microcephaly, hepatosplenomegaly, and blueberry muffin rash is classic for congenital intrauterine infection, with CMV being the most common cause. 1, 2

Primary Diagnostic Approach

Initial Serologic Testing

  • Test for IgM and IgG antibodies by ELISA or chemiluminescence immunoassay to distinguish acute from past infection, with IgM positive indicating acute/recent infection and IgG positive alone indicating past infection 2
  • The collective TORCH panel should focus on individual tests ordered according to clinical presentation rather than blanket testing, as the collective panel has low diagnostic yield 3

CMV-Specific Testing (Highest Priority)

  • CMV PCR from urine or saliva is essential, as CMV is the most frequent non-genetic cause of this constellation of findings, specifically associated with microcephaly, hepatosplenomegaly, and the blueberry muffin rash representing dermal erythropoiesis 1, 4
  • CMV accounts for 19.5% of symptomatic newborns presenting with microcephaly and is strongly associated with intracranial calcifications and white matter abnormalities 1
  • Skin biopsy of the blueberry muffin lesions will show extramedullary erythropoiesis, confirming the pathophysiology 4

Additional Diagnostic Studies

Neuroimaging

  • Obtain cranial ultrasound or brain MRI to evaluate for intracranial calcifications, white matter abnormalities, and polymicrogyria, which are characteristic of congenital CMV infection 1, 4
  • Bilateral periventricular calcifications and hyperechogenicity are particularly suggestive of CMV 4

Laboratory Evaluation

  • Complete blood count to assess for thrombocytopenia, which commonly accompanies congenital infections and contributes to the purpuric rash 1, 4
  • Liver function tests including direct bilirubin and transaminases, as hepatosplenomegaly with cholestasis is common 4
  • Coagulation studies to evaluate for coagulopathy associated with hepatic dysfunction 4

Other TORCH Components to Consider

  • Rubella serology: While rubella classically causes the blueberry muffin appearance, it is now rare due to vaccination but should still be tested given the clinical presentation includes microcephaly, hepatosplenomegaly, and purpuric skin lesions 1, 5
  • Toxoplasmosis serology: Can cause similar intracranial calcifications and hepatosplenomegaly, though less commonly presents with the blueberry muffin rash 6, 5
  • HSV PCR: Consider if there are vesicular lesions or maternal history of genital herpes 2, 5
  • Syphilis testing (RPR/VDRL): Should be included as part of the "Other" category in TORCH, particularly if maternal prenatal testing was inadequate 3, 5

Critical Pitfalls to Avoid

  • Do not delay CMV-specific testing while waiting for general TORCH panel results, as early antiviral treatment with ganciclovir or valganciclovir may be indicated for symptomatic congenital CMV infection 2
  • Do not assume negative maternal prenatal serology excludes congenital infection, as maternal infection may have been subclinical or occurred after prenatal testing 4
  • Consider non-infectious causes in the differential diagnosis of blueberry muffin baby, including hematologic malignancies, metabolic diseases (such as Gaucher disease), and vascular disorders, though the combination with microcephaly and hepatosplenomegaly strongly suggests TORCH infection 4, 7

Placental Testing

  • Request placental pathology if available, as histopathologic examination can reveal features suggestive of CMV or other congenital infections 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

TORCH Infections and Pregnancy Outcomes

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Congenital infections in Hong Kong: an overview of TORCH.

Hong Kong medical journal = Xianggang yi xue za zhi, 2020

Research

Toxoplasmosis in pregnancy: prevention, screening, and treatment.

Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC, 2013

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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