Neonatal Methemoglobinemia- A Case Series

Introduction

Cyanosis is bluish or bluish-purple discoloration of skin and mucus membrane. Cyanosis in newborn infants is usually caused by pulmonary conditions, congenital cyanotic heart disease or decreased cardiac output states. Rarely, it may also occur due to hematologic problems such as congenital or acquired methemoglobinemia.1^-10 We herewith report a series of three cases of neonatal methemoglobinemia.

Case Series

Case I

A 30+5 week gestation, preterm, female infant with birth weight of 720 grams was delivered by emergency lower segment cesarean section because of uncontrolled pregnancy-induced hypertension (PIH). Mother was receiving oral Nifedipine for PIH. On day 15 of life, when infant was established on full gavage feeds of mother’s expressed breast milk, infant was noticed to have cyanosis with lower oxygen saturations. Sepsis screen, chest x-ray, and 2D-Echo screen were unremarkable. An arterial blood gas (ABG) performed with cooximetry revealed methemoglobin levels of 20%. Infant responded well within 24 hours to IV methylene blue and vitamin-C therapy. Nifedipine, a known oxidizing agent in breast milk was considered to be the cause in this case.

Case II

A full-term male infant was admitted on day -22 of life with a history of diarrhoea. At admission, infant had features of sepsis. Sepsis screen was positive with a markedly raised C reactive protein (CRP) level (96.8 mg/L). Infant received IV Meropenem, oral Colistin, probiotics and zinc supplements. ABG with co-oximetry revealed metabolic acidosis with raised methemoglobin levels (13.7%). Gastrointestinal sepsis was considered to be the likely cause in this case. Infant responded to oral supplements of vitamin-C.

Case III

A 26+3 week preterm, 945 grams, male infant was born by spontaneous vaginal delivery. Antenatal period was otherwise unremarkable. Infant required ventilator support. There were features of early onset severe sepsis due to transmission of infection from mother-tofetus. Infant’s blood culture grew multi-drug resistant Klebsiella pneumoniae. Infant was treated with IV 

Colistin and Meropenem as per sensitivity pattern. Infant appeared cyanosed ABG with co-oximetry revealed metabolic acidosis with raised methemoglobin levels (7.4%). There was no evidence of structural abnormality on echo-cardiographs. Chest x-ray was unremarkable. Infant responded to IV methylene blue and oral vitamin-C administration. Meropenem was thought to be the most likely cause of methemoglobinemia in this case.

Discussion

All the three cases had cyanosis with low oxygen saturation levels. Acute pulmonary and cardiovascular diseases were excluded. The first and third case responded to IV methylene blue with oral vitamin C. Second case was treated with vitamin-C supplementation and responded to the same. Although we have not performed cytochrome b-5 reductase levels in all three cases, prompt response to therapy and non-recurrence of methemoglobinemia points finger to the attributed causes in each case.

Methemoglobin is the oxidized derivative form of hemoglobin in which the iron of the heme groups is changed from the ferrous (Fe++) to the ferric (Fe+++) state. It usually accounts for <1% of the total hemoglobin. Congenital methemoglobinemia is caused by either a genetically determined amino acid substitution in the globin moiety of the hemoglobin molecule or by a deficiency of one of the enzyme necessary for reduction of methemoglobin. Acquired methemoglobinemia is caused by exposure to various oxidizing agents.⁹ The effect of the methemoglobin formation is two-fold. First, methemoglobin is unavailable for transport of oxygen. Second, the presence of methemoglobin renders the oxygen dissociation curve more hyperbolic, shifting it to the left. The total effect is lowered capacity for unloading oxygen to the tissues and hence tissue susceptibility to anoxia and a state of functional anemia exists.¹⁰

Conclusion

Methemoglobinemia is not an uncommon entity in neonatal age group. A high index of suspicion for methemoglobinemia should be kept in mind as a differential diagnosis in cases of cyanosis without significant cardiac or pulmonary issues in the newborn.

Financial support

Nil.

Conflict of interests

Nil.