|Year : 2021 | Volume
| Issue : 4 | Page : 266-268
Targeted breast milk modification: A low-cost feeding option in young infants with citrullinemia
Saikat Patra, Swapnil Bhisikar, Pavan Kalamdani, Thaslima Kalathingal
Department of Neonatology, Lokmanya Tilak Municipal Medical College and General Hospital, Mumbai, Maharashtra, India
|Date of Submission||23-Aug-2021|
|Date of Decision||29-Oct-2021|
|Date of Acceptance||09-Nov-2021|
|Date of Web Publication||29-Nov-2021|
Dr. Saikat Patra
Department of Neonatology, Lokmanya Tilak Municipal Medical College and General Hospital, Sion, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: The management of urea cycle disorders (UCDs) needs use of nitrogen scavenger drugs and protein restricted special formulas. The latter is not easily accessible and expensive. Continued breastfeeding is poorly tolerated by most babies. In these circumstances, targeted breast milk modification can be lifesaving by reducing ammonia and preventing a catabolic state. Clinical Description: A term baby born by normal delivery was discharged at 48 h after successfully initiating breastfeeding. He developed lethargy, poor feeding, and seizures on the 4th day. Vitals were stable. Sepsis, hypoglycemia, hypoxic-ischemic encephalopathy, dyselectrolytemia, hepatic/renal derangement, structural brain anomalies, cerebral edema, and hemorrhage were ruled out. A UCD was suspected due to hyperammonemia without acidosis. Citrullinemia was established by elevated citrulline and no orotic acid. Management: Breastfeeding was stopped, nitrogen scavenger drugs started, and peritoneal dialysis performed. As specialized milk formula was unavailable, we started diluted breast milk mixed with corn starch and coconut oil to achieve protein restriction and provide appropriate carbohydrates, lipids, and energy. Dilution was gradually decreased. There was gradual improvement in sensorium with normalization of ammonia. The baby was well till 8 weeks but developed symptomatic hyperammonemia due to noncompliance with therapy. Conclusion: Targeted modification of breast milk may be the only viable option for feeding infants with UCD in extraordinary circumstances. However, its short- and long-term consequences need to be researched thoroughly.
Keywords: Breast milk, citrullinemia, neonate
|How to cite this article:|
Patra S, Bhisikar S, Kalamdani P, Kalathingal T. Targeted breast milk modification: A low-cost feeding option in young infants with citrullinemia. Indian Pediatr Case Rep 2021;1:266-8
|How to cite this URL:|
Patra S, Bhisikar S, Kalamdani P, Kalathingal T. Targeted breast milk modification: A low-cost feeding option in young infants with citrullinemia. Indian Pediatr Case Rep [serial online] 2021 [cited 2022 Jan 20];1:266-8. Available from: http://www.ipcares.org/text.asp?2021/1/4/266/331375
Urea cycle disorders (UCDs) are rare inborn errors of metabolism. The availability of better screening and diagnostic facilities has resulted in increased detection nowadays. These disorders require early diagnosis and treatment with nitrogen scavengers and protein-restricted special formulas. These protein-free formulas are expensive, and the high cost is a limiting factor in adequate management, especially in low- and middle-income countries.
We present a newborn who was diagnosed with citrullinemia, in whom we were unable to provide commercially available specialized formulae due to financial restraints. The aim is to share our experience in feeding the affected infant an indigenous modification of maternal breast milk using graded dilution and addition of cornstarch and coconut oil.
| Clinical Description|| |
A term male infant, born of a nonconsanguineous marriage to a primigravida mother, was delivered vaginally at a primary health-care facility. Antenatal period was uneventful. There was no history of any maternal sepsis setting or prolonged/precipitate labor. The baby cried immediately at birth, had a birth weight of 2.8 kg, and was discharged on the 2nd day of life after the establishment of breastfeeding. The baby developed lethargy, poor feeding, and multifocal clonic convulsions on the 4th day of life. The parents were migrant laborer's belonging to the lower socioeconomic strata.
At admission, the baby was lethargic, but the vitals were stable. On anthropometry, the weight was 2.7 kg, head circumference 34.2 cm, and length 48 cm. There was no evidence of dysmorphism, neurocutaneous markers, pallor, or icterus. The baby's cry, activity, and spontaneous movements were depressed, and there was minimal arousability. There was no cranial nerve involvement. Both pupils were constricted and reacted to light. The baby was hypotonic with depressed deep tendon and neonatal reflexes. Remaining systemic examination was normal. Investigations were planned to rule out the common causes of neonatal depression such as hypoglycemia, dyselectrolytemia, sepsis, renal, and/or hepatic derangement. The blood glucose, complete blood count, sepsis screen, liver, and renal function tests were normal. The cranial ultrasound did not reveal any abnormality. The arterial blood gas was normal, but serum ammonia and lactate were elevated, 885.9 μmol/L and 6.5 mmol/L, respectively. A differential diagnosis of an inborn error of metabolism with hyperammonemia was considered, possibly a UCD.
Management and outcome
Suitable investigations were ordered, and supportive management initiated. The baby was kept nil per orally (NPO), other than sodium benzoate (400 mg/kg/day), L-carnitine (200 mg/kg/day), thiamine (300 mg/day), riboflavin (100 mg/day), and Vitamin B12 (1 mg/day). Peritoneal dialysis was started with a short dwell time of 10 min. Parenteral nutrition was provided with 10% dextrose infusion (glucose infusion rate 8 mg/kg/min), lipids (3 g/kg/day), and a mixture of amino acids (0.5 g/kg/day). Elevated plasma citrulline levels of 1364.2 units/L on tandem mass spectrometry and absence of orotic aciduria on urinary gas chromatography-mass spectrometry established the diagnosis of citrullinemia. L-arginine (300 mg/kg/day) was added to sodium benzoate and carnitine. The serum ammonia level decreased to 230.2 μmol/L within 24 h of starting therapy. This decline was associated with a corresponding improvement in sensorium.
The parents were counseled about further workup and specific management. We were unable to get a gene mutation analysis done due to financial restraints. Specialized protein-restricted formula was not affordable. By the 10th day of life, it was decided to give the baby a trial of diluted breast milk mixed with corn starch and coconut oil, with energy and protein composition [Table 1] planned to be as close as possible to the commercially available formula that would provide appropriately high calories with minimal proteins. The pros and cons of this kind of feeding were discussed with the parents, and written informed consent was taken. The baby received gradual increment in feed volumes, calories, and proteins according to weight and tolerance. Clinical status and ammonia levels were closely monitored [Table 1]. Magnetic resonance imaging of the brain on day 12 of life revealed changes of hyperammonemic encephalopathy. The feed volumes reached maximal undiluted breast milk by day 34. No feed intolerance was observed and the serum ammonia levels continued to decline [Figure 1]. The baby was discharged on day 40 of life on exclusive breastfeeds with continuity of nitrogen scavenging medications. The weight was 3.1 kg, sensorium better, but mild appendicular hypotonia was present.
|Figure 1: Trend of serum ammonia levels (umol/L) with therapeutic interventions|
Click here to view
On follow-up at 8 weeks, the baby was on exclusive breastfeeds with normal ammonia levels. The baby had achieved social smile, but mild hypotonia persisted. At 3 months of age, the infant was re-admitted with vomiting for a day and lethargy for 8 h. On probing, it was elicited that the parents had stopped all medication for a week. On admission, vital signs were stable. The weight was 3.8 kg (<−3 standard deviation [SD]), length 58 cm (−2 SD), and head circumference 36 cm (<−3 SD). The baby was mildly neurologically depressed. The remaining examination was normal.
The only metabolic abnormality identified was elevated serum ammonia (370 μmol/L). The infant was kept NPO for 48 h and nitrogen scavenger medications restarted. Feeds were re-introduced, following the earlier schedule. The infant improved and was discharged after 10 days. The parents were counseled to continue breastfeeding, the nitrogen scavenger medication and the need for regular follow-up. However, the baby was lost to follow-up.
| Discussion|| |
The primary aim of therapy of infants with UCD is to reduce ammonia rapidly and provide minimal protein to prevent endogenous protein catabolism. Prognosis depends upon early and aggressive management of hyperammonemia. Management includes protein cessation/restriction, intravenous fluid and ammonia, scavenging medications,,,, and dialysis (ammonia >500 μmol/L). Enteral feeding is restarted after 48–72 h of stabilization, to prevent catabolism. Proteins are reintroduced when ammonia is <100 μmol/L. The total energy intake should be 120% (age-adjusted) with proteins at 1.4–2.1 g/kg/day. However, proteins are re-instituted at 25%–50% of expected intake, and gradually increased. If ammonia levels increase, special formulas are used, either in isolation or combined with natural proteins.
Further management requires specialized formulas, in addition to nitrogen scavengers. If not provided, there is a high risk of cognitive impairment, epilepsy, and death. However, these are expensive, not easily accessible, or not affordable. The cost of a single 60 ml feed of targeted breast milk preparation used for this baby was 3.6 cents (2.5 rupees) in comparison to 1.28 USD (95 rupees) for specialized formula, almost a fifth of the daily per capita Indian income. In this case, the breast milk was initially diluted to reduce the protein content. Coconut oil was used to provide calories. Corn starch was the main source of carbohydrates. It is already being used in neonates for persistent hypoglycemia and glycogen storage disorders. The concentration of breast milk was gradually increased till full undiluted breast milk feeding was reached.
Exclusive breastfeeding and nitrogen scavenging medications have been in used in some infants with UCD under strict monitoring, but it is poorly tolerated by many patients. That is why we considered using targeted breast milk modification following the principles of UCD management in this baby as the only available option. We could not find any previous similar reports of feeding on a literature search. Although as of now, this practice cannot be recommended as standard care, it may be considered as a viable option only in special circumstances, to tide over the metabolic derangement, and sustain enteral nutrition when there are no other alternatives. Although the level of ammonia was controlled in our baby, he developed microcephaly and the nutritional status was poor (though parental compliance was dubious). We were unable to monitor growth and development in this infant. Research on short-term and long-term implications of breast milk modification is warranted.
The authors wish to acknowledge the encouragement and support of Dr. Jayashree Mondkar and Dr. Swati Manerkar from Department of Neonatology, Lokmanya Tilak Municipal Medical College and General Hospital, Sion, Mumbai.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Sachdeva A. Dietary interventions for rare metabolic disorders – Now available in India! Indian Pediatr 2017;54:909-10.
Häberle J, Boddaert N, Burlina A, et al.
Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphanet J Rare Dis 2012;7:32.
Kumta NB. Inborn Errors of Metabolism (IEM) – An Indian perspective. Indian J Pediatr 2005;72:325-32.
Batshaw ML, Tuchman M, Summar M, et al
. A longitudinal study of urea cycle disorders. Mol Genet Metab 2014;113:127-30.
Singh RH, Rhead WJ, Smith W, et al.
Nutritional management of urea cycle disorders. Crit Care Clin 2005;21:S27-35.
Singh RH. Nutritional management of patients with urea cycle disorders. J Inherit Metab Dis 2007;30:880-7.
Gandhi K. Approach to hypoglycemia in infants and children. Transl Pediatr 2017;6:408-20.