Cow’s milk in infant diet is a risk factor for hypocalcemic seizures

INTRODUCTION / ВВЕДЕНИЕ

Seizures are common in infants, owing to inherent sensitivity of the developing brain to various insults [1]. The metabolic status alteration is one of the common cause of seizures [2]. Among the metabolic causes, hypocalcemia is one of the frequent causes [3]. Early diagnosis of hypocalcemic seizures is essential, because the management and prognostication is different from other causes of seizures [4].

The early introduction of cow’s milk into an infant’s diet before the age of 1 year is a dietary risk factor of hypocalcemic seizures. Studies have demonstrated that cow’s milk consumption correlates with an increased risk of hypocalcemia due it’s impact on the calcium-phosphorus ratio and parathyroid hormone [5][6]. The data on prevalence of hypocalcemic seizures are limited [7].

The current study hypothesizes that early introduction of cow’s milk significantly contributes to the risk of hypocalcemic seizures in children.

Objective: To investigate the prevalence and associated risk factors of hypocalcemic seizures in children aged 1 month to 2 years.

MATERIAL AND METHODS / МАТЕРИАЛ И МЕТОДЫ

Study design / Дизайн исследования

This 18-month prospective observational study was carried out in a tertiary care teaching hospital after institutional ethics committee approval. All children in the age group of 1 month to 2 years, presenting with seizures were enrolled in the study. Children previously enrolled in the study who were re-admitted during the study period were planned to be excluded. The study participants received standard care of seizures. The demographic details and the relevant risk factor details were entered in a pre-designed proforma.

Laboratory tests / Лабораторные тесты

The study participants with hypocalcemia were further tested for vitamin D, parathormone, alkaline phosphatase and magnesium levels. The serum calcium was measured using Arsenezo method. The serum magnesium was measured using Xylidyl method. The serum vitamin D and serum intact parathormone levels were measured using electro chemiluminescence method. The serum phosphorus was measured by phosphomolybdate method. The alkaline phosphatase level was estimated by para-nitrophenylphosphate and AMP-buffer¹ methods.

Hypocalcemia was defined as serum calcium level less than 8 mg/dl [8]. Serum vitamin D levels less than 20 ng/dl was defined as vitamin D deficiency [9]. Hypomagnesemia was defined as serum magnesium level less than 1.5 mg/dl [8].

Statistical analysis / Статистический анализ

Based on a previous study [10], with assumed prevalence of 30% of hypocalcemic seizures, a minimum sample size of 225 subjects was calculated at a power of 80%, confidence interval level of 95%, and marginal error rate of 0.06. Data were entered into Microsoft Excel database (Microsoft, USA) software. The statistical analysis was performed using SPSS Version 26 (IBM, USA). The categorical variables were expressed as frequency and percentage. The continuous variables were expressed as mean and standard deviation. The association between variables was tested using χ² test or Fischer’s exact test. A p-value of less than 0.05 was taken as significant.

RESULTS / РЕЗУЛЬТАТЫ

The prevalence of hypocalcemic seizures / Распространенность гипокальциемических приступов

A total of 225 children (121 (53.7%) boys, 104 (46.3%) girls) were enrolled in the study. The most common type of seizures was simple febrile seizures (n=104, 46.2%). The prevalence of hypocalcemic seizures comprised 3.6% (n=8). The other causes are shown in Table 1.

Association between demographic and other factors / Связь между демографическими и другими факторами

The association between demographic and other factors are shown in Table 2. The age and cow’s milk administration before the age of 1 year, was the significant factors associated with hypocalcemic seizures.

Biochemical profile of children with hypocalcemic seizures / Биохимический профиль детей с гипокальциемическими приступами

The biochemical profile of children with hypocalcemic seizures is shown in Table 3. All children with hypocalcemic seizures had vitamin D deficiency. The mean vitamin D level was 7.77 ng/dl. The alkaline phosphatase level was elevated in all the children with hypocalcemic seizures. The mean alkaline phosphatase level was 841.8 U/l. Out of the 8 children with hypocalcemic seizures, 7 (87.5%) had elevated parathormone levels. The mean parathormone level was 276.7 pg/dl. The serum magnesium level was low in 1 (12.5%) child with hypocalcemic seizures. The mean magnesium level was 1.7 mg/dl. The serum phosphorus level was normal in all of the 8 children with hypocalcemic seizures.

DISCUSSION / ОБСУЖДЕНИЕ

The prevalence of hypocalcemic seizures in the present study reached 3.6%. In the published studies, there is a wide range in prevalence, from 4.6 to 68.3% [6][7][10–13]. The difference in this prevalence rate may be attributed by difference in demography of the study population, study design with differences in inclusion criteria, level of ante-natal care, level of new-born and infant care, exposure to sunlight, and the pattern of complimentary feeding practices.

In our study, the mean age of children with hypocalcemic seizures was 4.5 months. A similar observation has been made in other published studies [14][15]. The higher metabolic demand for calcium and relative immature calcium homeostasis mechanism in early infants could underlie higher prevalence of hypocalcemic seizures in this age group [16].

All children with hypocalcemic seizures had generalised type of seizures in our study. Similar pattern of generalised type of hypocalcemic seizures has been reported earlier [6][7]. This is due to the generalised neuro-activation and excitability induced by hypocalcemia [17].

In our study, 87.5% of the children with hypocalcemic seizures received no vitamin D supplementation that agrees with earlier study [13]. This emphasises the fact that vitamin D supplements are essential in infants for various benefits including prevention of hypocalcemic seizures.

In our study, 37.5% of the children with hypocalcemic seizures had received cow’s milk feeding before the age of 1 year. This rate was 63.4% in a previously reported study [6]. The high phosphorus content in cow’s milk leads to hypocalcemia via increased deposition of calcium in bone tissue, hypoparathyroid state, and reduced absorption of calcium from the intestine [18][19].

In our study, all children with hypocalcemic seizure had hypovitaminosis D. Vitamin D deficiency as the common cause of hypocalcemic seizures has been reported in various studies [20–22]. Vitamin D is an essential component in calcium homeostasis. The deficiency of vitamin D results in reduced absorption of calcium from intestine resulting in hypocalcemia.

In our study, all children with hypocalcemic seizures had elevated alkaline phosphatase and normal phosphorus level. This finding has been observed in previously reported studies [15][23]. Phosphate levels were not low as expected in the cases of hypocalcemia and hypovitaminosis D. This may be due to early presentation of vitamin D deficiency, where parathyroid response has not started or late presentation of vitamin D deficiency, where there is resistance to parathyroid hormone [24].

CONCLUSION / ЗАКЛЮЧЕНИЕ

The hypocalcemic seizures should be considered in the evaluation of seizures in infants, particularly in young infants and when there is introduction of cow’s milk in infant diet, before the age of 1 year.