Key words: Plasma zinc levels, Young infants.

Zinc is one of the essential trace metals with varied functions in humans(1). It is involved in neurotransmission, immune activity, growth and development, some hormonal actions, sensory functions of taste and smell and wound healing(1). Zinc is a major regulatory ion in the metabolism of cells especially in tissues with a high cellular turnover(1). It plays a critical role in nucleic acid and protein synthesis. Hence the recommended daily allowances are relatively high at the time of growth and develop-ment(2). In infants the recommended dietary requirement of zinc is 1-2 mg/kg/day(3). Zinc deficiency has a profound effect on the rapidly proliferating tissues such as those found in young infants and children.

There are no sensitive and specific clinical signs of zinc deficiency in humans. No single plasma zinc level cut-off has been associated with any of the reported signs of zinc deficiency. While there is data on the plasma zinc levels in children there is only meager data on the levels in very young infants. Hence the primary objective of the current study was to estimate the plasma zinc levels in one-month-old infants. The secondary objective was to assess the association of plasma zinc level with gender and feeding type.

This was an observational study conducted from August 1998 to March 1999 in the Department of Pediatrics on babies born at Queen Mary hospital attached to the King George Medical College, Lucknow. Included were the term babies with birth weight ³2 Kg and whose parents resided in Lucknow city. Gestational age was determined on the basis of last menstrual period (LMP), when known. If LMP was not known. Ballard’s scoring(4) was used for the estimation of gestational age. The weight was taken within 3 hours of birth by a computerized weighing machine with a sensitivity of 1 gram. Babies with congenital malformations, birth asphyxia, sepsis and pyogenic meningitis were excluded.

The study population included neonates born on one randomly selected day of each week for seven months. Data was collected on the following neonatal variables: date and time of birth, Apgar score at one and five minutes, weight, length and head circum-ference, feeding type at the time of discharge, and any other morbidity during hospital stay. Data was also collected on the maternal variables like parity, religion, and socio-economic status.

For the estimation of plasma zinc level, with a power of 0.8. 2-tailed alpha of 0.95 for a standard deviation of 30 µg/dL in the study sample estimates assuming a difference of 20 µg/dL from the reported population mean of 100 µg/dL a minimum of 38 children were required. Eligible neonates were randomly allocated to two sub-groups, one with and the other without plasma zinc estimation at the 4-week follow-up. For the sub-group allocation eligible neonates were given a unique identification number which included the date of birth. If two or less babies were born on a particular day the plasma zinc estimation was to be done in both. However, if more than two eligible neonates were born on a particular day then two were randomly selected for plasma zinc estimation by a lottery draw without replacement. Parents were blind to the sub-group allotted to their neonate at the time of discharge.

Eligible neonates were called for a follow-up after 4 weeks. Those who came for the follow-up were enrolled in the study. Data was collected on weight, length, and feeding type. Blood was also collected for plasma zinc estimation in sub-group identified at the time of birth. A single medical officer collected clinical data.

Plasma zinc level was estimated by an atomic absorption spectrometer in the Industrial Toxicological Research Center, Lucknow.

Data was entered in dBase. EP16 statistical software(5) was used for data analysis. To test for association, chi-square test was used for categorical variables and student ‘t’ test and Pearson’s correlation coefficient for continuous variables. Linear regression was done to assess the association of weight gain in 4 weeks with the plasma zinc levels (controlling for sex and feeding type).

In the randomly selected days, 187-term babies weighing >2 kg were born. Of these, 4 and 3 were excluded as they had sepsis and birth asphyxia respectively. Of 180 term babies fulfilling all inclusion criteria only 116 (64.4%) returned after 4 weeks for a follow-up. Among these 59 (50.8%) were males and 57 (49.2%) were females. Parents of all these babies gave consent for the study. Their mean birth weight was 2.65 ± 0.27 Kg and mean gestational age was 37.87 ± 3.7 weeks. Of these only 59 (50.8%) were exclusively breast fed at one month of age. The mean weight gain in 4 weeks was 554.9 g and was similar in males and females. The mean weight gain was higher in the exclusively breast-fed infants ( 588.9 ± 229.9 g) than in others (546.4 ± 213.9 g) but the difference was not statistically significant (P = 0.3).

Table I__	Base-line Characteristics of 52 Infants with Plasma Zinc 
Estimation at Recruitment

Gestation (weeks)

37.99 ± 2.531

Birth weight (grams)

2.69   ±  0.25

Birth length (cm)

49.48  ± 2.14

Head circumference (cm)

32.33  ± 1.95

Plasma zinc levels (µg/dL)

107.69 ± 23.76

Maternal height (cm)

155.96 ± 5.5

From among the 116 neonates blood for plasma zinc estimation was drawn from 58 who were randomly selected for this at birth. Six out of 58 samples were hemolysed, hence excluded from the anlaysis. Among those sampled 25 (48.1%) were males and 27 (51.9%) were females; 30 (57.5%) were breast-fed and 22 (42.3%) were not breastfed. Their anthropometric data at birth are shown in Table I. At the time of recruitment the mean age was 31.6 ± 2.4 days, mean weight was 3.32 ± 0.423 Kg and mean length was 52.4 ± 2.07 cm.

The mean plasma zinc level was 107.69 ± 23.76 µg/dL (range 70 to 150 µg/dL). The mean hemoglobin level was 15.28 ± 2.01 g/dL. Males had statistically significantly higher mean plasma zinc levels than females (117.56 ± 23.84 µg/dL versus 98.56 ± 20.04 µg/dL; P = 0.003). There were no differences in the birth weight, weight at 4 weeks or weight gain in 4 weeks as well as in length at birth and at 4 weeks between males and females in this sub-group. There was no significant difference in mean plasma zinc levels between breast-fed and non-breast fed infants (110.5 ± 25.95 µg/dL vs 103.82 ± 20.33 µg/dL). There was no correlation between weight gain and plasma zinc level at 1 month of age. Controlling for sex and feeding of breast milk, there was no association of plasma zinc level and weight gain in linear regression model.

In the present study the mean plasma zinc level of 1-month-old infants was observed to be 107.69 ± 23.76 µg/dL. This is within the reported normal range of 64-118 µg/dL in the pediatric age group(6). Males had signifi-cantly higher plasma zinc level than females. This is unlike the reports by others(7) and has to be verified by larger studies. Plasma zinc levels in the breast-fed group and the non-breast fed group were similar.

Zinc content of breast milk is 0.235 mg/dL during the first 15 days(7,8) and thereafter 0.118 mg/dL till 15 months of lactation(9). It has been reported that plasma zinc levels of breast-fed infants fall gradually during the period of weaning(8) and thus they are at risk of zinc deficiency. The zinc content of cow’s as well as the usual formula milk is between 0.3 to 0.5 mg/dL, which is higher than that found in breast milk. Zinc from bovine and formula milk is sufficient to fulfill the daily requirement of infants(9). This may explain similar plasma zinc levels in the breast fed and artificially fed groups found in the current study.

Currently, different pharmaceutical companies are promoting the use of zinc in young infants. Multivitamin preparations with zinc are costlier than those without zinc, and there is no strong evidence favoring their use at this time. On the other hand, some caution has to be exercised while recommending zinc supplementation as this has been found to be associated with a higher risk of acute respiratory infections when compared to the non-supplemented group(10). There is, therefore, a need to assess the clinical benefits of zinc supplementation in very young children, as the plasma levels are poor markers of the zinc status(9).

The present study concludes that the plasma zinc levels at 1 month of age are normal in term babies with birth weight >2 kg. The clinical benefits of zinc supplementation in this group have to be established by further research.

Contributors: This work was done as MD thesis of Sriniwas. SA was responsible for study design, data analysis and manuscript. SK assisted in data analysis and manuscript wiring. RCC supervised laboratory analysis and assisted in interpretation of the results and manuscript writing.

Funding: None.

Competing interests: None stated.