Nigerian Journal of Clinical Practice

ORIGINAL ARTICLE
Year
: 2022  |  Volume : 25  |  Issue : 7  |  Page : 997--1003

Umbilical cord serum zinc in neonates delivered at the university of Nigeria teaching hospital, Enugu: Variation with gestational age


CL Olisaka1, KK Iloh1, IN Asinobi2, AC Ubesie1, AN Ikefuna1, BC Ibe1,  
1 Department of Paediatrics, University of Nigeria Teaching Hospital/University of Nigeria, Enugu, Enugu State, Nigeria
2 Department of Paediatrics, Enugu State University Teaching Hospital, Enugu, Enugu State, Nigeria

Correspondence Address:
Dr. K K Iloh
Department of Paediatrics, University of Nigeria Teaching Hospital/University of Nigeria, Enugu, Enugu State
Nigeria

Abstract

Background: Zinc is particularly involved in cellular growth, neurodevelopment, and immune function, which is critical for child survival. To reduce neonatal mortality in developing countries, cost-effective and evidence-based interventions that can enhance growth, development, and immunity, need to be considered. Determining the zinc levels of neonates and how it relates to both gestational age is therefore imperative. Subjects and Methods: A descriptive cross-sectional study was carried out at the University of Nigeria Teaching Hospital, aimed at determining the umbilical cord serum zinc levels among neonates and their relationship with their gestational age. Two hundred and seventy-five neonates of gestational ages 28 to 42 weeks were enrolled in the study. Serum zinc levels were determined using the flame atomic absorption spectrophotometer (AAS model no. FS 240 AA.USA, Agilent Technology Ltd.). Results: Among the 275 neonates, there were 27 (9.82%), 28 (10.18%), and 220 (80%) preterms, moderate-to-late preterms, and term neonates, respectively. The mean serum zinc level of all neonates was 87 ± 16.07 μg/dL and within the normal limit of serum zinc. Their mean serum zinc level increased with increasing gestational age (F = 90.424, P < 0.001). Very preterm and moderate-to-late preterm neonates had mean serum zinc levels of 65.13 μg/dL ± 6.15 and 69.85 μg/dL ± 9.63 μg/dL, respectively. Conclusion: This study revealed that though the overall mean serum zinc of neonates was normal, preterms (especially those of lower gestational ages) were zinc deficient. Routine zinc supplementation at birth should be considered in preterm neonates to reduce the untoward effects of zinc deficiency.



How to cite this article:
Olisaka C L, Iloh K K, Asinobi I N, Ubesie A C, Ikefuna A N, Ibe B C. Umbilical cord serum zinc in neonates delivered at the university of Nigeria teaching hospital, Enugu: Variation with gestational age.Niger J Clin Pract 2022;25:997-1003


How to cite this URL:
Olisaka C L, Iloh K K, Asinobi I N, Ubesie A C, Ikefuna A N, Ibe B C. Umbilical cord serum zinc in neonates delivered at the university of Nigeria teaching hospital, Enugu: Variation with gestational age. Niger J Clin Pract [serial online] 2022 [cited 2022 Aug 8 ];25:997-1003
Available from: https://www.njcponline.com/text.asp?2022/25/7/997/351451


Full Text



 Introduction



Zinc is a ubiquitous trace element, present in all the enzyme classes and vital for human metabolism.[1] It is important for the formation and function of various hormones, proteins, and growth factors.[2] In the brain, it is one of the most prevalent elements and plays a significant role in the developing brain, especially during the fetal and neonatal periods.[3] Specific processes in the brain that require zinc are cell replication, neurogenesis, myelination, the release of neurotransmitters, and cerebellar and hippocampal development.[3]

In the preterm brain, it is important in regulating the expression of neurotrophic factors that reduce apoptosis subsequent to different types of insults and also promote neuronal regeneration.[4] Preterm neonates are at high risk of hypoxic brain damage while its severity is reduced by the activity of zinc-dependent metallothioneins.[5] Zinc is also essential in the modulation of cerebral vascular tone. The reduced ability to control the tone of cerebral vessels is of critical importance in the development of hypoxic-ischemic injury and the occurrence of intraventricular hemorrhage in the preterm infant.[4]

Zinc is known to have anti-oxidant effects and is a cofactor for many enzymes, which are essential for optimal immune function.[2] It mitigates the response to environmental injury caused by oxidative stress and free radical-mediated diseases, as seen in necrotizing enterocolitis.[6] This is due to its activities in the intestine, which include regulation of intestinal permeability, epithelial cell growth, and development of immune responses.[7] It influences both the innate and acquired immune systems and is a potent mediator of host resistance to infection. Its key role in maintaining the structure and function of epithelial lining is an important aspect of innate immunity. This is an important first line of defense against infections.

Thus, zinc deficiency leads to compromised epithelial barrier of the skin, gastrointestinal, and respiratory tracts.[7] It can also lead to impaired chemotactic activities of polymorphonuclear leucocytes and phagocytic function of natural killer cells.[7] Cell-mediated immune disorders can also occur. Other manifestations of zinc deficiency in neonates include growth retardation, failure to thrive, dermatitis, diarrhea, poor appetite, delayed wound healing, rough skin, and behavioral changes.[5],[7],[8] Infantile and early childhood zinc deficiency have been associated with learning, psychomotor and neurobehavioral problems.[3]

Compared with their term counterparts, preterms are at increased risk of nutritional compromise, impaired growth, developmental delay, and increased susceptibility to infection and death.[9] In Egypt, Aajaz et al.[9] documented that the prevalence of zinc deficiency was 45% in neonates and more in preterm neonates than in term neonates.[9]

Most available studies have focused on the relationship between maternal serum zinc levels and fetal outcomes.[10],[11],[12] While some have also studied zinc levels at various ages beyond the neonatal period,[13],[14] those that studied zinc levels among neonates have conflicting reports on the relationship between serum zinc and gestational age.[15],[16] Furthermore, in Nigeria, there are few published studies on zinc levels in preterm neonates.[17],[18] The gestational age at which neonates are likely to develop zinc deficiency has not been ascertained. With the knowledge of the role of zinc in growth, immunity, and cognitive development, the assessment of umbilical cord serum zinc levels in neonates including preterm neonates and relate same to their gestational age at birth becomes relevant. The results obtained may identify neonates who are most likely to have zinc deficiency and may benefit from early zinc supplementation before their stores are depleted. In addition, it may be a template on which future studies on the subject may be developed.

 Subjects and Methods



Study location

The study was carried out in the labor ward, and obstetric theatre of the University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu State.

Study design

The study was descriptive and cross-sectional.

Study population

The subjects were neonates delivered at 28–42 completed weeks at the University of Nigeria Teaching Hospital (UNTH). The hospital has an annual delivery of 750 babies. The average number of preterm births per year as obtained from hospital records is 110 and stratified using the World Health Organization (WHO) classification of neonates.[19] into: moderate-to-late preterm (between 32 to <37 completed weeks of gestation) –57, very preterm (between 28 to <32 completed weeks of gestation) – 40, and extreme preterm (births before 28 completed weeks of gestation) –13. Term neonates are those born between 37 completed weeks and 42 completed weeks. For this study, extreme preterms were excluded.

Estimation of sample size

The sample size was determined using the appropriate formulae for proportions[20] with an attrition rate of 10%. The final sample size was 275 and reflected the birth rates at UNTH as follows: 51% (n = 28) for moderate-to-late preterm and 49% (n = 27) for very preterm neonates.

Ethical considerations

Ethical approval was obtained from the Health Research Ethics Committee (HREC) of the University of Nigeria Teaching Hospital. Only mothers who gave consent had their babies recruited into the study. Data from the completed proforma was stored in a private file and updated weekly on Statistical Package for Social Sciences (SPSS), which was stored in the researcher's private computer with a passcode to avoid unauthorized access. All relevant information pertaining to the study was kept in the sole custody of the researcher.

Sampling method

Subjects were enrolled consecutively using the convenience sampling method until the desired sample size of 275 was achieved. Recruitment was by proportionate representation based on the number of preterm and term deliveries in UNTH from January to December, 2018. The preterm neonates (20%) were recruited from two categories of preterms: very preterm (49%) and moderate-to-late preterm (51%). Thus, 27 and 28 preterm newborns were recruited from each category, respectively. The remaining (80%) were term neonates.

Included in the study were appropriate for gestational age (AGA) neonates whose parents gave written informed consent. Excluded were neonates whose mothers had chronic medical conditions, were on medications that could cause zinc deficiency, smoked cigarettes, or took alcohol during pregnancy (irrespective of quantity), and neonates with severe congenital malformations, and/or major systemic diseases evident at birth.

Subject recruitment/umbilical cord blood sample collection

After admission, stable expectant mothers in the first stage of labor, for cesarean section, or those who were at risk of preterm delivery were approached and given an explanation of the reason and nature of the study. Informed consent was obtained and relevant information was collected using case record forms. Social class was assigned based on the educational status of the mother and occupation of the father as described by Olusanya et al.[21] The last menstrual period (LMP) of the mother was also obtained either by recall from the mother, or from the medical records, if available.

After the neonate was delivered, 6 mL of blood was withdrawn from the umbilical vein into a syringe using standard procedures.[22] The obtained blood was transferred into a new, labeled, sterile plain sample bottle and placed in a sample bottle rack.

Estimation of cord serum zinc

The clotted blood sample was centrifuged at 3000 rpm for 5 min using a bench centrifuge (CSN-80, Medifield Equipment and Scientific Ltd, England). The serum was transferred using a micro-pipette into trace element-free tubes (plain cryovails) and labeled. One milliliter of serum for zinc analysis was stored inside a freezer in the hematology laboratory and frozen at −20°C until analysis, which was done every 2 weeks. Analysis for serum zinc was done using atomic absorption spectrophotometer.[23] To ensure quality control, out of every 10 samples, a sample containing a known amount of zinc was analyzed to confirm recovery.

Values were reported in microgram/deciliter (μg/dL). Cord serum zinc was classified as low when the value was less than 70 μg/dL and normal or adequate if the value was 70 μg/dL and above.[24]

Estimation of gestational age

Gestational age in weeks was calculated by summing up all the days from the last menstrual period and dividing the obtained figure by seven.[25] To strengthen this, the New Ballard scoring system was also used to estimate the gestational age.[26] This was then cross-checked against the gestational age obtained from the maternal last menstrual period. In mothers whose gestational age could not be ascertained from the LMP, the gestational age obtained from the New Ballard score[26] was used. Also, where there was a discrepancy between the two, the Ballard score was used.

The appropriateness of the baby's birth weight for gestational age was determined using WHO growth percentile charts.[27]

Data analysis

Analysis of the data was done using the International Business Machine-Statistical Package for Social Sciences (IBM-SPSS), version 20. Normality of data distribution was checked using graphical displays.

Continuous data such as gestational age and serum zinc were summarized as means and standard deviation while categorical data such as gestational age categories, gender, and socioeconomic class were presented as frequencies and percentages.

Normally distributed data were analyzed using parametric statistics. The Student's t test was used to analyze the difference in the mean serum zinc of males and females. Analysis of variance (ANOVA) was used to determine the variation in the mean of measurements between groups such as serum zinc at different categories of gestational age.

Relationships between continuous variables (e.g., gestational age and serum zinc) were established using Pearson correlation. Relationship between categories of zinc levels (low and normal) and groups of gestational age was established using Chi-square or Fisher's exact where applicable.

Logistic regression was used to test the extent of the relationship between zinc levels and categories of gestational age when these were significant at the univariate level. Statistical significance was set at P < 0.05. Results were presented in tables, charts, and prose.

 Results



Characteristics of the study participants

The study was carried out over a period of 8 months (February to September, 2018). A total of 275 neonates, who met the study criteria were recruited. Of these, 55 were preterms while 220 were term neonates. The preterm babies were categorized into two gestational age groups: very preterm (VP) and moderate-to late preterm (MLP). There were 27 and 28 preterm neonates in the two groups, respectively.

Seventy-seven (28%) neonates were from the upper social class, 135 neonates (49.1%) were from the middle socioeconomic class, and 63 (22.9%) were from the lower socioeconomic class.

There were 135 (49.1%) males and 140 (50.9%) females, giving a male to female ratio of 1:1.04.

Distribution of study subjects by gender and gestational age categories

[Table 1] shows the classification of study subjects by sex and gestational age. The distribution was similar in males and females (P = 0.317).{Table 1}

Gestational age and weights of the study participants

The mean gestational age of the participants was 37 weeks ± 3.09 weeks. The lowest gestational age was 28 weeks and the highest was 42 weeks.

The mean weight of the study participants was 3.00 ± 0.68 kg. Among the categories of neonates, the mean weight was 1.53 ± 0.18 kg for the very preterms, 2.29 ± 0.46 kg for the moderate-to-late preterms and 3.27.7 ± 0.37 kg for the term neonates.

Serum zinc level of study participants

The overall mean serum zinc of the neonates was 87.70 ± 16.07 μg/dL, which was above the normal limit of 70 μg/dL.

Prevalence of low serum zinc in preterm and term neonates

[Table 2] shows that the zinc in term neonates was lower than that in preterm neonates was (P < 0.001){Table 2}

Relationship between serum zinc and the gestational age of the study participants

[Figure 1] shows the linear relationship between gestational age and serum zinc (r = 0.604, P < 0.001).{Figure 1}

Distribution of serum zinc according to the gestational age categories of the study participants

The overall mean serum zinc of preterm neonates was (67.53 ± 6.38 μg/dL). Mean serum zinc was lowest in the very preterm group and highest in their term counterparts (F = 90.424, P < 0.001) as shown in [Table 3]. A post hoc multiple comparison showed that the mean serum zinc differed significantly between very preterm and term groups (P < 0.001). Also, mean serum zinc differed between moderate-to-late preterm and term groups (P < 0.001).{Table 3}

Prevalence of low serum zinc according to gestational age group

[Table 4] shows the prevalence of low serum zinc in three gestational age classes. The highest prevalence was observed with very preterm babies and the lowest, in term babies (P < 0.001).{Table 4}

Very preterm babies were 4.4 times as likely to have low zinc as their moderate-to-late preterm counterparts (Odds ratio = 4.4, P < 0.001) [Table 4]b. Similarly, very preterm babies were over 200 times as likely to be deficient as term babies (Odds ratio = 237.6, P < 0.001) while moderate-to-late preterm infants had 54 times the odds of being zinc deficient as term babies (Odds ratio = 54.0, P < 0.001) as shown in [Table 5].{Table 5}

 Discussion



The overall mean umbilical cord serum zinc levels of 87 μg/dL are within normal limits.[24] The normal serum zinc level in this study may be due to the fact that 80% of the study participants were apparently well-termed neonates who had maximum time in utero for iintrauterine accretion of zinc and are not likely to be zinc deficient. This was lower than the mean level documented in term neonates by Ofakunrin et al.,[28] in Jos, North Central Nigeria. The overall mean serum zinc values in this study could have been lowered with the enrolment of preterm neonates who were notprivileged to have enough time in utero for acquisition and storage of zinc, which occurs in the third trimester.

There was a significant positive relationship between serum zinc and gestational age. This is in keeping with the findings by Jeswani et al.,[16] and Abd-Elmagid et al.[29] who noted a similar relationship. Furthermore, a progressive increase in mean zinc levels with increasing gestational age was clearly depicted with the very preterm neonates having the lowest values and term babies having the highest.

The observation is in keeping with the knowledge that fetal zinc accretion increases with gesational age with 60–70% of zinc occurring in the third trimester. Contrary to this, Iqbal et al.[15] did not observe any significant relationship between the serum zinc of neonates and increasing gestational age. This may be explained by the fact that Iqbal and colleagues[15] recruited preterm babies, which skewed in favor of moderate-to-late preterm groups in contrast to the index study where almost equal number of preterms were recruited from the two preterm categories. These neonates though still preterm were more mature and expected to have improved zinc availability and growing zinc stores that occur in late gestation.[2] Further analysis to ascertain the relationship between serum zinc levels with gestational age revealed that the prevalence of hypozincemia was higher in preterm neonates than in term. This higher prevalence of hypozincemia in preterm neonates was also observed by Abd-Elmagid et al.[29] and Aajaz et al.[9] and reflects the shorter time in utero by preterm neonates to accumulate enough zinc stores as previously explained.

The index study also observed that the severity of prematurity also increased the likelihood of observing low zinc levels in subjects. Thus, even among preterm neonates, the very preterm babies were four times more likely to have low zinc levels than moderate-to-late preterm babies. The effect of gestational age on serum zinc is several times worse when very preterm babies are compared with term neonates. Its clinical relevance is noted when considering the number of preterm neonates born annually in Nigeria. The WHO states that in Nigeria 773,600 babies are born preterm each year.[30] Hence, this significant number of preterm babies are faced with the possibility of having low zinc levels and the attendant complications of zinc deficiency with the consequences being worse in neonates of lower gestational ages.

The reason for the normal serum zinc levels among the remaining 35% of preterm neonates is not clear and so needs further evaluation. It is also not clear why a few (2%) of term neonates who are expected to have accrued sufficient zinc in utero had low zinc. This finding of low zinc in some term neonates has been explained in some studies to be mainly due to very low maternal serum zinc levels,[16],[17] which was not explored in this study. This in turn may be due to maternal consumption of foods with high phytate content as is common in women from developing countries.[31] It is important to note, however, that the degree of maternal zinc deficiency is an important factor, but this relationship may be relevant only when maternal zinc levels are very low[28] as shown in the studies by Ofakunrin et al.[28] and Okonofua et al.[10] where the authors observed that mothers with low zinc surprisingly had neonates with normal zinc levels. This was explained to be due to the preferential transfer of zinc across the placenta in favor of the neonate, as well as a host-parasite relationship that exists between the fetuses and their mothers. Hence, these authors concluded that maternal serum zinc would affect the neonate's serum zinc only if the mother's zinc levels were very low.[10],[28] This perhaps may have been the situation in the few term neonates with low zinc in the present study.

 Conclusions



The neonates in this study had overall mean serum zinc that was within the normal. Low serum zinc was more prevalent among preterms than term neonates with very preterms being most likely to have a zinc deficiency.

It is, therefore, recommended that zinc supplementation may be administered to preterms and low birth weight neonates as well as those with low serum zinc at birth so as to enhance their growth and neurodevelopment.

Limitation of the study

Maternal serum zinc levels were not measured. Its inclusion should have aided the interpretation of the low serum zinc in neonates, especially preterms.

Acknowledgments

We acknowledge all the children who participated in the study.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the subjects representatives have given their consent that the subjects' clinical information to be reported in the journal. The subjects representative patients understood that study participants names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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