Trace elements are essential for all biological cell function. They play an important role during pregnancy and deficiencies during gestation may adversely affect both mother and fetus [7]. Essential elements in pregnant women and the fetus are affected by the major physiological changes occurring during pregnancy, in addition to the other significant factors such as maternal age, week of gestation, nutritional status, and living environment [8].
In the current study, the cord blood levels of copper and zinc in preterm neonates were significantly lower in comparison to full-term neonates. A highly significant positive correlation of serum copper and zinc levels with gestational age (r = 0.305 and p = 0.008) was observed.
The lower serum copper levels in preterms may be attributed to its increased need for fetal growth and development and its important role in erythropoiesis. This is also intensified by the immaturity of the liver to synthesize ceruloplasmin. Preterm and low-birth weight babies have low zinc levels due to deficient body stores, as 60% of fetal zinc is acquired during the last trimester of pregnancy [9].
Jafaar et al. reported increasing zinc levels with increasing gestational age [10]. Also, Boskabadi et al. in Japan reported lower cord blood zinc and copper in preterms relative to full-term neonates [11]. On the contrary, no significant difference was found between preterms and full terms in the study done by Sakha et al. in Iran [12]. On the contrary, Kojima et al. found lower zinc levels with increasing gestational age [6].
A significant relation was found between cord copper and zinc levels and the anthropometric measures. Full-term neonates showed higher levels of cord blood copper and zinc in AGA in comparison to SGA. However, in the preterm group, AGA showed significantly higher serum copper levels than SGA with no difference in serum zinc levels. So more mature babies had higher zinc and copper levels and the higher the level, the greater were the anthropometric measurements indicating more growth.
Amalia et al. reported that zinc and copper levels in normal neonates were significantly higher than in neonates with fetal growth restriction. Fetal growth restriction can occur due to placental insufficiency which causes defects in placental circulation and transport affecting nutrient transport [13]. The results of Zadrozna et al. research in Poland found a decrease in zinc levels by 37% and copper by 27% in neonates born with fetal growth restriction [14].
Ofakunrin et al. [15] and Abbas et al. [16] demonstrated a significant positive association between cord zinc concentration and birth weight, which suggests that zinc is an important element for fetal growth and development. Sultana et al. in agreement with our work showed a positive correlation between serum copper and mean birth weight of preterm and full-term neonates [17].
On the other hand, Kojima et al. [6] reported no difference in zinc levels in SGA than AGA preterm neonates similar to our results but they found higher copper levels in SGA rather than AGA. A study done in Bangladesh by Islam et al. [18] reported no significant difference in serum zinc level between preterm SGA and AGA babies. Also, Xiang and colleagues reported that serum zinc level in umbilical cord blood had no statistically significant effect on SGA and LGA [19].
Contrary to this work, evaluation of ten trace elements by Bermudez and colleagues showed that cord copper was the only one inversely and independently related to birth weight with highest concentrations found in the SGA group [20]. Marriott et al. reported no significant associations between height, weight, and head circumference with trace element levels except for a weak correlation between copper at term and head circumferences [21].
In the present study, comparing the maternal and neonatal levels revealed that the maternal serum copper and zinc levels were higher than the cord copper and zinc levels. A positive correlation was found between maternal and neonatal zinc and copper levels (r = 0.644 and p = 0.000; r = 0.625 and p = 0.000, respectively).
The higher maternal copper levels can be explained by the transfer of stored copper in maternal tissues (specially the liver) to the growing fetus. Also, the concentration of ceruloplasmin is elevated during gestation with an increased level in maternal blood than in cord blood [22]. Bermudez et al. also reported a positive correlation between cord copper and maternal serum levels [20].
However, Tsuzuki et al. [23] and Ofakunrin et al. [15] reported no significant difference between neonatal and maternal zinc and copper concentrations.
Other studies [5, 22, 24] found lower concentrations of copper and a higher level of zinc in cord blood than in maternal blood. The reduction in maternal zinc levels may be explained by numerous factors including elevated zinc uptake by the fetus and placenta, increased mobilization of plasma zinc to maternal erythrocytes, physiological dilution secondary to enhanced maternal blood volume, and reduced serum albumin for zinc binding during pregnancy. In addition, zinc transporters, as ZnT, present in the placenta, accelerate zinc uptake from the maternal blood to the fetus. Also, previous studies done by Sakha et al. [12] and Iqbal et al. [25] reported significantly lower maternal zinc levels in comparison to their neonates.
Lower zinc and copper in mothers of preterms was found in relation to zinc and copper of mothers of full terms. This is also confirmed by Sultana et al. [17] in Bangladesh who suggested that during pregnancy high levels of estrogen increase ceruloplasmin resulting in increased serum copper in full-term mothers.
Also Maamouri and colleagues stated the presence of a significant association between low birth weight and maternal zinc levels [4]. Many researchers around the world who found a positive correlation between maternal serum zinc and birth weight reported mothers with lower zinc levels to be 2.6 times more liable to deliver LBW babies than those with normal levels, and neonates with decreased zinc levels were 2.8 times more at risk of being LBW [10, 26, 27].
In the present study, there was no relation between the sex and level of serum zinc and copper. Zych and colleagues reported that neonatal gestational age, gender, and birth weight had no substantial impact on concentrations of trace elements in the cord blood except concentrations of iron which was statistically significantly correlated with gender of neonates [28].
In our study, univariate and multivariate linear regression analysis were performed to evaluate the factors affecting weight of neonates. Other than gestational age, only neonatal zinc and copper were independently associated with birth weight.