Maternal Serum Copper Concentration in Premature Rupture of Membrane: A Case-Control Study

MATERIALS AND METHODS

In this case-control study 60 pregnant women with premature rupture of membrane were selected as case group the control group consist of 60 pregnant women with normal delivery pain selected as control group. Both group were matched for maternal and pregnancy age. In case and control groups the pregnancy at term and pre-term were grouped independently. The tool for collected data was based on questionnaire contains demographic information. The questionnaire were filled for each pregnant woman face-to-face when arrived at the women hospital in Dezyani teaching center at Gorgan, Iran, a hospital located at south-east Caspian Sea. The control group further divided into those with term and pre term deliver. Two milliliter of blood was taken from each women and the serum was separated subsequently. The serum Copper was determined using Randox-Standards laboratory kit and spectrophotometer techniques.

The findings of this study were analyzed using kolmogorov-smironov and Mann-whitney statistical methods and were presented in table.

RESULTS

The reference range for female Serum copper concentration is 118-302 mic dL^-1 but this can be increased in the course of pregnancy up to the late stage of pregnancy.

Data analyzes of maternal serum copper concentration in this research project indicated the following results: The copper mean concentration were 201±86 and 207.4±88.5 in case and control groups in term pregnancies, respectively but this differences was not significant. The maternal serum concentration for case and control groups in pre-term pregnancies were 193±74.3 and 195.1±77.7.

Table 1:	Mean serum copper concentration of term and pre term pregnancy in normal and pre-mature rupture of membrane (PROM). Serum copper concentration (μg dL-1)

The normal maternal serum copper concentration pattern in case group was not been followed by kolmogorove-smirov statistical methods and therefore Mann-whitney statistical method was used instead to get a meaningful calculation, but based on either methods of analysis the mean differences was not significant for both case and control group as well (p>0.05). Although, it is appeared there is a slight decrease in the mean of maternal serum copper concentration among case group but statistically it was not significant.

The mean serum copper concentration in pregnant women leading to PROM in term and pre-term pregnancy were 201.4±86 and 193.1+74.3, respectively indicative of lower copper concentration in pre-term pregnancy in pre term case group compared to case with term pregnancy but again this differences was not significant (p>0.05).

Other findings in this study indicate that in general the mean serum concentration at term and pre-term in non-PROM pregnancy were 193.8+84.7 and 190.8±71.5 indicating slight decrease in maternal serum copper concentration in pre-term pregnancy. In addition the general the mean copper for all in pre-term pregnancies in case group was 195.1+77.7. The data analysis in this research project indicate that term pregnancy in both case and control groups showing an slightly higher mean concentration when compared internally among themselves which an indicative of importance maternal serum copper concentration for the outcome of pregnancy (Table 1).

DISCUSSION

Human metabolism crucially dependent on micronutrients such as Copper which play a vital role in metabolic pathways. The many biochemical reaction and particularly those with oxido-reduction capacities entirely associated with the presence of enough micronutrient including Copper, Zinc, Iron and many others such as vitamins. Copper within human bodies strongly attached to a protein called ceruloplasmin and Copper is not freely present in the blood circulation but is bounded with ceruloplasmin. The enzymes which utilize copper as their cofactors can consume oxygen as in oxido-reduction pathways, example in this area of metabolic pathways are verified, but chemical energy production in human within inner mitochondrial membrane and detoxification of many drugs and toxin within the liver entirely dependent on those enzyme and metaloprotein comprising copper as the core subsequent (Alebic-Juretic and Frkovic, 2005; Merker et al., 2005; Knutson, 2007; Uriu-Adams and Keen, 2005; Maia et al., 2007; Zhang et al., 2004; Pathak and Kapil, 2004).

Studies indicate that the micronutrients elements such as copper, zinc are crucial in reproduction cycle in human and copper deficiency during pregnancy might be correlated with some metabolic disorders such as congenital malformations, abortion and PROM premature rupture of membrane due to Copper involvement of such metabolic pathways leading to formation of proper and integrated membrane. In absence of such biochemical pathways the protein required for membrane biosynthesis is diminished leading to rupture and initiating PROM (Yasodhara et al., 1994). In general it seems the copper content of female is increased during pregnancy which can be considered as normal routine metabolic pathways as required by the new physiological conditions in female and the extra copper needed for the formation and the growth of new fetus. Many studies elaborate on the role which played by copper on healthy fetus and its deficiency in the premature rupture of membrane (Bro et al., 1988; McMichael et al., 1994; Fu, 1989).

Serum copper in pregnant female is transported through a tiny regulated system via placenta and the fetus receive the copper from pregnant mother, any metabolic disorder interfering with copper translocation into fetus most probably accompanied with fetus growth disorders and growth retardation, due to copper vital requirement for some metaloproteins urgently needed for divers metabolic function as part of energy production, growth and drug detoxifications (McArdle et al., 2008).

Copper metabolism closely correlated with other micronutrient particularly Iron and anemia due to Iron deficiency cannot be overcome unless serum copper value and some other metabolic disorders such diabetes corrected as well to avoid the effect of copper depletion on growing fetus (Serdar et al., 2006).

Abortion in pregnancy is a symptom with consequences and the reasons behind it which is not clearly elaborated in details, but the premature rupture of membrane due the malfunction in the biosynthesis of proteins due to copper deficiency requiring Copper as cofactor which leading to rupture of membrane prematurely. Based on such findings the role of copper as essential elements in the integrity of health pregnancy is well documented (Fu, 1989; Olivares and Uauy, 1996).

Although, data from many studies did not established a correlation between serum copper concentration during a routine and impaired pregnancies, but contrary to those reports maternal serum copper concentration can be used as prognostic value in predicting the out-come of pregnancy and growing fetus (Alvarez et al., 2007; Alebic-Juretic and Frkovic, 2005; Serdar et al., 2006; Merker et al., 2005; Knutson, 2007; Uriu-Adams and Keen, 2005; Zhang et al., 2004; Pathak and Kapil, 2004; McArdle et al., 2008; Gambling and McArdle, 2004; Schulpis et al., 2004; Meram et al., 2003; Baig et al., 2003; Frendo et al., 2000; Friel et al., 2005; Kantola et al., 2000).

CONCLUSION

There are some reports suggesting that drop in copper concentration can be seen in some disturbed pregnancies such as premature rupture of membrane, based on our data this conclusion can also been derived but even the absolute maternal copper serum concentration of women with premature rupture of membrane is lower in about 5-10% compared to healthy and routine pregnancy but it was not statistically significant. Whether this lower amount concentration of maternal copper among premature rupture of membrane pregnancies is a trigger factor in initiating the disruption of pregnancy it needs further comprehensive investigation.

Mean while the maternal serum concentration might be considered as clinical diagnostic index in pregnancy follow-up. If the assumption of intervening maternal copper concentration in initiating PROM is correct the serum copper concentration can be considered as medical diagnostic venue which can be played as important tool clinically when dealing with disturbed pregnancies.