The Concentration Of Micronutrients And Heavy Metals In .

HindawiJournal of PregnancyVolume 2019, Article ID 5062365, 7 pageshttps://doi.org/10.1155/2019/5062365Research ArticleThe Concentration of Micronutrients and Heavy Metals inMaternal Serum, Placenta, and Cord Blood: A Cross-SectionalStudy in Preterm BirthRima Irwinda, Noroyono Wibowo, and Atikah Sayogo PutriMaternal Fetal Division, Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Indonesia/Cipto MangunkusumoHospital, Jakarta 10430, IndonesiaCorrespondence should be addressed to Atikah Sayogo Putri; atikahsayogo@gmail.comReceived 10 October 2018; Revised 22 November 2018; Accepted 5 December 2018; Published 1 January 2019Academic Editor: Olav LapaireCopyright 2019 Rima Irwinda et al. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background. Preterm birth is still a global burden particularly in Indonesia. The suboptimal concentration of certain micronutrientsand heavy metals is hypothesized to play a role in the mechanism of preterm birth. Objective. This study aimed to analyze themicronutrients and heavy metals concentrations between subjects with term and preterm birth. Design. A cross-sectional studywas conducted during January–June 2017 in Cipto Mangunkusumo Hospital and Budi Kemuliaan Hospital, Jakarta, Indonesia.Subjects were divided into term and preterm birth groups. The measured outcomes were maternal serum, placental, and bloodcord concentration of zinc, copper, iron, selenium, manganese, mercury, lead, AtRA, and 25(OH)D. Results. A total of 51 pregnantwomen participated in this study. Term group had higher concentration of maternal serum AtRA (0.22 0.07 ng/mL versus 0.12 0.03 ng/mL, p 0.001), higher placental concentration of manganese {0.99 (0.38 – 1.78) 𝜇g/g versus 0.42 0.18 𝜇g/g, p 0.001},iron (252.16 170.61 𝜇g/g versus 78.45 51.73 𝜇g/g, p 0.001), copper {2.96 1.80 𝜇g/g versus 1.62 (0.70 – 3.88) 𝜇g/g, p 0.019}, zinc{58.34 (27.88 – 124.05) 𝜇g/g versus 28.41 (1.46 – 137.69) 𝜇g/g, p 0.011}, selenium (0.31 0.31 ng/g versus 0.14 0.20 ng/g, p 0.024),AtRA {21.7 10.69 ng/g versus 0.7 (0.42 – 5.10) ng/g, p 0.001}, and 25(OH)D {75.84 45.12 ng/g versus 18.00 (5 – 88) ng/g, p 0.001}, lower placental concentration of mercury (0.20 0.17 ng/g versus 20.47 41.35 ng/g, p 0.019) and lead (0.02 0.01 ng/gversus 0.81 1.43 ng/g, p 0.009), and higher cord blood concentration of copper {32.20 (16.30 – 69.60) 𝜇g/dL versus 20.60 (5.80– 53.30) 𝜇g/dL, p 0.006} and AtRA (0.16 0.04 versus 0.07 0.01, p 0.001). Conclusion. Preterm birth is associated with lowerconcentrations of micronutrients which play a role in antioxidant mechanism, as well as higher concentration of mercury and lead.1. IntroductionPreterm birth, defined as babies born alive before 37 weeksof pregnancy, remains the leading cause of mortality andmorbidity of children under the age of 5 in global scale,particularly in a developing country such as Indonesia. Asmuch as 15 out of 100 babies are delivered prematurely, contributing to 35.5% of neonatal death in the country [1]. Whileits incidence contributes to almost 50% of birth in CiptoMangunkusumo Hospital, Indonesia (2015–2017), the precisemechanism of preterm birth remains unclear. The cellularapoptosis that transmits an inflammatory signal, senescentplacental cells, and its changes in placental membrane werehypothesized to stimulate parturition, both term and pretermbirth, called as “common pathway.” The premature aging ofthe placenta caused by oxidative stress is believed to stimulatethe common pathway prematurely. Reactive Oxygen Stress(ROS), the source of oxidative stress, activates NF-kappaB which further stimulates COX-2 and proinflammatorycytokines. Infection and exogenous factor such as lead exposure also upregulate ROS, increasing the risk of preterm birth.Micronutrients such as trace elements and vitamins such ascopper, zinc, manganese, selenium, and vitamin A serve asendogenous antioxidant that counterbalances the oxidativestress, as well as regulating inflammatory response [2, 3].Micronutrients are essential inorganic constituents forhuman health although only needed in minute quantities.Suboptimal status of micronutrients, whether deficiencyor excess, could lead to detrimental pregnancy outcome,although it is difficult to identify since many pregnancy

2complications are often multifactorial. The knowledge oftrace elements and vitamins role has been progressive forthe past 40 years. Essential trace elements of the humanbody include iron (Fe), zinc (Zn), copper (Cu), selenium(Se), and manganese (Mn). These elements are related inso many enzymes that single trace element deficiency isoften not associated with specific clinical manifestation, butit manifests as a combination of various symptoms [4, 5].Studies have demonstrated the role of trace elementsalong with vitamin A and vitamin D in antioxidant activitywhich is very important in pregnancy. Preeclampsia, pretermbirth, and intrauterine growth restriction are among pregnancy complications related to inflammatory state. Micronutrients also play role in the division and differentiation of fetalcells and their development [5].Concentrations of micronutrients is affected by dietaryhabit, lifestyle, and environmental condition. Followingindustrial revolution, mercury (Hg) and lead (Pb) are gainingattention regarding environmental exposure and their effectsin the body. During pregnancy, even low lead concentrationcould have adverse effects such as developmental delays,low birthweight, and miscarriage. Contamination of mercuryoccurs primarily through the consumption of contaminatedseafood and rice grown in contaminated waters. It is activelytransported across the placenta and impairs fetal neurodevelopment [6, 7].We believe it is important to evaluate the status ofmicronutrients of pregnant women and whether its concentration is different between term and preterm birth inIndonesia. By gaining the knowledge about the exact roleof micronutrients in the pregnancy, better nutrient approachof pregnancy would be achieved to optimize the normalpregnancy and to reduce the incidence of pregnancy complications, particularly preterm birth.2. MethodsA cross-sectional study was conducted to expand the knowledge about the status of micronutrients in pregnant womenwho gave birth at term and preterm. The measured outcomes were maternal serum, placental, and blood cordconcentration of zinc, copper, iron, selenium, manganese,mercury, lead, AtRA, and 25(OH)D. Subjects were selectedby consecutive sampling technique.Sample was taken in Cipto Mangunkusumo NationalCentral General Hospital and Budi Kemuliaan Hospitalduring January–June 2017. This study has been approvedby Ethics Committee of Faculty of Medicine of UniversitasIndonesia (LB.01.01/X.2/179/2016).The inclusion criteria were pregnant women undergoingpreterm birth in 26–36 weeks of gestational age for thepreterm groups and 37 weeks of gestational age for theterm group and agreed to participate by signing informedconsent. The exclusion criteria were subjects with multiplepregnancies, intrauterine growth restriction (IUGR), fetalcongenital anomaly, preterm premature rupture of membrane (PPROM), and other comorbidities (hypertension inpregnancy, preeclampsia, gestational diabetes mellitus, heartdisease, and autoimmune disease).Journal of PregnancyTable 1: Characteristics of subjects.VariableAge (years)Body height (cm)BMI (kg/m2 )UAC 23.5 cm 23.5 cmTerm (n 25)27.68 (6.47)153.44 (5.79)21.75 (3.22)Preterm (n 26)24 (17 – 41)156.70 (4.81)22.17 (4.65)p0.463a0.034b0.707b6199170.127cBMI: body mass index, UAC: upper arm circumference.aMann-Whitney test. b Independent t-test. c Chi-square test.All of the samples were obtained soon after delivery. 15cc of maternal blood sample was obtained from the veinand then put into serum separator tube (SST) for AtRA and25(OH)D measurement as well as trace element clot activatortube to measure other trace elements. Samples were then sentwithin 30 minutes to Prodia Laboratory, Jakarta. Sampleswere centrifuged for 10 minutes and were kept at –80 C.Placental tissues were taken from marginal placenta and fullthickness-parenchymal placenta. Each sample was put intophosphate-buffered saline (PBS) solution and then kept at4 C for maximum 24 hours.Zinc, copper, iron, selenium, manganese, mercury, andlead were measured by Inductively Coupled Plasma-MassSpectrometry (ICP-MS) using Agilent-MS 7700x series. Samples were diluted to 2 mL with a matrix solution containing0.05 mL of concentrated ammonia, 1 mL of 0.01 M disodiumethylenediaminetetraacetate, 0.7 mL of Triton X-100, and 20mL of butanol per liter [8]. AtRA and 25(OH)D were measured by Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) technique with electrospray ionizationfollowing liquid-liquid extraction, solid-phase extraction,and derivatization with 4-phenyl-1,2,4-triazoline-3,5-dione(PTAD). The instruments used in the technique were AgilentLiquid Chromatography (LC) System 1290 with AgilentTriple Quad 6460 (LC/MS). In AtRA isomer separations, theretention times were set to 8.0 minutes for blood sample and14.3 minutes for placenta. All mass transitions used dwell timeof 50 ms and fragmentor voltage of 100V. Other parameterswere as follows: electron multiplier voltage 400V, nitrogengas flow rate 9 L/min, nebulizer pressure 40 psi, sheathgas temperature 250 C, sheath gas flow rate 7 L/min, andcapillary potential 3000V [9, 10]. The examinations wereperformed in Prodia Laboratory, Jakarta.Data was processed using IBM SPSS version 20 program.Data analysis was conducted using Shapiro-Wilk normalitytest, hypothesis test according to variable type and datanormality, and correlation test according to data normality.The data were supplemented with 95% confidence interval,with the significance limit being set to p 0.05.3. ResultsA total of 51 pregnant women were selected, divided into termgroup and preterm group. Table 1 presents characteristics ofsubjects. Participant flowchart is depicted in Figure 1. Body