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Оригінальні дослідження: клінічні науки Research: clinical sciences


UDC 618.3-008.6-06-092:612.014.46:(546.48+546.81)


LEAD AND CADMIUM AS RISK FACTORS

FOR DEVELOPMENT OF GESTATIONAL COMPLICATIONS


Nataliya Sukhodolska


Danylo Halytsky Lviv National Medical University Lviv, Ukraine,

natalia.suhodolska@gmail.com


Introduction. Considering intensive chemical environmental pollution, health care is one of the priority problems in modern medicine. Nowadays, heavy metals, particularly lead and cadmium, which are classified as global environmental pollutants, adversely affect public health. Even low concentrations of these metals and their compounds can accumulate and result in decrease of adaptive body reserves. Under such conditions, generative function is among the least protected and most susceptible ones. In this regard, the concept of reproductive health as a sensitive indicator of ecological problem was stated.


The aim of this study was to evaluate lead and cadmium levels in women’s blood in uncomplicated and complicated pregnancy and to assess the significance of their influence on the gestational process.


Materials and methods. Investigation of lead and cadmium content in the blood of 42 women with uncomplicated pregnancy and 50 women with gestation complicated by anemia (44.0 %) and threatened abortion (56.0 %) was carried out. Determination of metals was evaluated by inversion voltammetry method.


Results. An average concentration of lead in the blood of women with uncomplicated gestation corresponds to generally accepted levels. However, in 11.9 % of pregnant women, metal content was detected within 0.2 to 0.4 mg/l, which is rated as “carriage” and in 4.8 % of women, lead concentrations slightly exceeded the upper level of acceptable content (> 0.4 mg/l). Comparing the results with the data of the Center for Disease Control, physiologically acceptable level of lead (0.1 mg/l) was determined in 57.1 % of women with uncomplicated gestation. Exceeding of this level was detected in 42.9 % of pregnant women, which can cause hypertension in adults and leads to lower IQ, hearing, and growth in children. It is disturbing to determine the lead level above 0.45 mg/l in 11.1 % of women, which is too high and without timely medical aid is dangerous for children’s health.


The average level of lead in complicated pregnancy was defined as “alertness” (0,2-0,4 мг/л) and was

2.4 times higher than in women with uncomplicated course of gestation. The highest concentration of metal was recorded in the blood of women with threatened miscarriage, which was by 154.0 % higher than in uncomplicated pregnancy. At the same time, lead level in women with anemia exceeded the index in physiological gestation by 95.2 %. In comparison with the data of the Center for Disease Control (USA), physiologically acceptable level of lead was determined only in 12.0 % of women with complicated gestation. In 88.0 % of women (in anemia – 86.3 %, threatened abortion – 89.2 %), exceeding of the maximal physiologically acceptable level is observed. Among them, in 63.6 % cases lead concentrations ranged within 0.2-0.44 mg/l, which is regarded as being high for children and “alarming” for adults. Potentially harmful level of lead was observed in 25.0 % of women.


The level of cadmium in the blood of the women with physiological pregnancy corresponded to the known options for an average person (< 0.013 mg/l) and was slightly higher than recommended by the American Conference of Governmental Industrial Hygienists (0.005 mg/l). If compared with the approximate reference level of cadmium in the adults’ blood, cadmium content was determined within 0.005-0.01 mg/l in 33.4 % of women with uncomplicated gestation, which is estimated as the level of “alertness”, and potentially harmful levels were found in 9.5 % of cases (> 0,01 мг/л).

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Оригінальні дослідження: клінічні науки Research: clinical sciences


The average level of cadmium during complicated pregnancy exceeded acceptable level 3 times and 2.8 times the index in uncomplicated gestation. In 44.0 % of women, cadmium was determined in “alert” range, potentially harmful level was found in 40.0 %. The highest content of cadmium was recorded in threatened miscarriage which exceeded the index in physiological gestation 3.2 times. However, pregnant women with anemia had 2.4 times higher cadmium level than healthy ones.


Conclusions. Nowadays in ecological conditions with increased levels of abiotic substances, it is reasonable to implement detection of lead and cadmium contents into practical health care, especially in early gestation, as risk factors for development of gestational complications, which in its turn can protect the health of women and newborns.


Key words: pregnancy, lead, cadmium, gestational complications.


СВИНЕЦЬ ТА КАДМІЙ ЯК ЧИННИКИ РИЗИКУ РОЗВИТКУ ГЕСТАЦІЙНИХ УСКЛАДНЕНЬ


Наталія Суходольська


Львівський національний медичний університет імені Данила Галицького Львів, Україна,

natalia.suhodolska@gmail.com


Вступ. З урахуванням інтенсивного хімічного забруднення навколишнього середовища про- блема збереження здоров’я населення є одним із пріоритетних напрямків сучасної медицини. Сьогодні чималий вплив на стан здоров’я мають важкі метали, зокрема свинець та кадмій, які належать до категорії глобальних забруднювачів довкілля. Навіть у низьких концентра- ціях ці метали та їх сполуки здатні накопичуватись та призводити до зниження адаптацій- них резервів організму. За таких умов однією з найменш захищених і найбільш вразливих є генеративна функція, у зв’язку з чим, було сформульовано концепцію про репродуктивне здоров’я людини як чутливий індикатор екологічного неблагополуччя.


Мета роботи – дослідження вмісту свинцю та кадмію у крові жінок за неускладненого та усклад- неного перебігу вагітності й оцінка значущості їх впливу на перебіг гестаційного процесу.


Матеріали і методи. Досліджено вміст свинцю та кадмію в крові 42 жінок із неускладне- ною вагітністю та 50 жінок, в яких перебіг гестації ускладнився анемією (44,0 %) та загро- зою переривання вагітності (56,0 %). Визначення металів проводилось методом інверсійної вольтамперометрії.


Результати. Середня концентрація свинцю в крові жінок із неускладненою гестацією узгод- жується із загальноприйнятими рівнями, однак у 11,9 % вагітних вміст металу визначався в межах від 0,2 до 0,4 мг/л, що оцінюється як «металоносійство», а в 4,8 % жінок концентрація свинцю дещо перевищувала верхній рівень прийнятного вмісту (> 0,4 мг/л). При порівнянні із даними Центру з контролю за захворюваннями, то у 57,1 % жінок з неускладненою гес- тацією визначався фізіологічно прийнятний вміст свинцю (до 0,1 мг/л). Перевищення цього рівня виявлено у 42,9 % вагітних жінок, що може спричинити гіпертензію у дорослих та призвести до зниження IQ, слуху, темпів росту у дітей. Викликає занепокоєння визначення рівня свинцю понад 0,45 мг/л у 11,1 % жінок, що вважається дуже високим та без своєчасної медичної допомоги небезпечним для життя дитини.


Cередній рівень свинцю при ускладненій вагітності визначався в «насторожуючих» межах

(0,2-0,4 мг/л) й у 2,4 раза перевищував показник при неускладненій гестації. Найвища кон-

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Оригінальні дослідження: клінічні науки Research: clinical sciences


центрація металу зафіксована у крові жінок із загрозою викидня, що на 154,0 % більше, ніж при неускладненій вагітності. Водночас у вагітних жінок з анемією рівень свинцю на 95,2 % перевищував показник при фізіологічній гестації. Порівняно з даними США прийнятний рі- вень свинцю при ускладненій гестації визначався лише у 12,0 % жінок. У 88,0 % жінок з (при анемії у 86,3 %; при загрозі переривання – у 89,2 %) відзначається перевищення мак- симально фізіологічно прийнятного рівня. З них у 63,6 % вміст свинцю коливався в межах 0,2-0,44 мг/л, що розцінюється як високий щодо дітей та як «насторожуючий» стосовно до- рослого населення. У 25,0 % жінок виявлено потенційно небезпечний вміст свинцю.


Рівень кадмію у крові жінок з фізіологічним перебігом вагітності узгоджується з відомими показниками для умовної людини (до 0,013 мг/л) та незначно перевищує рекомендації аме- риканців (0,005 мг/л). При порівнянні з орієнтовними референтними рівнями кадмію у крові дорослого населення, то у 33,4 % жінок з неускладненою гестацією вміст металу визначався в межах 0,005-0,01 мг/л, що оцінюється як рівень «настороженості», а у 9,5 % виявлено потенційно шкідливий рівень (>0,01 мг/л).


Середній рівень кадмію при ускладненій вагітності втричі перевищував рівень нешкідливості (до 0,005 мг/л) та в 2,8 раза показник при неускладненій гестації. У 44,0 % жінок кадмій ви- значався в «насторожуючих» межах, а в 40,0 % виявлено потенційно шкідливий його рівень. Найбільший вміст кадмію зафіксовано при загрозі переривання вагітності, що в 3,2 рази пе- ревищував рівень при фізіологічній гестації. Водночас у жінок з анемією вміст кадмію був у 2,4 раза вищим, ніж у здорових вагітних.


Висновки. В сучасних екологічних умовах на фоні підвищеного надходження абіотичних речовин доцільним є впровадження в практичну охорону здоров’я дослідження вмісту в кро- ві свинцю та кадмію на ранніх термінах вагітності як чинників ризику розвитку гестаційних ускладнень, що в свою чергу забезпечить збереження здоров’я жінки та дитини.


Ключові слова: вагітність,свинець, кадмій, гестаційні ускладнення.


INTRODUCTION


Considering intensive chemical environmen- tal pollution, health care is one of the prior- ity problems in modern medicine [19]. Now- adays, heavy metals, particularly lead and cadmium, which are classified as global envi- ronmental pollutants, adversely affect public health. Even low concentrations of these met- als and their compounds can accumulate and result in decrease of adaptive body reserves. Under such conditions, generative function is among the least protected and most suscepti- ble ones [4, 23]. In this regard, the concept of reproductive health as a sensitive indicator of ecological problem was stated [7, 21].


Environmental pollution has an active harmful impact on children’s health, because of their high sensitivity to the effects of heavy metals through- out all periods of growth and development, in- cluding the intrauterine stage [6, 8, 9, 13].


High lead toxicity and ability to accumulate in organs and tissues endanger penetration


of metals into the human body via various routes with further development of various toxic effects, including remote and irrevers- ible ones due to the affection of the cell ge- nome [19, 20].


Correlation between elevated levels of lead in the blood and the development of threatened abortion and premature birth syndrome has been detected [12]; lead excess can cause miscarriage, intrauterine growth retardation, chronic fetal hypoxia, bleeding during pregnan- cy and labor, and occurrence of birth defects in infants [2, 5, 8, 14, 22]. Even very low levels of lead in the fetal blood can lead to a significant reduction of a child’s mental abilities [8].


In experiments on animals, it has been shown that inhalation of cadmium can cause fewer offspring and higher frequency of congenital malformations, namely embryotoxic and tera- togenic effects, and in adults – liver damage and alterations in the immune system [3, 15]. A controversial issue is the impact of high levels of placental cadmium on reduction of

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Оригінальні дослідження: клінічні науки Research: clinical sciences


neonatal anthropometric data (weight, height, chest circumference) [10, 16].


The acceptable concentration of lead in the blood for adults is considered 0.2 mg/l. The range 0.2-

0.4 mg/l is “alert” and rated as “metal carriage”. The exceeding of 0.4 mg/l is regarded as a po- tentially harmful level [11, 20].


The US Center for Disease Control developed officially acceptable medical standards of blood lead levels for children and adults, ac- cording to which the content below 0.1 mg/l is considered a physiologically acceptable maximum. If lead level in a pregnant wom- an’s blood is higher, the same level is likely to be in her newborn child, which can cause dis- orders of psychological development. In chil- dren, lead content 0.1-0.19 mg/l is estimated as increased, 0.2-0.44 mg/l – high, and 0.45-

0.69 mg/l – very high level; concentration above 0.7 mg/l is considered extremely high and requires immediate treatment [2].


An acceptable level of cadmium in the blood for an average person is considered

0.007 mg/l ranging within 0.004-0.013 mg/l [18], for occupational exposure, according to American Conference of Governmental Indus- trial Hygienists (ACGIH), – 0.005 mg/l [1]. The suggested reference levels of cadmium in adults’ blood are the following: a modified norm – up to 0.005 mg/l; the level of “alert- ness” – 0.005-0.01 mg/l; potentially harmful level – above 0.01 mg/l [11].


Thus, considering an increase in basic content of priority environmental pollutants, during pregnancy a woman’s body is under their harmful influence. In this regard, a scientif- ic search for risk factors of potential adverse effect on the gestation process for timely im- plementation of adequate preventive and cor- rective measures is an important issue. Thus, the aim of this study was to evaluate lead and cadmium levels in women’s blood in uncompli- cated and complicated pregnancy and to as- sess the significance of their influence on the gestational process.


MATERIALS AND METHODS


To achieve the aim, lead and cadmium levels in the blood of 92 pregnant women were investi- gated. The women were under medical super- vision in prenatal first city community clinic in

Lviv. The selection criteria were the following: the first trimester of pregnancy, homogeneity of social status, absence of physical, genetic and oncological diseases, burdened obstetric and gynecological history. The metal content in the blood was investigated in 42 women with uncomplicated pregnancy and 50 women with gestation complicated by anemia (44.0 %) and threatened abortion (56.0 %). The course of pregnancy was analyzed by statistical process- ing of primary documents – individual map of pregnant and parturient women (form 111/o).


Determination of metals was evaluated by in- version voltammetry method. Preparation of blood samples was conducted in the Central Research Laboratory and Laboratory of indus- trial toxicology of Danylo Halytsky Lviv Na- tional Medical University. Measurements were carried out using voltammetry analyzer AVА-2 in the Sanitary Epidemiological Station of Lviv Railway.


Results. An average concentration of lead in the blood of women with uncomplicated ges- tation was 0.124±0.017 mg/l, which corre- sponds to generally accepted levels. However, in 11.9 % of pregnant women, metal content was detected within 0.2 to 0.4 mg/l, which is rated as “carriage” [20]. Disturbing is the fact that in 4.8 % of women, lead concentrations slightly exceeded the upper level of accept- able content (> 0.4 mg/l). Thus, blood lead level corresponded to the existing norms in

83.3 % of women with physiological pregnan- cy, in the rest of women it exceeded the limit, that will contribute to a similar tendency to its content increase in a child’s blood.


Comparing the results with the data of the Center for Disease Control [2], physiologically acceptable level of lead (0.1 mg/l) was deter- mined in 57.1 % of women with uncomplicated gestation. Exceeding of this level was detected in 42.9 % of pregnant women, lead concentra- tions ranged within 0.1-0.19 mg/l in 61.1 % of them, which, according to the reviewed lit- erature [17], causes hypertension in adults and leads to lower IQ, hearing, and growth in children. According to data [2], children may have problems with behavior and learning. In

27.8 % of women, lead concentrations in the blood constituted from 0.2 to 0.44 mg/l, which causes neurological disorders and intellectual decline in children. It is disturbing to determine the lead level above 0.45 mg/l in 11.1 % of

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Оригінальні дослідження: клінічні науки Research: clinical sciences


women, which, according to the US data, is too high and without timely medical aid is danger- ous for children’s health.


The average level of lead in complicated preg- nancy was 0.295±0.027 mg/l, that is defined as “alertness” and was reliably (p<0.05) 2.4 times higher than in women with uncompli- cated course of gestation (Table 1). “Carriage” was found in 54.0 % of women, and potentially harmful level of lead (> 0.4 mg/l) was observed in 24.0 % of blood samples. The highest con- centration of metal – 0.315±0.033 mg/l was recorded in the blood of women with threat- ened miscarriage, which was by 154.0 % high- er (p<0.05) than in uncomplicated pregnancy. At the same time, lead level in women with anemia exceeded the index in physiological gestation by 95.2 % (p<0.05).


Тable 1.


Content of lead in the women’s blood (М ± m)


Course of pregnancy

Lead content, mg/l

Uncomplicated pregnancy

42


0.124±0.017

Complicated pregnancy

50

0.295±0.027*

Threatened abortion

28

0.315±0.033*

Anemia

22

0.242±0.034*


Note * – р<0.05 as compared with uncomplicated preg- nancy


In comparison with the data of the Center for Disease Control (USA), physiologically ac- ceptable level of lead was determined only in

12.0 % of women with complicated gestation. In 88.0 % of women (in anemia – 86.3 %, threatened abortion – 89.2 %), exceeding of the maximal physiologically acceptable level is observed. Among them, in 63.6 % cases lead concentrations ranged within 0.2-0.44 mg/l, which is regarded as being high for children and “alarming” for adults. In 25.0 % of wom- en, lead level was above 0.45 mg/l, which, as noted above, is considered potentially danger- ous for adults and without timely medical care is dangerous for children’s life.


It was established that the level of cadmium in the blood of the women with physiological pregnancy was equal to 0.0054±0.0008 mg/l,

i.e. relevant with the known options for an av- erage person (< 0.013 mg/l) and slightly high-

er than recommended by the American Con- ference of Governmental Industrial Hygienists

(0.005 mg/l). If compared with the approxi- mate reference level of cadmium in the adults’ blood [16], cadmium content was determined within 0.005 – 0.01 mg/l in 33.4 % of women with uncomplicated gestation, which is esti- mated as the level of “alertness”, and poten- tially harmful levels were found in 9.5 % of cases. Thus, cadmium content corresponded to the existing norms in 57.1 % of pregnant women among the total number of surveyed women with physiological pregnancy, in the rest women it exceeded this limit 1.8-2.2 times, which will promote an increase in its content in the children’s blood.


The average level of cadmium during compli- cated pregnancy was 0.0152±0.0025 mg/l, that exceeded thrice the acceptable level and 2.8 times (p<0.05) the index in uncom- plicated gestation (Table 2). In 44.0 % of women, cadmium was determined in “alert” range, potentially harmful level was found in

40.0 %. The highest content of cadmium – 0.0171±0.0031 mg/l – was recorded in threat- ened miscarriage which exceeded the index in physiological gestation 3.2 times (p<0.05). However, pregnant women with anemia had

2.4 times higher cadmium level (p<0.05) than healthy ones.


Тable 2.


Content of cadmium in the women’s blood (М ± m)



Course of pregnancy

Cadmium content, mg/l

Uncomplicated pregnancy

42

0.0054±0.0008

Complicated pregnancy

50

0.0152±0.0025*

Threatened abortion

28

0.0171±0.0031*

Anemia

22

0.0130±0.0035*


Note * – р<0.05 as compared with uncomplicated preg- nancy


Conclusions


In complicated gestation, the lead level was de- tected in the “alarming” range (0.2-0.4 mg/l) and was 2.4-3.1 times higher than recom- mended by the US researchers (0.1 mg/l), while the cadmium content exceeded accept- able level (0.005 mg/l) 3 times and 1.3-1.7 times – potentially harmful level (0.01 mg/l). The excess of acceptable levels of lead was de-

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Оригінальні дослідження: клінічні науки Research: clinical sciences


tected in 78.0 % of women with complicated pregnancy, of cadmium – in 84.0 %, whereas during the physiological gestation – in 16.7 % and 42.9 % women, respectively. Lead lev- els higher 1.9-2.5 times (p<0.05) and con- centration of cadmium higher 2.4-3.2 times (p<0.05) were found in all groups of women with complicated pregnancy compared with uncomplicated pregnancies.

Thus, nowadays in ecological conditions with increased levels of abiotic substances, it is reasonable to implement detection of lead and cadmium contents into practical health care, especially in early gestation, as risk fac- tors for development of gestational complica- tions, which in its turn can protect the health of women and newborns.


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    Оригінальні дослідження: клінічні науки Research: clinical sciences


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Cтаття надійшла 11.10.2016


Після допрацювання 02.12.2016


Прийнята до друку 16.11.2016