ABSTRACT
Background and Aim:
With the growth of the world’s economy and industrialization, lead (Pb) contamination in the environment has become a major issue on a global scale. Lead is typically linked to unfavorable pregnancy outcomes such as stillbirth, low birth weight preterm, and spontaneous abortion. In this study, we evaluated the blood lead levels of pregnant women and their birth outcomes attending an Indian tertiary care teaching hospital, those who were not exposed to any lead-associated industry or shops.
Methods:
A descriptive study was undertaken to evaluate blood lead estimation in pregnant women and umbilical blood lead levels in a community hospital. Blood samples from 104 mothers during the 1st trimester, 90 mothers during 3rd trimester, and from the umbilical cord were collected. Self-administered questionnaires were used to collect information on demographics, medical history, and concerns linked to pregnancy. Following acid digestion, the levels of lead in whole blood were determined by an atomic absorption spectrometer. The DNA damage in high blood lead-concentrated pregnant women was evaluated by comet assay methods.
Results:
Among 194 blood samples of pregnant women, 31 (15.98%) samples revealed ≥5 μg/dL blood lead levels. High lead concentration (≥5 µg/dL) in 1st trimester pregnant women, end of 3rd trimester and cord blood were detected 20.19%, 11.11% and 1.11% respectively. The mean blood lead levels in 1st trimester, 3rd trimester, and cord blood were 3.88 ± 3.19, 2.66 ± 1.82, and 1.53 ± 1.06 mg/dL, respectively. The blood lead concentrations were significantly higher in the 1st trimester of pregnancy than in the 3rd trimester of pregnancy (P < 0.0017). A positive correlation between maternal and infant blood lead levels was revealed (P < 0.0001). When the comet assay was used to assess the genotoxic consequences of elevated blood lead levels during pregnancy, higher amounts of DNA damage were found in the samples (P < 0.01).
Conclusion:
In this descriptive study, there was a significant amount of lead transferred from mother to baby through the placenta. All mothers were not exposed to lead-associated industry and most were housewives. This article may be viewed as an eye-opener for understanding the blood lead concentration during pregnancy to avoid abnormal birth outcomes. To minimize exposure to environmental lead, all possible measures should be undertaken.
Keywords: Blood lead level, comet assay, DNA damage, lead poisoning, newborn, reproductive toxicity
Introduction
A toxic heavy metal present in the crust of the Earth is lead (Pb). In most parts of the world, its widespread use has led to environmental damage, human exposure, and public health issues.[1] Inhalation, ingestion, cutaneous absorption, absorption through retained or embedded leaded foreign bodies, and trans-placental (endogenous) pathways are all possible ways to be exposed to lead and lead-containing substances. Lead is transferred to organs like the brain, kidneys, liver, and bones after it enters the body. Lead is stored by the body in the teeth and bones, where it gradually builds up. Lead levels in the blood are typically used to measure human exposure.[2]
For both adults and children, the nervous system is the primary site of lead toxicity. Exposure at high levels may cause delirium, convulsions, stupor, coma, or even death. In addition to these obvious signs and symptoms, lead toxicity can also cause anemia, gout, nephropathy, lead colic, ataxia, headaches, loss of appetite, weariness, muscle and joint pain, changes in behavior, and peripheral neuropathy.[3] Anemia, hypertension, renal impairment, immunological toxicity, and toxicity to the reproductive organs are further effects of lead exposure.[4]
During pregnancy, lead from bones is released into the blood. Increased lead levels have been linked to a number of negative pregnancy outcomes, for instance, gestational hypertension, spontaneous abortion, and low birth weight.[5] Lead is quickly absorbed via the placenta by passive diffusion, and fetal brain tissue has been discovered as early as the 1st trimester. Children are particularly susceptible to neurological problems brought on by lead exposure because of their developing brain systems.[6]
The placenta, which receives a lot of attention during pregnancy, is insufficient as a barrier to prevent the newborn from being exposed to harmful heavy metals, particularly lead. The environment is in danger from potential lead exposure from the placenta. Due to hormonal changes, deposits of lead that have been accumulating in the mother’s bones and teeth for years as a result of a polluted environment are released into her circulation during pregnancy.[6,7] Exposure to lead during a person’s prenatal and postnatal development can substantially disrupt their neurocognitive system, resulting in the onset of attention deficit hyperactivity disorder (ADHD). Lead is a neurotoxic metal. One research by Rísová et al.[8] provides a comprehensive review of the “toxic pathway” of lead via the mother’s body, the risks related to its buildup in the pregnant fetus, and transplacental transfer, as well as doable safeguards for all newborns.
Lead exposure has negative impacts on both children and adults at lower exposure levels than had previously been recognized. The first recommendations for lead exposure screening and management for pregnant and lactating women were published by the Centers for Disease Control and Prevention in 2010.[9,10]
Lead exposure has negative impacts on both children and adults at lower exposure levels than had previously been recognized. The first recommendations for lead exposure screening and management for pregnant and lactating women were published by the Centers for Disease Control and Prevention in 2010.[11,12]
It is generally known that a diet rich in calcium, iron, zinc, vitamin C, vitamin D, and vitamin E prevents the body from absorbing lead. Iron deficiency anemia is associated with high blood lead levels, which may potentially increase lead absorption.[13] Blood lead level screening during pregnancy is an important measure to identify potential lead exposure in expectant mothers. Exposure to lead during pregnancy can have detrimental effects on both the mother and the developing fetus. While the screening guidelines may vary between countries and medical organizations, it is generally recommended to consider lead screening for pregnant women who are at increased risk of exposure.
In this study, we estimated blood lead levels in pregnant women during 1st trimester, 3rd trimester mothers, from venous blood, and cord blood from newborn babies. High blood lead levels in pregnant women were correlated to their demographic data, clinical history, and birth outcome. The DNA damage in the high blood lead level was evaluated by comet assay.
Methodology
This descriptive study was approved by the Scientific Advisor Committee and Institutional Ethics Committee of ICMR-NIOH, Ahmedabad. After approval, we collected blood samples from 1st-trimester pregnant women, 3rd-trimester pregnant women, and cord blood of newborn babies attending the Obstetrics and Gynaecology Department of BJ Medical College. Before taking samples, the brief of the study was explained to the studied population, and interested one’s blood samples were collected with their consent form. With a self-prepared questionnaire, we documented the demographic and clinical history of the participants. The women residing in industrial areas or working in industrial occupations were excluded from this study. Women who are housewives, or with official jobs, agriculture jobs, and household jobs were included in this study. Two types of dietary were found during the questionnaire. Those who took pure vegetarian and nonvegetarian food were included in vegetarian and nonvegetarian groups, respectively. From the questionnaire, we found that participants’ drinking water sources were direct soil boring tap water, Government supplied water, i.e. municipally supplied water, and reverse osmosis (RO) water. The height of all the participants was documented with a wall-mounted height rod, and weights were measured by a weighing machine at the OPD of the Gynaecology department. A total volume of 3 mL of venous blood was collected aseptically in lead-free vacationer heparinized tubes for blood lead level estimation from all participants. After collection, all samples were preserved at −20°C for further analysis.
Blood digestion for estimation of lead
After using the wet digestion procedure, lead was assessed in whole blood. Teflon vessels and other laboratory goods were utilized in microwave digestion by placing in 10% (v/v) HNO3 for at least 24 h, then rinsing in deionized water before use, as per wet digestion technique for whole blood. The digestion process was conducted using the following procedures in accordance with the environmental protection agency (EPA) 3052 method [Figures 1 and 2].
Figure 1.
Flow chart for blood digestion for lead estimation
Figure 2.
Work flow from collected sample the blood lead estimation
Measurement of lead in digested blood samples
The standards and digested samples were cooled to room temperature. The atomic absorption spectrophotometer was aspirated with the standard solutions of 0, 10, 25, 50, 75, and 100 parts per billion (ppb). A graph illustrating the standards was made after standard readings were recorded. The standard graph was drawn with an R2 ≥0.99 throughout time [Figure 3]. The sample was then put into the graphite furnace of an atomic absorption spectrophotometer (Analyst 800, Perkin Elmer, USA) in a volume of 20 μL. The graph created from the sample measurements was used to estimate the lead levels in the samples.
Figure 3.
Standardization of lead concentration with correlation coefficient ≥99
Following the receipt of the blood lead report, the study population was split into two groups: those with low blood lead levels (<5 µg/dL) and those with high blood lead levels (5 µg/dL). All demographic information and clinical symptoms of the group under study were captured in the questionnaire. All of the individuals had thorough case histories that included information on their age, social standing, parity, eating habits, place of residence, potential occupational exposure, etc., The categorization or medical background of the patients had no bearing on the analysis.
DNA damage in Comet assay
In this comet assay technique, 10 μL of blood was mixed with 90 μL of Low-melting-point agarose (LMPA) (0.5% in Phosphate-buffered saline [PBS]) and was smeared on a slide that was sandwiched between 1st coat (1% normal melting point agarose [NMPA] in PBS) and 3rd coat (0.5% of LMPA in PBS). The cleaned and dried slides from gel electrophoresis were stained with ethidium bromide and examined under a fluorescence microscope. Using Comet Assay Software Project (CASP) software, the comet’s DNA damage score was calculated.
Results
In this descriptive study, all the participants were from the community hospital and no one was exposed to lead environmental industry. Among the total 194 blood samples of pregnant women, 31 (15.98%) revealed ≥5 μg/dL blood lead levels. In both 1st trimester (n = 104) and 3rd trimester (n = 90), pregnant women revealed high blood lead levels of 21 (20.19%) and 10 (11.11%), respectively. The blood lead concentrations were significantly higher in the 1st trimester of pregnancy than in the 3rd trimester (P = 0.0017).
There was no statistical significance in the education with respect to the blood levels of pregnant women [Figure 4]. The occupations of all participants were documented, and most of them were homemakers. There was no statistical significance of occupation with respect to high blood levels in pregnant women (P = 0.274) [Table 1]. In the 1st trimester group, the number of participants with vegetarian and nonvegetarian was 60 and 44, respectively. Among them, high (≥5 μg/L) blood lead levels were found in 9 and 12 participants of vegetarian and nonvegetarian food habits, respectively. In the 3rd trimester, the percentage of pure vegetarians and nonvegetarians with ≥5 μg/dL blood lead level was 6.67% and 13.33%, respectively. The Chi-square test revealed the association of nonvegetarian group having high blood levels as compared with the vegetarian group (P = 0.023) [Table 2]. Whereas, there was no statistical significance on the type of drinking water with blood levels (P = 0.284) [Table 3].
Figure 4.
Education of pregnant women with respect to lead concentration (n = 194)
Table 1.
Occupation of the studied population
| Collection of blood during pregnancy | Lead Concentration | Occupation type | Total | |||
|---|---|---|---|---|---|---|
|
| ||||||
| Housewife | Official job | Agriculture job | Household job | |||
| 1st trimester | ≥5 µg/dL | 18 | 1 | 0 | 2 | 21 |
| <5 µg/dL | 71 | 4 | 1 | 7 | 83 | |
| 3rd trimester | ≥5 µg/dL | 10 | 0 | 0 | 0 | 10 |
| <5 µg/dL | 61 | 6 | 11 | 2 | 80 | |
| Total | 160 | 11 | 12 | 11 | 194 | |
Table 2.
Dietary habits of pregnant women with respect to lead concentration
| Collection of blood during pregnancy | Lead Concentration | Dietary Habits | Total | |
|---|---|---|---|---|
|
| ||||
| Pure Vegetarian | Nonvegetarian | |||
| 1st trimester | ≥5 µg/dL | 9 (15%) | 12 (27.27%) | 21 |
| <5 µg/dL | 51 (85%) | 32 (72.73%) | 83 | |
| 3rd trimester | ≥5 µg/dL | 2 (6.67%) | 8 (13.33%) | 10 |
| <5 µg/dL | 28 (93.33%) | 52 (86.66%) | 80 | |
Table 3.
Type of drinking water used by studied population
| Collection of blood during pregnancy | Lead Concentration | Drinking water | Total | ||
|---|---|---|---|---|---|
|
| |||||
| Boring tap water | Municipal supplied water | RO water | |||
| 1st trimester | ≥5 µg/dL | 0 | 1 | 20 | 21 |
| <5 µg/dL | 4 | 12 | 67 | 83 | |
| 3rd trimester | ≥5 µg/dL | 2 | 2 | 6 | 10 |
| <5 µg/dL | 4 | 11 | 65 | 80 | |
All the 1st-trimester pregnant women had their height and weight collected, and the body mass index (BMI) was determined using the formula: weight (kg)/height2 (m)2. BMI below 18.5 was regarded as the underweight range, 18.5 to 24.9 as the healthy weight range, 25 to 29.9 as the overweight range, and 30 to 39.9 as the obese range. High blood lead levels had no statistically significant relationship with BMI (P = 0.574) [Table 4].
Table 4.
BMI of studied population
| Collection of blood during pregnancy | Lead Concentration | BMI | Total | |||
|---|---|---|---|---|---|---|
|
| ||||||
| <18.5 | 18.5–24.9 | 25–29.9 | 30–39.9 | |||
| 1st trimester | ≥ 5 µg/dL | 2 | 14 | 2 | 3 | 21 |
| < 5 µg/dL | 16 | 48 | 14 | 5 | 83 | |
| 3rd trimester | ≥ 5 µg/dL | 0 | 4 | 5 | 1 | 10 |
| < 5 µg/dL | 1 | 50 | 20 | 9 | 80 | |
The age of participants for both 1st trimester and 3rd trimester groups was documented during the collection of blood samples. Between the age group of 15–25 years, the concentration of ≥5 μg/dL, blood lead levels were 15. 38% and 6.66% in the 1st trimester and 3rd trimester, respectively. There was no statistical significance on the age of pregnant women with high blood lead levels (P = 0.127) [Table 5].
Table 5.
Age of the female during participant for this study
| Collection of blood during pregnancy | Lead Concentration | Age (years) | Total | |
|---|---|---|---|---|
|
| ||||
| 15–25 | 26–40 | |||
| 1st trimester | ≥5 µg/dL | 16 (15.38%) | 5 (4.80) | 21 (2019) |
| <5 µg/dL | 54 (51.92%) | 29 (27.88%) | 83 (79.80%) | |
| 3rd trimester | ≥5 µg/dL | 6 (6.66%) | 4 (4.44%) | 10 (11.11%) |
| <5 µg/dL | 49 (54.44%) | 31 (34.44%) | 80 (88.88%) | |
Gravidity is the number of times that a woman became pregnant. Out of 71 primigravida and 33 multigravida in the 1st trimester of pregnancy, 18 and 3 had high blood lead concentrations, respectively. Whereas, out of 48 primigravida and 32 multigravida, high blood lead levels were found in 3 and 7, respectively [Table 6].
Table 6.
Gravidity and parity of participants of samples collected from both 1st trimester and 3rd trimester pregnant women
| Collection of blood during pregnancy | Lead Concentration | Gravidity | Total | |
|---|---|---|---|---|
|
| ||||
| Primigravida | Multigravida | |||
| 1st trimester | ≥5 µg/dL | 18 | 3 | 21 |
| <5 µg/dL | 53 | 30 | 83 | |
|
| ||||
| Collection of blood during pregnancy | Lead concentration | Parity | Total | |
|
| ||||
| Primiparous | Multipara | |||
|
| ||||
| 3rd trimester | ≥5 µg/dL | 7 | 3 | 10 |
| <5 µg/dL | 52 | 28 | 80 | |
Regardless of whether the kid was delivered alive or not, the number of times a woman has given birth to a fetus with a gestational age of 24 weeks or more is known as parity. The distribution of study subjects according to their parity revealed that 21 had high blood lead concentration in their 1st trimester, out of which nine were nulliparous, four prime, and eight multipara. Similarly, high blood lead level was detected in 10 during 3rd trimester, out of which 7 were primiparous and 3 multiparous [Table 6].
Spontaneous abortion is the loss of pregnancy naturally before 20 weeks of gestation. With clinical history, we found 22 spontaneous miscarriages in the 1st trimester and among them, 6 had high blood lead levels. It was shown that high blood lead levels are associated with more spontaneous miscarriages than low blood lead levels (P = 0.173) [Table 7].
Table 7.
Spontaneous miss carriage
| Collection of blood during pregnancy | Lead Concentration | Spontaneous miss carriage | No miss carriage | Total |
|---|---|---|---|---|
| 1st trimester | ≥5 µg/dL | 6 (28.57%) | 15 (71.43%) | 21 (20.19%) |
| <5 µg/dL | 16 (19.27%) | 67 (80.72%) | 83 (79.80%) | |
| 3rd trimester | ≥5 µg/dL | 3 (30.0%) | 7 (70.0%) | 10 (11.11%) |
| <5 µg/dL | 9 (11.25%) | 71 (88.75%) | 80 (88.88%) |
Lead was shown to be passed from mothers to newborns via umbilical cord blood, as shown by the link between the maternal and umbilical cord blood lead levels. The correlation study revealed a substantial coefficient of correlation and a positive connection between the two variables (r = 0.47, DF = 175, and P = 0.0001) [Figure 5]. Blood lead levels of the infant from the mother that were ≥5 µg/dL were recorded [Table 8].
Figure 5.
Positive correlation of maternal blood lead levels to umbilical cord blood level
Table 8.
Status of new born baby of mother’s blood lead level >5 µg/dL at delivery
| Sample ID | Blood lead concentration in mother (vein blood) | Blood lead concentration in babies (cord blood) | Weight of baby | Maturity | APGAR | Status of baby |
|---|---|---|---|---|---|---|
| D1 | 11.7 | 5.669 | 2.7 | FT | 4/5/6 | NICU admission |
| D15 | 5.197 | 1.827 | 2.8 | FT | 7/8/9 | Live |
| D56 | 5.067 | 0.855 | 2.7 | FT | 7/8/9 | Live |
| D59 | 5.5 | 3.686 | 2.6 | FT | 7/8/9 | Live |
| D73 | 6.12 | 3.682 | 3 | FT | 7/8/9 | Live |
| D76 | 5.112 | 4.227 | 1.9 | 32 W | 0/1/3 | Death |
| D77 | 6.524 | 1.381 | 2.8 | FT | 7/8/9 | Live |
| D78 | 6.49 | 2.312 | 2.8 | FT | 7/8/9 | Live |
| D83 | 5.089 | 2.086 | 2.1 | FT | 7/8/9 | Live |
| D90 | 7.271 | 2.399 | 3.1 | FT | 8/8/9 | Live |
The genotoxicity study was carried out in all studied populations. High blood lead levels significantly increase DNA damage in pregnant women. It is observed that Pb content in blood was significantly correlated with DNA damage in the cord blood [Figure 6].
Figure 6.
(a) Comet assay of no blood lead of pregnant women, (b)Comet assay of high blood lead level in 1st trimester sample, (c) Comet assay of high blood lead level in 3rd trimester sample, (d) Comet assay of high blood lead level in cord blood
Discussion
Lead (Pb) and other toxic metals are linked to poor pregnancy outcomes. It was documented that lead exposure caused abnormal birth outcomes during pregnancy.[13,14] Uniquely, biological changes during pregnancy can make people more sensitive to toxic exposures. Through the air, food, water, and consumer goods, pregnant women are exposed to a variety of environmental toxins, including pesticides, plasticizers, and flame retardants. Despite the fact that the health dangers to women from the majority of chemicals are not well understood, exposure to Pb increases the risk of pregnancy-related hypertension problems. Pregnancy has been demonstrated to increase women’s health risks and vulnerability to environmental toxins.[15,16]
For pregnant women, even low amounts of lead exposure are dangerous. Pregnant women and their unborn children should undergo additional blood lead tests if their blood lead level (BLL) is more than 5 μg/dL.[17,18] According to our knowledge, this is the first study to look into pregnant women’s blood lead levels in a community hospital in Gujarat, India. Out of 194 pregnant women, 31 (15.98%) had blood lead levels above 5 μg/dL, according to our descriptive analysis. Another Indian study found that the maximum limit for lead content was 18.56 mg/L. In samples from the industry that were exposed, the levels of lead were discovered to be quite high and were mostly caused by its elements. Above findings demonstrated the potential risk that elevated lead levels could pose to both the mother and fetus.[19] According to our study, 21 out of 104 pregnant women had blood lead levels that were higher than 5 µg/dL in the 1st trimester. On the other hand, in 3rd trimester, 10 of the 90 pregnant women had blood lead levels that were less than 5 µg/dL. Age was linked to greater levels of Pb in cord blood samples, according to Bocca et al.[20] Compared with nulliparous women, multiparous women had lower levels of Pb in both maternal and cord blood. Nevertheless, our study found no statistically significant difference in age between pregnant women with high blood lead levels (P = 0.127).
The government has to raise awareness about Pb poisoning since it has substantial, negative effects on the whole community, including both adults and newborns. According to a 2012 World Health Organization (WHO) report, accidental poisoning is thought to be the cause of 193,460 yearly fatalities.[21] A recent study from the Saudi Arabian Medinah region found that mothers who lived close to industrial areas had higher lead levels in the samples of their breast milk than counterparts who have not had environmental exposure.[22,23]
In our investigation, the lead levels in maternal blood and cord blood were statistically different from one another (P = 0.0001) [Figure 5]. The relationship between the lead levels in the maternal and umbilical cord blood shows that a sizable quantity of blood lead level was transferred from the mother to the umbilical cord blood. The correlation analysis shows that there is a strong connection between the two variables (r = 0.47, DF = 175, and P = 0.0001) and that there is a positive relationship between them. Similar to this, a Saudi Arabian study discovered a significant correlation between maternal and cord blood lead levels, showing that lead is passed from the mother to the baby during pregnancy. The link between maternal blood lead concentrations and baby weight was found to be marginally significant. Consequently, exposure to low amounts of lead during pregnancy may be harmful.[24] Another Indian study from Lucknow found that intrauterine growth restriction (IUGR) cases had considerably higher maternal and cord blood lead levels than normal cases.[25] Lead concentrations during the prenatal period in a British metropolitan population were investigated and showed that lead was transferred from the placenta.[26] According to a recent study by Tian et al. in 2021,[27] lead and manganese were the main factors in the increased risk of neural tube abnormalities. There were significant lead correlations between maternal and umbilical cord blood. In comparison with values reported in other Brazilian and international investigations, the median lead and arsenic contents both in maternal and cord blood were greater. The lead levels in 25% of the umbilical cord blood samples were less than 5 µg/dL.[28,29]
Bluefish increased Pb levels in relation to food intake, whereas canned fish and seafood had an impact on As, Hg, Cu, and Se levels. The consumption of various meal types affected the levels of other elements including Mn and Pb.[30] The strongest evidence points to a connection between lead exposure and preeclampsia, albeit connections may not always be apparent at low exposure levels. More prospective epidemiological studies beginning in the preconception stage and continuing postpartum are necessary to evaluate the life cycle trajectory of environmental exposures and women’s reproductive and cardiovascular health.[31] In our study, it was shown that there was a higher blood Pb content in the nonvegetarian group compared with the vegetarian group (P = 0.023).
It was documented that low birth weight is caused by elevated Pb levels during pregnancy. Prenatal exposure to environmental heavy metals needs to be routinely monitored for the welfare of the unborn child (Turksoy et al., 2019).[32] However, our study did not find any evidence of decreased birth weight in pregnant women with high blood lead levels. In addition, it was discovered that spontaneous miscarriage occurs more frequently in high blood lead levels pregnant women.
A significant amount of Pb transferred to fetus observed in our study as cord blood sample showed high blood lead concentration. Taking calcium supplements while pregnant was significantly linked to having lower maternal blood lead levels (P = 0.010), according to research by Ladele et al.[33] It is important to consult with a healthcare professional or obstetrician for specific guidance on blood lead level screening during pregnancy. They can evaluate individual risk factors, local guidelines, and provide appropriate recommendations to ensure a healthy pregnancy and minimize the risks associated with lead exposure.
Conclusion
Pregnant women’s blood lead levels should be estimated in a big research with a wider population to impact public health and policy makers. Estimation of blood lead level used as a proxy marker during pregnancy. Increased lead levels during pregnancy are linked to low birth weight, spontaneous abortion, gestational hypertension, and poor neurodevelopment. All pregnant women should be screened for a blood lead level test, and for those with elevated levels, a guideline should be developed along with further treatment options.
Financial support and sponsorship
The study was executed by intramural ICMR-National Institute of Occupational Health funds.
Conflicts of interest
There are no conflicts of interest.
Acknowledgment
The authors are grateful to Dr. Ankit Viramgami, Scientist C and Dr. B. Rakesh, Scientist D for the statistical analysis for this study. Also thankful to Mr. Idris, Mrs. Sweta Gupta, and Mrs. Chauba Keshari for their technical support. We are grateful to the Director, ICMR-NIOH, Ahmedabad for the extended facility to carry out this study.
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