|Year : 2020 | Volume
| Issue : 2 | Page : 55-59
Pesticide risk and recurrent pregnancy loss in females of subhumid region of India
Akancha Pandey1, Shyam Pyari Jaiswar1, Nasreen Ghazi Ansari2, Sujata Deo1, Pushplata Sankhwar1, Shriya Pant3, Sushil Upadhyay4
1 Department of Obstetrics and Gynecology, King Georg's Medical University, Lucknow, Uttar Pradesh, India
2 Metal Analysis Laboratory, CSIR Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India
3 Department of Urology, King Georg's Medical University, Lucknow, Uttar Pradesh, India
4 Department of Biotechnology, Maharshi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana, India
|Date of Submission||01-Sep-2018|
|Date of Decision||25-Oct-2019|
|Date of Acceptance||27-Feb-2020|
|Date of Web Publication||7-May-2020|
Dr. Shyam Pyari Jaiswar
Department of Obstetrics and Gynecology, King George's Medical University, Lucknow . 226 003, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Objective: The objective of this study is to determine the level of pesticides and their role in cases of recurrent pregnancy loss (RPL). Materials and Methods: This was designed as a case–control study. Gas chromatography was used to characterize the pesticide level in 70 cases and 70 controls. Case refers to women with RPL, whereas controls refer to women with full-term delivery. Results: A higher level of pesticide, namely beta-hexachlorocyclohexane, malathion, chlorpyrifos, and fenvalerate was found in the case group as compared to control group (P < 0.05). Conclusions: The present study suggests that high exposure of pesticide (organochlorine and organophosphates) may increase the risk of RPL in females of the subhumid region of India.
Keywords: Organochlorine, organophosphate, recurrent pregnancy loss
|How to cite this article:|
Pandey A, Jaiswar SP, Ansari NG, Deo S, Sankhwar P, Pant S, Upadhyay S. Pesticide risk and recurrent pregnancy loss in females of subhumid region of India. Niger Med J 2020;61:55-9
|How to cite this URL:|
Pandey A, Jaiswar SP, Ansari NG, Deo S, Sankhwar P, Pant S, Upadhyay S. Pesticide risk and recurrent pregnancy loss in females of subhumid region of India. Niger Med J [serial online] 2020 [cited 2023 Dec 8];61:55-9. Available from: https://www.nigeriamedj.com/text.asp?2020/61/2/55/283915
| Introduction|| |
Based on the incidence of sporadic pregnancy loss, the incidence of recurrent pregnancy loss (RPL) should be approximately 1 in 300 pregnancies. Although the specific cause of RPL is not yet known, considerable evidence suggests that both genetics and the environment play an important role in the origin and evolution of this disease. Pesticides are the class of man-made environmental chemicals that can affect the body's development, growth, and hormone balance. Pesticides are usually designed to target a particular pest, but due to its broad range of toxicity, it can also be directed to other nontarget species. In the majority of cases, however, human exposure is unintentional.
Previous studies also examined the role of other factors such as infections, hormonal aberrations, menstrual irregularities, malnutrition, psychological conditions, stressful events, high alcohol, nicotine, and caffeine intake, but the results are inconsistent., In recent years, the high risk of miscarriages has been reported in smoking women. Settimi et al. also reported the positive association between pesticides exposure and increased risk of pregnancy loss. Pesticides exposure may also cause reproductive and developmental disorders. A definite cause of RPL can be identified only through intensive diagnostics.
Environmental pollutants or xenobiotics have been suspected for their strong role in causing RPL and other reproductive aberrations, but pesticides such as organochlorine (OCP) and organophosphate (OPP) are suggested as the main culprits. Pesticides such as dichlorodiphenyltrichloroethane and hexachlorocyclohexane are officially banned in India. However, they are still in use to control the disease-carrying vectors.
OCP and OPP both have a long half-life. These pesticides accumulate in the adipose tissue and thus enter into the food chain and circulate. On exposure through different means such as air, water, food, and soil, these may enter in blood circulation and can induce endocrinological disorders, immunological aberrations, oxidative damage, and eventually molecular damage.,, The roles of di chloro di phenyl tri chloro ethane (DDT) exposure in spontaneous pregnancy loss have previously been reported.,, However, more studies with diverse patient groups are required to establish the association of pesticides in the etiology of RPL. The present study was conducted to further investigate this claim. The levels of OCP and OPP were quantified and compared between the cases with repeated pregnancy loss and women having successful full-term delivery among the population of subhumid region of India.
| Materials and Methods|| |
After the agreement of the ethical committee, the womens' consent was obtained before they were included in the study. A total of 140 women were recruited between January 2012 and January 2015 from the Department of Obstetrics and Gynecology, King George's Medical University, Lucknow, Utter Pradesh, India. The two different groups were evaluated.
The first group included 70 patients (case group) having two or more spontaneous pregnancy loss before the 20th week of gestation.
The second group included 70 apparently healthy females (control group) having had one or more successful deliveries during the period of investigation.
The participants with diabetes mellitus, hypertension, tuberculosis, immunocompromised symptoms, any endocrine disorder and genital, colon or breast cancer, or any other malignancies were excluded from the study. All were interviewed to collect the information, including age, alcohol consumption, smoking/tobacco chewing, and family history.
Five milliliter of venous blood was collected from every women included in the study on the 21th day after the commencement of the menstrual cycle for the control group and before the 20th week of gestation for the case group. Serum was separated from all the samples by centrifugation at 1000 × g for 10 min and was stored at −20°C till further analysis.
Pesticides extraction and quantification
The estimation of pesticides, OPPs and OCPs, residue from blood was done according to the method of Bush et al. with minor modification. A total number of 14 pesticides (12°CP and 2 OPP) were selected for the study on the basis of their persistent nature and consumption rate. In brief, 1 ml of blood was taken in the separating funnel (100 ml) extracted with 10 ml hexane by shaken it at room temperature (30°C) for 10 min. The organic hexane layer was collected, and this process was repeated thrice; pooled hexane extract was collected. The organic layer (30 ml) was pooled together, collected, and dried by using a vacuum evaporator (IKA RV 10 digital). The concentrated sample was transferred into an autoinjector vial by passing through anhydrous sodium sulfate and dried with the flow of nitrogen. The sample was reconstituted to 1 ml before injection, sealed and loaded on to autoinjector for the analysis. The trace level pesticide (ppb) in the blood samples was analyzed using an Agilent technologies 7890A Gas Chromatograph, equipped with a micro-electron capture detector (ECD), capillary column DB-5MS (Perkin Elmer, CA, USA), and in an autoinjector Agilent technologies 7683B series split-less mode injector with an insert liner. The gas chromatograph temperature was programmed as follows: injector temperature: 250°C, oven temperature: initially ramped from 165°C to 180°C at a rate of 3°C, 200°C at a rate of 1.5°C, 230°C at a rate of 2°C, 260°C at a rate of 3.5°C, and finally to 280°C at a rate of 6°C/min withhold time of 1.5, 0.5, 0.5, 0.5, 2, and 2.5 min, respectively and ECD temperature was at 300°C.
The numerical tool for the demographic variables applied was the Chi-square test. The age, odd ratio, and confidence interval (95%) were substantiated by Vassar stats online calculator. The significance level of pesticides was evaluated by the nonparametric Mann–Whitney test. The univariate and multivariate binary logistic regression was carried out to find the strength of the association of the study parameters. The Hardy–Weinberg equilibrium was tested at each locus using the online available calculator. Statistical calculations were carried out using the advanced Statistical Package for the Social Sciences software version 16.0 (SPSS-16.0, IBM, Chicago, USA) Statistical Package for the Social Sciences provided by Institute of Business Management, India.
| Results|| |
We observed an elevated level of pesticide quartile in case with respect to the control group. [Table 1] shows OCPs and OPPs levels in case and control groups in terms of descriptive statistics. The Mann–Whitney U-test was used to calculate the significance difference between the groups. The result revealed that levels of pesticides, beta-hexachlorocyclohexane (β-HCH), γ-HCH, δ-HCH, chlorpyrifos, pp-DDD, and fenvalerate were statistically significantly higher in the patients of the case group as compared with the control group (all P < 0.05) [Table 1].
The results for all the 14 pesticides (12°CP and 2 OPP) were analyzed through the Mann–Whitney test. We observed statistically significantly higher levels of β-HCH (P: 0.04), γ-HCH (P: 0.001), δ-HCH (P: 0.002), chlorpyrifos (P: 0.001), pp-DDD (P: 0.001), and fenvalerate (P: 0.001) in the patients of the case group in comparison to the patients of the control group. These pesticides were known to be endocrine disrupting and carcinogenic. The distribution prototypes of different pesticides in case and control groups are shown in [Figure 1], [Figure 2], [Figure 3], [Figure 4]. [Figure 1] describes the level of OPP pesticides in both groups studied. [Figure 2] indicates the higher level of γ-HCH and δ-HCH in the case group as compared to the control group. Similarly, [Figure 3] and [Figure 4] show the higher level of β-HCH, DDT, and pp-DDD in the case group as compared to the control group, respectively.
|Figure 1: Level of organophosphate pesticides in control and recurrent miscarriage females|
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|Figure 2: Level of organochlorine pesticides in control and recurrent miscarriage for females|
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|Figure 4: Patterns of pesticides distribution in case and control groups|
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| Discussion|| |
The RPL and their causative factors are well demonstrated in this study and are compared with earlier studies., The impact of environmental exposure and oxidative stress in the etiology of RPL was evaluated, and the findings were corroborated with Pathak et al. The identification of environmental factors that enhance the threat of PCa must therefore be a goal for disease prevention. As previously outlined, pesticides and its derivatives, especially OCP (DDT, dioxins, and polychlorinated biphenyls) and OPP (malathion and chlorpysifos) possess weak estrogenic and androgenic effects. Their availability in the body may interfere at several control points in the hormone-signaling pathways. As a result, the response cascade of natural hormones can either be inhibited or excessively enhanced, at the wrong time, in the wrong tissue.
In this study, a statistically significant higher level of pesticides, namely β-HCH, γ-HCH, δ-HCH, chlorpysifos, pp-DDD, and fenvalerate (P < 0.005) is found in the case group compared to its control group. OCP pesticides exhibit hormonal activity in various tissues with mechanisms involving the steroidogenic pathway, receptor-mediated changes in protein synthesis, or anti-androgenic and estrogenic actions. Most of their endocrine effects are as a result of their ability to mimic 17-β-estradiol and may lead to miscarriage, but the evidence is inconclusive., It was established that the lipophilic nature of OCP pesticides disturbs the normal estrogen-progesterone balance, which is particularly important in the maintenance of pregnancy. Pathak et al. reported that high β-HCH levels in cord blood were associated with preterm labor and high γ-HCH levels were associated with a higher risk of recurrent miscarriage. In the earlier literatures, it was well established that cyfluthrin, a synthetic pyrethroid is a most frequently detected pesticide in the contaminants of breast milk in India., Thus, these synthetic chemicals play a key role as a health risk to nursing infants. The concentration of a potent pesticide, chlorpyrifos in umbilical cord blood was negatively associated with birth weight, size, and neurodevelopment among infants born to low-income minority mothers., This significance showed that the levels of pesticides are associated with an increased risk or excess incidence of pregnancy loss in the female population.
| Conclusions|| |
The current study demonstrates the importance of environmental factors in the context of RPL. Significantly higher levels of pesticides with endocrine-disrupting potential in cases suggest the possible role of these compounds as one of the causes of RPL. Increased pesticide level appears to indicate the increased levels of oxidative damage that has been associated with possible cause of RPL, and it may reflect indirect evidence of toxicity rather than a direct cause. However, our study has several limitations such as a small sample size. Moreover, we are also unable to determine if the observed association between γ-HCH and repeated miscarriages was due to the exposure of the mother during pregnancy or early childhood of an individual that affected their subsequent reproductive development. Furthermore, we must emphasize that toxicity depends on numerous additional factors such as genetic predisposition, dietary habits, and contamination with other pollutants. Hence, there is a need for further epidemiological studies with a larger cross-sectional population to be carried out to clearly determine the relationships between OCPs exposures and recurrent miscarriages along with the assessment of endocrine disruption, genetic polymorphism, and genetic environmental interaction.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Prins GS, Korach KS. The role of estrogens and estrogen receptors in normal prostate growth and disease. Steroids 2008;73:233-44.
Pandey MK, Rani R, Agrawal S. An update in recurrent spontaneous abortion. Arch Gynecol Obstet 2005;272:95-108.
Korrick SA, Chen C, Damokosh AI, Ni J, Liu X, Cho SI, et al
. Association of DDT with spontaneous abortion: A case-control study. Ann Epidemiol 2001;11:491-6.
Pineles BL, Park E, Samet JM. Systematic review and meta-analysis of miscarriage and maternal exposure to tobacco smoke during pregnancy. Am J Epidemiol 2014;179:807-23.
Settimi L, Spinelli A, Lauria L, Miceli G, Pupp N, Angotzi G, et al
. Spontaneous abortion and maternal work in greenhouses. Am J Ind Med 2008;51:290-5.
Hanke W, Jurewicz J. The risk of adverse reproductive and developmental disorders due to occupational pesticide exposure: An overview of current epidemiological evidence. Int J Occup Med Environ Health 2004;17:223-43.
Kumar A, Dayal P, Shukla G, Singh G, Joseph PE. DDT and HCH residue load in mother's breast milk: A survey of lactating mother's from remote villages in Agra region. Environ Int 2006;32:248-51.
Siddiqui MK, Srivastava S, Srivastava SP, Mehrotra PK, Mathur N, Tandon I. Persistent chlorinated pesticides and intra-uterine foetal growth retardation: A possible association. Int Arch Occup Environ Health 2003;76:75-80.
Tiemann U.In vivo
effects of the organochlorine pesticides DDT, TCPM, methoxychlor, and lindane on the female reproductive tract of mammals: A review. Reprod Toxicol 2008;25:316-26.
Gerhard I, Daniel V, Link S, Monga B, Runnebaum B. Chlorinated hydrocarbons in women with repeated miscarriages. Environ Health Perspect 1998;106:675-81.
Banerjee BD, Seth V, Ahmed RS. Pesticide induced oxidative stress: Perspective and trends. Rev Environ Health 2001;16:1-40.
Venners SA, Korrick S, Xu X, Chen C, Guang W, Huang A, et al
. Preconception serum DDT and pregnancy loss: A prospective study using a biomarker of pregnancy. Am J Epidemiol 2005;162:709-16.
Longnecker MP, Klebanoff MA, Dunson DB, Guo X, Chen Z, Zhou H, et al
. Maternal serum level of the DDT metabolite DDE in relation to fetal loss in previous pregnancies. Environ Res 2005;97:127-33.
Bush B, Snow J, Koblintz R. Polychlorobiphenyl (PCB) congeners, p, p'-DDE, and hexachlorobenzene in maternal and fetal cord blood from mothers in Upstate New York. Arch Environ Contam Toxicol 1984;13:517-27.
Baek KH, Lee EJ, Kim YS. Recurrent pregnancy loss: The key potential mechanisms. Trends Mol Med 2007;13:310-7.
Gupta S, Agarwal A, Banerjee J, Alvarez JG. The role of oxidative stress in spontaneous abortion and recurrent pregnancy loss: A systematic review. Obstet Gynecol Surv 2007;62:335-47.
Pathak R, Mustafa M, Ahmed RS, Tripathi AK, Guleria K, Banerjee BD. Association between recurrent miscarriages and organochlorine pesticide levels. Clin Biochem 2010;43:131-5.
Steinmetz R, Young PC, Caperell-Grant A, Gize EA, Madhukar BV, Ben-Jonathan N, et al
. Novel estrogenic action of the pesticide residue beta-hexachlorocyclohexane in human breast cancer cells. Cancer Res 1996;56:5403-9.
Saad AA, El-Sikaily AM, El-Badawi EL, El-Sawaf GA, Shaheen NE, Omar MM, et al
. Relation between some environmental pollutants and recurrent spontaneous abortion. Arabian J Chem 2016;9:S787-S94.
Sharma E, Mustafa M, Pathak R, Guleria K, Ahmed RS, Vaid NB, et al
. A case control study of gene environmental interaction in fetal growth restriction with special reference to organochlorine pesticides. Eur J Obstet Gynecol Reprod Biol 2012;161:163-9.
Pathak R, Ahmed RS, Tripathi AK, Guleria K, Sharma CS, Makhijani SD, et al
. Maternal and cord blood levels of organochlorine pesticides: Association with preterm labor. Clin Biochem 2009;42:746-9.
Corcellas C, Feo ML, Torres JP, Malm O, Ocampo-Duque W, Eljarrat E, et al
. Pyrethroids in human breast milk: Occurrence and nursing daily intake estimation. Environ Int 2012;47:17-22.
Sharma A, Gill JP, Bedi JS, Pooni PA. Monitoring of pesticide residues in human breast milk from Punjab, India and its correlation with health associated parameters. Bull Environ Contam Toxicol 2014;93:465-71.
Whyatt RM, Rauh V, Barr DB, Camann DE, Andrews HF, Garfinkel R, et al
. Prenatal insecticide exposures and birth weight and length among an urban minority cohort. Environ Health Perspect 2004;112:1125-32.
Huen K, Bradman A, Harley K, Yousefi P, Boyd Barr D, Eskenazi B, et al
. Organophosphate pesticide levels in blood and urine of women and newborns living in an agricultural community. Environ Res 2012;117:8-16.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
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