Influence of Domestic Exposure to Polycyclic Aromatic Hydrocarbons on Women's Periconceptional Stage and Associated Risk of Oral Cleft in Offspring

Abstract

Background:

Polycyclic aromatic hydrocarbons (PAHs) constitute a group of chemicals with an omnipresence in the environment and our surroundings. With their genotoxicity and carcinogenic nature, it has been proven to be monstrous in our daily life and, especially for pregnant women and their newborn.

Aim:

This questionnaire study was done to verify the influence of domestic exposure to polyaromatic hydrocarbons on women's periconceptional stage and risk of oral cleft in offspring in the suburban and the rural population of Mysore.

Methodology:

Two hundred pregnant women as patients from four different hospitals in Mysore were given a questionnaire to be filled with 24 parameters ranging from the knowledge to various means of exposure to the pregnant women with the PAH and the severity and the extent of the orofacial defect in the newborn.

Results:

It was determined that exposure of pregnant women to the smoke emanating from the method of cooking or heating to smoking (first or passive) and the direct inhalation of gas had the maximum effects on the association of cleft palate (60.7%) in unilateral followed by 90.9% in bilateral, 65.0% in soft tissue, and 76.2% in hard tissue cleft palate.

Conclusion:

The deleterious effects of the cooking and water heating measures practiced in the suburban and the rural population predisposed the pregnant women to significantly higher chances of offspring with the varied extent of the orofacial defect. There is an influence of domestic exposure to polycyclic aromatic hydrocarbons on women's periconceptional stage and risk of oral cleft in offspring.

INTRODUCTION

Polycyclic aromatic hydrocarbons (PAHs) or polynuclear aromatic hydrocarbons represent a group of naturally occurring chemicals in coal, crude oil, and gasoline.[1] PAHs are also produced and detected persistently in the environment as a result of incomplete combustion of organic matter such as coal, oil, gas, wood, garbage, tobacco products, and charbroiled meat.[2] PHAs generated by these means may bind with air or may form small free particles.[2] Studies suggest that inefficient burning process produces higher PAHs causing greater environmental effects due to their genotoxic and carcinogenic potential.[3] Domestically, PAHs are produced as a result of high temperature burning of wood, used for cooking purpose, especially, burning chemically treated wood such as creosote-treated wood, and even when burning coffee, peanuts, refined vegetable oil, and grains.[3] The different techniques of cooking such as open-air meat cooking like barbecue or even charring food over a fire further aggrandizes the production of PAH in the environment.[4] A variety of cosmetics such as shampoo and face wash are found to contain significant amount of PAHs and are derivatives of coal making it more viable in our daily and common lives. Naphthalene, a variation of PAH commonly used as mothballs further increases the risk of exposure to the harmful chemicals.[5] In addition, tobacco smoking causes significant exposure of PAHs to a large group of people from firsthand, secondhand, or even third smoking[6] thus, making the exposure to such harmful chemicals a part of our daily routine.

Recent studies confirm that the quantity of PAHs is at least ten times higher in urban cities than in rural environments. Thus, causing serious health problems such as oxidative stress, diabetes, inflammation, infertility, cardiovascular disease, and poor fetal development.[7] Pregnant women sustain a high risk of exposure to PAHs working in different environments, significant research and data affirm the presence of PAH-DNA in placental tissues, amniotic fluid of pregnant women, and umbilical cord blood of newborns.[8] PAH adducts which hold the capability to derange the cell's microenvironment, further affecting the susceptibility of the cell.[9] It also reduces the placental blood flow in pregnant women and causes periods of fetal hypoxia, further accentuating the harmful effects of the chemical exposure.[10] PAH exposure during pregnancy has already been linked to various developmental disorders such as intrauterine growth restriction, low birth weight, decreased chest circumference and increased cephalization index, small for gestational age birth, depressed verbal intelligence, increased risk of obesity, and even increased risk of acute lymphoblastic leukemia.[11,12] It also contributes to adverse neurodevelopmental disorders including neuroblastoma and defects in neural tube.[11] Children born with gastroschisis among occupationally exposed mothers confirmed the teratogenicity of the hydrocarbons. It further affirmed the increased risk of child being born with maxillofacial defects such as cleft lip with or without cleft of palate due to indifferent growth patterns and disturbances on exposure to the pregnant women.[13,14]

A cleft is a gap or split in the upper lip and/or palate. Together, these birth defects commonly are called “orofacial clefts.”[15] The birth prevalence of clefts is somewhere between 27,000 and 33,000 clefts/year in the Indian subcontinent.[16] The cleft can be further categorized into unilateral or bilateral cleft lip and palate, respectively, or into complete or partial. The orofacial defect carries the stigma of a difficult quality of life with respect to basic actions such as feeding or breathing. It even leads to further complications in the growth of the individual apart from the appearance.[15]

The environmental PAH levels in India is 668–672 ng/m³ which is an all-time alarmingly high according to the recent WHO report and just behind China 710–870 ng/m³.[3] This indicates serious health hazards for coming generations. Hence, the present study was conducted to determine if women's periconceptional exposure to PAHs was associated with the risk of oral clefts in offspring and to identify the contributing factors and the correlation with oral cleft deformity with the newborn.

METHODOLOGY

The present investigation is a questionnaire study based on 24 parameters and was carried out on a total number of 200 cleft patient mothers registered in JSS Dental College and Hospital (JSSDCH), JSS Medical College and Hospital (JSSMCH), Mysore Medical College and Research Institute (MMCRI) and St. Joseph Hospital registration centers at Mysore city, Karnataka, India. The study evaluated the relation and influence of PAH on women's periconceptional stage and risk of oral cleft in offspring. The patients registered (mother) in the JSSDCH, JSSMCH, MMCRI, and St. Joseph hospital with oral cleft defect were considered for the study. All were asked questions related to exposure to PAH during preconceptual and pregnancy.

The mothers were asked questions on verities of topics such as maternal illness, medication used, method of heating water, method of cooking, inhalation of gas, whether inhalation exposed was direct, indirect or both, and continuous, intermittent or both. Each parameter is assessed individually and correlated with the frequency of the cases to establish the correlation with the associative causative factors from the highest to the lowest impact factor.

The percentage frequency is estimated for each parameter and classified into four categories unilateral cleft palate (UCP), bilateral cleft palate, soft tissue cleft palate, and hard tissue cleft palate (HCP). The percentage frequency values were tabulated and subjected to statistical analysis to assess the correlation of each parameter and establish the association between the ingestion of PAHs and its influence on children born with cleft palate.

Covariates

Several covariates were considered associated with PAH exposure or oral cleft, and addition data were collected such as education, consanguineous marriage, preexisting diabetes, family history cleft, occupation of mother, consanguineous marriage, folic acid supplements, alcohol intake, smoking, and diet pattern. In the analysis, all covariates were treated qualitative variable.

RESULTS

All the 24 parameters were assessed individually to study its effect and the degree of effect on association with developing cleft palate [Table 1]. On evaluation with reference to the exposure of PAH, the method of heating water to the method of cooking, inhalation of smoke, and the exposure duration were assessed with its own different parameters. It was determined that exposure of pregnant women to the smoke emanating from method of cooking or heating with wood had the maximum effects on the association of cleft palate (60.7%) in unilateral followed by 90.9% in bilateral, 65.0% in soft tissue, and 76.2% in HCP [Graph 1]. Continuous inhalation of smoke had a greater effect (66.1%) followed by direct inhalation (51.8%) in the development of UCP.

Table 1.

Frequency table of the various parameter’s assessed with respect to unilateral, bilateral, soft tissue and hard tissue cleft palate

Parameter	UCP (%)	BCP (%)	SCP (%)	HCP (%)
Age of child
Below 10	32.1	34.1	55.0	27.5
Above 10	67.9	65.9	45.0	72.5
Age of mother
Below 30	58.9	27.3	85.0	35.0
Above 30	41.1	72.7	15.0	65.0
Child gender
Boy	53.6	61.4	70.0	53.8
Girl	46.4	38.6	30.0	46.2
Education of mother
Illiterate	21.4	2.3	30.0	8.8
Schooling	69.6	77.3	65.0	75.0
Pre-University	8.9	20.5	5.0	16.2
Education of father
Illiterate	1.8	0.0	0.0	1.2
Schooling	62.5	86.4	75.0	72.5
Pre-University	21.4	2.3	15.0	12.5
Graduate	14.3	11.4	10.0	13.8
Occupation of mother
Employed	44.6	43.2	50.0	42.5
Non employed	55.4	56.8	50.0	57.5
Consanguineous marriage
Yes	62.5	45.5	70.0	51.2
No	37.5	54.5	30.0	48.8
Number of previous births
1 or >1 live	42.9	15.9	35.0	30.0
Nil	57.1	84.1	65.0	70.0
Prepregnancy BMI
Under weight	32.1	29.5	25.0	31.0
Normal	51.8	61.4	55.0	56.2
Over weight	16.1	9.1	20.0	11.2
Preexisting diabetes
Yes	19.6	2.3	30.0	7.5
No	80.4	97.7	70.0	92.5
Medication taken
Yes	48.2	36.4	65.0	37.5
No	51.8	63.6	35.0	62.5
Diet pattern
Balanced	44.6	81.8	10.0	73.8
Un-balanced	55.4	18.2	90.0	26.2
Maternal illness
Yes	10.7	13.6	20.0	12.0
No	89.3	86.4	80.0	90.0
Folic acid
Yes	48.2	59.1	50.0	53.8
No	51.8	40.9	50.0	46.2
Smoking habit
No	100	100	100	100
Passive smoking
Yes	75.0	68.2	70.0	72.5
No	25.0	31.8	30.0	28.0
Alcohol consumption
No	100	100	100	100
Family history cleft
Yes	32.1	36.4	35.0	33.8
No	67.9	63.6	65.0	66.2
Method of heating water
Electric	7.1	0.0	5.0	3.8
Gas	10.7	6.8	10.0	8.8
Kerosene	25.0	13.6	5.0	23.8
Wood	57.1	77.3	80.0	62.5
Coal	0.0	2.3	0.0	1.2
Method of cooking
Gas	32.1	4.5	35.0	20.0
Kerosine	7.1	4.5	0.0	7.5
Wood	60.7	90.9	65.0	76.2
Exposure
Yes	73.2	84.1	65.0	81.2
No	26.8	15.9	35.0	18.8
Inhalation of gas
Direct	51.8	18.2	90.0	23.8
Indirect	21.4	52.3	10.0	41.2
Both	26.8	29.5	0.0	35.0
Continuous	66.1	38.6	75.0	48.8
Inter-mittent	33.9	61.4	25.0	51.2
Number of days worked
<1 week	37.5	18.2	35.0	27.5
>1 week	62.5	81.8	65.0	72.5

UCP: Unilateral cleft palate, BCP: Bilateral cleft palate, SCP: Soft tissue cleft palate, HCP: Hard tissue cleft palate

Graph 1.

Percentage distribution of type of cleft cases across methods of cooking

Statistical analysis

Pearson's Chi-squared test was done to determine whether there is a statistically significant difference between the expected frequencies and the observed frequencies in the parameters assessed. It was noted that with df of 2 and 3, respectively, there was a significant association between the education status of χ² as 70.82 and 126.72 of mother and father, respectively, with a P = 0 for each [Table 2]. The method of heating water and cooking also ranged to a significant association with a df of 4 and 2 with χ² of 142.7 and 77.36 with again an asymp. Significance of 0. This had a high association with the development of the cleft lip and palate with the duration and the extent of the exposure with a χ² = 31.36 to the development of the severity of the orofacial defect with being unilateral or bilateral or soft and hard tissue extent.

Table 2.

Chi-square test: Test statistics: Significance of each parameter denoting the severity

Parameters	χ 2	Df	Asymptotic significant
Age of child	11.56	1	0.001
Age of mother	1	1	0.317
Child gender	1.96	1	0.162
Education of mother	70.82	2	0
Education of father	126.72	3	0
Occupation of mother	1.44	1	0.23
Consanguineous marriage	1	1	0.317
Number of previous births	14.44	1	0
Prepregnancy BMI	27.98	2	0
Pregnancy BMI	21.14	2	0
Preexisting diabetes	57.76	1	0
Medication taken	1.96	1	0.162
Diet pattern	4.84	1	0.028
Maternal illness	57.76	1	0
Folic acid	0.36	1	0.549
Passive smoker	19.36	1	0
Family history cleft	10.24	1	0.001
Method of heating water	142.7	4	0
Method of cooking	77.36	2	0
Exposure	31.36	1	0
Inhalation of gas	1.34	2	0.512
Inhalation of gas	0.64	1	0.424
Number of days worked	17.64	1	0
Type of cleft 1	1.44	1	0.23
Type of cleft 2	36	1	0

BMI: Body mass index

DISCUSSION

This study conducted established a positive interrelation between exposure in pregnant women to PAHs and the associative risk of cleft palate in offspring. PAHs are classified as organic chemicals as solids they are mostly colorless, white, or pale yellow.[3] They constitute a pervasive group of distinctive chemically-related compounds with various structures and varied toxicity present in the environment.[2] PAHs are formed as a result of biological processes as products of incomplete combustion from either natural combustion sources (forest and brush fires) or man-made combustion sources (automobile emissions and cigarette smoke).[5] Being a common finding in the environment either through soil, air, or water, the general population is unavoidably exposed to such compounds.[17] Even though, a major source of PAH exposure for humans is cigarette smoking (active or secondhand), which holds moderate association to the probability of cleft palate in the offspring.[10] Various other factors have also been associated and are studied further to evaluate and establish the correlation between the various exposure methods and the chances of ill development in the neonate.[18]

PAHs which easily pass through the placenta due to its lipophilic nature constitute a pivotal role in affecting the neonates and their development during the gestation period upon maternal exposure.[7] According to various studies, maternal exposure to PAHs during gestation has been shown in mice to cause oral cleft in the offspring.[14,19] As per the reported data, the approximated transplacental dose of PAHs is relatively ten times lower than the dose in maternal tissues. The developing embryos may be as much as 10 times more susceptible than the mother to PAH-induced DNA damage.[10] Although the susceptibility of the excess risk is attributed to the genotype of the mother and/or fetus.[12] Various mechanisms of the teratogenicity of PAHs which include oxidative stress; changes in signal transduction pathways; the formation of bulky PAH-DNA adducts that result in a spectrum of cellular mutations that may be teratogenic or epigenetic changes, including DNA methylation.[9,20]

Perera et al. suggested the transplacental transfer of PAHs to the fetus could have significant impacts on fetal development.[14] A considerable number of studies established a reduction in head circumference at birth, corresponding with a repressed intelligence quotient and meager psychological functioning and school conduct in childhood.[8] Furthermore, exposure to PAHs is also a causative factor for restricted intrauterine growth, short gestational age, and preterm delivery.[11]

The various parameters assessed in this study [Graph 2] for the exposure and the associated risk of developing the cleft lip and palate in the offspring further substantiated the effect of PAH's exposure due to the multiple factors. From the method of heating water and cooking using various natural resources of gas, kerosene, wood or coal, and even electricity, it substantiated the use of wood which had the maximum amount of PAH generation affected the occurrence of the orofacial defect in the newborns. The duration and the type of exposure to the pregnant women in their gestational period also played a pivotal role in the extent of the orofacial defect from unilateral to bilateral or partial to complete. The direct exposure and the continuous exposure in the household doing common activities further accentuates the susceptibility to the congenital defect for the newborn. Direct inhalation of gas showed a significant association to the occurrence of this developmental anomaly in the newborn due to the increased amount of direct absorption and adsorption of the harmful chemicals. Adequate information for the exposure and its ill effects makes it an important causative factor for the severity and the occurrence of the congenital defect in such a number. Although the occurrence of the cleft lip and palate does have a genetic and hereditary predisposition, it was again found to be highly linked with the disturbances found in the formative stages upon the exposure to any mutating agent such as PAH as suggested by various studies.[9] The urban and the rural population with a difference of lifestyle and the insufficiency of the basic amenities makes it more difficult for the rural population especially.[21]

Graph 2.

Inhalation of gas Vs method of heating water

CONCLUSION

The study gave significant results of the association between the type and duration of the exposure to any material containing or combusting any amount of PAH in the gestational period to the occurrence of the craniofacial developmental defect in the newborns. It would be conclusive to say that the type, amount, and duration of exposure and the method of absorption are directly proportional to the development and the severity of the cleft lip and palate in the offspring.

Although the current study enlists out the most probable causes and the factors affecting the chances for a newborn predisposed to transplacental exposure of the PAHs. This study is subject to certain limitations.First, given the relatively moderate number of subjects, future studies with larger sample sizes are warranted to confirm or refute our findings. Second, only maternal exposure to PAHs and genetic susceptibilities were considered; however, the genetics of palate development is likely to be a complex interplay between both maternal and fetal genetic susceptibilities.[22] Therefore, future studies are needed to investigate the effects of fetal exposure, fetal genotypes, and the interaction between them on the risk of cleft palate.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.