Research Article

Annals of Health & Health Sciences

Vol. 1, No. 1 J anuary-J une 2014, 61-64
DOI: 10.5958/j.2322-0422.1.1.012
61
Hypospadias Risk among North-Indian Children
Ratika Samtani
1
*, Minu Bajpai
2
, PK Ghosh
3
, KN Saraswathy
4
1
Assistant Professor, Amity Institute of Anthropology, Amity University, Sector-125, Noida, Uttar Pradesh-201303, India
2
Professor, Department of Paediatric Surgery, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, Delhi-110029, India
3
Professor,
4
Assistant Professor, Department of Anthropology, University of Delhi, Delhi-110007, India
*Corresponding author email id: rsamtani@amity.edu
ABSTRACT
Objective: The objective of the study was to determine the incidence of hypospadias in Northern Indian region and to identify the
various risk factors involved. Materials and Methods: 101 boys with hypospadias of age 4-10 years old were prospectively
entered in the study along with 110 age-, geography-, ethnicity- and language-matched controls. Demographic and clinical data
pertaining to reproductive profile of the mother, occupation of the parents and family history of genital abnormalities in male blood
relatives were recorded for cases and controls. Frequency of hypospadias cases and birth defects registered with the AIIMS
Paediatric Surgery outpatient department from the years 2003-2011 was also scrutinised. Results: An increase trend in the
incidence of hypospadias from the year 2003 (7.66%) to the year 2011 (9.33%) was observed. Analysis of the demographic data of
cases on the basis of parental occupational status depicted a major group of children (72.27%) affected with hypospadias had their
parents from rural background having agriculture as their primary occupation. Conclusion: Although the causes of male genital
malformations are multifactorial, our data support the hypothesis that prenatal contamination of pesticides or exposure to endocrine-
disrupting chemicals may be a potential risk factor for hypospadias in India.
Keywords: Endocrine-disrupting chemicals, Agricultural community, India, Hypospadias, Multi-factorial
INTRODUCTION
Hypospadias is a malformation in which the urethral
meatus is located on the ventral side of the penis proximal
to the tip of the glans, occurring from the balanopreputial
sulcus to the perineal area. During the last decades,
numerous observations on adverse trends and rising
incidence of disorders affecting the male reproductive
tract have been reported from the world, especially in the
case of hypospadias having an incidence of 1 in every
250 male live births.
12
Concern has focused on whether
exposure to endocrine-disrupting chemicals (EDC) with
anti-androgenic activity is the cause of the increase. It
has been observed that the foetus is especially sensitive
to these endocrine disruptors (EDs) that can mimic or
interfere with the natural hormones that control
development. Common environmental factors that have
an impact on intrauterine growth and morphogenesis of
the genital tract are also considered to be the cause. In
recent decades, it has been found that parental
involvement in agriculture or parental exposure to
pesticides (being anti-androgenic in nature) to be
associated with higher risk of a wide range of congenital
malformations;
3,4,5
however, the results from many studies
are conflicting. Our previous case-control study
6
that
focused on the molecular basis of hypospadias highlighted
that the presence of leucine allele (mutant allele) among
individuals practicing farming was likely to increase their
propensity of having a child with hyposapdias. If at all,
EDCs with anti-androgenic like activity found among
pesticides is a risk factor for the development of
hypospadias, then it is a matter of serious concern
especially in Indian context where 70% of the populations
livelihood is based on farming and agricultural-based
activities, exposing them to the toxic effects of various
harmful agents.
62 Volume 1, Number 1, J anuary-J une 2014
Ratika Samtani et al.
The aim of the present study or the preliminary study
was to first examine the incidence of hypospadias in
Northern Indian region, to understand the communities
at risk and to evaluate the various risk factors in the
occurrence of hypospadias. As this is the first report on
Hypospadias in India, details from its incidence to risk
factors are covered as a part of a preliminary research.
MATERIALS AND METHODS
The study was carried out after obtaining the ethical
clearance from the Department of Anthropology,
University of Delhi and All India Institute of Medical
Sciences (AIIMS), New Delhi. A total of 101 boys with
hypospadias of 4-10 years old were prospectively entered
in the study. All cases were diagnosed at the Department
of Paediatric Surgery, All India Institute of Medical
Sciences, India. Preoperative position of the urethral
meatus was noted and phenotype was graded as mild,
medium or severe. Subjects with un-descended testis,
intersex disorders were excluded from the study. Only
subjects with 46 XY phenotypes were included in the
study. A total of 110 age, geography (North India), ethnicity
(white) and language (Indo-European) matched controls
from the general North Indian population without
hypospadias or any history of genital abnormalities were
collected via house-to-house surveys.
AIIMS is a multicentric hospital centred at New Delhi (a
multicultural city), in which patient group from almost all
castes, communities, regions subsist. Though the cases
collected (from hospital) in the present study belonged to
different communities making the samples heterogenous,
maximum care was taken to match the controls with
respect to communities observed among cases in order
to get a clear scenario on the prevalence of hypospadias
among Indian communities. All the communities included
in the present study can be considered to fall under North
Indian stock (Ancestral Northern Indian). Demographic
and clinical data pertaining to reproductive profile of the
mother, occupation of the parents and family history of
genital abnormalities in male blood relatives were
recorded for cases and controls.
Birth defects registered with the AIIMS Paediatric
outpatient department (OPD) from the years 2003-2011
were scrutinized and the data on the number of
hypospadias cases enrolled among them were calculated
from AIIMS OPD registries and its frequency distribution
was noted for the last 9 years.
RESULTS
Figure 1 depicted an increase trend in the incidence of
hypospadias from the year 2003 (7.66%) to the year 2011
(9.33%).
Community-wise distribution of hypospadias cases
showed a larger proportion of hypospadias cases (35.6%)
among an agricultural-based community, J ats, followed
Figure 1: Graphical representation of hypospadias incidence from the years 2003-2011
Annals of Health & Health Sciences 63
Hypospadias Risk among North-Indian Children
by Muslims (21.78%) and Brahmins (11.88%) residing in
Northern India. Analysis of the demographic data of cases
on the basis of parental occupational status depicted a
major group of children (72.27%) affected with
hypospadias had their parents from rural background
having agriculture as their primary occupation (Fig. 2).
Univariate analysis (Table 1) between cases and controls
with respect to maternal age at first conception, age at
menarche, birth weight of the affected child and folic
acid supplementation during pregnancy was not found to
be statistically significant (P>0.05). However, significant
Figure 2: Graphical representation/distribution of parental
exposure to pesticides among cases
Table 1: Potential risk factors and confounders for hypospadias, unadjusted ORs and 95% CIs
Characteristic Cases N=101 Controls N=110 Odds ratio 95% C.I P-val ue
Maternal age at first birth
Less than 20 years 22 (21.8%) 16 (14.5%) 1.00
21-30 years 76 (75.2%) 85 (77.2%) 0.65(0.31-1.32) 0.28
More than 30 years 03 (2.9%) 09 (8.2%) 0.24(0.05-1.04) 0.09
Age at menarche
<14 years 33 (32.7%) 38 (34.5%) 1.00
>14 years 68 (67.3%) 72 (65.5%) 1.08(0.61-1.92) 0.884
Birth weight of the affected child (g)
Normal (>2,500 g) 76 (75.2%) 93 (84.5%) 1.00
<2,500 25 (24.8%) 17 (15.5%) 1.8(0.9-3.57) 0.11
Folic acid supplements in pregnancy
Yes 49 (48.51%) 59(53.64%) 0.8(0.47-1.39) 0.49
No 52 (51.49%) 51(46.36 %) 1.00
Diet
Vegetarian 62 (61.39%) 43 (39.09%) 2.47(1.4-4.3) 0.001
Non-vegetarian 39 (38.61%) 67 (60.91%) 1.00
Abbreviations: CI, confidence interval; OR, odds ratio.
difference was observed between cases and controls with
respect to vegetarianism (P<0.05).
DISCUSSION
A trend in declining male reproductive health with respect
to hypospadias risk among Indian children was elucidated
in the present study (Figure 1). These figures might be
under-reported, especially in Indian context where the
topic of ambiguous genitalia being a sensitive subject, has
an enormous stigma attached. Due to this, the parents of
the affected child may not report their childs abnormality
and may further conceal it to prevent the traumatisations
caused by the society. These derived results are, however,
in agreement with other epidemiological studies and
surveillance programmes held world-wide.
7
Community-
wise distribution of hypospadias cases depicted larger
proportion of cases (35.6%) among an agricultural-based
community (Jats) residing primarily in the Northern Indian
belt. On comparing cases and controls with respect to
demographic and clinical data, only vegetarianism was
found to be associated with hypospadias (Table 1). These
results are in agreement with a previous report
8
which
suggests that vegetarians have a greater exposure to
phytoestrogens than omnivores thereby supporting the
possibility that phytoestrogens have a deleterious effect
on the developing male reproductive system.
64 Volume 1, Number 1, J anuary-J une 2014
Ratika Samtani et al.
On the basis of parental occupational status, a major group
of children (72.27%) affected with hypospadias had their
parents from rural background having agriculture as their
primary occupation, i.e., individuals adhering to
agricultural background are likely to be exposed to
pesticides, which are EDs and anti-androgenic in nature.
Though our study lacks the estimate of pesticide levels
among cases, its role in hypospadias causation cannot be
ruled out as foetal exposure to EDs with estrogen-like or
anti-androgen-like activity found among pesticides could
be a risk factor for hypospadias.
J ensen et al.
9
hypothesised that the detrimental changes
in male reproductive health that are becoming more
apparent may be caused by the developing foetus having
an altered exposure to EDCs with oestrogenic effects.
According to Laden et al.
10
even before the moment of
conception, the embryo is exposed to its mothers
background burden of persistent chemicals. Thus, an
increase in hypospadias incidence (as earlier suggested
by Baskin et al.
11
confirmed in the present study) could
be attributed to two major hypotheses - one is a greater
potential exposure of populations to the use of harmful
pesticides. Second, due to recent advances in surgical
techniques and assisted reproductive technologies, men
with such defects after surgical correction are able to
reproduce and are likely to transmit the genetic defects
to their offsprings.
6
The major issue in Indian context is
that there is a dearth of studies related to these issues
where large numbers of workers are engaged in
agricultural and farming practices and are being exposed
to various pesticides. This raises concern for health
managers and policy makers as pesticides being used
extensively in agricultural tracts are released into the
environment and come into human contact directly or
indirectly, thereby causing adverse effect on human
health. As this study brings out the possible role of EDs
in the aetiology of hypospadias, more replicative series
involving large-scale population screening and monitoring
of EDCs in the rural community are needed.
CONFLICT OF INTEREST
None of the contributing authors have any conflict of
interest.
ACKNOWLEDGEMENT
The present work would not have been possible without
the supporting staff of All India Institute of Medical
Sciences (AIIMS) and the people for facilitating the data
collection. This research received no specific grant from
any funding agency in the public, commercial or not-for-
profit sectors.
Ethical Clearance
The study was carried out after obtaining the ethical
clearance from the Department of Anthropology,
University of Delhi and All India Institute of Medical
Sciences (AIIMS), New Delhi.
REFERENCES
1. Paulozzi LJ , Erickson J D and J ackson RJ . Hypospadias trends
in two US surveillance systems. Pediatrics 1997; 100: 831.
2. Myrianthopoulos NC, Chung CS. Congenital malformations
in singletons: epidemiologic survey. Report from the
Collaborative Perinatal Project. Birth Defects Orig Artic Ser
1974; 10: 1.
3. Carbone P, Giordano F, Nori F, Mantovani A, Taruscio D,
Lauria L, Fig-Talamanca I. Cryptorchidism and hypospadias
in the Sicilian district of Ragusa and the use of pesticides.
Reprod Toxicol 2006; 22(1): 8-12.
4. Kristensen P, Irgens LM, Andersen A, Bye AS, Sundheim L.
Birth defects among offspring of Norwegian farmers, 1967-
1991. Epidemiology 1997; 8(5): 537-44.
5. Weidner I S, Mller H, J ensen TK, Skakkebaek NE.
Cryptorchidism and hypospadias in sons of gardeners and
farmers. Environ Health Perspect 1998; 106(12): 793-6.
6. Samtani R, Bajpai M, Vashishth K, Ghosh PK, Saraswathy
KN. Hypospadias Risk and Polymorphism in SRD5A2 and
CYP17 Genes: Case-Control Study Among Indian Children. J
Urol 2001; 185: 2334-2339.
7. Paulozzi LJ . International trends in rates of Hypospadias and
cryptorchidism. Environ Health Perspect 1999; 107: 297-302.
8. Rosselli M, Reinhart K, Imthurn B, Keller PJ , Dubey RK.
Cellular and Biochemical mechanisms by which environmental
oestrogens influence reproductive function. Hum Reprod
Update 2000; 6(4): 332-50.
9. J ensen T K, Toppari J , Keidig N, Skakkeback NE. Do
environmental estrogens contribute to the decline in male
reproductive health? Clin Chem 1995; 41: 1896-1901
10. Laden F, Neas LM, Spiegelman D, Hankinson SE, Willett WC,
Ireland K, Wolff MS, Hunter DJ . Predictors of plasma
concentrations of DDE and PCBs in e group of U.S. women.
Environ Health Perspect 1999; 107: 75-81.
11. Baskin LS, Himes K, Colborn T. Hypospadias and endocrine
disruption: is there a connection? Environ Health Perspect
2001; 109: 1175-1183.
How to cite this article: Samtani R, Bajpai M, Ghosh PK,
Saraswathy KN. Hypospadias Risk among North-Indian Children. Ann
Health & Health Sci 2014; 1(1): 61-64.