Seasonal Frequency in Esophageal Atresia/Tracheo-Esophageal Fistula: Is there an Environmental Etiology?

doi:10.4236/ss.2011.27084

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Surgical Science, 2011, 2, 385-387

doi:10.4236/ss.2011.27084 Published Online September 2011 (http://www.SciRP.org/journal/ss)

Seasonal Frequency in Esophageal

Atresia/Tracheo-Esophageal Fistula: Is there an

Environmental Etiology?

Christopher Bode, Adesoji Ademuyiwa, Sylvester Ikhisemojie

Pediatric Surgery Unit, Department of Surgery, College of Medicine of the University o f Lagos/Lagos University

Teaching Hosp i t al , Lagos, Nigeria

E-mail: [email protected]

Received May 13, 201 1; revised July 13, 2011; accepted August 9, 2011

Abstract

Background: Esophageal Atresia and Tracheo-Esophageal Fistula (EA/TEF) occurs sporadically and its eti-

ology is poorly understood. We observed six cases of EA/TEF within three weeks of October 2007 at the

Lagos University Teaching Hospital (LUTH), Nigeria. Aims: To analyze the monthly trends of presentation

of EA/TEF at the LUTH from 2002-7, test the hypothesis that the October figures were not due to chance

and correlate data with known local disease patterns. Setting: Lagos University Teaching Ho spital, Nigeria.

Patients, Materials, Method: A retrospective analysis of all EA/TEFs managed at the LUTH within stated

period. Results: 25 babies with EA/TEF presented over the period. 10 (40%) were seen in the month of Oc-

tober, 5 (20%) occurred in May while the rest were spread over the rest of the months. Chi-square analysis

confirmed that the EA/TEF cases occurred significantly more frequently in October (P < 0.001) and this ob-

servation was unlikely due to chance. Conclusions: There se ems to be a sea sonal variation in the occurrence

of EA/TEF in Lagos, with a significantly higher frequency in the month of October. 96% of mothers of ba-

bies with EA/TEF lived in low socioeconomic parts of Lagos. This study highlights the possibility of local

viral etiology of EA/TEF.

Keywords: Tracheo-Esophageal Fistula, Seasonal Etiology

1. Introduction

The etiology of oesophageal atresia with tracheo- eso-

phageal fistula (EA/TEF) has been a subject of intensive

investigations over the years but little if anything is

known about specific causative agents in humans [1 ]. No

definite seasonal variations or patterns have been dem-

onstrated for this condition [2]. Its occurrence is some-

times sporadic but these are confined to those with rare

familial genetic dispositions [3]. The unusual presenta-

tion of six new cases of EA/TEF to our Unit within three

weeks of October 2007 at the Lagos University Teaching

Hospital therefore prompted a search for possible envi-

ronmental factors that could have triggered the cluster.

We sought to analyze the trend and test the hypothesis

that the October 2007 figures were not due to chance and

correlate our data with known local disease patterns.

2. Materials/Methods

Records of all cases of esophageal atresia managed by

the Pediatric Surgical Unit at the LUTH between January

2002 and December 2007 were retrospectively compiled

and analyzed for date of presentation, age at presentation,

maternal age, tribe, maternal socio-economic locale, oc-

cupation, maternal last menstrual period, history of oc-

cupational exposure to chemical teratogens, and first-

trimester maternal illness.

Addresses of parents were categorized as affluent,

middle-class or low based on the demographic spread of

the Lagos metropolis. All the data were recorded onto a

protocol and analyzed using Microsoft Excel 2007. The

observed monthly frequency was subjected to Chi-square

analysis to assess whether the difference between the

observed and expected distributions could be attributed

386 C. BODE ET AL.

to chance and unless otherwise stated, P < 0.05 was con-

sidered statistically significant.

3. Results

25 babies with EA/TEF were seen within the study pe-

riod. There were 14 (56%) males and 11 (44%) females,

giving a male:female ratio of 1.2:1. Their ages ranged

from 10 hours to 25 days with a mean age of 8.8 ± 5.2

days at presentation. The babies were all full-term, with a

mean birth weight of 2.6 ± 0.4 kg (range 2.1 - 3.7 kg).

Seventeen (68 % ) of these babies were first borns.

Maternal age ranged from 20 - 31 years, with a mean

of 24.5 ± 3.3 years. All the 25 mothers were Nigerian.

There was no preponderance of any ethnic group or oc-

cupation among the mothers. None of the mothers gave

any history of exposure to heavy metals or known tera-

togens. None of the babies was prenatally diagnosed as

having EA/TEF. Twenty four mothers (96%) lived in

low socio-economic parts of Lagos.

3.1. Monthly Frequency of EA/TEF Occurence

Table 1 shows the monthly frequency of EA/TEF over

the five year period under re view. Th e month s of Januar y,

February, July and September recorded one case each

while 2 cases were recorded for each of March, June and

August. Five cases were seen in May while 10 were re-

corded in October. April, November and December re-

corded none.

The expected monthly distribution was 25/12 = 2.08

cases per month, assuming that all cases occurred with

equal frequency over a twelve month period. This was

subjected to the Ch i-square analysis, to examine whether

the difference between the observed and expected distri-

butions was attributable to chance. A low P-value of <

0.001 obtained did not support the null hypothesis that

there was no difference between the observed and ex-

pected distributions. Rather, it supported the alternative

hypothesis that the difference observed was unlikely to

Table 1. Observed monthly trends 2002-7.

be due to chance, and thus, the occurrence of a seasonal

variation in the occurrence of EA/TEF was real.

3.2. Maternal Last Menst rual Period

The two peak periods of May and October raised the

specter of possible seasonal environmental teratogenic

events early in the first trimester. We therefore sought

the last menstrual periods of the mothers and this showed

that the babies born in May were conceived in August

while the October ones were conceived in January.

4. Discussion

This is the first known report of a seasonal occurrence of

EA/TEF from Africa to the best of our knowledge. A

wide search of the local and international literature re-

vealed no similar occurrence. It is interesting to know

that the babies born in October and May were conceived

in January and August respectfully. August, January and

April are months when seasons change in Lagos. These

three periods constitute peak seasons of viral loads in

Lagos (during which there occurs widespread respiratory

and gastro-enteric infections) and we had earlier shown

these periods of seasonal changes to be associated with

the highest frequency of idiopathic intussusceptions in

the Lagos metropolis [4]. Our previous studies had re-

ported adenoviruses in 40% of idiopathic intussuscep-

tions [5]. Similarly, Olaleye et al. [6] showed that the

peak incidence of influenza infections occurred between

April and September and during the harmattan season in

November among children in Ibadan, a large Nigerian

city 130 km northeast of Lagos. These periods coincide

roughly with the occurrence of idiopathic intussuscep-

tions and therefore of the exposure to viruses that may

likely be causative agents for EA/TEF. This notion is

underscored by the earlier suggestion that viral terato-

genicity in EA/TEF constitutes part of atresias involving

the biliary, anorectal and esophageal tracts [7]. Addi-

tional support for our hypothesis comes from the studies

of Ozimek et al. [8] who observed a clustering and cyclic

variation in the occurrence of EA/TEF similar to that of

infectious hepatitis in North Carolina.

We thus hypothesize that a possible exposure of preg-

nant mothers to respiratory and gastrointestinal viral

agents in the first trimester during these periods inter-

fered in some yet unknown way with the esophageal

embryogenesis to cause the EA/TEF. The long interval

between teratogenicity and postnatal diagnosis would

seem to separate these events by several months and

possibly distract the attention of investigators from fo-

cusing on that phase of development. Future studies

should aim at identifying viral markers in babies born

Month Frequency

Jan 1

Feb 1

March 2

April 0

May 5

June 2

July 1

August 2

Sept 1

Oct 10

Nov 0

Dec 0

Total 25

C. BODE ET AL.

387

under similar conditions as well as in their mothers.

4.1. Limitations

This was a retrospective observational study occasioned

by the occurrence of a cluster of EA/TEF noticed in Oc-

tober 2007. The gestational gap between the intrauterine

teratogenic insult to the esophagus and the postnatal

presentation of EA/TEF limited the possible elucidation

of viral fingerprints in the babies and their mothers. Our

institution had difficulties with theatre facilities which

were under repairs in 2005 - 2006 and consequently,

experienced a reduction in the number of referrals to our

Unit during this period.

4.2. Conclusions

Our study suggests that there is a seasonal variation in

the occurrence of EA/TEF in Lagos with a significantly

higher frequency in the month of October. 96% of moth-

ers of babies with EA/TEF lived in low socioeconomic

parts of Lagos. Fu ture studies should be directed to id en-

tifying possible viral teratogens in this group of new-

borns.

5. References

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Esophageal Atresia and Congenital Diaphragmatic Hernia:

Results of a Case-Controlled Study,” Birth Defects Re-

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82, No. 2, 2008, pp. 98-105. doi:10.1002/bdra.20423

[2] C. Fraser, P. A. Baird and A. D. Sadovnick, “A Com-

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Teratology, Vol. 36, No. 3, 1987, pp. 363-369.

[3] M. Van Staey, S. De Bies, M. T. Matton and J. De Roose,

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[5] C. O. Bode and S. A. Omilabu, “Viral Isolates of Intus-

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[6] O. D. Olaleye, S. A. Omilabu, A. O. Olabode and A. H.

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doi:10.1620/tjem.181.49

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