Growth and Development Assessment of Children (1-5 Years) Operated for Tracheoesophageal Fistula/Esophageal Atresia: A Case Control study.

INTRODUCTION: Among children, esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) is one of the major and common congenital anomalies. It is a life-threatening emergency and at birth may be associated with three C's coughing, choking, and cyanosis. It requires surgical interventions in the early neonatal period. The postsurgical period is associated with poor growth which can be developmental outcomes particularly in the first 5 years of life and attributed to postsurgical complications. The aim of the study is to assess and compare the growth and development of the children (1-5 years) operated for TEF/EA attending Pediatric Surgery OPD/admitted inwards at APC, PGIMER, Chandigarh versus healthy controls.
MATERIALS AND METHODS: A case-control study was conducted on age-matched 40 children aged between 1 and 5 years operated for TEF/EA and healthy controls. The sampling technique for cases was total enumeration and for controls was purposive sampling. Tools used were socio-demographic sheets of children, clinical profile of children, Trivandrum Development Screening chart, and Vineland Social Maturity Scale for Indian adaptation.
RESULTS: Majority 33 (82.5%) of children had distal TEF and more than two-third 28 (70%) have undergone primary repair. More than one-third 14 (35%) had a respiratory infection, 12 (30%) anastomosis leakage and 6 (15%) had Gastroesophageal reflux (GER) as one of the early and late postoperative complications. More than one-fourth 11 (27.5%) of TEF/EA operated children had less weight, 11 (30%) had less height and 16 (40%) had less weight for height for their reference age. A significant difference was found for height for age, weight for height, and social maturity among children who had TEF repair as compared to their healthy counterparts.
CONCLUSION: Growth monitoring reflected (more than one-fourth of children were underweight and stunted while more than one-third were wasted) and showed development delay in TEF/EA operated children as compared to healthy controls. Copyright:

INTRODUCTION

Esophageal atresia (EA), with or without tracheoesophageal fistula (TEF), is a developmental defect of the upper gastrointestinal tract in which the continuity between the upper and lower esophagus is lost. EA can occur with or without TEF.[1] EA and/or tracheo-oesophageal fistula are common congenital malformations occurring in about 1 in 2500–4500 births where there have been several described anatomical variants.[23]

Embryologically trachea originate from an endodermal outgrowth of the ventral wall of the foregut at 3 weeks of gestation. The classification of EA anomalies is based on the location of the atresia and the presence of any associated fistula to the trachea. The primary types of EA are EA with distal TEF (85%), isolated EA without TEF (8%), TEF without atresia or H-type TEF (4%), EA with proximal TEF (3%), and EA with proximal TEF (<1%).[4]

These neonates are surgically repaired by primary repair, or staged repair and sometimes redo surgery may be required after primary failure. Primary reconstruction has become a standard for managing TEF/EA, except for long gap EA. TEF/EA is associated with prolonged hospitalization due to anastomotic leak, the need for ventilator care, and postsurgical complications.[2] Regardless of the surgical procedure approach, those children who have postoperative complications which ultimately affect their quality of life.[56] Postoperative complications include dysphagia, frequent respiratory infections and choking, Gastroesophageal reflux Disease (GERD), leak strictures, hearing problems, speech problems, and development delay.[1237] Though there has been a significant improvement in the survival of children born with TEF/EA, these children continue to face many physical, emotional, learning, and behavioural problems.[12] These children must require long-term follow-up to address the postoperative complications and other problems.

During follow-up, it has been found that many children were malnourished as they were underweight, stunted, and had head circumference less than for their reference age.[689] In addition to that many studies have also reported that early childhood of these children is associated with gross motor and cognitive development delay.[891011]

Most of the available studies from the region are on the clinical profile of the disease, growth parameters, postoperative complications, and long-term outcome of TEF/EA, and based on retrospective data, which might have under-evaluated the effect of long-term complications on the growth of children. The resource constraints of developing nations specially from south east asia, is an added challenge in optimizing treatment and followup of these children. Keeping this in view the present study was planned to assess the growth and development of children and their comparison with healthy controls. Hence, that special attention can be given to underweight, stunted children, and need of special clinics including dieticians, speech pathologists, and growth monitoring specialists can be highlighted to ensure the global development of these children.

MATERIALS AND METHODS

Using a quantitative approach in case–control design, growth, and development of 40 children (1–5 years) operated for TEF/EA was assessed in outpatient department/surgical wards and compared with corresponding healthy controls selected from day-care centers of Chandigarh and immunization clinic. A 3-year's database retrieved from the Medical Record Department and operation theater. Data of total registered TEF/EA children (1–5 years) in the hospital (n = 187) between January 2015 to May 2018 was retrieved. Out of 187 patients, 7 patients left against medical advice (LAMA). Total operated cases were 180 of which 84 patients expired. The researcher tried to contact 96 survived patients. Out of that 37 patients couldn't be contacted and 19 were not willing to come for follow up due to their family and financial issues. Only 38 children came for follow-up in OPD and 2 were admitted in wards along with their caregivers were enrolled in the study [Figure 1]. Prior permission, thus 4o children was obtained from the Institute of Ethics Committee and informed written consent was taken from the caregivers before data collection. Data was collected from the caregivers who reported in OPD by interview method. Children were assessed for weight, height, mid-upper arm circumference, and skinfold thickness. Developmental functioning and social maturity of children were assessed by using Trivandrum Development Screening Chart (TDSC) and Vineland Social maturity Scale (VSMS). After collecting data from cases corresponding to healthy controls were matched with respect to age and socio-economic status of caregivers and the same process of data collection was followed. The educational status of the parents could not be matched due to large discrepancy in this data subset. Later children with primary repair and stage repair were grouped in two groups and data was analyzed for the above-mentioned growth and development parameters.

Figure 1

Consort diagram

Data was recorded, coded, and entered into Statistical Package for the Social Sciences (SPSS)20 by International Business Machines Corporation (IBM), New York. Statistical analysis was carried out with SPSS version 20.0. Data were analyzed using descriptive and inferential statistics.

RESULTS

Majority of the children were toddlers. The mean age of both groups was 1.69 + 0.68. More than half of the children 24 (60.0%) (37, 92.5%), 21 (52.5%) were male followed by 16 (40.0%) and 19 (47.5%) females, respectively, in both groups. Most 33 (82.5%) had distal TEF followed by pure EA in 4 children (10%). More than two-third 28 (70%) have undergone primary repair whereas more than one-fourth 12 (30%) had staged repair of which 9 (22.5%) recovered with stage repair and 3 (7.5%) reported with failed primary repair. 14 children (30%) developed a respiratory infection, 12 children (30%) had anastomosis leakage and 6 (15%) had GER as one of the early and late postoperative complications. 7 children required one-time balloon dilatation, 3 had two times and 2 had three times or more dilatation [Table 1].

Table 1

Disease profile of the children operated for tracheoesophageal fistula/esophageal atresia (n=40)

Variable	Category	Frequency, n (%)
Type of TEF	Distal TEF	33 (82.5)
	Pure EA	4 (10.0)
	H type fistula	2 (5.0)
	Proximal TEF	1 (2.5)
Type of surgery	Primary repair	28 (70.0)
	Stage repair	9 (22.5)
	Stage repair after failed primary repair	3 (7.5)
Postoperative complications	Absent	4 (10.0)
	Anastomotic leak/stricture	12 (30.0)
	GER	6 (15.0)
	Recurrent TEF	2 (5.0)
	Winging of scapula	2 (5.0)
	Pneumonia	14 (35.0)
Balloon dilatation (n=12)	One time	7 (58.3)
	Two times	3 (25.0)
	Three times or more	2 ( 16.7)

TEF: Tracheoesophageal fistula, EA: Esophageal atresia, GER: Gastroesophageal reflux

Physical parameters Z score of 13–60 months subjects

More than three fourth 35 (87.5%) in the control group were normal children for the weight for age and mean Z score was − 1.08 ± 0.64 and − 0.81 ± 0.74 in both groups. More than one-fourth 11 (27.5%) in the case group, 5 children (12.5%) in the control group were underweight and mean Z score was − 2.8 ± 0.84 and − 2.33 ± 0.53 for underweight children in both groups. 28 (70%) children in patient group while all 40 (100%) in the control group were normal for height for age and mean Z score was − 0.47 ± 1.20 and − 0.27 ± 0.69 for normal height for age children in both groups. 12 children (30%) were stunted in the case group while none in the control group. Mean Z score for stunted children was − 3.03 ± 1.19 in the patient group. There was a significant difference P = 0.001 between mean Z score for height for age among both the groups. More than half 24 (60%), 26 (65%) of the children were normal for the weight for height in both groups. The mean Z score was − 0.85 ± 0.75 and − 0.30 ± 1.16 for the normal weight for height in both groups. There was a significant difference at P = 0.001 between weights for height among both the groups. More than one-third 16 (40%), 14 (35%) of children were wasted, and mean score was − 3.57 ± 0.74 and − 3.17 ± 1.07 for wasted children in both groups [Table 2a and Figure 1].

Table 2a

Physical parameters Z score of 13-60 months subjects (n=80)

Physical parameter	Cases (n=40), n (%)	Controls (n=40), n (%)	χ2, df, P	Mean±SD		t, df, P
				Cases	Controls
Weight for age (kg)
Normal (+2-−2 SD)	29 (72.5)	35 (87.5)	2.81, 1, 0.94	−1.08±0.64	−0.81±0.74	1.61, 62, 0.15
Underweight (−2-−3 SD)	11 (27.5)	5 (12.5)		−2.8±0.84	−2.33±0.53	1.8, 14, 0.34
Height for age (cm)
Normal (+2-−2 SD)	28 (70)	40 (100)	18.74, 1, 0.002#	−0.47±1.20	−0.27±0.69	0.89, 66, 0.001
Stunted (−2-−3 SD)	12 (30)	-		−3.03±1.19	-	-
Weight for height
Normal (+2-−2 SD)	24 (60)	26 (65)	1.39, 1, 0.49	−0.85±0.75	−0.30±1.16	2.00, 48, 0.001
Wasted (−2-−3 SD)	16 (40)	14 (35)		−3.57±0.74	−3.17±1.07	1.17, 28, 0.57

#Fisher’s exact test. SD: Standard deviation

Physical parameters Z score of 13–60 months subjects with primary and stage repair

More than two-thirds 20 (71.5%) of children with primary repair, three fourth 9 (75%) of children with stage repair were normal for the weight for age and mean Z score was − 0.72 ± 0.80 and − 1.00 ± 0.60 for the normal weight for age children in both groups. 8 children (28.5%) with primary repair, 3 children with stage repair (25%) were underweight. The mean Z score was − 2.46 ± 0.38 and − 3.7 ± 1.05 for underweight children in both groups. There was a significant difference P = 0.010 between mean Z score for the weight for age among both the groups. 19 children (67.8%) with the primary repair (66.7%) with stage repair were normal for height for age. Mean Z score was − 0.57 ± 1.2 and − 0.41 ± 1.08 for normal height for age children in both groups. 9 children (32.2%) with the primary repair 4 children (33.3%) with stage repair were stunted in both groups. Mean Z score for stunted children was − 2.41 ± 1.37 and − 3.34 ± 0.31 in both groups. There was a significant difference P = 0.051 between mean Z score for height for age among both the groups. 18 (64.2%) and 8 (66.7%) children were normal for the weight for height in both groups. The mean Z score was − 0.16 ± 1.21 and − 0.56 ± 1.07 for the normal weight for height in both groups. 10 (35.8%), 4 (33.3%) of children were wasted in both groups. The mean and score was − 2.90 ± 1.25 and − 3.17 ± 0.70 for wasted children in both groups. There was a significant difference at P = 0.010 and 0.051 between weights for age and heights for age in both groups [Table 2b].

Table 2b

Physical parameters Z score of 13-60 months subjects with primary and stage repair (n=40)

Physical parameter	Cases with primary repair (n=28), n (%)	Cases with stage repair (n=12), n (%)	χ2, df, P	Mean±SD		t, df, P
				Cases with primary repair	Cases with stage repair
Weight for age (kg)
Normal (+2-−2 SD)	20 (71.5)	9 (75)	1.08, 1, 0.018	−0.72±0.80	−1.00±0.60	0.91, 27, 0.047
Underweight (−2-−3 SD)	8 (28.5)	3 (25)		−2.46±0.38	−3.7±1.05	3.23, 9, 0.010
Height for age (cm)
Normal (+2-−2 SD)	19 (67.8)	8 (66.7)	2.023, 1, 0.002	−0.507±1.28	−0.41±1.08	1.94, 26, 0.335
Stunted (−2-−3 SD)	9 (32.2)	4 (33.3)		−2.41±1.37	−3.34±0.31	1.30, 10, 0.051
Weight for height
Normal (+2-−2 SD)	18 (64.2)	8 (66.7)	1.39, 1, 0.49	−0.169±1.21	−0.56±1.07	0.77, 22, 0.483
Wasted (−2-−3 SD)	10 (35.8)	4 (33.3)		−2.90±1.25	−3.17±0.70	0.77, 14, 0.504

SD: Standard deviation

Trivandrum Development Screening Chart (TDSC) test characteristics of 13–60 months subjects

As per TDSC majority 12 (70.6%), 16 (94.1%) of children had tested negative in both groups. Out of 34 children who were of 13–24 months of age, only 2 (11.8%) children had test positive (1 item delay), whereas in the patient group, the tested was negative for all the children. The children who were of age 25–36 months, majority 17 (85%), 15 (75%) had tested negative in both of the children, the groups. While in the same age group 3 children (15%) had tested positive (1 item delay) in the control group. In the age group, 37–60 months, 2 childrten (66.667%) in patient group and 3 (100%) children in the control group had tested negative while 1 child had tested positive (2 item delay). As per the Fisher exact test, no significant difference between development parameters was found in both groups in terms of developmental parameters [Table 3a].

Table:-3(a)

TDSC test characteristics of 13-60 months subjects n=80

Age (months)	TDSC	Case	Control	Fisher Exact test, (df), P
13-24(n=34)	Test negative*Test positive**(1 item delay)Test positive (2 item delay)Test positive (>2 item delay)	12 (70.6)-2 (11.8)3 (17.6)	16 (94.1)1 (5.9)--	4.80 (3) 0.15
25-36(n=40)	Test negativeTest positive (1 item delay)Test positive ( 2 item delay)	17 (85)-2 (10)	15 (75)3 (15)2 (10)	4.54 (3) 0.19
37-60(n=6)	Test negativeTest positive ( 2 item delay)	2 (66.7)1 (33.3)	3 (100)-	1.20 (1) 0.27

*- test negative means no delay, ** test positive means delay present

Trivandrum Development Screening Chart (TDSC) test characteristics of 13–60 months subjects with primary and stage repair

In the majority 22 (78.5%), 9 (975%) of children test was negative in both groups. 2 children (7.2%) with the primary repair while 2 (16.7%) children with stage repair had tested positive (1 item delay). Less than one-fourth 4 (14.3%) and 1 (0.3%) of children had test positive (2 item delay). No significant difference between development parameters was found in both groups. This means that subjects were comparable for TDSC test characteristics among both the groups [Table 3b].

Table 3b

TDSC test characteristics of 13-60 months subjects with primary and stage repair(n=40)

TDSC	Cases with primary repair (n=28), n (%)	Cases with stage repair (n=12), n (%)	χ2, df, P
Test negative*	22 (78.5)	9 (75)	1.014, 2, 0.602
Test positive** (1 item delay)	2 (7.2)	2 (16.7)
Test positive (2 item delay)	4 (14.3)	1 (8.3)

*test negative means no delay, **test positive means delay present, TDSC: Trivandrum development screening chart

Vineland Social Maturity Scale (VSMS) parameters of subjects

As per VSMS children assessed for three parameters: VSMS score, social age (SA), and social quotient (SQ). The mean VSMS score of children between 13 and 24 months was 21.13 ± 5.56 and 22.59 ± 4.71 in cases and controls respectively and this difference was statistically significant at P = 0.001. The mean VSMS score of children between 25 and 36 months was 37.81 ± 3.25, 39.25 ± 2.33 in cases and controls, respectively, and this difference was statistically significant at P = 0.004. The mean score of subjects between 37 and 60 months was 41.80 ± 11.53, 50.00 ± 2.82 in both groups.

Mean SA of subjects between 13 and 24 months was 1.24 ± 0.32 and 1.33 ± 0.27 in both groups and there was a significant difference at P = 0.001 between mean SA. Mean SA of subjects between 25 and 36 months was 2.37 ± 0.43 and 2.59 ± 0.22, respectively, and there was a significant difference at P = 0.007 between mean SA in both groups. Mean SA of subjects between 37 and 60 months was 2.93 ± 1.30 and 4 ± 0.42 in both groups. This means that cases had a significantly lower SA as compared to controls in age groups between 13–24 months and 25–36 months.

Mean SQ of subjects between 13 and 24 months was 86.23 ± 10.21 and 89.78 ± 16.75 in both groups and groups had a significant difference at P = 0.001 between SQ. Mean SQ of subjects between 25 and 36 months was 90.69 ± 7.28, 90.90 ± 3.28 in both groups, respectively. Mean SQ of subjects between 37 and 60 months was 74.55 ± 2.69, 90.03 ± 3.48 in both groups This means that cases had significantly lower SQ scores as compared to controls only in 13–24 months age group [Table 4a].

Table 4a

Vineland Social Maturity Scale parameters of subjects

VSMS parameters	Age (months)	Mean±SD		t, df, P
		Case	Control
VSMS score	13-24	21.13±5.56	22.59±4.71	4.09, 33, 0.001
	25-36	37.81±3.25	39.25±2.33	1.29, 39, 0.004
	37-60	41.80±11.53	50.00±2.82	0.87, 5, 0.68
Social age	13-24	1.24±0.32	1.33±0.27	4.35, 33, 0.001
	25-36	2.37±0.43	2.59±0.22	0.862, 39, 0.007
	37-60	2.93±1.30	4±0.42	0.87, 5, 0.74
Social quotient	13-24	86.23±10.21	89.78±16.75	2.97, 33, 0.001
	25-36	90.69±7.28	90.90±3.28	0.356, 39, 0.39
	37-60	74.55±26.69	90.03±3.48	−1.010, 5, 0.074

VSMS: Vineland Social Maturity Scale, SD: Standard deviation

Social skills development in various domains in children operated for TEF/EA as measured by VSMS in groups. There is a significant difference at P = 0.001, 00.02 between self-help dressing and socialization domains in both groups [Figure 2].

Figure 2

Social skills development in children operated for tracheoesophageal fistula/esophageal atresia as measured by Vineland Social maturity Scale

Vineland Social Maturity Scale parameters of subjects with primary and stage repair

As per VSMS children assessed for three parameters: VSMS score, SA and SQ. The mean VSMS score of children between 13 and 60 months was 28.38 ± 10.19, 24.83 ± 11.26 in children with primary and stage repair, respectively. Mean SA of subjects between 13 and 60 months was 1.71 ± 0.70 and 1.52 ± 0.77 in both groups. Mean SQ of subjects between 13 and 60 months was 87.27 ± 13.4, 83.34 ± 11.4 in both groups. The subjects were comparable for VSMS parameters among both the groups [Table 4b].

Table 4b

Vineland Social Maturity Scale parameters of subjects with primary and stage repair (n=40)

VSMS parameters	Cases with primary repair (n=28)	Cases with stage repair (n=12)	t, df, P
VSMS score	28.38±10.19	24.83±11.26	0.70, 20, 0.488
Social age	1.71±0.70	1.52±0.77	0.68, 20, 0.501
Social quotient	87.27±13.4	83.44±11.4	0.61, 20, 0.546

VSMS: Vineland Social Maturity Scale

DISCUSSION

Several recent studies have reported that the majority of the children had distal TEF and pure EA and the overall morbidity is significant, Which may be related to the initial surgical approach and technique.[2612] In the study, investigator found that the majority of the children had distal TEF and only a few had pure EA. A most recent study from north India described that, primary esophageal repair may not suffice alone. A combination of other surgical techniques must be kept in mind to deal with the complications of long gap, anastomotic leak and anastomotic strictures. In this study, investigator also observed similar findings.[12]

The major finding of the study revealed that children operated for TEF/EA had delay in physical parameters, SA, SQ, self-help dressing, and socialization domain as compared to healthy controls. The TEF/EA operated children were underweight, stunted, and wasted as compared to healthy controls. Children with primary repair had better growth as compared to stage repair.

Multiple studies from institutions all over the world assessing postoperative complications found respiratory infection, stricture, anastomotic leak, GER, recurrent TEF etc.[112] We also observed a similar pattern of postoperative complications in the North Indian population. To manage these postoperative complications one time, two-time, or even multiple times balloon dilation adopted.[12]

A very recent study from North India on “Developmental Status of Children Operated for EA with or with out staged repair Tracheoesophageal Fistula Along with Maternal Stress, Their Quality of life, and Coping Abilities” showed that Developmental delay was present in children operated for EA with or without caused significant stress among mothers, affecting their QOL for which the emotional outlet was the most commonly used coping strategy.[12] The result was comparable for the development delay in the present study.

Many of the studies done to assess the growth and development of these TEF-operated children and reported that more one-fourth of operated children had weight and height less than for their reference age.[2] However, most recent study highlighted a higher percentage for underweight and a lesser percentage for stunted children.[12] These findings were comparable to the present study findings in terms of underweight and stunted children percentages. Investigator found two different groups based on the method adopted for defect correction and tried to compare the growth parameters of the two. Later on, it was found that the children who underwent multiple procedures and anesthesia had a significant difference in growth parameters in terms of weight and height for their reference age which was a major highlight of the study findings.

The children with advancing age expected to have social maturity regarding eating, dressing, locomotion, occupation, self-direction, and socialization.[13] During development assessment, it is found that social development quotient delay in locomotion, self-help dressing domain, self-help general, self-help eating, communication, and socialization domain, on the other hand, normal development has been reported in the occupation domain.[12] The result of the present study also showed social maturity lacking in different domains like self-help general, self-help eating, self-help dressing, locomotion, eating, occupation, and socialization in TEF/EA-operated children which affect their overall growth and development. As there were no differences between cases and control at older ages that means as they grow to learn skills and become better but still lacking in some of the domains which are highlighted in the study.

Among cases and controls, though a significant difference has been found between height for age and weight for height in growth parameters and social development, both the groups were comparable for the rest of the parameters under study. Significance difference was found among children with primary repair and staged repair between weight for age and height for the age that means if children undergoing multiple procedures and anesthesia had a significant difference in growth parameters in terms of weight and height for their reference age, this was a major highlight of the study findings.

This could be attributed to the smaller sample size which was a major limitation of the study due to the limited time frame for data collection. This could further jeopardize the generalization of findings. To achieve the long-term effect and generalization of findings of TEF/EA operated children on growth and development a large sample size, regular follow-up, and longitudinal data collection study are required. However, growth and development assessment of TEF/EA-operated children versus healthy controls was beneficial in making the comparison required for the study.

CONCLUSION

Growth monitoring reflected that more than one-fourth of children were underweight and stunted while more than one-third were wasted. Children who underwent repair were underweight and stunted as compared to children with primary repair. Development showed that social skill development was lacking in self-help dressing and socialization domain delay in TEF/EA operated children as compared to healthy controls.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.