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Estimation of Thymic size in preterm and term Neonates by ultrasonography in tertiary health centre of western Maharastra.

INTRODUCTION: The thymus which is a central lymphoid organ which plays an important role for proliferation, differential and selection of T lymphocytes that are responsible for cellular immunity. (1) The thymus develops from the endoderm of the third pharyngeal pouch (which also gives rise to the inferior parathyroid glands). Early in development, this pouch is cut off, both from the pharyngeal wall and from the surface ectoderm. (2) The first lymphocytes appear in the thymus during ninth week of gestation (Jeppesen et al. 2003). The thymus grows and enlarges continuously between the prenatal period and puberty. Moreover, during its a prenatal development, the size of fetal thymus is in close relationship with T-cell output.

The development and maturation of primary lymphoid organs and peripheral blood leukocytes occur throughout gestation but is not complete until after birth.

There are certain immunological peculiarities in preterm neonates like defective mucosal and skin barrier, low levels of secretory immunoglobulins, alkaline pH of stomach, low complement levels, defective phagocytocysis, smaller number of CD4 and CD8 cells and decreased response to pathogens. (3)

Previous studies conducted by Ivana Musilova et al, (4) established a nomogram for the transverse diameter of the fetal thymus in uncomplicated singleton pregnancies between 19 and 38 weeks of gestation. The purpose of our study is to conduct a sonography study on thymus and establish values for thymic index in new born babies of gestational age ranging from 28 to 40 weeks gestational age and correlate thymic size with various birth parameters like birth weight, birth length, gestational age, sex of neonate and mode of delivery.

MATERIALS AND METHODS: This is a prospective observational study conducted in the Krishna Institute of Medical Sciences hospital, Karad. Eighty Consecutive asymptomatic neonates who had supervised antenatal period are included in the study. The gestational age is assessed from date of last menstrual period and ballard score. In a case of extremely preterm neonates only neonates are included in our study those who have received one course of antenatal steroids 24 hours prior to delivery, this is not to to study the effect of antenatal steroids on thymic size. Neonates having maternal history of diabetes and hypertension, maternal history of HIV, TORCH, hepatitis , maternal history of pregnancy induced hypertension and eclampsia, maternal history of ante partum haemorrhage are excluded from the study, also preterm with birth asphyxia, meconium aspiration syndrome, preterm with congenital anomalies are excluded from the study.

The weight is measured on an electronic weighing scale. The length is measured using an infantometer. The measurement is taken on same equipment and by same observer. The ultrasonographic measurement of thymus is performed on day 4 to day 6 of postnatal age by the single radiologist. The thymic size is measured sonographically using Siemens Acuson x 300PE system and a 7.5MHZ probe. The thymus is examined in longitudinal and transverse planes by transsternal approach, parasternal and suprasternal approach as explained by Hasselbalch H. (5)

To obtain standardized thymic size values the measurement is performed during expiration when the thymus has the widest transverse diameter. By transsternal approach the maximum transverse diameter, right lobe anterioposterior dimension and left lobe anterioposterior dimension is measured. The longitudinal diameter of the largest lobe is measured by parasternsal and suprasternal approach. The thymic index which measures thymic volume or thymic size is calculated by multiplying the transverse diameter, longitudinal diameter of largest lobe and anterioposterior diameter of largest lobe (saggital area). The thymic index is measured in cubic centimeter. The correlation between thymic index and birth weight, birth length, gestational age and sex is assessed by using unpaired t test and pearson correlation coefficient.

RESULTS: Eighty neonates were included in the study. Among eighty neonates, sixty of them were preterm and twenty were terms. Preterm group further divided into three groups. Twenty of these were around gestational age 28 to 30 weeks, twenty of these were around gestational age 31 to 33 weeks, twenty of these around gestational age 34 to 37 week and twenty were term neonates.

38 were males and 42 were females. Mean thymic index of male neonates is compared with mean thymic index of female neonates. Assuming the values are sampled from Guassian distribution. The mean thymic index of these is compared by using unpaired t-test. The t value is 0. 9110 and two tailed p value is 0. 3644. In our study the gender of the neonate has no effect on the thymus volume (Table no. 1).

39 were born by normal delivery and 41 were born by cesarean section. Mean thymic index of neonates born by normal vaginal delivery is compared with mean thymic index of neonates born by caesarian section. Assuming the values are sampled from Guassian distribution. The mean thymic index of these is compared by using unpaired t- test. The t value is 0.09564 and the two tailed p value is 0.9235, which is more than 0.005. In our study the mode of delivery has no impact on the thymus volume (Table no. 2).

The neonates were divided into four groups depending on their gestational age. The mean gestational age, mean birth weight, mean birth length, mean longitudinal diameter, mean transverse diameter and sagital area of the largest lobe were calculated from which their thymic index was derived (Table No. 3).

Mean thymic index of these four groups of various gestational ages are calculated and compared by ANOVA (One-way Analysis of Variance) by using Tukey-Kramer multiple comparison test (Table No. 4).

The mean thymic index of group A (28 TO 30WK) is comparable to mean thymic index of group B (31 to 33wk) whereas mean thymic index of other groups differ significantly (Table No. 4).

Positive correlation between thymic index and gestational age (Figure 1), TI and Birth weight (Figure 2) and also the positive correlation between TI and Birth length was plotted (Figure 3).

In our study thymic index has highest positive correlation to birth weight followed by gestational age (Table No. 5).

DISCUSSION: The thymus which is a central lymphoid organ is located mainly in anterior superior mediastinum in front of the heart and behind the sternum sometimes it extends to inferior mediastinum. The unique feature of thymus is in its variation in size and shape. The thymus, a lymphoepithelial organ, is the main site of T-lymphocytes that orchestrate cell mediated immune function, which generally corresponds to its functional capacity and predicts early childhood survivorship. (6) Since thymus can be easily visiualised on sonography in the infantile period it can be used to access its size.

Many authors conducted imaging studies to study the echogenicity of the thymus. Rajiv et al, (7) conducted sonographic study mainly to study the variation in the echogenicity of the thymus. The thymic appearance was described in terms of its echogenicity and echopattern, which were compared with that of the liver, spleen and the thyroid. Its echogenicity was measured quantitatively by the measurement of the echogenicity number.

Many ultrasonographic studies have attempted to establish standards for thymic size in infancy (Hasselbalch, (5) et al 1999, Kizilcan et al 1995, Varga et al, (8) 2011, Yekeler et al, (9) 2004). These studies tend to rely on healthy well-nourished infants in habitant sanitary, urban environment.

The thymus is susceptible to acute involution upon prenatal & postnatal malnutrition (Chandra 1992, Savino et al 2002), stress harmones (Savino & Dardene 2000), maternal smoking (Zeyrek et al 2008) so in our study the neonates having antenatal intranatal and postnatal risk factors are excluded from the study.

Ivana Musilova et al conducted sonographic study to determine the transverse diameter of the fetal thymus and in his study he presented nomogram for the transverse diameter of the 198 healthy foetal thymus in uncomplicated singleton pregnancies between 19 and 38 weeks of gestation. similarly in our study instead of transverse diameter, thymic index which measures accurate dimensions of the thymus is calculated in neonates of various gestational ages from 28 to 40 weeks.

We calculated the mean value of thymic index for the particular gestational ages.

In the study conducted by Rajiv Azad (7) et al in 200 healthy term neonates found the overall thymic index dimensions and the thymic index in particular in the Indian neonates, are lower probably because of the lower birth weight, which correlated significantly with the thymic index. (r=0.29, p<0.001). In our study when compared to other studies conducted in north india and western countries the mean thymic index in all gestational age groups is less probably because of low nutritional status of parents when compared to north Indian and western country population.

In comparison of the mean thymus size between term and preterm neonates, we found that the term (5.642 [+ or -] 1.178 [cm.sup.3]) group had significantly greater values than the preterm (2.596 [+ or -] 0.984 [cm.sup.3]) group. Previous studies had similar results and considered that they were related closely to parameters such as health status, intrauterine growth, and birth weight. (9)

S. Magu et al, (10) and I. Varga, (8) et al found no difference in thymic dimensions when they compared the difference in the thymic size between the newborns born in two different ways (spontaneously and operatively). Some of authors like Rajiv et al included only those neonates neonates that are born by normal vaginal delivery since according to him thymic size is known to be affected by stress. Similarly in our study mode of delivery had no impact on thymic dimensions.

The main goal of our study was to determine the thymic dimensions of neonates of various gestational ages in uncomplicated pregnancies with secondary aim to study the effect of gender and mode of delivery on thymic dimensions. The mean thymic index of group A (28 TO 30WK) was comparable to mean thymic index of group B (31 to 33wk) whereas mean thymic index of other groups differed significantly.

CONCLUSION: The thymus plays a pivot role in cell mediated immunity. It plays an important role in providing a suitable microenvironment for the proliferation, differentiation and selection of T lymphocytes. Functional assessment of thymus requires immunofluoresce, flow cytometry, immunohistological studies which are expensive and not easily available. Thymic size which generally corresponds to its functional capacity can be easily estimated by ultrasonography which can be alternative method for functional assessment of thymus. Measuring the thymic size by estimating the thymic index also help in predicting the gestational age but large number of prospective studies are required to establish the standard values of thymic index for particular gestational age. Over all mean thymic index in our study is less as compared to western studies probably because of low nutritional status of population of this region. The thymus size had highest positive correlation to birth weight.

DOI: 10.14260/jemds/2015/932

REFERENCES:

(1.) Geenen V, Brilot F. Role of the thymus in the development of tolerance and autoimmunity towards the neuroendocrine system. Ann N Y Acad Sci 2003; 1992: 186-95.

(2.) Inderbir Singh. A Text Book of Embryology, 9th Edi p. 29.

(3.) Seidel BM, Schulze B, Schubert S, Borte M. Oral mucosal immunocompetence in preterm infants in the first 9 months of life. Eur J Pediatr. 2000; 159: 789.

(4.) Ivana Musilova, Marian Kacerovsky, Tatana Reslova, Jindrich Tosner. Ultrasound measurement of the transverse diameter of the fetal thymus in uncomplicated single ton pregnancies. Neuroendocrinology Letters. 2010; 31 (6): 101-105.

(5.) Hasselbalch H, Nelson MB, Jeppensen D, Pedersen JF, Karkov J. Sonographic measurement of thymus in infants. Eur Radiol. 1996; 6 (5): 700-3.

(6.) Abbas A, Lichtman A. Basic immunology. Functions and disorders of the immune system. 3rd edition Philadelphia; 2011: p. 66-67.

(7.) Rajiv Azad, Sarita Magu, Gathiwala G Sonographic assessment of the thymus in healthy neonates from North India. Journal of Clinical and Diagnostic Research. 2011; 15 (7).

(8.) Ivan Varga, Alexandra Uhrinova, Frantisek Toth, Jana Mistinova. Assessment of thymic morphology using ultrasound in full term newborns. Surgical and Radiologic Anatomy. 2011; 33 (8): 689-695.

(9.) Yekeler. E, Tambag A, Tambag A, et al. Analysis of the thymus in 151 healthy infants from 0 to 2 years of age. J Ultrasound med. 2004; 23: 1321-6.

(10.) Magu S, Gathwala G, A Parihar A, Sonographic measurement of thymic size in preterm infants, Indian J Paed, 2012; 79 (6); 764-768.

TD--Transverse Diameter; APD--Anteroposterior Diameter; LD--Longitudinal Diameter; SA Sagittal Area; LL--Largest Lobe; TI--Thymic Index.

TI--Thymic Index; BW--Birth Weight; GA--Gestational Age.

[FIGURE 1 OMITTED]

[FIGURE 2 OMITTED]

[FIGURE 3 OMITTED]

Sharanabasav Kirdi [1], Rajkunvar Langade [2], Sunil Rodagi [3], Snehal Surana [4], Amit Galgali [5]

NAME ADDRESS EMAIL ID OF THE CORRESPONDING AUTHOR:

Dr. Sharanabasav Kirdi, Resident, Department of Pediatrics, Krishna Institute of Medical Sciences, Deeemed University, Malkapur, Karad-415110, Maharashtra. E-mail: drsharan88@gmail.com

AUTHORS:

[1.] Sharanabasav Kirdi

[2.] Rajkunvar Langade

[3.] Sunil Rodagi

[4.] Snehal Surana

[5.] Amit Galgali

PARTICULARS OF CONTRIBUTORS:

[1.] Junior Resident, Department of Paediatrics, Krishna Institute of Medical Sciences, Deemed University, Karad.

[2.] Associate professor, Department of Paediatrics, Krishna Institute of Medical Sciences, Deemed University, Karad.

[3.] Junior Resident, Department of Paediatrics, Krishna Institute of Medical Sciences, Deemed University, Karad.

[4.] Junior Resident, Department of Paediatrics, Krishna Institute of Medical Sciences, Deemed University, Karad.

[5.] Junior Resident, Department of Paediatrics, Krishna Institute of Medical Sciences, Deemed University, Karad.

FINANCIAL OR OTHER COMPETING INTERESTS: None

Date of Submission: 11/04/2015.

Date of Peer Review: 13/04/2015.

Date of Acceptance: 29/04/2015.

Date of Publishing: 05/05/2015.
Table 1: Number of males, females and
their respective mean thymic index

Sex       Sample Size   Mean Thymic Index in [cm.sup.3]

Male          38          3.548 [+ or -] 1.312
Female        42          3.212 [+ or -] 1.900

Table 2: Mode of delivery & mean thymic index

Mode of      Sample Size   Mean Thymic Index in cm3
delivery

Normal           39         3. 375 [+ or -] 1.536

Caesarean        41         3. 410 [+ or -] 1. 725
section

Table 3: Mean gestational age, mean birth weight,
mean birth length and their mean thymic index

Gestational Age     Mean Weight in kg      Mean Length in cm

27 to 30 wk        1.149 [+ or -] 0.305   41.15 [+ or -] 2.58
31 to 33 wk        1.481 [+ or -] 0.206   43.90 [+ or -] 1.88
34 to 37 wk        1.823 [+ or -] 0.130   47.35 [+ or -] 1.61
>37 wk             3.048 [+ or -] 0.366    49.6 [+ or -] 0.59

Gestational Age       Mean TD in mm       Mean APD of LL in mm

27 to 30 wk        14.08 [+ or -] 3.80    10.34 [+ or -] 4.23
31 to 33 wk        15.30 [+ or -] 4.68     9.87 [+ or -] 5.20
34 to 37 wk        16.80 [+ or -] 4.67    13.35 [+ or -] 4.20
>37 wk             19.82 [+ or -] 1.70    12.46 [+ or -] 1.22

Gestational Age    Mean LD of LL in mm    Mean SA of LL in cm2

27 to 30 wk        15.13 [+ or -] 5.11     1.36 [+ or -] 0.55
31 to 33 wk        18.24 [+ or -] 2.51     1.72 [+ or -] 1.07
34 to 37 wk        17.18 [+ or -] 3.10     2.27 [+ or -] 0.98
>37 wk              22.72 [+ or -] 260     2.81 [+ or -] 0.49

Gestational Age       Mean TI in cm3

27 to 30 wk        2.0016 [+ or -] 0.50
31 to 33 wk        2.445 [+ or -] 0.46
34 to 37 wk        3.352 [+ or -] 1.05
>37 wk             5.642 [+ or -] 1.17

Table 4: Comparison of thymic index in various
gestational age after application of anova test

Comparison            Mean Difference of   P Value
                         Thymic Index

Group A vs Group B         -0.4439         P>0.05
Group A vs Group C          -1.393         P<0.001
Group A vs Group D          -3.641         P<0.001
Group B vs Group C         -0.9494         P<0.01
Group B vs Group D          -3.197         P<0.001
Group C vs Group D          -2.247         P<0.001

Table 5: Positive correlation between thymic index,
birth weight, birth length and gestation age

Correlation    r value   P value
between

TI & BW        0.8438    P<0.0001
TI & BL        0.7390    P<0.0001
TI & GA        0.8257    P<0.0001
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Title Annotation:ORIGINAL ARTICLE
Author:Kirdi, Sharanabasav; Langade, Rajkunvar; Rodagi, Sunil; Surana, Snehal; Galgali, Amit
Publication:Journal of Evolution of Medical and Dental Sciences
Article Type:Clinical report
Geographic Code:9INDI
Date:May 7, 2015
Words:2684
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