Volume 17 Issue 3

Table of Content - Volume 17 Issue 3 - March 2021

Estimation of thyroid stimulating hormone level in cord blood of newborns and its determinants

Sam Varghese¹, K P Shiyas^2*

¹Associate Professor, Department of Paediatrics, SNIMS, Chalakka, Kunnukara, Ernakulam, Kerala, INDIA.

²Associate Professor, Department of Paediatrics, Al Azhar Medical College, Thodupuzha, Kerala, INDIA.

Email: drshiyas@hotmail.com

Abstract Background: Congenital hypothyroidism (CH) is one of the preventable causes of mental retardation. The ease of identification and treatment of congenital hypothyroidism through neonatal screening has significantly brought down the incidence of mental retardation. This study was conducted to detect, diagnose and treat congenital hypothyroidism among the newborns and to find the maternal and neonatal determinants of the same. Methods: 500 live newborns delivered in the Obstetrics and Gynaecology Department of Dr. D.Y Patil Medical College who had fulfilled the inclusion criteria were screened for the cord blood TSH level after obtaining informed consent from the patient’s guardian/relative. Automated chemiluminescence test using the Immulite 2000 kit was done to obtain the TSH values. Results: Among the study subjects, 481 (96.2%) had their TSH values in the normal range between 0.5 mIU/ml and 20 mIU/ml. There was significant difference between the TSH values in newborns with birthweight < 2.5kgs (6.36 ± 3.57 mIU/ml) and ≥ 2.5 kgs (2.86 ± 2.88 mIU/ml) (P value <0.0001). The difference in TSH value was also significant among newborns born to mothers with gestational age < 36 weeks and ≥ 36 weeks. Conclusion: The gestational age of the mother at delivery and the birthweight of the newborns have statistically significant influence on the TSH values of the newborns and thereby congenital hypothyroidism. Cord blood TSH estimation, though a good screening tool, cannot be used alone as a diagnostic marker. Clinical correlation and repeat confirmatory tests are essential for identifying CH.

Keywords: Congenital Hypothyroidism, Cord Blood, Neonate, Thyroid Stimulating Hormone.

INTRODUCTION

Neurodevelopment compromise or mental retardation is more common terms, is one of the most severe and disabling illness an individual can suffer. It leaves the afflicted person unable to function at an optimum potential, as compared to the peers. One cannot live a normal life and is often treated unkindly by the uninformed general public. Although he or she may be oblivious to the severe nature of the illness, the affected person does not have relief from physical and mental suffering. So, the individual is doomed to a slow and painful existence in this world. Neither does one meet an early death. This causes a major physical, mental and financial burden on the family, the community and the nation as a whole. The causes for mental retardation are varied, some are preventable as in congenital hypothyroidism (CH) or phenylketonuria and others inevitable as in a child with an inborn error of metabolism with no known or effective means of detection or treatment. However, all attempts should be made whenever feasible to prevent mental retardation. Of the preventable causes of mental retardation, CH is the commonest¹. It is also the easiest to treat, and most effective to detect early. Because of the lack of specific signs and symptoms in the first weeks of life, the most important tool for the early diagnosis of CH is a newborn screening programme². Several studies confirm that children with CH identified by newborn screening and treated early in life have normal physical and intellectual development³. This emphasizes the paramount need to run a neonatal screening programme to detect and initiate treatment of CH at the earliest. Almost all developed nations and several developing nations have ongoing screening programmes which were started in the late 1970s ^{4 – 15}. Hence, this study for CH was launched to detect, diagnose and treat CH among the babies born in D.Y. Patil Medical College, Pimpri with a vision to provide an ongoing service and extend these services to nearby smaller hospitals. A national agenda for identifying and treating infants with CH would be the desired ultimate goal.

METHODOLOGY

500 live newborns delivered in the Obstetrics and Gynaecology Department of Dr. D.Y Patil Medical College who had fulfilled the inclusion criteria were screened for the cord blood TSH level after obtaining informed consent from the patient’s guardian/relative. Newborns delivered outside the medical college during the study period but admitted in the Dr. D.Y Patil Medical College for various reasons were excluded from the study. Similarly, newborns with major congenital anomalies, who were < 800 grams or less than 27 weeks gestation and whose residence is more than 25 kilometres from the hospital were excluded from the study. The infants born during the study period were screened for TSH levels in their cord blood. Within 5 minutes after delivery of the baby, cord blood from the placental end of the severed cord, was collected and sent to the laboratory for estimation of serum TSH level. The details about each of these infants, their mothers, the type of delivery and the addresses of the parents and phone numbers were collected as per the proforma. In families who did not have a phone, a neighbour’s phone number, if available was noted. Parents were given information about CH before the collection of the cord blood sample and subsequently, if a second blood sample were to be collected in the event of an abnormal level being obtained on the first cord blood sample. The result of the cord blood TSH estimation was available usually by 48 to 72 hours. All infants with a cord blood TSH value of <0.5 mIU/ml and ≥20 mIU/ml were marked and those families were notified immediately. A letter containing information about the result was given to them and explanation was also provided. A second blood sample was collected for repeating serum TSH and to estimate serum Total T4 and Free T4 concentration at 3 weeks of age. From the placental end of the severed umbilical cord, 3 ml of blood was collected into labelled centrifuge tubes and refrigerated at 2 – 8^o C, in wire racks. Samples were sent within an hour of collection to the laboratory, where the blood was centrifuged within 3 hours and serum TSH estimation was done. Cord blood TSH was estimated by the automated chemiluminescence system, using the beta subunit of the thyroid stimulating hormone. In the event that the TSH was ≥ 20 mIU/ml or <0.5 mIU/ml, a repeat TSH along with Total T4 and Free T4 was done at 3 weeks of age by an automated chemiluminescence test using the Immulite 2000 kit. The data was collected using Microsoft excel and analysed using SPSS version 16. All study variables were analysed using descriptive statistical methods like frequencies and percentages for categorical variables and mean with standard deviation for continuous variables. Z test was done to find the significant associations.

RESULTS

Out of 500 newborns enrolled 260 (52%) had their mothers within the age group of 21 – 25 years and 118 (23.6%) belonged to the age group of <20 years (Table 1). In the study group, 328 (65.6%) newborns had gestational age between 36 weeks to 40 weeks. 113 (22.6%) were above 40 weeks of gestation and 59 (11.8%) were below 36 weeks. The mean TSH value of newborns with gestational age <36 weeks was 7.73± 3.32 mIU/ml and in those with gestational age > 36 weeks was 3.19 ± 3.06 mIU/ml. (Z value 9.93 and P value <0.0001).

Table 1: Distribution of cases according to maternal age

Age (in years)	No of cases	Percentage
<=20	118	23.6
21 – 25	260	52.0
26 – 30	108	21.6
31 – 35	13	2.6
36 – 40	1	0.2
Total	500	100

In the study, number of primipara were 168 (33.6%) and multipara were 332 (66.4%). The mean TSH values of newborns of primipara mothers were 3.63 ± 3.22 mIU/ml whereas in newborns born to multipara mothers, the mean TSH values were 3.78 ± 3.52 mIU/ml which was statistically insignificant (p value >0.05). The number of FTND deliveries in the study were 331 (66.2%) and that of LSCS deliveries were 169 (33.8%). Although statistically insignificant, the mean TSH values of FTND deliveries was 3.84 ± 3.71 mIU/ml as against the mean TSH values of LSCS deliveries being 3.49 ± 2.77 mIU/ml (Table 2).

Table 2: Comparison of TSH with various maternal and neonatal determinants

Factors		TSH level (mIU/ml)	Z value	P value
Gestational age	Less than 36 weeks	7.73 ± 3.32	9.93	<0.0001
	≥ 36 weeks	3.19 ± 3.06
Gravida	Primi	3.63 ± 3.22	0.48	>0.05
	Multi	3.78 ± 3.52
Mode of delivery	FTND	3.84 ± 3.71	1.18	>0.05
	LSCS	3.49 ± 2.77
Gender of the baby	Male	3.48 ± 3.39	1.82	>0.05
	Female	4.04 ± 3.43
Birth weight	< 2.5Kg	6.36 ± 3.57	9.91	<0.0001
	≥2.5Kg	2.86 ± 2.88

The number of male newborns enrolled was 284 (56.8%) against 216 (43.2%) female newborns. The mean TSH values in male and female newborns were 3.48 ± 3.39 mIU/ml and 4.04 ± 3.43 mIU/ml, respectively which was not statistically significant. The number of newborns weighing <2.5 kgs were 124 (24.8%) and those with birth weight ≥ 2.5kgs were 376 (75.2%). The mean TSH values in newborns with birthweight < 2.5kgs were 6.36 ± 3.57 mIU/ml as against 2.86 ± 2.88 mIU/ml in newborns with birthweight ≥ 2.5 kgs, which was statistically significant (Z value 9.91 and P value <0.0001).

Table 3: Cord blood TSH levels of newborns in study group

TSH level (mIU/ml)	No of cases	Percentage
0.5 – 20 (Normal)	481	96.2
<0.5 (Low)	17	3.4
>20 (High)	2	0.4
Total	500	100

In the study group, among 500 newborns, 481 (96.2%) had their TSH values between 0.5 mIU/ml and 20 mIU/ml which were normal. 17 (3.4%) of them had their values <0.5 mIU/ml and 2 (0.4%) had values > 20 mIU/ml (Table 3). Among the 17 newborns who had TSH values <0.5mIU/ml, the gestational age ranged between 33.6 weeks to 41 weeks with birth weight between 2.5 kgs to 3.75 kgs. Two out of 500 newborns in the study who had TSH values > 20 mIU/ml were full term male babies delivered vaginally to multipara mothers. The repeat TSH, total T4 and Free T4 values at 3 weeks were within normal limits in those newborns who had cord blood TSH > 20 mIU/ml.

DISCUSSION

For paediatrics, responsibility begins with the birth of a newborn. The WHO/UNICEF and MCI have published guidelines to paediatricians stating that it is the responsibility of every paediatrician to know the status of each patient in their care. Several important developments have been made in the field of screening of cord blood for TSH levels as a result of various research done globally including India in the last 40 years. In the study, 500 normal newborns born in Dr. D. Y. Patil hospital Pimpri were included and their cord blood TSH levels were estimated. 260 (52.0%) mothers were between the ages of 21-25 years, while 118 (23.6%) belonged to < 20 years of age. 108 (21.6%) were in the age group of 26 – 30 years. There was only 1 (0.2%) mother within 36 – 40 years. The remaining 13 (2.6%) were between 31 – 35 years. There was no history of consanguineous marriage among these women. None of the mothers were on any drugs and clinically the thyroid status was normal. The newborns were enrolled irrespective of the socio-economic status or religion. The gestational age wise distribution of the subjects in the study group showed that 328 (65.6%) newborns had gestational age between 36 – 40 weeks and 113 (22.6%) were between 40 – 44 weeks. Only 59 (11.8%) of newborns had gestational age between 32 – 36 weeks. The mean TSH values in newborns with gestational age <36 weeks were 7.72 ± 3.32 mIU/ml which was much more than what was observed in newborns with gestational age ≥ 36 weeks which was 3.19 ± 3.06 mIU/ml with Z value of 9.93 and P value <0.0001 that makes it highly significant statistically. Similar observations were reported by Oddie et al. in his study in California, where there was a progressive decrease in mean concentration of serum TSH from 30 – 45 weeks of gestation¹⁶. This is attributed to progressive increase in feedback sensitivity to suppression of TSH release by thyroid hormone. The comparison of mean TSH values of newborns depending on the mode of delivery showed that those delivered by FTND had values at 3.84 ± 3.71 mIU/ml and those delivered by LSCS had values at 3.49 ± 2.77 mIU/ml. There was no statistical significance. There are two contradictory studies. Lao and Panesar from Hong Kong reported lower TSH levels in babies born by caesarean section, supporting the hypothesis that parturition stress is a major cause of TSH surge in newborns¹⁷. On contrary, Clemens and Neumann from Hamburg in their study found elevated TSH levels in those babies born by caesarean section¹⁸. The distribution of newborns by their sex showed that, there were 284 males and 216 females (M:F ratio: 57: 43) in the study. The mean TSH value stood at 3.48 ± 3.39 mIU/ml for males and 4.04 ± 3.43 mIU/ml for females which did not show any significant difference between the groups. The study group was divided into two, depending on the birth weight of the newborns with the cut off being 2.5 Kgs. There were 124 (24.8%) newborns who weighed < 2.5Kgs and 376 (75.2%) weighed ≥ 2.5 Kgs. Comparing the mean TSH values in the group showed that, the newborns with birthweight < 2.5 Kgs had higher values at 6.36 ± 3.57 mIU/ml than those with birthweight ≥ 2.5 Kgs at 2.86 ± 2.88 mIU/ml (p value <0.0001), making the difference highly significant. Frank et al., in their study had shown higher levels of TSH in cord blood in LBW babies¹⁹. In the study, of the 500 neonates 96.2% had cord blood TSH values in nomal range (>0.5 mIU/ml to < 20 mIU/ml). 3.4% had low (<0.5mIU/ml) and 0.4% had high (>20mIU/ml) TSH values. The cord blood TSH values in 17 newborns out of the 500 was < 0.5 mIU/ml. The perinatal factor observed in these newborns were that the birthweight ranged between 2.5 kgs to 3.75 kgs. All were full term normal deliveries, except for 3 who delivered by LSCS. Among the 17 newborns with low TSH, 10 were males and 7 were females. The maternal age ranged between 19 – 31 years and the gestational age was between 33.6 weeks to 41 weeks. The 17 newborns were reviewed back at the age of 3 weeks to do a repeat TSH, total T4 and Free T4 levels. The repeat values in these 17 newborns were normal at 3 weeks ruling out the possibility of hyperthyroidism or central hypothyroidism where in the TSH may be normal or low. But the confirmatory test results proved that it was not the case. Two out of 500 newborns in the study had TSH values in their cord blood > 20 mIU/ml. The perinatal factor identified in those study subjects were that maternal age ranged between 23 – 25 years with gestational age between 36.1 to 37.3 weeks. These newborns were recalled at the age of 3 weeks to do a repeat assay of TSH, Total T4 and Free T4 to exclude the possibility of congenital hypothyroidism. The repeat values in these newborns were within normal limits at the follow-up. These babies were examined for any features suggestive of congenital hypothyroidism which was also found to be negative.

CONCLUSION

The gestational age has a significant influence on the cord blood TSH values in newborns with a progressively decreasing trend in the TSH levels from 32 weeks up to 42 weeks of gestational age. The birth weight has a statistically significant influence on the cord blood TSH values with LBW (< 2.5 kgs) babies having higher TSH values than those weighing ≥ 2.5 kgs. The age of the mother, parity and the mode of delivery did not have any significant influence on cord blood TSH values. The sex of the newborn also does not affect the cord blood TSH values. Cord blood TSH estimation, though a good screening tool, cannot be used alone as a diagnostic marker. Clinical correlation and repeat confirmatory tests (TSH, Total T4, Free T4) are essential for identifying CH.

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