Screening for congenital hypothyroidism by using cord blood thyroid stimulating hormone (CBTSH) levels in neonates

ABSTRACT

Background:

Congenital hypothyroidism (CH) is the most common preventable cause of mental retardation in children. Hypothyroidism in the neonatal period is always overlooked, and delayed discovery results in the most devastating outcomes, such as mental retardation, stressing the importance of newborn screening, which is one of the major achievements in preventive medicine. According to previous studies, Thyroid-Stimulating Hormone (TSH) screening is more specific for identifying CH. TSH levels in umbilical cord blood remain an easy and useful means to screen for congenital hypothyroidism, and it is widely documented that maternal and neonatal factors influence Cord Blood Thyroid Stimulating Hormone (CBTSH) levels. The current study was conducted to screen for and determine the effects of various perinatal and maternal variables on CBTSH levels.

Objectives:

To evaluate the incidence of congenital hypothyroidism using CBTSH) levels and to examine the influence of maternal and perinatal factors on these levels.

Material and Methods:

This cross-sectional study included 106 neonates. Samples were collected from the neonatal ward of a tertiary care hospital in urban south Karnataka, India. An umbilical cord blood sample was collected, and the CBTSH assay was performed using the electrochemiluminescence method. The data obtained were statistically analyzed.

Result:

In the present study, the mean cord blood TSH level was 6.20 ± 5.90 μIU/ml. There was a statistically significant association between the mean CBTSH level and maternal complications (Age, mode of delivery, gravida, and prenatal hypothyroidism status). A higher CBTSH level was found in preterm babies with an APGAR score of <7, vaginal deliveries, primigravida, male sex, and low-birth-weight babies.

Conclusion:

This study found a significant association between CBTSH levels and maternal health problems. Preterm newborns with an appearance, pulse, grimace, activity, and respiration score of <7, normal vaginal delivery, primigravida, male sex, and low birth weight had higher CBTSH levels.

Introduction

Congenital hypothyroidism (CH) is the most common preventable cause of mental retardation in children. CH is described as inadequate thyroid hormone production in infants.[1] The thyroid hormones play a crucial role in the development of the central nervous system.[2] Inadequate thyroid hormone synthesis during this period can lead to neurological complications.[3] CH is a serious condition that causes improper brain development.[4] The overall prevalence of CH was 1 in 722 births.[5] Clinical symptoms of congenital hypothyroidism do not appear at birth. Early diagnosis and treatment are essential for preventing mental impairment. Thus, early detection and treatment of congenital hypothyroidism can prevent intellectual disability and optimize growth and developmental outcomes.[6] Multiple screening programs have been initiated to address the critical need for early detection and treatment.[7] In India, major obstacles to universal newborn screening include awareness, cost, advocacy, public policy, and politics.[8] Congenital hypothyroidism screening remains the most significant and successful strategy for reducing the prevalence of mental retardation in the population.[1] Early detection is important, either by thyroid stimulating hormone (TSH) or T4 estimation, or both by newborn screening. Cord blood TSH (CBTSH) estimation has high sensitivity, but various maternal and perinatal factors affect the CBTSH levels.[9] Cord blood (CB) remains a very practical alternative for screening purposes as it is very difficult to call back babies once discharged. It is painless and usually not affected by neonatal surge. Current research suggests cord blood collection as a substitute method to identify the prevalence of congenital hypothyroidism and determine the number of maternal and neonatal variables that may influence TSH levels in cord blood.[9] The current study aimed to evaluate the incidence of congenital hypothyroidism using cord blood thyroid-stimulating hormone (CBTSH) levels and examine the influence of maternal and perinatal factors on these levels. Perinatal factors such as gestational age, birth weight, method of delivery, sex, and APGAR score, as well as maternal factors such as age, mode of delivery, gravida, and prenatal hypothyroidism status. Very few studies have been conducted on the Indian population.

Objectives

• To assess CBTSH as a measure for screening for congenital hypothyroidism.

• To investigate the impact of perinatal and maternal factors on CBTSH level variations in neonates.

Materials and Methods

This cross-sectional study was conducted from January 2023 to December 2023 on 106 neonates in the maternity unit of the tertiary care hospital, Belagavi. Infants were selected using a simple random selection method. Immediately after birth, 5 ml of cord blood was collected from the placental end of the cord in a dry test tube. Serum was extracted from the blood samples and used to estimate TSH levels. Electrochemiluminescence immunoassay (“ECLIA”) was used to conduct the tests. Ethical committe Institution Ref no. MDC/JNMCIEC/33 Dated 17/03/2023.

Data entry was performed in an Excel spreadsheet, and analysis was performed using SPSS 24.

Inclusion criteria

• All newborns above 32 weeks are included in the study.

Exclusion criteria

• Neonates with major congenital malformations.

• Neonates needing NICU admission (critical illness, medications, and interventions affect the thyroid hormone levels).

• Parents who refused consent.

Results

This cross-sectional study included 106 neonates and aimed to estimate cord blood TSH levels as a screening tool for congenital hypothyroidism. The data obtained were tabulated and subjected to statistical analyses. The results obtained are systematically described here along with the tables [Tables 1-3].

Table 1.

Number of subjects according to the CBTSH levels

CBTSH level (μIU/ml)	n	%
1.0-10	96	90.6
>10.0–20.0	10	9.4
Total	106	100

Table 3.

Effect of maternal factors on cord blood thyroid stimulating hormone (CBTSH) levels

Parameter	n	%	CBTSH (µIU/ml)	SD	P
Mother age
18–25	62	58.5	5.97	5.71	0.882
26–35	41	38.7	6.48	6.34
Above 35	3	2.8	7.12	4.18
Mode of delivery
LSCS	66	62.3	5.6	5.21	0.178
Vaginal delivery (VD)	40	37.7	7.19	6.82
Maternal complication
No	80	75.5	5.38	4.43	0.011*
Yes	26	24.5	8.74	8.66

Table 2.

Profile of subjects according to neonatal factors along with mean CBTSH levels

Parameter	n	%	CBTSH (µIU/ml)	SD	P
Gestational age
Preterm	38	36.2	6.33	6.39	0.884
Term	67	63.8	6.16	5.68
APGAR score
<5	1	0.9	5.37	.	0.307
5–7	44	41.5	5.17	2.53
>7	61	57.5	6.96	7.4
Birth order
Primi	54	50.9	7.14	6.99	0.095
Multi	52	49.1	5.23	4.33
Baby gender
Male	52	49.1	7.34	7.24	0.051
Female	54	50.9	5.11	3.98
Birth weight
LBW	45	42.5	6.41	6.07	0.757
Normal	61	57.5	6.05	5.8

Discussion

Screening for congenital hypothyroidism requires the need of the hour. Universal screening is currently an accepted technique for infants worldwide. However, in India, an attempt was made to screen neonates for congenital hypothyroidism at various centers in 2007 by ICMR, but a national program does not exist at present.[10] The method of screening method was also not uniform. Various cut-off values have been used in different studies.[11] but it has been accepted to use a cut-off of >20 μIU/ml for recall.[12] and none had TSH >20 μIU/ml hence, our recall rate was 0%.

CBTSH levels are affected by various maternal and neonatal factors.[9] Cord blood is easy to collect and noninvasive. Initial screening with CBTSH is a rapid and noninvasive screening method.[13]

A total of 106 neonates were enrolled in the study, and the mean CBTSH level was 6.20 μIU/ml, which was similar to other studies, with mean TSH levels ranging from 6.13 μIU/ml to 10 μIU/ml.[14] In a few studies, the mean CBTSH level was >10 μIU/ml.[15]

Our study found that preterm neonates had higher CBTSH levels than term babies, which is consistent with the results of other studies. However, there was no significant difference in the relationship between the two groups. These findings are in agreement with those of previous studies.[9] Some studies have concluded that term babies have higher CBTSH levels than preterm and post-term newborns.[13]

In our study, neonates with an APGAR score >7 had higher CBTSH levels, but the difference was not statistically significant. Other studies have found that neonates with a low APGAR score had statistically significant CBTSH levels.[15]

In the present study, we discovered that primigravida had a greater CBTSH level, which is consistent with other studies. However, the difference was not statistically significant, and further studies support our findings.[16]

We found that male newborns had a higher CBTSH level than female newborns. Several studies have also reported similar results.[17] Sunil Raj et al.[18] observed no link between baby sex and CBTSH levels. In this study, we observed that CBTSH levels did not differ significantly between sexes, although these findings were consistent with those of previous research.[19]

In the present study, we found that infants with low birth weight (LBW) had higher CBTSH levels. This finding is in agreement with those of other studies.[20] However, we did not observe any statistically significant difference in LBW based on CBTSH levels, which is consistent with other studies.[21] Pawar et al.[22] found a statistically significant difference between birth weight and CBTSH level. On the other hand, some studies reported that there was no relationship between CBTSH level and birth weight.[16]

This study found that neonates born to women over the age of 30 years had greater CBTSH levels, which is consistent with previous research that has demonstrated a rising trend in CBTSH with increasing maternal age.[18] However, some studies have found no correlation between maternal age and TSH level[19] although others, such as Lain et al.[20] found a favorable association between maternal age and TSH level.

In this study, we found that neonates with normal vaginal birth had higher CBTSH levels, which is consistent with previous findings. This difference can be explained on the basis of a surge in catecholamine secretion during the process of parturition, and this can be more in asphyxiated newborns and vaginally delivered newborns than in those born by elective caesarean section.[23,24] Other studies found that CBTSH levels were slightly higher in lower segment caesarean section (LSCS) deliveries than in regular vaginal births.[13] However, the difference was not statistically significant, and the findings were consistent with those of other investigations.[13] Another study conducted by Lakshminarayana, et al. found that the mean CBTSH was higher in neonates delivered by norma lvaginal mode than LSCS the difference was that it was statistically significant.[16]

This study found that the CBTSH levels were higher in newborns with maternal difficulties. This finding indicates a statistically significant difference in CBTSH levels. There were no significant variations in CBTSH levels based on maternal illnesses, such as gestational diabetes, hypertension, hyperthyroidism, or hypothyroidism, and TSH levels were unaffected.[25,26]

Conclusion

Cord blood collection for TSH estimation is a simple, noninvasive, and successful screening method. The current study found a statistically significant association between CBTSH levels and maternal complications. The study indicated that preterm babies with an APGAR score < 7, vaginal deliveries, primigravidas, male babies, and low-birth-weight babies have greater levels of CBTSH.

Limitation

The sample size was less

• Large population-based investigations are needed.

• Nationwide protocol for screening and treatment of CH is needed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.