Congenital hypothyroidism (CH) is the most common preventable cause of intellectual disability and developmental delay in infants globally. It is primarily caused by an underdeveloped or absent thyroid gland or defects in thyroid hormone synthesis, which, if left undiagnosed and untreated, can result in lifelong neurological impairments. Early clinical signs of hypothyroidism in newborns are often subtle or even absent, making timely screening essential for diagnosis.[1]

Neonatal screening for CH is widely accepted as an effective public health measure, enabling early detection and treatment to prevent adverse outcomes. The American Academy of Pediatrics issued clinical guidelines for CH in 2006, while the European Society for Paediatric Endocrinology revised guidelines in 2010 and introduced updated recommendations in 2014. Several screening methods are available, with primary measurement of thyroid-stimulating hormone (TSH), accompanied by backup free thyroxine (FT4) testing, regarded as the most reliable. Optimal screening utilizes sensitive TSH assays with age-adjusted cutoffs, and an ideal protocol may combine both T4 and TSH measurements for improved accuracy.[2]

Since the 1970s, radioimmunoassay techniques have enabled the measurement of blood thyroxine (T4) at nanomolar concentrations, facilitating newborn screening via dried blood spots. Early methods focused on total T4 and TSH measurements, but screening with only T4 lacks specificity due to factors such as prematurity, illness, and thyroxine-binding globulin deficiency causing false positives. Advances in TSH assay sensitivity have led most countries to adopt primary TSH-based screening, which effectively detects primary CH but not central hypothyroidism.[3]

CH is more closely associated with small for gestational age (SGA) infants than with prematurity. This association may be due to thyroid hormone deficiency disrupting growth pathways, impairing protein synthesis, and reducing insulin-like growth factor-1 (IGF-1) activity. Additionally, inadequate thyroid hormone levels can compromise placental function, restricting fetal oxygen and nutrient supply and contributing to SGA. In contrast, prematurity is often related to immature hypothalamic-pituitary-thyroid axis function leading to transient hypothyroxinemia rather than true CH.[4]

In India, the incidence of CH is higher—approximately 1 in 1000 live births—attributed to ethnic factors, increased survival of very low birth weight neonates, and endemic iodine deficiency zones. Despite this, a nationwide neonatal screening program has yet to be fully implemented. The Indian Society for Pediatric and Adolescent Endocrinology (ISPAE) last issued practice guidelines in 2018 to address CH screening and management.[5]

Aims and Objectives

This multicentric study aims

1. To determine the prevalence of congenital hypothyroidism among neonates born in secondary-level healthcare facilities under the Navi Mumbai Municipal Corporation.
2. To study the characteristics of these newborns.

Place & Duration of study:

The study was conducted over one year i.e. Jan 2023 to Dec 2023 across four centers:

Navi Mumbai Municipal Corporation’s 

1. General Hospital, Vashi
2. General Hospital, Nerul
3. Mother and child hospial, Belapur
4. General Hospital Airoli

Navi Mumbai Municipal Corporation serves a large population and operates multiple secondary healthcare hospitals throughout the district.

Source of Data: The data for this study was collected retrospectively from neonates born at above four secondary-level healthcare centers under the Navi Mumbai Municipal Corporation Maharashtra, India.

Study Design

This was a retrospective observational study analyzing data of neonates screened for congenital hypothyroidism (CH) during the study period.

Sample Size

A total of 4989 neonates were included in the study, representing the newborn population delivered at the four centers during the study period.

Inclusion Criteria

All neonates born at the participating centers within the specified study period were eligible for inclusion.

Exclusion Criteria

Neonates were excluded from the study if any of the following applied:

1. Mothers were on medications known to affect thyroid function, including antithyroid drugs, anticancer agents, or antipsychotics.
2. Unwilling mothers.
3. Neonates who were very sick at birth or died before 48 hours of life.

Procedure and Methodology

Eligible newborns were enrolled following the institutional protocol. Each neonate was assigned a unique identification number for study tracking. Blood samples were collected between 48 to 72 hours after birth using a sterile neonatal lancet via heel prick. A single drop of blood was applied onto a designated circle (approximately 1/2 inch diameter) on specialized filter paper cards designed for dried blood spot (DBS) collection. The blood spots were air-dried at room temperature and transported under strict bio-safety protocols to a reference laboratory, where they were stored at -80°C until analysis. TSH levels were measured using a standardized immunoassay validated for neonatal screening. The results were available within 7 days of sample collection.

Follow-up and Interpretation: Newborns with TSH levels below 10 mIU/mL on day 3 were considered normal and no further testing was conducted. Those with TSH levels ≥20 mIU/mL were diagnosed as having CH and treatment was initiated immediately with thyroxine supplementation at a dose of 10-15 mcg/kg/day. These infants were also referred to a pediatric endocrinology clinic for further evaluation and management.

Newborns with borderline TSH values between 10-19 mIU/mL were called between days 10-14 for retesting that included TSH and free thyroxine (FT4) assays, via venous blood sampling. Families of these newborns received counseling about CH and the importance of follow-up. If repeat tests remained abnormal, these infants were also classified as CH cases and referred for urgent endocrine consultation.

Sample Processing

TSH and FT4 assays were performed using automated chemiluminescent immunoassay analyzers, ensuring high sensitivity and specificity for neonatal screening. Quality control measures were strictly adhered to throughout the laboratory process.

Statistical Methods

Data analysis was performed using chi-square tests to assess associations between categorical variables. Descriptive statistics, including means, medians, and standard deviations (SD), were calculated for continuous variables. A p-value of <0.05 was considered statistically significant.

Data Collection

Data were extracted from hospital records, laboratory reports, and follow-up documentation, then entered into a secure database for analysis. Confidentiality and data integrity were maintained throughout the study.

Table 1: Center wise distribution of enrolled children as per birth weight

The distribution of enrolled neonates according to birth weight across the four study centers is summarized in Table 1. Out of the total 4989 newborns, the largest group consisted of babies weighing between 2.5 and 3 kg, totaling 2082 infants, followed by those in the 2 to 2.5 kg category with 1342 babies. The smallest birth weight group, comprising infants under 1 kg, accounted for only 18 neonates. Among the centers, Vashi had the highest number of enrolled subjects at 2311, followed by Nerul with 1487, Airoli with 1002, and Belapur with 189. Vashi center consistently reported higher numbers across most birth weight categories, especially in the 1 to 1.5 kg and 2.5 to 3 kg ranges. The data reflect a comprehensive sample representative of varying birth weights within the Navi Mumbai region.

Table 2: Co-relation of demographic characteristics of study population with TSH

Table 2 presents the correlation of demographic variables with TSH levels among the 4989 neonates. The majority of the study population (2985 males and 1989 females) exhibited TSH levels ≤10 mIU/mL, considered within normal limits. Only 15 subjects had TSH levels exceeding 10 mIU/mL, with 9 falling between 10 and 19 mIU/mL and 6 exceeding 20 mIU/mL, indicating a suspected or confirmed hypothyroid state. No significant gender differences were observed in TSH distribution. Regarding gestational age, 4571 full-term and 418 preterm neonates were studied, with most maintaining normal TSH values. Birth weight analysis showed that of 1760 neonates with low birth weight, 8 were showing elevated TSH levels amounting to prevalence of 0.45%, while of 3229 normal birth weight 7 were elevated TSH amounting to the prevalence of 0.21 % (P value o<0.05) i.e. 7 were appropriate for gestational age (AGA) and 8 were small for gestational age (SGA). Thirteen of these infants were born via normal delivery and 2 through cesarean section. This highlights a stronger association of elevated TSH with SGA status rather than prematurity or delivery method.

The mean TSH value of the total study population was 8.23 with SD 9.32 (Min - 2.3 Max - 26.4 and Median 9.31) The mean TSH value of the male study population was 8.18 with SD 5.2 (Min - 2.45 Max -23.2 and Median - 9.1) &The mean TSH value of the female study population was 8.36 with SD - 6.03(Min - 2.3 Max - 26.4 and Median - 7.5). The mean TSH value of the preterm baby study population was 7.4 with SD - 5.7 (Min - 2.5 Max - 25.3 and Median-7.2). The mean TSH value of the low birth weight baby study population was 9.8 with SD - 4.75 (Min - 6.3 Max - 25.2 and Median- 9.5)

Table 3: Characteristics of study population with TSH > 20 mIU/ml N = 6

Focusing on neonates with TSH values above 20 mIU/mL, 6 newborns were identified: 4 males and 2 females. Among them, 4 were full-term and 2 preterm, while 4 were appropriate for gestational age (AGA) and 2 were small for gestational age (SGA).

Table 4: Correlation of Serial TSH values along with FT4 value and Congenital Hypothyroid status.

Table 4 depicts details of TSH values on day 3 and follow-up investigations on day 10. Of the 15 suspected cases. 9 neonates had TSH between 10 and 19 mIU/mL on day 3; upon repeat testing, 6 of these showed normalized TSH (<10 mIU/mL) and normal FT4 levels (>1.33), indicating transient hypothyroidism or false positives. The remaining 3 maintained borderline TSH values but normal FT4, falling into undetermined category warranting follow-up. 6 neonates had TSH levels >20 mIU/mL on day 3, and on day 10, their TSH ranged between 10 and 19 mIU/mL and FT4 values below 1.33 mIU/ml confirming persistent congenital hypothyroidism. Overall, 6 neonates were diagnosed with congenital hypothyroidism and initiated on treatment and 3 are having undetermined status. This careful follow-up approach allowed differentiation between transient thyroid dysfunction and true CH, ensuring timely management.

The present multicentric study involving 4989 neonates across four healthcare centers in Navi Mumbai revealed a wide distribution of birth weights, with the majority of newborns weighing between 2.5 and 3 kg (2082 neonates), followed by the 2 to 2.5 kg category (1342 neonates). This birth weight distribution aligns with national Indian data, where a substantial proportion of newborns fall within the low to normal birth weight range, reflecting ongoing challenges related to maternal nutrition and antenatal care. Agrawal P et al.(2015)[6] & Kiess W et al.(2018)[7]. Vashi center, with the highest enrollment (2311 neonates), consistently reported more infants across all weight categories compared to other centers, suggesting possible demographic or referral pattern variations.

Analysis of thyroid-stimulating hormone (TSH) levels in relation to demographic variables demonstrated that the majority of neonates (over 99%) had TSH ≤10 mIU/mL, consistent with normal thyroid function. Only 15 neonates exhibited elevated TSH levels (≥10 mIU/mL), of whom 6

Were diagnosed with congenital hypothyroidism (CH). This prevalence (approximately 1.2 per 1000 live births) is comparable to reported rates in other Indian studies, which range from 1 to 2 per 1000 live births, higher than in many Western populations, likely due to regional iodine deficiency and genetic factors Anjum A et al.(2014)[8] & Chiesa A et al.(2013)[9]. Gender distribution did not significantly affect CH prevalence, echoing findings by Parks JS et al.(2010)[10] who reported no significant sex predilection in CH occurrence.

Regarding gestational age, no significant difference in TSH elevation was observed between full-term and preterm neonates, corroborating studies that suggest prematurity per se is less strongly associated with CH than with transient hypothyroxinemia or immature hypothalamic-pituitary-thyroid axis function Dalili S et al.(2012)[11]. However, birth weight showed a significant association with elevated TSH levels, particularly in small for gestational age (SGA) infants, as evidenced by 8 of the 15 infants with TSH >10 mIU/mL being SGA. This supports previous research indicating that chronic intrauterine growth restriction, as in SGA babies, is more closely linked to CH due to disrupted thyroid hormone synthesis and placental insufficiency Klosinska M et al.(2022)[12] & Wassner AJ.(2018)[13].

Mode of delivery did not significantly correlate with TSH values, aligning with multiple studies that found no influence of cesarean versus vaginal delivery on neonatal thyroid function screening results Deng K et al.(2018)[14]. The follow-up testing protocol employed, involving repeat TSH and FT4 measurements between days 10 and 14 in borderline cases, allowed differentiation between transient thyroid dysfunction and true CH. This approach is supported by guidelines from the American Academy of Pediatrics and European Society for Paediatric Endocrinology, which recommend repeat testing in cases with intermediate TSH elevations to avoid overtreatment Razavi Z et al.(2012)[15] & Hashemipour M et al.(2018)[16].

This multicentric study conducted across four secondary healthcare centers in Navi Mumbai demonstrates that congenital hypothyroidism (CH) affects approximately 1.17 per 1000 live births in the studied population, which is consistent with previously reported higher prevalence rates in India compared to global averages. The study confirms a significant association between low birth weight, particularly small for gestational age (SGA) status, and elevated TSH levels indicating CH, highlighting birth weight as an important risk factor. In contrast, gestational age, gender, and mode of delivery showed no significant correlation with CH prevalence. The findings underscore the feasibility and critical importance of routine neonatal screening for CH in resource-limited settings to enable early diagnosis and timely initiation of thyroxine therapy, thus preventing irreversible neurodevelopmental deficits. The protocol of initial TSH screening at 48-72 hours, followed by repeat TSH and FT4 testing in borderline cases, proved effective in distinguishing true CH from transient thyroid dysfunction, ensuring accurate diagnosis and appropriate management. Overall, this study supports the urgent need for expansion and strengthening of neonatal CH screening programs across India, with particular attention to vulnerable groups such as low birth weight infants.

Limitations of the Study

1. The retrospective study design relied on existing hospital records, which may have incomplete or missing data, leading to potential documentation bias.
2. The study was conducted at only four secondary healthcare centers in Navi Mumbai, limiting the generalizability of findings to other regions or healthcare settings.
3. The sample size, while adequate for prevalence estimation, was relatively small for detailed subgroup analyses or to detect rare forms of hypothyroidism, such as central congenital hypothyroidism.
4. Maternal factors influencing thyroid function, such as iodine status, nutritional status, and genetic predispositions, were not evaluated.
5. The study excluded very sick neonates and those who died before 48 hours of life, possibly leading to underestimation of congenital hypothyroidism prevalence among critically ill newborns.
6. Follow-up was limited to the neonatal period up to 14 days; late-onset or transient hypothyroidism cases developing after this period might have been missed.
7. Screening was primarily TSH-based and did not include detection of central hypothyroidism or other rare thyroid disorders.
8. Socioeconomic and environmental factors that might affect neonatal thyroid function were not assessed.

Funding Agency: No external funding Agency

Conflicts of Interest: None

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