Congenital hypothyroidism (CH) is a thyroid hormone deficiency syndrome in newborns resulting from incomplete thyroid development and decreased thyroid hormone biosynthesis or thyroid-stimulating hormone (TSH) secretion [1]. The reported global incidence of CH is approximately 1 in 3,000–4,000 live births, with higher rates in several Asian regions and in upper middle income countries, underscoring the need for robust newborn screening programs [1,2]. In India, studies suggest that the prevalence may be higher than the global average, making early detection particularly relevant in local settings [2,3]. Newborn screening for CH is typically performed using thyroid stimulating hormone (TSH) and/or thyroxine (T4) estimation, as timely initiation of levothyroxine therapy within the first weeks of life is crucial to prevent irreversible neurodevelopmental impairment [1,4-6]. While dried blood spot sampling at 3–5 days of life is widely practiced, the use of umbilical cord blood for TSH or T4 estimation has emerged as a practical alternative, especially in resource limited settings where post discharge follow up and recall of newborns can be challenging [1,4-6]. Cord blood TSH measurement has shown high sensitivity for detecting CH, although its values can be influenced by various maternal and perinatal factors, necessitating the definition of appropriate cut off levels and local reference ranges [1,4-6]. Several Indian and international studies have evaluated cord blood thyroid profiles to estimate the proportion or incidence of CH among inborn neonates and to assess the feasibility of using cord blood as a primary screening tool [4,7-9]. These studies report variable proportions of CH and highlight regional differences, but consistently reinforce that CH remains a significant public health concern and that early, hospital based screening strategies can substantially reduce the burden of preventable neurodevelopmental disability [4,7-9]. Against this background, estimating the proportion of congenital hypothyroidism among all newborns delivered in Sir T. Hospital, Bhavnagar, Gujarat, using cord blood thyroid profile in a prospective observational design is essential to generate local epidemiological data, evaluate the utility of cord blood screening in this population, and guide future screening policies and follow up protocols.

This prospective observational study was conducted at Sir T. Hospital, Bhavnagar, Gujarat, a tertiary care teaching hospital, with active collaboration between the Departments of Pediatrics and Obstetrics and Gynaecology. The study included all live-born neonates delivered at the institution during the study period and aimed to determine the proportion of congenital hypothyroidism using cord blood thyroid profile screening. The study was carried out over a total duration of nine months, from July 2023 to April 2024, comprising six months of data collection followed by three months dedicated to data analysis. Prior to initiation, approval was obtained from the Scientific Review Committee and the Institutional Review Board, and the study was registered with the Clinical Trials Registry–India. Written informed consent was obtained from parents or legal guardians after providing a detailed explanation of the study objectives, procedures, potential risks, and benefits in a language they understood. All live-born neonates delivered at Sir T. Hospital during the study period were eligible for inclusion provided informed consent was obtained and complete medical records were available. Stillbirths, neonatal deaths, preterm neonates born before 35 weeks of gestation, very low birth weight infants weighing less than 1500 grams, neonates requiring resuscitation or intensive care, and cases in which consent was refused were excluded to minimize confounding factors related to altered thyroid physiology. Cord blood samples were collected immediately after delivery under sterile conditions following clamping and cutting of the umbilical cord. Approximately 5–10 mL of cord blood was drawn from the umbilical vein and transported promptly to the laboratory under controlled conditions. The samples were analyzed for thyroid-stimulating hormone (TSH), free triiodothyronine (T3), and free thyroxine (T4) levels using automated immunoassay techniques. TSH levels were measured using highly sensitive immunoassays, while free T3 and free T4 levels were estimated using enzyme-linked immunosorbent assay or radioimmunoassay methods, depending on laboratory availability. Initial screening was based primarily on cord blood TSH levels, with values between 1.9 and 11.5 mIU/L considered normal. Neonates with TSH levels exceeding 11.5 mIU/L and/or low free T3 or free T4 levels were flagged for further evaluation. Confirmatory testing was performed at 72 hours of life using venous blood samples. Persistent elevation of TSH levels above 17.6 mIU/L in conjunction with low free T4 confirmed the diagnosis of congenital hypothyroidism. Thyroid ultrasonography was subsequently performed in confirmed cases to identify structural abnormalities such as thyroid dysgenesis, ectopia, or agenesis. All demographic, clinical, laboratory, and imaging data were meticulously recorded using standardized data collection forms and subsequently entered into a secure electronic database. Statistical analysis was performed using IBM SPSS Statistics version 29, with Microsoft Excel used for preliminary data management and visualization. Descriptive statistics were employed to summarize demographic and clinical variables, while inferential statistics including chi-square test and independent t-test were applied as appropriate to identify associations and potential predictors of congenital hypothyroidism. A p-value of less than 0.05 was considered statistically significant.

A total of 509 live-born neonates were included in the study, and cord blood thyroid profile analysis was successfully performed for all participants immediately after birth. Table 1. Gestational Age Distribution of Study Population (n = 509) Gestational Age (weeks) Frequency Percentage (%) 35 33 6.5 36 78 15.3 37 100 19.6 38 105 20.6 39 107 21.0 40 56 11.0 41 21 4.1 42 9 1.8 Total 509 100 The gestational age of the study population ranged from 35 to 42 weeks. The highest proportion of neonates were delivered at 39 weeks of gestation (21.0%), followed by 38 weeks (20.6%) and 37 weeks (19.6%) (Table 1). The least number of deliveries occurred at 42 weeks (1.8%). The mean gestational age was 37.94 ± 1.67 weeks, with a median of 38 weeks and a mode of 39 weeks, indicating a predominantly term population. Table 2. Gender Distribution of Neonates Gender Number Percentage (%) Male 251 49.3 Female 258 50.7 Total 509 100 Among the 509 neonates, 258 (50.7%) were females and 251 (49.3%) were males, showing an almost equal gender distribution. Table 3. Cord Blood Thyroid Hormone Levels (n = 509) Parameter Mean ± SD Median Range TSH (mIU/L) 6.29 ± 2.15 5.90 2.10 – 29.00 Free T3 (pg/mL) 1.53 ± 0.31 1.46 0.12 – 2.32 Free T4 (ng/dL) 1.42 ± 0.18 1.43 0.29 – 1.80 The mean cord blood TSH level was 6.29 ± 2.15 mIU/L, with values ranging from 2.10 to 29.00 mIU/L. The median TSH value was 5.9 mIU/L, and the interquartile range was 4.89–7.65 mIU/L. The mean cord blood free T3 level was 1.53 ± 0.31 pg/mL, while the mean free T4 level was 1.42 ± 0.18 ng/dL. Both free T3 and free T4 values demonstrated relatively symmetrical distributions, with median values closely approximating the means (Table 3). Independent t-test analysis demonstrated no significant gender-based differences in cord blood thyroid hormone levels, including TSH (p = 0.867), free T3 (p = 0.638), and free T4 (p = 0.933). Similarly, gestational age did not differ significantly between neonates with and without congenital hypothyroidism (p > 0.05). Although a mean difference of 1.67 weeks was observed, the confidence interval crossed zero, indicating no meaningful association between gestational age and hypothyroidism. Table 4. Mode of Delivery Mode of Delivery Frequency Percentage (%) Normal vaginal 330 64.8 Caesarean 173 34.0 Assisted vaginal (vacuum) 6 1.2 Total 509 100 Most neonates were delivered by normal vaginal delivery (64.8%), followed by caesarean section (34.0%). Assisted vaginal deliveries using vacuum accounted for 1.2% of cases (Table 4). Table 5. Screening Outcome for Congenital Hypothyroidism Congenital Hypothyroidism Frequency Percentage (%) Absent 508 99.8 Present 1 0.2 Total 509 100 Out of the 509 neonates screened using cord blood thyroid profile, only one neonate (0.2%) had abnormal results requiring confirmatory venous testing at 72 hours of life. This neonate demonstrated persistently elevated venous TSH (34 mIU/L) along with low free T3 and free T4 levels, confirming the diagnosis of congenital hypothyroidism. The remaining 508 neonates (99.8%) had normal thyroid function. Incidence of Congenital Hypothyroidism The incidence of congenital hypothyroidism in the present study population was 0.2% (1 in 509 live births).

In the present study, cord blood thyroid-stimulating hormone (CBTSH) levels were assessed in 509 newborns. The mean CBTSH value was 6.29 mIU/L, which is lower than that reported by Subhash Poyekar et al., who documented a mean value of 8.9 mIU/L [10]. The median and mode in the present cohort were 5.9 mIU/L and 6.55 mIU/L, respectively, with a standard deviation of 2.146, compared with a higher standard deviation of 7.3 reported in the same comparative study [10]. The observed CBTSH values ranged from 2.10 to 29 mIU/L. Only one newborn had a CBTSH level exceeding the predefined cut-off of 11.5 mIU/L, warranting repeat thyroid evaluation at 72 hours using venous blood sampling, in accordance with established screening recommendations [10]. Cord blood free T3 and free T4 levels were also evaluated in all 509 neonates. The mean free T3 concentration (1.53 pg/mL) was marginally higher than the mean free T4 concentration (1.423 ng/dL). The median values closely approximated the respective modal values for both hormones, suggesting a near-symmetrical distribution. The greater standard deviation observed for free T3 (0.309 pg/mL) compared with free T4 (0.180 ng/dL) indicates relatively wider variability in T3 levels. Only one newborn demonstrated free T3 and free T4 values below the reference range, suggesting an abnormal thyroid profile. Follow-up venous blood thyroid function testing at 72 hours of life was performed in the single neonate with abnormal cord blood findings. This evaluation revealed a markedly elevated TSH level of 34 mIU/L accompanied by low free T3 (1.06 pg/mL) and free T4 (1.1 ng/dL), confirming the diagnosis of congenital hypothyroidism. The gestational age of the study population ranged from 35 to 42 weeks, with a predominance of term neonates. The highest proportion of births occurred at 39 weeks (21.0%), while only 1.8% were delivered at 42 weeks. The mean gestational age was 37.94 weeks, with a median of 38 weeks and a mode of 39 weeks, reflecting a largely term cohort. The study included an almost equal distribution of male (49.3%) and female (50.7%) neonates, yielding a male-to-female ratio of approximately 1:1.03. Given that only one case of congenital hypothyroidism was identified, no meaningful association between gender and congenital hypothyroidism could be established, a limitation also acknowledged in similar low-incidence studies [11,12]. Regarding the mode of delivery, the majority of neonates were delivered via normal vaginal delivery (64.8%), followed by caesarean section (34.0%) and assisted vaginal delivery (1.2%). Owing to the single confirmed case of congenital hypothyroidism, correlation between delivery mode and thyroid hormone variation could not be assessed. Previous studies have reported significantly lower CBTSH levels in neonates delivered by elective caesarean section compared with vaginal delivery, attributed to reduced catecholamine surge during labor [13,14]. However, other investigators have found no significant association between mode of delivery and neonatal TSH levels [15]. Analysis of variance revealed no statistically significant association between cord blood thyroid hormone levels (TSH, free T3, free T4) and gender (p > 0.05). While some studies have reported higher TSH levels in male neonates [16], several others corroborate the absence of sex-related differences, consistent with the findings of the present study [17,18]. Similarly, independent t-test analysis showed no significant association between gestational age and the presence of congenital hypothyroidism (p > 0.05). Although a mean gestational age difference of 1.67 weeks was observed, the confidence interval crossed zero, indicating that this difference may be attributable to chance. The relationship between gestational age and TSH levels remains inconsistent in the literature, with reports of increasing TSH levels with advancing gestation [18,19], higher levels in preterm neonates [20], and no significant association in other cohorts [21]. These discrepancies suggest population-specific influences and underline the need for further investigation. Overall, cord blood thyroid screening identified one confirmed case of congenital hypothyroidism among 509 newborns, corresponding to an incidence of approximately 1 in 509. This incidence falls within the range reported across India, where congenital hypothyroidism prevalence varies from 1 in 248 to 1 in 1700 live births [22,23]. The findings support the utility of cord blood thyroid screening as an effective initial strategy for early detection of congenital hypothyroidism, enabling prompt diagnosis and timely intervention.

The incidence of congenital hypothyroidism in this cohort was 1 in 509 live births. Cord blood thyroid screening proved to be a feasible and effective method for early detection of CH and may serve as a valuable screening strategy in similar settings.

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