Analysis of Risk Factors and Screening Results of Neonatal Congenital Hypothyroidism in a Tertiary Care Center of Southern China

**Background:** Congenital hypothyroidism (CH) is a common neonatal endocrine disease and one of the most preventable causes of nervous system developmental disorders. Early screening, diagnosis, and treatment significantly improve prognosis. While genetic and environmental factors contribute to CH, maternal gestational factors and fetal growth are closely linked to its development. This study aimed to explore risk factors for neonatal CH and factors influencing false-positive results in CH screening, with particular attention to small for gestational age (SGA) status, which has been less studied in this context.

**Methods:** This retrospective study was conducted at Boai Hospital of Zhongshan Affiliated to Southern Medical University, including data from January 2016 to December 2021. The case group comprised 255 neonatal patients with CH who completed screening and diagnostic confirmation. The false-positive screening group included 366 neonates with positive initial CH screening results (TSH > 8.5 μIU/mL on dried blood spot collected 48 hours to 7 days after birth) but normal thyroid function on reexamination. The control group consisted of 246 healthy neonates with negative newborn screening results, matched by gender and date of birth. Observational indicators included gestational age, birth weight, maternal age, SGA (birth weight below 10th percentile for gestational age), maternal pregestational BMI, gestational method, and gestational diseases (thyroid disease, diabetes mellitus, hypertension, anemia, hepatitis). Univariate analysis using chi-square tests was performed, followed by multivariate logistic regression for statistically significant variables. SPSS 19.0 was used, with P<0.05 considered statistically significant.

**Key Results:** Among 255 CH patients, there were 150 males and 105 females (male:female ratio 1.43:1). No statistically significant differences were found among the three groups for gestational age, birth weight, or maternal age (P>0.05). Univariate analysis revealed significant differences in SGA proportion (χ²=11.943, P=0.003), maternal gestational diabetes mellitus (χ²=6.857, P=0.032), gestational thyroid disease (χ²=6.999, P=0.03), and assisted reproduction technology use (χ²=9.732, P=0.008) among the three groups. Multivariate logistic regression showed that gestational thyroid disease (OR=8.452, 95% CI:1.051–67.982, P=0.045) and gestational diabetes mellitus (OR=2.654, 95% CI:1.051–6.706, P=0.039) were significant risk factors for neonatal CH, while assisted reproduction was a protective factor (OR=0.194, 95% CI:0.041–0.911, P=0.038). For false-positive screening results, SGA (OR=2.556, 95% CI:1.027–6.361, P=0.044), gestational thyroid disease (OR=7.801, 95% CI:1.03–59.057, P=0.047), gestational diabetes mellitus (OR=2.731, 95% CI:1.18–6.322, P=0.019), and assisted reproduction (OR=0.28, 95% CI:0.102–0.765, P=0.013) were all significant influencing factors.

**Clinical Implications:** This study demonstrates that maternal gestational thyroid disease and diabetes mellitus significantly increase the risk of neonatal CH, while assisted reproduction appears protective—a finding that requires further investigation. SGA neonates are more likely to have false-positive CH screening results, likely due to transient hypothyroidism related to intrauterine growth restriction and postnatal nutritional improvement. The authors suggest that hypothyroidism in SGA neonates may be temporary, with TSH levels normalizing within months, necessitating close follow-up rather than immediate treatment. The study emphasizes that clinicians should consider these perinatal factors when interpreting CH screening results to avoid both misdiagnosis and missed diagnosis. Limitations include lack of analysis of genetic predisposition, environmental exposure, iodine deficiency, and failure to account for multiple concurrent maternal conditions or to classify CH by type (permanent vs. transient).