**Background:** Vitamin D deficiency is a global health concern with particular risks during pregnancy, where it may affect maternal thyroid and parathyroid function. The fetus depends entirely on maternal thyroid hormones during the first trimester, making maternal vitamin D status potentially critical for fetal neurodevelopment and skeletal growth. This study aimed to evaluate the relationship between vitamin D deficiency and thyroid/parathyroid hormone levels in Palestinian women during the first trimester of pregnancy.
**Methods:** This case-control study was conducted at three main clinical centers in Gaza city and North Gaza (Al-Remal, Al-Sorani, and Jabaliya Clinical Centers) from April 2019 to April 2020. A total of 200 females aged 18–40 years were enrolled: 100 pregnant women in the first trimester (gestational weeks 6–12) as the case group and 100 apparently healthy non-pregnant women as controls, matched by frequency matching for age, number of pregnancies, and age of marriage. Exclusion criteria included age under 18 or over 40 years, special diets, pre-existing hypothyroidism, use of levothyroxine, heparin, glucocorticoids, or beta-blockers, and chronic illnesses. Serum samples were collected after a 12-hour overnight fast and analyzed using ELISA methods for vitamin D, free thyroxine (fT4), free triiodothyronine (fT3), thyroid stimulating hormone (TSH), parathyroid hormone (PTH), anti-thyroglobulin (anti-TG), and anti-thyroid peroxidase (anti-TPO) antibodies. Statistical analysis was performed using SPSS version 21 with ANOVA, chi-square, Spearman correlation, and independent-samples t-tests.
**Key Results:** The mean age of pregnant women was 25.0±4.4 years versus 25.4±5.5 years for controls. The majority of pregnant women (57.0%) were aged 18–25 years. BMI was significantly higher in pregnant women compared to controls (29.6±5.3 vs 25.6±4.8 kg/m², P<0.001, 15.6% change). Serum vitamin D levels were significantly lower in pregnant women compared to controls (14.7±8.8 vs 37.2±4.8 ng/mL, P<0.001, -60.5% change). Among pregnant women, 16.0% had severe deficiency (mean 9.4±0.4 ng/mL), 60.0% had deficiency (mean 11.3±0.9 ng/mL), and 24.0% had insufficiency (mean 24.2±1.5 ng/mL). TSH levels were significantly lower in pregnant women (1.8±1.2 vs 2.3±1.1 μIU/mL, P=0.003, -21.7% change), while fT4 levels were significantly higher (1.4±0.3 vs 1.2±0.3 ng/dL, P<0.001, 13.9% change). fT3 showed a non-significant increase (2.50±0.6 vs 2.40±0.70 pg/mL, P=0.300). Both anti-TPO (27.9±9.7 vs 33.1±11.9 IU/mL, P<0.001, -15.7% change) and anti-TG (39.3±18.5 vs 51.3±21.9 IU/mL, P<0.001, -23.5% change) were significantly lower in pregnant women. PTH was non-significantly decreased (24.7±27.7 vs 26.8±18.2 pg/mL, P=0.540, -7.8% change). Pearson correlation analysis revealed significant positive correlations between vitamin D and fT4 (r=0.243, P<0.05), fT3 (r=0.272, P<0.05), and anti-TPO (r=0.297, P<0.05). Significant negative correlations were found between vitamin D and maternal age (r=-0.195, P<0.05), TSH (r=-0.620, P<0.05), and PTH (r=-0.164, P<0.05).
**Clinical Implications:** This study demonstrates a high prevalence (76%) of vitamin D deficiency/insufficiency among first-trimester pregnant women in Gaza, with significant associations with thyroid function parameters. The inverse correlation between vitamin D and TSH, along with positive correlations with fT4 and fT3, suggests that vitamin D status may influence the hypothalamic-pituitary-thyroid axis during early pregnancy. The decline in thyroid autoantibodies during pregnancy likely reflects physiological immunosuppression. The non-significant decrease in PTH with a significant negative correlation to vitamin D is consistent with known calcium homeostatic mechanisms. These findings support routine vitamin D screening and supplementation in early pregnancy, particularly in populations with limited sun exposure, to potentially optimize maternal thyroid function and reduce risks of adverse pregnancy outcomes including preeclampsia, gestational diabetes, and impaired fetal development. Limitations include the case-control design which cannot establish causality, and the single-region setting which may limit generalizability.