Background Interpretation of thyroid function tests during pregnancy needs trimester-related reference intervals from pregnant populations with minimal risk for thyroid dysfunction. While India has become iodine sufficient after two decades of salt iodisation, there is no normative data for thyroid function from healthy pregnant women of this country.Aims and objectives To determine trimester-specific reference ranges for free triiodothyronine (FT 3 ), free thyroxine (FT 4 ) and thyrotropin (TSH) from healthy pregnant Indian women.Design Cross-sectional study in a reference population of pregnant women.Setting Primary care level obstetric department in India.Population Women with uncomplicated pregnancy in any trimester.Methods Five hundred and forty-one apparently healthy pregnant women with uncomplicated single intrauterine gestations reporting to the Armed Forces Clinic in any trimester were consecutively recruited. Clinical examination, thyroid ultrasound for echogenicity and nodularity and estimation of FT 3 , FT 4 , TSH and antithyroid antibodies (antithyroperoxidase [anti-TPO] and antithyroglobulin [anti-Tg]) using electrochemiluminescence technique were carried out. From this entire sample, a disease-and risk-free reference population was obtained by excluding those with any known factor that could affect thyroid function or those who were being treated for thyroid dysfunction.Main outcome measure None.Results Of the 541 consecutive pregnant women in different trimesters enrolled for the study, 210 women were excluded. The composition of reference population comprising 331 women was 107 in first trimester, 137 in second trimester and 87 in third trimester. The 5th and 95th percentiles values were used to determine the reference ranges for FT 3 , FT 4 and TSH. The trimester-wise values in the first, second and third trimesters were: FT 3 (1.92-5.86, 3.2-5.73 and 3.3-5.18 pM/l), FT 4 (12-19.45, 9.48-19.58 and 11.32-17.7 pM/l) and TSH (0.6-5.0, 0.44-5.78 and 0.74-5.7 iu/ml), respectively. Analysis of mean, median values for FT 3 , FT 4 and TSH between each trimester showed no significant difference in FT 3 and TSH values (95% CI). However, FT 4 showed significant variation between trimesters with values decreasing with advancing gestational age (P value: first versus second = 0.015, first versus third = 0.003 and second versus third = not significant). Women with antibody positivity and hypoechogenicity of thyroid gland had significantly higher TSH values when compared with women with antibody negativity and normoechogenicity.Conclusions Reference ranges of FT 3 , FT 4 and TSH have been established for pregnant Indian women using 5th and 95th percentiles.

25-Hydroxy vitamin D (25(OH)D)deficiency is linked with predisposition to autoimmune type 1 diabetes and multiple sclerosis. Our objective was to assess the relationship between serum 25(OH)D levels and thyroid autoimmunity. Subjects included students, teachers and staff aged 16-60 years (total 642, 244 males, 398 females). Serum free thyroxine, thyroid-stimulating hormone (TSH), and thyroid peroxidase autoantibodies (TPOAb), intact parathyroid hormone and 25(OH)D were measured by electrochemiluminescence and RIA, respectively. Thyroid dysfunction was defined if (1) serum TSH $ 5 mU/ml and TPOAb . 34 IU/ml or (2) TSH $ 10 mU/ml but normal TPOAb. The mean serum 25(OH)D of the study subjects was 17·5 (SD 10·2) nmol/l with 87 % having values #25 nmol/l. TPOAb positivity was observed in 21 % of subjects. The relationship between 25(OH)D and TPOAb was assessed with and without controlling for age and showed significant inverse correlation (r 2 0·08, P¼ 0·04) when adjusted for age. The prevalence of TPOAb and thyroid dysfunction were comparable between subjects stratified according to serum 25(OH)D into two groups either at cut-off of #25 or . 25 nmol/l or first and second tertiles. Until recently, vitamin D deficiency was considered to be rare in India because of abundant sunshine (1,2) . However, a systematic study carried out in the year 2000 in Delhi showed the presence of low 25-hydroxy vitamin D (25(OH)D) in a majority of subjects including newborns, their mothers, healthy physicians, nurses, soldiers and those with vitiligo and albinism. Based on these study groups, subnormal serum 25(OH)D levels of Asian Indians could be linked to their skin pigmentation and poor sunshine exposure (1,3) . Subsequently, a series of studies have documented widespread hypovitaminosis D in north as well as south India (3 -5) . Besides bone mineral homeostasis, 25(OH)D deficiency has been associated with a wide range of non-skeletal effects including predisposition towards autoimmune disorders (6 -8) .The demonstration of vitamin D receptor in monocytes, dendritic cells and activated T cells indicates significant interaction between vitamin D and the immune system (6,7) . While the molecular mechanisms linking vitamin D with autoimmunity are under investigation, in vitro studies indicate an immunomodulatory effect of 1,25(OH)D on Th 1 , Th 2 , T regulator and dendritic cells leading to a shift towards activation of Th2 cells (6,7) . Clinical relevance of the mechanism is indicated by a number of studies showing increased prevalence of autoimmune disease such as multiple sclerosis in Canada and the northern part of the USA receiving less sunshine. Vitamin D supplementation resulted in decreased prevalence of autoimmune disorders such as type 1 diabetes and multiple sclerosis. A recent meta-analysis showed 29 % reduction in the risk of type 1 diabetes in children receiving vitamin D supplementation (9,10)

The present cross-sectional study was conducted to determine the vitamin D status of pregnant Indian women and their breast-fed infants. Subjects were recruited from the Department of Obstetrics, Armed Forces Clinic and Army Hospital (Research and Referral), Delhi. A total of 541 apparently healthy women with uncomplicated, single, intra-uterine gestation reporting in any trimester were consecutively recruited. Of these 541 women, 299 (first trimester, ninety-seven; second trimester, 125; third trimester, seventy-seven) were recruited in summer (April -October) and 242 (first trimester, fifty-nine, second trimester, ninety-three; third trimester, ninety) were recruited in winter (November -March) to study seasonal variations in vitamin D status. Clinical, dietary, biochemical and hormonal evaluations for the Ca -vitamin D-parathormone axis were performed. A subset of 342 mother -infant pairs was re-evaluated 6 weeks postpartum. Mean serum 25-hydroxyvitamin D (25(OH)D) of pregnant women was 23·2 (SD 12·2) nmol/l. Hypovitaminosis D (25(OH)D ,50 nmol/l) was observed in 96·3 % of the subjects. Serum 25(OH)D levels were significantly lower in winter in the second and third trimesters, while serum intact parathormone (iPTH) and alkaline phosphatase levels were significantly higher in winter in all three trimesters. A significant negative correlation was found between serum 25(OH)D and iPTH in mothers (r 20·367, P¼0·0001) and infants (r 2 0·56, P¼ 0·0001). A strong positive correlation was observed between 25(OH)D levels of mother -infant pairs (r 0·779, P¼ 0·0001). A high prevalence of hypovitaminosis D was observed in pregnancy, lactation and infancy with no significant inter-trimester differences in serum 25(OH)D levels.

A high prevalence of osteoporosis was observed in elderly Indian subjects. pDXA has high negative predictive value, making it a useful tool in population screening for osteoporosis.