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​Cihat Şen, ​Nicola Volpe

Cecilia Villalain, Daniel Rolnik, M. Mar Gil

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Murat Yayla

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Resul Arısoy

The correlation of thyroid hormone levels and gestational weeks in amniotic fluid at second trimester

Ahmet Kale, Nurten Akdeniz, Ebru Kale, Ahmet Yalınkaya, Murat Yayla

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The correlation of thyroid hormone levels and gestational weeks in amniotic fluid at second trimester. Perinatal Journal 2006;14(1):14-18

Author(s) Information

Ahmet Kale1,
Nurten Akdeniz1,
Ebru Kale2,
Ahmet Yalınkaya1,
Murat Yayla3

  1. Dicle Üniversitesi Tıp Fakültesi, Kadın Doğum Anabilim Dalı- Diyarbakır TR
  2. Dicle Üniversitesi Tıp Fakültesi, Biyokimya Anabilim Dalı- Diyarbakır TR
  3. Haseki Hastanesi, Kadın Doğum Kliniği- İstanbul TR
Publication History
Conflicts of Interest

No conflicts declared.

The purpose of this study was to determine thyroid hormone levels of amniotic fluid and correlate with gestasional
125 pregnant women underwent amniocentesis procedure for prenatal diagnosis were inclueded in study between
May 2004 and May 2005. Thyroid hormone levels were analyzed with using Roche E170 Modular analytics (Hitachi, Japan) system. Statistical analyses were performed by using One-Way Anova test. A value of p<0.05 was considered statistically significant
The mean age of patients was 34.5 ± 5.6 (21-40) The mean gestational age of patients who underwent amniocentesis
was 17.88 ± 1.58 (16-20) Karyotype analysis of all patients was normal. Amniotic fluid levels of total and free T4 increased progressively with gestasional age (p< 0.001). Although total T3 , free T3 and TSH levels did not increase with gestasional age (p>0.05). 
The levels of thyroxine (T4) hormone in amniotic fluid was higher than T3 and TSH hormones. The need of thyroxine
(T4) hormone increased with gestasional age.

Thyroid hormone, amniotic fluid, gestational age.

Thyroid hormones that accelerate tissue growth synthesis through DNA and RNA synthesis are necessary for normal growth and development. Thyroid hormones are responsible for dendritic and axonal development, synaptogenesis, neuronal migration, myelinization, and cerebral differentiation in fetal period.(1)
Thyroid follicles and T4 synthesis was detected in 10 week-fetus. As from 10th week, a growth in fetal serum TSH, T4 and Thyroid binding globulin levels was detected. Total and free T4 level reaches the adolescent levels in 36th week. On the fourth hour following the birth, serum T3 and T4 hormones reach the peak level. Since iodotironin deiodinaz activity was high in placenta, transforming T3 and T4 into the inactive metabolites T3 and T4, TSH, T3 and T4 trespass to the fetus at low level.(3) 
The purpose of this study was to determine thyroid hormone levels of amniotic fluid and correlate with gestational ages.
125 pregnant women underwent amniocentesis procedure for prenatal diagnosis were included in study between May 2004 and May 2005. All 16-20 weeks pregnants who are suggested amniocentesis accepted this suggestion. Before amniocentesis, both mother and father filled and signed amniocentesis approval form. Pregnancy age was measured by Toshiba SSH-140A, 3.5 MHz convex probe colored Doppler ultrasonography device, according to the BPD (biparietal diameter) and AC (abdominal circumference) measurements. After abdominal cleaning and cleaning of probe with povidine iodine, accompanied by the ultrasonography,transabdominal amniocentesis was applied. Punctures were performed by single usage spinal injectors varying 20-22 gauge. Thyroid hormone analysis were studied in first two mP amnion fluid before amnion fluid necessary for cytogenetic analysis was taken. Total T3 and T4 free triiodothyronine (f T3), free thyroxine (f T4) and thyroid stimulant hormone (TSH) analysis were performed by Roche E170 Modular analytics (Hitachi, Japan) system, Roche commercial kit. The cases were divided into 5 groups for amniocentesis. Group I; 16th pregnancy week (n=25), group II; 17th pregnancy week (n=25), group III 18th pregnancy week (n=25),group IV 19th pregnancy week (n=25), group V, 20th pregnancy week (n=25). During the pregnancy, the patients with thyroid or systemic diseases weren’t included into the study. All data were transferred to the software and this study was analyzed prospectively. Statistical analyses were performed by using One-Way ANOVA test. A value of p<0.05 was considered statistically significant.
125 pregnant women underwent amniocentesis procedure for prenatal diagnosis, were included in study between May 2004 and May 2005. The mean age of patients was 34.5 ± 5.6 (21-40). The mean gestational age of patients who underwent amniocentesis was 17.88 ± 1.58 (16-20). A Positive triple test applied to 82 cases (65.6), advanced age to 20 cases (16%), maternal anxiety to 18 cases (14.4%), and amniocentesis applied to 5 cases because of mal obstetric anamnesis. Karyotype analysis of all patients was normal. 
Total T3 and T4 free triiodothyronine (f T3), free thyroxine (f T4) and thyroid stimulant hormone (TSH) values varying according to the gestational weeks, are shown in Table 1. Amniotic fluid levels of total and free T4 increased progressively with gestational age (p<0.001) (Figure 1). Although total T3, free T3 and TSH levels did not progressively increase with gestational age (p>0.05) (Figures 2 and 3).
Clinical and experimental researches proved that thyroid hormones are essential for normal cerebral development in early fetal period and that has specific effects on olfactory bulbus, in sub ventricular zone of cerebral cortex, and in hippocampus.(1) It affects thyroid hormones, mitochondrial energy metabolism in short and long term.(5) It affects the lipid distribution of fetal thyroid hormones and bone differentiation in histological level.(6)
Rajatipi et al7 observed the presence of the thyroid hormone receptors in fetus lung, on 13th gestational week. This situation proves that thyroid hormones have a role in fetal lung development in early gestational weeks.
Fetal thyroid gland isn’t functional until 12th week. Fetus is under the influence of maternal thyroid hormones within the first trimester.(8)Pop et al (9) showed that the level of free T4 in early gestational period are strong indicators for motor and mental development of the infant after the birth. 
Fetal thyroid hormones are also increased in cases of vaginal delivery, prolongation of the second gestation period, fetal umbilical fetal distress, painting amnion fluid by meconium, and forceps and vacuum usage that the fetus is exposed to the intrauterine stress.(10,11) Ward et al(12) noted that maternal cardiac diseases, preeclampsia, HIV infection, diabetes mellitus have no effect on fetal thyroid hormones.A growth in fetal serum TSH, T4 and thyroid binding globulin levels occurs. TH, T4 and T3 levels reach the peak level in second trimester and they tend to decrease until the next term. In last trimester, T4 and TSH levels are higher than maternal levels however total T4 and T3 are lower. For Fetal thyroid hormone metabolism, second and third trimesters are critical transition period.(13) 
Polk et al(14) showed that total T4, and free T4 levels are augment along with gestational weeks and serum T3 levels are low. Klein et al(15) observed that fetal serum T4, free T4 and thyroid binding globulin levels are in a significant increase between 26th and 33rd gestational weeks, as from 34th gestational week; there isn’t any change in these parameters.Sack et al determined that amniotic fluid T4 levels are progressively elevated before 20th week, however T3 levels didn’t give a progressive increase.(16) 
In our study, total T4 levels and free thyroxin (fT4) levels in amniotic fluid increased progressively between 16 and 20th gestational weeks (p<0.001). Although total T3 , free T3 and TSH levels did not increase with gestational week (p>0.05) In fetal period, normal cerebral development, fetal bone and lung differentiation and similar cases that thyroid hormones influence, thyroxin (T4) hormone is effective and the need for this hormone increased as gestational weeks go by. Although T3, free T3 and TSH levels did not progressively increase with gestational age, their presence in amnion fluid make us think that they contribute to the fetal development.

1.Lavado-Autric R, Auso E, Garcia-Velasco JV, Arufe Mdel C, Escobar del Rey F, Berbel P. Early maternal hypothyroxinemia alters histogenesis and cerebral cortex cytoarchitecture of the progeny. J Clin Invest 2003; 111: 1073-82. 
2.Thorpe-Beeston JG, Nicolaides KH, McGregor AM. Fetal thyroid function. Thyroid 1992; 2: 207-17.
3.Roti E, Gnudi A, Braverman LE. The placental transport, synthesis and metabolism of hormones and drugs which affect thyroid function. Endocr Rev 1983; 4: 131-49.
4.Hadj-Sahraoui N, Seugnet I, Ghorbel MT, Demeneix B. Hypothyroidism prolongs mitotic activity in the post-natal mouse brain. Neurosci Lett 2000; 280: 79 82. 
5.Wrutniak-Cabello C, Casas F, Cabello G. Thyroid hormone action in mitochondria. J Mol Endocrinol 2001; 26: 67-77. 
6.Geloso JP, Hemon P, Legrand J, Legrand C, Jost A. Some aspects of thyroid physiology during the perinatal period. General and Comparative Endocrinology Gen Comp Endocrinol 1986; 10: 191-7. 
7.Rajatapiti P, Kester MH, de Krijger RR, Rottier R, Visser TJ, Tibboel D. Expression of glucocorticoid, retinoid, and thyroid hormone receptors during human lung development. J Clin Endocrinol Metab 2005; 90: 4309-4314.
8.Calvo RM, Jauniaux E, Gulbis B, Asuncion M, Gervy C, Contempre B, Morreale de Escobar G. Fetal tissues are exposed to biologically relevant free thyroxine concentrations during early phases of development. J Clin Endocrinol Metab 2002; 87: 1768 1777. 
9.Pop VJ, Kuijpens JL, van Baar AL, Verkerk G, van Son MM, de Vijlder JJ, Vulsma T, Wiersinga WM, Drexhage HA, Vader HL. Low maternal free thyroxine concentrations during early pregnancy are associated with impaired psychomotor development in infancy. Clin Endocrinol 1999; 50: 149 155. 
10.Fukuda S. Correlation between function of the pituitary thyroid axis and metabolism of catecholamines by the fetus at delivery. Clin Endocrinol 1987; 27: 331-338. 
11.Chan LY, Leung TN, Lau TK Influences of perinatal factors on cord blood thyroid-stimulating hormone level. Acta Obstet Gynecol Scand 2001; 80: 1014-8.
12.Ward LS, Kunii IS, de Barros Maciel RM. Thyroid-stimulating hormone levels in cord blood are not influenced by non-thyroidal mothers' diseases. Sao Paulo Med J 2000; 118:144-7. 
13.Hume R, Simpson J, Delahunty C, van Toor H, Wu SY, Williams FL, Visser TJ. Human fetal and cord serum thyroid hormones: developmental trends and interrelationships. J Clin Endocrinol Metab 2004; 89: 4097-103.
14.Polk DH. Thyroid hormone metabolism during development. Reprod Fertil Dev 1995; 7: 469-77. 
15.Klein AH, Oddie TH, Parslow M, Foley TP Jr, Fisher DA. Developmental changes in pituitary-thyroid function in the human fetus and newborn. Early Hum Dev 1982; 6: 321-30. 
16.Sack J, Fisher DA, Hobel CJ, Lam R. Thyroxine in human amniotic fluid. J Pediatr 1975; 87: 364-8.

Tablo 1.
Thyroid hormone values in amnion fluid, varying with gestational week.
Figure 1.
Total T4 and free thyroxin levels in amnion fluid, varying with gestational week
Figure 2.
Total T3 and free thyroxin levels in amnion fluid, varying with gestational week.
Figure 3.
Thyroid stimulant hormone TSH level in amnion fluid, varying with gestational week