Abstract
Keywords
UGR Fetal Growth Retardation Thyroid Dysfunction Thyroid Disease
Fulltext
Maternal thyroid function changes during pregnancy and inadequate adaptation to these changes results in thyroid dysfunction (1, 2). Some of these alterations in thyroid function occur due to increased thyroid hormone-binding globulin (TBG) concentration, increased iodine clearance in the kidneys, and thyrotrophic effect of human chorionic gonadotropin (HCG) (3, 4). In previous studies, the prevalence of overt hypothyroidism was 1% to 1.5%, (1-9) and prevalence of subclinical hypothyroidism was 5% to 8% (8, 10). The main pregnancy complications of hypothyroidism were anemia, preeclampsia, prematurity, low-birth weight (LBW), fetal distress in labor, fetal death, and congenital hypothyroidism, and neurocognitive deficits in children. Subclinical hypothyroidism might be associated with preterm delivery and low Apgar score (1-3, 11, 12). Overt hyperthyroidism and subclinical hyperthyroidism affects about 0.2% to 0.8% and 0.4% to 1% of pregnancies, respectively (1-3, 13). Maternal hyperthyroidism may cause preterm delivery, intrauterine growth restriction (IUGR), and neonatal thyrotoxicosis (1-3, 14). According to the last published guidelines on 2012 for the management of thyroid dysfunction during pregnancy and postpartum, "Universal screening of healthy women for thyroid dysfunction before pregnancy is not recommended" and "The committee could not reach agreement with regard to screening recommendations for all newly pregnant women." Increased knowledge about the interaction between the thyroid and pregnancy has changed our view about the definition and diagnosis of thyroid dysfunction in pregnancy (15-18); for example, we have recently found that thyroid stimulating hormone (TSH) level of 2.5 mIU/L in the first trimester has been accepted as the upper limit of normal range (15). This fact has an important implication in interpretation of the previous literature as well as a critical effect on diagnosis of clinical hypothyroidism. Considering these changes, the American thyroid association has published a new guideline in 2011 for an accurate diagnosis and management of thyroid disease in pregnancy. This guideline determined the normal limits of TSH in the second trimester as 0.2 to 3 mIU/L and free thyroxin (FT4) as 12 to 30 pmol/L (15). Subsequent to these changes in definition of thyroid diseases in pregnancy, it is necessary to reevaluate the accurate prevalence of thyroid diseases in pregnancy and their mentioned effects in previous studies (1-3, 12-14).
Recent changes in definition of thyroid diseases in pregnancy has resulted in changes in interpretation of previous studies about the prevalence and effect of thyroid diseases on pregnancy outcomes after 2011. In addition, due to lack of sufficient data about the prevalence and pregnancy outcomes of thyroid disease in Iran, this prospective study aimed to evaluate the prevalence of thyroid diseases and its outcomes in pregnancy in Fars Province, south of Iran.
Out of 600 enrolled women in our study, 14 refused to follow the study. Ultimately, 586 women participated in our investigation to the end. The mean of participants age was 25.6 ± 3.6 years, mean of their weight was 63.4 ± 9.1 kg, and the mean of their height was 162.5 ± 6.7 cm. Fourteen women (2.4%) had clinical hypothyroidism, 66 (11.3%) had subclinical hypothyroidism, 2 (0.3%) had subclinical hyperthyroidism, and 7 (1.2%) had overt hyperthyroidism. isolated hypothyroxinemia was diagnosed in 1.4% of patients. General characteristics of the mothers (height, weight, and age) in each category are summarized in Table 1. Only one mother was cigarette smoker. There was no significant difference in general characteristics of mothers in different thyroid function categories (P > 0.05). The mean of gestational age at delivery was 38 ± 1.9 weeks. The mean of the newborns head circumference was 35.4 ± 1.7 cm, mean of their weight was 2599 ± 385 g, and mean of their length was 50.9 ± 2.8 cm. The neonates had an Apgar score of 8.4 ± 1.1 at first minute of delivery. General characteristics of the neonates are categorized according to maternal thyroid function in Table 2.
| Category | I | II | III | IV | V | P value | Total |
|---|---|---|---|---|---|---|---|
| Frequency, No. (%) | 14 (2.4) | 66 (11.3) | 497 (84.8) | 2 (0.3) | 7 (1.2) | 586 (100) | |
| Age, y | 27 ± 4 | 25.8 ± 3.5 | 25.5 ± 3.6 | 24.4 ± 2.1 | 26.3 ± 2.9 | 0.543 | 25.6 ± 3.6 |
| Weight, kge | 65.1 ± 11.6 | 61.9 ± 9 | 63.6 ± 9 | 74 ± 1.4 | 59.4 ± 3.1 | 0.11 | 63.4 ± 9.1 |
| Height, cm | 161.7 ± 4.5 | 162.6 ± 3.3 | 162.5 ± 7.2 | 166.5 ± 0.7 | 161 ± 4.4 | 0.102 | 162.5 ± 6.7 |
| BMI, kg/m2 | 24.8 ± 3.4 | 23.4 ± 2.9 | 29.3 ± 1.18 | 26.7 ± 0.73 | 22.9 ± 1.4 | 0.140 | 17.4 ± 3.2 |
| sBP, mm Hg | 115.3 ± 21.3 | 110.9 ± 20.6 | 110.4 ± 15 | 100 ± 0.1 | 107.8 ± 8.1 | 0.243 | 105.44 ± 18.15 |
| dBP, mm Hg | 78.6 ± 11.3 | 76.9 ± 10.1 | 76.3 ± 10.5 | 70 ± 7.07 | 77.2 ± 7.6 | 0.769 | 74.07 ± 11.03 |
| Gestation at Delivery, wk | 38.1 ± 3.1 | 37.8 ± 1.9 | 38.1 ± 1.9 | 38.6 ± 0.71 | 38.3 ± 1.5 | 0.747 | 38 ± 1.9 |
| Cigarette Smoker | 0 | 1 | 0 | 0 | 0 | 1 (0.2) | |
| Mode of Delivery, Number of CS | 2 (14.3) | 12 (18.2) | 81 (16.3) | 0 (0) | 0 (0) | 0.513 | 95 (16.2) |
| Category | I | II | III | IV | V | Total | P Value |
|---|---|---|---|---|---|---|---|
| Frequency | 14 (2.4) | 66 (11.3) | 497 (84.8) | 2 (0.3) | 7 (1.2) | 586 (100) | - |
| Gestational Age, wk | 38.1 ± 3.1 (38.8) | 37.8 ± 1.9 (38.3) | 38 ± 1.9 (38.4) | 38.6 ± 0.7 (38.6) | 38.3 ± 1.4 (38.4) | 38 ± 1.9 (38.3) | 0.747 |
| Head Circumference, cm | 35.2 ± 1.1 (35.3) | 35.4 ± 1.4 (35.8) | 35.4 ± 1.8 (35.8) | 36 ± 0.4 (36) | 34.8 ± 1.1 (35.3) | 35.4 ± 1.7 (35.7) | 0.25 |
| Weight, g | 2677 ± 428 (2740 | 2563 ± 468 (2610) | 2603 ± 372 (2640) | 2550 ± 70 (2550) | 2502 ± 466 (2400) | 2599 ± 385 (2635) | 0.763 |
| Length, cm | 51.1 ± 3.3 (51) | 50.6 ± 3.3 (51.3) | 50.9 ± 2.7 (51) | 51 ± 2.8 (51) | 51.7 ± 3.3 (52) | 50.9 ± 2.8 (51) | 0.102 |
| Apgar Score, 1st Minute | 8.5 ± 1.3 (9) | 8.2 ± 1.4 (9) | 8.4 ± 1.1 (9) | 10 ± 0 (10) | 8.1 ± 1.2 (9) | 8.4 ± 1.1 (9) | 0.125 |
There was no significant difference between gestational age, head circumference, weight, length, and Apgar score of neonates in different thyroid function categories (P > 0.05). Distribution of serum TSH had a non-Gaussian distribution. After logarithmic transformation (log and ln), normality was not achieved. Therefore, the rank numbers of 2.5th to 97.5th percentiles were used to estimate the lower and the upper limits of the reference interval, respectively. 2.5th, 25th, 50th, 75th, and 97.5th percentiles for FT3 and FT4, which had normal distribution, were calculated by frequency analysis. These percentiles were calculated for TSH, FT3, and FT4. All data are summarized in Table 3. Median (interquartile range) for subclinical hypothyroidism and overt hypothyroidism was 3.65 (3.18-4.93) and 12.1 (4.42-15.22), respectively.
| Thyroid Function Tests | Observed Percentiles | ||||
|---|---|---|---|---|---|
| 2.5th | 25th | 50th | 75th | 97.5th | |
| TSH, mIU/L | 0.51 | 1.18 | 1.68 | 2.4 | 4.9 |
| FT3, pmol/L | 8 | 11.1 | 12.8 | 14.5 | 17.7 |
| FT4, pmol/L | 7.85 | 10.68 | 12.36 | 14.29 | 17.89 |
We have investigated the normal distribution of TSH in our 586 pregnant women and showed that our range for the level of TSH in Iran was higher than the ATA ranges (15). Our data were similar to those of previous reported from India and Iran in which the ranges of TSH in the second trimester were about 0.43 to 5.78 and 0.5 to 4.1 mIU/L, respectively (26-28). Differences in laboratory methods, differences in kits, maternal iodine status, and ethnic, genetic, and environmental factors in our and other similar studies could explain these differences. On the other hand, other studies report a lower range for TSH level (29-33). After publishing the ATA guideline, we have found some studies in which the thyroid function status was evaluated according to this guideline (3, 7, 21). The present study provides, for the first time, the data about the thyroid function status in Iranian pregnant women according to this new guideline. We found that prevalence of hypothyroidism in pregnancy was 13.7% (clinical, 2.4%; and subclinical, 11.3%). In addition, 1.4% of our pregnant women had isolated hypothyroxinemia. According to previous reports, prevalence of clinical hypothyroidism in pregnant women ranged from 1% to 3.5% and subclinical hypothyroidism ranged from 4% to 31% (1-8, 22). Prevalence of hyperthyroidism of pregnant women was 1.5% in our study (subclinical, 0.3%; and over, 1.2%). In previous reports, prevalence of hyperthyroidism was reported as 0.2% to 2% (1-8, 22). One of the causes of variation in prevalence of thyroid dysfunction might be variation in definition of normal range for TSH in different studies. The ATA recommendations could orchestrate the investigations about the prevalence and effects of thyroid dysfunction and prevent the errors in our interpretations and clinical judgment about the detrimental effects of thyroid dysfunction on pregnancy outcomes. Hypertension is one of the most important health problems related to both overt hypothyroidism and hyperthyroidism (1, 34) and to a lesser extent, to subclinical thyroid dysfunction (35). The prevalence of preeclampsia was 6.3% in our pregnant women. Its prevalence was 6%, 7.5%, and 0% in euthyroid mothers, mothers with hypothyroidism, and mothers with hyperthyroidism, respectively. Although the prevalence of preeclampsia was higher in pregnant women with hypothyroidism, this difference was not statistically significant. A few investigations have reported that overt hypothyroidism increases the incidence of preeclampsia (8, 9); however most of the studies showed no significant association (1, 3, 7). Prevalence of preterm delivery was 13%, 21%, and 11.1% in euthyroid mothers, mothers with hypothyroidism, and mothers with hyperthyroidism, respectively. We have found that thyroid dysfunction did not associate with preterm delivery. Spontaneous abortion and preterm delivery have been reported in 17% to 31% of all pregnancies (36, 37). The majority of them have no known risk factor (6). One of the known risk factors is clinical or subclinical hypothyroidism (38-40). Allan et al. showed that TSH level > 6 mIU/L was significantly associated with a higher frequency of pregnancy loss (39); however, one recent study showed no significant associations between TSH level and the risk of preterm delivery (41). We showed that the association of clinical hypothyroidism and preterm delivery might be due to secondary confounding factors such as maternal BMI, age, and preeclampsia. Our study showed that both hyperthyroidism and hypothyroidism are associated with IUGR. A subclinical hypothyroidism of mother increases the risk of IUGR by 2.18 times. Overt hyperthyroidism increases the risk of IUGR for about 4.57 times. Consistent with our results, previous reports revealed that subclinical hypothyroidism was associated with IUGR (5, 8, 42). It might be due to the essential role of thyroid hormones in growth and maturation of many tissues of the fetus like the brain, bones, and muscles (43). We revealed that hypothyroidism is associated with low Apgar score and mothers with subclinical hypothyroid have 2.15 times greater risk for having low Apgar score neonates. Consistent with our results, Goel et al. showed a higher risk of fetal distress in mothers with subclinical or clinical hypothyroidism (44). It seems that hypothyroidism exerts irreversible influences on the placenta and fetus during pregnancy and decreases the fetal ability to tolerate stress and therefore, neonates present with low Apgar scores at birth (45). Thyroid peroxidase antibody was not evaluated, which was a limitation to our study. Therefore, future studies should evaluate thyroid autoantibodies in addition to TFT. In our study, we found that the hypothyroidism during pregnancy, even in subclinical form, could cause IUGR and low Apgar score. Although prevalence of hyperthyroidism in our pregnant women was very low, it could be associated with IUGR. Interventional studies are required to determine whether early diagnosis and treatment of thyroid diseases, even in the subclinical form, prevent their adverse effect on the fetus in Iranian pregnant women.
References
-
1.
Thyroid dysfunction and autoantibodies during pregnancy as predictive factors of pregnancy complications and maternal morbidity in later life.
-
2.
The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology.
-
3.
Thyroid dysfunction and autoantibodies in early pregnancy are associated with increased risk of gestational diabetes and adverse birth outcomes.
-
4.
Thyroid associated components in serum during normal pregnancy.
-
5.
Maternal thyroid function in the first twenty weeks of pregnancy and subsequent fetal and infant development: a prospective population-based cohort study in China.
-
6.
Maternal thyroid disease and preterm delivery.
-
7.
Neonatal outcomes and birth weight in pregnancies complicated by maternal thyroid disease.
-
8.
Overt and subclinical thyroid dysfunction among Indian pregnant women and its effect on maternal and fetal outcome.
-
9.
Thyroid autoimmunity and hypothyroidism before and during pregnancy.
-
10.
Epidemiology and prevention of clinical and subclinical hypothyroidism.
-
11.
Thyroid disorders of pregnancy.
-
12.
Perinatal outcome in hypothyroid pregnancies.
-
13.
Hyperthyroidism in pregnancy.
-
14.
Low birth weight and preeclampsia in pregnancies complicated by hyperthyroidism.
-
15.
Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum.
-
16.
Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society Clinical Practice Guideline.
-
17.
Subclinical hypothyroidism during pregnancy: position statement from the American Association of Clinical Endocrinologists.
-
18.
Tandem mass spectrometry improves the accuracy of free thyroxine measurements during pregnancy.
-
19.
Neonatal thyroid status in an area of iodine sufficiency.
-
20.
Experiences in the prevention, control and elimination of iodine deficiency disorders: a regional perspective.
-
21.
Diagnosis and management of gestational hypertension and preeclampsia.
-
22.
New definition of small for gestational age based on fetal growth potential.
-
23.
Determinants of low birth weight: methodological assessment and meta-analysis.
-
24.
Epidemiology and causes of preterm birth.
-
25.
The Apgar score has survived the test of time.
-
26.
Trimester-specific reference ranges for thyroid hormones in Iranian pregnant women.
-
27.
Establishment of reference range for thyroid hormones in normal pregnant Indian women.
-
28.
Establishment of the trimester-specific reference range for free thyroxine index.
-
29.
The reference range and within-person variability of thyroid stimulating hormone during the first and second trimesters of pregnancy.
-
30.
Evaluation of maternal thyroid function during pregnancy: the importance of using gestational age-specific reference intervals.
-
31.
Reference intervals for thyroid hormones in pregnant Chinese women.
-
32.
Gestation-specific thyroxine and thyroid stimulating hormone levels in the United States and worldwide.
-
33.
Ethnic differences in maternal thyroid parameters during pregnancy: the Generation R study.
-
34.
Effects of thyroid hormone on the cardiovascular system.
-
35.
Subclinical thyroid dysfunction and blood pressure: a community-based study.
-
36.
A prospective study of early pregnancy loss.
-
37.
Incidence of early loss of pregnancy.
-
38.
Overt and subclinical hypothyroidism complicating pregnancy.
-
39.
Maternal thyroid deficiency and pregnancy complications: implications for population screening.
-
40.
Circulating thyroid hormone concentrations and placental thyroid hormone receptor expression in normal human pregnancy and pregnancy complicated by intrauterine growth restriction (IUGR).
-
41.
The thyroid and pregnancy: a novel risk factor for very preterm delivery.
-
42.
Subclinical hypothyroidism and pregnancy outcomes.
-
43.
Long-term growth in juvenile acquired hypothyroidism: the failure to achieve normal adult stature.
-
44.
Maternal and perinatal outcome in pregnancy with hypothyroidism.
-
45.
Perinatal outcome of children born to mothers with thyroid dysfunction or antibodies: a prospective population-based cohort study.