Thyroid Function of Pregnant Women and Perinatal Outcomes in North Macedonia

Thyroid diseases are the second most common endocrine disorders in the reproductive period of women. They can be associated with intrauterine growth restriction (IUGR), preterm delivery, low Apgar score, low birthweight (LBW) or fetal death. The aim of the present study is to explore thyroid dysfunction and its relationship with some poor perinatal outcomes (Apgar Score, low birthweight, and preterm delivery).

Methods

Dried blood spot samples from 358 healthy pregnant women were analyzed for thyroid stimulating hormone (TSH), total thyroxine (TT4), and thyroglobulin (Tg). Neonatal data were collected upon delivery. Four groups were formed based on thyroid function tests (TFTs).

Results

Of the 358 tested women, 218 (60.72%) were euthyroid. Isolated hypo thyroxinemia was present in 132 women (36.76%), subclinical hyperthyroidism in 7 women (1.94%), and overt hypothyroidism in 1 (0.28%). The perinatal outcomes IUGR (p = 0.028) and Apgar score 1 minute (p = 0.015) were significantly different between thyroid function test [TFT]-distinct groups. In the multiple regression analysis, TT4 showed a statistically significant inverse predictive impact on LBW (p < 0.0001), but a positive impact of Tg on LBW (p = 0.0351).

Conclusion

Thyroid hormones alone do not have a direct impact on neonatal outcomes, but the percentage of their participation in the total process cannot be neglected. Based on the regression analysis, we can conclude that TT4 and Tg can be used as predictors of neonatal outcome, expressed through birthweight and Apgar score. The present study aims to contribute to determine whether a test for thyroid status should become routine screening during pregnancy.

Keywords:
thyroid stimulating hormone; total thyroxine; thyroglobulin; perinatal outcomes; low birth weight

Demographic values	n	% of total
1^st trimester	64	17.82%
2^nd trimester	100	27.85%
3^rd trimester	194	54.03%
	Mean ± SD	25^th – 75^th P(min - max)
Age (years old)	29.27 ± 5.5	25 - 33
BMI (kg/m²)	27.14 ± 4.7	23.44–29.63
Gestational week at birth	38.43 ± 2.54	37.7–40.0
Thyroid function values
TSH (mU/L)	0.54 ± 0.33	0.3–0.7
TT4 (nmol/L)	103.92 ± 28.7	24 - 195.2
Tg (µg/L)	11.6 ± 9.01	5.53–15.49

Group	TSH level	TT4 level	No. (%) of pregnant women in the group
1. Normal thyroid function	normal(0.1 to 3.7 mIU/L)	normal,slightly increased	218 (60.72%)
2. Isolated hypo thyroxinemia	normal(0.1 to 3.7 mIU/L)	depressed	132 (36.76%)
3. Subclinical hyperthyroidism	suppressed (<0.1 mIU/L)	normal	7 (1.94%)
4. Subclinical hypothyroidism	elevated (3 to 10 mIU/L)	normal	0 (0.0%)
5. Overt hypothyroidism	elevated (> 3.7 mIU/L)	low (for TSH < 10mIU/L)any level (for TSH ≥ 10 mIU/L	1 (0.27%)
6. Overt hyperthyroidism	suppressed (< 0.1 mIU/L)	high (or irrelevant)	0 (0.0%)

Groups	1	2	3	4
Mode of delivery	Normal thyroid function (n = 218)	Isolated hypothyroxinemia (n = 132)	Subclinical hyperthyroidism (n = 7)	Overt hypothyroidism (n = 1)	F	p-value
Normal spontaneous delivery	127 (58.25)	61 (46.21)	5 (71.42)	0	2.6975	0.068
CS total	91 (41.74)	71 (53.78)	2 (28.57)	1
- CS for fetal distress	28 (30.76)	10 (7.57)	1 (14.28)	1	1.1334	0.323
- CS for dystotia/dysproprtion	25 (27.47)	11(8.33)	1 (14.28)	0	4.175	0.024
Fetal outcomes
Preterm births	28 (12.84)	13 (9.84)	0	0	0.804	0.448
IUGR	9 (4.12)	3 (2.27)	0	0	3.594	0.028
LBW	29 (13.30)	17 (12.87)	1 (14.28)	0	0.517	0.597
Apgar score (1 minute) < 7	13 (5.96)	6 (4.54)	2 (28.57)	/	4.252	0.018
Mother characteristics
Median age (years old)	29	29	32	26	1.299	0.274
Median BMI, kg/m²	26.44	27.43	23.23	27.12	4.091	0.018

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[1] Address for correspondence Maja Avramovska, MD, PhD, Filip Vtori Makedonski 37/4/26, Bitola, North Macedonia (e-mail: dr.avramovska@gmail.com).

Dependent Y	LBW
Regression Equation
Independent variables	βst coefficient	Std. Error	t	*p-value*	r_partial	r_semipartial	exp (βst)
(Constant)	2.5225
TT4	- 0.01124	0.0009484	- 11.854	< 0.0001	- 0.5391	0.5388	0.98767
Tg	0.006294	0.002975	2.116	0.0351	0.1135	0.09616	1.00631
Significance level							p < 0.0001