Medical treatment in pregnant women with subclinical hypothyroidism: systematic review and meta-analysis

Abuhadba-Cayao, Katia Andrea; Talavera, Jesús E.; Vera-Ponce, Víctor Juan; Cruz-Vargas, Jhony A. De La

doi:10.1590/1806-9304202200020003

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REVIEW • Rev. Bras. Saude Mater. Infant. 22 (2) • Apr-Jun 2022 • https://doi.org/10.1590/1806-9304202200020003 copy

Medical treatment in pregnant women with subclinical hypothyroidism: systematic review and meta-analysis

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objectives:

to determine the effectiveness of medical therapy in reducing complications associated with subclinical hypothyroidism during pregnancy.

Methods:

in 2021, a systematic review of available cohort studies was carried out in three databases, with no publication date limit. Study selection and data extraction were performed in duplicate. Random-effects meta-analysis was performed, and odds ratios were calculated, with the corresponding 95% confidence intervals. Cohort risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). The certainty of the evidence was assessed using the GRADE methodology.

Results:

five studies were included for qualitative and quantitative synthesis. A statistically significant relationship was found between medical treatment in pregnant women with subclinical hypothyroidism with respect to spontaneous abortion (p=0.03; OR=0.77; CI95%=0.61-0.97), and no statistically significant relationship was found for delivery preterm (p=0.46; OR=1.11; CI95%=0.85-1.44), nor for abrupt placentae (p=0.56; OR=1.60; CI95%=0.33-7.66). Three studies were at moderate risk of bias, and two were at low risk of bias. In all the results the certainty was very low.

Conclusions:

medical treatment of subclinical hypothyroidism during pregnancy can have a beneficial effect in reducing cases of spontaneous abortion.

Key words:
Subclinical hypothyroidism; Thyroxine; Preterm labor; Placental abruption; Miscarriage

Author (Country)	Average age, inclusion or exclusion criteria	Population^* * Population: Pregnant women diagnosed with subclinical hypothyroidism; ** Definition of subclinical hypothyroidism: elevated TSH concentration (greater than 2.5mlU/L) with concurrent normal thyroid hormone concentrations.	Intervention	Control	Follow-up	Outcome	Funding	Conflict of interest
Bernardi et al.¹⁶16 Bernardi LA, Cohen RN, Stephenson MD. Impact of subclinical hypothyroidism in women with recurrent early pregnancy loss. Fertil Steril. 2013 Aug; 100 (5): 1326-31.	(EEUU)	• Age 22-42 years. • Inclusion criteria: history of miscarriage <10s gestation. • Exclusion criteria: multiple pregnancies, miscarriage due to chromosomopathies.	I: 69 C:221 I₁:24 I₂:15	I: SCHC: Euthyroid l₁:SCH-levothyroxine l₂:SCH-No treatment	Prenatal checkups	Immediate	• Spontaneous abortion • Preterm labor	University of Chicago	Undeclared
Maraka et al.⁴4 Maraka S, Mwangi R, McCoy RG, Yao X, Sangaralingham LR, Ospina NMS, et al . Thyroid hormone treatment among pregnant women with subclinical hypothyroidism: US national assessment. BMJ. 2017 Jan; 356: i6865.	(EEUU)	• Age: 18-55 years. • Inclusion criteria: diagnosis before 4 weeks after the first checkup or 3 months later. • Exclusion criteria: women without health insurance coverage, multiple gestations.	I:843 C:4562	I: SCH-levothyroxine C: SCH-No treatment	Prenatal checkups	Immediate	• Spontaneous abortion • Preterm labor •Abruptio placentae	Self-financed	All authors have completed the ICMJE uniform disclosure form.
Nazarpour et al.⁷7 Nazarpour S, Tehrani FR, Simbar M, Tohidi M, Minooee S, Rahmati M, et al. Effects of levothyroxine on pregnant women with subclinical hypothyroidism, negative for thyroid peroxidase antibodies. J Clin Endocrinol Metab. 2018 Mar; 103 (3): 926-35.	(Irán)	• Age 27 years. • Inclusion criteria: having been part of the ehran Thyroid and Pregnancy Study • Exclusion criteria: multigestation, TPOAb+	I: 183 C:183	I: SCH-levothyroxine C: SCH-No treatment	Prenatal checkups	During gestation	• Pretermdelivery •Abruptioplacentae	Research Institute for Endocrine Sciences	No conflict of interest
Sharmeen et al.¹⁷17 Sharmeen M, Shamsunnahar PA, Laita TR, Chowdhury SB. Overt and subclinical hypothyroidism among Bangladeshi pregnant women and its effect on the fetomaternal outcome. Bangladesh Med Res Counc Bull. 2014 Aug; 40 (2): 52-7.	(Bangladesh)	• Age 15-44 years • Inclusion criteria: diagnosis within 6 months prior to the study. • Exclusion criteria: multigestation, chronic pathologies.	I: 29 C:21 I₁:26 I₂:3	I: SCHC: Euthyroid l₁:SCH-levothyroxine l₂:HSC-No treatment	Prenatal checkups	During gestation	• Spontaneous abortion	Self-financed	Undeclared
Wang et al.¹⁵15 Wang S, Teng WP, Li JX, Wang WW, Shan ZY. Effects of maternal subclinical hypothyroidism on obstetrical outcomes during early pregnancy. J Endocrinol Invest. 2012 Mar; 35 (3): 322-5.	(China)	• Age: 19-45 years. • Inclusion criteria: first trimester pregnant. • Exclusion criteria: multigestation, chronic pathologies.	I: 168 C:542 l₁:28 I₂:168	I: SCHC: Euthyroid l₁:SCH-levothyroxine l₂:SCH-No treatment	Prenatal checkups	During gestation	• Spontaneous abortion • Preterm delivery	Self-financed	Undeclared

Certainty assessment		No. of patients		Effect		Certainty
No. of studies	Study design	Medical treatment treatment	No medical	Relative	Absolute
No. of studies	Study design	Medical treatment treatment	No medical	(CI95%)	(CI95%)
Spontaneous abortion
3	Observational studies	105/893 (11.8%)	619/4580 (13.5%)	OR=0.77	28 less per 1000	⊕OOO
3	Observational studies	105/893 (11.8%)	619/4580 (13.5%)	(0.61 - 0.97)	(from 48 minus to 4 minus)	VERY LOW
Preterm delivery
3	Observational studies	78/1166 (6.7%)	265/4773 (5.6%)	OR=1.11	6 less per 1000	⊕OOO
3	Observational studies	78/1166 (6.7%)	265/4773 (5.6%)	(0.85 - 1.44)	(from 8 minus to 23 more)	VERY LOW
Abrupto placentae
2	Observational studies	10/1026 (1.0%)	36/4745 (0.8%)	OR=1.60	4 more per 1000	⊕OOO
2	Observational studies	10/1026 (1.0%)	36/4745 (0.8%)	(0.33 - 7.66)	(from 5 minus to 48 more)	VERY LOW

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[1] Authors’ contribution

Abuhadba-Cayao KA, Talavera JE, Vera-Ponce VJ, and De La Cruz-Vargas JA contributed significantly to the conception, design, analysis, and interpretation of the data. Abuhadba-Cayao KA, Vera-Ponce VJ and De La Cruz-Vargas JA made relevant contributions to the methodology of the article. Abuhadba-Cayao KA and Talavera JE prepared the first draft of the manuscript. All authors reviewed the entire manuscript and approved the final version.

The authors declare not to have any interest conflicts.