Association between maternal thyroid function and risk of gestational hypertension and pre-eclampsia: a systematic review and individual-participant data meta-analysis

Toloza, Freddy J.K.; Derakhshan, Arash; Männistö, Tuija; Bliddal, Sofie; Popova, Polina; Carty, David; Chen, Liangmiao; Taylor, Peter; Mosso, Lorena; Oken, Emily; Suvanto, Eila; Itoh, Sachiko; Kishi, Reiko; Bassols, Judit; Auvinen, Juha; López‐Bermejo, Abel; Brown, Suzanne J.; Boucai, Laura; Hisada, Aya; Yoshinaga, Jun; Shilova, Ekaterina S.; Grineva, Elena; Vrijkotte, Tanja G. M.; Sunyer, Jordi; Jiménez-Zabala, Ana; Riaño‐Galán, Isolina; Lopez-Espinosa, Maria-José; Prokop, Larry J.; Ospina, Naykky Singh; Brito, Juan P.; Rodríguez-Gutiérrez, René; Alexander, Erik K.; Chaker, Layal; Pearce, Elizabeth N.; Peeters, Robin P.; Feldt‐Rasmussen, Ulla; Guxens, Mònica; Chatzi, Leda; Delles, Christian; Lennep, Jeanine E. Roeters van; Pop, Victor J M; Lu, Xuemian; Walsh, John P.; Nelson, Scott M.; Korevaar, Tim I M; Maraka, Spyridoula

doi:10.1016/s2213-8587(22)00007-9

Cited by 64 publications

(58 citation statements)

References 74 publications

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“…It is important to communicate these risks in absolute numbers rather than a relative form and highlight that it remains more likely for the outcome to not occur, because the psychological stress from a ‘thyroid diagnosis’ can sometimes outweigh any risks related to the underlying lab abnormality. Moreover, there is no data to suggest that TPOAb positivity is associated with other adverse pregnancy outcomes such as pre-eclampsia or (abnormal) birth weight [ 18 , 19 ]. There are some positive and some negative studies on the association of maternal TPOAb positivity and child IQ [ 20 , 21 ], but those data are too sparse and heterogeneous to draw any conclusions from at this time.…”

Section: Risk Of Adverse Outcomesmentioning

confidence: 99%

Euthyroid Thyroperoxidase Antibody Positivity during Pregnancy, to Treat or Not to Treat?

Korevaar¹

2022

Endocrinol Metab

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Thyroperoxidase antibody (TPOAb) positivity is a well-known risk factor for thyroid dysfunction during pregnancy and is associated with a suboptimal response to thyroidal stimulation by human chorionic gonadotropin. About 75% of TPOAb positive women are euthyroid and there seems to be a higher risk of predominantly miscarriage and preterm birth in this subgroup. Nonetheless, clinical decision making with regards to gestational levothyroxine treatment remains difficult due to a lack of large randomized trials. Future studies assessing dose-dependent associations and additional biomarkers that can distinguish low-risk from high-risk individuals will be key in disentangling the crude clinical data.

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Section: Risk Of Adverse Outcomesmentioning

confidence: 99%

Euthyroid Thyroperoxidase Antibody Positivity during Pregnancy, to Treat or Not to Treat?

Korevaar¹

2022

Endocrinol Metab

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“…Individual-participant data meta-analyses of cohorts which included >40 000 mother−child pairs showed no effect of maternal subclinical hyperthyroidism on risks for preterm birth, small-for-gestational-age infants, preeclampsia, or gestational hypertension [21,22 ▪▪ ,23 ▪▪ ]. Both a higher and a lower TSH level were associated with a higher risk of preeclampsia whereas FT4 concentrations were not related to the outcomes measured [23 ▪▪ ]. Overall, current evidence suggests that mild thyroid hormone over-replacement is unlikely to confer significant obstetric risks.…”

Section: Effects Of Overtreating Maternal Hypothyroidism During Pregn...mentioning

confidence: 90%

“…A landmark cohort study assessing 25 765 women with singleton pregnancies found that subclinical hyperthyroidism was not associated with any adverse pregnancy outcomes [56]. Individual-participant data meta-analyses of cohorts which included >40 000 mother−child pairs showed no effect of maternal subclinical hyperthyroidism on risks for preterm birth, small-for-gestational-age infants, preeclampsia, or gestational hypertension [21,22 ▪▪ ,23 ▪▪ ]. Both a higher and a lower TSH level were associated with a higher risk of preeclampsia whereas FT4 concentrations were not related to the outcomes measured [23 ▪▪ ].…”

Section: Effects Of Overtreating Maternal Hypothyroidism During Pregn...mentioning

confidence: 99%

“…Meta-analyses of cohort studies have demonstrated increased risk of preterm birth, preeclampsia, pregnancy loss, placental abruption, premature rupture of membranes, infants born small for gestational age, and neonatal death in subclinically hypothyroid pregnant women (Table 1) [17,21,22 ▪▪ ,23 ▪▪ ]. A recent large-scale Chinese cohort study assessed preconception TSH levels in over 5.8 million women and found a J-shaped association: both low and high TSH levels (compared to the optimal preconception TSH range of 0.37–2.49 mIU/L) were associated with higher risks for preterm birth, infants born small for gestational age, and perinatal infant death [24 ▪ ].…”

Section: Indications For Treatment Of Maternal Thyroid Hypofunctionmentioning

confidence: 99%

“…A 2016 meta-analysis of 18 cohort studies reported increased risk for pregnancy loss (relative risk [RR] 2.01, 95% CI 1.66–2.44), placental abruption (RR 2.14, 95% CI 1.23–3.70), premature rupture of membranes (RR 1.43, 95% CI 1.04–1.95), and neonatal death (RR 2.58, 95% CI 1.41–4.73) in subclinically hypothyroid women compared to euthyroid women [48]. A series of individual participant-level data meta-analyses including 15 or more cohort studies and over 40 000 mother-child pairs have recently demonstrated that, compared to euthyroidism, subclinical hypothyroidism is associated with increased risk of preterm birth (OR 1.29, 95% CI 1.01–1.64) [21], small-for-gestational-age infants (OR 1.24, 95% CI 1.04–1.48) [22 ▪▪ ], lower mean birth weight (mean difference −38 g) [22 ▪▪ ], and higher risk of preeclampsia (OR 1.53, 95% CI 1.09–2.15) [23 ▪▪ ]. A single-blind randomized clinical trial in Iran assigned 366 TPO Ab negative subclinically hypothyroid women with TSH ranging 2.5–10.0 mIU/l to LT4 treatment (1 μg/kg/day) versus no treatment starting at 12 weeks’ gestation.…”

Section: Effects Of Undertreating Maternal Hypothyroidism During Preg...mentioning

confidence: 99%

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Under and overtreatment with thyroid hormone replacement during pregnancy

Peng

Maraka

Pearce

2022

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

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Purpose of review Among pregnant women on thyroid hormone replacement therapy undertreatment is common, while overtreatment is rare. Both deficient and excessive maternal thyroid hormone have been related to adverse maternofetal and long-term offspring outcomes, although studies' results are inconsistent. This review aims to discuss recent evidence regarding the effects of under-and overtreatment with thyroid hormone replacement during pregnancy and how current practices could be improved. Recent findingsWhether or not thyroid hormone therapy needs to be initiated for maternal subclinical hypothyroidism remains unclear, but recent meta-analyses have confirmed associations between adverse maternal, neonatal, and offspring outcomes in both overt and subclinical hypothyroidism. Subclinical hyperthyroidism in pregnancy is related to fewer adverse outcomes. Current adherence to levothyroxine during pregnancy and medication counseling by healthcare providers are suboptimal.

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Effects of treating subclinical hypothyroidism in pregnancy in India: Are we treating too many for little gain? A retrospective cohort study

Ram,

Thirunavukkarasu,

Shyam

et al. 2023

Intl J Gynecology & Obste

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ObjectiveTo assess the impact of treatment of subclinical hypothyroidism (SCH) on short‐term pregnancy outcomes.MethodData from 4526 consecutive women with singleton pregnancies who delivered between January 2015 and December 2017 were analyzed. SCH was defined as a thyroid‐stimulating hormone (TSH) level between 2.5 and 10 mU/mL with normal free thyroxine. Of those with SCH, some were treated but others were not. These two groups were compared using χ2 and Student t tests for categorical and continuous variables, respectively. Multiple logistic regression models, adjusted for maternal age, body mass index, parity, gestation at TSH measurement, and gestational diabetes mellitus status, were used to investigate the effect of treatment on pregnancy and neonatal outcomes.ResultsIn all, 1227 (27.1%) of 4526 women had SCH, of whom 393 (32.0%) were treated. The mean age and body mass index were similar in both groups. The mean gestation at measuring of TSH was 11.7 ± 6.5 weeks. There was no significant difference in pregnancy or neonatal outcomes between the two groups. A sub‐group analysis when SCH was defined as TSH 4.0 mU/mL or greater showed a higher rate of large for gestational age and lower rates of low birth weight and small for gestational age in the treated group.ConclusionsThe prevalence of SCH based on the international guidelines threshold is high in India. Treatment of SCH did not show any difference in pregnancy and neonatal outcomes in this study.

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Association between maternal thyroid function and risk of gestational hypertension and pre-eclampsia: a systematic review and individual-participant data meta-analysis

Cited by 64 publications

References 74 publications

Euthyroid Thyroperoxidase Antibody Positivity during Pregnancy, to Treat or Not to Treat?

Euthyroid Thyroperoxidase Antibody Positivity during Pregnancy, to Treat or Not to Treat?

Under and overtreatment with thyroid hormone replacement during pregnancy

Effects of treating subclinical hypothyroidism in pregnancy in India: Are we treating too many for little gain? A retrospective cohort study

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