TSH elevation associated with pregnancy problems

TSH (thyroid stimulating hormone) when elevated even within the 'normal' range at preconception, can result in adverse pregnancy outcomes. Further evidence for this was presented in a study, recently published in Clinical Endocrinology, that examines whether subclinical hypothyroidism (SCH) has negative effects on pregnancy.

"Subclinical hypothyroidism (SCH), defined as elevated TSH and normal free T4 (fT4) levels, with an incidence of 2–13·7%, is the most common thyroid disorder during pregnancy. SCH has also been associated with adverse foeto-maternal outcomes..."

Thyroid hormone levels before pregnancy

Adverse effects of SCH during the first trimester and after have been documented in earlier studies, but there has been much less data for preconception thyroid hormone levels.

"To the best of our knowledge, this study was the first large-scale study to investigate the association between maternal TSH levels within the 6 months before conception and the risk of adverse pregnancy outcomes in a population at low risk. The second aim was to determine whether the first-trimester specific reference range or nonpregnant reference range for TSH should be applied during preconception evaluation."

This was a large study, with 248,501 pairs of volunteer couples recruited from a free National Pre-pregnancy Checkups Project from 2010 to 2012 in China, out of which 184,611 women who later became pregnant were examined by measuring maternal thyroid stimulating hormone within 6 months before conception.

"Participants were grouped according to TSH: 0·48–2·49 mIU/l (n = 133 232, 72%), 2·50–4·28 mIU/l (n = 44 239, 24%) and 4·29–10·0 mIU/l (n = 7140, 4%). Multivariable logistic regression models were used to study the association between TSH and pregnancy outcomes."

Preconception TSH elevation increases risk of adverse pregnancy outcomes

Even when within what is often still considered the normal non-pregnant range, thyroid stimulating hormone elevation predicted pregnancy problems.

"The overall incidence of adverse pregnancy outcomes was 28·6%. Compared with TSH 0·48–2·50 mIU/l, TSH 2·50–4·29 mIU/l was associated with spontaneous abortion [aOR: 1·10,], preterm birth (aOR: 1·09) and operative vaginal delivery (aOR: 1·15, 95% CI: 1·09–1·21), while TSH 4·29–10 mIU/l was correlated with spontaneous abortion (aOR: 1·15), stillbirth (aOR: 1·58), preterm birth (aOR: 1·20), caesarean section (aOR: 1·15) and large for gestational age (LGA) infants (aOR: 1·12)."

The authors discuss the implication of these odds ratios that are small yet significant.

"The present study involving 194 154 subjects demonstrated that preconception high TSH was associated with a small but significant increased risk of overall adverse pregnancy outcomes, including spontaneous abortion, preterm birth and LGA infants, regardless of whether we used first-trimester-specific upper limit (2·50 mIU/l) or nonpregnant reference upper limit (4·29 mIU/l). Our data support that women planning a pregnancy within 6 months should be regarded as 'pregnant status' and that closer observation may be required once TSH levels exceed 2·50 mIU/l, rather than the nonpregnant reference upper limit."

Clinicians should also bear in mind:

"Borderline TSH elevation has been shown to portend deleterious impacts on various pregnancy outcomes. In the present study, we found that the higher the preconception TSH, the higher the incidence of adverse pregnancy outcomes. This was concordant with other studies, although they measured TSH during pregnancy, rather than before conception. Thyroid hormones themselves directly affect foetal development and utero-placental maturation; hence, maternal hypothyroidism can influence pregnancy outcomes, especially in early gestation."

Regarding case management, the authors conclude:

"...preconception high TSH levels were associated with a small but significant increased risk of overall adverse events, including preterm birth, CS delivery and LGA infants, even within normal nonpregnant range. TSH <2·5 mIU/l is more suitable for the assessment of women planning a pregnancy in China, but one should not make a hasty decision to initiate treatment at this point without repeating TSH measurement and checking TPO antibody status. Prospective randomized controlled trials examining the role of levothyroxine supplement in mildly hypothyroid prepregnant women are warranted in the future."

See also Subclinical hypothyroidism in pregnancy.