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Meta-Analysis
. 2018 Apr;88(4):575-584.
doi: 10.1111/cen.13550. Epub 2018 Feb 8.

Maternal thyroid hormone insufficiency during pregnancy and risk of neurodevelopmental disorders in offspring: A systematic review and meta-analysis

William Thompson  1 , Ginny Russell  2   3 , Genevieve Baragwanath  4 , Justin Matthews  1   3 , Bijay Vaidya  4   5 , Jo Thompson-Coon  1
Affiliations
Meta-Analysis

Maternal thyroid hormone insufficiency during pregnancy and risk of neurodevelopmental disorders in offspring: A systematic review and meta-analysis

William Thompson et al. Clin Endocrinol (Oxf). 2018 Apr.

Abstract

Background: In the last 2 decades, several studies have examined the association between maternal thyroid hormone insufficiency during pregnancy and neurodevelopmental disorders in children and shown conflicting results.

Aim: This systematic review aimed to assess the evidence for an association between maternal thyroid hormone insufficiency during pregnancy and neurodevelopmental disorders in children. We also sought to assess whether levothyroxine treatment for maternal thyroid hormone insufficiency improves child neurodevelopment outcomes.

Methods: We performed systematic literature searches in MEDLINE, EMBASE, PSYCinfo, CINAHL, AMED, BNI, Cochrane, Scopus, Web of Science, GreyLit, Grey Source and Open Grey (latest search: March 2017). We also conducted targeted web searching and performed forwards and backwards citation chasing. Meta-analyses of eligible studies were carried out using the random-effects model.

Results: We identified 39 eligible articles (37 observational studies and 2 randomized controlled trials [RCT]). Meta-analysis showed that maternal subclinical hypothyroidism and hypothyroxinaemia are associated with indicators of intellectual disability in offspring (odds ratio [OR] 2.14, 95% confidence interval [CI] 1.20 to 3.83, P = .01, and OR 1.63, 95% CI 1.03 to 2.56, P = .04, respectively). Maternal subclinical hypothyroidism and hypothyroxinaemia were not associated with attention deficit hyperactivity disorder, and their effect on the risk of autism in offspring was unclear. Meta-analysis of RCTs showed no evidence that levothyroxine treatment for maternal hypothyroxinaemia or subclinical hypothyroidism reduces the incidence of low intelligence quotient in offspring.

Limitations: Although studies were generally of good quality, there was evidence of heterogeneity between the included observational studies (I2 72%-79%).

Conclusion: Maternal hypothyroxinaemia and subclinical hypothyroidism may be associated with intellectual disability in offspring. Currently, there is no evidence that levothyroxine treatment, when initiated 8- to 20-week gestation (mostly between 12 and 17 weeks), for mild maternal thyroid hormone insufficiency during pregnancy reduces intellectual disability in offspring.

Keywords: autism; hypothyroxinaemia; intelligent quotient; pregnancy; subclinical hypothyroidism; thyroid.

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Figures

Figure 1
Figure 1
The PRISMA diagram showing search strategy and exclusion criteria at each step
Figure 2
Figure 2
Meta‐analysis of studies on association between maternal subclinical hypothyroidism and indicators of intellectual disability in offspring. ES, Odds ratio point estimate; negative association, trait associated with decreased odds of neurodevelopmental impairment; positive association, trait associated with increased odds of neurodevelopmental impairment
Figure 3
Figure 3
Meta‐analysis of studies on association between maternal hypothyroxinaemia and indicators of intellectual disability in offspring. ES, Odds ratio point estimate; negative association, trait associated with decreased odds of neurodevelopmental impairment; positive association, trait associated with increased odds of neurodevelopmental impairment
Figure 4
Figure 4
Meta‐analysis of RCTs on the effect of levothyroxine treatment for maternal subclinical hypothyroidism and hypothyroxinaemia on IQ of offspring. ES, Odds ratio point estimate; negative association, trait associated with decreased odds of neurodevelopmental impairment; positive association, trait associated with increased odds of neurodevelopmental impairment
See this image and copyright information in PMC

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