Dataset Information

Association of Maternal Mild Hypothyroidism With Offspring Neurodevelopment in TPOAb-Negative Women: A Prospective Cohort Study

ABSTRACT:

Objectives

Adequate maternal thyroid hormone availability is crucial for fetal neurodevelopment, but the role of maternal mild hypothyroidism is not clear. We aim to investigate the association of maternal mild hypothyroidism with neurodevelopment in infants at 1 year of age among TPOAb-negative women.

Methods

The present study was conducted within the Jiangsu Birth Cohort. A total of 793 mother–infant pairs were eligible for the present study. Maternal thyroid function was assessed by measuring serum thyroid-stimulating hormone, free thyroxine, and thyroid peroxidase antibodies. Neurodevelopment of infants was assessed by using the Bayley Scales of Infant and Toddler Development third edition screening test (Bayley-III screening test).

Results

In the multivariate adjusted linear regression analyses, infants of women with subclinical hypothyroidism and isolated hypothyroxinemia were associated with decreased receptive communication scores (β = −0.68, p = 0.034) and decreased gross motor scores (β = −0.83, p = 0.008), respectively. Moreover, infants of women with high-normal TSH concentrations (3.0–4.0 mIU/L) and low FT4 concentrations were significantly associated with lower gross motor scores (β = −1.19, p = 0.032), while no differences were observed in infants when the mothers had a high-normal TSH concentration and normal FT4 levels.

Conclusions

Maternal subclinical hypothyroidism is associated with decreased receptive communication scores in infants at 1 year of age. In addition, maternal TSH concentration greater than 4.0 mIU/L and maternal isolated hypothyroxinemia are associated with impaired gross motor ability of infants, especially in infants of women with high-normal TSH concentrations (3.0–4.0 mIU/L).

SUBMITTER: Wang Q

PROVIDER: S-EPMC9278520 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionSubclinical hypothyroidism (SCH) during pregnancy is reported to have detrimental impact on pregnancy and child development. However, its treatment indications require further investigation in different thyroid peroxidase antibody (TPOAb) status.Material and methodsThis was a secondary analysis of a Chinese prospective cohort in a real-world setting. Pregnant women with gestational SCH were enrolled at the first antenatal visit and grouped by TPOAb positivity. Child neurodevelopment was assessed by the Gesell development diagnosis scale (GDDS) at one, three, six, 12, and 24 months of age. Subgroup analyses and sensitivity analyses were also conducted.Clinical trial registrationClinicalTrials.gov NCT01744743.ResultsFrom January 2012 to December 2013, a total of 171 participants were enrolled, including 116 of SCH with TPOAb negative (SCH-TPOAb [-]) and 55 of SCH with TPOAb positive (SCH-TPOAb [+]). Compared to women in the SCH-TPOAb (+) group, those in the SCH-TPOAb (-) group had lower thyroid-stimulating hormone (TSH) levels at enrollment and 12-16+6 gestational weeks, and unexpectedly higher TSH levels at 30-34+6 gestational weeks and delivery, with a correspondingly lower levothyroxine dosage throughout pregnancy (all p < 0.05). Offspring in the SCH-TPOAb (-) group displayed lower GDDS scores at one year old than did their counterparts (adjusted p < 0.05), which was possibly related to the worse thyroid function control of maternal SCH-TPOAb (-). No statistically significant difference was found in the GDDS assessments of children at one, three, six, and 24 months of age. These results were also confirmed in subgroup analyses stratified by maternal thyroid characteristics at enrollment, namely TSH levels, free levothyroxine (T4 ) levels, and anti-thyroglobulin antibody (TgAb) status, as well as in sensitivity analyses excluding participants with no levothyroxine treatment at enrollment.ConclusionsIn the current clinical practice, infants born to mothers with SCH-TPOAb (-) displayed slightly lower neurodevelopmental scores at one year old than did those born to mothers with SCH-TPOAb (+) but this difference was not seen at two years.

Project description:BackgroundAnti-thyroid peroxidase antibody (TPOAb) positivity can contribute to inhibit thyroxine synthesis. Gut microbiota can interact with metabolic or immune diseases. However, dynamics of gut microbiota from the second (T2) to the third trimester (T3) in women with TPOAb-positive/negative subclinical hypothyroidism (TPOAb+/TPOAb- SCH) have not been reported. Therefore, we aimed to evaluate whether gut microbiota can be potential therapeutic targets for managing TPOAb+ SCH.MethodsIn this single-center prospective cohort study, we observed gut microbiota dynamics by sequencing 16S rRNA from fecal samples collected in T2 (20-23+ 6 weeks) and T3 (28-33+ 6 weeks). TPOAb+/TPOAb- SCH were stratified depending on whether or not they used levothyroxine (LT4) during the pregnancy (LT4+/LT4-). Microbiome bioinformatics analyses were performed using QIIME2. The linear discriminant analysis effect size (LEfSe) was used for the quantitative analysis of biomarkers. Functional profiling was performed with PICRUSt2.ResultsDistinct gut microbiota dynamics from T2 to T3 were noted in the TPOAb- (n = 68) and TPOAb+ (n = 64) SCH groups. The TPOAb+ LT4- group was characterized by enriched bacterial amplicon sequence variants (ASVs) of Prevotella in T2 and Bacteria, Lachnospirales, Lachnospiraceae, Blautia, and Agathobacter in T3 and by depleted ASVs of Gammaproteobacteria, Enterobacterales, and Enterobacteriaceae in T2 and Actinobacteriota, Coriobacteriia, Actinobacteria, Coriobacteriales, Bifidobacteriales, Bifidobacteriaceae, Bifidobacterium, Dorea formicigenerans, and Bifidobacterium longum in T3. The TPOAb+ LT4+ group was characterized by enriched bacterial ASVs of Blautia, Streptococcus salivarius, and Bifidobacterium longum in T3 and by depleted ASVs of Bacteroidota, Bacteroidia, Bacteroidales, and Prevotella in T2 and Agathobacter in T3. Moreover, we identified 53 kinds of metabolic functions that were mainly involved in sugar, lipid, and amino acid metabolism.ConclusionsOur results indicated that low dynamics of gut microbiota composition and high dynamics of its metabolic function from T2 to T3 were associated with TPOAb+ SCH. We concluded that gut microbiota could be new targets for treatment of TPOAb+ SCH during pregnancy.Trial registrationThis study was retrospectively registered at the Chinese Clinical Trial Registry (registration number ChiCTR2100047175 ) on June 10, 2021.

Project description:BackgroundIron plays a role in many key processes in the developing brain. During pregnancy, iron supplementation is widely recommended to prevent and treat iron deficiency; however, the prevalence of iron deficiency and the risk of iron overload vary greatly between populations. Evidence on the role of high levels of maternal ferritin, a storage iron marker during pregnancy in relation to offspring neurodevelopment is lacking.ObjectiveOur main objective was to examine if maternal ferritin levels during pregnancy are associated with child cognitive and motor abilities.MethodsWe included Dutch mother-child dyads from the prospective population-based Generation R Study, born in 2002-2006. We compared children whose mothers had high (standard deviation score >+1) or low (standard deviation score <-1) early-pregnancy ferritin to children whose mothers had intermediate ferritin (reference group) using linear regression. Children underwent non-verbal intelligence and language tests at 4-9 years (cognitive abilities), finger-tapping and balancing tests at 8-12 years (motor abilities), and structural magnetic resonance imaging at 8-12 years (brain morphology). Covariates were child age, sex, maternal intelligence quotient estimate, age, body-mass-index, education, parity, smoking and alcohol use.ResultsOf the 2479 mother-child dyads with data on maternal ferritin and at least one child neurodevelopmental outcome, 387 mothers had low (mean = 20.6 µg/L), 1700 intermediate (mean = 64.6 µg/L) and 392 high (mean = 170.3 µg/L) early-pregnancy ferritin. High maternal ferritin was associated with 2.54 points (95% confidence interval -4.16, -0.92) lower child intelligence quotient and 16.02 cm3 (95% confidence interval -30.57, -1.48) smaller brain volume. Results remained similar after excluding mothers with high C-reactive protein. Low maternal ferritin was not associated with child cognitive abilities. Maternal ferritin was unrelated to child motor outcomes.ConclusionHigh maternal ferritin during pregnancy was associated with poorer child cognitive abilities and smaller brain volume. Maternal iron status during pregnancy may be associated with offspring neurodevelopment.

Project description:Pregnant women are at high risk of developing subclinical hypothyroidism (SCH), and anti-thyroid peroxidase antibody (TPOAb) positivity can further inhibit thyroxine synthesis. Emerging evidence indicates that intestinal flora can modulate metabolic and immune homeostasis. The characteristics of intestinal flora of TPOAb-positive women with SCH in their second trimester of pregnancy have not been reported. This single-center prospective observational cohort study investigated gut microbial composition and metabolic function using sequencing of the 16S rRNA gene in fecal samples from 75 TPOAb-positive women with SCH and 90 TPOAb-negative women with SCH during their second trimester of pregnancy. Women were treated with no levothyroxine (LT4), low-dose LT4 (≤50ug/d), or high-dose LT4 (>50ug/d). Taxonomic analysis showed Firmicutes and Bacteroidetes were the dominant phyla, followed by Actinobacteria and Proteobacteria. Faecalibacterium, Bacteroides, Prevotella 9, Bifidobacterium, Subdoligranulum, Lachnospira, and Megamonas were the predominant genera. The intestinal flora of TPOAb-positive women with SCH who received no LT4 was characterized by bacterial amplicon sequence variants (ASVs)/operational taxonomic units (OTUs) enriched in the genus Subdoligranulum. The intestinal flora of TPOAb-positive women with SCH who received low-dose or high-dose LT4 were characterized by bacterial ASVs/OTUs depleted of the species Ruminococcus sp._or Bacteroides massiliensis, respectively. A total of 19 metabolic functions of intestinal flora, mainly involving lipid and amino acid metabolism, discriminated TPOAb-positive and TPOAb-negative women with SCH. Our study suggests that there are differences in the composition and metabolic function of intestinal flora of TPOAb-positive and TPOAb-negative women with SCH treated with different doses of LT4 in the second trimester of pregnancy. The findings provide insight into intestinal flora as novel targets for the treatment of TPOAb-positive women with SCH during pregnancy.

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