Association Between Neonatal Thyroid Function and Anogenital Distance from Birth to 48 Months of Age

BackgroundEvidence from animal studies has indicated that neonatal thyroid function is vital for the reproductive development. Anogenital distance (AGD), a sensitive biomarker of the fetal hormonal milieu, can be used to predict adult reproductive disorders. However, few human studies have examined the association between neonatal thyroid function and AGD. We aimed to explore their associations in a birth cohort study.MethodsConcentrations of thyroid stimulating hormone (TSH) and thyroid hormones (THs), including total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), and free thyroxine (FT4) were measured in cord plasma in the Shanghai-Minhang Birth Cohort. The offspring AGD (AGDAP [anus–penis] and AGDAS [anus–scrotum] for boys and AGDAC [anus–clitoris] and AGDAF [anus–fourchette] for girls), body weight and anogenital index (AGI = AGD/weight [mm/kg]) were obtained at each follow-up visit. In total, 344 children (194 boys and 150 girls) with cord plasma concentrations of THs and TSH and at least one AGD measurement at birth and at 6, 12, and 48 months of age were included. Multiple linear regression and generalized estimating equation (GEE) models were used to examine the associations of cord plasma concentrations of THs and TSH with AGI.ResultsMultiple linear regression models showed inverse associations of TT4, FT3, and FT4 with female AGI, although statistical significance was only reached at birth, 6 and 48 months of age. These associations were also found in GEE models: higher TT4 and FT4 concentrations were associated with lower AGIAC (TT4: β = -0.27, 95% CI: -0.50, -0.03 for middle vs. lowest tertile; FT4: β = -0.38, 95% CI: -0.61, -0.16 for middle and β = -0.30, 95% CI: -0.55, -0.04 for highest vs. lowest tertile). Besides, girls with the highest tertile of FT3 concentrations had lower AGIAF than those with the lowest tertile (the highest vs. lowest tertile: β = -0.22, 95% CI: -0.36, -0.08). Positive associations between TSH and AGI at birth and at 12 months of age were observed in boys.ConclusionsThis study provides further evidence on the effects of neonatal thyroid function on reproductive development at an early life stage.

Iodine contrast prior to or during pregnancy and neonatal thyroid function: a systematic review

Objective Thyroid dysfunction is a known side effect of iodinated contrast media. There is some evidence to suggest that iodinated contrast media administered to pregnant women may cause thyroid dysfunction not only in themselves but also in their offspring. Here, we systematically evaluated literature on the use of iodinated contrast media prior to or during pregnancy on the offspring’s thyroid function. Design Systematic review of published literature. Materials and methods Relevant studies were identified by PubMed, EMBASE and The Cochrane Library up to June 5, 2020. All study designs, reporting on the foetal or neonatal thyroid function after exposure to iodinated contrast media prior to or during pregnancy, were included. We undertook random effects meta-analysis and pooled the estimates as proportions with 95% CIs. Results We identified 402 articles, of which 26 were included. Six studies reported (n = 369) on exposure to iodinated contrast media prior to pregnancy by hysterosalpingography and 20 studies (n = 670) on exposure to these media during pregnancy by amniofetography, urography or CT. There was low to high risk of bias. The proportion of (transient) neonatal thyroid dysfunction was 0.0% (95% CI: 0.0–2.9% based on 3 studies) for hysterosalpingography, 2.25% (95% CI: 0.03–6.55% based on 2 studies) for amniofetography and 0.0% (95% CI: 0.0–0.02% based on 5 studies) for CT. There was a tendency towards an increased risk of thyroid dysfunction with higher amounts of contrast used. Conclusions Exposure to iodinated contrast media prior to or during pregnancy may increase the risk of thyroid dysfunction in offspring. We recommend keeping the amount of contrast used as low as possible.

Moderate Iodine Deficiency Is Common in Pregnancy but Does Not Alter Maternal and Neonatal Thyroid Function Tests

IntroductionAn Israeli national survey found that 85% of pregnant women had urinary iodine content (UIC) levels below the adequacy range (<150 µg/L). Widespread desalinated water usage and no national fortification plan are possible causes. Studies assessing relationships between iodine status and maternal and neonatal thyroid function provided varying results. Our aims were to determine whether iodine deficiency was associated with altered maternal or neonatal thyroid function and the factors leading to iodine deficiency.MethodsA cross-sectional study including 100 healthy women without prior thyroid disease, in their first trimester of a singleton pregnancy were recruited from an HMO clinic in central Israel. The women were followed from their first trimester. All women completed a 24-h dietary recall and life habits questionnaires. We tested for UIC, maternal and neonatal thyroid function, maternal autoantibodies, and neonatal outcomes.ResultsMedian UIC in our cohort was 49 µg/L [25%–75% interquartile range (IQR) 16-91.5 µg/L], with 84% below adequacy range. No correlation was found between iodine deficiency and maternal or neonatal thyroid function which remained within normal ranges. Antibody status did not differ, but thyroglobulin levels were significantly higher in iodine insufficient subjects. UIC was higher in women consuming an iodine containing supplement. There was no association between UIC and dietary iodine content or water source.ConclusionsModerate iodine deficiency is common in our healthy pregnant women population. Our data imply that moderate iodine deficiency in pregnancy seem sufficient to maintain normal maternal and neonatal thyroid function.

Thyroid function in neonates conceived after hysterosalpingography with iodinated contrast

STUDY QUESTION Does exposure to preconceptional hysterosalpingography (HSG) with iodinated oil-based contrast affect neonatal thyroid function as compared to iodinated water-based contrast? SUMMARY ANSWER Preconceptional HSG with iodinated contrast did not influence the neonatal thyroid function. WHAT IS KNOWN ALREADY HSG is a commonly applied tubal patency test during fertility work-up in which either oil- or water-based contrast is used. Oil-based contrast contains more iodine compared to water-based contrast. A previous study in an East Asian population found an increased risk of congenital hypothyroidism (CH) in neonates whose mothers were exposed to high amounts of oil-based contrast during HSG. STUDY DESIGN, SIZE, DURATION This is a retrospective data analysis of the H2Oil study, a randomized controlled trial (RCT) comparing HSG with the use of oil- versus water-based contrast during fertility work-up. After an HSG with oil-based contrast, 214 women had an ongoing pregnancy within 6 months leading to a live birth compared to 155 women after HSG with water-based contrast. PARTICIPANTS/MATERIALS, SETTING, METHODS Of the 369 women who had a live born infant, 208 consented to be approached for future research and 138 provided informed consent to collect data on the thyroid function tests of their offspring (n = 140). Thyroid function tests of these children were retrieved from the Dutch neonatal screening program, which includes the assessment of total thyroxine (T4) in all newborns, followed by thyroid-stimulating hormone only in those with a T4 level of ≤ −0.8 SD score. Furthermore, amount of contrast medium used and time between HSG and conception were compared between the two study groups. MAIN RESULTS AND THE ROLE OF CHANCE Data were collected from 140 neonates conceived after HSG with oil-based (n = 76) or water-based (n = 64) contrast. The median T4 concentration was 87.0 nmol/l [76.0–96.0] in the oil group and 90.0 nmol/l [78.0–106.0] in the water group (P = 0.13). None of the neonates had a positive screening result for CH. The median amount of contrast medium used was 9.0 ml [interquartile range (IQR), 6.0–11.8] in the oil-group and 10.0 ml [IQR, 7.5–14.0] in the water group (P = 0.43). No influence of the amount of contrast on the effect of contrast group on T4 concentrations was found (P-value for interaction, 0.37). LIMITATIONS, REASONS FOR CAUTION A relatively small sample size and possible attrition at follow-up are limitations of this study. Although our results suggest that the use of iodinated contrast media for HSG is safe for the offspring, the impact of a decrease in maternal thyroid function on offspring neurodevelopment could not be excluded, as data on maternal thyroid function after HSG and during conception were lacking. WIDER IMPLICATIONS OF THE FINDINGS As HSG with oil-based contrast does not affect thyroid function of the offspring, there is no reason to withhold this contrast to infertile women undergoing HSG. Future studies should investigate whether HSG with iodinated contrast influences the periconceptional maternal thyroid function and, consequently, offspring neurodevelopment. STUDY FUNDING/COMPETING INTEREST(S) This study received no funding. The original H2Oil RCT was an investigator-initiated study that was funded by the two academic institutions (Academic Medical Center and VU University Medical Center) of the Amsterdam UMC. The funders had no role in study design, collection, analysis and intrepretation of the data. I.R. reports receiving travel fee from Guerbet. C.B.L. reports speakers fee from Ferring in the past and research grants from Ferring, Merck and Guerbet. K.D. reports receiving travel fee and speakers fee from Guerbet. B.W.M. is supported by a NHMRC Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for ObsEva, Merck KGaA and Guerbet and travel and research grants from Merck KGaA and Guerbet. V.M. reports receiving travel fee and speakers fee as well as research grants from Guerbet. The other authors do not report conflicts of interest. TRIAL REGISTRATION NUMBER Netherlands Trial Register NTR 7526 (Neonates born after the H2Oil study), NTR 3270 (original H2Oil study), www.trialregister.nl

Role of Maternal Thyroid-Stimulating Immunoglobulin in Graves' Disease for Predicting Perinatal Thyroid Dysfunction

Objective To assess maternal thyroid-stimulating immunoglobulin (TSI) as a predictor of neonatal thyroid hyperthyroidism in pregnancies complicated by Graves' disease. Methods This is a 10-year retrospective study of patients with a history of Graves' disease and elevated TSI activity level defined as 1.3 times the normal. All subjects underwent cordocentesis for ultrasound findings of suspected fetal thyrotoxicosis (fetal tachycardia, oligohydramnios, hydrops, and thyromegaly). Neonatal diagnosis was made based on neonatal thyroid function testing or symptoms. Results Fourteen patients were included in the study, seven with active Graves' disease requiring antithyroid drug (“ATD group”) and seven with iatrogenic hypothyroidism on levothyroxine (“levothyroxine group”). Four cases (57%) of neonatal thyrotoxicosis were diagnosed in the levothyroxine group compared with two cases (28%) in the ATD group. The lowest maternal TSI level at which a neonate did not develop hyperthyroidism was 2.6 for the levothyroxine group and 2.5 for the ATD group. The odds ratio of a neonate from the levothyroxine group developing hyperthyroidism compared with one from the ATD group is 3.3 (95% confidence interval: 0.4–30.7). Conclusion For patients with Graves' disease, those with iatrogenic hypothyroidism and TSI > 2.5 times the basal level are at the highest risk for neonatal thyrotoxicosis.