Gestational diabetes, thyroid disease may increase odds for congenital hypothyroidism
Click Here to Manage Email Alerts
Key takeaways:
- Women with gestational diabetes or gestational thyroid disease are more likely to have a child with congenital hypothyroidism.
- Assisted reproduction technology lowers odds for congenital hypothyroidism.
Women with gestational diabetes or gestational thyroid disease are more likely to give birth to a child with congenital hypothyroidism than women without either condition, according to study data.
In findings published in the Journal of Multidisciplinary Healthcare, researchers compared data from newborns with congenital hypothyroidism with a control group of healthy newborns. In addition to gestational diabetes and gestational thyroid disease being linked to increased odds for neonatal congenital hypothyroidism, use of assisted reproduction technology was associated with lower the likelihood of congenital hypothyroidism.
“In the first and second trimesters of pregnancy, the fetal demand for thyroid hormones depends on the maternal supply; in the third trimester, the maternal thyroid hormones help the fetus use the thyroid hormones,” Anru Wang, of the department of pediatrics at The Second Affiliated Hospital of Nanjing Medical University in China, and colleagues wrote. “Therefore, maternal factors during gestation and factors influencing the thyroid development of neonates contribute to neonatal congenital hypothyroidism.”
Researchers collected data from 255 newborns diagnosed with congenital hypothyroidism from 2016 to 2021. Thyroid-stimulating hormone levels were measured using dried blood spots collected 2 to 7 days after birth. Newborns with a TSH level greater than 8.5 IU/mL underwent a thyroid function reexamination to confirm the congenital hypothyroidism diagnosis. The congenital hypothyroidism group was matched, 1:1, by sex, date of birth and neonatal disease screening results to a control group of 246 newborns without congenital hypothyroidism. Researchers also collected data from 366 newborns who had a false-positive result for congenital hypothyroidism with normal thyroid function during reexamination. Researchers collected gestational age, birth weight, maternal gestational age, maternal pregestational BMI, gestational method and gestational disease.
Univariate analysis was performed using data from 143 newborns in the control group, 140 with congenital hypothyroidism and 335 who had a false-positive screening for congenital hypothyroidism. There were differences in the rates of maternal gestational diabetes (X2 = 6.857; P = .032), gestational thyroid disease (X2 = 6.999; P = .03) and the use of assisted reproduction technology (X2 = 9.732; P = .008) between the three groups.
In multivariable logistic regression analysis, mothers with gestational thyroid disease (OR = 8.452; 95% CI, 1.051-67.982) and gestational diabetes (OR = 2.654; 95% CI, 1.051-6.706) were more likely to have offspring with congenital hypothyroidism than those without either condition. Mothers who used assisted reproduction technology were less likely to give birth to a child with congenital hypothyroidism than those who did not use assisted reproduction (OR = 0.194; 95% CI, 0.041-0.911).
Mothers who had a child who was small for gestational age (OR = 2.556; 95% CI, 1.027-6.361), had gestational thyroid disease (OR = 7.801; 95% CI, 1.03-59.057) or had gestational diabetes (OR = 2.731; 95% CI, 1.18-6.322) were more likely to have offspring with a false-positive result for congenital hypothyroidism than mothers without thyroid disease, gestational diabetes or a child who was small for gestational age. The use of assisted reproduction technology was associated with a lower likelihood for a false-positive congenital hypothyroidism result (OR = 0.28; 95% CI, 0.102-0.765).
“Previous studies have suggested that compared with single infants conceived naturally, there was no significant increase in the incidence of congenital hypothyroidism in infants conceived with the assistance of artificial insemination,” the researchers wrote. “Based on our study, it is speculated that assisted reproduction does not increase the incidence of congenital hypothyroidism and may even reduce it. More studies are needed to test this speculation in the future.”
Perspective
Back to Top
Located at a tertiary care center in China, the authors had opportunity to evaluate an unusually large number of neonates for thyroid function, finding that 621 failed thyroid newborn screening using a TSH cutoff of 8.5 μIU/mL. Of those, 255 were confirmed to have congenital hypothyroidism, while 366 failed newborn screening but did not have persistent TSH elevation (false positive). Also included were 245 infants with normal newborn screening, matched to congenital hypothyroidism infants for sex and date of birth. We are not provided with the total number of infants who underwent newborn screening.
This article concluded, “Neonatal congenital hypothyroidism and positive screening results are influenced by assisted reproduction, gestational thyroid dysfunction, gestational diabetes mellitus, and small for gestational age.”
Of note, the study found that both congenital hypothyroidism and false positive infants had higher rates of maternal hypothyroidism, gestational diabetes and small for gestational age birth than did controls. Numbers for assisted reproduction were very small, limiting the ability to claim a protective effect.
Of note, the authors used a P value of < .05 to call significance; however, they made more than 10 comparisons without adjusting for multiple comparisons. Thus technically, to call a result significant, the P value should have reached < .01 or .005. In this context, only small for gestational age reached significance, in spite of the large number in the study. In our study (Rose SR, et al. J Pediatr. 2021;doi:10.1016/j.jpeds.2021.11.003), we also found association of low birth weight with persistent TSH elevation at 36 weeks corrected for gestational age.
Certainly, there remains ongoing concern about influences on the fetus of unrecognized or undertreated maternal hypothyroidism. Studies have shown that maternal hypothyroidism is associated with a higher OR of developing adverse pregnancy outcomes, such as anemia, premature rupture of membranes, preeclampsia, high Caesarean rates and offspring low birth weight (Nazarpour S, et al. Arch Gynecol Obstet. 2022;doi:10.1007/s00404-021-06226-0; Mahadik K, et al. BMC Pregnancy Childbirth. 2020;doi:10.1186/s12884-020-03448-z).
In our updated guideline for management of congenital hypothyroidism (Rose SR, et al. Pediatr. 2023;doi:10.1542/peds.2022-060420), we indicated, “When combined maternal and fetal hypothyroidism are present — as may occur with severe iodine deficiency or untreated maternal hypothyroidism — significant neurodevelopmental impairment can occur despite adequate postnatal levothyroxine therapy. This highlights the importance of timely prenatal care that includes careful detection and management of maternal thyroid disease before and during pregnancy.” Guidelines for care of hypothyroidism in pregnant women have been published (Alexander EK, et al. Thyroid. 2017;doi:10.1089/thy.2016.0457).
Hypothyroidism may be present in 4% to 10% of pregnant women. I agree that newborns born to mothers with hypothyroidism during the pregnancy should undergo thyroid function testing in the first month of life to ensure their normal thyroid function (Venugopalan L, et al. J Pediatr Endocrinol Metab. 2020;doi:10.1515/jpem-2020-0349).
Collapse
Click Here to Manage Email Alerts