In-utero and newborn factors and thyroid cancer incidence in adult women in the Sister Study cohort

Sep 24, 2026

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Thyroid cancer is often diagnosed at younger adult ages, but causal pathways remain unclear. This study examined whether in-utero and newborn characteristics are associated with differentiated thyroid cancer (DTC) incidence in adult women. Using 47,913 cancer-free participants from the Sister Study cohort (baseline 2003–2009), Cox regression models adjusted for attained age and race/ethnicity assessed DTC during follow-up.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages8

Reading Time20 min

AccessFree to download

Background

Methods

Study sample

Results

Conclusions

Introduction

[www.nature.com/bjc](www.nature.com/bjc British)[ British](www.nature.com/bjc British) Journal of Cancer ARTICLE OPEN Epidemiology In-utero and newborn factors and thyroid cancer incidence in adult women in the Sister Study cohort Thi-Van-Trinh Tran 1, Katie M. O’Brien2, Rebecca Troisi 3, Dale P. Sandler 2 and Cari M. Kitahara 1 ✉ This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2025 BACKGROUND: Thyroid cancer is diagnosed at relatively young ages compared to other adult cancers, for reasons that remain unclear. Our study aimed to investigate associations of in-utero and newborn characteristics with differentiated thyroid cancer (DTC) incidence in adult women. METHODS: From the [U.S. nationwide](U.S. nationwide) Sister Study cohort, we included 47,913 cancer-free women at baseline (2003–2009). We assessed associations of participants’ in-utero and newborn characteristics and DTC during follow-up using Cox regression models adjusted for attained age (timescale) and race/ethnicity. RESULTS: During follow-up (median = 13.1 years), 239 incident DTC cases were identiﬁed. Higher DTC incidence was associated with maternal pre-pregnancy or gestational diabetes (hazard ratio [HR] = 2.36, 95%CI = 0.97–5.74, 5 affected cases), gestational hypertension or hypertension-related disorders (HR = 1.99, 95%CI = 1.20–3.32, 16 affected cases), and higher birth weight (HR per kg= 1.24, 95%CI = 0.95–1.60) . Births occurring at least two weeks before the due date were associated with lower DTC incidence (HR = 0.47, 95%CI = 0.23–0.97, 8 affected cases) . In a model simultaneously adjusted for all these factors, all exposures remained associated with DTC incidence. We observed no associations for other in-utero and newborn characteristics. CONCLUSIONS: These ﬁndings contribute to a growing body of evidence that in-utero exposures related to maternal metabolic abnormalities may inﬂuence thyroid cancer risk later in life. | | British Journal of Cancer (2025) 132:1056–1063; [https://doi.org/10.1038/s41416-025-03004-6](https://doi.org/10.1038/s41416-025-03004-6) | | | --- | --- | --- | | | | | INTRODUCTION Thyroid cancer has emerged as the ﬁfth most common cancer diagnosed among women globally, with most cases classiﬁed as differentiated thyroid cancer (DTC) [1] . Yet, the etiology of thyroid cancer remains largely unknown, with obesity and childhood exposure to ionizing radiation among the few established modiﬁable risk factors [2] . The disease is diagnosed at relatively young ages compared to most other adulthood cancers [2], suggesting a potential etiologic role of early-life exposures [3, 4] . Throughout gestation, the developing thyroid is highly susceptible to endogenous (e.g., maternal iodine deﬁciency, thyroid dysfunction, diabetes, ﬂuctuations in maternal and placental estrogen levels) [5–9] and exogenous (e.g., cigarette smoking, endocrine-disrupting chemicals [EDCs]) stressors. These factors may disrupt fetal thyroid function [10, 11], expose the fetus to elevated levels of growth factors [12] and sex steroid hormones [13], which have been suggested to contribute to thyroid cancer development in adulthood [3, 4, 14–16] . Some epidemiologic studies have suggested positive associations for factors reﬂecting fetal hormone exposures, including maternal and congenital thyroid disorders [17], higher birth weight [17–19], postpartum hemorrhage [17], and hyperemesis gravidarum [20], lending some support to the hypothesis that the gestational period is a susceptible exposure window in thyroid carcinogenesis. However, evidence on the impact of in-utero and birth characteristics on subsequent risk of thyroid cancer remains scarce. To contribute to the limited research on this topic, we prospectively evaluated associations of a wide range of selfreported in-utero and newborn factors with DTC incidence in the Sister Study, a large [U.S. nationwide](U.S. nati

FAQs

What was the study’s main goal regarding thyroid cancer risk?

To investigate whether in-utero and newborn characteristics are associated with the incidence of differentiated thyroid cancer (DTC) in adult women.

How was the Sister Study cohort used in this analysis?

A total of 47,913 cancer-free women at baseline (2003–2009) were included, and DTC incidence during follow-up was analyzed using Cox regression models adjusted for attained age and race/ethnicity.

Which in-utero or newborn factors were linked to higher DTC incidence?

Higher DTC incidence was associated with maternal pre-pregnancy or gestational diabetes, gestational hypertension or hypertension-related disorders, and higher birth weight. Births at least two weeks before the due date were associated with lower DTC incidence.

Sep 24, 2026

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