IMPORTANCE Differentiated thyroid cancer (DTC) is commonly diagnosed in women of child-bearing age, but whether pregnancy influences the prognosis of DTC remained controversial. OBJECTIVE This systematic review and meta-analysis aimed to summarize and appraise the existing evidence of the impact of pregnancy on the prognosis of patients previously treated for DTC. DATA SOURCES We searched PubMed, Embase, Web of Science, Cochrane, and Scopus until February 2023. STUDY SELECTION Studies of patients diagnosed and treated for DTC before pregnancy reporting the recurrence/progression condition of DTC were included. Case reports and studies failing to identify the time of diagnosis or initial treatment were excluded. DATA EXTRACTION AND SYNTHESIS Meta-analyses were conducted according to MOOSE guideline. Data extraction was conducted by two independent investigators with a standard form. Pooled effect estimates were calculated in a random-effects model. MAIN OUTCOMES AND MEASURES DTC recurrence/progression and the type of recurrence/progression (structural or biochemical). RESULTS Among the 10 included studies (n = 625), 4 (n = 143) of them compared the pregnancy group with the non-pregnancy group while the remaining 6 (n = 482) only included the pregnant patients. The pooled proportion of recurrence/progression in all pregnant patients was 13% (95% CI, 6%, 25%). Compared with the non-pregnancy group, the pooled odds ratio of recurrence/progression in the pregnancy group was 0.75 (95% CI, 0.45, 1.23). Two included studies focused on patients with distant metastasis and also did not observe difference in disease recurrence/progression between the pregnancy group and the non-pregnancy group [OR, 0.51 (95% CI, 0.14-1.87)]. Six included studies also reported response to therapy status prior to pregnancy, and the pooled proportion for recurrence/progression in pregnant DTC patients with excellent response (n=287), indeterminate response (n=44), biochemical incomplete response (n=41) and structural incomplete response (n=70) was 0.00 (95% CI, 0.00-0.86), 0.09 (95% CI, 0.00-0.99), 0.20 (95% CI, 0.06-0.46) and 0.45 (95% CI, 0.17-0.76), respectively. There was a trend for an increasingly higher risk of recurrence/progression from excellent, indeterminate, biochemical incomplete to structural incomplete response to therapy (P<0.05). CONCLUSIONS AND RELEVANCE: Pregnancy appears to have a minimal impact on the prognosis of DTC with initial treatment. Clinicians may pay more attention to the progression of DTC among pregnant women with biochemical and/or structural persistence.

IMPORTANCE Differentiated thyroid cancer (DTC) is increasingly common in women of reproductive age. However, whether pregnancy increases the risk of progression/recurrence of DTC after treatment remains controversial due to the effect of confounding. OBJECTIVE To assess the effect of pregnancy on structural or biochemical progression in patients previously treated for DTC in a retrospective cohort using propensity score matching (PSM). DESIGN, SETTING, AND PARTICIPANTS This cohort study included 123 pregnant women and 1,376 non-pregnant women after initial treatment for DTC at Peking University Third Hospital between January 2012 and December 2022. To control the effect of confounding, we carefully matched pregnancy (n = 102) and non-pregnancy groups (n = 297) in terms of age, Hashimoto's thyroiditis, lymph node dissection, extra-thyroid invasion, initial risk of recurrence after treatment, and time interval between treatment and last follow up by using PSM. EXPOSURES DTC patients became pregnant after previous treatment. MAIN OUTCOMES AND MEASURES The risk of structural or biochemical progression was assessed in the pregnancy and PSM matched non-pregnancy groups, respectively. Conditional logistics regression models were used to control important confounders and consider the matching properties of the data. RESULTS At baseline, the pregnancy (n = 102) and non-pregnancy groups (n = 297) were balanced in all matched variables (standardized differences <10% and P > 0.05). After a mean follow-up of approximately 4.5 years, we observed no evidence of difference between the two groups in growth in the size of existing metastatic foci [2 (2.0 %) vs. 2 (0.7 %); P = 0.346], percentage of patients developing new lymph node metastases [4 (3.9 %) vs. 21 (7.1 %); P = 0.519], node growth in the contralateral thyroid lobe [4 (3.9 %) vs. 16 (5.4 %); P = 0.324 ], or biochemical progression [2 (2.0 %) vs. 9 (3.0 %); P = 0.583]. Results from conditional logistic regressions and several sensitivity analyses also showed no evidence of association of pregnancy with the risk of progression, after adjusting for potential confounders of age, tumor size, initial risk stratification, Hashimoto's thyroiditis, lymph node dissection, the time interval between treatment and follow-up, and achievement of TSH inhibition target (P = 0.354). The pregnancy-progression association observed longer than 4.5 years showed no evidence of difference with that observed shorter than 4.5 years (P for interaction was 0.283). We further classified the pregnancy patients into 3 subgroups based on the time interval between treatment and pregnancy (< 1 year, 1-2 years, ≥ 2 years) and found that the shorter the time interval, the higher the risk of DTC progression (P for trend was 0.043). CONCLUSIONS AND RELEVANCE The risk of DTC progression/recurrence in the pregnant women was not higher than that in the well-matched, non-pregnant women. For young women previously treated for DTC, disease progression might not be a concern for their future pregnancy plan, but it seems safer to wait an appropriate amount of time before pregnancy.

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ObjectiveTo explore effects of the INSR genotype on the waist circumference reduction after a lifestyle-based obesity intervention.MethodsThis was a nested study in a cluster-randomized controlled trial conducted from September 2018 to June 2019 in Beijing, China. Four schools (200 children) were randomized to the intervention group (diet and physical activity) and 4 schools (193 children) were randomized to the control group (usual practice without a focus on obesity prevention). We followed up children at 9 months (the end of the intervention) and 31 months (22 months after the intervention), and genotyped 7 independent SNPs in the INSR gene. We assessed genetic effects on changes in five waist-related indicators [waist circumference, waist-to-hip ratio (whr), waist-to-height ratio (WHtR), waist circumference adjusted by BMI (WCadjBMI), waist-to-hip ratio adjusted by BMI (WHRadjBMI)] from baseline to 9 months and from 9 months to 31 months in the intervention and control group, respectively, and compared whether genetic effects differed by group (i.e., gene-group interaction).ResultsFrom baseline to 9 months, we found that INSR rs7508679, rs10420008, rs11883325, and rs4804416 modified the intervention effects on changes in all waist-related indicators (all P < 0.05). In the control group, the effect allele was associated with greater increases in waist-related indicators, whereas opposite-directional associations were observed in the intervention group. Such interactions between SNPs and group assignment were almost not observed from 9 months to 31 months.ConclusionOur data suggested that children carrying effect alleles of rs7508679, rs10420008, rs11883325, or rs4804416 may benefit more from a lifestyle intervention for obesity prevention, but the effect appeared to be attenuated in the long term.