TY - JOUR
T1 - Defining Gestational Thyroid Dysfunction Through Modified Nonpregnancy Reference Intervals
T2 - An Individual Participant Meta-analysis
AU - Osinga, Joris A.J.
AU - Nelson, Scott M.
AU - Walsh, John P.
AU - Ashoor, Ghalia
AU - Palomaki, Glenn E.
AU - López-Bermejo, Abel
AU - Bassols, Judit
AU - Aminorroaya, Ashraf
AU - Broeren, Maarten A.C.
AU - Chen, Liangmiao
AU - Lu, Xuemian
AU - Brown, Suzanne J.
AU - Veltri, Flora
AU - Huang, Kun
AU - Männistö, Tuija
AU - Vafeiadi, Marina
AU - Taylor, Peter N.
AU - Tao, Fang Biao
AU - Chatzi, Lida
AU - Kianpour, Maryam
AU - Suvanto, Eila
AU - Grineva, Elena N.
AU - Nicolaides, Kypros H.
AU - D'Alton, Mary E.
AU - Poppe, Kris G.
AU - Alexander, Erik
AU - Feldt-Rasmussen, Ulla
AU - Bliddal, Sofie
AU - Popova, Polina V.
AU - Chaker, Layal
AU - Visser, W. Edward
AU - Peeters, Robin P.
AU - Derakhshan, Arash
AU - Vrijkotte, Tanja G.M.
AU - Pop, Victor J.M.
AU - Korevaar, Tim I.M.
N1 - Publisher Copyright:
© 2024 The Author(s). Published by Oxford University Press on behalf of the Endocrine Society.
PY - 2024/11/1
Y1 - 2024/11/1
N2 - Background: Establishing local trimester-specific reference intervals for gestational TSH and free T4 (FT4) is often not feasible, necessitating alternative strategies. We aimed to systematically quantify the diagnostic performance of standardized modifications of center-specific nonpregnancy reference intervals as compared to trimester-specific reference intervals. Methods: We included prospective cohorts participating in the Consortium on Thyroid and Pregnancy. After relevant exclusions, reference intervals were calculated per cohort in thyroperoxidase antibody-negative women. Modifications to the nonpregnancy reference intervals included an absolute modification (per. 1 mU/L TSH or 1 pmol/L free T4), relative modification (in steps of 5%) and fixed limits (upper TSH limit between 3.0 and 4.5 mU/L and lower FT4 limit 5-15 pmol/L). We compared (sub)clinical hypothyroidism prevalence, sensitivity, and positive predictive value (PPV) of these methodologies with population-based trimester-specific reference intervals. Results: The final study population comprised 52 496 participants in 18 cohorts. Optimal modifications of standard reference intervals to diagnose gestational overt hypothyroidism were -5% for the upper limit of TSH and +5% for the lower limit of FT4 (sensitivity,. 70, CI, 0.47-0.86; PPV, 0.64, CI, 0.54-0.74). For subclinical hypothyroidism, these were -20% for the upper limit of TSH and -15% for the lower limit of FT4 (sensitivity, 0.91; CI, 0.67-0.98; PPV, 0.71, CI, 0.58-0.80). Absolute and fixed modifications yielded similar results. CIs were wide, limiting generalizability. Conclusion: We could not identify modifications of nonpregnancy TSH and FT4 reference intervals that would enable centers to adequately approximate trimester-specific reference intervals. Future efforts should be turned toward studying the meaningfulness of trimester-specific reference intervals and risk-based decision limits.
AB - Background: Establishing local trimester-specific reference intervals for gestational TSH and free T4 (FT4) is often not feasible, necessitating alternative strategies. We aimed to systematically quantify the diagnostic performance of standardized modifications of center-specific nonpregnancy reference intervals as compared to trimester-specific reference intervals. Methods: We included prospective cohorts participating in the Consortium on Thyroid and Pregnancy. After relevant exclusions, reference intervals were calculated per cohort in thyroperoxidase antibody-negative women. Modifications to the nonpregnancy reference intervals included an absolute modification (per. 1 mU/L TSH or 1 pmol/L free T4), relative modification (in steps of 5%) and fixed limits (upper TSH limit between 3.0 and 4.5 mU/L and lower FT4 limit 5-15 pmol/L). We compared (sub)clinical hypothyroidism prevalence, sensitivity, and positive predictive value (PPV) of these methodologies with population-based trimester-specific reference intervals. Results: The final study population comprised 52 496 participants in 18 cohorts. Optimal modifications of standard reference intervals to diagnose gestational overt hypothyroidism were -5% for the upper limit of TSH and +5% for the lower limit of FT4 (sensitivity,. 70, CI, 0.47-0.86; PPV, 0.64, CI, 0.54-0.74). For subclinical hypothyroidism, these were -20% for the upper limit of TSH and -15% for the lower limit of FT4 (sensitivity, 0.91; CI, 0.67-0.98; PPV, 0.71, CI, 0.58-0.80). Absolute and fixed modifications yielded similar results. CIs were wide, limiting generalizability. Conclusion: We could not identify modifications of nonpregnancy TSH and FT4 reference intervals that would enable centers to adequately approximate trimester-specific reference intervals. Future efforts should be turned toward studying the meaningfulness of trimester-specific reference intervals and risk-based decision limits.
UR - http://www.scopus.com/inward/record.url?scp=85206594629&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85206594629&partnerID=8YFLogxK
U2 - 10.1210/clinem/dgae528
DO - 10.1210/clinem/dgae528
M3 - Article
C2 - 39083675
AN - SCOPUS:85206594629
SN - 0021-972X
VL - 109
SP - e2151-e2158
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 11
ER -
