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 - Lopez-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 - Maennistoe, 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
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:
© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.
PY - 2024/7/31
Y1 - 2024/7/31
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 - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=eur_pure&SrcAuth=WosAPI&KeyUT=WOS:001297398500001&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1210/clinem/dgae528
DO - 10.1210/clinem/dgae528
M3 - Review article
C2 - 39083675
SN - 0021-972X
VL - 109
SP - e2151-e2158
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 11
M1 - dgae528
ER -