Cohen, A. S.

Furtado, J. D.

Giovannucci, E. L.

Granstrøm, C.

Gørtz, S.

Halldorsson, T. I.

Langhoff-Roos, J.

Lykke, J. A.

Nielsen, P. H.

Olsen, S. F.

Strøm, M.

Thorne-Lyman, A. L.

Wohlfahrt, J.

Zhou, W.

EBioMedicine

Opin visindi

EBioMedicine 51 (2020) 102619Contents lists available at ScienceDirectEBioMedicinejournal homepage: www.elsevier.com/locate/ebiomCorrigendumCorrigendum to ‘Plasma concentrations of long chain N-3 fatty acids inearly and mid-pregnancy and risk of early preterm birth’Olsen S.F.a,b,*, Halldorsson T.I.a,c, Thorne-Lyman A.L.b,d, Strøm M.a,e, Gørtz S.a, Granstrøm C.a,Nielsen P.H.a, Wohlfahrt J.a, Lykke J.A.f, Langhoff-Roos J.f, Cohen A.S.g, Furtado J.D.b,Giovannucci E.L.b,h, ZhouW.i,ja Centre for Fetal Programming, Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmarkb Department of Nutrition, Harvard TH Chan School of Public Health, Boston, USAc Faculty of Food Science and Nutrition, University of Iceland, Reykjavik, Icelandd Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, USAe Faculty of Natural and Health Sciences, University of the Faroe Islands, Torshavn, Faroe Islandsf Department of Obstetrics, Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Denmarkg Department of Congenital Diseases, Statens Serum Institut, Copenhagen, DenmarkhDepartment of Epidemiology, Harvard TH Chan School of Public Health, Boston, USAi Key Lab. of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai, Chinaj School of Public Health, Fudan University, Shanghai, ChinaIn connection with a new ongoing project, it recently came to theknowledge of the author group that a substantial proportion of theplasma samples used in our study had already been thawed prior tothe conduct of our study. Prior thawing of these samples was done inconnection with an earlier unrelated study conducted by otherresearchers. This new knowledge prompted an examination ofwhether, and how, this previous thawing of part of the samples inour study might impact the results and conclusions that we hadreported in the article.As can be seen in (the new) Corrigendum Table 1, for the first tri-mester samples the proportion that had not been thawed was 89%(297/333) in the control group, whereas in the case group only 21%(77/367) had not been thawed before; for the second trimester sam-ples the difference between controls and cases was even more pro-nounced, with 95% (326/342) of control samples and 16% (60/366) ofcase samples not having been thawed. As can be seen in the columnsto the right in this table, plasma concentrations of EPA+DHA weresubstantially lower in samples that had been thawed. This applied toboth first and second trimester samples, and patterns were similarfor cases and controls.Accounting for thawing by adjustment in a multivariable modelIn Corrigendum Table 2, Panels A-i and B-i, we report associationsbetween plasma fatty acids and early preterm risk using logisticregression to adjust for thawing and storing temperatures (see sec-tion 3.3 in original article). As we had reported in Table 2 Panel A ofthe original paper, for the 1st sample, before adjustment for thawing,DOI of original article: http://dx.doi.org/10.1016/j.ebiom.2018.07.009.* Corresponding author at: Centre for Fetal Programming, Department of Epidemiol-ogy Research, Statens Serum Institut, Copenhagen, Denmark.E-mail address: sfo@ssi.dk (O. S.F.).https://doi.org/10.1016/j.ebiom.2019.1026192352-3964/© 2019 The Author(s). Published by Elsevier B.V. This is an open access article unwomen in the lowest quintile (Q1) appeared to have 5.54 times (95%confidence interval 3.86 to 8.02 to 15.79, p < 0.0001) increased oddsof early preterm birth, whereas women in the second to the lowestquintile (Q2) appeared to have 2.05 (95% CI 1.36 to 3.09, p < 0.0006)times increased odds, compared to women in the aggregated highestthree quintiles (Q3+Q4+Q5). In this new analysis, after adjustmentfor differential thawing and storing temperatures, the odds ratio esti-mates for the lowest quintile for the 1st sample attenuated from 5.54to 1.29 times (95% confidence interval 0.73 to 2.23, p = 0.38) and from2.05 to 0.84 (95% CI 0.47 to 1.49, p = 0.57), respectively, meaning thatthe observed associations for the 1st sample disappeared after thisadjustment (Corrigendum Table 2, Panels A-i). For the 2nd sample(Panel B-i), before any adjustment, women in the lowest quintileappeared to have 9.33 times (95% confidence interval 6.42 to 13.74,p < 0.0001) increased odds of early preterm birth, whereas womenin the second to the lowest quintile appeared to have 2.73 (95% CI1.78 to 4.20, p < 0.0001) times increased odds, compared to womenin the aggregated highest three quintiles. After the additional adjust-ment, however, the odds ratio estimates were attenuated from 9.33to 2.13 times (95% confidence interval 1.18 to 3.79, p = 0.01) and from2.73 to 1.12 (95% CI 0.57 to 2.14, p = 0.73), respectively. In the article,we had also reported on results obtained from analyses where theEPA+DHA measurements had been based on the mean of the 1st and2nd sample. In these analyses, after co-variate adjustment, women inQ1 appeared to have a 10.27 times (95% confidence interval 6.80 to15.79, p < 0.0001) increased risk, whereas women in Q2 appeared tohave a 2.86 (95% CI 1.79 to 4.59, p < 0.0001) times increased risk ofearly preterm birth, compared to women in Q3+Q4+Q5; these resultswere reported in the abstract. However, when further adjustment ismade for thawing and freezer temperatures, these two estimateschanged to 1.42 (0.65 to 3.03, p = 0.4) and 1.11 (0.50 to 2.41, p = 0.8),respectively.der the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)Corrigendum Table 1Sample treatment according of case and control status and in relation to EPA+DHA plasma concentrations.Prior thawings Controls (n = 333) Preterm cases (n = 367) Mean of EPA+DHA%Controls Preterm casesn % n % Mean SEM Mean SEMNumber of thawings, sample 10 297 89 77 21 2.05 0.03 1.91 0.071 34 10 163 44 1.80 0.07 1.42 0.032+ 2 1 127 35 1.22 0.18 1.32 0.03Number of thawings, sample 20 326 95 60 16 2.04 0.03 1.79 0.091 15 4 243 66 1.72 0.17 1.45 0.032+ 1 0.3 63 17 1.69  1.39 0.07Corrigendum Table 2Association between EPA+DHA concentrations and risk of early preterm birth. Shown are results for EPA+DHA measurements based on all 1st trimester samples (Panel A-i),based on 1st trimester samples but including only those samples that had never been thawed (Panel A-ii), based on all 2nd trimester samples (Panel B-i), and based on 2ndtrimester samples but including only those samples that had never been thawed (Panel B-ii).Controls Cases Crude Adjusted for thawing andtemperature1Controls Cases Further adjusted forcovariates2OR (95% CI) P-Value OR (95% CI) P-Value OR (95% CI) P-ValueA-i: 1st trimester samplesAll included (unselected)Test for association in spline regression .. < 0.0001 .. 0.90 .. 0.98Test for linear v. spline association .. 0.0002 .. 0.78 .. 0.92EPA + DHA categorized into quintiles .. < 0.0001 .. 0.41 .. 0.30Q1: 0.37 – 1.48 67 192 5.54 (3.86; 8.02) < 0.0001 1.29 (0.73, 2.23) 0.38 67 192 1.24 (0.68, 2.25) 0.48Q2: 1.48 – 1.81 67 71 2.05 (1.36; 3.09) 0.0006 0.84 (0.47, 1.49) 0.57 67 71 0.74 (0.40, 1.36) 0.34Q3+4+5: 1.81 – 4.74 199 103 1 .. 1 .. 199 103 1 1A-ii: 1st trimester samplesAnalysis restricted to never thawedTest for association in spline regression .. 0.36 .. 0.69 ..Test for linear v. spline association .. 0.56 .. 0.53 ..EPA + DHA categorized into quintiles3 .. 0.26 .. 0.88 ..Q1: 0.37 – 1.48 53 9 0.57 (0.25; 1.18) 0.13 0.87 (0.37, 1.91) 0.74Q2: 1.48 – 1.81 56 12 0.72 (0.35; 1.40) 0.34 0.85 (0.40, 1.72) 0.66Q3+4+5: 1.81 – 4.74 188 56 1 .. 1 ..B-i: 2nd trimester samplesAll included (unselected)Test for association in spline regression .. < 0.0001 .. 0.026 .. 0.10Test for linear v. spline association .. < 0.0001 .. 0.033 .. 0.069EPA + DHA categorized into quintiles .. < 0.0001 .. 0.035 .. 0.064Q1: 0.47 – 1.42 68 226 9.33 (6.42; 13.74) < 0.0001 2.13 (1.18, 3.79) 0.01 68 226 1.92 (1.02, 3.60) 0.045Q2: 1.43 – 1.74 69 67 2.73 (1.78; 4.20) < 0.0001 1.12 (0.57, 2.14) 0.73 69 67 0.90.(0.45, 1.79) 0.78Q33+4+5: 1.74 – 4.95 205 73 1 .. 1 .. 205 73 1 ..B-ii: 2nd trimester samplesAnalysis restricted to never thawedTest for association in spline regression .. 0.10 .. 0.36 ..Test for linear v. spline association .. 0.073 .. 0.23 ..EPA + DHA categorized into quintiles3 .. 0.18 .. 0.16 ..Q1: 0.47 – 1.42 61 17 1.87 (0.95; 3.58) 0.070 1.95 (0.98, 3.78) 0.056Q2: 1.43 – 1.74 64 13 1.36 (0.65; 2.72) 0.40 1.23 (0.58, 2.50) 0.58Q33+4+5: 1.74 – 4.95 201 30 1 .. 1 ..1 Analyses were adjusted for differences in thawings (0, 1, 2 times) and temperatures (-20, -80, -196°C); for the analyses restricted to samples that had never beenthawed (Panels A-ii and B-ii), analyses were adjusted for temperatures.2 Further adjusted for covariates: Maternal age, maternal height, parity, maternal pre-pregnancy BMI, SES, cohabitation, residence and smoking; coded as in the originalarticle. For the analyses restricted to samples that had never been thawed (Panels A-ii and B-ii), entering all the covariates simultaneously into the model was not possibledue lack of convergence; however, taking the covariates in one by one was passible, and this had only limited effect on the estimates of association (data not shown butavailable from the authors).3 Cut points for defining quintiles of the samples that had never been thawed (Panel A-ii), are based on the ‘unselected’ controls (Panel A-i).2 O.S.F. et al. / EBioMedicine 51 (2020) 102619Accounting for thawing by means of restrictionLimiting the analysis to only comprise plasma samples that hadnot been thawed prior to our study reduced numbers available foranalysis, particularly in the case groups. Restriction resulted in thefollowing estimates (adjusted for temperature differences): Forthe 1st sample (Corrigendum Table 2, Panel A-ii), the odds ratio forearly preterm birth in the lowest quintile v. the aggregated highestthree quintiles was 0.87 (95% CI 0.37 to 1.91, p = 0.7), whereas theodds ratio for early preterm birth in the second to the lowest quin-tile v. the aggregated highest three quintiles was 0.85 (95% CI 0.40to 1.72, p = 0.7). For the 2nd sample (Panel B-ii), the correspondingfigures were 1.95 (95% CI 0.98 to 3.78, p = 0.06) and 1.23 (95% CI0.58 to 2.50, p = 0.6), respectively.O.S.F. et al. / EBioMedicine 51 (2020) 102619 3ConclusionsClearly, accounting for thawing substantially affected allestimates. Notably, all associations for the early sample wereattenuated to include the null, whereas an association  albeitseverely attenuated compared to the initially reported association seemed to remain for the mid-pregnancy sample with a dou-bling of the risk in the lowest quintile compared to the aggre-gated highest three quintiles. These patterns are still compatiblewith a preventive effect of EPA+DHA against preterm birth inwomen with a low intake, and with the possibility that the timedynamic of this relationship may be a fast one as seen in a ran-domized controlled trial [1] (see Figures 1 and 2 and discussionon page 1948).We recommend that the study be replicated based on other materials.Reference[1] Olsen SF, Halldorsson TI, Li M, Strøm M, Mao Y, Che Y, Wang Y, Duan F, Olsen J,Zhou W. Examining the effect of fish oil supplementation in chinese pregnantwomen on gestation duration and risk of preterm delivery. J Nutr 2019 pii:nxz153. doi: 10.1093/jn/nxz153.

Corrigendum to 'Plasma concentrations of long chain N-3 fatty acids in early and mid-pregnancy and risk of early preterm birth'

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Corrigendum to 'Plasma concentrations of long chain N-3 fatty acids in early and mid-pregnancy and risk of early preterm birth'

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