Evaporation of serum after long-term biobank storage: A chemical analysis of maternal serum from a large Danish pregnancy screening registry

Cecilie S. Uldbjerg; Karina M. Sørensen; Christian H. Lindh; Panu Rantakokko; Russ Hauser; Anders Juul; Anna-Maria Andersson; Elvira V. Bräuner

doi:10.1371/journal.pone.0293527

Abstract

Background

Relying on freezer stored biospecimens is preferred in epidemiolocal studies exploring environmental pregnancy exposures and later offspring health. Storage duration may increase the pre-analytical variability, potentially adding measurement uncertainty. We investigated evaporation of maternal serum after long-term biobank storage using ions (sodium, Na⁺; chloride, Cl^-) recognized for stability and relatively narrow normal biological reference ranges in human serum.

Methods

A chemical analysis study of 275 biobanked second trimester maternal serum from a large Danish pregnancy screening registry. Serum samples were collected between 1985–1995 and stored at -20°C. Ion concentrations were quantified with indirect potentiometry using a Roche Cobas 6000 analyzer and compared according to storage time and normal biological ranges in second trimester. Ion concentrations were also compared with normal biological variation assessed by baseline Na⁺ and Cl^- serum concentrations from a separate cohort of 24,199 non-pregnant women measured before freezing with the same instrument.

Results

The overall mean ion concentrations in biobanked serum were 147.5 mmol/L for Na⁺ and 109.7 for Cl^-. No marked linear storage effects were observed according to storage time. Ion concentrations were consistently high across sampling years, especially for specific sampling years, and a relatively large proportion were outside respective normal ranges in second trimester: 38.9% for Na⁺ and 43.6% for Cl^-. Some variation in concentrations was also evident in baseline serum used as quality controls.

Conclusions

Elevated ion concentrations suggest evaporation, but independent of storage duration in the present study (27–37 years). Any evaporation may have occurred prior to freezer storage or during the first 27 years. Other pre-analytical factors such as low serum volume have likely influenced the concentrations, particularly given the high within year variability. Overall, we consider the biobanked serum samples internally comparable to enable their use in epidemiological studies.

Citation: Uldbjerg CS, Sørensen KM, Lindh CH, Rantakokko P, Hauser R, Juul A, et al. (2023) Evaporation of serum after long-term biobank storage: A chemical analysis of maternal serum from a large Danish pregnancy screening registry. PLoS ONE 18(10): e0293527. https://doi.org/10.1371/journal.pone.0293527

Editor: Ping-I (Daniel) Lin, University of New South Wales, AUSTRALIA

Received: January 13, 2023; Accepted: October 15, 2023; Published: October 26, 2023

Copyright: © 2023 Uldbjerg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: The data used in this study are governed and maintained centrally by the Danish National Biobank. Data are not publicly available and anonymized data can only be accessed after approval by the Danish National Biobank (mail@nationalbiobank.dk) and the Danish Data Protection Agency.

Funding: The salaries of AJ, EVB, RH and CSU were partially supported by a grant from the National Institute of Health (Grant no. 1R01CA236816-01A1). EVB was also partially supported by grants from the Danish Health Foundation (Helsefonden, grant no. 18-B-0016, Aase and Ejnar Danielsen Foundation, grant no. 10-002122, Svend Andersen Foundation, grant no 81A-01 and Familien Erichsens Mindefond, grant no.6000073). There was no additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interest exist.

Introduction

Human biospecimens used in research present opportunities for the purpose of studying environmental exposures and health. Many epidemiological studies make efforts to establish effects of chemical exposures in fetal life on long-term health, which require access to exposure data collected already during the pregnancy. Importantly, several pregnancy cohorts have emerged during past decades, providing unique resources for studying these prenatal exposures [1,2]. Millions of biological samples have been collected as part of these cohorts and are stored in biorepository freezers for future research [3–9]. A growing number of studies have now attempted to accurately measure a range of chemical exposures in biobanked maternal biospecimen in order to provide insights into the role of the prenatal environment on offspring health [10–14]. The usefulness of biobanked samples for epidemiological research many years after its collection largely depends on the extent to which sample preservation has affected the chemical levels [15]. Supposed evaporation from the tubes during years of storage may result in increased concentrations of the analytes of interest, which would then appear erroneously high; a particular concern if storage effects are not similar across samples. Along with storage time, other pre-analytical variations and errors may also introduce differential effects on the quality of biological samples and influence analysis results, including inappropriate sample handling, insufficient mixing of samples, variability in sample container material, geometry, and volume, hemolysis etc. Unfortunately, the pre-analytical phase is rarely taken into consideration in research projects intended to use biobanked samples for estimating chemical exposures.

The Danish Pregnancy Screening Registry is a large cohort with available blood samples from almost 130,000 pregnant women collected through a pregnancy screening program from 1979 until 1996. From 1985 onward, maternal serum was stored at the Danish National Biobank for future research, including a recently initiated project investigating prenatal exposures to endocrine disrupting chemicals and later testicular cancer. In a separate cohort, we have previously observed that serum was affected differently by evaporation over years of storage [16], and we hypothesize that chemical concentrations in this present collection of samples may therefore be skewed toward higher concentrations in older samples, potentially affecting the quality of our samples and validity of future regression analyses.

In this study, we aimed to investigate the effect of long-term storage at -20°C on evaporation by quantifying serum ion concentrations of sodium, Na⁺ and chloride, Cl^-. Analyses of these closely regulated ions may reveal evaporation dependent changes in concentrations of analytes of interest during long-term storage.

Methods and materials

Study design

A chemical analysis study of evaporation of biobanked serum after storage at -20°C by investigating serum concentrations of selected ions (sodium, Na⁺ and chloride, Cl^-), known to be stable in stored human serum and with much studied and relatively narrow human biological normal ranges.

Data source and study material

We accessed biobanked maternal serum samples from the Danish Pregnancy Screening Registry, a large cohort of Danish pregnant women who participated in a pregnancy screening program from 1985 until 1996. Blood samples were collected from pregnant women during their second trimester of pregnancy (gestational weeks 14 to 22). The entire collection of samples is maintained at the Danish National Biobank (Statens Serum Institut in Copenhagen, Denmark).

For the present study, a total of 275 serum samples were randomly selected with an even distribution of 25 samples per sampling year (25 consecutive samples of separate individuals from the same randomly selected box of samples from a given year between 1985 to 1995).

Sample handling and storage conditions

Blood collection for serum was performed once for each pregnant woman. After blood was drawn, samples were allowed to clot. Clotted blood samples were centrifuged at 4°C at 3,000 rpm before the supernatants of serum were pipetted for storage. The sample handling procedure at the time was transport at ambient temperature until freezing. The collection of serum samples is stored at -20°C in 2 ml cryotubes with screw caps. The collection of serum samples contains between 1–2 ml per sample, but some individual tubes may contain less than 1 ml.

Ion analyses

The concentrations of Na⁺ and Cl^- were measured by an indirect potentiometry assay using an ion-selective electrode (Cobas 6000 Roche/Hitachi, Basel, Switzerland), known to provide stable analysis for a wide range of analytes [17]. The analyses were performed in 2022 at the Danish National Biobank, Statens Serum Institute, Copenhagen, Denmark, all in a random single batch. Prior to ion analyses, the samples were thawed at room temperature for ≤2 hours. The samples were hereafter thoroughly mixed on a whirl mixer for at least 5 seconds and then immediately after manually pipetted into Cobas cups (300 μl). The pipette was pre-wetted by aspirating and dispensing an amount of the sample a few times before transferring to the cups. The process of mixing and pipetting was done for batches of 25 samples, such that 25 samples were pipetted followed by ion analysis. The next batch of 25 samples were prepared, while the prior 25 samples were ion analyzed. The samples were automatically diluted by the analytical instrument prior to analysis. All samples were analyzed using the same calibrator. The instrument measured the serum aliquots from the center of the cup and provided an error message in case of insufficient serum volume.

The normal biological ranges in maternal serum during second trimester of pregnancy for each ion are Na⁺_{second trimester}: 129–148 mmol/L and Cl^-_{second trimester}: 97–109 mmol/L) [18]. The concentrations of both Na⁺ and Cl^- have wider normal ranges during pregnancy compared to non-pregnant adult populations [18].

Non-frozen (baseline) quality control samples

To elucidate normal biological variation, we compared ion concentrations in our biobanked maternal serum samples to ion concentrations measured in quality controls serum samples before being freezer stored. These baseline serum samples were provided from 24,199 non-pregnant women from a separate cohort collected between 2015 to 2019. The baseline samples were centrifuged at 21°C, 3100 RPM, 10 min and stored for <24 hours in a climate chamber prior to measuring the ions. As provided by the laboratory, the normal biological ranges in serum for healthy adults are Na⁺_{non-pregnant adults}: 136–145 mmol/L and Cl^-_{non-pregnant adults}: 98–107 mmol/L [19].

Measurements from both biobanked serum and baseline quality control serum were performed at the same laboratory and using same methods and analytical instrument, although in different years.

Statistical analyses

Mean and median concentrations of ions (overall and yearly) with respective standard deviations and 25^th-75^th percentiles were calculated and compared directly to the respective normal biological ranges of each ion in second trimester of pregnancy. Ion concentrations according to storage time were visualized (overall and yearly) and coefficients of determination (R²) were calculated for trends over time (27–37 years of storage). For comparison, ion concentrations of baseline quality control samples were also visualized. All analyses were performed in Excel (Microsoft Office 15) and SAS Studio (2018, SAS Institute Inc., Cary, NC, USA).

Results

In the set of 275 randomly selected biobanked serum samples, the minimum to maximum freezer storage time was 27 to 37 years. The overall mean ion concentrations for the entire storage period were 147.5 mmol/L for Na⁺ and 109.7 mmol/L for Cl^- (Table 1). A large proportion of individual ion concentrations were measured outside the normal biological ranges in second trimester for the respective ion of interest: 38.9% for Na⁺; and 43.6% for Cl^-. Of these, the majority (Na⁺/Cl^-: 106/116) were above normal ranges while only one for Na⁺ and four for Cl^- were below. The proportion of ion concentrations outside normal biological ranges were highest in sampling year 1990, corresponding to 32 years of storage, for both Na⁺ (80%) and Cl^- (100%). According to concentrations for specific sampling years, a noteworthy high within year variation compared with normal ranges was observed across all sampling years, for both ions (Table 1, S1A and S1B Fig).

Download:

Table 1. Serum concentrations of Na⁺ and Cl^- in 275 biobanked pregnancy serum samples according to sampling year and compared to 24,199 baseline serum samples from non-pregnant women.

https://doi.org/10.1371/journal.pone.0293527.t001

There were no marked secular (linear) trends in the concentrations according to storage time for any of the investigated ions, with R² coefficients of 0.023 for Na⁺ and 0.039 for Cl^- (Fig 1). Some single sampling years appeared to have more individual samples with very high concentrations (outliers), both evident for Na⁺ and Cl^-, for which reason trends in concentrations of samples were not entirely stable across years. We post hoc checked some of these individual outliers to confirm their visual conditions; some outlier samples had sufficient volume, while others were observed to have a very low volume, which may have led to a relatively higher evaporation, thus potentially resulting in increased concentrations. However, we observed no consistent differences related to sample volume.

Download:

Fig 1. The concentrations of sodium, Na⁺ and chloride, Cl^- (mmol/L) in biobanked serum samples from pregnant women (n = 275) according to storage time in years and compared to normal biological ranges in second trimester of pregnancy.

https://doi.org/10.1371/journal.pone.0293527.g001

Considering the baseline serum samples in non-pregnant women, a much lower proportion was outside the normal biological ranges for non-pregnant healthy adults. Specifically, 906 (3.7%) and 1049 (4.3%) were outside normal ranges for Na⁺ and Cl^-, respectively (Table 1). In contrast to biobanked serum samples, these baseline serum concentrations were mainly below the respective normal biological ranges (Na⁺/Cl^-: 91%/72%). Some extreme variation in the individual concentrations was also observed (Fig 2).

Download:

Fig 2. The concentrations of sodium, Na⁺ and chloride, Cl^- (mmol/L) in baseline serum samples before freezer storage.

https://doi.org/10.1371/journal.pone.0293527.g002

Discussion and conclusions

In this study investigating evaporation of biobanked maternal serum stored at -20°C between 27 to 37 years, we observed no marked linear effects on ion concentrations of Na⁺ and Cl^- according to freezer storage time. However, we did observe elevated concentrations of both ions compared to respective normal biological ranges in second trimester of pregnancy, implying some degree of evaporation of the samples. Given the sample handling procedure at the time without immediate freezing, the evaporation may very well have happened even before biobank storage. But without having samples stored shorter periods of time as a comparison, such as within the 0-to-27-year period, it remains unknown if very long-term storage impacts evaporation or pre-analytical factors play more of a role. Although independent of storage time, the higher concentrations of ions were inconsistent for some sampling years and the overall variation in concentrations in biobanked serum were somewhat larger than the normal biological variation observed in baseline serum prior to storage.

Na⁺ and Cl^- are regulated within a relatively narrow reference range in healthy individuals and abnormal levels therefore serve as a good proxy for evaporation of serum after years of freezing. Thus, the pattern of results with noteworthy high ion concentrations, especially for specific sampling years, may suggests evaporation and indicate that samples were not identically affected by storage and/or pre-analytical factors. We recognize these concerning discrepancies, but given the small sample size, we were not able to expect ion concentrations to cluster around the mean normal range value. It is not possible to determine if any conditions changed in the sample handling procedure around year 1990 to explain the slightly higher concentrations but it may also be a coincidence with only few samples investigated per year. The relatively large within year variation observed across all sampling years is suspected to be caused by the low volume of some samples, but differential serum volume does not explain the entire variation. The baseline serum ion concentrations measured prior to storage used as quality controls also confirm that some normal variation may be expected, although the two data sets are inherently difficult to compare, as the baseline data consider non-pregnant women, while pregnant women are known to have higher variability in Na⁺ and Cl^- serum concentrations (wider normal ranges). We acknowledge the high concentrations and large variations observed within and between years but the reasons for these are largely speculative and may have been caused by a number of pre-analytical factors, where storage time is simply be one of them.

The effect of certain storage and sample handling conditions on the stability of frozen biospecimen has already been studied in various contexts [3,15,20–25], typically to validate bioresources prior to analytical processes. A systematic review from 2014 [3] evaluated current literature relevant to the stability of specific biomarkers in human fluid and determined potential variations associated with different storage temperatures (-20 to -196°C). Another study [26] has postulated that pre-freezing handling such as time and transport until processing/freezing may be factors contributing to variability in concentrations. Effects of different procedures in the laboratory prior to chemical analyses can also lead to erroneous results and represent a pre-analytical bias, including insufficient mixing of thawed serum, insufficient mixing during previous pipetting events, pipetting manually or with the use of robots, accidentally loose lids, variability in tubes, volume and gel etc. [27–29]. Taken together, all these observations from previous studies demonstrate the importance of pre-analytical activities on the usefulness of biobanked samples for epidemiological research. In the present study, we were unable to investigate these specific sample handling protocols and storage conditions, but we acknowledge that the pre-analytical phase should be considered in order determine the reliability of any results of serum sample analyses. Evaporation is simply one factor that can contribute to analytical error. Noteworthy, our biobanked samples were handled by the same protocol, and any variability is expected to be the same across cases and controls, reducing any systematic exposure misclassification bias in future disease-oriented epidemiological studies.

A limitation of our study was that investigating repeated measurements of ion concentrations or comparing with ion concentrations in fresh serum from the same individuals was not possible. This would have been preferred in order to accurately quantify the degree of evaporation. In addition, we were not able to measure ion concentrations in the entire pregnancy screening registry due to costs and prioritization in the use of valuable biobanked biospecimen. We acknowledge that it would be preferable to measure individual ion concentrations for all samples and thereafter adjust each sample based on expected evaporation rate accordingly. But we do not expect this to be a substantial problem given the large number of available samples within the cohort of biobanked samples and since our future analyses will aim at investigating general trends at the group level and not biomonitoring trends according to the individual exposures. Another limitation is that the shortest storage time was 27 years so we could not explore the full range from before storage up to 37 years of storage. This may have provided more insight into effects of long-term storage versus short-term storage of several years.

In conclusion, the elevated ion concentrations of biobanked maternal serum samples stored at -20°C were independent of storage duration in the present study (27 to 37 years). On this basis, we do not recommend applying a duration-depended correction factor to quantified chemical concentrations in future epidemiological studies using these samples. The generally high ion concentrations often outside normal biological reference ranges in second trimester may suggest some evaporation of the samples, especially for specific sampling years, but we speculate that other unknown pre-analytical factors also influence the variations in concentrations. Insufficient serum volume may be of particular concern in this context. On balance, we consider the biobanked serum samples internally comparable over the investigated period of biobank storage and of sufficient quality to be used in future epidemiological studies. Close matching for sampling year can be a necessary approach in the research design. Further, optimal pre-analytical procedures such as sufficient volume and mixing prior to chemical analysis are important components for obtaining reliable chemical results.

Supporting information

S1 Fig.

a. The concentrations of sodium, Na⁺ in biobanked serum samples from pregnant women according to specific sample years. b. The concentrations of chloride, Cl^- in biobanked serum samples from pregnant women according to specific sample years.

https://doi.org/10.1371/journal.pone.0293527.s001

(TIF)

Acknowledgments

We want to acknowledge all the pregnant women who participated in the pregnancy screening program and provided blood samples to the study. We also want to thank Anne Tjønneland and Jytte Halkjær from the Danish Cancer Society for providing the additional ion data of the baseline female population.

References

1. Larsen PS, Kamper-Jørgensen M, Adamson A, Barros H, Bonde JP, Brescianini S, et al. Pregnancy and birth cohort resources in europe: a large opportunity for aetiological child health research. Paediatr Perinat Epidemiol. 2013;27: 393–414. pmid:23772942
- View Article
- PubMed/NCBI
- Google Scholar
2. Vrijheid M, Casas M, Bergström A, Carmichael A, Cordier S, Eggesbø M, et al. European birth cohorts for environmental health research. Environ Health Perspect. 2012;120: 29–37. pmid:21878421
- View Article
- PubMed/NCBI
- Google Scholar
3. Hubel A, Spindler R, Skubitz APN. Storage of Human Biospecimens: Selection of the Optimal Storage Temperature. https://home.liebertpub.com/bio. 2014;12: 165–175. pmid:24918763
- View Article
- PubMed/NCBI
- Google Scholar
4. Pukkala E, Andersen A, Berglund G, Gislefoss R, Gudnason V, Hallmans G, et al. Nordic biological specimen banks as basis for studies of cancer causes and control—more than 2 million sample donors, 25 million person years and 100,000 prospective cancers. Acta Oncol. 2007;46: 286–307. pmid:17450464
- View Article
- PubMed/NCBI
- Google Scholar
5. Jellum E, Andersen A, Lund-Larsen P, Theodorsen L, Orjasaeter H. Experiences of the Janus Serum Bank in Norway. Environ Health Perspect. 1995;103 Suppl: 85–8. pmid:7635118
- View Article
- PubMed/NCBI
- Google Scholar
6. Bach CC, Liew Z, Bech BH, Nohr EA, Fei C, Bonefeld-Jorgensen EC, et al. Perfluoroalkyl acids and time to pregnancy revisited: An update from the Danish National Birth Cohort. Environ Heal A Glob Access Sci Source. 2015;14: 1–8. pmid:26148742
- View Article
- PubMed/NCBI
- Google Scholar
7. Henriksen LS, Mathiesen BK, Assens M, Krause M, Skakkebæk NE, Juul A, et al. Use of stored serum in the study of time trends and geographical differences in exposure of pregnant women to phthalates. Environ Res. 2020;184: 109231. pmid:32087443
- View Article
- PubMed/NCBI
- Google Scholar
8. Rønningen KS, Paltiel L, Meltzer HM, Nordhagen R, Lie KK, Hovengen R, et al. The biobank of the Norwegian Mother and Child Cohort Study: a resource for the next 100 years. Eur J Epidemiol. 2006;21: 619–625. pmid:17031521
- View Article
- PubMed/NCBI
- Google Scholar
9. Bone JN, Pickerill K, Woo Kinshella ML, Vidler M, Craik R, Poston L, et al. Pregnancy cohorts and biobanking in sub-Saharan Africa: a systematic review. BMJ Glob Heal. 2020;5: e003716. pmid:33243854
- View Article
- PubMed/NCBI
- Google Scholar
10. Pierik FH, Klebanoff MA, Brock JW, Longnecker MP. Maternal pregnancy serum level of heptachlor epoxide, hexachlorobenzene, and beta-hexachlorocyclohexane and risk of cryptorchidism in offspring. Environ Res. 2007;105: 364–369. pmid:17532317
- View Article
- PubMed/NCBI
- Google Scholar
11. Cohn BA, Cirillo PM, Christianson RE. Prenatal DDT exposure and testicular cancer: a nested case-control study. Arch Environ Occup Health. 2010;65: 127–134. pmid:20705572
- View Article
- PubMed/NCBI
- Google Scholar
12. Longnecker MP, Klebanoff MA, Brock JW, Zhou H, Gray KA, Needham LL, et al. Maternal serum level of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene and risk of cryptorchidism, hypospadias, and polythelia among male offspring. Am J Epidemiol. 2002;155: 313–322. pmid:11836195
- View Article
- PubMed/NCBI
- Google Scholar
13. Rignell-Hydbom A, Lindh CH, Dillner J, Jönsson BAG, Rylander L. A Nested Case-Control Study of Intrauterine Exposure to Persistent Organochlorine Pollutants and the Risk of Hypospadias. PLoS One. 2012;7: e44767. pmid:23028613
- View Article
- PubMed/NCBI
- Google Scholar
14. Jensen MS, Norgaard-Pedersen B, Toft G, Hougaard DM, Bonde JP, Cohen A, et al. Phthalates and perfluorooctanesulfonic acid in human amniotic fluid: temporal trends and timing of amniocentesis in pregnancy. Environ Health Perspect. 2012;120: 897–903. pmid:22398305
- View Article
- PubMed/NCBI
- Google Scholar
15. Hubel A, Aksan A, Skubitz APN, Wendt C, Zhong X. State of the art in preservation of fluid biospecimens. Biopreserv Biobank. 2011;9: 237–244. pmid:24850337
- View Article
- PubMed/NCBI
- Google Scholar
16. Andersson AM, Jensen TK, Juul A, Petersen JH, Jørgensen T, Skakkebæk NE. Secular decline in male testosterone and sex hormone binding globulin serum levels in Danish population surveys. J Clin Endocrinol Metab. 2007;92: 4696–4705. pmid:17895324
- View Article
- PubMed/NCBI
- Google Scholar
17. Smolcic VS, Bilic-Zulle L, Fisic E. Validation of methods performance for routine biochemistry analytes at Cobas 6000 analyzer series module c501. Biochem medica. 2011;21: 182–190. pmid:22135859
- View Article
- PubMed/NCBI
- Google Scholar
18. Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol. 2009;114: 1326–1331. pmid:19935037
- View Article
- PubMed/NCBI
- Google Scholar
19. Tietz N. Fundamentals of Clinical Chemistry. 5th ed. Burtis C, Ashwood E, editors. Philadelphia: W.B. Saunders; 2001.
20. Holl K, Lundin E, Kaasila M, Grankvist K, Afanasyeva Y, Hallmans G, et al. Effect of long-term storage on hormone measurements in samples from pregnant women: the experience of the Finnish Maternity Cohort. Acta Oncol. 2008;47: 406–412. pmid:17891670
- View Article
- PubMed/NCBI
- Google Scholar
21. Kluger HM, Hoyt K, Bacchiocchi A, Mayer T, Kirsch J, Kluger Y, et al. Plasma markers for identifying patients with metastatic melanoma. Clin Cancer Res. 2011;17: 2417–2425. pmid:21487066
- View Article
- PubMed/NCBI
- Google Scholar
22. Männistö T, Surcel HM, Bloigu A, Ruokonen A, Hartikainen AL, Järvelin MR, et al. The effect of freezing, thawing, and short- and long-term storage on serum thyrotropin, thyroid hormones, and thyroid autoantibodies: implications for analyzing samples stored in serum banks. Clin Chem. 2007;53: 1986–1987. pmid:17954505
- View Article
- PubMed/NCBI
- Google Scholar
23. Haslacher H, Szekeres T, Gerner M, Ponweiser E, Repl M, Wagner OF, et al. The effect of storage temperature fluctuations on the stability of biochemical analytes in blood serum. Clin Chem Lab Med. 2017;55: 974–983. pmid:27988499
- View Article
- PubMed/NCBI
- Google Scholar
24. Gislefoss RE, Grimsrud TK, Mørkrid L. Stability of selected serum hormones and lipids after long-term storage in the Janus Serum Bank. Clin Biochem. 2015;48: 364–369. pmid:25523301
- View Article
- PubMed/NCBI
- Google Scholar
25. Gislefoss RE, Grimsrud TK, Mørkrid L. Long-term stability of serum components in the Janus Serum Bank. Scand J Clin Lab Invest. 2008;68: 402–409. pmid:18752145
- View Article
- PubMed/NCBI
- Google Scholar
26. Carlsen Bach C, Brink Henriksen T, Bossi R, Bech BH, Fuglsang J, Olsen J, et al. Perfluoroalkyl Acid Concentrations in Blood Samples Subjected to Transportation and Processing Delay. PLoS One. 2015;10: e0137768. pmid:26356420
- View Article
- PubMed/NCBI
- Google Scholar
27. Ekström U, Apelqvist J, Hansson E, Bodin T, Wegman DH, Abrahamson M, et al. Insufficient mixing of thawed serum samples leading to erroneous results–experience from a field study and use of a correction procedure. 2019;80: 99–105. pmid:31847598
- View Article
- PubMed/NCBI
- Google Scholar
28. Jackson DH, Banks RE. Banking of clinical samples for proteomic biomarker studies: A consideration of logistical issues with a focus on pre-analytical variation. PROTEOMICS–Clin Appl. 2010;4: 250–270. pmid:21137047
- View Article
- PubMed/NCBI
- Google Scholar
29. Bonini P, Plebani M, Ceriotti F, Rubboli F. Errors in Laboratory Medicine. Clin Chem. 2002;48: 691–698. pmid:11978595
- View Article
- PubMed/NCBI
- Google Scholar

[ref1] 1. Larsen PS, Kamper-Jørgensen M, Adamson A, Barros H, Bonde JP, Brescianini S, et al. Pregnancy and birth cohort resources in europe: a large opportunity for aetiological child health research. Paediatr Perinat Epidemiol. 2013;27: 393–414. pmid:23772942
View Article
PubMed/NCBI
Google Scholar

[2] View Article

[3] PubMed/NCBI

[4] Google Scholar

[ref2] 2. Vrijheid M, Casas M, Bergström A, Carmichael A, Cordier S, Eggesbø M, et al. European birth cohorts for environmental health research. Environ Health Perspect. 2012;120: 29–37. pmid:21878421
View Article
PubMed/NCBI
Google Scholar

[6] View Article

[7] PubMed/NCBI

[8] Google Scholar

[ref3] 3. Hubel A, Spindler R, Skubitz APN. Storage of Human Biospecimens: Selection of the Optimal Storage Temperature. https://home.liebertpub.com/bio. 2014;12: 165–175. pmid:24918763
View Article
PubMed/NCBI
Google Scholar

[10] View Article

[11] PubMed/NCBI

[12] Google Scholar

[ref4] 4. Pukkala E, Andersen A, Berglund G, Gislefoss R, Gudnason V, Hallmans G, et al. Nordic biological specimen banks as basis for studies of cancer causes and control—more than 2 million sample donors, 25 million person years and 100,000 prospective cancers. Acta Oncol. 2007;46: 286–307. pmid:17450464
View Article
PubMed/NCBI
Google Scholar

[14] View Article

[15] PubMed/NCBI

[16] Google Scholar

[ref5] 5. Jellum E, Andersen A, Lund-Larsen P, Theodorsen L, Orjasaeter H. Experiences of the Janus Serum Bank in Norway. Environ Health Perspect. 1995;103 Suppl: 85–8. pmid:7635118
View Article
PubMed/NCBI
Google Scholar

[18] View Article

[19] PubMed/NCBI

[20] Google Scholar

[ref6] 6. Bach CC, Liew Z, Bech BH, Nohr EA, Fei C, Bonefeld-Jorgensen EC, et al. Perfluoroalkyl acids and time to pregnancy revisited: An update from the Danish National Birth Cohort. Environ Heal A Glob Access Sci Source. 2015;14: 1–8. pmid:26148742
View Article
PubMed/NCBI
Google Scholar

[22] View Article

[23] PubMed/NCBI

[24] Google Scholar

[ref7] 7. Henriksen LS, Mathiesen BK, Assens M, Krause M, Skakkebæk NE, Juul A, et al. Use of stored serum in the study of time trends and geographical differences in exposure of pregnant women to phthalates. Environ Res. 2020;184: 109231. pmid:32087443
View Article
PubMed/NCBI
Google Scholar

[26] View Article

[27] PubMed/NCBI

[28] Google Scholar

[ref8] 8. Rønningen KS, Paltiel L, Meltzer HM, Nordhagen R, Lie KK, Hovengen R, et al. The biobank of the Norwegian Mother and Child Cohort Study: a resource for the next 100 years. Eur J Epidemiol. 2006;21: 619–625. pmid:17031521
View Article
PubMed/NCBI
Google Scholar

[30] View Article

[31] PubMed/NCBI

[32] Google Scholar

[ref9] 9. Bone JN, Pickerill K, Woo Kinshella ML, Vidler M, Craik R, Poston L, et al. Pregnancy cohorts and biobanking in sub-Saharan Africa: a systematic review. BMJ Glob Heal. 2020;5: e003716. pmid:33243854
View Article
PubMed/NCBI
Google Scholar

[34] View Article

[35] PubMed/NCBI

[36] Google Scholar

[ref10] 10. Pierik FH, Klebanoff MA, Brock JW, Longnecker MP. Maternal pregnancy serum level of heptachlor epoxide, hexachlorobenzene, and beta-hexachlorocyclohexane and risk of cryptorchidism in offspring. Environ Res. 2007;105: 364–369. pmid:17532317
View Article
PubMed/NCBI
Google Scholar

[38] View Article

[39] PubMed/NCBI

[40] Google Scholar

[ref11] 11. Cohn BA, Cirillo PM, Christianson RE. Prenatal DDT exposure and testicular cancer: a nested case-control study. Arch Environ Occup Health. 2010;65: 127–134. pmid:20705572
View Article
PubMed/NCBI
Google Scholar

[42] View Article

[43] PubMed/NCBI

[44] Google Scholar

[ref12] 12. Longnecker MP, Klebanoff MA, Brock JW, Zhou H, Gray KA, Needham LL, et al. Maternal serum level of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene and risk of cryptorchidism, hypospadias, and polythelia among male offspring. Am J Epidemiol. 2002;155: 313–322. pmid:11836195
View Article
PubMed/NCBI
Google Scholar

[46] View Article

[47] PubMed/NCBI

[48] Google Scholar

[ref13] 13. Rignell-Hydbom A, Lindh CH, Dillner J, Jönsson BAG, Rylander L. A Nested Case-Control Study of Intrauterine Exposure to Persistent Organochlorine Pollutants and the Risk of Hypospadias. PLoS One. 2012;7: e44767. pmid:23028613
View Article
PubMed/NCBI
Google Scholar

[50] View Article

[51] PubMed/NCBI

[52] Google Scholar

[ref14] 14. Jensen MS, Norgaard-Pedersen B, Toft G, Hougaard DM, Bonde JP, Cohen A, et al. Phthalates and perfluorooctanesulfonic acid in human amniotic fluid: temporal trends and timing of amniocentesis in pregnancy. Environ Health Perspect. 2012;120: 897–903. pmid:22398305
View Article
PubMed/NCBI
Google Scholar

[54] View Article

[55] PubMed/NCBI

[56] Google Scholar

[ref15] 15. Hubel A, Aksan A, Skubitz APN, Wendt C, Zhong X. State of the art in preservation of fluid biospecimens. Biopreserv Biobank. 2011;9: 237–244. pmid:24850337
View Article
PubMed/NCBI
Google Scholar

[58] View Article

[59] PubMed/NCBI

[60] Google Scholar

[ref16] 16. Andersson AM, Jensen TK, Juul A, Petersen JH, Jørgensen T, Skakkebæk NE. Secular decline in male testosterone and sex hormone binding globulin serum levels in Danish population surveys. J Clin Endocrinol Metab. 2007;92: 4696–4705. pmid:17895324
View Article
PubMed/NCBI
Google Scholar

[62] View Article

[63] PubMed/NCBI

[64] Google Scholar

[ref17] 17. Smolcic VS, Bilic-Zulle L, Fisic E. Validation of methods performance for routine biochemistry analytes at Cobas 6000 analyzer series module c501. Biochem medica. 2011;21: 182–190. pmid:22135859
View Article
PubMed/NCBI
Google Scholar

[66] View Article

[67] PubMed/NCBI

[68] Google Scholar

[ref18] 18. Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol. 2009;114: 1326–1331. pmid:19935037
View Article
PubMed/NCBI
Google Scholar

[70] View Article

[71] PubMed/NCBI

[72] Google Scholar

[ref19] 19. Tietz N. Fundamentals of Clinical Chemistry. 5th ed. Burtis C, Ashwood E, editors. Philadelphia: W.B. Saunders; 2001.

[ref20] 20. Holl K, Lundin E, Kaasila M, Grankvist K, Afanasyeva Y, Hallmans G, et al. Effect of long-term storage on hormone measurements in samples from pregnant women: the experience of the Finnish Maternity Cohort. Acta Oncol. 2008;47: 406–412. pmid:17891670
View Article
PubMed/NCBI
Google Scholar

[75] View Article

[76] PubMed/NCBI

[77] Google Scholar

[ref21] 21. Kluger HM, Hoyt K, Bacchiocchi A, Mayer T, Kirsch J, Kluger Y, et al. Plasma markers for identifying patients with metastatic melanoma. Clin Cancer Res. 2011;17: 2417–2425. pmid:21487066
View Article
PubMed/NCBI
Google Scholar

[79] View Article

[80] PubMed/NCBI

[81] Google Scholar

[ref22] 22. Männistö T, Surcel HM, Bloigu A, Ruokonen A, Hartikainen AL, Järvelin MR, et al. The effect of freezing, thawing, and short- and long-term storage on serum thyrotropin, thyroid hormones, and thyroid autoantibodies: implications for analyzing samples stored in serum banks. Clin Chem. 2007;53: 1986–1987. pmid:17954505
View Article
PubMed/NCBI
Google Scholar

[83] View Article

[84] PubMed/NCBI

[85] Google Scholar

[ref23] 23. Haslacher H, Szekeres T, Gerner M, Ponweiser E, Repl M, Wagner OF, et al. The effect of storage temperature fluctuations on the stability of biochemical analytes in blood serum. Clin Chem Lab Med. 2017;55: 974–983. pmid:27988499
View Article
PubMed/NCBI
Google Scholar

[87] View Article

[88] PubMed/NCBI

[89] Google Scholar

[ref24] 24. Gislefoss RE, Grimsrud TK, Mørkrid L. Stability of selected serum hormones and lipids after long-term storage in the Janus Serum Bank. Clin Biochem. 2015;48: 364–369. pmid:25523301
View Article
PubMed/NCBI
Google Scholar

[91] View Article

[92] PubMed/NCBI

[93] Google Scholar

[ref25] 25. Gislefoss RE, Grimsrud TK, Mørkrid L. Long-term stability of serum components in the Janus Serum Bank. Scand J Clin Lab Invest. 2008;68: 402–409. pmid:18752145
View Article
PubMed/NCBI
Google Scholar

[95] View Article

[96] PubMed/NCBI

[97] Google Scholar

[ref26] 26. Carlsen Bach C, Brink Henriksen T, Bossi R, Bech BH, Fuglsang J, Olsen J, et al. Perfluoroalkyl Acid Concentrations in Blood Samples Subjected to Transportation and Processing Delay. PLoS One. 2015;10: e0137768. pmid:26356420
View Article
PubMed/NCBI
Google Scholar

[99] View Article

[100] PubMed/NCBI

[101] Google Scholar

[ref27] 27. Ekström U, Apelqvist J, Hansson E, Bodin T, Wegman DH, Abrahamson M, et al. Insufficient mixing of thawed serum samples leading to erroneous results–experience from a field study and use of a correction procedure. 2019;80: 99–105. pmid:31847598
View Article
PubMed/NCBI
Google Scholar

[103] View Article

[104] PubMed/NCBI

[105] Google Scholar

[ref28] 28. Jackson DH, Banks RE. Banking of clinical samples for proteomic biomarker studies: A consideration of logistical issues with a focus on pre-analytical variation. PROTEOMICS–Clin Appl. 2010;4: 250–270. pmid:21137047
View Article
PubMed/NCBI
Google Scholar

[107] View Article

[108] PubMed/NCBI

[109] Google Scholar

[ref29] 29. Bonini P, Plebani M, Ceriotti F, Rubboli F. Errors in Laboratory Medicine. Clin Chem. 2002;48: 691–698. pmid:11978595
View Article
PubMed/NCBI
Google Scholar

[111] View Article

[112] PubMed/NCBI

[113] Google Scholar

Figures

Abstract

Background

Methods

Results

Conclusions

Introduction

Methods and materials

Study design

Data source and study material

Sample handling and storage conditions

Ion analyses

Non-frozen (baseline) quality control samples

Statistical analyses

Results

Discussion and conclusions

Supporting information

S1 Fig.

Acknowledgments

References