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Accounting for urinary dilution in peri-implantation samples: implications for creatinine adjustment and specimen pooling.

ABSTRACT: This study examines critical issues in accounting for urinary dilution in peri-implantation samples used to assess environmental exposures. Early pregnancy could impact creatinine excretion, which could bias biomarker measurement and interpretation when creatinine adjustment is used. We compared creatinine levels pre-implantation with levels soon after implantation at 3-6 weeks gestation. Using data and urine specimens from 145 women who conceived, we used linear mixed models to estimate the effect of pregnancy on creatinine concentrations. We also studied whether creatinine adjustment is biased when using pooled, within-person samples rather than averaging individually-adjusted results. For this, we grouped 2655 daily urinary estrogen metabolite and associated creatinine measures into 762 mathematically-constructed sample pools, and compared averaged individual measures with pooled measures using weighted kappa coefficients and t-tests. Urinary creatinine concentration declined an average of 14% (95% CI: -19, -11%) from pre- to post-implantation. While there was strong correlation between results based on the two creatinine adjustment methods, adjustment based on pooled specimens introduced a small 3% (95% CI: 2, 4%) underestimation of the analyte compared with averaging individually-adjusted samples. Postimplantation creatinine declines could introduce errors in biomonitoring results when comparing exposure measures from pre- and post-implantation. Though pooled creatinine adjustment underestimated adjusted analyte concentrations, the bias was small and agreement excellent between pooled and averaged individually-adjusted assessments.

SUBMITTER: Rosen Vollmar AK

PROVIDER: S-EPMC7671945 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Accounting for urinary dilution in peri-implantation samples: implications for creatinine adjustment and specimen pooling.

Rosen Vollmar Ana K AK Johnson Caroline H CH Weinberg Clarice R CR Deziel Nicole C NC Baird Donna D DD Wilcox Allen J AJ Jukic Anne Marie Z AMZ

Journal of exposure science & environmental epidemiology 20200518 2

This study examines critical issues in accounting for urinary dilution in peri-implantation samples used to assess environmental exposures. Early pregnancy could impact creatinine excretion, which could bias biomarker measurement and interpretation when creatinine adjustment is used. We compared creatinine levels pre-implantation with levels soon after implantation at 3-6 weeks gestation. Using data and urine specimens from 145 women who conceived, we used linear mixed models to estimate the eff ...[more]

PMID: 32424331

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Project description:Study questionDoes sexual intercourse in the implantation time window (5-9 days after ovulation) reduce fecundability?Summary answerAfter adjustment for intercourse in the fecund window and clustering by couple, there was no association between intercourse in the implantation time window and fecundity.What is known alreadyPrevious research has suggested an association between intercourse in the peri-implantation time window (5-9 days after estimated ovulation) and reduced fecundability.Study design, size, durationWe used data from the FERTILI study, a prospective observational study conducted in five European countries, with data collected from 1992 to 1996.Participants/materials, setting, methodsWomen who were experienced in fertility awareness tracking kept a daily diary of cervical mucus observations, basal body temperature measurements, coitus and clinically identified pregnancy. We estimated the day of ovulation as cycle length minus 13 days. From 661 women, 2606 cycles had intercourse during the fecund window (from 5 days before to 3 days after the estimated day of ovulation), resulting in 418 pregnancies (conception cycles). An established Bayesian fecundability model was used to estimate the fecundability ratio (FR) of peri-implantation intercourse on fecundability, while adjusting for each partner's age, prior pregnancy, the couple's probability of conception and intercourse pattern(s). We conducted sensitivity analyses estimating ovulation as cycle length minus 12 days, or alternatively, as the peak day of estrogenic cervical mucus.Main results and the role of chanceThere was no effect of peri-implantation intercourse on fecundability: adjusted FR for three or more acts of peri-implantation intercourse versus none: 1.00, 95% credible interval: 0.76-1.13. Results were essentially the same with sensitivity analyses. There was an inverse relationship between frequency of intercourse in the fecund window and intercourse in the peri-implantation window.Limitations, reasons for cautionWomen with known subfertility were excluded from this study. Many couples in the study were avoiding pregnancy during much of the study, so 61% of otherwise eligible cycles in the database were not at meaningful risk of pregnancy and did not contribute to the analysis. Some couples may not have recorded all intercourse.Wider implications of the findingsWe believe the current balance of evidence does not support a recommendation for avoiding intercourse in the peri-implantation period among couples trying to conceive.Study funding/competing interest(s)No external funding. The authors have no potential competing interests.Trial registration numberN/A.

Dataset Information

Accounting for urinary dilution in peri-implantation samples: implications for creatinine adjustment and specimen pooling.

Publications

Accounting for urinary dilution in peri-implantation samples: implications for creatinine adjustment and specimen pooling.

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