Preconception health may have intergenerational influences. We have formed the PrePARED (Preconception Period Analysis of Risks and Exposures influencing health and Development) research consortium to address methodological, conceptual, and generalisability gaps in the literature.
Objectives
The consortium will investigate the effects of preconception exposures on four sets of
Outcomes
(1) fertility and miscarriage; (2) pregnancy-related conditions; (3) perinatal and child health; and (4) adult health outcomes.
Population
A study is eligible if it has data measured for at least one preconception time point, has a minimum of selected core data, and is open to collaboration and data harmonisation.
Design
The included studies are a mix of studies following women or couples intending to conceive, general-health cohorts that cover the reproductive years, and pregnancy/child cohort studies that have been linked with preconception data. The majority of the participating studies are prospective cohorts, but a few are clinical trials or record linkages.
Methods
Data analysis will begin with harmonisation of data collected across cohorts. Initial areas of interest include nutrition and obesity; tobacco, marijuana, and other substance use; and cardiovascular risk factors.
PRELIMINARY
Results
Twenty-three cohorts with data on almost 200 000 women have combined to form this consortium, begun in 2018. Twelve studies are of women or couples actively planning pregnancy, and six are general-population cohorts that cover the reproductive years; the remainder have some other design. The primary focus for four was cardiovascular health, eight was fertility, one was environmental exposures, three was child health, and the remainder general women's health. Among other cohorts assessed for inclusion, the most common reason for ineligibility was lack of prospectively collected preconception data.
Conclusions
The consortium will serve as a resource for research in many subject areas related to preconception health, with implications for science, practice, and policy.
PrePARED consortium, preconception exposures health, intergenerational health effects, preconception period research, environmental exposures reproduction, preconception cohort study, developmental origins health, preconception nutrition, epigenetic preconception, preconception care outcomes
PMID 31659792 31659792 DOI 10.1111/ppe.12592 10.1111/ppe.12592 Harville et al. 2019, Harville 2019
Cite this article
Harville, E. W., Mishra, G. D., Yeung, E., Mumford, S. L., Schisterman, E. F., Jukic, A. M., Hatch, E. E., Mikkelsen, E. M., Jiang, H., Ehrenthal, D. B., Porucznik, C. A., Stanford, J. B., Wen, S. W., Harvey, A., Symons Downs, D., Yajnik, C., Santillan, D., Santillan, M., McElrath, T. F., . . . Wise, L. A. (2019). The Preconception Period analysis of Risks and Exposures Influencing health and Development (PrePARED) consortium. Paediatric and perinatal epidemiology, 33(6), 490-502. https://doi.org/10.1111/ppe.12592
Harville EW, Mishra GD, Yeung E, Mumford SL, Schisterman EF, Jukic AM, et al. The Preconception Period analysis of Risks and Exposures Influencing health and Development (PrePARED) consortium. Paediatr Perinat Epidemiol. 2019;33(6):490-502. doi:10.1111/ppe.12592
Harville, E. W., et al. "The Preconception Period analysis of Risks and Exposures Influencing health and Development (PrePARED) consortium." Paediatric and perinatal epidemiology, vol. 33, no. 6, 2019, pp. 490-502.
Keywords
Adult, Biomedical Research/methods/organization & Administration, Child Health, Female, Humans, Infant Health, Infertility/etiology, Intersectoral Collaboration, Male, Maternal Exposure/adverse Effects, Paternal Exposure/adverse Effects, Preconception Care/methods, Pregnancy, Pregnancy Complications/etiology, Prenatal Exposure Delayed Effects/etiology, Research Design, Research Support As Topic, Birthweight, Cohort Studies, Common Data Elements, Fertility, Preconception Care, Pregnancy, Research Design
Sanders JN et al., 2016·Paediatr Perinat Epidemiol·
Most cohort-based research for subfertility has been conducted in clinic-based cohorts, which may differ from population-based cohorts. We retrospectively recruited parallel cohorts of subfertile women: one by sampling two specialty fertility clinics in Utah, and one by population-based sampling based on marriage and birth records. The index date (of first clinic visit or subfertility status) was between 2000 and 2009, and we linked the women recruited to subsequent birth certificate records through December 2010. We enrolled 459 women through clinic-based sampling and 501 women through population-based sampling. Clinic-based women were older, had higher annual household income and more likely to have had a most intensive treatment of intrauterine insemination (31%) or in vitro fertilisation (46%) than women from population recruitment (19% and 14% respectively). Conversely, they were less likely to have received no medical treatment (9%) compared to women from population recruitment (41%). For both types of sampling, prior to eligibility screening, non-responders were less likely to link to a live birth than responders: 51% vs. 58% for clinic-based, and 69% vs. 76% for the population-based with an index date in 2004. Population-based sampling for subfertility cohort research identifies women who were more likely to have had less intensive treatment or no treatment. However, in both clinic-based and population-based sampling, women who have had a live birth are more likely to respond to retrospective recruitment.
Diagnosis of endometriosis is a challenge. The recent development of a saliva-based micro-ribonucleic acid (miRNA) signature for the diagnosis of endometriosis may enable a timelier and less invasive approach, but this requires external validation.
The prospective, multicenter validation of the salivary miRNA signature of endometriosis (ENDOmiRNA) study aimed to assess the diagnostic accuracy, validate the biological reproducibility, and evaluate the clinical utility of a saliva miRNA signature of endometriosis. The study population comprised patients 18 to 43 years of age with signs and symptoms suggestive of endometriosis, who were recruited from diverse medical settings. Patients received a diagnosis of endometriosis by imaging, laparoscopic procedure, or both. All patients who were determined to not have endometriosis were classified as controls (and all underwent laparoscopy). Assessment of endometriosis status based on the saliva miRNA signature was established blinded to patients' endometriosis status, as determined by imaging and/or laparoscopy and/or histology.
The external validation population was composed of 971 patients, including patients from a prior interim analysis, with an overall endometriosis prevalence of 77%. The saliva miRNA signature had an accuracy (defined as the probability of correct classification for both positive and negative results) of 96.6% (95% confidence interval [CI], 95.2 to 97.6%), a sensitivity of 97.3% (95% CI, 96.4 to 98.0%), a specificity of 94.1% (95% CI, 91.0 to 96.4%), a positive predictive value of 98.2% (95% CI, 97.3 to 98.9%), a negative predictive value of 91.3% (95% CI, 88.3 to 93.4%), a positive likelihood ratio of 16.6 (95% CI, 10.8 to 26.9), and a negative likelihood ratio of 0.03 (95% CI, 0.02 to 0.04). Among patients with surgical confirmation of the diagnosis, misclassification, underestimation, and overestimation rates were 4.6%, 2.4%, and 2.2%, respectively, for the saliva miRNA signature and 27.2%, 15.1%, and 12.2%, respectively, for imaging (either transvaginal ultrasound, magnetic resonance imaging, or both).
This prospective, multicenter external validation study demonstrated the accurate performance of a saliva-based miRNA signature for the diagnosis of endometriosis in this cohort. (Funded by Ziwig; ClinicalTrials.gov number, NCT05244668.).
Young-Wolff KC et al., 2024·JAMA internal medicine
Many studies have evaluated whether in utero cannabis exposure is associated with fetal and neonatal outcomes, yet little is known about whether prenatal cannabis use is associated with maternal health outcomes during pregnancy. To evaluate whether prenatal cannabis use is associated with maternal health outcomes during pregnancy. DESIGN, SETTING, This population-based retrospective cohort study included pregnancies in Northern California from January 2011 to December 2019 that lasted 20 weeks or longer and were screened for prenatal cannabis use. Prenatal cannabis use was defined as any self-reported use during early pregnancy or a positive toxicology test result based on universal screening at entrance to prenatal care (approximately 8-10 weeks' gestation). Self-reported frequency of use (daily, weekly, monthly or less, never, unknown), use defined only by self-report, and use defined only by toxicology test results were examined. Electronic health record data were used to define the following outcomes: gestational hypertension, preeclampsia, eclampsia, gestational diabetes, gestational weight gain greater and less than guidelines, placenta previa, placental abruption, placenta accreta, and severe maternal morbidity. Adjusted risk ratios (aRRs) were calculated using a modified Poisson regression. The sample (n = 316 722 pregnancies; 250 221 unique individuals) included 84 039 (26.5%) Asian/Pacific Islander, 20 053 (6.3%) Black, 83 145 (26.3%) Hispanic, and 118 333 (37.4%) White individuals; the mean (SD) age was 30.6 (5.4) years. Overall, 20 053 (6.3%) screened positive for prenatal cannabis use; 2.9% were positive by self-report, 5.3% by toxicology testing, and 1.8% by both. The frequency of cannabis use was 1930 (0.6%) daily, 2345 (0.7%) weekly, 4892 (1.5%) monthly or less, and 10 886 (3.4%) unknown. Prenatal cannabis use was associated with greater risk of gestational hypertension (aRR, 1.17; 95% CI, 1.13-1.21), preeclampsia (aRR, 1.08; 95% CI, 1.01-1.15), weight gain less than (aRR, 1.05; 95% CI, 1.01-1.08) and greater than (aRR, 1.09; 95% CI, 1.08-1.10) guidelines, and placental abruption (aRR, 1.19; 95% CI, 1.05-1.36). The pattern of results was similar when defining prenatal cannabis use only by self-report or only by toxicology testing, and associations between the frequency of prenatal cannabis use and outcomes varied with outcome. The results of this cohort study suggest that prenatal cannabis use was associated with several adverse maternal health outcomes during pregnancy. Continued research is needed to understand whether characteristics of prenatal cannabis use (eg, dose, mode, and timing) moderate these associations.
The discovery of a saliva-based micro–ribonucleic acid (miRNA) signature for endometriosis in 2022 opened up new perspectives for early and noninvasive diagnosis of the disease. The 109-miRNA saliva signature is the product of miRNA biomarkers and artificial intelligence (AI) modeling. We designed a multicenter study to provide external validation of its diagnostic accuracy. We present here an interim analysis. The first 200 patients included in the multicenter prospective ENDOmiRNA Saliva Test study (NCT05244668) were included for interim analysis. The study population comprised women from 18 to 43 years of age with a formal diagnosis of endometriosis or with suspected endometriosis. Epidemiologic, clinical, and saliva sequencing data were collected between November 2021 and March 2022. Genomewide miRNA expression profiling by small RNA sequencing using next-generation sequencing (NGS) was performed, and a random forest algorithm was used to assess the diagnostic accuracy. In this interim analysis of the external validation cohort, with a population prevalence of 79.5%, the 109-miRNA saliva diagnostic signature for endometriosis had a sensitivity of 96.2% (95% confidence interval [CI], 93.7 to 97.3%), specificity of 95.1% (95% CI, 85.2 to 99.1%), positive predictive value of 95.1% (95% CI, 85.2 to 99.1%), negative predictive value of 86.7% (95% CI, 77.6 to 90.3%), positive likelihood ratio of 19.7 (95% CI, 6.3 to 108.8), negative likelihood ratio of 0.04 (95% CI, 0.03 to 0.07), and area under the receiver operating characteristic curve of 0.96 (95% CI, 0.92 to 0.98). The use of NGS and AI in the sequencing and analysis of miRNA provided a saliva-based miRNA signature for endometriosis. Our interim analysis of a prospective multicenter external validation study provides support for its ongoing investigation as a diagnostic tool. (Funded by Ziwig and the Conseil Régional d’Ile de France [Grant EX024087]; ClinicalTrials.gov number, NCT05244668.)