key: cord-0315187-k6qbofzf
authors: Stout, M. J.; Chubiz, J.; Raghuraman, N.; Zhao, P.; Tuuli, M. G.; Wang, L. V.; Cahill, A.; Cuculich, P. S.; Wang, Y.; Jungheim, E. S.; Herzog, E. D.; Fay, J.; Schwartz, A. L.; Macones, G. A.; England, S. K.
title: A Multidisciplinary Prematurity Research Cohort Study
date: 2021-09-29
journal: nan
DOI: 10.1101/2021.09.28.21264264
sha: 661a071952d1ffcee11fd12ca773f34623265a10
doc_id: 315187
cord_uid: k6qbofzf

Background Worldwide, 10% of babies are born preterm, defined as a live birth before 37 weeks of gestation. Preterm birth is the leading cause of neonatal death, and survivors face lifelong risks of adverse outcomes. New approaches with large sample sizes are needed to identify strategies to predict and prevent preterm birth. The primary aims of the Washington University Prematurity Research Cohort Study were to conduct three prospective projects addressing possible causes of preterm birth and provide data and samples for future research. Study Design Pregnant patients were recruited into the cohort between January 2017 and January 2020. Consenting patients were enrolled into the study before 20 weeks' gestation and followed through delivery. Participants completed demographic and lifestyle surveys; provided maternal blood, placenta samples, and cord blood; and participated in up to three projects focused on underlying physiology of preterm birth: cervical imaging (Project 1), circadian rhythms (Project 2), and uterine magnetic resonance imaging and electromyometrial imaging (Project 3). Results A total of 1260 participants were enrolled and delivered during the study period. Of the participants, 706 (56%) were Black/African American, 494 (39%) were nulliparous, and 185 (15%) had a previous preterm birth. Of the 1260 participants, 1220 (97%) delivered a live infant. Of the 1220 with a live birth, 163 (14.1%) had preterm birth, of which 74 (6.1%) were spontaneous preterm birth. Of the 1220 participants with a live birth, 841 participated in cervical imaging, 1047 contributed data and/or samples on circadian rhythms, and 39 underwent uterine magnetic resonance imaging. Of the 39, 25 underwent electromyometrial imaging. Conclusion We demonstrate feasibility of recruiting and retaining a diverse cohort in a complex prospective, longitudinal study throughout pregnancy. The extensive clinical, imaging, survey, and biologic data obtained will be used to explore cervical, uterine, and endocrine physiology of preterm birth and can be used to develop novel approaches to predict and prevent preterm birth.

longitudinal study throughout pregnancy. The extensive clinical, imaging, survey, and biologic data 54 obtained will be used to explore cervical, uterine, and endocrine physiology of preterm birth and can be 55 used to develop novel approaches to predict and prevent preterm birth. 56 57 58 59 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted September 29, 2021. ; https://doi.org/10.1101/2021.09.28.21264264 doi: medRxiv preprint INTRODUCTION delivery for multiple studies. This team was available 24 hours a day, seven days a week, 365 days a year, 114 and each spent approximately 25% of their effort on the three Prematurity Research Center projects. In 115 addition, two statisticians provided analytic support, and a scientific editor reviewed all scientific 116 presentations and reports.

Patients were approached for enrollment at their initial prenatal appointment at two obstetric clinics on the 120 Washington University Medical Campus. One clinic primarily serves patients with public health insurance, 121 and the other primarily serves patients with private health insurance. All potential participants were offered 122 enrollment into projects 1 and 2. Participants were seen at study visits longitudinally throughout pregnancy 123 and at delivery. Study visits were scheduled to obtain data and samples in each of the three trimesters 124 ( Figure 1 ). All study visits were aligned as much as possible with routine obstetric care to minimize 125 inconvenience to the participants. When additional visits were needed outside of routine medical care 126 visits, appointments were scheduled during routine business hours at the participant's convenience. For follow-up and retention, participants were contacted by phone and/or text messages to remind them of 7 medical record releases were requested to obtain delivery data. The case report form used to collect 141 pregnancy outcome data is shown in Table 1 . days, ensuring continuous data collection. Research staff called, texted, or emailed participants to remind 171 them to bring the devices back to the next study visit after the two-week data capture period, or they arranged a courier service for retrieval. If the device was not returned, self-addressed, stamped envelopes were mailed to participants' addresses with a letter requesting return of the device and offering a $20 gift 174 card if they did so.

176 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted September 29, 2021. ; https://doi.org/10.1101/2021.09.28.21264264 doi: medRxiv preprint participate in Project 3. Participants included those at low risk for preterm birth (defined as a normal cervical 178 length at anatomy screen and no history of spontaneous preterm birth) and those at high risk for preterm 179 birth (defined as a previous spontaneous preterm birth less than 35 weeks or a cervical length less than 2 180 cm during the index pregnancy). Those in the low-risk group underwent uterine magnetic resonance 181 imaging (MRI) at 37 weeks' gestation, and those in the high-risk group underwent MRI at 24, 28, and 32 182 weeks' gestation. Once patients presented for induction or in spontaneous labor and were in active labor 183 (defined as greater than 4 cm dilation and regular contractions), body surface potential mapping was 184 performed for approximately one hour. The combined uterine MRI and body surface potential mapping 185 resulted in data used for electromyometrial imaging (EMMI), which has been described elsewhere (9-12).

MRI was performed in a 3T Siemens Prisma/Vida whole-body MRI Scanner with a radial volume 187 interpolated breath-hold examination fast T1-weighted sequence. Patients who also consented to be a part 

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint 

Demographic characteristics of the 1260 participants are described in n/a Difficult Life Circumstances n/a n/a n/a 654 NIH Diet Questionnaire n/a n/a n/a 751 A total of 1220 participants had live births.

A total of 63 participants provided consent to undergo uterine MRI and electrical mapping of the uterus 264 (electromyometrial imaging [EMMI]) at labor ( Table 6) . A total of 24 (17 low-risk, 7 high-risk) participants 265 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this this version posted September 29, 2021. ; https://doi.org/10.1101/2021.09.28.21264264 doi: medRxiv preprint group and 5 in the high-risk group underwent EMMI at labor (Table 6, 7) . Reasons for missed EMMI shut-down (2), and emergent cesarean section (2). Among those who underwent both MRI and EMMI, 271 none of the low-risk participants and two of the high-risk participants delivered preterm ( EMMI, electromyometrial imaging; L&D, Labor and Delivery; MRI, magnetic resonance imaging . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted September 29, 2021. ; https://doi.org/10.1101/2021.09.28.21264264 doi: medRxiv preprint

The primary intent of establishing this cohort was to identify causes of, and develop novel diagnostics to 283 predict, preterm birth. Analyses of data from surveys, swabs, specimens, and imaging are ongoing for the 284 three projects. Specimens are also banked for future research to identify both risk factors and potential 285 biomarkers. The data and specimens we collected will be useful for addressing maternal and neonatal 286 health disparities. This is because over 50% of the participants were Black, and all lived in the St. Louis,

Missouri, area, where Black women have a 50% higher risk of preterm birth than white women (5). 

Study participants were more likely to comply with study procedures that could be timed with clinical 297 appointments or labs (e.g., blood draws, surveys done in waiting room or exam room). Fewer data and 298 specimens were collected in the third trimester than in the first and second trimesters. In part, this was 299 because some participants delivered before their third trimester study visit.

The Prematurity Research Cohort Study has generated a rich set of data and specimens that can be used 303 to test hypotheses pertaining to mechanisms of preterm birth and preventive targets. This dataset and 304 specimen bank will also allow investigators to explore new questions regarding preterm birth, use imaging 305 and biomarkers to assess preterm birth risk in the first trimester, and identify modifiable lifestyle factors 306 that increase risk of preterm birth (6). Our cohort was predominantly those with the highest risk of preterm 307 birth: women of color and women with socioeconomic stressors. Our cohort had a higher percentage of 308 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted September 29, 2021. ; https://doi.org/10.1101/2021.09.28.21264264 doi: medRxiv preprint and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted September 29, 2021. ; https://doi.org/10.1101/2021.09.28.21264264 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted September 29, 2021. ; https://doi.org/10.1101/2021.09.28.21264264 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted September 29, 2021. ; https://doi.org/10.1101/2021.09.28.21264264 doi: medRxiv preprint Supplemental . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted September 29, 2021. ; https://doi.org/10.1101/2021.09.28.21264264 doi: medRxiv preprint

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