Top

Published in:

Open Access 01-12-2024 | Premature Birth | Study Protocol

INSIGHT-2: mechanistic studies into pregnancy complications and their impact on maternal and child health—study protocol

Authors: Carlotta Valensin, Emilie J. M. Côté, Daniela Pereira-Carvalho, Rachael A. Gardner, Glen Nishku, Caitlin L. Giles, Carolyn Gill, Anna Brockbank, Lisa Story, Andrew H. Shennan, Natalie Suff, Deena L. Gibbons, Rachel M. Tribe

Published in: Reproductive Health | Issue 1/2024

Abstract

Background

Pregnancy and early childhood cohorts provide a framework for investigating the complex interplay between early-life exposures and health outcomes, thereby informing prevention strategies and interventions to improve maternal and child health. In this paper, we outline the objectives, methodologies and expected contributions of INSIGHT-2, a comprehensive cohort study dedicated to advancing our understanding of pregnancy and pregnancy complications towards improving the health and well-being of mothers and their offspring.

Methods

Over the course of 5 years, the study aims to establish a diverse cohort of 1700 pregnant women and to follow up their children up to 2 years of age. Recruitment targets participants with healthy pregnancies, preexisting conditions, and/or risk factors for pregnancy complications or later child health problems. Clinical and lifestyle data and a range of biological samples will be collected, providing a comprehensive resource for biomarker investigations and cross-sectional analyses. It is anticipated that the cohort will continue beyond this initial 5-year plan.

Discussion

By gathering a wide range of biological samples and using diverse analytical techniques, this study supports broad participation, potential replication and collaboration across various sites. The extensive collection of longitudinal data and samples not only facilitates current investigations but also establishes a biobank for future research. The exploration of pre-pregnancy and pregnancy factors that may contribute to disease processes and impact fetal well-being and future health will provide a comprehensive picture of disease mechanisms in both mothers and children, facilitating the identification of biomarkers for the prediction, diagnosis, and management of pregnancy complications. Additionally, our diverse population allows for the capture of various pregnancy complications and outcomes, enhancing external validity and addressing health disparities. This comprehensive design ultimately aims to improve maternal and child health outcomes by providing a valuable longitudinal study of the relationships among the in utero environment, pregnancy management, and long-term maternal and child health, ensuring that findings are relevant and beneficial to a broader population.

Available only for authorised users

Perinatal Mortality Surveillance | MBRRACE-UK | NPEU [Internet]. [cited 2024 Mar 25]. Available from: https://www.npeu.ox.ac.uk/mbrrace-uk/reports/perinatal-mortality-surveillance

Aughey H, Jardine J, Knight H, Gurol-Urganci I, Walker K, Harris T, et al. Iatrogenic and spontaneous preterm birth in England: a population-based cohort study. BJOG Int J Obstet Gynaecol. 2023;130(1):33–41.CrossRef

Hendy E, Vousden N, Shennan A, Chappell L. OP 35 Incidence of pre-eclampsia in the UK in 2016–17. Pregnancy Hypertens Int J Womens Cardiovasc Health. 2017;1(9):25.

Farrar D, Simmonds M, Griffin S, Duarte A, Lawlor DA, Sculpher M, et al. Prevalence of gestational diabetes in the UK and Republic of Ireland: a systematic review. In: The identification and treatment of women with hyperglycaemia in pregnancy: an analysis of individual participant data, systematic reviews, meta-analyses and an economic evaluation [Internet]. NIHR Journals Library; 2016 [cited 2024 Oct 9]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK401113/

Nakshine VS, Jogdand SD. A comprehensive review of gestational diabetes mellitus: impacts on maternal health, fetal development, childhood outcomes, and long-term treatment strategies. Cureus. 2023;15(10): e47500.PubMedPubMedCentral

Neiger R. Long-term effects of pregnancy complications on maternal health: a review. J Clin Med. 2017;6(8):76.PubMedPubMedCentralCrossRef

Zhang J, Meikle S, Trumble A. Severe maternal morbidity associated with hypertensive disorders in pregnancy in the United States. Hypertens Pregnancy. 2003;22(2):203–12.PubMedCrossRef

Basso O, Rasmussen S, Weinberg CR, Wilcox AJ, Irgens LM, Skjaerven R. Trends in fetal and infant survival following preeclampsia. JAMA. 2006;296(11):1357–62.PubMedCrossRef

Côté-Corriveau G, St-Georges J, Luu TM, Ayoub A, Auger N. Preterm birth and risk of hospitalisation for complex chronic conditions during childhood and adolescence. Acta Paediatr. 2024;113(12):2610–8.PubMedCrossRef

10.

Seaton SE, Agarwal R, Draper ES, Fenton AC, Kurinczuk JJ, Manktelow BN, et al. Estimated neonatal survival of very preterm births across the care pathway: a UK cohort 2016–2020. Arch Dis Child Fetal Neonatal Ed [Internet]. 2023 Apr 20 [cited 2023 Sep 29]; Available from: https://fn.bmj.com/content/early/2023/04/20/archdischild-2022-324987

11.

Feng Q, Ireland G, Gilbert R, Harron K. Data Resource Profile: a national linked mother–baby cohort of health, education and social care data in England (ECHILD-MB). Int J Epidemiol. 2024;53(3):dyae065.

12.

Wright J, Small N, Raynor P, Tuffnell D, Bhopal R, Cameron N, et al. Cohort profile: the born in Bradford multi-ethnic family cohort study. Int J Epidemiol. 2013;42(4):978–91.PubMedCrossRef

13.

Fraser A, Macdonald-Wallis C, Tilling K, Boyd A, Golding J, Davey Smith G, et al. Cohort profile: the Avon longitudinal study of parents and children: ALSPAC mothers cohort. Int J Epidemiol. 2013;42(1):97–110.PubMedCrossRef

14.

Kooijman MN, Kruithof CJ, van Duijn CM, Duijts L, Franco OH, van IJzendoorn MH, et al. The Generation R Study: design and cohort update 2017. Eur J Epidemiol. 2016;31(12):1243–64.

15.

O’Connor T, Best M, Brunner J, Ciesla AA, Cunning A, Kapula N, et al. Cohort profile: Understanding Pregnancy Signals and Infant Development (UPSIDE): a pregnancy cohort study on prenatal exposure mechanisms for child health. BMJ Open. 2021;11(4): e044798.PubMedPubMedCentralCrossRef

16.

Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) - Bioservices Projects [Internet]. [cited 2024 Aug 29]. Available from: https://www.gapps.org/Home/BioservicesProjects

17.

Fettweis JM, Serrano MG, Brooks JP, Edwards DJ, Girerd PH, Parikh HI, et al. The vaginal microbiome and preterm birth. Nat Med. 2019;25(6):1012–21.PubMedPubMedCentralCrossRef

18.

Han X, Ghaemi MS, Ando K, Peterson LS, Ganio EA, Tsai AS, et al. Differential dynamics of the maternal immune system in healthy pregnancy and preeclampsia. Front Immunol. 2019;11(10):1305.CrossRef

19.

Rasmussen M, Reddy M, Nolan R, Camunas-Soler J, Khodursky A, Scheller NM, et al. RNA profiles reveal signatures of future health and disease in pregnancy. Nature. 2022;601(7893):422–7.PubMedPubMedCentralCrossRef

20.

Zhang G, Feenstra B, Bacelis J, Liu X, Muglia LM, Juodakis J, et al. Genetic associations with gestational duration and spontaneous preterm birth. N Engl J Med. 2017;377(12):1156–67.PubMedPubMedCentralCrossRef

21.

Pruski P, Correia GDS, Lewis HV, Capuccini K, Inglese P, Chan D, et al. Direct on-swab metabolic profiling of vaginal microbiome host interactions during pregnancy and preterm birth. Nat Commun. 2021;12(1):5967.PubMedPubMedCentralCrossRef

22.

Chandiramani M, Seed PT, Orsi NM, Ekbote UV, Bennett PR, Shennan AH, et al. Limited relationship between cervico-vaginal fluid cytokine profiles and cervical shortening in women at high risk of spontaneous preterm birth. PLoS ONE. 2012;7(12): e52412.PubMedPubMedCentralCrossRef

23.

Abbott DS, Chin-Smith EC, Seed PT, Chandiramani M, Shennan AH, Tribe RM. Raised trappin2/elafin protein in cervico-vaginal fluid is a potential predictor of cervical shortening and spontaneous preterm birth. PLoS ONE. 2014;9(7): e100771.PubMedPubMedCentralCrossRef

24.

Chin-Smith EC, Hezelgrave NL, Tribe RM. Host defense peptide expression in human cervical cells and regulation by 1,25-Dihydroxyvitamin D3 in the presence of cytokines and bacterial endotoxin. Reprod Sci Thousand Oaks Calif. 2018;25(8):1208–17.CrossRef

25.

Flaviani F, Hezelgrave NL, Kanno T, Prosdocimi EM, Chin-Smith E, Ridout AE, et al. Cervicovaginal microbiota and metabolome predict preterm birth risk in an ethnically diverse cohort. JCI Insight [Internet]. 2021 Aug 23 [cited 2023 Oct 17];6(16). Available from: https://insight.jci.org/articles/view/149257

26.

Hezelgrave NL, Seed PT, Chin-Smith EC, Ridout AE, Shennan AH, Tribe RM. Cervicovaginal natural antimicrobial expression in pregnancy and association with spontaneous preterm birth. Sci Rep. 2020;10(1):12018.PubMedPubMedCentralCrossRef

27.

Camunas-Soler J, Gee EPS, Reddy M, Mi JD, Thao M, Brundage T, et al. Predictive RNA profiles for early and very early spontaneous preterm birth. Am J Obstet Gynecol. 2022;227(1):72.e1-72.e16.PubMedCrossRef

28.

Horrocks V, Hind CK, Wand ME, Fady PE, Chan J, Hopkins JC, et al. Nuclear magnetic resonance metabolomics of symbioses between bacterial vaginosis-associated bacteria. mSphere. 2022;7(3):e0016622.

29.

Garcia M, Downs J, Russell A, Wang W. Impact of biobanks on research outcomes in rare diseases: a systematic review. Orphanet J Rare Dis. 2018;13(1):202.PubMedPubMedCentralCrossRef

30.

Huang K, Si S, Chen R, Wang C, Chen S, Liang Y, et al. Preterm birth and birth weight and the risk of type 1 diabetes in chinese children. Front Endocrinol [Internet]. 2021 [cited 2023 Oct 4];12. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079970/

31.

Crump C, Sundquist J, Sundquist K. Preterm birth and risk of type 1 and type 2 diabetes: a national cohort study. Diabetologia. 2020;63(3):508–18.PubMedCrossRef

32.

Frontiers | Gestational diabetes mellitus and preeclampsia: correlation and influencing factors [Internet]. [cited 2023 Oct 17]. Available from: https://doi.org/10.3389/fcvm.2022.831297/full

33.

Ethnic group, England and Wales—Office for National Statistics [Internet]. [cited 2024 Apr 29]. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/culturalidentity/ethnicity/bulletins/ethnicgroupenglandandwales/census2021

34.

Demography | Lambeth Council [Internet]. [cited 2024 Aug 29]. Available from: https://www.lambeth.gov.uk/adult-social-care-and-health/health-and-wellbeing/lambeth-health-profile/health-wellbeing-profile/demography

35.

Carson LE, Azmi B, Jewell A, Taylor CL, Flynn A, Gill C, et al. Cohort profile: the eLIXIR Partnership—a maternity–child data linkage for life course research in South London, UK. BMJ Open. 2020;10(10): e039583.PubMedPubMedCentralCrossRef

36.

Gravett MG, Menon R, Tribe RM, Hezelgrave NL, Kacerovsky M, Soma-Pillay P, et al. Assessment of current biomarkers and interventions to identify and treat women at risk of preterm birth. Front Med [Internet]. 2024 Jul 26 [cited 2024 Aug 11];11. Available from: https://doi.org/10.3389/fmed.2024.1414428/full

37.

Watson HA, Carlisle N, Seed PT, Carter J, Kuhrt K, Tribe RM, et al. Evaluating the use of the QUiPP app and its impact on the management of threatened preterm labour: a cluster randomised trial. PLoS Med. 2021;18(7): e1003689.PubMedPubMedCentralCrossRef

38.

Carter J, Anumba D, Brigante L, Burden C, Draycott T, Gillespie S, et al. The Tommy’s Clinical Decision Tool, a device for reducing the clinical impact of placental dysfunction and preterm birth: protocol for a mixed-methods early implementation evaluation study. BMC Pregnancy Childbirth. 2022;22(1):639.PubMedPubMedCentralCrossRef

39.

Pociot F, Lernmark Å. Genetic risk factors for type 1 diabetes. The Lancet. 2016;387(10035):2331–9.CrossRef

40.

Yue Y, Tang Y, Tang J, Shi J, Zhu T, Huang J, et al. Maternal infection during pregnancy and type 1 diabetes mellitus in offspring: a systematic review and meta-analysis. Epidemiol Infect. 2018;146(16):2131–8.PubMedPubMedCentralCrossRef

41.

A prospective study of the role of coxsackie B and other enterovirus infections in the pathogenesis of IDDM. Childhood Diabetes in Finland (DiMe) Study Group - PubMed [Internet]. [cited 2024 Feb 22]. Available from: https://pubmed.ncbi.nlm.nih.gov/7789630/

42.

Elfving M, Svensson J, Oikarinen S, Jonsson B, Olofsson P, Sundkvist G, et al. Maternal enterovirus infection during pregnancy as a risk factor in offspring diagnosed with type 1 diabetes between 15 and 30 years of age. J Diabetes Res. 2008;28(2008): e271958.CrossRef

43.

Allen DW, Kim KW, Rawlinson WD, Craig ME. Maternal virus infections in pregnancy and type 1 diabetes in their offspring: Systematic review and meta-analysis of observational studies. Rev Med Virol. 2018;28(3): e1974.PubMedCrossRef

44.

Isaacs SR, Roy A, Dance B, Ward EJ, Foskett DB, Maxwell AJ, et al. Enteroviruses and risk of islet autoimmunity or type 1 diabetes: systematic review and meta-analysis of controlled observational studies detecting viral nucleic acids and proteins. Lancet Diabetes Endocrinol. 2023;11(8):578–92.PubMedCrossRef

45.

Couture C, Brien ME, Boufaied I, Duval C, Soglio DD, Enninga EAL, et al. Proinflammatory changes in the maternal circulation, maternal–fetal interface, and placental transcriptome in preterm birth. Am J Obstet Gynecol. 2023;228(3):332.e1-332.e17.PubMedCrossRef

46.

Musa E, Salazar-Petres E, Arowolo A, Levitt N, Matjila M, Sferruzzi-Perri AN. Obesity and gestational diabetes independently and collectively induce specific effects on placental structure, inflammation and endocrine function in a cohort of South African women. J Physiol. 2023;601(7):1287–306.PubMedCrossRef

47.

Ding J, Maxwell A, Adzibolosu N, Hu A, You Y, Liao A, et al. Mechanisms of immune regulation by the placenta: Role of type I interferon and interferon-stimulated genes signaling during pregnancy. Immunol Rev. 2022;308(1):9–24.PubMedPubMedCentralCrossRef

48.

Isolation of single cells from human uterus in the third trimester of pregnancy: myometrium, decidua, amnion and chorion | Oxford Open Immunology | Oxford Academic [Internet]. [cited 2024 Jul 24]. Available from: https://academic.oup.com/ooim/article/3/1/iqac010/6842331

49.

Chandiramani M, Di Renzo GC, Gottschalk E, Helmer H, Henrich W, Hoesli I, et al. Fetal fibronectin as a predictor of spontaneous preterm birth: a European perspective. J Matern-Fetal Neonatal Med Off J Eur Assoc Perinat Med Fed Asia Ocean Perinat Soc Int Soc Perinat Obstet. 2011;24(2):330–6.

50.

Uus A, Zhang T, Jackson LH, Roberts TA, Rutherford MA, Hajnal JV, et al. Deformable Slice-to-Volume registration for motion correction of fetal body and placenta MRI. IEEE Trans Med Imaging. 2020;39(9):2750–9.PubMedPubMedCentralCrossRef

51.

Williams AJK, Thrower SL, Sequeiros IM, Ward A, Bickerton AS, Triay JM, et al. Pancreatic volume is reduced in adult patients with recently diagnosed type 1 diabetes. J Clin Endocrinol Metab. 2012;97(11):E2109–13.PubMedCrossRef

52.

Penno MAS, Oakey H, Augustine P, Taranto M, Barry SC, Colman PG, et al. Changes in pancreatic exocrine function in young at-risk children followed to islet autoimmunity and type 1 diabetes in the ENDIA study. Pediatr Diabetes. 2020;21(6):945–9.PubMedCrossRef

53.

Waiswa P, Akuze J, Moyer C, Kwesiga D, Arthur S, Sankoh O, et al. Status of birth and pregnancy outcome capture in Health Demographic Surveillance Sites in 13 countries. Int J Public Health. 2019;64(6):909–20.PubMedCrossRef

54.

Côté EJM, Benton M, Gardner R, Tribe R. Balancing benefits and risks of exercise in pregnancy: a qualitative analysis of social media discussion. BMJ Open Sport Exer Med. 2024;10:e002176.CrossRef

55.

Yuste Gómez A, Ramos Álvarez M del P, Bartha JL. Influence of diet and lifestyle on the development of gestational diabetes mellitus and on perinatal results. Nutrients. 2022;14(14):2954.

56.

Perry A, Stephanou A, Rayman MP. Dietary factors that affect the risk of pre-eclampsia. BMJ Nutr Prev Health. 2022;5(1):118–33.PubMedPubMedCentralCrossRef

57.

Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16(9):606–13.PubMedPubMedCentralCrossRef

58.

Spitzer RL, Kroenke K, Williams JBW, Löwe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006;166(10):1092–7.PubMedCrossRef

59.

Taylor JM. Psychometric analysis of the Ten-Item Perceived Stress Scale. Psychol Assess. 2015;27(1):90–101.PubMedCrossRef

60.

Hegarty K, Valpied J. Composite Abuse Scale Manual. 2013.

61.

Piolanti A, Offidani E, Guidi J, Gostoli S, Fava GA, Sonino N. Use of the Psychosocial Index: a sensitive tool in research and practice. Psychother Psychosom. 2016;85(6):337–45.PubMedCrossRef

62.

Montagnoli C, Zanconato G, Cinelli G, Tozzi AE, Bovo C, Bortolus R, et al. Maternal mental health and reproductive outcomes: a scoping review of the current literature. Arch Gynecol Obstet. 2020;302(4):801–19.PubMedCrossRef

63.

Traylor CS, Johnson JD, Kimmel MC, Manuck TA. Effects of psychological stress on adverse pregnancy outcomes and nonpharmacologic approaches for reduction: an expert review. Am J Obstet Gynecol Mfm. 2020;2(4): 100229.PubMedPubMedCentralCrossRef

64.

Pastor-Moreno G, Ruiz-Pérez I, Henares-Montiel J, Petrova D. Intimate partner violence during pregnancy and risk of fetal and neonatal death: a meta-analysis with socioeconomic context indicators. Am J Obstet Gynecol. 2020;222(2):123-133.e5.PubMedCrossRef

65.

Simpson E, Bradley J, Poliakov I, Jackson D, Olivier P, Adamson AJ, et al. Iterative development of an online dietary recall tool: INTAKE24. Nutrients. 2017;9(2):118.PubMedPubMedCentralCrossRef

66.

Marshall NE, Abrams B, Barbour LA, Catalano P, Christian P, Friedman JE, et al. The importance of nutrition in pregnancy and lactation: lifelong consequences. Am J Obstet Gynecol. 2022;226(5):607–32.PubMedCrossRef

67.

O’Hara S, Zelesco M, Sun Z. Cervical length for predicting preterm birth and a comparison of ultrasonic measurement techniques. Australas J Ultrasound Med. 2013;16(3):124–34.PubMedPubMedCentralCrossRef

68.

Badir S, Mazza E, Zimmermann R, Bajka M. Cervical softening occurs early in pregnancy: characterization of cervical stiffness in 100 healthy women using the aspiration technique. Prenat Diagn. 2013;33(8):737–41.PubMedCrossRef

69.

Myatt L, Eschenbach DA, Lye SJ, Mesiano S, Murtha AP, Williams SM, et al. A standardized template for clinical studies in preterm birth. Reprod Sci. 2012;19(5):474–82.PubMedCrossRef

70.

van’t Hooft J, Alfirevic Z, Asztalos E, Biggio J, Dugoff L, Hoffman M, et al. CROWN initiative and preterm birth prevention: researchers and editors commit to implement core outcome sets. BJOG Int J Obstet Gynaecol. 2018;125(1):8–11.

Title: INSIGHT-2: mechanistic studies into pregnancy complications and their impact on maternal and child health—study protocol
Authors: Carlotta Valensin
Emilie J. M. Côté
Daniela Pereira-Carvalho
Rachael A. Gardner
Glen Nishku
Caitlin L. Giles
Carolyn Gill
Anna Brockbank
Lisa Story
Andrew H. Shennan
Natalie Suff
Deena L. Gibbons
Rachel M. Tribe
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Premature Birth
Biomarkers
Type 1 Diabetes
Published in: Reproductive Health / Issue 1/2024
Electronic ISSN: 1742-4755
DOI: https://doi.org/10.1186/s12978-024-01911-0

Seeking information and services associated with reproductive health among rural Peruvian young adults: exploratory qualitative research from Amazonas, Peru

Open Access
Sexually Transmitted Infection
Research

Clinical breakage, slippage and acceptability of two commercial ultra-thin polyurethane male condoms compared to a commercial thin latex condom: a randomised, masked, 3 way crossover, multi centre controlled study (SAGCS 2)

Open Access
Research

“I am putting my fear on them subconsciously”: a qualitative study of contraceptive care in the context of abortion bans in the U.S.

Open Access
Contraception
Research

Health care providers attitude towards safe abortion care and its associated factors in Northwest, Ethiopia, 2021: a health facility-based cross-sectional study

Open Access
Public Health
Research

Influence of menstrual pain and symptoms on activities of daily living and work absenteeism: a cross-sectional study

Open Access
Research

Tanzanian adolescents’ attitudes toward abortion: innovating video vignettes in survey research on health topics

Open Access
Research

Keynote series | Spotlight on menopause

Menopause
Video Series

Menopause can have a significant impact on the body, with effects ranging beyond the endocrine and reproductive systems. Learn about the broader systemic effects of menopause, so you can help patients in your clinics through the transition.

Launching: Thursday 12th December 2024

Prof. Martha Hickey

Dr. Claudia Barth

Dr. Samar El Khoudary

Developed by: Springer Medicine