Risk of Chronic Diseases in Young Adults Born Preterm: Relationship With Inflammation and Oxidative Stress Biomarkers.

The purpose of the HAPI project is to study the overall health of preterm infants once they reach adulthood. The investigators would like to compare the health of adults born preterm with that of adults born full-term. They would also like to find the early signs, or biomarkers, of chronic diseases such as high blood pressure, diabetes, osteoporosis, and chronic lung diseases.

Such biomarkers would allow for early diagnosis and prevention. Furthermore, the investigators would like to understand why some people born preterm are more likely to develop chronic disease. They believe that inflammation and oxidative stress may play a part. Oxidative stress is present when the body is not able to defend itself against oxygen-derived products that can damage our cells.

To carry out this study, the investigators will examine 6 aspects of the health: (1) heart and circulation, (2) kidneys, (3) lungs, (4) metabolism - sugars and fats in the blood, (5) bones, and (6) eyes.

Study Overview

• Status: Completed
• Conditions: Prematurity; Extreme
• Intervention / Treatment: Other: preterm birth

Detailed Description

The participants, from both groups will spend a whole day at St. Justine's hospital. Upon arrival after an overnight fast, vital signs and anthropometric measures are taken. Then blood and urine are obtained as well and a pregnancy test is performed for women. After inserting a intravenous catheter, around 55 mL of blood is taken and sent to the biochemistry department and to our laboratory. A oral glucose tolerance test is also performed with blood sampling over 2hours.

Then a renal and carotid ultrasounds, as well as a osteodensitometry test (bone mineral density and body muscle/fat composition) are done. Ophtalmology exam is realized by ophtalmologist, including visual acuity, contrast and fundus photograph, then the participants are provided with a standardized light lunch.

A thorough cardiac ultrasound, as well as assessment of major arteries (aorta, carotid, brachial) structure and function are performed. Pulmonary function tests are done before a fitness test for VO2 max, and repeated with bronchodilatator after the fitness test.

Prior to leaving, participants are given a ambulatory blood pressure monitor for them to carry for 24 consecutive hours over the following 2 days.

Prior to the study day, participants are sent questionnaires to be filled in advance by themselves and by each of their parent. During the study day, other questionnaires regarding their lifestyles and medical condition are also filled. Overall, information is obtained about:

(1) Socio-economic status: Occupation, education level and income of participant and parents. (2) Family history: Parental health (including maternal pregnancies) and familial (1st and 2nd degree) premature history of cardiovascular diseases (CVD), type-2 diabetes, chronic pulmonary or renal diseases. (3) Personal medical history: Current medication use (including anti-inflammatory medications), medical history, current symptoms, and growth parameters from birth to present (according to medical records and child health care booklet), age at menarche.

(4) Health-related behaviors: (a) regular physical activities (Minnesota and Huet validated questionnaires) (b) Smoking and alcohol consumption. (c) Diet assessed through the validated and self-administered 73-item Food Frequency Questionnaire (FFQ). (d) SF-36 Health Survey.

In addition to the study protocol, the subjects are invited to contribute extra biosamples to our blood (3 ml) and urine (1 ml) biobank.

• Study Type: Observational
• Enrollment (Actual): 200

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H3T 1C5
      • StJustine's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 29 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All adults born at GA<29 wks at CHU Sainte-Justine, the Royal Victoria Hospital, and the Jewish General Hospital, Montreal, in 1987-97. For each EPT subject, a friend control matched on sex is selected to control in part for lifestyle and social factors (e.g. diet, physical activity, health care visits), and environmental exposure that may affect inflammatory status and disease risk. Indeed, given the known link between lower socio-economic status, lifestyle habits and CVD risk factors, and that women from lower SES and with poor lifestyle behaviors are at increased risk to deliver prematurely, a friend control, who is more likely to have evolved in a similar milieu, will allow us to better isolate the effect of preterm birth on studied outcomes from socio-environmental factors.

Description

Inclusion Criteria:

EPT :

• Birth at GA<29 wks
• Age 18-29 years at the time of assessment (age of peak human physiological function)

Terms:

• Birth at GA ≥37 wks
• Born in Quebec, to account for health care access during pregnancy and throughout infancy/childhood
• Birth date within 2 years of index case
• Age 18-29 years at the time of assessment
• Same self-reported race as preterm participant.

Exclusion Criteria:

Both groups :

• Currently pregnant due to X-ray related risks
• Severe neurosensory deficit preventing test completion.
• In case of twins (or +), if both fulfil inclusion criteria, only one will selected (random) to participate to the study

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Extremely preterm (EPT); All adults born at gestational age (GA) <29 wks at CHU Sainte-Justine (CHUSJ), the Royal Victoria Hospital (RVH), and the Jewish General Hospital (JGH), Montreal, in 1987-97. Inclusion criteria: (a) Birth at GA<29 wks, (b) age 18-29 years at the time of assessment (age of peak human physiological function). Exclusion criteria: (a) currently pregnant due to X-ray related risks, (b) severe neurosensory deficit preventing test completion. In case of twins (or +), if both fulfil inclusion criteria, only one will selected (random) to participate to the study.	Other: preterm birth; The study compares young adult subjects born premature (< 29 weeks) versus term (-> 37 weeks)
Term or controls; Same-sex friends identified by EPT subject who have accepted to be contacted. Inclusion criteria: (a) Birth at GA ≥37 wks, (b) born in Quebec, to account for health care access during pregnancy and throughout infancy/childhood, (c) birth date within 2 years of index case, (d) age 18-29 years at the time of assessment, (e) same self-reported race as preterm participant. Exclusion criteria: (a) currently pregnant due to X-ray related risks, (b) severe neurosensory deficit preventing test completion.	Other: preterm birth; The study compares young adult subjects born premature (< 29 weeks) versus term (-> 37 weeks)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Markers of inflammation	Blood samples for measurements of biomarkers of inflammation are collected in the morning the day of the visit. Monocyte chemoattractant-1 (pg/mL), Interleukine-6 (pg/mL), tumor necrosis factor-alpha (pg/mL), intercellular adhesion molecule-1 (pg/mL), vascular cell adhesion molecule-1 (pg/mL), high-sensitivity C-reactive protein (pg/mL).	1 hour
Markers of oxydative stress in the blood	Blood samples for measurements of biomarkers of oxidative stress are collected in the morning the day of the visit. Blood : Glutathione (GSH and GSSG (nmol/mg of proteins)) and Redox potential using the Nernst equation and the values of GSH and GSSG (mV).	1 hour
Markers of oxydative stress in the urine	Urine 8-prostaglandin F2-alpha (pg/mL).	1 hour
Markers of oxydative stress in the plasma	Oxidized LDL (U/L)	1 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CVD risk factors and indicators of (sub)clinical disease: blood pressure	Blood pressure (mmHg)	1 hour
CVD risk factors and indicators of (sub)clinical disease: Cardiac structure and function by echocardiography- LV hypertrophy #1	Cardiac structure and function by echocardiography. Left ventricle hypertrophy determined by the LV mass (g) indexed to body surface area (BSA in m2) giving a unit of g/m2.	30 min
CVD risk factors and indicators of (sub)clinical disease: Cardiac structure and function by echocardiography- LV hypertrophy #2	Cardiac structure and function by echocardiography. Left ventricle hypertrophy determined by the interventricular septum thickness (cm).	30 min
CVD risk factors and indicators of (sub)clinical disease: Cardiac structure and function by echocardiography -LV hypertrophy #3	Cardiac structure and function by echocardiography. Left ventricle hypertrophy determined by LV dysfunction (%) or by endocardial fractional shortening (%)	30 min
CVD risk factors and indicators of (sub)clinical disease: Arterial structure and function by ultrasound.	Arterial structure and function (mm) will be measured using a Dopller ultrasound.	1 hour
CVD risk factors and indicators of (sub)clinical disease: Adiposity measures #1	Body mass index in kg/m2, calculating using the weight in kg and the height in m	15 min
CVD risk factors and indicators of (sub)clinical disease: Adiposity measures #2	Using lean and fat body (g) m	30 min
CVD risk factors and indicators of (sub)clinical disease: glucose homeostasis	Plasma fasting glucose (mmol/L) and insulin (mmol/L) and different times after a 75 g of glucose load.	2 hours
CVD risk factors and indicators of (sub)clinical disease: Fasting lipid profile	Plasma triglycerides (mmol/L), HDL (mmol/L) and LDL (mmol/L).	1 hour
CVD risk factors and indicators of (sub)clinical disease: kidneys functions #1	Urinary protein excretion (albumin/creatinine ratio, mg/mmol), eGFR cystatin C (cystatin C : mg/L) (mL/min/1.73 m2). The formula use the cystatin C values in mg/mL, the standardized serum cystatin min and max, the age (in years) and the sex (female: 0.932, male : 1).	30 min
CVD risk factors and indicators of (sub)clinical disease: kidneys functions #2	Use of the eGFR cystatin C formula (cystatin C : mg/L) (mL/min/1.73 m2). The formula use the cystatin C values in mg/mL, the standardized serum cystatin min and max, the age (in years) and the sex (female: 0.932, male : 1).	15 min
CVD risk factors and indicators of (sub)clinical disease: pulmonary functions #1	FEV (%)	30 min
CVD risk factors and indicators of (sub)clinical disease: pulmonary functions #2	Airflow obstruction (FEV1/FVC ratio, no units).	30 min
CVD risk factors and indicators of (sub)clinical disease: Questionnaires #1	Determinants of health. Questionnaires about socio-economics status, family history, personal medical history.	2 hours
CVD risk factors and indicators of (sub)clinical disease: Questionnaires #2	Determinants of health. Maternal obstetrical and subjects neonatal history.	2 hours
CVD risk factors and indicators of (sub)clinical disease: Questionnaires #3	Determinants of health. Health-related behaviors	2 hours
CVD risk factors and indicators of (sub)clinical disease: Questionnaires #4	Determinants of health. Food frequency questionnaire	2 hours

Collaborators and Investigators

• Sponsor: St. Justine's Hospital
• Collaborators: McGill University Health Centre/Research Institute of the McGill University Health Centre; Jewish General Hospital
• Investigators: Principal Investigator: Anne Monique Nuyt, MD, St. Justine's Hospital; Principal Investigator: Thuy Mai Luu, MD, St. Justine's Hospital

Publications and helpful links

General Publications

• Ravizzoni Dartora D, Flahault A, Pontes CNR, He Y, Deprez A, Cloutier A, Cagnone G, Gaub P, Altit G, Bigras JL, Joyal JS, Mai Luu T, Burelle Y, Nuyt AM. Cardiac Left Ventricle Mitochondrial Dysfunction After Neonatal Exposure to Hyperoxia: Relevance for Cardiomyopathy After Preterm Birth. Hypertension. 2022 Mar;79(3):575-587. doi: 10.1161/HYPERTENSIONAHA.121.17979. Epub 2021 Dec 28.
• Dartora DR, Flahault A, Luu TM, Cloutier A, Simoneau J, White M, Lapointe A, Villeneuve A, Bigras JL, Altit G, Nuyt AM. Association of Bronchopulmonary Dysplasia and Right Ventricular Systolic Function in Young Adults Born Preterm. Chest. 2021 Jul;160(1):287-296. doi: 10.1016/j.chest.2021.01.079. Epub 2021 Feb 5.
• Gervais AS, Flahault A, Chan T, Bastien-Tardif C, Al-Simaani A, Cloutier A, Luu TM, Abadir S, Nuyt AM. Electrocardiographic features at rest and during exercise in young adults born preterm below 30 weeks of gestation. Pediatr Res. 2020 Aug;88(2):305-311. doi: 10.1038/s41390-020-0814-9. Epub 2020 Mar 2.
• Flahault A, Paquette K, Fernandes RO, Delfrate J, Cloutier A, Henderson M, Lavoie JC, Masse B, Nuyt AM, Luu TM; HAPI collaborating group*. Increased Incidence but Lack of Association Between Cardiovascular Risk Factors in Adults Born Preterm. Hypertension. 2020 Mar;75(3):796-805. doi: 10.1161/HYPERTENSIONAHA.119.14335. Epub 2020 Jan 27.
• Paquette K, Fernandes RO, Xie LF, Cloutier A, Fallaha C, Girard-Bock C, Mian MOR, Lukaszewski MA, Masse B, El-Jalbout R, Lapeyraque AL, Santos RA, Luu TM, Nuyt AM. Kidney Size, Renal Function, Ang (Angiotensin) Peptides, and Blood Pressure in Young Adults Born Preterm. Hypertension. 2018 Oct;72(4):918-928. doi: 10.1161/HYPERTENSIONAHA.118.11397.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2011
• Primary Completion (Actual): March 29, 2017
• Study Completion (Actual): April 29, 2017

Study Registration Dates

• First Submitted: July 28, 2017
• First Submitted That Met QC Criteria: August 24, 2017
• First Posted (Actual): August 25, 2017

Study Record Updates

• Last Update Posted (Actual): November 3, 2022
• Last Update Submitted That Met QC Criteria: November 2, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: young adults; inflammation; extremely preterm; CVD risks factors; chronic health conditions; term
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Inflammation; Chronic Disease
• Other Study ID Numbers: HAPI clinical project

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: all IPD that underlie results in a publication
• IPD Sharing Time Frame: Starting 1 year after all results of the study are published.
• IPD Sharing Access Criteria: Request of collaboration through data access will be examined by the PI's.
• IPD Sharing Supporting Information Type: Study Protocol; Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No