SD-OCT Measurement of the Human Retina in Pregnancy With Pre-existing or De Novo Hypertension and Without Hypertension

NCT04286217 | Active Not Recruiting

• 1 other identifier: REB15-0374
• Study Type: observational
• Target: 155
• Locations: 0 countries
• Sites: N/A

Brief Summary

The complications of long-standing severe and acute severe elevations in systemic blood pressure (hypertension) may involve large vessels as well as smaller vessels, these latter comprising what is known as the microcirculation. Diseases of the microcirculation include stroke, dementia, and end stage renal disease to name a few. The microcirculation of the brain (and kidneys) possess a reflex called autoregulation that protects the downstream organ from fluctuations in blood pressure and blood flow. The neurosensory retina of the eye is a forward extension of brain and has a similar microcirculation to that of brain, including the presence of blood retinal barriers and the ability to autoregulate. One of the consequences of very severe hypertension is breakthrough of the autoregulatory reflex with hyperperfusion injury and edema formation. Currently, physicians and scientists have no tools to visualize or measure the human microcirculation or the autoregulatory reflex. SD-OCT is an advanced imaging technology that has a spatial resolution 1000-10,000 times greater than CT or MRI. It is the standard of care for identification and follow-up of structural diseases of the eye. The question this research proposal attempts to answer is whether SD-OCT is able to detect edema or other evidence of structural damage in the eyes in patients in the midst of, or following an episode of very severe hypertension. Pregnant women were chosen to be the focus of this study because: 1) pregnant women are generally young and would be expected to possess a normal microcirculation, 2) the occurrence of new-onset hypertension in pregnancy is high, occurring in 5-10% of all pregnancies, 3) there are established prediction rules that allow one to select and compare women at high- or low-risk of developing hypertension in pregnancy, and finally 4) the spectrum of hypertensive injury in pregnancy ranges from minor elevations in systemic blood pressures to eclampsia, the most severe, life-threatening form of hypertensive injury possible. All this is occurs within a 9-month time window defining human pregnancy. Thus, the investigators are proposing to examine the eyes of women using SD-OCT at low- and high-risk of developing hypertension in pregnancy to determine if, when and how this injury is occurring and its relationship to blood pressures.

Conditions

Pregnancy Induced Hypertension; Pregnancy Related

Keywords

human pregnancy; hemodynamic changes in pregnancy; macular thickness; microcirculation; autoregulation; spectral domain optical coherence tomography

Outcome Measures

Primary Outcomes (1)

• SD-OCT measured change in retinal macular thickness during pregnancy at each gestational period for all study subgroups

  The observed change in retinal macular thickness at each gestational period referenced to its baseline measurement in the non-pregnant state will be characterized using both our clinical decision support tool and summary statistics and comparisons made between each subgroup in the study. Some subgroups such as those examining pre-existing and do novo hypertension, or those looking separately at gestational hypertension and preeclampsia may be combined if the pattern of end-tissue response of the retina is the same.

  At < 20 weeks gestation, from 20 weeks gestation up to before delivery, and at delivery

Secondary Outcomes (1)

• Relationship of mean arterial blood pressure to observed macular response in pregnancy at each gestational interval for all study subgroups

  At < 20 weeks gestation, from 20 weeks gestation up to before delivery, and at delivery

Other Outcomes (1)

• Relationship of breach of microcirculatory autoregulatory integrity of the eye, if observed, to breach in other regional circulations

  At < 20 weeks gestation, from 20 weeks gestation up to before delivery, and at delivery

Study Arms (14)

No prior hypertension (HTN); no HDP in pregnancy

No pre-existing hypertension, incident pregnancy not complicated by a hypertensive event

No prior HTN; de novo HDP, GH type; no macular injury

No pre-existing hypertension, incident pregnancy complicated by new onset gestational hypertension, but no abnormal SD-OCT findings in the eye

No prior HTN; de novo HDP, GH type; macular injury found

No pre-existing hypertension, incident pregnancy complicated by new onset gestational hypertension, with abnormal SD-OCT findings in the eye consistent with possible hyperperfusion injury

No prior HTN; de novo HDP, PE type; no macular injury

No pre-existing hypertension, incident pregnancy complicated by new onset preeclampsia, but no abnormal SD-OCT findings in the eye

No prior HTN; de novo HDP, PE type; macular injury found

No pre-existing hypertension, incident pregnancy complicated by new onset preeclampsia, with abnormal SD-OCT findings in the eye consistent with possible hyperperfusion injury

No prior HTN; no HDP in pregnancy; postpartum HDP

No pre-existing hypertension, incident pregnancy not complicated by a hypertensive event, patient developed postpartum HDP, either gestational hypertension or preeclampsia, with abnormal SD-OCT findings in the eye consistent with possible hyperperfusion injury

Pre-existing HTN; no HDP in pregnancy

Pre-existing hypertension, incident pregnancy not complicated by a hypertensive event

Pre-existing HTN; de novo HDP, GH type; no macular injury

Pre-existing hypertension, incident pregnancy complicated by new onset gestational hypertension, but no abnormal SD-OCT findings in the eye

Pre-existing HTN; de novo HDP, GH type; macular injury found

Pre-existing hypertension, incident pregnancy complicated by new onset gestational hypertension, with abnormal SD-OCT findings in the eye consistent with possible hyperperfusion injury

Pre-existing HTN; de novo HDP, PE type; no macular injury

Pre-existing hypertension, incident pregnancy complicated by new onset preeclampsia, but no abnormal SD-OCT findings in the eye

Pre-existing HTN; de novo HDP, PE type; macular injury found

Pre-existing hypertension, incident pregnancy complicated by new onset preeclampsia, with abnormal SD-OCT findings in the eye consistent with possible hyperperfusion injury

Pre-existing HTN; no HDP in pregnancy; postpartum HDP

Pre-existing hypertension, incident pregnancy not complicated by a hypertensive event, patient developed postpartum HDP, either gestational hypertension or preeclampsia,with abnormal SD-OCT findings in the eye consistent with possible hyperperfusion injury

Other causes of macular injury leading to HDP

Other causes of abnormal SD-OCT findings in the eye consistent with possible hyperperfusion injury leading to HDP, either gestational hypertension or preeclampsia

Other causes of macular injury not leading to HDP

Other causes of abnormal SD-OCT findings in the eye consistent with possible hyperperfusion injury not leading to HDP

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Pregnant women aged 18-45 years and at \< 20 weeks gestation will be recruited from an outpatient obstetrical internal medicine clinic at the Foothills Medical Centre in Calgary, Canada into 2 cohorts depending upon their risk for developing a hypertensive disorder of pregnancy (HDP).

You may qualify if:

• Cohort I Women at Low-risk for Developing an HDP (possessing none of the high risk variables outlined in Cohort II below)
• Cohort II Women at High-risk for Developing an HDP
• chronic hypertension
• prior preeclampsia
• prior gestational hypertension
• chronic kidney disease, or
• ≥ 2 of the following: age \>35 years, body mass index (BMI) \> 30 kg/m2, twin or multiple gestation pregnancy, non-Caucasian ethnicity

You may not qualify if:

• pre-existing type 1 or type 2 diabetes mellitus
• vasculitis
• known or observed retinal disease at enrolment

Sponsors & Collaborators

• University of Calgary: lead

Related Publications (5)

• Huang J, Liu X, Wu Z, Xiao H, Dustin L, Sadda S. Macular thickness measurements in normal eyes with time-domain and Fourier-domain optical coherence tomography. Retina. 2009 Jul-Aug;29(7):980-7. doi: 10.1097/IAE.0b013e3181a2c1a7.

  PMID: 19584656 BACKGROUND

• Conti E, Zezza L, Ralli E, Caserta D, Musumeci MB, Moscarini M, Autore C, Volpe M. Growth factors in preeclampsia: a vascular disease model. A failed vasodilation and angiogenic challenge from pregnancy onwards? Cytokine Growth Factor Rev. 2013 Oct;24(5):411-25. doi: 10.1016/j.cytogfr.2013.05.008. Epub 2013 Jun 22.

  PMID: 23800655 BACKGROUND

• Kanasaki K, Kalluri R. The biology of preeclampsia. Kidney Int. 2009 Oct;76(8):831-7. doi: 10.1038/ki.2009.284. Epub 2009 Aug 5.

  PMID: 19657323 BACKGROUND

• Magee LA, Pels A, Helewa M, Rey E, von Dadelszen P; Canadian Hypertensive Disorders of Pregnancy Working Group. Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy: executive summary. J Obstet Gynaecol Can. 2014 May;36(5):416-41. doi: 10.1016/s1701-2163(15)30588-0. English, French.

  PMID: 24927294 BACKGROUND

• Wolf M, Shah A, Jimenez-Kimble R, Sauk J, Ecker JL, Thadhani R. Differential risk of hypertensive disorders of pregnancy among Hispanic women. J Am Soc Nephrol. 2004 May;15(5):1330-8. doi: 10.1097/01.asn.0000125615.35046.59.

  PMID: 15100374 BACKGROUND

MeSH Terms

Conditions

Hypertension, Pregnancy-Induced

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Robert J Herman, MD

  University of Calgary

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2020
• First Posted: February 26, 2020
• Study Start: October 30, 2013
• Primary Completion: December 31, 2024
• Study Completion (Estimated): December 31, 2026
• Last Updated: November 22, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share