Clinical trial NCT02890836: Blood Pressure, Antihypertensive Treatment and Preeclampsia in Pregnant Wom-en With Pre-existing Diabetes
Official title: Blood Pressure, Antihypertensive Treatment and Preeclampsia in Pregnant Wom-en With Pre-existing Diabetes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pregnancy in Diabetics
Keywords: Blood pressure
Hypertension
White coat hypertension
Preeclampsia
Anti-hypertensiva
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Odense University Hospital
First posted: 2016-09-07
Enrollment: 513
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: A cohorte of unselected consecutive pregnant women with pre-existing type 1 and type 2 diabetes will be included.

Brief summary: Aim: First, to investigate the prevalence of a) confirmed hypertension, b) white coat hypertension and c) normal blood pressure in pregnant women with pre-existing diabetes. Second, to explore the prevalence of preeclampsia and preterm delivery in women with pre-existing diabetes with a) confirmed hypertension, b) white coat hypertension and c) normal blood pressure before entering the third trimester of pregnancy. Third, to explore the influence of lifestyle, gestational weight gain and mental well-being on confirmed hypertension and preeclampsia in pregnant women with diabetes.The recruitment period was in 2018 extended to 2020 to perform the following studies: First whether home BP in early pregnancy is superior to office BP to predict preeclampsia. Second to evaluate the prevalence of preeclampsia after initiation of a new treatment strategy including prophylactic aspirin and, in case of insufficiency, vitamin D supplementation.

Design: A prospective multicentre observational study where approximately 400 pregnant women with pre-existing diabetes are offered measurements of office blood pressure (BP) and home BP for three days three times during pregnancy as well as when the routinely measured office BP exceeds 135/85 mmHg. The prevalence of confirmed hypertension (office BP \>135/85 mmHg and home BP \>130/80 mmHg) and white coat hypertension (office BP \>135/85 mmHg but home BP ≤130/80 mmHg) will be determined. Women with confirmed hypertension are offered antihypertensive treatment mainly with methyldopa. In women with a) confirmed hypertension, b) white coat hypertension, and c) normal blood pressure before entering third trimester of pregnancy, the prevalence of preeclampsia and preterm delivery will be evaluated. Possible side effects of antihypertensive treatment including impaired fetal haemodynamics and lower infant birth weight will be recorded. The women will complete food diaries and questionnaires on lifestyle and mental health three times in pregnancy in order to evaluate the influence of these parameters on hypertension and preeclampsia.

Detailed description: Design: Home blood pressure and office blood pressure as predictors of preeclampsia will be evaluated in the total cohort. From February 2018, the routine care includes treatment with prophylactic aspirin in all women with pre-existing diabetes and screening for vitamin D insufficiency, treated with vitamin D depending on the severity of the insufficiency. The prevalence of preeclampsia after initiation of the new treatment strategy will be evaluated. The women included from 2016-2018, where aspirin was only initiated if other risk factors to preeclampsia apart from diabetes were present, will be used for comparison.

Eligibility criteria: Inclusion Criteria:

Inclusion criteria for pregnant women with diabetes:

* Women with pre-existing diabetes, older than 18 years and referred to The Center for Pregnant Women with Diabetes, Rigshospitalet, or the Centre for Diabetes and Pregnancy, Odense University Hospital, with a live singleton or twin pregnancy before 20 weeks during the inclusion period.
* Women with diabetes diagnosed in pregnancy before 20 weeks (HbA1c ≥48 mmol/mol) may also be included as having type 2 diabetes.
* Sufficient Danish language skills to read and understand the patient information sheet and to converse.

Inclusion criteria for pregnant healthy women without diabetes:

* Women above 18 years of age, with a live singleton pregnancy, referred to a nuchal translucency scan at 11-14 weeks at The Department of Obstetrics, Rigshospitalet.
* Sufficient Danish language skills to read and understand the patient information sheet and to converse.

Exclusion Criteria:

Exclusion criteria for both study groups:

• Women diagnosed with severe diseases that could possibly bias BP measurements or pregnancy outcome. This is judged by the principal investigators.

Primary outcomes:
measure: Confirmed hypertension
timeFrame: 2 years
measure: White coat hypertension
timeFrame: 2 years
measure: Preeclampsia
timeFrame: 4 years
measure: Early preeclampsia
timeFrame: 4 years
measure: Preterm birth
timeFrame: 4 years
measure: Early preterm delivery (international)
timeFrame: 4 years
measure: Early preterm delivery (Danish)
timeFrame: 4 years
Secondary outcomes:
measure: Gestational hypertension
timeFrame: 4 years
measure: Chronic hypertension
timeFrame: 4 years
Other outcomes:
measure: Infant birth weight SD-score
timeFrame: 4 years
measure: Large for gestational age
timeFrame: 4 years
measure: Small for gestational age
timeFrame: 4 years
measure: Ponderal index
timeFrame: 2 years
measure: Gestational weight gain
timeFrame: 4 years
measure: Caesarean section
timeFrame: 4 years
measure: Shoulder dystocia
timeFrame: 4 years
measure: Degree of rupture
timeFrame: 2 years
measure: Duration from induction of labour to delivery
timeFrame: 2 years
measure: Duration of active labour
timeFrame: 2 years
measure: Major congenital malformations
timeFrame: 4 years
measure: Perinatal mortality
timeFrame: 4 years
measure: Perinatal morbidity
timeFrame: 4 years
measure: Neonatal hypoglycaemia (Danish definition)
timeFrame: 4 years
measure: Neonatal hypoglycaemia (common international)
timeFrame: 4 years
measure: Jaundice
timeFrame: 4 years
measure: Transient tachypnea of the newborn
timeFrame: 4 years
measure: Apgar score
timeFrame: 4 years
measure: Microalbuminuria
timeFrame: 4 years
measure: Diabetic nephropathy
timeFrame: 4 years
measure: Diabetic retinopathy
timeFrame: 4 years
measure: Kidney involvement
timeFrame: 4 years
measure: Pulsatility index (PI) of the middle cerebral artery (MCA) measured with Doppler flow measurements
timeFrame: 2 years
measure: Pulsatility index (PI) of the umbilical artery (UA) measured with Doppler flow
timeFrame: 2 years
measure: Ratio of the pulsatility index (PI) of the middle cerebral artery and the umbilical artery
timeFrame: 2 years
measure: Body mass index (BMI)
timeFrame: 4 years
Locations:
city: Copenhagen
country: Denmark
facility: Center for Pregnant Women with Diabetes
state: Kbh Ø
Study officials:
References:
citation: Do NC, Vestgaard M, Asbjornsdottir B, Andersen LLT, Jensen DM, Ringholm L, Damm P, Mathiesen ER. Home Blood Pressure for the Prediction of Preeclampsia in Women With Preexisting Diabetes. J Clin Endocrinol Metab. 2022 Aug 18;107(9):e3670-e3678. doi: 10.1210/clinem/dgac392.
citation: Asbjornsdottir B, Vestgaard M, Do NC, Ringholm L, Andersen LLT, Jensen DM, Damm P, Mathiesen ER. Prevalence of anxiety and depression symptoms in pregnant women with type 2 diabetes and the impact on glycaemic control. Diabet Med. 2021 Mar;38(3):e14506. doi: 10.1111/dme.14506. Epub 2021 Jan 8.
citation: Do NC, Vestgaard M, Asbjornsdottir B, Nichum VL, Ringholm L, Andersen LLT, Jensen DM, Damm P, Mathiesen ER. Physical activity, sedentary behavior and development of preeclampsia in women with preexisting diabetes. Acta Diabetol. 2020 May;57(5):559-567. doi: 10.1007/s00592-019-01459-7. Epub 2019 Nov 28.
citation: Vestgaard M, Asbjornsdottir B, Ringholm L, Andersen LLT, Jensen DM, Damm P, Mathiesen ER. White coat hypertension in early pregnancy in women with pre-existing diabetes: prevalence and pregnancy outcomes. Diabetologia. 2019 Dec;62(12):2188-2199. doi: 10.1007/s00125-019-05002-9. Epub 2019 Oct 18.