Preeclampsia and Fetal Heart Malformations: Looking to Maternal Heart

Official title

Preeclampsia e Malformazioni Cardiache Fetali: Uno Sguardo al Cuore Materno

Overview

The goal of this study is to describe the maternal hemodynamic parameters detected by UltraSonic Cardiac Output Monitor (USCOM®) in women carrying a fetus with a congenital heart disease (CHD) and to possibly describe an association between those parameters and the presence of a fetal cardiac anomaly. It will also learn about: * the number of cases of preeclampsia in our population of women carrying fetuses with CHD * the relationship between maternal hemodynamic profile and maternal and perinatal outcome * the associations between maternal hemodynamic parameters and the specific heart defect subtype * the relationship between maternal hemodynamic parameters and fetal cardiac parameters in our population. The haemodynamic evaluation will be performed at the time of diagnosis of CHD and then every two weeks until delivery. A further evaluation will be performed immediately after delivery (within 72 hours).

Detailed description

The following maternal hemodynamic indices will be evaluated: heart rate (HR) (beats per min; bpm), mean arterial pressure (mmHg), stroke volume (mL), cardiac output (CO) (L/min), systemic vascular resistance (dynes/s/cm5). Data on the demographic and pregnancy characteristics of participants, hemodynamic and ultrasound investigations, perinatal and delivery features will be also collected. In particular, the following variables will be included in the study: type of congenital heart defect, gestational age at diagnosis, fetal weight (EFW) and fetal weight centile at diagnosis of CHD and at the last scan before delivery, mean uterine arteries pulsatility index (UtA-PI), fetal umbilical artery (UA-PI) and middle cerebral artery pulsatility index (MCA-PI) at diagnosis and at the last scan before delivery, maternal age, height, pre-pregnancy weight and gestational weight gain, systolic and diastolic blood pressure values (maximum and minimum values), presence of proteinuria, biochemical maternal assessment (maximun and miminum values of creatinine and uric acid level, platelet count, liver enzyme level), incidence of hypertensive disorders of pregnancy, antihypertensive drug administration (type and dosage) including magnesium sulfate, antenatal steroid administration, mode of delivery and indications, gestational age at delivery, birthweight and birthweight centile, need of respiratory or cardiac support, neonatal intensive care unit admission and number of days, major neonatal complications, maternal morbidities (HELLP, eclampsia, intravascular disseminate coagulation, post-partum hemorrhage), and mortality. The following definitions of hypertensive disorders will be used, according to the International Society for the Study of Hypertension in Pregnancy (ISSHP) 2018 criteria (14): chronic hypertension (CH) will be defined as hypertension (≥140/90mmHg) that predates pregnancy or is present prior to 20 weeks' gestation; gestational hypertension was defined as de-novo hypertension (≥ 140/90 mmHg) after 20 weeks' gestation; and preeclampsia (PE) will be defined as de-novo hypertension (≥ 140/90 mmHg) after 20 weeks' gestation with coexisting proteinuria, other maternal organ dysfunction or fetal growth restriction; preeclampsia superimposed to chronic hypertension (PE-CH).

Interventions

• Device UltraSonic Cardiac Output Monitor (USCOM®)
  Using USCOM, the haemodynamic evaluation will be performed at the time of diagnosis of congenital heart desease and then every two weeks until delivery. A further evaluation will be performed immediately after delivery (within 72 hours).

Primary outcome measures

• Maternal hemodynamic parametrics changes (Cardiac Output, assessed by USCOM® system) in pregnancies complicated by congenital heart diseases and immediately after delivery [Time frame: 36 months]
• Maternal hemodynamic parametrics changes (Systemic vascular resistance, assessed by USCOM® system) in pregnancies complicated by congenital heart diseases and immediately after delivery [Time frame: 36 months]

Secondary outcome measures (12)

• Prevalence of cases of preeclampsia in our population of pregnancies complicated by congenital heart disease [Time frame: 36 months]
• Correlation between maternal hemodynamic profile (Cardiac Output) and perinatal outcome [Time frame: 36 months]
• Correlation between maternal hemodynamic profile (Systemic vascular resistance) and perinatal outcome [Time frame: 36 months]
• Correlation between maternal hemodynamic profile and perinatal outcome (gestational age at delivery) [Time frame: 36 months]
• Correlation between maternal hemodynamic profile and perinatal outcome (birthweight) [Time frame: 36 months]
• Correlation between maternal hemodynamic profile and perinatal outcome (birthweight centile) [Time frame: 36 months]
• Correlation between maternal hemodynamic profile and perinatal outcome (need of respiratory or cardiac support) [Time frame: 36 months]
• Correlation between maternal hemodynamic profile and perinatal outcome (neonatal intensive care unit admission) [Time frame: 36 months]
• Correlation between maternal hemodynamic profile and perinatal outcome (number of days in neonatal intensive care unit) [Time frame: 36 months]
• Correlation between maternal hemodynamic profile and perinatal outcome (major neonatal complications) [Time frame: 36 months]
• Correlation coefficients between the maternal hemodynamic parameters (Cardiac output) to the specific heart defect type [Time frame: 36 months]
• Correlation coefficients between the maternal hemodynamic parameters (Systemic vascular resistance) to the specific heart defect type [Time frame: 36 months]

Eligibility criteria

Inclusion criteria

• Informed consent accepted
• Maternal Age ≥ 18 years
• Singleton pregnancy with a viable fetus at >20 weeks of gestation, with a diagnosis of congenital heart disease detected on antenatal ultrasound assessment and postnatally confirmed

Exclusion criteria

• Multiple pregnancy
• Pregnancy complicated by aneuploidy, genetic syndrome, or major structural fetal abnormality
• Maternal congenital heart disease (GUCH)
• Maternal known cardiac disease

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Other

Study locations

Italy · 1 center

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Francesco Vito 1, 00168 — Roma

Publications

• Vinayagam D, Patey O, Thilaganathan B, Khalil A. Cardiac output assessment in pregnancy: comparison of two automated monitors with echocardiography. Ultrasound Obstet Gynecol. 2017 Jan;49(1):32-38. doi: 10.1002/uog.15915. PMID 26970353
• Hodgson LE, Venn R, Forni LG, Samuels TL, Wakeling HG. Measuring the cardiac output in acute emergency admissions: use of the non-invasive ultrasonic cardiac output monitor (USCOM) with determination of the learning curve and inter-rater reliability. J Intensive Care Soc. 2016 May;17(2):122-128. doi: 10.1177/1751143715619186. Epub 2015 Dec 10. PMID 28979476
• Brown MA, Magee LA, Kenny LC, Karumanchi SA, McCarthy FP, Saito S, Hall DR, Warren CE, Adoyi G, Ishaku S; International Society for the Study of Hypertension in Pregnancy (ISSHP). Hypertensive Disorders of Pregnancy: ISSHP Classification, Diagnosis, and Management Recommendations for International Practice. Hypertension. 2018 Jul;72(1):24-43. doi: 10.1161/HYPERTENSIONAHA.117.10803. No abstract ava PMID 29899139
• Melchiorre K, Giorgione V, Thilaganathan B. The placenta and preeclampsia: villain or victim? Am J Obstet Gynecol. 2022 Feb;226(2S):S954-S962. doi: 10.1016/j.ajog.2020.10.024. Epub 2021 Mar 24. PMID 33771361
• Masini G, Foo LF, Tay J, Wilkinson IB, Valensise H, Gyselaers W, Lees CC. Preeclampsia has two phenotypes which require different treatment strategies. Am J Obstet Gynecol. 2022 Feb;226(2S):S1006-S1018. doi: 10.1016/j.ajog.2020.10.052. Epub 2021 Jun 10. PMID 34774281
• Miremberg H, Gindes L, Schreiber L, Raucher Sternfeld A, Bar J, Kovo M. The association between severe fetal congenital heart defects and placental vascular malperfusion lesions. Prenat Diagn. 2019 Oct;39(11):962-967. doi: 10.1002/pd.5515. Epub 2019 Jul 17. PMID 31254468
• Thilaganathan B. Preeclampsia and Fetal Congenital Heart Defects: Spurious Association or Maternal Confounding? Circulation. 2017 Jul 4;136(1):49-51. doi: 10.1161/CIRCULATIONAHA.117.028816. No abstract available. PMID 28674092
• Boyd HA, Basit S, Behrens I, Leirgul E, Bundgaard H, Wohlfahrt J, Melbye M, Oyen N. Association Between Fetal Congenital Heart Defects and Maternal Risk of Hypertensive Disorders of Pregnancy in the Same Pregnancy and Across Pregnancies. Circulation. 2017 Jul 4;136(1):39-48. doi: 10.1161/CIRCULATIONAHA.116.024600. Epub 2017 Apr 19. PMID 28424221

Identifiers

NCT: NCT07092644 · 7552 · Ethic Committee Gemelli

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗