SCRIPT: Sickle Cell Risk in Pregnancy Tool
NCT Number: NCT06529042
Acronym: SCRIPT
Status: ENROLLING_BY_INVITATION
Study Type: OBSERVATIONAL
Conditions: Sickle Cell Disease|Pregnancy, High Risk|Pregnancy Complications
Interventions: OTHER: Non-Interventional
Sponsor: Mount Sinai Hospital, Canada
Collaborators: Centre hospitalier de l'Université de Montréal (CHUM)|Johns Hopkins University|Providence Health & Services
Sex: FEMALE
Age: CHILD, ADULT
Enrollment: 1000
Study Design: Observational Model: |Time Perspective: p
Start Date: 2024-07
Completion Date: 2026-12
Locations: Johns Hopkins University, Baltimore, Maryland, 21218, United States|Providence Health Care, Vancouver, British Columbia, V5Z 1M9, Canada|Centre hospitalier de l'Université de Montréal, Montréal, Quebec, H2X 0C1, Canada

Summary:
Sickle Cell Disease (SCD), common in persons of Black ancestry, affects the shape of hemoglobin, the oxygen-carrying part of red blood cells (RBC). It is characterized by many complications, the most dreaded of which are related to pregnancy - affecting both the mother and unborn child. Compared to those without SCD, people with SCD have more adverse pregnancy outcomes (APO): 6x maternal mortality, 2x preeclampsia \& preterm birth, 4x risk of having a baby not growing well in the womb \& stillbirth. There is also greater need for access to care (7x higher hospitalization often multiple times lasting days to months). Yet up to 30% of SCD pregnancies are uncomplicated.

Treatments in pregnancy are limited and carry risks. A method to distinguish pregnancies at high-risk of APO that may benefit from these potentially risky treatments, from those likely to be uncomplicated, is urgently needed. To meet this need, the investigators developed a calculator to estimate pregnancy complication risk, using single-centre data. Its accuracy and precision will now be evaluated with international information from several centers by testing the calculator, and adjusting it as needed, using already available pregnancy-data from study centres in several countries. Those age \>16 years, who have a confirmed SCD genotype, pregnancy with one baby, and pregnancy care and birth at a participating study centre will be included. Pregnancy care for the participants will be up to their doctors, with no changes based on the study. SCRIPT - the new tool - will guide future care by predicting who may benefit from specific treatments, reducing harm to low-risk individuals \& will allow selection of high-risk patients for a future trials to determine whether currently available and novel treatments in well-selected patients can improve APO sufficiently to balance treatment-related harms.

Primary Outcome Measures: Presence of Adverse Pregnancy Outcome, Yes, if any of the following events first noted during the pregnancy within the study period: acute anemia (yes, no), cardiac complication (yes, no), pulmonary complication (yes, no), hepatobiliary complication (yes, no), MSK complication (yes, no), splenic complication (yes, no), neurologic complication (yes, no), renal complication (yes, no); multi-organ failure (yes, no), venous thromboembolism (yes, no), vaso-occlusive event with admission (yes, no), red cell transfusion (yes, no), maternal mortality (yes, no), hypertensive disorder of pregnancy (yes, no), preterm birth (yes, no), small for gestational age (yes, no), or perinatal mortality (yes, no); defined based on published classifications., During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Secondary Outcome Measures: Presence of Acute Anemia, Yes, if any of: hyperhemolysis \[clinical diagnosis\], acute splenic sequestration; hepatic sequestration, or aplastic crisis; defined based on published classification, During pregnancy (until delivery of infant, up to 42 weeks of gestation)|Presence of Cardiac Complications, Yes, if any of: congestive heart failure, cardiomyopathy, cardiomegaly, or arrhythmia; defined based on published classification, During pregnancy (until delivery of infant, up to 42 weeks of gestation)|Presence of Pulmonary Complications, Yes, if any of: acute chest syndrome; pneumonia, or pulmonary hypertension; defined based on published classification, During pregnancy (until delivery of infant, up to 42 weeks of gestation)|Presence of Hepato-Biliary Complications, Yes, if any of: cholecystitis, cholelithiasis; cholecystectomy; cholestasis of pregnancy, or viral hepatitis; defined based on published classification, During pregnancy (until delivery of infant, up to 42 weeks of gestation)|Presence of Musculo-Skeletal Complications, Yes, if any of: avascular necrosis, ulcer, myositis, or osteomyelitis; defined based on published classification, During pregnancy (until delivery of infant, up to 42 weeks of gestation)|Presence of Neurologic Complications, Yes, if any of: silent cerebral infarct, cerebrovascular accident, cerebral aneurysm, transient ischemic attack, or Moya-Moya syndrome; defined based on published classification, During pregnancy (until delivery of infant, up to 42 weeks of gestation)|Presence of Renal Complications, Yes, if any of: acute kidney injury, proteinuria, pyelonephritis, or hematuria; defined based on published classification, During pregnancy (until delivery of infant, up to 42 weeks of gestation)|Presence of Multi-Organ Failure, Consultant's opinion in chart note specifying a diagnosis of "MOF" during current study pregnancy; clinical diagnosis, During pregnancy (until delivery of infant, up to 42 weeks of gestation)|Presence of Venous Thromboembolism, Yes, if any of: deep vein thrombosis, pulmonary embolism, atypical site venous thrombosis, or cerebral venous sinus thrombosis (CVST); defined based on published classification, During pregnancy (until delivery of infant, up to 42 weeks of gestation)|Presence of Vaso-Occlusive Event with Admission, Vaso-Occlusive Event (VOE): New onset pain lasting \>4 hrs in current study pregnancy, for which there is no explanation other than vaso-occlusion, and which requires presentation for acute care - patient self-report, During pregnancy (until delivery of infant, up to 42 weeks of gestation)|Provision of Red Blood Cell Transfusion, Yes, if any of: simple transfusion in pregnancy, exchange transfusion (manual exchange or erythrocytapheresis), or prophylactic transfusion, During pregnancy (until delivery of infant, up to 42 weeks of gestation)|Occurrence of Maternal Mortality, Maternal death during current study pregnancy and up to 6 months postpartum, During pregnancy (until delivery of infant, up to 42 weeks of gestation) and continuing to 6 months postpartum|Presence of Hypertensive Disorder of Pregnancy, Yes, if any of: Gestational Hypertension (gHTN) \[persistent de novo HTN over 20 weeks' GA in absence of features of preeclampsia\], Pre-eclampsia (PET) \[gHTN + \>1 new onset conditions \>20 weeks GA - proteinuria or maternal organ/uteroplacental dysfunction\], Eclampsia \[new onset seizures in context of pre-eclampsia\]; or HELLP Syndrome \[Evidence of Hemolysis, Elevated Liver Enzymes, Low Platelets in context of pre-eclampsia\], During pregnancy (until delivery of infant, up to 42 weeks of gestation)|Occurrence of Preterm Birth, Preterm birth (\< 37+0 weeks GA) during current study pregnancy, During pregnancy (until delivery of infant, up to 42 weeks of gestation)|Presence of Small for Gestational Age (SGA) Size, Birthweight \<10th centile for gestational age, At delivery of infant|Occurrence of Perinatal Mortality, Intrauterine fetal demise (IUFD) \[absence of FHR at or after 20 weeks' gestation\] or Neonatal Death (NND) \[death before 28 days of life, following live birth\], During pregnancy (until delivery of infant, up to 42 weeks of gestation) and up to 28 days after birth)