BACKGROUND: Quality of life and survival in Cystic Fibrosis (CF) have improved dramatically, making family planning a feasible option. Maternal and perinatal outcomes in women with CF (wwCF) are similar to those seen in the general population. However, the effect of undergoing multiple pregnancies is unknown. METHODS: A multinational-multicenter retrospective cohort study. Data was obtained from 18 centers worldwide, anonymously, on wwCF 18-45 years old, including disease severity and outcome, as well as obstetric and newborn complications. Data were analyzed, within each individual patient to compare the outcomes of an initial pregnancy (1st or 2nd) with a multigravid pregnancy (≥3) as well as secondary analysis of grouped data to identify risk factors for disease progression or adverse neonatal outcomes. Three time periods were assessed - before, during, and after pregnancy. RESULTS: The study population included 141 wwCF of whom 41 (29%) had ≥3 pregnancies, "multiparous". Data were collected on 246 pregnancies, between 1973 and 2020, 69 (28%) were multiparous. A greater decline in ppFEV1 was seen in multiparous women, primarily in pancreatic insufficient (PI) wwCF and those with two severe (class I-III) mutations. Multigravid pregnancies were shorter, especially in wwCF over 30 years old, who had high rates of prematurity and newborn complications. There was no effect on pulmonary exacerbations or disease-related complications. CONCLUSIONS: Multiple pregnancies in wwCF are associated with accelerated respiratory deterioration and higher rates of preterm births. Therefore, strict follow-up by a multidisciplinary CF and obstetric team is needed in women who desire to carry multiple pregnancies.

CF Center University Hospital Olomouc and Faculty of Medicine Palacky University Olomouc Czech Republic

Charite Hospital Berlin Germany

Department of Biomedical Sciences Humanitas University Milan Italy; IRCCS Humanitas Research Hospital Respiratory Unit Milan Italy

Department of Obstetrics and Gynecology Mount Scopus Hadassah Hebrew University Medical Center Jerusalem Israel

Department of Pediatrics University of Pittsburgh School of Medicine Pittsburgh USA; Center for Innovative Research on Gender Health Equity University of Pittsburgh Pittsburgh PA USA

Faculty of Medicine Hebrew University of Jerusalem Israel

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Respiratory Unit and Cystic Fibrosis Center Italy; Department Pathophysiology and Transplantation University of Milan Italy

Graub CF Center Schneider Children's Medical Center Petach Tikva and Sackler School of Medicine Tel Aviv University Israel

Hospital Universitari Vall d'Hebron Barcelona Spain

Instituto Nacional del Tórax Santiago Chile

Johns Hopkins University School of Medicine Baltimore MD USA

Pediatric Pulmonary Institute and CF Center Ruth Rappaport Children's Hospital Rambam Medical Center and the Technion Israel Institute of Technology Haifa Israel

Pediatric Pulmonary Unit and Cystic Fibrosis Center Hadassah Medical Center Jerusalem Israel; Faculty of Medicine Hebrew University of Jerusalem Israel

Pediatric Pulmonary Unit Shaare Zedek Medical Center Jerusalem Israel

Pediatric Pulmonary Unit Soroka University Medical Center Ben Gurion University of the Negev Beer Sheva Israel

Pediatric Pulmonology and Cystic Fibrosis Unit Hospital Clinico Universitario Virgen de la Arrixaca Murcia Spain

Pediatric Pulmonology and Cystic Fibrosis Unit Hospital Exequiel González Cortés Chile

Pulmonology Institute and CF Center Carmel Medical Center and the Technion Israel Institute of Technology Haifa Israel

Safra Sheba Medical Center Ramat Gan Israel

Wellcome Wolfson Institute for Experimental Medicine Queen's University Belfast Ireland

Respir Med. 2025 Jan;236:107890. doi: 10.1016/j.rmed.2024.107890. PubMed

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