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2545 Fertility and Pregnancy in Patients with Congenital Neutropenia: Experience of the French Severe Chronic Neutropenia Registry in 565 Patients Above Age of 15 Years

Program: Oral and Poster Abstracts
Session: 201. Granulocytes, Monocytes, and Macrophages: Poster II
Hematology Disease Topics & Pathways:
Research, Biological therapies, epidemiology, Bone Marrow Failure Syndromes, Inherited Marrow Failure Syndromes, Clinical Research, health outcomes research, Genetic Disorders, Diseases, Therapies, Immunotherapy, registries, Maternal Health
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Aurelia Alimi, MD1*, Evrard Nika, MD2*, Blandine Beaupain3*, Claire Fieschi4*, Flore Sicre De Fontbrune5*, Nathalie Aladjidi, MD6*, Despina Moshous, MD, PhD7*, Aline Moignet.Autrel, MD8*, Coralie Mallebranche, MD9*, Martin Biosse Duplan, MD10*, Christine Bellanne-Chantelot, PhD11,12* and Jean Donadieu, MD, PhD13

1Hopital Trousseau, AP-HP Registre Français des Neutropénies Congénitales, Service d’Hémato-oncologie Pédiatrique,, PARIS, FRA
2Hopital Trousseau, AP-HP Registre Français des Neutropénies Congénitales, Service d’Hémato-oncologie Pédiatrique,, paris, France
3Hopital Trousseau, APHP Registre Français des Neutropénies Congénitales, Service d’Hémato-oncologie Pédiatrique,, PARIS, FRA
4Service d'Immunopathologie Clinique, Saint Louis hospital, AP-HP, Paris, France
5French Référence Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria, Paris, France
6Pellegrin Hospital, CIC1401, INSERM CICP, Bordeaux University Hospital, Pediatric Hemato-Immunology, Bordeaux, AL, FRA
7APHP-Université de Paris Cité, Hôpital Necker Enfants Malades,, Unité d’Immuno Hématologie Rhumatologie Pédiatriques, Paris, France
8Service d'Hématologie, CHU de Rennes, RENNES, France
9immuno-hemato-oncology Unit, Univ Angers, Nantes Université, Inserm, CNRS, CRCI2NA, SFR ICAT, CHU Angers,, Angers, FRA
10Hôpital Bretonneau, AP-HP, Service de Médecine Bucco-Dentaire,, Paris, France
11Département de Génétique Médicale, APHP-Sorbonne Université, Hôpital Pitié Salpêtrière, Paris, FRA
12Centre De Genetique, Paris, FRA
13Hopital Trousseau, Paris, France

INTRODUCTION: Congenital neutropenia (CN) are characterized by chronic neutropenia with frequent co-morbidities. Approximately 30 different entities have been described with various clinical phenotypes and genotypes (PMID: 28875503). As survival rates and life expectancy improve, fertility and pregnancies becomes a common issue. Only one study had addressed this question, reporting 38 pregnancies in women with idiopathic neutropenia (n=6) or CN (n=16) (PMID: 24997149).

METHODS: As of the last update at the end of June 2023, the French SCN registry enrolled 988 patients with a CN diagnosis, including 565 patients (282 males, 283 females) aged > 15 years old. The cumulative duration between 15 and 50 years of age for the total cohort is 8043 person-years, which can be considered as the years of potential fertility. For this study, we recorded the number of offspring, pregnancy outcomes, use of Granulocyte Colony Stimulating Factor (GCSF) during pregnancy, newborn outcomes and complications during pregnancy. Total fertility rate was calculated according to standard methodology (http://www.csss.washington.edu/Papers/wp97.pdf)


Among the 565 patients who may potentially be fertile, 109 patients (77 female among 283; 32 male among 282) became parents and a total of 211 offspring were recorded (table 1). In addition, medical termination of 5 pregnancies was performed in 5 patients with dominant CN disorders (ELANE and GATA2) following prenatal diagnosis. Globally, the total fertility rate in women was 3.4%, higher than the 2.1% rate in the general population in France. The fertility rate was heterogeneous, as some rare forms of CN may suffer from sterility (e.g. USB1 or CLPB heterozygous), or low fertility (e.g. SBDS, G6PC3 or GSDIb) whereas quite normal fertility was observed in others such as ELANE or GATA2. The parents’ median age at first birth was 27 years (min, max: 18, 41 years). Among the 77 females who became pregnant, 39 received GCSF prior to the first conception; 14/32 males had received GCSF. No GCSF was initiated during pregnancy. GCSF was maintained on various schedules during the pregnancy in 24 pregnancies. Among the 24 babies born after receiving GCSF in utero, no malformations were observed. As expected, some offspring (n=54) were shown to have the the same genetic defect as their affected parent, in agreement with the autosomal dominant inheritance, mainly ELANE-CN or GATA2. Noteworthy, two post-HSCT (indicated for MDS) pregnancies were underwent in ELANE-CN whereas one mother has received chemotherapy for a solid tumour before pregnancy. We observed one severe intrapartum complication (eclampsia) in a woman with USB1-CN. Among the 211 births, prematurity (< 37 weeks) was present in 13 cases, IUGR (mean weight 2141 g and mean height 42 cm) in 15 cases, and macrosomia in 11 cases (mean weight 3774 g). Two early deaths due to prematurity and enterocolitis and 1 cerebral anoxo ischemia from a twin pregnancy were observed.

CONCLUSION: In France, two-third of the patients with congenital neutropenia are adult. The total fertility rate in this population appears to be similar to the general population; although fertility is reduced in some subtypes of CN. No teratogenic effect of GCSF has been observed, but numbers are rather small.

Disclosures: Sicre De Fontbrune: Alexion, AstraZeneca Rare Disease: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Sobi: Honoraria, Research Funding; Samsung: Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH