Pregnancy outcomes in mothers of offspring with inherited bone marrow failure syndromes

Abstract

Background: Children with inherited bone marrow failure syndromes (IBMFSs) may be symptomatic in utero, resulting in maternal and fetal problems during the pregnancy. Subsequent pregnancies by their mothers should be considered "high risk". Methods:We retrospectively analyzed outcomes of 575 pregnancies in 165 unaffected mothers of offspring with Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SDS) for events noted during pregnancy, labor, and delivery. We compared outcomes of pregnancies with affected and unaffected offspring within each group of mothers and with the general population. Results:The rates of miscarriage (12-20%), elective abortion (5-10%), and live birth (68-78%) among mothers of all IBMFS groups were similar and comparable with general population rates but recurrent miscarriages (≥2) were significantly more common in mothers of offspring with DBA and SDS. Offspring with FA were more frequently born small for gestational age (SGA) than unaffected babies (39% vs. 4%) and had fetal malformations (46%) with 18% having three or more, often necessitating early delivery and surgery; offspring with DC had higher rates of SGA (39% vs. 8%) and fetal distress (26% vs. 3%); and offspring with DBA had fetal hypoxia (19% vs. 1%) leading to preterm and emergency cesarean deliveries (26% vs. 6%). Offspring with early-onset severe phenotypes had the most prenatal and peripartum adverse events. Conclusion:We identified the high-risk nature of pregnancies in mothers with IBMFS-affected fetuses, suggesting the need for prepregnancy counseling and monitoring of subsequent pregnancies by high-risk fetal-maternal specialists.

Functional profiling of single CRISPR/Cas9-edited human long-term hematopoietic stem cells

“…Thus, it is possible that in these particular cases, germline GATA1 mutations severely constrained fetal blood development inducing an unidentified compensatory mechanism to allow for a more normalized megakaryocytic development. This selective pressure is further supported by the fact that mothers of children with Diamond Blackfan anemia have increased numbers of miscarriages 52 .…”

Telomeres and Telomerase Activity in the Human Placenta

“…Combination with immunostaining allows the simultaneous identification of specific cell types. The assay requires very few cells (10)(11)(12)(13)(14)(15).…”

“…Moreover, increased incidence of diabetes mellitus was identified in patients suffering from those pathologies [14]. Inherited bone marrow failure syndromes threaten also the prenatal development due to fetal malformations and intrauterine growth retardation accompanied with an abnormally small placenta [15].…”

Fanconi anemia and dyskeratosis congenita/telomere biology disorders: Two inherited bone marrow failure syndromes with genomic instability

“…Pregnancies in patients with FA are rare; less than 50 pregnancies, regardless of transplant status, have been reported in the literature ( 4 ). Reproductive complications in women with FA include decreased fertility, preeclampsia, increased premature births and C-sections, and declined maternal hematopoiesis during pregnancy ( 281 ). Reproductive and pregnancy outcomes in women with DC/TBD have recently been explored in a group of 26 women older than 16 years who had a total of 80 pregnancies ( 282 ).…”