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The ARID1A gene is an infrequent cause of Coffin-Siris syndrome (CSS) and has been associated with severe to profound developmental delays and hypotonia in addition to characteristic craniofacial and digital findings. We present three fetuses and a male neonate with ventriculomegaly/hydrocephalus, absence of the corpus callosum (ACC), cerebellar hypoplasia, retinal dysplasia, lung lobulation defects, renal dysplasia, imperforate or anteriorly placed anus, thymus hypoplasia and a single umbilical artery. Facial anomalies included downslanting palpebral fissures, wide-spaced eyes, low-set and posteriorly rotated ears, a small jaw, widely spaced nipples and hypoplastic nails. All fetuses had heterozygous variants predicting premature protein truncation in ARID1A (c.4886dup:p.Val1630Cysfs*18; c.4860dup:p.Pro1621Thrfs*27; and c.175G>T:p.Glu59*) and the baby’s microarray demonstrated mosaicism for a deletion at chromosome 1p36.11 (arr[GRCh37] 1p36.11 (26,797,508_27,052,080)×1~2), that contained the first exon of ARID1A. Although malformations, in particular ACC, have been described with CSS caused by pathogenic variants in ARID1A, prenatal presentations associated with this gene are rare. Retinal dysplasia, lung lobulation defects and absent thymus were novel findings in association with ARID1A variants. Studies in cancer have demonstrated that pathogenic ARID1A variants hamper nuclear import of the protein and/or affect interaction with the subunits of SWI/SNF complex, resulting in dysregulation of the PI3K/AKT pathway and perturbed PTEN and PIKC3A signaling. As haploinsufficiency for PTEN and PIKC3A can be associated with ventriculomegaly/hydrocephalus, aberrant expression of these genes is a putative mechanism for the brain malformations demonstrated in patients with ARID1A variants.

To characterize trends of an influenza diagnosis at delivery hospitalization and its association with severe maternal morbidity.We conducted a repeated cross-sectional analysis of delivery hospitalizations using the Nationwide Inpatient Sample from 2000 to 2018. We assessed the association between an influenza diagnosis at delivery hospitalization and severe maternal morbidity excluding transfusion per Centers for Disease Control and Prevention criteria. Secondary outcomes included maternal death and morbidity measures associated with influenza (mechanical intubation and ventilation, sepsis and shock, and acute respiratory distress syndrome [ARDS]) and obstetric complications (preterm birth and hypertensive disorders of pregnancy). We assessed trends of severe maternal morbidity by annual influenza season and the association between influenza and severe maternal morbidity using multivariable log-linear regression, adjusting for demographic, clinical, and hospital characteristics.Of 74.7 million delivery hospitalizations, 23 per 10,000 were complicated by an influenza diagnosis. The rate of severe maternal morbidity was higher with an influenza diagnosis compared with those without influenza (86-410 cases vs 53-70 cases/10,000 delivery hospitalizations). Women with an influenza diagnosis at delivery hospitalization were at an increased risk of severe maternal morbidity compared with those without influenza (2.3 vs 0.7%; adjusted risk ratio 2.24, 95% CI 2.17-2.31). This association held for maternal death, mechanical intubation, sepsis and shock, and ARDS-as well as obstetric complications, including preterm birth and hypertensive disorders of pregnancy.Pregnant women with influenza are at increased risk of severe maternal morbidity, as well as influenza-related maternal and obstetric complications. These results emphasize the importance of primary prevention and recognition of influenza infection during pregnancy to reduce downstream maternal morbidity and mortality.