An international internet survey of the experiences of 1,714 mothers with a late stillbirth: The STARS cohort study

Background: Stillbirth occurring after 28 weeks gestation affects between 1.5-4.5 per 1,000 births in high-income countries. The majority of stillbirths in this setting occur in women without risk factors. In addition, many established risk factors such as nulliparity and maternal age are not amenable to modification during pregnancy. Identification of other risk factors which could be amenable to change in pregnancy should be a priority in stillbirth prevention research. Therefore, this study aimed to utilise an online survey asking women who had a stillbirth about their pregnancy in order to identify any common symptoms and experiences. Methods: A web-based survey. Results: A total of 1,714 women who had experienced a stillbirth >3 weeks prior to enrolment completed the survey. Common experiences identified were: perception of changes in fetal movement (63 % of respondents), reports of a "gut instinct" that something was wrong (68 %), and perceived time of death occurring overnight (56 %). A quarter of participants believed that their baby's death was due to a cord issue and another 18 % indicated that they did not know the reason why their baby died. In many cases (55 %) the mother believed the cause of death was different to that told by clinicians. Conclusions: This study confirms the association between altered fetal movements and stillbirth and highlights novel associations that merit closer scrutiny including a maternal gut instinct that something was wrong. The potential importance of maternal sleep is highlighted by the finding of more than half the mothers believing their baby died during the night. This study supports the importance of listening to mothers' concerns and symptoms during pregnancy and highlights the need for thorough investigation of stillbirth and appropriate explanation being given to parents

Maternal sleep practices and stillbirth: Findings from an international case‐control study

BackgroundLate stillbirth, which occurs ≥28 weeks' gestation, affects 1.3-8.8 per 1000 births in high-income countries. Of concern, most occur in women without established risk factors. Identification of potentially modifiable risk factors that relate to maternal behaviors remains a priority in stillbirth prevention research. This study aimed to investigate, in an international cohort, whether maternal sleep practices are related to late stillbirth.MethodsAn Internet-based case-control study of women who had a stillbirth ≥28 weeks' gestation within 30 days before completing the survey (n = 153) and women with an ongoing third-trimester pregnancy or who had delivered a live born child within 30 days (n = 480). Bivariate and multivariate logistic regressions were used to determine unadjusted and adjusted odds ratios (OR and aOR, respectively) with 95% confidence intervals (95% CIs) for stillbirth.ResultsSleeping >9 hours per night in the previous month was associated with stillbirth (aOR 1.75 [95% CI 1.10-2.79]), as was waking on the right side (2.27 [1.31-3.92]). Nonrestless sleep in the last month was also found to be associated with stillbirth (1.73 [1.03-2.99]), with good sleep quality in the last month approaching significance (1.64 [0.98-2.75]). On the last night of pregnancy, not waking more than one time was associated with stillbirth (2.03 [1.24-3.34]). No relationship was found with going to sleep position during pregnancy, although very few women reported settling in the supine position (2.4%).ConclusionsLong periods of undisturbed sleep are associated with late stillbirth. Physiological studies of how the neuroendocrine and autonomic system pathways are regulated during sleep in the context of late pregnancy are warranted

Altered Differentiation Potential of Gaucherâs Disease iPSC Neuronal Progenitors due to Wnt/β-Catenin Downregulation

Summary: Gaucherâs disease (GD) is an autosomal recessive disorder caused by mutations in the GBA1 gene, which encodes acid β-glucocerebrosidase (GCase). Severe GBA1 mutations cause neuropathology that manifests soon after birth, suggesting that GCase deficiency interferes with neuronal development. We found that neuronopathic GD induced pluripotent stem cell (iPSC)-derived neuronal progenitor cells (NPCs) exhibit developmental defects due to downregulation of canonical Wnt/β-catenin signaling and that GD iPSCsâ ability to differentiate to dopaminergic (DA) neurons was strikingly reduced due to early loss of DA progenitors. Incubation of the mutant cells with the Wnt activator CHIR99021 (CHIR) or with recombinant GCase restored Wnt/β-catenin signaling and rescued DA differentiation. We also found that GD NPCs exhibit lysosomal dysfunction, which may be involved in Wnt downregulation by mutant GCase. We conclude that neuronopathic mutations in GCase lead to neurodevelopmental abnormalities due to a critical requirement of this enzyme for canonical Wnt/β-catenin signaling at early stages of neurogenesis. : In this article, Feldman and colleagues describe a new mechanism linking severe GBA1 mutations to neurodevelopmental defects through Wnt/β-catenin downregulation. Using GD iPSCs as a model, the authors show that the ability of neuronopathic GD NPCs to differentiate to DA neurons is strikingly reduced due to early loss of DA progenitors and that lysosomal dysfunction may be directly involved in canonical Wnt downregulation. Keywords: Gaucherâs disease, GBA1, glucocerebrosidase, neuronal progenitors, dopaminergic development, iPSCs, Wnt/β-catenin, lysosomal storage disease, neurodegeneratio