Association of germinal matrix hemorrhage volume with neurodevelopment and hydrocephalus.

OBJECTIVE: The objective of this study was to evaluate whether volumetric measurements on early cranial ultrasound (CUS) in high-grade germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) are associated with hydrocephalus and neurodevelopmental metrics. METHODS: A retrospective case series analysis of infants with high-grade GMH-IVH admitted to the St. Louis Children's Hospital neonatal intensive care unit between 2007 and 2015 who underwent neurodevelopmental testing using the Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) at 2 years of corrected age was performed. GMH volume, periventricular hemorrhagic infarction volume, and frontotemporal horn ratio were obtained from direct review of neonatal CUS studies. Univariate and multivariable regression models were used to evaluate the association between hemorrhage volumes and hydrocephalus requiring permanent CSF diversion with ventricular shunt or endoscopic third ventriculostomy with or without choroid plexus cauterization and composite Bayley-III cognitive, language, and motor scores. RESULTS: Forty-three infants (29 males, mean gestational age 25 weeks) met the inclusion criteria. The mean age at time of the CUS with the largest hemorrhage volume or first diagnosis of highest grade was 6.2 days. Nineteen patients underwent treatment for hydrocephalus with permanent CSF diversion. In multivariable analyses, larger GMH volume was associated with worse estimated Bayley-III cognitive (left-sided GMH volume: p = 0.048, total GMH volume: p = 0.023) and motor (left-sided GMH volume: p = 0.010; total GMH volume: p = 0.014) scores. Larger periventricular hemorrhagic infarction volume was associated with worse estimated Bayley-III motor scores (each side p < 0.04). Larger left-sided (OR 2.55, 95% CI 1.10-5.88; p = 0.028) and total (OR 1.35, 95% CI 1.01-1.79; p = 0.041) GMH volumes correlated with hydrocephalus. There was no relationship between early ventricular volume and hydrocephalus or neurodevelopmental outcomes. CONCLUSIONS: Location-specific hemorrhage volume on early CUS may be prognostic for neurodevelopmental and hydrocephalus outcomes in high-grade GMH-IVH.

A qualitative analysis of patient and caregiver experiences with myelomeningocele through online discussion boards.

PURPOSE: Patients and caregivers impacted by myelomeningocele (MMC) use online discussion board forums to create community and share information and concerns about this complex medical condition. We aim to identify the primary concerns expressed on these forums with the goal of understanding gaps in care that may merit investment of resources to improve care received by this population. METHODS: Anonymous posts from online MMC discussion boards were compiled using internet search engines. Posts were then analyzed using an adaptation of the Grounded Theory Method, a three-step system involving open, axial, and selective coding of the data by two independent researchers to identify common themes. RESULTS: Analysis of 400 posts written primarily by parents (n = 342, 85.5%) and patients (n = 45, 11.25%) yielded three overarching themes: questions surrounding quality of life, a lack of support for mothers of children with MMC, and confusion with a complex healthcare system. Many posts revealed concerns about management and well-being with MMC, including posts discussing symptoms and related conditions (n = 299, 75.75%), treatments (n = 259, 65.75%), and emotional aspects of MMC (n = 146, 36.5%). Additionally, families, especially mothers, felt a lack of support in their roles as caregivers. Finally, in 118 posts (29.5%), patients and families expressed frustration with navigating a complex healthcare system and finding specialists whose opinions they trusted. CONCLUSIONS: MMC is a complex medical condition that impacts patients and families in unique ways. Analysis of online discussion board posts identified key themes to be addressed in order to improve the healthcare experiences of those impacted by MMC.

Head growth in patients with myelomeningocele treated with prenatal and postnatal surgery.

OBJECTIVE: The need for permanent CSF diversion is lower in patients who have undergone prenatal surgery for myelomeningocele (MMC) than in those who have undergone postnatal closure. Differences in brain development and head growth between treatment groups are not known, particularly for those who do not require surgical treatment for hydrocephalus. The objective of this study was to determine differences in head growth and to generate MMC-specific head circumference (HC) growth curves for patients who underwent either prenatal or postnatal surgery. METHODS: The authors retrospectively identified patients from St. Louis Children's Hospital who were treated for MMC between 2016 and 2021. HC data were obtained from birth until the most recent follow-up or hydrocephalus treatment. Nonlinear least-squares regression analysis was performed to fit the data into four models: two-term power, Gompertz, West ontogenetic, and Weibull. Subsequently, the curves were assessed for their utility in predicting hydrocephalus treatment. RESULTS: Sixty-one patients (29 females [47.5%], 25 [41%] underwent prenatal surgery, mean gestational age at birth 36.6 weeks) were included in the study. The Weibull model best fit the HC data (prenatal adjusted R2 = 0.95, postnatal adjusted R2 = 0.95), while the Gompertz model had the worst fit (prenatal adjusted R2 = 0.56, postnatal adjusted R2 = 0.39) across both cohorts. Prenatal MMC repair patients had significantly larger HC measurements than their postnatal repair counterparts. The 50th percentile of the Weibull curve was determined as a useful threshold for hydrocephalus treatment: children with HC measurements that crossed and remained above this threshold were significantly more likely to have hydrocephalus treatment regardless of time of MMC repair (prenatal relative risk [RR] 10.0 [95% CI 1.424-70.220], sensitivity 85.7% [95% CI 0.499-0.984], and specificity 82.4% [95% CI 0.600-0.948]; postnatal RR 4.750 [95% CI 1.341-16.822], sensitivity 90.5% [95% CI 0.728-0.980], and specificity 75.0% [95% CI 0.471-0.924]). The HC growth curves of the MMC patients treated prenatally were significantly larger than the WHO HC curves (p < 0.001). CONCLUSIONS: The Weibull model was identified as the HC growth curve with the best fit for MMC patients and serves as a useful predictor of hydrocephalus treatment. For MMC patients with hydrocephalus, prenatal repair patients fit the model well but postnatal repair patients did not, potentially indicating different mechanisms of hydrocephalus development. Those treated prenatally had significantly larger HC measurements compared with both the general population and those treated postnatally. Further study is needed to understand the long-term cognitive outcomes and optimal management of clinically asymptomatic patients with large HC measurements who were treated prenatally for MMC.

Predictors and timing of hydrocephalus treatment in patients undergoing prenatal versus postnatal surgery for myelomeningocele.

OBJECTIVE: Although hydrocephalus rates have decreased with intrauterine surgery for myelomeningocele (MMC), 40%-85% of children with MMC still go on to develop hydrocephalus. Prenatal ventricle size is known to be associated with later development of hydrocephalus; however, it is not known how prediction measures or timing of hydrocephalus treatment differ between pre- and postnatal surgery for MMC. The goal of this study was to determine anatomical, clinical, and radiological characteristics that are associated with the need for and timing of hydrocephalus treatment in patients with MMC. METHODS: The authors retrospectively identified patients from Barnes Jewish Hospital or St. Louis Children's Hospital between 2016 and 2021 who were diagnosed with MMC prenatally and underwent either pre- or postnatal repair. Imaging, clinical, and demographic data were examined longitudinally between treatment groups and hydrocephalus outcomes. RESULTS: Fifty-eight patients were included (27 females, 46.6%), with a mean gestational age at birth of 36.8 weeks. Twenty-three patients (39.7%) underwent prenatal surgery. For the overall cohort, the ventricle size at prenatal ultrasound (HR 1.175, 95% CI 1.071-1.290), frontal-occipital horn ratio (FOHR) at birth > 0.50 (HR 3.603, 95% CI 1.488-8.720), and mean rate of change in head circumference (HC) in the first 90 days after birth (> 0.10 cm/day: HR 12.973, 95% CI 4.262-39.486) were identified as predictors of hydrocephalus treatment. The factors associated with hydrocephalus in the prenatal cohort were FOHR at birth > 0.50 (HR 27.828, 95% CI 2.980-259.846) and the rate of change in HC (> 0.10 cm/day: HR 39.414, 95% CI 2.035-763.262). The factors associated with hydrocephalus in the postnatal cohort were prenatal ventricle size (HR 1.126, 95% CI 1.017-1.246) and the mean rate of change in HC (> 0.10 cm/day: HR 24.202, 95% CI 5.119-114.431). FOHR (r = -0.499, p = 0.008) and birth HC (-0.409, p = 0.028) were correlated with time to hydrocephalus across both cohorts. For patients who underwent treatment for hydrocephalus, those in the prenatal surgery group were significantly more likely to develop hydrocephalus after 3 months than those treated with postnatal surgery, although the overall rate of hydrocephalus was significantly higher in the postnatal surgery group (p = 0.018). CONCLUSIONS: Clinical and imaging factors associated with hydrocephalus treatment differ between those receiving pre- versus postnatal MMC repair, and while the overall rate of hydrocephalus is lower, those undergoing prenatal repair are more likely to develop hydrocephalus after 3 months of age. This has implications for clinical follow-up timing for patients treated prenatally, who may live at a distance from the treatment site.

A toolkit for converting Gal4 into LexA and Flippase transgenes in Drosophila.

Drosophila has been a powerful model system for biological studies due to the wide range of genetic tools established for it. Among these tools, Gal4 is the most abundant, offering unparalleled tissue and developmental stage specificity for gene manipulation. In comparison, other genetic reagents are far fewer in choices. Here we present a genetic toolkit for converting Gal4 strains into LexA and Flippase transgenes through simple genetic crosses and fluorescence screening. We demonstrate the proof-of-principle by converting ten Gal4 lines that exhibit diverse tissue specificities and examined the activity patterns of the converted LexA and Flippase lines. Gal4-to-LexA and Flp conversion is fast and convenient and should greatly expand the choices of LexA and Flp for binary expression and FRT-based mosaic analysis, respectively, in Drosophila.