Perinatal Institute

In asthma, augmented airway wall smooth muscle (ASM) bulk is a major remodeling feature, promoted by increased transforming growth factor (TGF)-β1 and connective tissue growth factor (CTGF). Runt-related transcription factor-2 (RUNX2) represses TGF-β1-induced CTGF through interactions with SMAD3. This study aimed to investigate the expression and role of RUNX2 in asthmatic and nonasthmatic ASM cells. mRNA and protein were detected by microarray, PCR, and western blot in nonasthmatic and asthmatic ASM cells. Immunohistochemistry identified RUNX2 in lung tissues from asthmatic patients and nonasthmatic subjects. Different RUNX2 isoforms were transfected into immortalized-asthmatic ASM cells, and markers of inflammation and airway remodeling were measured. RUNX2 alternatively spliced forms were examined in bronchial biopsies from asthmatic and healthy subjects. The abundance of RUNX2 was decreased in isolated ASM cells from asthmatic compared with nonasthmatic subjects. The ASM layer around airways in lung tissue sections from asthmatic and nonasthmatic patients had a heterogeneous pattern of RUNX2 protein detection. TGF-β1 stimulation increased RUNX2/RUNX2 variant 1 mRNA in nonasthmatic but not asthmatic ASM cells, facilitating SMAD3 activation and nuclear translocation in asthmatic ASM cells. RUNX2 isoform overexpression in immortalized asthmatic ASM cells failed to alter markers of inflammation (IL-6) but significantly reduced markers of remodeling (CTGF), ASM cell hypertrophy (GSK-3β and desmin), and proliferation (pSer795 Rb and α-tubulin). In bronchial biopsies, RUNX2 mRNA splicing was higher in asthmatic patients compared with healthy subjects. These data suggest RUNX2 plays a role in the homeostasis of healthy airways. Restoring RUNX2 may provide a new therapeutic approach for asthma.

Among infants born very preterm (≤32 weeks' gestation), we compared weight-for-age ≤10th percentile (10%ile) at 36 weeks to malnutrition guidelines using z-score changes and evaluated predictors of malnutrition. Infants (extremely low birthweight (ELBW) n = 699; very low birthweight (VLBW) n = 878) were classified using (1) ≤10%ile and (2) malnutrition categories with z-score changes. Multiple logistic regression identified predictors of malnutrition. 13% of ELBW (n = 91) and 15% of VLBW (n = 131) infants were classified as moderately/severely malnourished by losses of z-scores while weighing >10%ile. Infants with chronic lung disease and/or who had any ventilator use had an increased risk of moderate/severe malnutrition with z-scores. Notably, a loss of ≤0.8 z-scores was not associated with any postnatal clinical risk factors. The use of ≤10%ile for weight-for-age as a cut-off to identify growth concerns at 36 weeks postmenstrual age misclassified many preterm infants compared to malnutrition categories using z-scores.

To evaluate the effect of attending neonatologist presence on first attempt neonatal intubation success and adverse events. Retrospective review of National Emergency Airway Registry for Neonates (NEAR4NEOS) intubations October 2014-December 2022. Univariate and multivariate analyses were performed to estimate associations between attending presence and outcomes. Among 12,652 intubation encounters, attendings were present for 8391 (66%) intubations by more junior operators. On univariate analysis, attending presence was associated with higherfirst attempt intubation success (OR 1.11, 95% CI 1.04-1.2). However, on multivariate analysis, attending presence was associated with lower first attempt success (aOR 0.78, 95% CI 0.70-0.86) and intubation requiring ≥3 intubation attempts (aOR 1.39, 95% CI 1.21-1.60). After adjustment, attending presence was associated with lower odds of first attempt intubation success. Reasons for this may include appropriate anticipation of high-risk intubations, altered team dynamics or unmeasured confounding biases.

BackgroundEffects of antenatal Lyme disease (LD) exposure on the pregnant patient, placenta, and fetus and subsequent child outcomes are not well known. To date, there have been no obstetrical pathology and long-term neurodevelopmental follow-up studies of infants exposed to LD during pregnancy. A first-of-its-kind pilot study (NCT06026969) is being conducted at Children’s National Hospital in Washington, DC.MethodsThis study aims to assess the feasibility of recruiting pregnant patients with LD and following their pregnancy outcomes and children’s neurodevelopment through age 18 months. Pregnant adults in the U.S. or Canada can participate if they have met CDC criteria for acute LD during their current pregnancy or post-treatment Lyme disease syndrome (PTLDS) within 5 years.ResultsAs of May 2025, 9 participants (4 with acute LD, 5 with PTLDS) have enrolled in the study. Successful recruitment methods have included posting in LD-focused social media groups and partnering with trusted stakeholders (doctors, nonprofit organizations) to share details about the study. All enrolled participants have learned about the study online. Fifty additional people have completed an interest screener; reasons for non-enrollment include not meeting CDC criteria for LD/PTLDS (n=15) or diagnosis outside of the eligibility window (n=7), not being pregnant at the time of eligibility assessment (n=5), them declining participation (n=6), or eligibility assessment in progress (n=17).Eight participants have given birth to date; 100% have completed neurodevelopmental follow-up and a qualitative interview about their experience with LD/PTLDS during pregnancy. Four have completed prenatal and/or postnatal imaging. Placentas have been successfully processed by all birth hospitals in preparation for further analysis.ConclusionWhile recruitment/enrollment are complex, there is robust interest from the pregnant LD/PTLDS patient population in contributing to research. Reducing financial barriers (e.g., travel costs), early communication with birth hospitals about placenta collection, partnering with trusted stakeholders, and using targeted marketing strategies have contributed to success in enrolling participants at this infrequent intersection of LD and pregnancy.DisclosuresRoberta L. DeBiasi, MD, MS, Pfizer: Grant/Research Support Sarah B. Mulkey, MD, PhD, Pfizer: Advisor/Consultant

Human milk is critical for maternal-infant health, yet concerns about cannabis exposure through milk may discourage breastfeeding. We examined the relationship between breastfeeding and developmental outcomes among infants with prenatal cannabis exposure. We used a regional perinatal data repository from an academic hospital system with universal maternal urine drug testing. Breastfeeding status was obtained from birth certificates. Developmental delay was identified through ICD-9/10 billing codes for delayed milestones or speech disorders. Infants whose mother tested positive for cannabis at delivery were included. Descriptive statistics compared demographic characteristics by breastfeeding status, and logistic regression estimated the odds of developmental delay. Among 1,520 infants born from 2013 to 2019 with a maternal positive drug test for cannabis at delivery, 818 (54%) were not breastfed, and 702 (46%) were breastfed. In unadjusted analysis, not breastfeeding was associated with increased odds of developmental delay (OR: 1.32, 95% CI: 1.00-1.76). After adjusting for maternal tobacco use, prematurity, and birth year, this association was no longer statistically significant (OR: 1.24, 95% CI: 0.93-1.67). In this study, developmental outcomes did not differ by breastfeeding status among infants with prenatal cannabis exposure. These findings support current guidance from professional organizations that cannabis use is not a contradiction to breastfeeding. Further research with larger sample sizes and detailed longitudinal data is needed to better assess the potential protective role of breastfeeding against developmental delay and safety in the context of maternal cannabis use.