Background

Apnea of Prematurity (AOP) is common, affecting the majority of infants born at <34 weeks gestational age. Apnea and periodic breathing are accompanied by intermittent hypoxia (IH). Animal and human studies demonstrate that IH exposure contributes to multiple pathologies, including retinopathy of prematurity (ROP), injury to sympathetic ganglia regulating cardiovascular action, impaired pancreatic islet cell and bone development, cerebellar injury, and neurodevelopmental disabilities. Current standard of care for AOP/IH includes prone positioning, positive pressure ventilation, and methylxanthine therapy; these interventions are inadequate, and not optimal for early development.

Objective

The objective is to support breathing in premature infants by using a simple, non-invasive vibratory device placed over limb proprioceptor fibers, an intervention using the principle that limb movements trigger reflexive facilitation of breathing.

Methods

Premature infants (23-34 wks gestational age), with clinical evidence of AOP/IH episodes were enrolled 1 week after birth. Caffeine treatment was not a reason for exclusion. Small vibration devices were placed on one hand and one foot and activated in 6 hour ON/OFF sequences for a total of 24 hours. Heart rate, respiratory rate, oxygen saturation (SpO2), and breathing pauses were continuously collected.

Results

Fewer respiratory pauses occurred during vibration periods, relative to baseline (p<0.005). Significantly fewer SpO2 declines occurred with vibration (p<0.05), relative to control periods. Significantly fewer bradycardic events occurred during vibration periods, relative to no vibration periods (p<0.05).

Conclusions

In premature neonates, limb proprioceptive stimulation, simulating limb movement, reduces breathing pauses and IH episodes, and lowers the number of bradycardic events that accompany aberrant breathing episodes. This low-cost neuromodulatory procedure has the potential to provide a non-invasive intervention to reduce apnea, bradycardia and intermittent hypoxia in premature neonates.

Trial registration

ClinicalTrials.gov NCT02641249.

Purpose

We exposed premature infants to womb-like sounds to evaluate such exposure on breathing and cardiovascular patterns. We hypothesized that these sounds would reduce apnea and intermittent hypoxemia, enhance parasympathetic outflow, and improve cardiovascular patterns.

Methods

A total of 20 cases and 5 control infants at ≤32-36 weeks corrected gestational age participated in a prospective observational cohort study. Twenty-four hours of continuous ECG, respiratory and oxygen saturation data were collected in all infants. Womb-like sounds were played intermittently in 6-hour blocks. Salivary samples were collected at study beginning and end for cortisol. Apnea, intermittent hypoxemia, and bradycardia were evaluated, and heart rate variability was assessed by time domain and spectral techniques.

Results

Intermittent hypoxemia and bradycardia significantly declined after sound exposure. No significant differences in apnea, cortisol levels, or heart rate variability were evident among the study infants.

Conclusions

Exposing premature infants to womb-like sounds has the potential to reduce hypoxemic and bradycardic events, and be used as an intervention to stabilize breathing and cardiac control in preterm infants.

Objective

Reducing environmental noise benefits premature infants in neonatal intensive care units (NICU), but excessive reduction may lead to sensory deprivation, compromising development. Instead of minimal noise levels, environments that mimic intrauterine soundscapes may facilitate infant development by providing a sound environment reflecting fetal life. This soundscape may support autonomic and emotional development in preterm infants. We aimed to assess the efficacy and feasibility of external non-invasive recordings in pregnant women, endeavoring to capture intra-abdominal or womb sounds during pregnancy with electronic stethoscopes and build a womb sound library to assess sound trends with gestational development. We also compared these sounds to popular commercial womb sounds marketed to new parents.

Study design

Intra-abdominal sounds from 50 mothers in their second and third trimester (13 to 40 weeks) of pregnancy were recorded for 6 minutes in a quiet clinic room with 4 electronic stethoscopes, placed in the right upper and lower quadrants, and left upper and lower quadrants of the abdomen. These recording were partitioned into 2-minute intervals in three different positions: standing, sitting and lying supine. Maternal and gestational age, Body Mass Index (BMI) and time since last meal were collected during recordings. Recordings were analyzed using long-term average spectral and waveform analysis, and compared to sounds from non-pregnant abdomens and commercially-marketed womb sounds selected for their availability, popularity, and claims they mimic the intrauterine environment.

Results

Maternal sounds shared certain common characteristics, but varied with gestational age. With fetal development, the maternal abdomen filtered high (500-5,000 Hz) and mid-frequency (100-500 Hz) energy bands, but no change appeared in contributions from low-frequency signals (10-100 Hz) with gestational age. Variation appeared between mothers, suggesting a resonant chamber role for intra-abdominal space. Compared to commercially-marketed sounds, womb signals were dominated by bowel sounds, were of lower frequency, and showed more variation in intensity.

Conclusions

High-fidelity intra-abdominal or womb sounds during pregnancy can be recorded non-invasively. Recordings vary with gestational age, and show a predominance of low frequency noise and bowel sounds which are distinct from popular commercial products. Such recordings may be utilized to determine whether sounds influence preterm infant development in the NICU.

It is unclear if SARS CoV-2 infection during pregnancy is associated with adverse neurodevelopmental repercussions to infants. We assessed pediatric neurodevelopmental outcomes in children born to mothers with laboratory-confirmed SARS CoV-2 infection during pregnancy. Neurodevelopmental outcomes of in-utero exposed children were compared to that of pre-pandemic control children in Los Angeles (LA), CA, USA and Rio de Janeiro, Brazil. Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III), the gold standard tool for evaluating neurodevelopment until 36 months of age and Ages and Stages Questionnaires (ASQ-3), a frequently used screening instrument for evaluating neurodevelopment in this same age group were the assessment tools used. Developmental delay (DD) was defined as having a score < - 2 SD below the norm (< 70) in at least one of three Bayley-III domains, (cognitive, motor or language) or a score below the cut-off (dark zone) in at least one of five ASQ-3 domains (communication, gross motor, fine motor, problem solving, personal-social). Exposed children were born between April 2020 and December 2022 while control children were born between January 2016 to December 2019. Neurodevelopmental testing was performed in 300 children total: 172 COVID-19 exposed children between 5-30 months of age and 128 control children between 6-38 months of age. Bayley-III results demonstrated that 12 of 128 exposed children (9.4%) had DD versus 2 of 128 controls (1.6%), p = 0.0007. Eight of 44 additional exposed children had DD on ASQ-3 testing. Fully, 20 of 172 exposed children (11.6%) and 2 of 128 control children (1.6%), p = 0.0006 had DD. In Rio, 12% of exposed children versus 2.6% of controls, p = 0.02 had DD. In LA, 5.7% of exposed children versus 0 controls, p = 0.12 had DD. Severe/critical maternal COVID-19 predicted below average neurodevelopment in the exposed cohort (OR 2.6, 95% CI 1.1-6.4). Children exposed to antenatal COVID-19 have a tenfold higher frequency of DD as compared to controls and should be offered neurodevelopmental follow-up.