SARS CoV-2 detected in neonatal stool remote from maternal COVID-19 during pregnancy.

BACKGROUND: In utero transmission of SARS coronavirus 2 (SARS-CoV-2) has not been fully investigated. We investigated whether newborns of mothers with COVID-19 during pregnancy might harbor SARS-CoV-2 in the gastrointestinal tract. METHODS: This cohort study investigated stool from 14 newborns born at 25-41 weeks admitted at delivery to our urban academic hospital whose mothers had COVID-19 during pregnancy. Eleven mothers had COVID-19 resolved more than 10 weeks before delivery. Newborn stool was evaluated for SARS-CoV-2 RNA, Spike protein, and induction of inflammatory cytokines interleukin-6 (IL-6) and interferon-γ (IFN-γ) in macrophages. RESULTS: Despite negative SARS CoV-2 nasal PCRs from all newborns, viral RNAs and Spike protein were detected in the stool of 11 out of 14 newborns as early as the first day of life and increased over time in 6. Stool homogenates from all 14 newborns elicited elevated inflammatory IL-6 and IFN-γ from macrophages. Most newborns were clinically well except for one death from gestational autoimmune liver disease and another who developed necrotizing enterocolitis. CONCLUSIONS: These findings suggest in utero transmission of SARS-CoV-2 and possible persistent intestinal viral reservoirs in the newborns. Further investigation is required to understand the mechanisms and their clinical implications. IMPACT: SARS-CoV-2 RNAs or Spike protein was detected in the stool of 11 out of 14 preterm newborns born to mothers with resolved COVID-19 weeks prior to delivery despite negative newborn nasal PCR swabs. These novel findings suggest risk of in utero SARS-CoV-2 transmission to the fetal intestine during gestation. The presence of SARS-CoV-2 RNAs and Spike protein in the intestines of newborns may potentially impact the development of the gut microbiome and the immune system; the long-term health impact on the preterm infants should be further investigated.

Early neonatal mortality is modulated by gestational age, birthweight and fetal heart rate abnormalities in the low resource setting in Tanzania - a five year review 2015-2019.

BACKGROUND: Early Neonatal mortality (ENM) (< 7 days) remains a significant problem in low resource settings. Birth asphyxia (BA), prematurity and presumed infection contribute significantly to ENM. The study objectives were to determine: first, the overall ENM rate as well as yearly ENM rate (ENMR) from 2015 to 2019; second, the influence of decreasing GA (< 37 weeks) and BW (< 2500 g) on ENM; third, the contribution of intrapartum and delivery room factors and in particular fetal heart rate abnormalities (FHRT) to ENM; and fourth, the Fresh Still Birth Rates (FSB) rates over the same time period. METHODS: Retrospective cohort study undertaken in a zonal referral teaching hospital located in Northern Tanzania. Labor and delivery room data were obtained from 2015 to 2019 and included BW, GA, fetal heart rate (FHRT) abnormalities, bag mask ventilation (BMV) during resuscitation, initial temperature, and antenatal steroids use. Abnormal outcome was ENM < 7 days. Analysis included t tests, odds ratios (OR), and multivariate regression analysis. RESULTS: The overall early neonatal mortality rate (ENMR) was 18/1000 livebirths over the 5 years and did not change significantly comparing 2015 to 2019. Comparing year 2018 to 2019, the overall ENMR decreased significantly (OR 0.62; 95% confidence interval (CI) 0.45-0.85) as well as infants ≥37 weeks (OR 0.45) (CI 0.23-0.87) and infants < 37 weeks (OR 0.57) (CI 0.39-0.84). ENMR was significantly higher for newborns < 37 versus ≥37 weeks, OR 10.5 (p < 0.0001) and BW < 2500 versus ≥2500 g OR 9.9. For infants < 1000 g / < 28 weeks, the ENMR was ~ 588/1000 livebirths. Variables associated with ENM included BW - odds of death decreased by 0.55 for every 500 g increase in weight, by 0.89 for every week increase in GA, ENMR increased 6.8-fold with BMV, 2.6-fold with abnormal FHRT, 2.2-fold with no antenatal steroids (ANS), 2.6-fold with moderate hypothermia (all < 0.0001). The overall FSB rate was 14.7/1000 births and decreased significantly in 2019 when compared to 2015 i.e., 11.3 versus 17.3/1000 live births respectively (p = 0.02). CONCLUSION: ENM rates were predominantly modulated by decreasing BW and GA, with smaller/ less mature newborns 10-fold more likely to die. ENM in term newborns was strongly associated with FHRT abnormalities and when coupled with respiratory depression and BMV suggests BA. In smaller newborns, lack of ACS exposure and moderate hypothermia were additional associated factors. A composite perinatal approach is essential to achieve a sustained reduction in ENMR.

Neonatal Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

This 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations (CoSTR) for neonatal life support includes evidence from 7 systematic reviews, 3 scoping reviews, and 12 evidence updates. The Neonatal Life Support Task Force generally determined by consensus the type of evidence evaluation to perform; the topics for the evidence updates followed consultation with International Liaison Committee on Resuscitation member resuscitation councils. The 2020 CoSTRs for neonatal life support are published either as new statements or, if appropriate, reiterations of existing statements when the task force found they remained valid. Evidence review topics of particular interest include the use of suction in the presence of both clear and meconium-stained amniotic fluid, sustained inflations for initiation of positive-pressure ventilation, initial oxygen concentrations for initiation of resuscitation in both preterm and term infants, use of epinephrine (adrenaline) when ventilation and compressions fail to stabilize the newborn infant, appropriate routes of drug delivery during resuscitation, and consideration of when it is appropriate to redirect resuscitation efforts after significant efforts have failed. All sections of the Neonatal Resuscitation Algorithm are addressed, from preparation through to postresuscitation care. This document now forms the basis for ongoing evidence evaluation and reevaluation, which will be triggered as further evidence is published. Over 140 million babies are born annually worldwide (https://ourworldindata.org/grapher/births-and-deaths-projected-to-2100). If up to 5% receive positive-pressure ventilation, this evidence evaluation is relevant to more than 7 million newborn infants every year. However, in terms of early care of the newborn infant, some of the topics addressed are relevant to every single baby born.

Randomized Study of Delayed Cord Clamping of 30 to 60 Seconds in the Larger Infant Born Preterm.

In a randomized study of infants born preterm (gestational age 28-34 6/7 weeks), we evaluated delayed cord clamping for 30 (n = 50) vs 60 (n = 55) seconds. The primary outcome of initial hematocrit differed by 2.8% (P = .006), being greater with 60 seconds. There were no differences in secondary outcomes and no adverse consequences between groups. These findings should serve as a stimulus to many centers that are reluctant to implement delayed cord clamping in this targeted larger premature population.

Relationships of biological and environmental factors to cognition of preterm infants in the toddler and preschool periods.

One hundred and nine preterm infants were studied to examine the relative effects of biologic/neurologic factors (length of hospital stay, 18 month cognitive status) and environment (socioeconomic status) on cognition in the toddler (18 months) and preschool periods (3 years). Length of hospital stay was significantly related to toddler cognitive outcome, and less so to preschool outcome. Socioeconomic status predicted only preschool cognitive outcome and not toddler outcome. Cognitive status at 18 months significantly predicted 3 year outcome, and there was relatively little change between those periods. Together, cognitive status at 18 months and socioeconomic status significantly predicted preschool IQ, accounting for 34% of the variance. Results showed that perinatal biologic risks became less salient while socioeconomic status became increasingly important at the preschool period. Relative lack of change in cognitive status indicated the importance of early cognitive evaluation in preterm infants.

Intermittent fetal heart rate monitoring using a fetoscope or hand held Doppler in rural Tanzania: a randomized controlled trial.

BACKGROUND: Neonatal mortality is a global challenge, with an estimated 1.3 million intrapartum stillbirths in 2015. The majority of these were found in low resource settings with limited options to intrapartum fetal heart monitoring devices. This trial compared frequency of abnormal fetal heart rate (FHR) detection and adverse perinatal outcomes (i.e. fresh stillbirths, 24-h neonatal deaths, admission to neonatal care unit) among women intermittently assessed by Doppler or fetoscope in a rural low-resource setting. METHODS: This was an open-label randomized controlled trial conducted at Haydom Lutheran Hospital from March 2013 through August 2015. Inclusion criteria were; women in labor, singleton, cephalic presentation, normal FHR on admission (120-160 beats/minute), and cervical dilatation ≤7 cm. Verbal consent was obtained. RESULTS: A total of 2684 women were recruited, 1309 in the Doppler and 1375 in the fetoscope arms, respectively. Abnormal FHR was detected in 55 (4.2%) vs 42 (3.1%). (RR = 1.38; 95%CI: 0.93, 2.04) in the Doppler and fetoscope arms, respectively. Bag mask ventilation was performed in 80 (6.1%) vs 82 (6.0%). (RR = 1.03; 95%CI: 0.76, 1.38) of neonates, and adverse perinatal outcome was comparable 32(2.4%) vs 35(2.5%). (RR = 0.9; 95%CI: 0.59, 1.54), in the Doppler and fetoscope arms, respectively. CONCLUSION: This trial failed to demonstrate a statistically significant difference in the detection of abnormal FHR between intermittently used Doppler and fetoscope and adverse perinatal outcomes. However, FHR measurements were not performed as often as recommended by international guidelines. Conducting a randomized controlled study in rural settings with limited resources is associated with major challenges. TRIAL REGISTRATION: This clinical trial was registered on April 2013 with registration number NCT01869582 .

Using statistical process control methods to trace small changes in perinatal mortality after a training program in a low-resource setting.

OBJECTIVE: To trace and document smaller changes in perinatal survival over time. DESIGN: Prospective observational study, with retrospective analysis. SETTING: Labor ward and operating theater at Haydom Lutheran Hospital in rural north-central Tanzania. PARTICIPANTS: All women giving birth and birth attendants. INTERVENTION: Helping Babies Breathe (HBB) simulation training on newborn care and resuscitation and some other efforts to improve perinatal outcome. MAIN OUTCOME MEASURE: Perinatal survival, including fresh stillbirths and early (24-h) newborn survival. RESULT: The variable life-adjusted plot and cumulative sum chart revealed a steady improvement in survival over time, after the baseline period. There were some variations throughout the study period, and some of these could be linked to different interventions and events. CONCLUSION: To our knowledge, this is the first time statistical process control methods have been used to document changes in perinatal mortality over time in a rural Sub-Saharan hospital, showing a steady increase in survival. These methods can be utilized to continuously monitor and describe changes in patient outcomes.

Planned home birth and the association with neonatal hypoxic ischemic encephalopathy.

OBJECTIVE: To evaluate the association between planned home birth and neonatal hypoxic ischemic encephalopathy (HIE). METHODS: This is a case-control study in which a database of neonates who underwent head cooling for HIE at our institution from 2007 to 2011 was linked to New York City (NYC) vital records. Four normal controls per case were then randomly selected from the birth certificate data after matching for year of birth, geographic location, and gestational age. Demographic and obstetric information was obtained from the vital records for both the cases and controls. Location of birth was analyzed as hospital or out of hospital birth. Details from the out of hospital deliveries were reviewed to determine if the delivery was a planned home birth. Maternal and pregnancy characteristics were examined as covariates and potential confounders. Logistic regression was used to determine the odds of HIE by intended location of delivery. RESULTS: Sixty-nine neonates who underwent head cooling for HIE had available vital record data on their births. The 69 cases were matched to 276 normal controls. After adjusting for pregnancy characteristics and mode of delivery, neonates with HIE had a 44.0-fold [95% confidence interval (CI) 1.7-256.4] odds of having delivered out of hospital, whether unplanned or planned. Infants with HIE had a 21.0-fold (95% CI 1.7-256.4) increase in adjusted odds of having had a planned home birth compared to infants without HIE. CONCLUSION: Out of hospital birth, whether planned home birth or unplanned out of hospital birth, is associated with an increase in the odds of neonatal HIE.

Neonatal and Maternal Temperature Regulation During and After Delivery.

An important goal of obstetric anesthesia is to provide for the safety and comfort of the mother as well as to optimize physiologic outcomes for the neonate. Markers of neonatal physiologic outcome include cord umbilical artery pH and Apgar scores. Neonatal temperature has often been overlooked by anesthesiologists as an important physiologic outcome measure, but it may be significantly affected by operating room conditions and obstetric anesthesia technique at cesarean delivery. There is a dose-dependent increase in mortality with decreasing body temperature as well as an increased likelihood for more severe early respiratory distress. Multiple neonate-focused strategies have been shown to decrease the incidence of neonatal hypothermia. Because fetal temperature is affected by maternal temperature, strategies to mitigate maternal hypothermia at the time of delivery may also be important in preventing neonatal hypothermia. This focused review will examine the importance of neonatal temperature and discuss its relationship to maternal temperature as well as strategies for maintaining neonatal normothermia after delivery.

Omega-3 fatty acids modulate neonatal cytokine response to endotoxin.

Neonatal immune response is characterized by an uncompensated pro-inflammatory response that can lead to inflammation-related morbidity and increased susceptibility to infection. We investigated the effects of long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) pre-treatment on cytokine secretion to low-concentration endotoxin (lipopolysaccharide, LPS) in THP-1 monocytes and neonatal cord blood (CB) from healthy full-term infants. Pre-treatment of THP-1 cells, with either n-3 PUFA at 25 or 100 µM significantly reduced IL-6, IL-10, and IL-12 secretion while DHA, but not EPA, reduced TNF-α response to LPS. DHA inhibition was stronger compared to EPA and effective at the low concentration. The same concentrations of n-3 PUFAs inhibited IL-12 but not IL-10 cytokine response in whole CB from 9 infants pre-treated for 24 h. To assess clinical relevance for acute response to LPS, the effects of low-concentration DHA at 25 µM or 12.5 µM were assessed before and after LPS exposure of isolated CB mononuclear cells from 20 infants for 1 h. When added before or after LPS, physiologic DHA treatment produced significant concentration-dependent inhibition of TNF-α, IL-6, IL-1ß, and IL-8 secretion. The results demonstrate prophylactic and therapeutic modulation of neonatal cytokine response to LPS and provide proof-of-concept that low-concentration administration of n-3 PUFA could attenuate or resolve neonatal inflammatory response.

How Much Training Is Enough? Low-Dose, High-Frequency Simulation Training and Maintenance of Competence in Neonatal Resuscitation.

INTRODUCTION: Facemask ventilation is a crucial, but challenging, element of neonatal resuscitation.In a previously reported study, instructor-led training using a novel neonatal simulator resulted in high-level ventilation competence for health care providers (HCPs) involved in newborn resuscitation. The aim of this study was to identify the optimal frequency and dose of simulation training to maintain this competence level. METHODS: Prospective observational study of HCPs training through 9 months. All training was logged. Overall ventilation competence scores were calculated for each simulation case, incorporating 7 skill elements considered important for effective ventilation.Overall scores and skill elements were analyzed by generalized linear mixed effects models using frequency (number of months of 9 where training occurred and total number of training sessions in 9 months) and dose (total number of cases performed) as predictors. Training loads (frequency + dose) predictive of high scores were projected based on estimated marginal probabilities of successful outcomes. RESULTS: A total of 156 HCPs performed 4348 training cases. Performing 5 or more sessions in 9 months predicted high global competence scores (>28/30). Frequency was the best predictor for 4 skill elements; success in maintaining airway patency and ventilation fraction was predicted by performing training in, respectively, 2 and 3 months of 9, whereas for avoiding dangerously high inflating pressures and providing adequate mask seal, 5 and 6 sessions, respectively, over the 9 months, predicted success. Skills reflecting global performance (successful resuscitation and valid ventilations) and ventilation rate were more dose-dependent. CONCLUSIONS: Training frequency is important in maintaining neonatal ventilation competence. Training dose is important for some skill elements. This offers the potential for individualized training schedules.

Reducing NICU Unplanned Extubations From Tube Dislodgement.

OBJECTIVES: Unplanned extubations (UEs) can be a frequent problem and are associated with adverse outcomes. This quality improvement initiative sought to reduce UEs from tube dislodgement in a level IV NICU utilizing methods applicable to other ICUs and performed with minimal monetary funds. METHODS: From January 2019 to July 2023, an interdisciplinary quality improvement team used the Model for Improvement and performed sequential interventions to improve the outcome measure of UEs per 100 ventilator days. Process measures included adherence to a modified, site-specific UE care bundle derived from the Solutions for Patient Safety network, whereas the number of endotracheal tube-related pressure injuries was used as a balancing measure. Statistical process control charts and established rules for special cause variation were applied to analyze data. RESULTS: Sequential interventions reduced the rate of UEs from a baseline of 2.3 to 0.6 UEs per 100 ventilator days. Greater than 90% adherence with the UE care bundle and apparent cause analysis form completion occurred since December 2020. There were no endotracheal tube-related pressure injuries. CONCLUSIONS: A sustained reduction in UEs was demonstrated. Leveraging a multidisciplinary team allowed for continuous UE analysis, which promoted tailored consecutive interventions. UE care bundle audits and the creation of a postevent debrief guide, which helped providers share a common language, were the most impactful interventions. Next steps include disseminating these interventions to other ICUs across our hospital enterprise. These low-cost interventions can be scalable to other NICUs and PICUs.

Capacity Building in Remote Facilitation of Newborn Resuscitation.

The past decade has been notable for widespread dissemination of newborn resuscitation training in low-resource settings through simplified training programs including Helping Babies Breathe. Since 2020, implementation efforts have been impacted by restrictions on travel and in-person gatherings with the SARS-CoV-2 pandemic, prompting the development of alternative methods of training. While previous studies have demonstrated feasibility of remote neonatal resuscitation training, this perspective paper covers common barriers identified and key lessons learned developing a cadre of remote facilitators. Challenges of remote facilitation include mastering videoconferencing platforms, establishing personal connections, and providing effective oversight of skills practice. Training sessions can be used to support facilitators in acquiring comfort and competency in harnessing videoconferencing platforms for effective facilitation. Optimization of approaches and investment in capacity building of remote facilitators are imperative for effective implementation of remote neonatal resuscitation training.

Neurodevelopmental Outcome at 6 Months Following Neonatal Resuscitation in Rural Tanzania.

Early bag-mask ventilation (BMV) administered to non-breathing neonates at birth in the presence of birth asphyxia (interruption of placental blood flow) has reduced neonatal mortality by up to 50% in low- and middle-income countries. The neurodevelopmental outcome of neonates receiving BMV remains unknown. Using the Malawi Developmental Assessment Tool (MDAT), infants who received BMV at birth were assessed at 6 months, evaluating gross motor, fine motor, language and social skills. A healthy cohort with no birth complications was assessed with the same tool for comparison. Mean age-adjusted MDAT z-scores were not significantly different between the groups. The number of children having developmental delay defined as a z-score ≤ -2 was significantly higher in the resuscitated cohort for the fine motor and language domain and overall MDAT z-score. The prevalence of clinical seizures post discharge was significantly higher in the resuscitated group and was associated with neurodevelopmental delay. Infants with developmental delay or seizures were more likely to have a 5 min Apgar < 7 and a longer duration of BMV. Most children receiving BMV at birth are developing normally at 6 months. Still, there are some children with impaired development among resuscitated children, representing a subgroup of children who may have suffered more severe asphyxia.

Use of Suctioning during Newborn Resuscitation and Its Effects on Heart Rate in a Low-Resource Setting, Tanzania.

Suctioning of newborns immediately after birth, as part of delivery room resuscitation, is only recommended if the airway is obstructed. The aim of this study was to describe the use of suctioning during newborn resuscitation among survivors versus those who died within 3 days and potential suction-related heart rate responses and associations to newborn characteristics. This was a retrospective observational study from July 2013 to July 2016 in a referral hospital in rural Tanzania. Research assistants observed and documented all deliveries, newborn resuscitations were video-recorded, and newborn heart rates were captured with a dry-electrode electrocardiogram. Liveborn infants ≥34 weeks gestation who received ventilation and with complete datasets were eligible. All 30 newborns who died were included, and a total of 46 survivors were selected as controls. Videos were annotated and heart rate patterns were observed before and after the suction events. Suctioning was performed more frequently than recommended. No differences were found in suctioning characteristics between newborns who died versus those who survived. In 13% of suction events, a significant heart rate change (i.e., arrhythmia or brief/sustained >15% fall in heart rate) was observed in relation to suctioning. This represents a potential additional harm to already depressed newborns undergoing resuscitation.

Cardiopulmonary resuscitation in low-resource settings: a statement by the International Liaison Committee on Resuscitation, supported by the AFEM, EUSEM, IFEM, and IFRC.

Most recommendations on cardiopulmonary resuscitation were developed from the perspective of high-resource settings with the aim of applying them in these settings. These so-called international guidelines are often not applicable in low-resource settings. Organisations including the International Liaison Committee on Resuscitation (ILCOR) have not sufficiently addressed this problem. We formed a collaborative group of experts from various settings including low-income, middle-income, and high-income countries, and conducted a prospective, multiphase consensus process to formulate this ILCOR Task Force statement. We highlight the discrepancy between current cardiopulmonary resuscitation guidelines and their applicability in low-resource settings. Successful existing initiatives such as the Helping Babies Breathe programme and the WHO Emergency Care Systems Framework are acknowledged. The concept of the chainmail of survival as an adaptive approach towards a framework of resuscitation, the potential enablers of and barriers to this framework, and gaps in the knowledge are discussed, focusing on low-resource settings. Action points are proposed, which might be expanded into future recommendations and suggestions, addressing a large diversity of addressees from caregivers to stakeholders. This statement serves as a stepping-stone to developing a truly global approach to guide resuscitation care and science, including in health-care systems worldwide.

The two-thumb technique using an elevated surface is preferable for teaching infant cardiopulmonary resuscitation.

OBJECTIVES: To determine whether the two-thumb technique is superior to the two-finger technique for administering chest compressions using the floor surface and the preferred location for performing infant cardiopulmonary resuscitation (CPR) (ie, floor, table, or radiant warmer). STUDY DESIGN: Twenty Neonatal Resuscitation Program trained medical personnel performed CPR on a neonatal manikin utilizing the two-thumb vs two-finger technique, a compression to ventilation ratio of 30:2 for 2 minutes in random order on the floor, table, and radiant warmer. RESULTS: Compression depth favored the two-thumb over two-finger technique on the floor (27 ± 8 mm vs 23 ± 7), table (26 ± 7 mm vs 22 ± 7), and radiant warmer (29 ± 4 mm vs 23 ± 4) (all P < .05). Per individual subject, the compression depth varied widely using both techniques and at all surfaces. More variability between compressions was observed with the two-finger vs two-thumb technique on all surfaces (P < .05). Decay in compression over time occurred and was greater with the two-finger vs two-thumb technique on the floor (-5 ± 7 vs -1 ± 6 mm; P < .05) and radiant warmer (-3 ± 6 vs -0.3 ± 2 mm; P < .05), compared with the table (-3 ± 9 vs -4 ± 5 mm). Providers favored the table over radiant warmer, with the floor least preferred and most tiring. CONCLUSIONS: The two-thumb technique is superior to the two-finger technique, achieving greater depth, less variability, and less decay over time. The table was considered most comfortable and less tiring. The two-thumb technique should be the preferred method for teaching lay persons infant CPR preferably using an elevated firm surface.