Retrospectively Assessed Muscle Tone and Skin Colour following Airway Suctioning in Video-Recorded Infants Receiving Delivery Room Positive Pressure Ventilation.

Background: Recently, the International Liaison Committee on Resuscitation published a systematic review that concluded that routine suctioning of clear amniotic fluid in the delivery room might be associated with lower oxygen saturation (SpO2) and 10 min Apgar score. The aim of this study was to examine the effect of delivery room airway suctioning on the clinical appearance, including muscle tone and skin colour, of video-recorded term and preterm infants born through mainly clear amniotic fluid. Methods: This was a single-centre observational study using transcribed video recordings of neonatal stabilizations. All infants who received delivery room positive pressure ventilation (PPV) from August 2014 to November 2016 were included. The primary outcome was the effect of airway suctioning on muscle tone and skin colour (rated 0−2 according to the Apgar score), while the secondary outcome was the fraction of infants for whom airway suction preceded the initiation of PPV as a surrogate for "routine" airway suctioning. Results: Airway suctioning was performed in 159 out of 302 video recordings and stimulated a vigorous cry in 47 (29.6%) infants, resulting in improvements in muscle tone (p = 0.09) and skin colour (p < 0.001). In 43 (27.0%) infants, airway suctioning preceded the initiation of PPV. Conclusions: In this single-centre observational study, airway suctioning stimulated a vigorous cry with resulting improvements in muscle tone and skin colour. Airway suctioning was often performed prior to the initiation of PPV, indicating a practice of routine suctioning and guideline non-compliance.

Video-Recorded Airway Suctioning of Clear and Meconium-Stained Amniotic Fluid and Associated Short-Term Outcomes in Moderately and Severely Depressed Preterm and Term Infants.

BACKGROUND: The aim of this study was to investigate delivery room airway suctioning and associated short-term outcomes in depressed infants. METHODS: This is a single-centre prospective observational study of transcribed video recordings of preterm (gestational age, GA < 37 weeks) and term (GA ≥ 37 weeks) infants with a 5 min Apgar score ≤ 7. We analysed the association between airway suctioning, breathing, bradycardia and prolonged resuscitation (≥10 min). For comparison, non-suctioned infants with a 5 min Apgar score ≤ 7 were included. RESULTS: Two hundred suction episodes were performed in 19 premature and 56 term infants. Breathing improved in 1.9% of premature and 72.1% of term infants, and remained unchanged in 84.9% of premature and 27.9% of term infants after suctioning. In our study, 61 (81.3%) preterm and term infants who were admitted to the neonatal intensive care unit experienced bradycardia after airway suctioning. However, the majority of the preterm and more than half of the term infants were bradycardic before the suction procedure was attempted. Among the non-airway suctioned infants (n = 26), 73.1% experienced bradycardia, with 17 non-airway suctioned infants being admitted to the neonatal intensive care unit. There was a need for resuscitation ≥ 10 min in 8 (42.1%) preterm and 32 (57.1%) term infants who underwent airway suctioning, compared to 2 (33.3%) preterm and 19 (95.0%) term infants who did not receive airway suctioning. CONCLUSIONS: In the infants that underwent suctioning, breathing improved in most term, but not preterm infants. More non-suctioned term infants needed prolonged resuscitation. Airway suctioning was not directly associated with worsening of breathing, bradycardia, or extended resuscitation needs.

Estimated daily intake of phthalates, parabens, and bisphenol A in hospitalised very low birth weight infants.

Very low birth weight infants (VLBW, birth weight (BW) < 1500 g) are exposed to phthalates, parabens and bisphenol A (BPA) early in life. We estimated daily intake (EDI) of these excipients in 40 VLBW infants the first and fifth week of life while hospitalised. Based on urinary samples collected in 2010, EDI was calculated and compared to the tolerable daily intake (TDI) with hazard quotients (HQs) evaluated. A HQ > 1 indicates that EDI exceeded TDI with increased risk of adverse health effects. EDI was higher in VLBW infants compared to term-born infants and older children. VLBW infants born at earlier gestational age (GA), or with lower BW, had higher EDI than infants born at later GA or with higher BW. First week median EDI for BPA was higher than TDI in 100% of infants, in 75% for di(2-ethylhexyl) phthalate (DEHP), 90% for the sum of butyl benzyl phthalate (BBzP), di-n-butyl phthalate (DnBP), DEHP and di-iso-nonyl phthalate (DiNP) = ∑BBzP+DnBP+DEHP+DiNP, and in 50% of infants for propylparaben (PrPa), indicating increased risk of adverse effects. Fifth week EDI remained higher than TDI in all infants for BPA, in 75% for DEHP and ∑BBzP+DnBP+DEHP+DiNP, and 25% of infants for PrPa, indicating prolonged risk. Maximum EDI for di-iso-butyl phthalate was higher than TDI suggesting risk of adverse effects at maximum exposure. VLBW infants born earlier than 28 weeks GA had higher EDI, above TDI, for PrPa compared to infants born later than 28 weeks GA. Infants with late-onset septicaemia (LOS) had higher EDI for DEHP, ∑BBzP+DnBP+DEHP+DiNP and BPA, above TDI, compared to infants without LOS. More 75% of the infants' EDI for DEHP and ∑BBzP+DnBP+DEHP+DiNP, 25% for PrPa, and 100% of infants' EDI for BPA, were above TDI resulting in HQs > 1, indicating increased risk of adverse health effects.

Corrigendum: Management of the unexpected difficult airway in neonatal resuscitation.

[This corrects the article DOI: 10.3389/fped.2021.699159.].

Management of the Unexpected Difficult Airway in Neonatal Resuscitation.

A "difficult airway situation" arises whenever face mask ventilation, laryngoscopy, endotracheal intubation, or use of supraglottic device fail to secure ventilation. As bradycardia and cardiac arrest in the neonate are usually of respiratory origin, neonatal airway management remains a critical factor. Despite this, a well-defined in-house approach to the neonatal difficult airway is often lacking. While a recent guideline from the British Pediatric Society exists, and the Scottish NHS and Advanced Resuscitation of the Newborn Infant (ARNI) airway management algorithm was recently revised, there is no Norwegian national guideline for managing the unanticipated difficult airway in the delivery room (DR) and neonatal intensive care unit (NICU). Experience from anesthesiology is that a "difficult airway algorithm," advance planning and routine practicing, prepares the resuscitation team to respond adequately to the technical and non-technical stress of a difficult airway situation. We learned from observing current approaches to advanced airway management in DR resuscitations in a university hospital and make recommendations on how the neonatal difficult airway may be managed through technical and non-technical approaches. Our recommendations mainly pertain to DR resuscitations but may be transferred to the NICU environment.

High urinary concentrations of parabens and bisphenol A in very low birth weight infants.

Very low birth weight infants (VLBW; birth weight < 1500 g) are treated with pharmaceuticals and medical equipment containing parabens and bisphenol A (BPA). Parabens are used in pharmaceuticals, whereas BPA in medical equipment where concentrations are rarely reported in hospitalised VLBW infants. We measured urinary concentrations of parabens and BPA and hypothesised high and increasing concentrations in infants born at lower gestational ages (GAs), and among infants with bronchopulmonary dysplasia (BPD) and late-onset septicaemia (LOS) due to higher exposure from pharmaceuticals and medical equipment. Urinary samples were collected during the first (n = 38) and fifth (n = 36) week of life. Methylparaben, ethylparaben, propylparaben, butylparaben, and BPA concentrations were measured using ultra high-performance liquid chromatography coupled to tandem mass spectrometry. VLBW infants had very high urinary concentrations of parabens and BPA compared to term infants and older children. The Σ paraben concentration was higher than detected in previous studies on premature infants. Lower GA at birth was associated with higher concentrations of parabens and BPA. Infants born before 28 weeks GA had higher first week concentrations of propylparaben (38.6 vs. 9.05 ng/mL, p = 0.007), butylparaben (0.28 vs. 0.09 ng/mL, p = 0.05) and fifth week concentrations of BPA (15.1 vs. 6.02 ng/mL, p = 0.02) than infants born after 28 weeks GA. Infants with LOS and BPD had higher fifth week concentrations of BPA than infants without LOS and BPD (LOS: 14.2 vs. 6.77 ng/mL, p = 0.07; BPD: 18.6 vs. 7.62 ng/mL, p = 0.05).

Enhanced nutrient supply and intestinal microbiota development in very low birth weight infants.

BACKGROUND: Promoting a healthy intestinal microbiota may have positive effects on short- and long-term outcomes in very low birth weight (VLBW; BW < 1500 g) infants. Nutrient supply influences the intestinal microbiota. METHODS: Fifty VLBW infants were randomized to an intervention group receiving enhanced nutrient supply or a control group. Fecal samples from 45 infants collected between birth and discharge were analyzed using 16S ribosomal RNA (rRNA) amplicon sequencing. RESULTS: There was considerable individual variation in microbiota development. Microbial richness decreased towards discharge in the controls compared to the intervention group. In the intervention group, there was a greater increase in diversity among moderately/very preterm (MVP, gestational age ≥ 28 weeks) infants and a steeper decrease in relative Staphylococcus abundance in extremely preterm (EP, gestational age < 28 weeks) infants as compared to controls. Relative Bifidobacterium abundance tended to increase more in MVP controls compared to the intervention group. Abundance of pathogens was not increased in the intervention group. Higher relative Bifidobacterium abundance was associated with improved weight gain. CONCLUSION: Nutrition may affect richness, diversity, and microbiota composition. There was no increase in relative abundance of pathogens among infants receiving enhanced nutrient supply. Favorable microbiota development was associated with improved weight gain.

Intestinal microbiota development and gestational age in preterm neonates.

The intestinal microbiota is an important contributor to the health of preterm infants, and may be destabilized by a number of environmental factors and treatment modalities. How to promote the development of a healthy microbiota in preterm infants is largely unknown. We collected fecal samples from 45 breastfed preterm very low birth weight (birth weight < 1500 g) infants from birth until 60 days postnatal age to characterize the intestinal microbiota development during the first weeks of life in preterm infants. Fecal microbiota composition was determined by 16S rRNA amplicon sequencing. The main driver of microbiota development was gestational age; antibiotic use had strong but temporary effects and birth mode had little influence. Microbiota development proceeded in four phases indicated by the dominance of Staphylococcus, Enterococcus, Enterobacter, and finally Bifidobacterium. The Enterococcus phase was only observed among the extremely premature infants and appeared to delay the microbiota succession. The results indicate that hospitalized preterm infants receiving breast milk may develop a normal microbiota resembling that of term infants.

Enhanced nutrient supply to very low birth weight infants is associated with higher blood amino acid concentrations and improved growth.

BACKGROUND & AIMS: Customized nutrient supply is vital to ensure optimal growth among very low birth weight infants (birth weight < 1500 g). The supply of amino acids is especially important due to their impact on protein synthesis and growth. The objectives of this study were to evaluate the impact of enhanced nutrition on growth, blood concentrations of amino acids, and explore possible associations between amino acid concentrations and common neonatal morbidities. We hypothesized higher amino acids levels and growth velocity among infants on enhanced nutrient supply. METHODS: This randomized controlled trial was performed in three university neonatal intensive care units in Oslo, Norway. Fifty very low birth weight infants were randomized to a control or intervention group. Within 24 h after birth, infants in the intervention group received enhanced supply of energy, amino acids, lipids, long-chain polyunsaturated fatty acids and vitamin A, whereas the control group received a standard nutrient supply. The intervention continued until 52 weeks postmenstrual age or until a body weight of 5.5 kg was reached. Amino acid analyses were performed at birth, day 3, 5 weeks of age and 5 months corrected age. Detailed information about nutrient intake, morbidities, blood amino acid concentrations and growth velocity were collected from 44 infants (6 infants excluded). High-performance liquid chromatography was used for amino acid analysis. RESULTS: The intervention group (n = 23) received higher supply of proteins, with higher blood concentrations of amino acids measured at 5 weeks of age, and improved growth velocity (mean 17.4 vs 14.3 g/kg/day, p < 0.001) at 36 weeks postmenstrual age, compared to the control group (n = 21). The correlation between concentrations of branched chain amino acids (leucine, isoleucine and valine) and growth was stronger and more positive among infants: a) in the control group (correlation coefficient ≥ 0.68, p ≤ 0.004); b) born with birth weight appropriate for gestational age (correlation coefficient ≥ 0.53, p ≤ 0.009) and c) not diagnosed with septicemia (correlation coefficient ≥ 0.63, p ≤ 0.005). CONCLUSION: Enhanced nutrient supply to very low birth weight infants led to higher blood amino acid concentrations and improved growth. The correlations between amino acid concentrations and growth velocity were weaker in the intervention group as compared to the control group. This could reflect an upper threshold for protein synthesis and growth with our intervention, whereas a potential for further growth with increasing amino acid supply was possible for the control group. CLINICAL TRIAL REGISTRATION NO: NCT01103219.

Enhanced nutrition improves growth and increases blood adiponectin concentrations in very low birth weight infants.

BACKGROUND: Adequate nutrient supply is essential for optimal postnatal growth in very low birth weight (VLBW, birth weight<1,500 g) infants. Early growth may influence the risk of metabolic syndrome later in life. OBJECTIVE: To evaluate growth and blood metabolic markers (adiponectin, leptin, and insulin-like growth factor-1 (IGF-1)) in VLBW infants participating in a randomized nutritional intervention study. DESIGN: Fifty VLBW infants were randomized to an enhanced nutrient supply or a standard nutrient supply. Thirty-seven infants were evaluated with growth measurements until 2 years corrected age (CA). Metabolic markers were measured at birth and 5 months CA. RESULTS: Weight gain and head growth were different in the two groups from birth to 2 years CA (weight gain: pinteraction=0.006; head growth: pinteraction=0.002). The intervention group improved their growth z-scores after birth, whereas the control group had a pronounced decline, followed by an increase and caught up with the intervention group after discharge. At 5 months CA, adiponectin concentrations were higher in the intervention group and correlated with weight gain before term (r=0.35) and nutrient supply (0.35≤r≤0.45). Leptin concentrations correlated with weight gain after term and IGF-1 concentrations with length growth before and after term and head growth after term (0.36≤r≤0.53). CONCLUSION: Enhanced nutrient supply improved early postnatal growth and may have prevented rapid catch-up growth later in infancy. Adiponectin concentration at 5 months CA was higher in the intervention group and correlated positively with early weight gain and nutrient supply. Early nutrition and growth may affect metabolic markers in infancy.Clinical Trial Registration (ClinicalTrials.gov) no.: NCT01103219.

Increased levels of phthalates in very low birth weight infants with septicemia and bronchopulmonary dysplasia.

Very low birth weight infants (VLBW; birth weight<1500g) are exposed to potentially harmful phthalates from medical devices during their hospital stay. We measured urinary phthalate concentrations among hospitalized VLBW infants participating in a nutritional study. Possible associations between different phthalates and birth weight (BW), septicemia and bronchopulmonary dysplasia (BPD) were evaluated. Forty-six VLBW infants were enrolled in this randomized controlled nutritional study. The intervention group (n=24) received increased quantities of energy, protein, fat, essential fatty acids and vitamin A, as compared to the control group (n=22). The concentrations of 12 urinary phthalate metabolites were measured, using high-performance liquid chromatography coupled to tandem mass spectrometry, at 3 time points during the first 5weeks of life. During this study, the levels of di (2-ethylhexyl) phthalate (DEHP) metabolites decreased, whereas an increasing trend was seen regarding metabolites of di-iso-nonyl phthalate (DiNP). Significantly higher levels of phthalate metabolites were seen in infants with lower BW and those diagnosed with late onset septicemia or BPD. A significant positive correlation between the duration of respiratory support and DEHP metabolites was observed (p≤0.01) at 2.9weeks of age. Birth weight was negatively associated with urinary phthalate metabolite concentrations. Infants with lower BW and those diagnosed with septicemia or BPD experienced prolonged exposure from medical equipment containing phthalates, with subsequent higher levels of phthalate metabolites detected. Clinical Trial Registration no.: NCT01103219.

Improved Visual Perception in Very Low Birth Weight Infants on Enhanced Nutrient Supply.

BACKGROUND: Optimal nutrient supply to very low birth weight (VLBW: BW <1,500 g) infants is important for growth and neurodevelopment. Growth restriction is common among these infants and may be associated with neurocognitive impairments. OBJECTIVES: To compare an enhanced nutrient supply to a routine supply given to VLBW infants and to evaluate the effects on visual perception of global form and motion measured by visual event-related potentials (VERP). METHODS: A total of 50 VLBW infants were randomized to an intervention group that received an increased supply of energy, protein, fat, essential fatty acids, and vitamin A or a control group that received standard nutritional care. At 5 months' corrected age the infants were examined using VERP to investigate the responses to global form and motion. VERP were analysed at the first (f1) and third (f3) harmonics of the stimulus frequency. RESULTS: Data from 31 subjects were eligible for analysis. The motion VERP responses for the f1 and f3 components were stronger in the area near the posterior midline region in the intervention group compared to the controls in the group analyses (p = 0.02 and p = 0.001, respectively). CONCLUSION: The results showed a more consistent response to global motion among infants receiving enhanced nutrition. The intervention may have improved visual perception of global motion.

Enhanced nutrient supply to very low birth weight infants is associated with improved white matter maturation and head growth.

BACKGROUND: Extrauterine growth restriction is common among very low birth weight infants (VLBW, BW <1,500 g). Optimal postnatal nutrient supply is essential to limit growth restriction and ensure adequate growth and neurodevelopment. OBJECTIVES: We compared an enhanced postnatal nutrient supply to a standard supply and evaluated the effects on growth velocity, head circumference growth and cerebral maturation - the latter by magnetic resonance diffusion tensor imaging (DTI). We hypothesized increased growth velocity, head circumference growth and decreased mean diffusivity (MD) in cerebral white matter (WM) areas, suggesting improved cerebral maturation among infants on the enhanced nutrient supply. METHODS: In this randomized controlled trial, infants on the enhanced nutrient supply received increased amounts of energy, protein, fat, essential fatty acids and vitamin A until discharge. DTI was performed close to term equivalent age. Outcomes were growth velocity, head circumference growth and WM mean diffusivity. RESULTS: Among the 50 included infants, 14 in the intervention group and 11 controls underwent a successful DTI. Infants on the enhanced diet achieved improved growth velocity (16.5 vs. 13.8 g/kg/day, p = 0.01) and increased head circumference (Δz score: 0.24 vs. -0.12, p = 0.15). A significantly lower MD was seen in a large WM area such as the superior longitudinal fasciculi (1.19 × 10(-3) vs. 1.24 × 10(-3) mm(2)/s, p = 0.04, adjusted for age when scanned). CONCLUSIONS: Enhanced nutrient supply to VLBW infants is associated with improved growth velocity, increased head circumference growth and decreased regional WM mean diffusivity, suggesting improved maturation of cerebral connective tracts.

Urinary metabolite profiles in premature infants show early postnatal metabolic adaptation and maturation.

OBJECTIVES: Early nutrition influences metabolic programming and long-term health. We explored the urinary metabolite profiles of 48 premature infants (birth weight < 1500 g) randomized to an enhanced or a standard diet during neonatal hospitalization. METHODS: Metabolomics using nuclear magnetic resonance spectroscopy (NMR) was conducted on urine samples obtained during the first week of life and thereafter fortnightly. RESULTS: The intervention group received significantly higher amounts of energy, protein, lipids, vitamin A, arachidonic acid and docosahexaenoic acid as compared to the control group. Enhanced nutrition did not appear to affect the urine profiles to an extent exceeding individual variation. However, in all infants the glucogenic amino acids glycine, threonine, hydroxyproline and tyrosine increased substantially during the early postnatal period, along with metabolites of the tricarboxylic acid cycle (succinate, oxoglutarate, fumarate and citrate). The metabolite changes correlated with postmenstrual age. Moreover, we observed elevated threonine and glycine levels in first-week urine samples of the small for gestational age (SGA; birth weight < 10th percentile for gestational age) as compared to the appropriate for gestational age infants. CONCLUSION: This first nutri-metabolomics study in premature infants demonstrates that the physiological adaptation during the fetal-postnatal transition as well as maturation influences metabolism during the breastfeeding period. Elevated glycine and threonine levels were found in the first week urine samples of the SGA infants and emerged as potential biomarkers of an altered metabolic phenotype.

Enhanced feeding and diminished postnatal growth failure in very-low-birth-weight infants.

OBJECTIVE: The aim of the present study was to determine whether an increased supply of energy, protein, essential fatty acids, and vitamin A reduces postnatal growth failure in very-low-birth-weight infants. METHODS: Fifty infants with birth weight <1500 g were randomized to an intervention (n = 24) or a control (n = 26) feeding protocol within 24 hours after birth. Forty-four infants were included in the final analysis. This study was discontinued because of an increased occurrence of septicemia in the intervention group. RESULTS: The intervention group had a lower mean birth weight (P = 0.03) and a higher proportion of infants small-for-gestational age (P = 0.04) than the control group. Other baseline characteristics were similar. The median (interquartile range) energy and protein supplies during the first 4 weeks of life were higher in the intervention group: 139 (128-145) versus 126 (121-128) kcal · kg · day (P < 0.001) and 4.0 (3.9-4.2) versus 3.2 (3.1-3.3) g · kg · day (P < 0.001). The infants in the intervention group regained birth weight faster (P = 0.001) and maintained their z scores for weight and head circumference from birth to 36 weeks' postmenstrual age (both P < 0.001). The median (interquartile range) growth velocity was 17.4 (16.3-18.6) g · kg · day in the intervention group and 13.8 (13.2-15.5) g · kg · day in the control group (P < 0.001). In line with the improved growth in the intervention group, the proportion of growth-restricted infants was 11 of 23 both at birth and at 36 weeks' postmenstrual age, whereas this proportion increased among the controls from 4 of 21 to 13 of 21 (P = 0.04). CONCLUSIONS: Enhanced supply of energy, protein, essential fatty acids, and vitamin A caused postnatal growth along the birth percentiles for both weight and head circumference.

Enhanced feeding in very-low-birth-weight infants may cause electrolyte disturbances and septicemia--a randomized, controlled trial.

BACKGROUND & AIMS: High supply of protein and energy has been introduced to very-low-birth-weight infants to improve growth and cognitive development. The aim of this study was to compare two different feeding strategies on postnatal growth and clinical outcome during neonatal hospitalization. METHODS: Fifty very-low-birth-weight infants were randomized to either an enhanced or a standard feeding protocol within 24 h after birth. Chi-square and T-tests were applied. RESULTS: First week protein, fat and energy supply was significantly higher in the intervention group compared to the control group (all P < 0.001). After inclusion of 50 patients we observed a higher occurrence of septicemia in the intervention group, 63% vs. 29% (P = 0.02), and no more patients were included. The infants in the intervention group demonstrated improved postnatal growth, but they also disclosed significant electrolyte deviations during the first week of life with hypophosphatemia, hypokalemia and hypercalcemia. First week phosphate nadir was lower in the infants experiencing septicemia (1.23 (0.50) mmol/L) as compared to the infants without (1.61 (0.61) mmol/L) (P = 0.03). CONCLUSION: Our study implies that enhanced feeding may induce electrolyte imbalances in VLBW infants, and that deleterious side effects similar to those seen in refeeding syndrome may occur. ClinicalTrials.gov, number NCT01103219 and the EudraCT number is 2010-020464-38.