Newborn Response Research Articles

Developmental Changes of Muscle Synergies in an Infant's Walking.

Primitive stepping is one of the primitive reflexes in newborns in response to external stimuli. It is known that primitive stepping disappears about two months after birth, but its role and the relationship with voluntary gait acquired later are still unknown. In this study, we extracted muscle synergies, spatiotemporal coordination patterns of muscle activities, from EMG measured in one infant during growth (4-18 weeks of age) using non-negative matrix factorization (NMF). We found that a synergy changed before and after the disappearance of the primitive stepping, and others maintained the recruited muscles but changed the onset timing of the activations.

The effect of acute somatic pain on the killing activity of neutrophils in newborn rats

The immune system is subject to all sorts of influences. Pain is one of them, accompanying an organism’s existence. It is essential to be aware of and account for age-related characteristics of the innate immunity in order to adequately assess their dynamics in ontogenesis. The literature is scarce on the changes to the killing activity of neutrophils occurring in newborns in response to acute pain. The aim of this study was to detect potential changes to the phagocytic activity of neutrophils in response to an algogenic stimulus in newborn rats. The experiments were carried out in 3-5-day-old rats. Two groups were formed: the control group and the main group, in which acute pain was modelled. Blood samples were collected 2, 30–60 and 120–180 minutes after exposure to the algogenic stimulus. The microbicidal activity of neutrophils was measured using a spectrophotometric modification of the spontaneous/stimulated nitroblue tetrazolium (NBT) reduction test. The results were compared using the Mann-Whitney U test. In the first hour following pain modeling, the stimulated NBT reduction test demonstrated an increase in the measured parameters from 71.5 to 87.4 a.u. (р < 0.001); the spontaneous NBT reduction test showed an increase from 50.7 to 58.6 a.u. (p < 0.01) 30 to 60 min after exposure. The most pronounced change of the microbicidal activity coefficient was observed 2 min after pain modeling, increasing from 1.40 to 1.72 a.u (р < 0.001). By the end of the experiment, the measured parameters approximated their initial values. During the analysis, we accounted for the fact that the neutrophil response to the algogenic stimulus was unfolding in the setting of microbial colonization occurring in newborns.

Effect of maternal immunization against pertussis in Medellin and the metropolitan area, Colombia, 2016–2017

BackgroundIn 2013, pertussis immunization (Tdap) for pregnant women was implemented in Colombia to protect newborns in response to increased pertussis incidence. ObjectiveTo assess the effect of Tdap maternal immunization on the concentration of mother/umbilical cord antibodies and the occurrence of pertussis in infants during their first six months of life. MethodsA cohort study in eight randomly selected hospitals in Medellin and metropolitan area of Antioquia, Colombia was conducted in 2015–2016. IgG PT antibody levels in paired maternal and umbilical cord sera were measured from 805 mothers immunized recruited during labor and 200 mothers recruited during the prenatal care before immunization and followed until delivery. Antibodies were analyzed by commercial ELISA kits. 896 infants were followed to detect acute respiratory infections and paroxysms of coughing, inspiratory whoop, apnea, cyanosis or post-tussive vomiting. For laboratory confirmation, B. pertussis- specific real time PCR was performed. ResultsWe observed a high prevalence of titers >100 IU/mL (mother: 18.40% [95% CI 16–21%]; umbilical cord: 23.1% [95% CI 19.2–27.4%]), positive correlation of umbilical cord and maternal antibodies, higher antibody concentration in vaccinated than in non-vaccinated mothers and significant difference in antibody levels before and after vaccination (Wilcoxon test p = 0.000). The trans placental transport ratio was higher if the mother was vaccinated between 26 and 30 weeks of pregnancy and maximum eight weeks before delivery. Two cases of pertussis were confirmed in infants (incidence of 1.99 per 1000). ConclusionThe expected effect of Tdap maternal vaccination against pertussis was observed.

Gene-specific DNA methylation in newborns in response to folic acid supplementation during the second and third trimesters of pregnancy: epigenetic analysis from a randomized controlled trial

Emerging evidence suggests that maternal folate status can impact cognitive development in childhood. Folate-dependent DNA methylation may provide a biological mechanism to link folate status during pregnancy with cognition in the offspring. The objective was to investigate the effect of continued folic acid (FA) supplementation beyond the first trimester of pregnancy on DNA methylation in cord blood of epigenetically controlled genes related to brain development and function. Using available cord blood samples (n=86) from the Folic Acid Supplementation in the Second and Third Trimesters (FASSTT) trial in pregnancy, we applied pyrosequencing techniques to analyze cord blood DNA at 9 candidate loci known to be regulated by methylation, including some previously implicated in observational studies: the widely dispersed retrotransposon long interspersed nuclear element-1 (LINE-1) and 8 single-copy loci (RBM46, PEG3, IGF2, GRB10, BDNF, GRIN3B, OPCML, and APC2). The newborns of mothers who received ongoing FA (400 µg/d) through the second and third trimesters, compared with placebo, had significantly lower overall DNA methylation levels at LINE-1 (56.3% ± 1.7% compared with 57.2% ± 2.1%; P = 0.024), IFG2 (48.9% ± 4.4% compared with 51.2% ± 5.1%; P = 0.021), and BDNF (2.7% ± 0.7% compared with 3.1% ± 0.8%; P = 0.003). The effect of FA treatment on DNA methylation was significant only in female offspring for IGF2 (P=0.028) and only in males for BDNF (P=0.012). For GRB10 and GRIN3B, we detected no effect on overall methylation; however, individual cytosine-phosphate-guanine sites showed significant DNA methylation changes in response to FA. Continued supplementation with FA through trimesters 2 and 3 of pregnancy results in significant changes in DNA methylation in cord blood of genes related to brain development. The findings offer a potential biological mechanism linking maternal folate status with neurodevelopment of the offspring, but this requires further investigation using a genome-wide approach. This trial was registered at www.isrctn.com as ISRCTN19917787.

TLR expression, phagocytosis and oxidative burst in healthy and septic newborns in response to Gram-negative and Gram-positive rods

The objective was to investigate whether phagocytes from healthy and septic newborns have a developmental deficiency in their capacity to recognize, phagocytize and generate hydrogen peroxide (H2O2) in response to Escherichia coli and Staphylococcus aureus. TLR expression and phagocytic ability of neutrophils and monocytes from 44 healthy preterm and term neonates, from 13 newborns with late-onset sepsis and from 24 healthy adults were determined using flow cytometry, and H2O2 production was measured by dihydrorhodamine test. TLR-2 and TLR-4 expressions were similar among the groups. The phagocytic ability of monocytes and neutrophils exposed to E. coli and S. aureus in healthy and septic neonates was significantly reduced compared to that of adults. Monocytes from septic newborns exposed to E. coli had higher H2O2 production than those of the other groups. The oxidative burst of monocytes exposed to S. aureus was reduced in preterm newborns compared with term ones and those with sepsis, and no differences were found in the oxidative burst of neutrophils. Even with the ability to recognize bacteria, a decreased clearance of pathogens can cause an imbalance in the immune response, which could lead to a predisposition to sepsis. Once established, the increased production of cytokines and ROS in an attempt to control the infection as well as the lack of full phagocytic activity leads to persistence of the pathogen and a state of constant inflammation.

Responsiveness of Human Neonates to the Odor of 5α-Androst-16-en-3-one: A Behavioral Paradox?

The odorous steroid 5α-androst-16-en-3-one (AND) occurs in numerous biological fluids in mammals, including man, where it is believed to play a chemocommunicative role. As AND was recently detected in milk and amniotic fluid, sensitivity and hedonic responses to this substance were assessed in human neonates. To this aim, respiration and facial expressions were recorded in 3-day-old newborns in response to aqueous solutions of AND, ranging from 500ng/mL to 0.5 fg/mL. Although analyses of respiratory rate did not lead to clear-cut results, the newborns changed their facial expressions at concentrations not detected by adults in a triangle test. Newborns displayed negative facial actions of longer duration to AND relative to an odorless control. Thus, AND may be considered to be offensive to newborns, which is a counterintuitive outcome as they are exposed to this compound in the womb (and it should therefore be familiar), in milk, and on the mother's skin surface (and it should therefore be conditioned as positive). Multiple reasons for this perceptual-behavioral paradox are discussed.

Investigação de um sistema de alimentação em recém-nascidos prematuros a partir de estimulação gustativa

Objetivo investigar a existência do sistema de alimentação em recém-nascidos prematuros a partir da estimulação gustativa. Métodos estudo experimental, analítico, duplo-cego. Participaram 90 recém-nascidos prematuros, de uma maternidade pública de Sergipe. O teste foi filmado, constituindo-se por três momentos de cinco minutos. O primeiro e último momento sem realizar estímulo, o segundo momento com estimulação gustativa, sendo que os recém-nascidos foram divididos em dois grupos (água ou sacarose). Foram estudados os comportamentos específicos sucção de mão direita e esquerda, protrusão de língua e movimentos de sucção nos estados comportamentais sono profundo, sono leve, sonolento, agitado/irritado e choro. Para caracterizar a população foram utilizadas média, desvio-padrão e prevalências. Foi utilizado o teste não paramétrico Mann-Whitney para comparação de médias. O teste de Spearman verificou correlação entre estados comportamentais e comportamentos específicos em cada momento do teste. O valor de p foi significante quando menor que 0,05. Resultados independente do estímulo administrado, a correlação aumentou em todos os comportamentos específicos. Comparando os grupos separadamente, após a estimulação, observou-se aumento de correlação em sucção de mão direita e protrusão de língua para ambos os grupos. O mesmo aconteceu em sucção, com exceção do estado agitado/irritado. Após a estimulação, houve maior correlação para o comportamento de sucção de mão esquerda no grupo sacarose quando comparado ao grupo água. Os resultados evidenciam que estímulos gustativos podem contribuir na prontidão para alimentação nesta população. Conclusões evidenciou-se nos recém-nascidos prematuros aumento de correlação para os comportamentos específicos relacionados ao sistema de alimentação, após estimulação oral, o que vislumbra a possibilidade da estimulação gustativa ser utilizada para ativação de um sistema de alimentação em recém-nascidos prematuros.

Maternal vitamin D deficiency causes smaller muscle fibers and altered transcript levels of genes involved in protein degradation, myogenesis, and cytoskeleton organization in the newborn rat

Epidemiologic data reveal associations between low serum concentrations of 25-hydroxyvitamin D (25(OH)D) and higher risk of falls and muscle weakness. Fetal stage is critical for the development of skeletal muscle, but little information is available on the impact of maternal vitamin D deficiency on muscles of offspring. To investigate the morphology and transcriptome of gastrocnemius muscle in newborns in response to maternal vitamin D deficiency, 14 female rats were fed either a vitamin D₃ deficient (0 IU/kg) or a vitamin D₃ adequate diet (1000 IU/kg) 8 weeks prior to conception, during pregnancy, and lactation. Analysis of cholecalciferol, 25(OH)D₃ and 1,25-dihydroxyvitamin D₃ show that dams fed the vitamin D deficient diet and their newborns suffered from a relevant vitamin D deficiency. Muscle cells of vitamin D deficient newborns were smaller than those of vitamin D adequate newborns (p < 0.05). Muscle transcriptome of the newborns revealed 426 probe sets as differentially expressed (259 upregulated, 167 downregulated) in response to vitamin D deficiency (fold change ≥1.5, p < 0.05). The effected genes are involved in protein catabolism, cell differentiation and proliferation, muscle cell development, and cytoskeleton organization. Maternal vitamin D deficiency has a major impact on morphology and gene expression profile of skeletal muscle in newborns.

Efeitos da estimulação gustativa nos estados comportamentais de recém-nascidos prematuros

OBJETIVO: Observar os estados comportamentais apresentados por recém-nascidos prematuros a partir de oferta de estímulos gustativos. MÉTODOS: Estudo experimental, analítico, duplo cego. Participaram 90 recém-nascidos prematuros nascidos em uma maternidade pública de Sergipe. O teste foi filmado, dividido em três etapas de cinco minutos. Na primeira e na última, não houve estímulo; na segunda aconteceu estimulação gustativa, sendo que os recém-nascidos foram divididos em dois grupos (água ou sacarose para análise 12%). Os estados comportamentais observados foram sono profundo, sono leve, sonolento, alerta, irritado/agitado e choro. Os dados foram analisados estatisticamente. RESULTADOS: No grupo sacarose houve correlação forte nos estados comportamentais sono leve e alerta, durante e após a estimulação, e redução de correlação nos estados sonolento, agitado/irritado e choro. Já no grupo água, após a estimulação houve aumento de correlação nos estados agitado/irritado e choro. CONCLUSÃO: A permanência ou mudança do estado comportamental do recém-nascido prematuro foi influenciada positivamente pela administração de estímulo gustativo, apontando para o possível uso da sacarose na contribuição de estados comportamentais favoráveis nessa população.

Metabolic Response to Stress in the Neonate Who Has Surgery

After completing this article, readers should be able to: 1. Describe the basic metabolic pathways involved in neonatal nutrition. 2. Describe the effect of stress on nutrition and metabolism in the neonate undergoing surgery. 3. Describe the differences in the metabolic response to stress between an adult and a neonate. Over the past 4 decades, there have been remarkable improvements in our ability to care for critically ill infants. Progress in surgical and critical care of neonates has led to improved survival rates. Our understanding of the nutritional requirements of infants continues to advance. In contrast to years past, practitioners caring for critically ill infants undergoing surgery today have various nutritional options, including specialized parenteral and enteral formulations. Although our understanding of host defense and nutritional support continues to evolve, the interplay between the immune system and metabolism is being investigated. Hence, we are improving the match between the infant’s energy expenditure and nutritional requirements. Critical to further progress is additional understanding of the metabolic response of a neonate to surgical stress. All living organisms require energy to survive. Fuel sources enter into complex metabolic cascades to form the ultimate energy substrate, adenosine triphosphate (ATP), a fuel needed to drive and maintain all physiologic systems. Under stressful conditions, intrinsic substrate mobilizes to synthesize additional energy substrate. In essence, host substrate is mobilized for the promotion of healing after injury. Cytokines, released in response to injury, drive the catabolic response to stress, but in abundance, as with the systemic inflammatory response syndrome (SIRS), cytokines are detrimental to the organism. The nutritional requirements of a neonate are significantly greater than those of an adult because not only are there requirements for substrate intake to fulfill basic metabolic needs, but there are metabolic needs to maintain rapid and continued growth and development. Furthermore, the metabolic response …

Electric Brain Responses Obtained From Newborn Infants to Changes in Duration in Complex Harmonic Tones

Event-related brain potentials of 10 full-term newborns in response to duration changes in complex, harmonic tones known to elicit prominent mismatch negativity (MMN) response in adults were investigated. Here we report that duration changes elicited prominent MMN responses in all newborns tested. In contrast, MMN has been reported in as little as 50% of the infants in some previous studies using other sound attributes. When the infant MMN latency was compared with that obtained from adults, and 4- as well as 8-year-old children, it was found that the MMN latency was a bit later in newborns than in older age groups. This result is consistent with previous findings. The MMN amplitude, however, was surprisingly large in infants compared to older children.

ONTOGENY OF RAT PULMONARY ALVEOLAR MACROPHAGE FUNCTION: EVIDENCE FOR A SELECTIVE DEFICIENCY IN IL-10 AND NITRIC OXIDE PRODUCTION BY NEWBORN ALVEOLAR MACROPHAGES

Alveolar macrophages (AM) play a crucial role in host defence by secretion of a large repertoire of biological response modifiers (BRM) following challenge. Newborns manifest increased susceptibility to lung infections, suggesting a deficiency in AM-mediated host defence. Thus, we investigated the ontogeny of BRM production by resting and stimulated AM. We analysed the capacity of rat AM to produce mRNA specific for a range of cytokines including tumour necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-10, IL-12, IL-18, and the enzyme inducible nitric oxide synthase, in response to in vitro lipopolysaccharide (LPS) challenge. We report that production of nitric oxide by newborn AM under conditions of maximal stimulation was impaired. In addition, expression of IL-10 was only minimally upregulated in AM from newborns in response to LPS compared to adults. Inability to upregulate expression of IL-10 appeared to be influenced by microenvironmental factors, since peritoneal macrophages from newborns responded to LPS with significant upregulation of IL-10. Furthermore, when newborn AM were precultured in vitro, IL-10 responsiveness to LPS was partially restored. In contrast, cytokines such as TNF-α, IL-1, IL-6, IL-12 and IL-18 appeared to be expressed at adult levels by newborn AM. These results demonstrate that there may be functional differences in AM of newborns compared to adults, and these may be specific to the tissue compartment.

Pain in the preterm neonate: behavioural and physiological indices

The impact of invasive procedures on preterm neonates has received little systematic attention. We examined facial activity, body movements, and physiological measures in 56 preterm and full-term newborns in response to heel lancing, along with comparison preparatory and recovery intervals. The measures were recorded in special care and full-term nurseries during routine blood sampling. Data analyses indicated that in all measurement categories reactions of greatest magnitude were to the lancing procedure. Neonates with gestational ages as short as 25–27 weeks displayed physiological responsivity to the heel lance, but only in the heart rate measure did this vary with gestational age. Bodily activity was diminished in preterm neonates in general, relative to full-term newborns. Facial activity increased with the gestational age of the infant. Specificity of the response to the heel lance was greatest on the facial activity measure. Identification of pain requires attention to gestational age in the preterm neonate.

92 CARDIOPULMONARY EFFECTS OF A PATENT DUCTUS ARTERIOSUS

The premature newborn's response to increasing degrees of Lt→Rt PDA shunt is unknown. In 14 fetal lambs at 128d gestation (term 147d), we infiltrated the ductus with formalin and placed a mechanical occluder about it so that its patency could be regulated. 3d later the lamb was delivered, given sheep surfactant, paralyzed and mechanically ventilated. Microsphere measurements of left ventricular output (LVO) and its distribution were made prior to and 1.25 h after a change in ductus patency. Twenty four changes from open→closed or closed→open were assigned randomly from 3 to 7 h after delivery. Lambs with ductus shunts < 50% LVO (38%) had a significant increase in LVO (167 vs. 268 ml/kg/min:closed vs. open) with no change in effective systemic blood flow or BP. There was a significant increase in coronary flow but no change in flow to the kidneys, GI tract, brain, or carcass (ml/100 gm/min). Although lambs with shunts > 50% LVO (65%) had a significant increase in LVO (164 vs. 300 ml/kg/min), there was a significant decrease in effective systemic blood flow and BP. There were significant decreases in flow to the kidneys, GI tract, brain and carcass. Coronary flow was unchanged but there was a decrease in subendocardial flow. There was no change in HR or pulmonary compliance at either degree of shunt. Preterm lambs are capable of compensating for moderate degrees of PDA shunt by increasing preload and increasing stroke volume; highe degrees of shunt significantly decrease organ blood flow.

Amount of Sucking When a Sucking Object Is Readily Available to Human Newborns

In order to find out how much sucking human newborns evidence when a sucking object is readily available, pacifiers were given to 10 newborns in response to the spontaneous occurrence of empty sucking, rooting, and mouthing and were left in their mouths until the babies relinquished them. The spontaneous occurrence of these behaviors and of finger sucking was also observed in a control group of 10 babies. Both groups were observed continually during the 2 hours before a feeding and the first hour afterward, starting before the very first feeding and continuing at regular 24-hour intervals for 4 days. The amount of time spent sucking a pacifier or finger(s) was recorded for both groups. The results indicated that the newborns spent about half an hour per hour sucking a pacifier starting on the very first day of life, and that this did not vary with feeding experience. They also indicated that some newborns in the control group sucked their fingers, 1 for considerable periods of time. The results suggest that human newborns, like other newborn mammals, program considerable sucking time for themselves regardless of whether or not milk is forthcoming.

Amount of Sucking When a Sucking Object Is Readily Available to Human Newborns

In order to find out how much sucking human newborns evidence when a sucking object is readily available, pacifiers were given to 10 newborns in response to the spontaneous occurrence of empty sucking, rooting, and mouthing and were left in their mouths until the babies relinquished them. The spontaneous occurrence of these behaviors and of finger sucking was also observed in a control group of 10 babies. Both groups were observed continually during the 2 hours before a feeding and the first hour afterward, starting before the very first feeding and continuing at regular 24-hour intervals for 4 days. The amount of time spent sucking a pacifier or finger(s) was recorded for both groups. The results indicated that the newborns spent about half an hour per hour sucking a pacifier starting on the very first day of life, and that this did not vary with feeding experience. They also indicated that some newborns in the control group sucked their fingers, 1 for considerable periods of time. The results suggest that human newborns, like other newborn mammals, program considerable sucking time for themselves regardless of whether or not milk is forthcoming.

In-vitro release of K + from the developing submandibular gland of early postnatal rats

The release studied by incubating tissue slices in an enriched, oxygenated medium in the presence and absence of secretagogues indicated that slices from 1-day-old rats released K + in response to carbamylcholine, but not in response to epinephrine. The response to carbamylcholine was dose-related, with a 12.6 ± 1.3 per cent release at a concentration of 2 × 10 −5M. Epinephrine did not induce K + release in concentrations from 2 × 10 −7 to 2 × 10 −5M. Glands from 7- and 14-day-old rats released a similar amount as those of new-borns in response to carbamylcholine and by 21 days of age the glands released 21.5 ± 1.9 per cent of their K + content upon exposure to 2 × 10 −5 M carbamylcholine. A response to epinephrine (2 × 10 −5 M) was first detected at 14 days of age, when the slices released 8.3 ± 1.2 per cent of their K +. Slices of 21-day-old rats showed a 17.9 ± 1.3 per cent K + release in response to this dose. As in adult glands, the net amount of K + released by the developing postnatal gland seems to be the result of two opposing mechanisms, a passive efflux and an active re-uptake which depends on the activation of an ouabain-sensitive Na +-K + -ATPase. The passive efflux component was similar in glands from different postnatal ages and was enhanced by secretagogues. The extent of active uptake, on the other hand, decreased with increasing postnatal age. As in the adult, the net release of K + depended on the presence of Ca2 + in the incubation medium, but the sensitivity of the response to Ca 2+ omission varied in accord with the age of the animals and with the stimulant used. It is speculated that proacinar and terminal tubular cells may be involved in K + release in the early postnatal period.

Effect of Environmental Temperature on Glucose-induced Insulin Response in the Newborn Rat

Blood glucose and plasma insulin and glucagon concentrations were determined in full-term rats delivered by cesarean section and exposed to 37 degrees C. or 24 degrees C. environmental temperature during the first hours of extrauterine life. When newborn rats were maintained at thermal neutrality (37 degrees C.), a transient period of hypoglycemia of two hours occurred, associated with a rapid fall in plasma insulin and a rise in plasma glucagon concentrations. During cold exposure (24 degrees C.), the blood glucose level remained stable over the four hours studied; the decrease of plasma insulin was sluggish while the rise of plasma glucagon was unchanged. In newborn rats maintained at 37 degrees C., an intraperitoneal glucose load one hour after delivery produced a marked rise in blood glucose and plasma insulin concentrations one hour later. The distribution of experimental points suggested a sigmoidal dose-response curve. By contrast in newborn rats kept at room temperature (24 degrees C.) the same glucose load did not induce any increase in plasma insulin in spite of hyperglycemia. However, phentolamine resulted in pronounced plasma insulin rise in hypothermic newborns in response to glucose administration. From these observations it is concluded that the in-vivo unresponsiveness of the beta cells to glucose at birth, reported by others, is mainly due to the experimental conditions.