Response Of Preterm Infants Research Articles

Skin-to-skin contact reduces near-infrared spectroscopy pain responses in premature infants during blood sampling.

This study investigated if skin-to-skin contact could provide pain relief, measured with near-infrared spectroscopy (NIRS), during venepuncture in premature infants. Ten infants born at 26-35 weeks of gestation were examined during a blood-sampling procedure with venepuncture under two different conditions: in skin-to-skin contact with their mother or lying in their incubator or crib. A double-channel NIRS device was used, and oxygen saturation and heart rate were measured using pulse oximetry. The infant's face and the pulse oximetry values were videotaped throughout the procedures, so that we could carry out a pain assessment using the Premature Infant Pain Profile-Revised (PIPP-R). We found a significantly smaller increase in oxygenated haemoglobin on the contralateral side during venepuncture when the infants were in skin-to-skin contact with their mothers, compared to when they were laying in their incubator or crib. When venepuncture was compared with a sham procedure, oxygenated haemoglobin increased significantly more with the infant in the incubator or crib than held skin-to-skin, but no significant differences could be seen in the PIPP-R results between the two groups. This study showed that skin-to-skin contact between premature infants and their mothers during venepuncture had a pain-relieving effect.

Issues of vaccination in premature infants: an overview

Premature infants (PI) are neonates born <37 weeks gestational age, with different PI subgroups being identified according to gestational age and birth weight. Prematurity is associated with increased morbidity and perinatal mortality, since yields increased risk for a number of pathological features and negative outcomes related mainly to the extent of all organs and functions' immaturity. Among these conditions, neonatal and post-natal infections play a major role. PI feature increased odds of infections and infections-related morbidity throughout their first months of life. Among all preventative, anti-infective strategies, active vaccination is a key point for PI. The most common vaccine-preventable diseases in PI are whooping cough, Haemophilus influenzae type-b (Hib) meningitis, invasive pneumococcal disease, rotavirus gastroenteritis, influenza. International guidelines recommend to deliver active immunization following the chronological timing (=counting the weeks of actual birth), and not following the corrected gestational age (=counting the weeks of life starting from the expected moment of birth). However, vaccinations in PI are often performed later than recommended, or even less than expected, as shown by recent studies carried out in Italy assessing significantly decreased rates of active immunization in PI. This somewhat poor adherence to the international guidelines is related to concerns about weaker immune responses in PI, and possible adverse events. Nonetheless, several studies have shown that vaccines administered to PIs have excellent safety profiles, fully comparable to term infants. Transient, benign episodes of apnea, with or without associated bradycardia, have been occasionally described in PI occurring up to 48 hours post-immunization. Though no significant morbidity nor long-term sequelae has been associated with these events, it is advisable to monitor these episodes for 48 hours after the completion of vaccination. Vaccines are immunogenic, generally safe and well tolerated in all infants including PI. Noteworthy, only vaccines specifically authorized for use in premature infants should be used in PIs. The most immature neonates (i.e., ELBW infants) should receive their first dose of vaccine during hospitalization, in order to allow such risky groups of infants achieving sufficiently protective immunization before their discharge. This strategy also allows for adequate monitoring of cardiorespiratory function, and ultimately improves adhesion to the vaccination programs. Strategies aiming at promoting education and awareness about vaccination practices and recommendations in PI should be reinforced. The ultimate aim is to increase delivery of effective protection against vaccine-preventable diseases to these vulnerable patients since their discharge from the NICU.

Pupillary Size and Light Reflex in Premature Infants

ABSTRACTThe authors examined pupillary light reflexes to both red and blue stimuli using infrared video-pupillography in premature infants. Pupillary light reflexes were obtained in response to 470 nm blue and 635 nm red stimuli with varying intensities of 10 cd/m2 and 100 cd/m2. Red stimuli did not evoke a pupillary response in premature infants. However, blue stimuli produced a pupillary reflex, and the extent of the reaction was dependent on the intensity of the stimulus. These results suggest that in premature infants, the origin of light reflex may be mediated predominately by melanopsin-containing retinal ganglion cells.

Rhinovirus-induced airway cytokines and respiratory morbidity in severely premature children.

Rhinovirus (RV) has been linked to the pathogenesis of asthma. Prematurity is a risk factor for severe RV infection in early life, but is unknown if RV elicits enhanced pro-asthmatic airway cytokine responses in premature infants. This study investigated whether young children born severely premature (<32wks gestation) exhibit airway secretion of Th2 and Th17 cytokines during natural RV infections and whether RV-induced Th2-Th17 responses are linked to more respiratory morbidity in premature children during the first 2yrs of life. We measured Th2 and Th17 nasal airway cytokines in a retrospective cohort of young children aged 0-2yrs with PCR-confirmed RV infection or non-detectable virus. Protein levels of IL-4, IL-13, TSLP, and IL-17 were determined with multiplex immunoassays. Demographic and clinical variables were obtained by electronic medical record (EMR) review. The study comprised 214 children born full term (n=108), preterm (n=44) or severely premature (n=62). Natural RV infection in severely premature children was associated with elevated airway secretion of Th2 (IL-4 and IL-13) and Th17 (IL-17) cytokines, particularly in subjects with history of bronchopulmonary dysplasia. Severely premature children with high RV-induced airway IL-4 had recurrent respiratory hospitalizations (median 3.65 hosp/yr; IQR 2.8-4.8) and were more likely to have at least one pediatric intensive care unit admission during the first 2yrs of life (OR 8.72; 95% CI 1.3-58.7; p=0.02). Severely premature children have increased airway secretion of Th2 and Th17 cytokines during RV infections, which is associated with more respiratory morbidity in the first 2yrs of life.

Low level of tracheal cellular fibronectin in extremely premature infants with funisitis: Relationship with respiratory distress 1 month after birth

Funisitis reflects the fetal systemic inflammatory response in premature infants. Macrophages and neutrophils have been identified as key elements in the inflammatory process of the lungs, and secrete proteases that cause the destruction of the extracellular matrix (ECM). Fibronectin (FN) is the major constituent of the pulmonary ECM and exists in multiple isoforms arising from alternative RNA splicing. Extra domain A (EDA) is the major alternatively spliced segment, and the expression of EDA containing FN (EDA + FN) in the lungs is associated with distal pulmonary cell proliferation during alveolar formation. To study the relationship between the presence of funisitis and EDA + FN levels in the tracheal aspirate fluid (TAF) of infants of less than 28 weeks' gestation. The subjects included in this study were 26 extremely premature infants of <28 weeks' gestation at <24 hr of age, from whom the TAF was collected. These preterm infants were divided into two groups according to placental histology. The funisitis (+) group (n = 9) was compared with the funisitis (-) group (n = 17). The TAF supernatants were analyzed for IL-1β, IL-6, IL-8, neutrophil elastase, and EDA + FN using enzyme-linked immunosorbent assay (ELISA). There were no significant differences in gestational age or birthweight between these groups. The funisitis (+) group had a significantly higher ventilator setting (inspired O(2) × mean airway pressure) at Day 28 than the funisitis (-) group. In the TAF, the concentrations of IL-1β were significantly higher in the funisitis (+) group than in the funisitis (-) group, as were the concentrations of neutrophil elastase. The concentrations of EDA + FN were significantly lower in the funisitis (+) group than in the funisitis (-) group. Decreased EDA + FN in TAF might be one of the risk factors leading to respiratory distress in extremely premature infants with funisitis.

Immunogenicity, safety and tolerability of vaccinations in premature infants

Infections are more common and generally more severe in neonates and young children than in older children and adults, mainly because immune defenses are functionally impaired in early life. The seriousness of the infectious problems of premature infants (PIs) is proportional to how premature they are, but irrespective of this, they are more serious than those of full-term infants because their immune system is compromised to a greater extent. This review analyzes our knowledge of the characteristics of the developing immune system, the impact of possible impairments on immunization, the real response of PIs to vaccines and the safety and tolerability of different vaccines. Overall, the data indicate that PIs should follow the same vaccination schedule as that generally used for full-term infants, without correcting for prematurity and regardless of birthweight. However, there is an urgent need for further studies concerning the use of recently marketed vaccines and those that will be marketed in the near future.

Optimum Click Rate for Neurodevelopmental Evaluation Using Auditory Brainstem Response in Premature Infants

To determine the optimal click rate (CR) for neurodevelopmental assessment using auditory brainstem evoked response (ABR) in preterm infants. A prospective study was performed in 17 preterm infants at 34 weeks' postmenstrual age. Three separate ABRs were performed a few minutes apart on each subject using three different click rates (CRs): 19.9/s, 29.9/s, and 69.9/s. An ABR response with waves I, III, and V identifiable and measurable was defined as a pass response. The CR associated with the highest frequency of pass responses was considered optimal, or if two CRs were tied for the highest frequency, then the faster of the two CR was deemed best. The frequency of pass responses for 29.9/s and 19.9/s CR was 100% and was significantly higher compared with 82% frequency with 69.9/s CR. There was no difference in latencies, interpeak latencies, and amplitudes of waves between 19.9/s and 29.9/s CR; however, standard deviations of interpeak latencies were larger with 19.9/s compared with 29.9/s CR. Our data suggest that 29.9/s is the optimal CR for neurodevelopmental assessment using ABR. Because of smallest variance in interpeak latencies, the sample size requirement will be lowest using 29.9/s CR with secondary reduction in cost and time.

Pain assessment in premature infants treated with intravitreal antiangiogenic therapy for retinopathy of prematurity under topical anesthesia

To evaluate the physiological and behavioral pain response in premature infants receiving intravitreal bevacizumab injection (IVB) for retinopathy of prematurity (ROP) under topical anesthesia. A prospective interventional non-comparative case series. Premature infants with high-risk prethreshold or threshold ROP received IVB using topical anesthesia with tetracaine eye drops. A Premature Infant Pain Profile was used to assess the pain response during the procedure. Nine premature infants requiring bilateral IVB therapy were included in the study. Mean gestational age was 28.7 ± 1.3 weeks, and birth weight was 1,200 ± 194 grams. The mean total pain score was found to be 8.7 ± 2.4 (range 5-14), indicating generally mild pain during the procedure. Eye squeeze was the most prominent indicator of pain. Most changes occurred at the beginning, with the insertion of the lid speculum and were hardly noted during the rest of the procedure including the injection itself. Topical anesthesia with tetracaine is an effective method for the relief of pain associated with intravitreal injections in premature infants with ROP.

Vaccinating premature infants in a Special Care Baby Unit in the UK: results of a prospective, non-inferiority based, pragmatic case series study

Premature infants are at greater risk of infections in part because of impaired functioning of external barriers, innate and adaptive systems. For similar immunological reasons, diminished responses to particular vaccines have also been reported. This study, utilising a prospective, pragmatic case series approach was designed to show non-inferiority of antibody response in premature infants to diphtheria, tetanus, Haemophilus influenzae type b conjugate (Hib), meningococcal C conjugate (MenC) and pneumococcal conjugate (PnC) vaccines between immunization in a routine clinical situation rather than a vaccine trial. A secondary objective was to determine the effect of gestational age on antibody response to these vaccines. The case series comprised 131 infants born at ≤ 32 weeks gestation and managed on the Special Care Baby Unit (SCBU) of a District General Hospital in Stockport, UK. For diphtheria and tetanus, 98.3% and 100% of premature infants respectively developed a minimum protective antibody response; 86.6% were protected against Men C. However, only 67.8% preterm infants achieved anti-polyribosylribitolphosphate (PRP) antibodies >0.15μg against Hib, with only 34.7% having a level ≥1.0μg, and responses to the different pneumococcal serogroups ranged from 67.5% against serotype 6B to 92.5% against serogroup 19F. In comparison to term infants, preterm infants were less likely to achieve protective levels against MenC and Hib: there were no significant differences in the proportions of infants protected against diphtheria and tetanus. Protection was inferior to expected based on published premature infant clinical trial data for Hib and particular pneumococcal serotypes; data for Men C were also lower than expected.

Effects of Multiple Courses of Antenatal Betamethasone on the Auditory Brainstem Responses of Premature Infants

We thank Dr Church for his letter regarding our observational study on the effect of multiple courses of antenatal betamethasone on auditory neural maturation. We are glad to see that he also found no effect on auditory neural maturation after exposure to multiple courses of antenatal betamethasone. These findings provide external validity to our findings. To help Dr Church prepare his manuscript, we have attempted to clarify and answer the questions that he raised. 1. The median number of betamethasone courses given to the pregnant women …

Efficacy of Sucrose to Reduce Pain in Premature Infants during Eye Examinations for Retinopathy of Prematurity

Eye examinations for retinopathy of prematurity (ROP) are painful to the neonate. The use of topical anesthetic for eye examinations to evaluate ROP is routine in our neonatal intensive care unit (NICU), but does not completely suppress painful responses. Sweet solutions have been shown to reduce procedural pain in newborns. To examine whether the addition of sucrose 24% to topical anesthetic improves procedural pain control during the ROP eye examination. Neonates born at < or = 30 weeks' gestation were included in this placebo-controlled, double-blind, crossover study. Patients were randomly assigned to receive treatment with either proparacaine HCl ophthalmic solution 0.5% plus 2 mL of sucrose 24% or proparacaine HCl ophthalmic solution 0.5% plus 2 mL of sterile water (placebo) prior to an eye examination. In a subsequent eye examination, each patient received the alternate treatment. Oral sucrose and sterile water were prepared in the pharmacy in identical syringes, and physicians, nurses, and pharmacists in the NICU were blinded to the treatment given. Pain was measured using the Premature Infant Pain Profile (PIPP) scoring system, which measures both physical and physiologic measures of pain, and the scores were simultaneously assessed by 2 study nurses. PIPP scores were recorded 1 and 5 minutes before and after the eye examination and during initial placement of the eye speculum. The same ophthalmologist performed all eye examinations. Several different definitions of a pain response were investigated. Twenty-three infants were studied, with 12 receiving sucrose and 11 receiving placebo as the first treatment. For 3 of the 5 definitions of pain response, patients experienced significantly less pain at speculum insertion with sucrose than with placebo. After the ROP examination, pain responses were similar with either sucrose or placebo. Oral sucrose may reduce the immediate pain response in premature infants undergoing eye examination for ROP.

The Effect of Infant Massage on Weight Gain, Physiological and Behavioral Responses in Premature Infants

The purpose of this study was to evaluate the premature infants' responses to infant massage (tactile and kinesthetic stimulation). These responses measured by weight, physiological (vagal tone, heart rate, oxygen saturation) and behavioral responses (behavioral states, motor activities, and behavioral distress). This study was conducted using an equivalent control pretest-posttest design. The sample was divided into two groups of 13 infants with gestational age less than 36 weeks at birth, birth weight less than 2000 g, and no congenital anomalies. The experimental group received the massage intervention twice daily for 10 days. The data were collected for 10 minutes prior to and 10 minutes after the massage. The vagal tone was significantly higher after massage than before massage in the experimental group, while no change in the control group. The experimental group had significantly higher scores for awake state and motor activity than the control group. Significantly greater awake state, more fidgeting or crying, and increased motor activity were reported after massage than before massage. The results of this study showed that massage therapy might enhance optimal physiological responses and behavioral organization of premature infants. Nursing staff in the NICU can use massage to promote the infant's capability to respond positively to his environment and to provide developmental support for healthy premature infants.

High cord blood IL-10 levels in preterm newborns with respiratory distress syndrome

BackgroundThe development of respiratory distress syndrome (RDS) is closely related to fetal immaturity, although the participation of inflammatory mechanisms also seems to be likely. We previously reported high interleukin-10 (IL-10) levels in cord blood from preterm infants. In the present study, we investigate the possible role of IL-10 and IL-12 in preterm newborns with RDS, a disease that is also closely related to gestational age Patients and methodsCord blood levels of IL-10 and IL-12 (p70 + p40) were determined by ELISA in 20 preterm infants who later developed RDS, in 21 preterm infants without RDS and in 31 full term newborns. In 11 patients follow-up samples could be also obtained between 2 and 14 days of life ResultsPreterm infants with RDS showed higher IL-10 (27 vs 10.8 pg/mL; p: 0.0003) and lower IL-12 (188 vs 384; p: 0.002) levels in cord blood than premature infants without RDS and full term newborns (IL-10: 3.2 pg/mL, p: 0.0001; IL-12: 352 pg/mL; p: 0.002). The differences remained statistically significant after correction for the effect of gestational age between both preterm groups ConclusionsThe results obtained may be related to an immature cytokine response in premature infants, but the IL-12/IL-10 imbalance found in our patients also supports the hypothesis that inflammation plays a role in RDS

Effects of sponge bathing on vagal tone and behavioural responses in premature infants.

The purpose of this study was to evaluate the effects of sponge bathing on physiological (vagal tone, heart rate, heart period, oxygen saturation) and behavioural responses in newly born premature infants in the intensive care unit of a university hospital in South Korea. A convenience sample was taken of 40 infants who were between 27 and 36 weeks gestational age at birth and free of congenital defects. The infants' physiological parameters were recorded 10 min before, during and after bathing. To determine behavioural status, tools were modified from the instruments used in a previous study by Scafidi et al. (1990). Analysis of the results showed that the premature infants reacted to sponge bathing with decreases in vagal tone and heart period and increases in heart rate. Oxygen saturation did not demonstrate any remarkable alteration during bathing. Also, there were no significant differences in behavioural signs, motor activity and behavioural distress. Results of this study indicated that nurses in a neonatal intensive care unit should decide according to a premature infant's physiological state whether or not to give a sponge bath.

Bilirubin and serial auditory brainstem responses in premature infants.

To determine the usefulness of the bilirubin-albumin (B:A) molar ratio (MR) and unbound bilirubin (UB) as compared with serum total bilirubin (TB) in predicting bilirubin encephalopathy as assessed by auditory brainstem responses (ABR) in infants of 28 to 32 weeks' gestational age. During a 2-year period, serial ABRs were obtained on 143 infants of 28 to 32 weeks' gestational age during the first postnatal week. Waveforms were categorized on the basis of response replicability and the presence of waves III and V. Wave V latencies were also serially analyzed when measurable for individual infants. Maturation of the ABR was defined as abnormal when the waveform category worsened and/or latency increased during the study interval. Serum albumin was analyzed at 48 to 72 hours of age in all patients. Serum TB was analyzed as clinically indicated. Aliquots of the same samples were also analyzed for UB in a subset of infants. The mean peak TB concentration (10.1 +/- 1.7 mg/dL) for the 71 infants with normal ABR maturation was not significantly different from the mean peak TB (10.2 +/- 2.1 mg/dL) in the 24-hour period preceding the ABR's first showing abnormal maturation in the other 55 infants. However, in infants with UB analyzed, the mean peak UB (0.62 +/- 0.20 vs 0.40 +/- 0.15 microg/dL) was significantly higher in the infants with abnormal maturation (n = 25) than in infants with normal maturation (n = 20). The B:A MR results were equivocal. In the entire study population, there was no difference in B:A MR between infants with normal versus abnormal ABR maturation. However, in the subset of infants in whom UB was measured, although TB was not different, there was a significant difference in B:A MR. Based on receiver-operating characteristic curves, a UB level of 0.5 microg/dL was the best discriminator with a sensitivity of 70% and a specificity of 75%. The proportion of infants who had UB >0.5 microg/dL and UB </=0.5 microg/dL and who had abnormal ABR, maturation was 0.81 and 0.33, respectively, with a significant difference in the incidence of transient bilirubin encephalopathy among these 2 groups. The relative risk of abnormal ABR maturation with UB >0.5 microg/dL compared with UB </=0.05 microg/dL was 2.45 (95% confidence interval: 1.33-4.49). UB is a more sensitive predictor than either serum bilirubin or B:A MR of abnormal ABR maturation, and hence transient bilirubin encephalopathy in premature newborns with hyperbilirubinemia.

Effects of a Sensory Stimulation on Weight Gain, Behavioral State, and Physiological Responses in Premature Infants

【Purpose: The purpose of this study was to examine the effects of sensory stimulation on premature infants. Method: Thirty three premature infants admitted to NICU of D University Hospital in C city were randomly assigned in two groups (Experimental group: 16, Control group:17). For the experimental group, tactile and kinesthetic stimulation developed by Dr. Field was applied 2 times a day for 10 days. Behavioral state was measured using the Anderson Behavioral State Scale (ABSS). Heart rate, respiration, and oxygen saturation were obtained for each infant before and after sensory stimulation. Hypothesis testing was done using the $\chi$ $^2$ - test, student t-test, and repeated measures of ANOVA. Result: Hypothesis 1: There was a significant difference in the daily body weight gain between experimental and control group (F= 40.77, p= .0001). Hypothesis 2: There was a significant difference in the frequency of 'inactive awake state' between two groups ( $\chi$ $^2$ = 39 39.778, p= .001). Hypothesis 3: There were significant differences in the mean of heart rate and $O_2$ saturation between two groups (t= -2.174, p= .037; t= 3.080, p= .005). However, there was no significant difference in the mean of respiration rate between two groups (t= -1.966, p= .581). Conclusion: The effectiveness of a sensory stimulation on weight gain and behavioral state in premature infants was supported. Further study is recommended to develop a sensory stimulation method as an independent nursing intervention for premature infant.】

Timing of Vaccinations in Premature Infants

Preterm infants have immunological immaturities that may impact on vaccine responses. Larger premature infants mount immune responses to vaccines that are similar to those of full term infants, but very premature infants (<30 weeks' gestation at birth) have specific defects in vaccine responsiveness. The immunogenicity of diphtheria, tetanus and pertussis antigens is similar in full term and premature infants. Poliovirus vaccines, however, do not always stimulate adequate antibody responses in premature infants. The immunogenicity of Haemophilus influenzae type b conjugate vaccines varies widely in studies of premature infants, and may be affected both by choice of conjugate protein and by the infant's overall health. Hepatitis B vaccine given at birth appears poorly immunogenic in infants with birthweights <1750g, with delay in the administration of the first dose yielding improved immunogenicity. Sick premature infants may suffer increased episodes of apnoea following vaccine administration. Persistence of immunity, the quality of the immune response, and evaluation of the specific tolerability and immunogenicity of new vaccines in premature infants are topics needing further research. Although it is generally true that recommendations for vaccination of term infants are applicable to premature infants, it is not always specifically true. Optimal care of preterm infants requires attention to the exceptions to this generalisation.

Response of Premature Infants with Prolonged Feeding Intolerance to Cisapride

Response of Premature Infants with Prolonged Feeding Intolerance to Cisapride

Cortisol Response in Premature Infants during Inhaled Beclomethasone Therapy† 984

Cortisol Response in Premature Infants during Inhaled Beclomethasone Therapy† 984

Inhaled Nitric Oxide Response in Premature Infants with Persistent Pulmonary Hypertension 1623

Background: Persistent pulmonary hypertension (PPHN) is a significant cause of neonatal morbidity and mortality frequently associated with diseases of term and near-term infants. In recent years, it has also been recognized in preterm infants with respiratory distress syndrome (RDS). We report our experience of inhaled nitric oxide (INO) use in critically ill premature infants with PPHN.