Breast Milk and Glucose for Pain Relief in Preterm Infants: A Noninferiority Randomized Controlled Trial

OBJECTIVE: The study goal was to compare the efficacy of expressed breast milk (EBM) versus 25% glucose on pain responses of late preterm infants during heel lancing. METHODS: In a noninferiority randomized controlled trial, a total of 113 newborns were randomized to receive EBM (experimental group [EG]) or 25% glucose (control group [CG]) before undergoing heel lancing. The primary outcome was pain intensity (Premature Infant Pain Profile [PIPP]) and a 10% noninferiority margin was established. Secondary outcomes were incidence of cry and percentage of time spent crying and adverse events. Intention-to-treat (ITT) analysis was used. RESULTS: Groups were similar regarding demographics and clinical characteristics, except for birth weight and weight at data collection day. There were lower pain scores in the CG over 3 minutes after lancing (P<.001). A higher number of infants in the CG had PIPP scores indicative of minimal pain or absence of pain (P = .002 and P = .003 on ITT analysis) at 30 seconds after lancing, and the mean difference in PIPP scores was 3 (95% confidence interval: 1.507-4.483). Lower incidence of cry (P = .001) and shorter duration of crying (P = .014) were observed for CG. Adverse events were benign and self-limited, and there was no significant difference between groups (P = .736 and P = .637 on ITT analysis). CONCLUSIONS: Results based on PIPP scores and crying time indicate poorer effects of EBM compared with 25% glucose during heel lancing. Additional studies exploring the vol and administration of EBM and its combination with other strategies such as skin-to-skin contact and sucking are necessary. Pediatrics 2012;129:664-670

Maternal factors regulating preterm infants' responses to pain and stress while in maternal kangaroo care

The relationship between maternal factors and the response of preterm infants to pain and stress experienced during heel puncture while in maternal kangaroo care was investigated. This descriptive study included 42 mothers and their preterm infants cared for in a neonatal unit. Data were collected in the baseline, procedure, and recovery phases. We measured the neonates' facial actions, sleep and wake states, crying, salivary cortisol levels, and heart rate, in addition to the mothers' behavior, salivary cortisol levels, and mental condition. The influence of the maternal explanatory variables on the neonatal response variables were verified through bivariate analysis, ANOVA, and multiple regression. The mothers' behavior and depression and/or anxiety did not affect the neonates' responses to pain and stress, though the mothers' levels of salivary cortisol before the procedure explained the variance in the neonates' levels of salivary cortisol after the procedure (p=0.036). Additionally, the mothers' baseline levels of salivary cortisol along with the neonates' age explained the variance in the neonates' heart rate (p=0.001). The ability of mothers to regulate their own stress contributed to the infants' responses to pain and stress.

Does the neonatal clinical risk for illness severity influence pain reactivity and recovery in preterm infants?

Background: The biobehavioural pain reactivity and recovery of preterm infants in the neonatal period may reflect the capacity of the central nervous system to regulate neurobiological development. Objective: The aim of the present study was to analyse the influence of the neonatal clinical risk for illness severity on biobehavioural pain reactivity in preterm infants. Methods: Fifty-two preterm infants were allocated into two groups according to neonatal severity of illness, as measured by the Clinical Risk Index for Babies (CRIB). The low clinical risk (LCr) group included 30 neonates with CRIB scores <4, and the high clinical risk (HCr) group included 22 neonates with CRIB scores >= 4. Pain reactivity was assessed during a blood collection, which was divided into five phases (baseline, antisepsis, puncture, recovery-dressing and recovery-resting). Behavioral pain reactivity was measured using the scores, and magnitude of responses in Neonatal Facial Coding System (NFCS) and Sleep-Wake States Scale (SWS). The heart rate was continuously recorded. Results: The HCr demonstrated a higher magnitude of response on the SWS score from the baseline to the puncture phase than the LCr. Also, the HCr exhibited a higher mean heart rate and minimum heart rate than the LCr in the recovery-resting phase. In addition, the HCr exhibited a higher minimum heart rate from the baseline to the recovery-resting phase than the LCr. Conclusion: The infants exhibiting a high neonatal clinical risk showed high arousal during the puncture procedure and higher physiological reactivity in the recovery phase.

Pain in preterm infants: effects of sex, gestational age, and neonatal illness severity

Neonates hospitalized in a neonatal intensive care unit are exposed to many painful and stressful procedures. Biobehavioral pain reactivity in preterm infants during the neonatal period may reflect the capacity of the central nervous system to regulate arousal and neurobiological organization. We review empirical studies on the effects of sex, gestational age, and neonatal illness severity on pain reactivity in children born preterm. A literature search was conducted using PubMed, Institute of Scientific Information Web of Science, PsycINFO, Latin American and Caribbean Health Sciences Literature, and Scientific Electronic Library Online databases. Additionally, a special search was performed in online journals that publish pain studies including Pain, Early Human Development, European Journal of Pain, and Pain Management Nursing. The literature search covered the period from 2004 to 2009. Data were extracted according to predefined inclusion and exclusion criteria. Of the 18 studies reviewed, 16 analyzed gestational age, 13 examined neonatal illness severity, and eight focused on sex. Most of the studies analyzed more than one of these three variables. The majority of the studies found effects of gestational age (n = 14) and neonatal illness severity (n = 11) on pain responses. Only two studies found an influence of sex on infant pain responses. In conclusion, gestational age and neonatal illness severity influence pain responses in infants born preterm. Further studies should be conducted to examine the influence of sex on pain responses.

Proactive management of extreme prematurity: disagreement between obstetricians and neonatologists

Objective: To verify, in extremely preterm infants, if disagreement between obstetricians and neonatologists regarding proactive management is associated with early death. Study Design: Prospective cohort of 484 infants with 23(0/7) to 26(6/7) weeks, without malformations, born from January 2006 to December 2009 in eight Brazilian hospitals. Pro-active management was defined as indication of >= 1 dose of antenatal steroid or cesarean section (obstetrician) and resuscitation at birth according to the international guidelines (neonatologist). Main outcome was neonatal death in the first 24 h of life. Result: Obstetricians and neonatologists disagreed in 115 (24%) patients: only neonatologists were proactive in 107 of them. Disagreement between professionals increased 2.39 times the chance of death in the first day (95% confidence interval 1.40 to 4.09), adjusted for center and maternal/neonatal clinical conditions. Conclusion: In infants with 23 to 26 weeks of gestation, disagreement between obstetricians and neonatologists, translated as lack of antenatal steroids and/or vaginal delivery, despite resuscitation procedures, increases the odds of death in the first day. Journal of Perinatology (2012) 32, 913-919; doi:10.1038/jp.2012.28; published online 29 March 2012

Differences in walking attainment ages between low-risk preterm and healthy full-term infants

Objective: To compare gross motor development of preterm infants (PT) without cerebral palsy with healthy full-term (FT) infants, according to Alberta Infant Motor Scale (AIMS); to compare the age of walking between PT and FT; and whether the age of walking in PT is affected by neonatal variables. Methods: Prospective study compared monthly 101 PT and 52 FT, from the first visit, until all AIMS items had been observed. Results: Mean scores were similarity in their progression, except from the eighth to tenth months. FT infants were faster in walking attainment than PT. Birth weight and length and duration of neonatal nursery stay were related to walking delay. Conclusion: Gross motor development between PT and FT were similar, except from the eighth to tenth months of age. PT walked later than FT infants and predictive variables were birth weight and length, and duration of neonatal intensive unit stay.

Bioelectrical impedance vector analysis (BIVA) in stable preterm newborns

Objective: To observe the behavior of the plotted vectors on the RXc (R - resistance - and Xc - reactance corrected for body height/length) graph through bioelectrical impedance analysis (BIVA) and phase angle (PA) values in stable premature infants, considering the hypothesis that preterm infants present vector behavior on BIVA suggestive of less total body water and soft tissues, compared to reference data for term infants. Methods: Cross-sectional study, including preterm neonates of both genders, in-patients admitted to an intermediate care unit at a tertiary care hospital. Data on delivery, diet and bioelectrical impedance (800 mA, 50 kHz) were collected. The graphs and vector analysis were performed with the BIVA software. Results: A total of 108 preterm infants were studied, separated according to age (< 7 days and >= 7 days). Most of the premature babies were without the normal range (above the 95% tolerance intervals) existing in literature for term newborn infants and there was a tendency to dispersion of the points in the upper right quadrant, RXc plan. The PA was 4.92 degrees (+/- 2.18) for newborns < 7 days and 4.34 degrees (+/- 2.37) for newborns >= 7 days. Conclusion: Premature infants behave similarly in terms of BIVA and most of them have less absolute body water, presenting less fat free mass and fat mass in absolute values, compared to term newborn infants.

Practices of use of nasal intermittent positive pressure ventilation (NIPPV) in neonatology in northeastern Brazil

Objective: To investigate the use of nasal intermittent positive pressure ventilation (NIPPV) in level three neonatal intensive care units (NICU) in northeastern Brazil. Methods: This observational cross-sectional survey was conducted from March 2009 to January 2010 in all level three NICUs in northeastern Brazil that are registered in the Brazilian Registry of Health Establishments (Cadastro Nacional de Estabelecimentos de Saude, CNES) of the Ministry of Health. Questionnaires about the use of NIPPV were sent to the NICU directors in each institution. Statistical analysis was conducted using the software Epi-Info 6.04 and double data entry. A chi-square test was used to compare variables, and the level of statistical significance was set at p <= 0.05. Results: This study identified 93 level three NICUs in northeastern Brazil registered in CNES, and 87% answered the study questionnaire. Most classified themselves as private institutions (30.7%); 98.7% used NIPPV; 92.8 % adapted mechanical ventilators for NIPPV and used short binasal prongs as the interface (94.2%). Only 17.3% of the units had a protocol for the use of NIPPV. Mean positive inspiratory pressure and positive end-expiratory pressure were 20.0 cmH(2)O (standard deviation [SD]: 4.47) and 5.0 cmH(2)O (SD: 0.84). Conclusion: NICUs in northeastern Brazil use nasal intermittent positive pressure ventilation, but indications and ventilation settings are not the same in the different institutions.

Solid-phase microextraction combined with comprehensive two-dimensional gas chromatography for fatty acid profiling of cell wall phospholipids

The combination of solid-phase microextraction (SPME) with comprehensive two-dimensional gas chromatography is evaluated here for fatty acid (FA) profiling of the glycerophospholipid fraction from human buccal mucosal cells. A base-catalyzed derivatization reaction selective for polar lipids such as glycerophospholipid was adopted. SPME is compared to a miniaturized liquidliquid extraction procedure for the isolation of FA methyl esters produced in the derivatization step. The limits of detection and limits of quantitation were calculated for each sample preparation method. Because of its lower values of limits of detection and quantitation, SPME was adopted. The extracted analytes were separated, detected, and quantified by comprehensive two-dimensional gas chromatography with flame ionization detection (FID). The combination of SPME and comprehensive two-dimensional gas chromatography with FID, using a selective derivatization reaction in the preliminary steps, proved to be a simple and fast procedure for FA profiling, and was successfully applied to the analysis of adult human buccal mucosal cells.

Factors Associated with Height Catch-Up and Catch-Down Growth Among Schoolchildren

In developed countries, children with intrauterine growth restriction (IUGR) or born preterm (PT) tend to achieve catch-up growth. There is little information about height catch-up in developing countries and about height catch-down in both developed and developing countries. We studied the effect of IUGR and PT birth on height catch-up and catch-down growth of children from two cohorts of liveborn singletons. Data from 1,463 children was collected at birth and at school age in Ribeirao Preto (RP), a more developed city, and in Sao Luis (SL), a less developed city. A change in z-score between schoolchild height z-score and birth length z-score >= 0.67 was considered catch-up; a change in z-score <=-0.67 indicated catch-down growth. The explanatory variables were: appropriate weight for gestational age/PT birth in four categories: term children without IUGR (normal), IUGR only (term with IUGR), PT only ( preterm without IUGR) and preterm with IUGR; infant's sex; maternal parity, age, schooling and marital status; occupation of family head; family income and neonatal ponderal index (PI). The risk ratio for catch-up and catch-down was estimated by multinomial logistic regression for each city. In RP, preterms without IUGR (RR = 4.13) and thin children (PI<10th percentile, RR = 14.39) had a higher risk of catch-down; catch-up was higher among terms with IUGR (RR = 5.53), preterms with IUGR (RR = 5.36) and children born to primiparous mothers (RR = 1.83). In SL, catch-down was higher among preterms without IUGR (RR = 5.19), girls (RR = 1.52) and children from low-income families ( RR = 2.74); the lowest risk of catch-down (RR = 0.27) and the highest risk of catch-up (RR = 3.77) were observed among terms with IUGR. In both cities, terms with IUGR presented height catch-up growth whereas preterms with IUGR only had height catch-up growth in the more affluent setting. Preterms without IUGR presented height catch-down growth, suggesting that a better socioeconomic situation facilitates height catch-up and prevents height catch-down growth.

Comparison of physical properties of two exogenous surfactants: new parameter.

The pulmonary surfactant has essential physical properties for normal lung function. The most important property is the surface tension. In this work, it was evaluated the surface tension of two commercial exogenous surfactants used in surfactant replacement therapy, poractant alfa (Curosurf, Chiesi Farmaceuticals, Italy) and beractant (Survanta, Abbott Laboratories, USA) using new parameters. A Langmuir film balance (Minitrough, KSV Instruments, Finland) was used to measure surface tension of poractant alfa and beractant samples. For both samples, we prepared a solution of 1 mg/m dissolved in chloroform (100π`), which was applied over a subphase of milli-Q water (175 ml) in the chamber of the balance. The chamber has two moving barriers that can change its surface area between a maximal value of 112.5 cm 2 , and a minimal value of 22.5 cm 2, defining a balance cycle. Each surfactant had its surface tension evaluated during 20 balance cycles for three times. Four quantities were calculated from the experiment: Minimum Surface Tension (MTS), defined as the surface tension at minimal surface area during the first cycle; Mean Work Cycle (MWC), defined as the mean hysteresis area of the measured surface tension curve of the last 16 balance cycles; Critical Active Surface Area in Compression (CASAC) or in Expansion (CASAE), defined as the maximal chamber area where the surfactant is active on the surface in compression or expansion. The t-test was applied to verify for statistical significance of the results. Comproved with the MST is the same reported in literature, the differences between MWC, CASAC, and CASAE were statistically significant (p<0.001). The MWC, CASAC and CASAE were higher for poractant alfa than for beractant. A higher MWC for poractant alfa means higher elastic recoil of the lung in comparison with beractant. Using a different methodology, our results showed that poractant alfa is probably more effective in a surfactant replacement therapy than beractant due the use of poractant alfa in relation to the use of beractant in preterm infants with Respiratory Distress Syndrome (RDS).

Characterization of the motor performance in infants with a diagnosis of Cerebral Palsy in process of rehabilitation: the importance of the proactivity of caregivers

Introduction: The progress in technology, associated to the high survival rate in premature newborn infants in neonatal intensive care units, causes an increase in morbidity. Individuals with CP present complex motor alterations, with primary deficits of abnormal muscle tone affecting posture and voluntary movement, alteration of balance and coordination, decrease of force, and loss of selective motor control with secondary problems of contractures and bone deformities. Objective: The aim of this work is to describe the spontaneous movement and strategies that lead infants with cerebral palsy to move. Methods: Seven infants used to receive assistance at the Essential Stimulation Center of CIAM (Israeli Center for Multidisciplinary Support - Philanthropic Institution), with ages ranging between six and 18 months with diagnosis of Cerebral Palsy (CP) were assessed. Results: The results show the difficulty presented by the infants with respect to the spontaneous motor functions and the necessity of help from the caregiver in order to perform the functional activity (mobility). Prematurity prevails as the major risk factor among the complications. Conclusion: The child development can be understood as a product of the dynamic interactions involving the infant, the family, and the context. Thus, the social interactions and family environment in which the infant live may encourage or limit both the acquisition of skills and the functional independence.

Salivary IgA antibody responses to Streptococcus mitis and Streptococcus mutans in preterm and fullterm newborn children

Objectives: The intensities and specificities of salivary IgA antibody responses to antigens of Streptococcus mutans, the main pathogen of dental caries, may influence colonization by these organisms during the first 1.5 year of life. Thus, the ontogeny of salivary IgA responses to oral colonizers continues to warrant investigation, especially with regard to the influence of birth conditions, e.g. prematurity, on the ability of children to efficiently respond to oral microorganisms. In this study, we characterised the salivary antibody responses to two bacterial species which are prototypes of pioneer and pathogenic microorganisms of the oral cavity (Streptococcus mitis and Streptococcus mutans, respectively) in fullterm (FT) and preterm (PT) newborn children. Methods: Salivas from 123 infants (70 FT and 53 PT) were collected during the first 10 h after birth and levels of IgA and IgM antibodies and the presence of S. mutans and S. mitis were analysed respectively by ELISA and by chequerboard DNA-DNA hybridization. Two subgroups of 24 FT and 24 PT children were compared with respect to patterns of antibody specificities against S. mutans and S. mitis antigens, using Western blot assays. Cross-adsorption of 10 infant's saliva was tested to S. mitis, S. mutans and Enterococcus faecalis antigens. Results: Salivary levels of IgA at birth were 2.5-fold higher in FT than in PT children (Mann-Whitney; P < 0.05). Salivary IgA antibodies reactive with several antigens of S. mitis and S. mutans were detected at birth in children with undetectable levels of those bacteria. Adsorption of infant saliva with cells of S. mutans produced a reduction of antibodies recognizing S. mitis antigens in half of the neonates. The diversity and intensity of IgA responses were lower in PT compared to FT children, although those differences were not significant. Conclusion: These data provide evidence that children have salivary IgA antibodies shortly after birth, which might influence the establishment of the oral microbiota, and that the levels of salivary antibody might be related to prematurity. (C) 2011 Elsevier Ltd. All rights reserved.

Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: a systematic review and metaanalysis of individual patient data

OBJECTIVE: To determine whether the use of vaginal progesterone in asymptomatic women with a sonographic short cervix (<= 25 mm) in the midtrimester reduces the risk of preterm birth and improves neonatal morbidity and mortality. STUDY DESIGN: Individual patient data metaanalysis of randomized controlled trials. RESULTS: Five trials of high quality were included with a total of 775 women and 827 infants. Treatment with vaginal progesterone was associated with a significant reduction in the rate of preterm birth <33 weeks (relative risk [RR], 0.58; 95% confidence interval [CI], 0.42-0.80), <35 weeks (RR, 0.69; 95% CI, 0.55-0.88), and <28 weeks (RR, 0.50; 95% CI, 0.30-0.81); respiratory distress syndrome (RR, 0.48; 95% CI, 0.30-0.76); composite neonatal morbidity and mortality (RR, 0.57; 95% CI, 0.40-0.81); birthweight <1500 g (RR, 0.55; 95% CI, 0.38-0.80); admission to neonatal intensive care unit (RR, 0.75; 95% CI, 0.59-0.94); and requirement for mechanical ventilation (RR, 0.66; 95% CI, 0.44-0.98). There were no significant differences between the vaginal progesterone and placebo groups in the rate of adverse maternal events or congenital anomalies. CONCLUSION: Vaginal progesterone administration to asymptomatic women with a sonographic short cervix reduces the risk of preterm birth and neonatal morbidity and mortality.

Extremely slow feeding in a tropical drilling ectoparasite, Vitularia salebrosa (King and Broderip, 1832) (Gastropoda: Muricidae), on molluscan hosts from Pacific Panama

This study documents one of the slowest feeding behaviors ever recorded for a muricid gastropod in one of the most biotically rigorous regions on the planet. In Pacific Panama, Vitularia salebrosa attacks mollusks by drilling through their shells. The duration of attacks estimated by isotope sclerochronology of oyster shells collected during attacks in progress range from 90 to 230 days, while experimental observation of interactions documented one attack greater than 103 days. The prolonged nature of attacks suggests that V. salebrosa is best characterized as an ectoparasite than as a predator, which is the ancestral condition in the Muricidae. An ectoparasitic lifestyle is also evident in the unusual interaction traces of this species, which include foot scars, feeding tunnels and feeding tubes, specialized soft anatomy, and in the formation of male-female Pairs, which is consistent with protandrous hermaphroditism, as is typical in sedentary gastropods. To delay death of its host, V. salebrosa targets renewable resources when feeding, such as blood and digestive glands. A congener, Vitularia miliaris from the Indo-Pacific, has an identical feeding biology The origin and persistence of extremely slow feeding in the tropics challenges our present understanding of selective pressures influencing the evolution of muricid feeding behaviors and morphological adaptations. Previously, it has been suggested that faster feeding is advantageous because it permits predators to spend a greater proportion of time hiding in enemy-free refugia or to take additional prey, the energetic benefits of which could be translated into increased fecundity or defenses. The benefits of exceptionally slow feeding have received little consideration. In the microhabitat preferred by V. salebrosa (beneath boulders), it is possible that prolonged interactions with hosts decrease vulnerability to enemies by reducing the frequency of risky foraging events between feedings . Ectoparasitic feeding through tunnels by V. salebrosa may also reduce competitive interactions with kleptoparasites (e.g., crabs, snails) that steal food through the gaped valves of dead or dying hosts.