Hypothermia and Early Neonatal Mortality in Preterm Infants

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

There is no difference in nitric oxide metabolites and neonatal outcome between premature infants born to pre-eclamptic and those born to normotensive women

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Selenium and vitamin A and E in the nutrition of very low-birth weight preterm infants

Deficient antioxidant defenses in preterm infants have been implicated in diseases such as bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, periventricular leukomalacia, and intraventricular hemorrhage. The antioxidant properties of selenium, vitamin A, and vitamin E make these elements important in the nutrition of Very Low-Birth Weight (VLBW) infants. Selenium is a component of glutathione peroxidase, an enzyme that prevents the production of free radicals. The decrease in plasma selenium in VLBW infants in the first month after birth makes evident that preterm infants have low selenium store and require supplementation by parenteral and enteral nutrition. A meta-analysis, with only three trials, showed that selenium supplementation did not affect mortality, and the incidence of neonatal chronic lung disease or retinopathy of prematurity, but was associated with a reduction in lateonset sepsis. Most VLBW infants and extremely Low-Birth Weight Infants (ELBW) are born with low vitamin A stores and need vitamin A supplementation by intramuscular or enteral route. Low plasma retinol concentrations increase the risk of chronic lung disease/bronchopulmonary dysplasia and long-term respiratory disabilities in preterm infants. There is evidence that vitamin A supplementation decreases the mortality or oxygen requirement at one month of age, and oxygen requirement at 36 weeks’ postmenstrual age. Vitamin E blocks natural peroxidation of polyunsaturated fatty acids from lipid layers of cell membranes. VLBW infants have a decrease in plasma concentrations in the first month after birth suggesting the need of vitamin E supplementation. A meta-analysis on vitamin E supplementation concluded that vitamin E did not affect mortality, risk of bronchopulmonary dysplasia, and necrotizing enterocolitis but reduced the risk of intraventricular hemorrhage and increased the risk of sepsis. Serum vitamin E concentrations higher than 3.5 mg/dL are associated with a decrease in the risk of severe retinopathy of prematurity, and blindness, but also with an increase in neonatal sepsis. Caution is recommended with the supplementation of high doses of parenteral vitamin E and supplementation that increases serum levels above 3.5 mg/dL. In conclusion: although it is known that preterm infants are deficient in selenium, vitamin A and E, more studies are required to determine the best way to supplement and the impact of supplementation on neonatal outcome.

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.

Lung-function tests in neonates and infants with chronic lung disease: tidal breathing and respiratory control

This paper is the fourth in a series of reviews that will summarize available data and critically discuss the potential role of lung-function testing in infants with acute neonatal respiratory disorders and chronic lung disease of infancy. The current paper addresses information derived from tidal breathing measurements within the framework outlined in the introductory paper of this series, with particular reference to how these measurements inform on control of breathing. Infants with acute and chronic respiratory illness demonstrate differences in tidal breathing and its control that are of clinical consequence and can be measured objectively. The increased incidence of significant apnea in preterm infants and infants with chronic lung disease, together with the reportedly increased risk of sudden unexplained death within the latter group, suggests that control of breathing is affected by both maturation and disease. Clinical observations are supported by formal comparison of tidal breathing parameters and control of breathing indices in the research setting.

Preference for cute infants does not depend on their ethnicity or species: Evidence from hypothetical adoption and donation paradigms

Results of previous work suggest a preference of adult observers for cute compared to less cute infants. In Study 1 we investigated whether the preference for cute infants depends on the ethnicity and species of the infant. We simultaneously presented two faces (one cute and one less cute) and asked Caucasian participants to choose the infant to whom they would rather give a toy (Task 1) and which infant they would rather adopt (Task 2). The infants were Caucasian or African human babies, or dog puppies. For all face categories and in both tasks we found a strong preference for cute infants. A possible reason for preferring cute infants may be that cute infants look healthier than less cute infants. To investigate whether cuteness is associated with the assessment of health we conducted Study 2. Faces of Caucasian and African infants and dog puppies were rated for cuteness and health. The findings revealed a significant relationship between health and cuteness evaluation across all stimuli. We suggest that one reason why cute infants are preferred might be because they are perceived as being healthier.

Development of visual evoked responses to tritan,red-green and luminance stimuli in human infants

The principal aim of this work was to investigate the development of the S-cone colour-opponent pathway in human infants aged 4 weeks to 6 months. This was achieved by recording transient visual evoked responses to pattern-onset stimuli along a tritanopic confusion axis (tritan stimuli) at and around the adult isoluminant match. For comparison, visual evoked responses to red-green and luminance-modulated stimuli were recorded from the same infants at the same ages. Evoked responses were also recorded from colour-normal adults for comparison with those of the infants. The transient VEP allowed observation of response morphology as luminance differences were introduced to the chromatic stimuli. In this way, an estimate of isoluminance was possible in infants. Estimated isoluminant points for a group of six infants aged 6 to 10 weeks closely approximated the adult isoluminant match. This finding has implications for the use of photometric isoluminance in infant work, and suggests that photopic spectral sensitivity is similar in infants and adults. Abnormalities of the visual evoked responses to tritan, red-green and luminance-modulated stimuli in an infant with cystic fibrosis are reported. The results suggest abnormal function of the retino-striate visual pathway in this infant, and it is argued that these may be secondary to his illness, although data from more infants with cystic fibrosis are needed to clarify this further. A group of nine healthy infants demonstrated evoked responses to tritan stimuli by 4 to 10 weeks and to red-green stimuli by 6 to 11 weeks post-term age. Responses to luminance-modulated stimuli were present in all nine infants at the earliest age tested, namely 4 weeks post-term. The slightly earlier age of onset of evoked responses to tritan stimuli than for red-green may be explained by the relatively lower cone contrast afforded by red-green stimuli. Latency of the evoked response to both types of chromatic stimuli and to luminance-modulated stimuli decreased with age at a similar rate, suggesting that the visual pathways transmitting luminance and chromatic information mature at similar rates in young infants.

Improving the care of preterm infants: before, during, and after, stabilisation in the delivery room

Introduction Up to 10% of infants require stabilisation during transition to extrauterine life. Enhanced monitoring of cardiorespiratory parameters during this time may improve stabilisation outcomes. In addition, technology may facilitate improved preparation for delivery room stabilisation as well as NICU procedures, through educational techniques. Aim To improve infant care 1) before birth via improved training, 2) during stabilisation via enhanced physiological monitoring and improved practice, and 3) after delivery, in the neonatal intensive care unit (NICU), via improved procedural care. Methods A multifaceted approach was utilised including; a combination of questionnaire based surveys, mannequin-based investigations, prospective observational investigations, and a randomised controlled trial involving preterm infants less than 32 weeks in the delivery room. Forms of technology utilised included; different types of mannequins including a CO2 producing mannequin, qualitative end tidal CO2 (EtCO2) detectors, a bespoke quantitative EtCO2 detector, and annotated videos of infant stabilisation as well as NICU procedures Results Manual ventilation improved with the use of EtCO2 detection, and was positively assessed by trainees. Quantitative EtCO2 detection in the delivery room is feasible, EtCO2 increased over the first 4 minutes of life in preterm infants, and EtCO2 was higher in preterm infants who were intubated. Current methods of heart rate assessment were found to be unreliable. Electrocardiography (ECG) application warrants further evaluation. Perfusion index (PI) monitoring utilised in the delivery room was feasible. Video recording technology was utilised in several ways. This technology has many potential benefits, including debriefing and coaching in procedural healthcare, and warrants further evaluation. Parents would welcome the introduction of webcams in the NICU. Conclusions I have evaluated new methods of improving infant care before, during, and after stabilisation in the DR. Specifically, I have developed novel educational tools to facilitate training, and evaluated EtCO2, PI, and ECG during infant stabilisation. I have identified barriers in using webcams in the NICU, to now be addressed prior to webcam implementation.

Iron status in early life and associations with developmental outcomes

Infants and young children are at particular risk of iron deficiency and its associated consequences for growth and development. The main objectives of this thesis were to quantify iron intakes, status and determinants of status in two year olds; explore determinants of neonatal iron stores; investigate associations between iron status at birth and two years with neurodevelopmental outcomes at two years and explore the influence of growth on iron status in early childhood, using data from the Cork BASELINE (Babies after SCOPE: Evaluating Longitudinal Impact using Neurological and Nutritional Endpoints) Birth Cohort Study (n=2137). Participants were followed prospectively with interviewer-led questionnaires and clinical assessments at day 2 and at 2, 6, 12 and 24 months. At two years, there was a low prevalence of iron deficiency and iron deficiency anaemia in this cohort, representing the largest study of iron status in toddlers in Europe, to date. The increased consumption of iron-fortified products and compliance with recommendations to limit unmodified cows’ milk intakes in toddlers has contributed to the observed improvements in status. Low serum ferritin concentrations at birth, which reflect neonatal iron stores, were shown to track through to two years of age; delivery by Caesarean section, being born small-for-gestational age and maternal obesity and smoking in pregnancy were all associated with significantly lower neonatal iron stores. Despite a low prevalence of iron deficiency in this cohort, both a mean corpuscular volume <74fl and ferritin concentrations <20μg/l were associated with lower neurodevelopmental outcomes at two years. An inverse association between growth in the second year of life and iron status at two years was also observed. This thesis has presented data from one of the largest, extensively-characterised cohorts of young children, to date, to explore iron and its associations with growth and development.

Agreement of Mixed Venous Carbon Dioxide Tension (PvCO2) and Transcutaneous Carbon Dioxide (PtCO2) Measurements in Ventilated Infants

Background: Noninvasive transcutaneous carbon dioxide monitoring has been shown to be accurate in infants and children, limited data are available to show the usefulness and limitations of partial transcutaneous carbon dioxide tension (PtCO2) value. Objectives: The current study prospectively determines the effectiveness and accuracy of PtCO2 measurements in newborns. Materials and Methods: Venous blood gas sampling and monitoring of the PtCO2 level (TCM TOSCA, Radiometer) were done simultaneously. All measurements are performed on mechanically ventilated infants. Partial venous carbon dioxide tension (PvCO2) values divided into three groups according to hypocapnia (Group 1: < 4.68 kPa), normocapnia (Group 2: 4.68–7.33 kPa), hypercapnia (Group 3: > 7.33 kPa) and then PvCO2 and PtCO2 data within each group were compared separately. Results: A total of 168 measurements of each PvCO2 and PtCO2 data were compared in three separated groups simultaneously (13 in Group 1, 118 in Group 2, and 37 in Group 3). A bias of more than ± 0.7 kPa was considered unacceptable. PtCO2 was related to PvCO2 with acceptable results between the two measurements in hypocapnia (mean difference 0.20 ± 0.19 kPa) and normocapnia (0.002 ± 0.30 kPa) groups. On the other hand in hypercapnia group PtCO2 values were statistically significant (P < 0.001) and lower than PvCO2 data (mean difference 0.81 ± 1.19 kPa) Conclusions: PtCO2 measurements have generally good agreement with PvCO2 in hypocapnic and normocapnic intubated infants but there are some limitations especially with high level of CO2 tension. Monitoring of PtCO2 is generally a useful non-invasive indicator of PvCO2 in hypocapnic and normocapnic infants.

Assessment of Risk Factors and Prognosis in Asphyxiated Infants

Background: Asphyxia is considered an important cause of morbidity and mortality in neonates. This condition can affect many vital organs including the central nervous system and may eventually lead to death or developmental disorders. Objectives: Considering the high prevalence of asphyxia and its adverse consequences, the present study was conducted to evaluate the risk factors for birth asphyxia and assess their correlation with prognosis in asphyxiated infants. Patients and Methods: This two-year follow-up cohort study was conducted on 260 infants (110 asphyxiated infants and 150 healthy neonates) at Mashhad Ghaem Hospital during 2007 - 2014. Data collection tools consisted of a researcher-designed questionnaire including maternal and neonatal information and clinical/laboratory test results. The subjects were followed-up, using Denver II test for 6, 12, 18, and 24 months (after discharge). For data analysis, t-test was performed, using SPSS version 16.5. P value ≤ 0.05 was considered statistically significant. Results: Of 260 neonates, 199 (76.5%) and 61 (23.5%) cases presented with normal neonatal outcomes and with abnormal neonatal outcomes (developmental delay), respectively. Variables such as the severity of asphyxia (P = 0.000), five-minute Apgar score (P = 0.015), need for ventilation (P = 0.000), and severity of acidosis at birth (P = 0.001) were the major prognostic factors in infants with asphyxia. Additionally, prognosis was significantly poorer in boys and infants with dystocia history (P = 0.000). Conclusions: Prevalence of risk factors for developmental delay including the severity of asphyxia need for mechanical ventilation, and severity of acidosis at birth, dystocia, and Apgar score were lower in surviving infants; therefore, controlling these risk factors may reduce asphyxia-associated complications.

Effect of room temperature transport vials on DNA quality and phylogenetic composition of faecal microbiota of elderly adults and infants

Background: Alterations in intestinal microbiota have been correlated with a growing number of diseases. Investigating the faecal microbiota is widely used as a non-invasive and ethically simple proxy for intestinal biopsies. There is an urgent need for collection and transport media that would allow faecal sampling at distance from the processing laboratory, obviating the need for same-day DNA extraction recommended by previous studies of freezing and processing methods for stool. We compared the faecal bacterial DNA quality and apparent phylogenetic composition derived using a commercial kit for stool storage and transport (DNA Genotek OMNIgene GUT) with that of freshly extracted samples, 22 from infants and 20 from older adults. Results: Use of the storage vials increased the quality of extracted bacterial DNA by reduction of DNA shearing. When infant and elderly datasets were examined separately, no differences in microbiota composition were observed due to storage. When the two datasets were combined, there was a difference according to a Wilcoxon test in the relative proportions of Faecalibacterium, Sporobacter, Clostridium XVIII, and Clostridium XlVa after 1 week's storage compared to immediately extracted samples. After 2 weeks' storage, Bacteroides abundance was also significantly different, showing an apparent increase from week 1 to week 2. The microbiota composition of infant samples was more affected than that of elderly samples by storage, with significantly higher Spearman distances between paired freshly extracted and stored samples (p

Mode of oral iron administration and the amount of iron habitually consumed do not affect iron absorption, systemic iron utilisation or zinc absorption in iron-sufficient infants: a randomised trial

Different metabolic pathways of supplemental and fortification Fe, or inhibition of Zn absorption by Fe, may explain adverse effects of supplemental Fe in Fe-sufficient infants. We determined whether the mode of oral Fe administration or the amount habitually consumed affects Fe absorption and systemic Fe utilisation in infants, and assessed the effects of these interventions on Zn absorption, Fe and Zn status, and growth. Fe-sufficient 6-month-old infants (n 72) were randomly assigned to receive 6·6 mg Fe/d from a high-Fe formula, 1·3 mg Fe/d from a low-Fe formula or 6·6 mg Fe/d from Fe drops and a formula with no added Fe for 45 d. Fractional Fe absorption, Fe utilisation and fractional Zn absorption were measured with oral (⁵⁷Fe and ⁶⁷Zn) and intravenous (⁵⁸Fe and ⁷⁰Zn) isotopes. Fe and Zn status, infection and growth were measured. At 45 d, Hb was 6·3 g/l higher in the high-Fe formula group compared with the Fe drops group, whereas serum ferritin was 34 and 35 % higher, respectively, and serum transferrin 0·1 g/l lower in the high-Fe formula and Fe drops groups compared with the low-Fe formula group (all P<0·05). No intervention effects were observed on Fe absorption, Fe utilisation, Zn absorption, other Fe status indices, plasma Zn or growth. We concluded that neither supplemental or fortification Fe nor the amount of Fe habitually consumed altered Fe absorption, Fe utilisation, Zn absorption, Zn status or growth in Fe-sufficient infants. Consumption of low-Fe formula as the only source of Fe was insufficient to maintain Fe stores.

The development and validation of Australian indices of child development - Part II : validity support

The two outcome indices described in a companion paper (Sanson et al., Child Indicators Research, 2009) were developed using data from the Longitudinal Study of Australian Children (LSAC). These indices, one for infants and the other for 4 year to 5 year old children, were designed to fill the need for parsimonious measures of children’s developmental status to be used in analyses by a broad range of data users and to guide government policy and interventions to support young children’s optimal development. This paper presents evidence from Wave 1data from LSAC to support the validity of these indices and their three domain scores of Physical, Social/Emotional, and Learning. Relationships between the indices and child, maternal, family, and neighborhood factors which are known to relate concurrently to child outcomes were examined. Meaningful associations were found with the selected variables, thereby demonstrating the usefulness of the outcome indices as tools for understanding children’s development in their family and socio-cultural contexts. It is concluded that the outcome indices are valuable tools for increasing understanding of influences on children’s development, and for guiding policy and practice to optimize children’s life chances.

Higher accumulation of polybrominated diphenyl ethers in infants than in adults

Pooled serum samples collected from 8132 residents in 2002/03 and 2004/05 were analyzed to assess human polybrominated diphenyl ether (PBDE) concentrations from specified strata of the Australian population. The strata were defined by age (0−4 years, 5−15 years, < 16 years, 16−30 years, 31−45 years, 46−60 years, and >60 years); region; and gender. For both time periods, infants and older children had substantially higher PBDE concentrations than adults. For samples collected in 2004/05, the mean ± standard deviation ΣPBDE (sum of the homologue groups for the mono-, di-, tri-, tetra-, penta-, hexa-, hepta-, octa-, nona-, and deca-BDEs) concentrations for 0−4 and 5−15 years were 73 ± 7 and 29 ± 7 ng g−1 lipid, respectively, while for all adults >16 years, the mean concentration was lower at 18 ± 5 ng g−1 lipid. A similar trend was observed for the samples collected in 2002/03, with the mean ΣPBDE concentration for children <16 years being 28 ± 8 ng g−1 lipid and for the adults >16 years, 15 ± 5 ng g−1 lipid. No regional or gender specific differences were observed. Measured data were compared with a model that we developed to incorporate the primary known exposure pathways (food, air, dust, breast milk) and clearance (half-life) data. The model was used to predict PBDE concentration trends and indicated that the elevated concentrations in infants were primarily due to maternal transfer and breast milk consumption with inhalation and ingestion of dust making a comparatively lower contribution.