Aerobic Capacity of Preterm Children with Very Low Birth Weight at School Age and its Associated Factors.

INTRODUCTION: Respiratory morbidities of preterm infants can cause significant ventilatory impairment thus compromising the aerobic capacity in childhood and adolescence. Therefore, the present study was conducted to evaluate the aerobic capacity in school age preterm children with VLBW and its associated factors. METHODS: A cross-sectional study was conducted among preterm born with VLBW and term children, both aged 6-9 years. An individualized symptom-limited treadmill testing protocol performed aerobic capacity. Measured variables: oxygen pulse (PuO2), percentage of maximum heart rate for age (%HR max), tidal volume/inspiratory capacity ratio (TV/IC), oxygen consumption (VO2) peak, and the ratio of the anaerobic threshold of gas exchange to the predicted percentage of maximum VO2 (VO2@LA/%VO2 max.pred.) were compared between groups. Univariate and multiple linear regression analyses were used to determine the factors associated with aerobic capacity. RESULTS: Thirty-four preterm and 32 term children were included. Similar VO2 peak and the other variables were observed. The development of bronchopulmonary dysplasia (BPD) and being obese/overweight was positively associated with %HR max. The Z-score for height/age and birth weight <1000g was positively associated with PuO2 and peak VO2, and negatively associated with overweight/obesity and female sex. CONCLUSIONS: Aerobic capacity was similar in both groups. Sex, development of BPD, birth weight <1000g and factors related to body growth, such as Z-score for height/age and overweight/obesity, were associated with aerobic capacity in preterm children with VLBW.

Association between thoracic musculoskeletal abnormalities and lung function in preterm infants.

INTRODUCTION: In view of the difficulties and risks of performing lung function tests in infants and the hypothesis that children with abnormal pulmonary test may exhibit thoracic musculoskeletal alterations. OBJECTIVES: This study aimed to determine the frequency of abnormal lung function and their relationship. MATERIALS AND METHODS: This was a cross-sectional study with children from 6 to 12 months of corrected age, born at a gestational age of <37 weeks and with a birthweight ≤1500 g, who were subjected to a lung function test and photogrammetry--an objective and non-invasive procedure. To verify the association between the thoracic musculoskeletal abnormalities and measure changes in lung function, univariate linear regression was used. The level of statistical significance was setted at P < 0.05. RESULTS: Of the 38 infants, 12 (31.6%) exhibited abnormal lung function, including 9 (23.7%) with obstructive function and 3 (7.9%) with restrictive function. A significant association was noted between forced expiratory volume at 0.5 second <-2 z score and the acromion/xiphoid process/acromion angle (ß = 4.935); forced vital capacity <-2 z score and the angle of the manubrium/left acromion/trapezium (ß = 0.033) and forced expiratory volume at 0.5 second and forced vital capacity ratio <-2 z score and the inframammillary point/xiphoid process/inframammillary point angle (ß = 0.043). CONCLUSION: Preterm infants with very low birthweight presented a high frequency of abnormal lung function, particularly obstructive type and thoracic musculoskeletal abnormalities were associated with changes in lung function.

Pulmonary function in former very low birth weight preterm infants in the first year of life.

BACKGROUND: Pulmonary function in former preterm infants may be compromised during childhood. OBJECTIVES: To assess pulmonary function in very-low-birth-weight preterm infants at 6-12 months of corrected age and analyze the factors associated with abnormal pulmonary function. METHODS: Cross-sectional study with preterm infants at 6-12 months of corrected age with birth weight <1500 g. Children with malformations or affected by neuromuscular and respiratory diseases were excluded. Forced expiratory flows were assessed using the chest compression technique, and volumes were measured by total body plethysmography. Pulmonary function parameters in preterm infants were compared to a control group of same-aged children born at term. RESULTS: We studied 51 preterm and 37 infants born at term. Preterm infants had: gestational age at birth (30.0 ±â€¯2.5 weeks), birth weight (1179 ±â€¯247 g), 27.5% had bronchopulmonary dysplasia, and 45% received mechanical ventilation. Preterm infants had lower median z-scores in comparison to term infants for the following parameters (p < 0.05): FVC (-0.3 vs. 0.7), FEV0.5 (-0.5 vs. 0.9), FEV0.5/FVC (-0.6 vs. -0.5), FEF50 (-0.4 vs. 0.9), FEF75 (-0.3 vs. 0.8), FEF85 (-0.1 vs. 0.6) and FEF25-75 (-0.5 vs. 1.1). No term child had abnormal lung function, compared to 39.2% of preterm infants (p = 0.001). Factors associated with abnormal pulmonary function were lower gestational age at birth, small for gestational age, need for mechanical ventilation and presence of recurrent wheezing. CONCLUSIONS: Preterms had a high prevalence of abnormal pulmonary function and lower pulmonary function in comparison to term infants. Prematurity, intrauterine growth restriction, respiratory support and recurrent wheezing were associated with abnormal pulmonary function.

Humoral immune response to measles and varicella vaccination in former very low birth weight preterm infants.

INTRODUCTION: Immune response to vaccination in infants born prematurely may be lower than in infants born at full-term. Some clinical factors might be associated with humoral immune response. OBJECTIVES: The objectives of this study were to compare the immune response to measles and varicella vaccination in infants born prematurely with those born at full-term and to analyze factors associated with measles and varicella antibody levels. METHODS: Prospective study including two groups of infants aged 12 months. One group of infants born prematurely with birth-weight <1500g and who were in follow-up at the outpatient clinic for preterm infants at the institution and other group of infants born at full-term. Infants with malformations, primary immunodeficiency diseases, born to HIV-positive mothers or who had received plasma or immunoglobulin transfusions five months before or three weeks after vaccination were excluded. Plasma antibodies were measured by ELISA and factors associated with antibody levels were assessed by linear regression. RESULTS: Sixty-five premature and 56 full-term infants were included. The percentage of immune individuals after vaccination against measles (100% vs. 100%) and varicella (92.5% vs. 93.2%) were similar in both groups, as well as the antibody levels against measles (2.393 vs. 2.412UI/mL; p=0.970) and varicella (0.551 vs. 0.399UI/mL; p=0.114). Use of antenatal corticosteroids decreased measles antibody levels whereas breastfeeding for more than six months increased varicella antibody levels. CONCLUSIONS: Humoral responses to measles and varicella were similar between infants born prematurely and full-term infants. Measles antibody levels were negatively associated with antenatal corticosteroid use; varicella antibodies were positively associated with prolonged breastfeeding.

Humoral immune response to measles and varicella vaccination in former very low birth weight preterm infants

ABSTRACT Introduction: Immune response to vaccination in infants born prematurely may be lower than in infants born at full-term. Some clinical factors might be associated with humoral immune response. Objectives: The objectives of this study were to compare the immune response to measles and varicella vaccination in infants born prematurely with those born at full-term and to analyze factors associated with measles and varicella antibody levels. Methods: Prospective study including two groups of infants aged 12 months. One group of infants born prematurely with birth-weight <1500 g and who were in follow-up at the outpatient clinic for preterm infants at the institution and other group of infants born at full-term. Infants with malformations, primary immunodeficiency diseases, born to HIV-positive mothers or who had received plasma or immunoglobulin transfusions five months before or three weeks after vaccination were excluded. Plasma antibodies were measured by ELISA and factors associated with antibody levels were assessed by linear regression. Results: Sixty-five premature and 56 full-term infants were included. The percentage of immune individuals after vaccination against measles (100% vs. 100%) and varicella (92.5% vs. 93.2%) were similar in both groups, as well as the antibody levels against measles (2.393 vs. 2.412 UI/mL; p = 0.970) and varicella (0.551 vs. 0.399 UI/mL; p = 0.114). Use of antenatal corticosteroids decreased measles antibody levels whereas breastfeeding for more than six months increased varicella antibody levels. Conclusions: Humoral responses to measles and varicella were similar between infants born prematurely and full-term infants. Measles antibody levels were negatively associated with antenatal corticosteroid use; varicella antibodies were positively associated with prolonged breastfeeding.

Neonatal screening for severe combined immunodeficiency in Brazil.

OBJECTIVE: To apply, in Brazil, the T-cell receptor excision circles (TRECs) quantification technique using real-time polymerase chain reaction in newborn screening for severe combined immunodeficiency and assess the feasibility of implementing it on a large scale in Brazil. METHODS: 8715 newborn blood samples were collected on filter paper and, after DNA elution, TRECs were quantified by real-time polymerase chain reaction. The cutoff value to determine whether a sample was abnormal was determined by ROC curve analysis, using SSPS. RESULTS: The concentration of TRECs in 8,682 samples ranged from 2 to 2,181TRECs/µL of blood, with mean and median of 324 and 259TRECs/µL, respectively. Forty-nine (0.56%) samples were below the cutoff (30TRECs/µL) and were reanalyzed. Four (0.05%) samples had abnormal results (between 16 and 29TRECs/µL). Samples from patients previously identified as having severe combined immunodeficiency or DiGeorge syndrome were used to validate the assay and all of them showed TRECs below the cutoff. Preterm infants had lower levels of TRECs than full-term neonates. The ROC curve showed a cutoff of 26TRECs/µL, with 100% sensitivity for detecting severe combined immunodeficiency. Using this value, retest and referral rates were 0.43% (37 samples) and 0.03% (3 samples), respectively. CONCLUSION: The technique is reliable and can be applied on a large scale after the training of technical teams throughout Brazil.

Response to immunization in children born to renal transplant recipients using immunosuppressive drugs during gestation.

The use of immunosuppressive drugs can impair vaccination responses. When used during pregnancy, they may interfere with the development of the fetus's immune system. However, little is known regarding their influence on infant's response to vaccinations. Twenty-seven children born to renal transplant mothers (Tx) taking immunosuppressive drugs and 31 healthy children had the humoral immune response and reactogenicity to tetanus, Haemophilus influenzae type b (Hib) and 7 pneumococcal serotypes evaluated. The evolution of BCG vaccine scar was also registered. Antibodies were measured by ELISA. Lymphocyte immunophenotyping was performed on cord blood and at 7-8 months of age. Among Tx neonates, 82.4% had low B lymphocyte numbers at birth, and 29.4% had also low numbers of other lymphocyte subpopulations. Nevertheless, all children developed protective antibodies with similar antibody concentrations to the control group. Vaccine reactogenicity was similar in both groups and BCG healing was uneventful.

Factors associated with red blood cell transfusions in very-low-birth-weight preterm infants in Brazilian neonatal units.

BACKGROUND: Preterm infants in neonatal intensive care units frequently receive red blood cells (RBC) transfusions due to the anemia of prematurity. A number of variables related to gestational age, severity of illness and transfusion practices adopted in the neonatal unit where the neonate was born may contribute to the prescription of RBC transfusions. This study aimed to analyse the frequency and factors associated with RBC transfusions in very-low-birth-weight preterm infants. METHODS: A prospective cohort of 4283 preterm infants (gestational age: 29.9 ± 2.9 weeks; birth weight: 1084 ± 275 g) carried out at 16 university hospitals in Brazil between January 2009 and December 2011 was analysed. Factors associated with RBC transfusions were evaluated using univariate and multiple logistic regression analysis. RESULTS: A total of 2208 (51.6%) infants received RBC transfusions (variation per neonatal unit: 34.1% to 66.4%). RBC transfusions were significantly associated with gestational age (OR: -1.098; 95%CI: -1.12 to -1.04), SNAPPE II score (1.01; 1.00-1.02), apnea (1.69; 1.34-2.14), pulmonary hemorrhage (2.65; 1.74-4.031), need for oxygen at 28 days of life (1.56; 1.17-2.08), clinical sepsis (3.22; 2.55-4.05), necrotising enterocolitis (3.80; 2.26-6.41), grades III/IV intraventricular hemorrhage (1.64; 1.05-2.58), mechanical ventilation (2.27; 1.74-2.97), use of umbilical catheter (1.86; 1.35-2.57), parenteral nutrition (2.06; 1.27-3.33), >60 days of hospitalization (5.29; 4.02-6.95) and the neonatal unit where the neonate was born. CONCLUSIONS: The frequency of RBC transfusions varied among neonatal intensive care units. Even after adjusting for adverse health conditions and therapeutic interventions, the neonatal unit continued to influence transfusion practices in very-low birth-weight infants.

[Availability of physical therapy assistance in neonatal intensive care units in the city of São Paulo, Brazil]. / Disponibilidade de assistência fisioterapêutica em unidades de terapia intensiva neonatal na cidade de São Paulo.

OBJECTIVE: To describe the characteristics of physical therapy assistance to newborns and to provide a profile of physical therapists working in intensive care units in the city of São Paulo, Brazil. METHODS: This cross-sectional study was conducted in every hospital in São Paulo city that had at least one intensive care unit bed for newborns registered at the National Registry of Health Establishments in 2010. In each unit, three types of physical therapists were included: an executive who was responsible for the physical therapy service in that hospital (chief-physical therapists), a physical therapist who was responsible for the physical therapy assistance in the neonatal unit (reference-physical therapists), and a randomly selected physical therapist who was directly involved in the neonatal care (care-physical therapists). RESULTS: Among the 67 hospitals eligible for the study, 63 (94.0%) had a physical therapy service. Of those hospitals, three (4.8%) refused to participate. Thus, 60 chief-PTs, 52 reference-physical therapists, and 44 care-physical therapists were interviewed. During day shifts, night shifts, and weekends/holidays, there were no physical therapists in 1.7%, 45.0%, and 13.3% of the intensive care units, respectively. Physical therapy assistance was available for 17.8±7.2 hours/day, and each physical therapist cared for 9.4±2.6 newborns during six working hours. Most professionals had completed at least one specialization course. CONCLUSION: Most neonatal intensive care units in the city of São Paulo had physical therapists working on the day shift. However, other shifts had incomplete staff with less than 18 hours of available physical therapy assistance per day.

Perception of pain and distress in intubated and mechanically ventilated newborn infants by parents and health professionals.

BACKGROUND: An understanding of perceptions of parents and health caregivers who assist critically ill neonates is necessary to comprehend their actions and demands. Therefore this study aim to analyze the agreement among parents, nurse technicians and pediatricians regarding the presence and intensity of pain and distress in mechanically ventilated and intubated newborn infants. METHODS: Cross-sectional study comprising 52 infants and 52 trios of adults composed of one parent, one nurse technician, and one pediatrician who all observed the same infant. All infants were intubated and under mechanical ventilation and were not handled during the observations. Each newborn was simultaneously observed by the trio of adults for 1 minute to evaluate the presence of pain and distress. The intensity of pain and distress that the adults believed was felt by the infants was marked in a visual analogical scale. Adults' agreement about the simultaneous presence of pain and distress in each infant was analyzed by marginal homogeneity and Cochran tests. The agreement about the intensity of pain and distress in each infant was studied by Bland-Altman plot and intraclass correlation coefficient (ICC). RESULTS: The assessments of pain and distress were heterogeneous in all three investigated groups of adults as determined by the results of a Bland-Altman plot. The presence of distress was more frequently reported compared with pain (marginal heterogeneity, p < 0.01). The pain and distress scores in each adult group were not correlated as shown by ICC [parents, 0.36 (95% CI: 0.01-0.63); nurses 0.47 (0.23-0.66); pediatricians, 0.46 (0.22-0.65)]. CONCLUSIONS: Adults systematically underscore pain in comparison to distress in mechanically ventilated newborns, without recognizing the association between them.

Functional capacity during exercise in very-low-birth-weight premature children.

OBJECTIVES: The functional capacity of children born prematurely with very-low-birth weight was compared with that of children born at full-term using the six-minute walk test (6MWT) and the ten-minutes shuttle walk test (10MSWT). The factors affecting walking distance were analyzed. METHODS: A cross-sectional study was conducted with two groups of children aged 6-9 years, matched by sex and age. One group included children born before 37 weeks of gestation weighing <1,500 g and the second group included children born at term. Both groups were submitted to the 6MWT and 10MWST, performed on the same day with an interval of 20 min between tests and the sequence of the tests was randomized, by sealed-envelope technique. Physiological parameters were measured at the beginning and end of each test. The walking distance and factors affecting the walking distance were analyzed. RESULTS: Thirty-seven children born prematurely and 37 born at term were studied. The premature children walked shorter distances in the 6MWT (480.9 ± 80.5 m vs. 518.3 ± 51.8 m, P = 0.010) than term children, and both groups walked similar distances in the 10MSWT (391.5 ± 99.0 m vs. 406.1 ± 79.2 m, P = 0.487). By multiple linear regression analysis, adjusted for confounders, walking distance was associated with height (OR: 3.6) and oxygen dependency at 28 days (OR: -67.7) in the 6MWT (P < 0.001) and with height (OR: 4.9) and oxygen dependency at 28 days (OR: -91.0) in the 10MSWT (P < 0.001). CONCLUSION: In conclusion, this study suggests that children born prematurely with very low birth weight, especially those who had bronchopulmonary dysplasia present limited functional capacity during exercise.

Immune response to tetanus booster in infants aged 15 months born prematurely with very low birth weight.

OBJECTIVES: To compare humoral and cellular immune responses to tetanus booster vaccination in infants born prematurely with those born at full term and identify factors associated with the humoral response. METHODS: A prospective study was carried out on children born prematurely and with a birth weight <1500g and with infants born at full term. At 15 months (pre-vaccination) and 18 months (post-vaccination), anti-tetanus antibodies were measured by ELISA; the intracellular interferon-gamma percentages of CD4+ T and CD8+ T cells after in vitro stimulation with tetanus toxoid were determined by flow cytometry. Chi-squared or Fisher's exact test was used to compare categorical variables. Student's t-test or Mann-Whitney test was used to compare numerical variables. Regression analysis was performed to determine factors associated with humoral immunity. Statistical significance was considered if p<0.05. RESULTS: Sixty-four premature and 54 full-term infants were studied. The proportion of children immune against tetanus at 15 and 18 months was similar in both groups. The geometric mean of the antibodies was lower among the premature children at 15 months (p=0.025) and was similar in both groups at 18 months (p=0.852). The percentages of CD4+ and CD8+ T cells expressing intracellular IFN-γ were similar in both groups at 15 and 18 months. Gestational age <32 weeks was associated with a reduction of -0.116IU/mL in the level of antibodies at 15 months. Breastfeeding >6 months was associated with a 3.5-fold greater chance of optimal protective (≥0.1IU/mL) antibody level against tetanus at 15 months and an increase of 0.956IU/mL in the level of antibodies at 18 months. CONCLUSIONS: Humoral and cellular response following a tetanus booster was similar in both groups. Premature infants exhibited lower levels of anti-tetanus antibodies at 15 months of age, with the lowest levels in those born at a gestational age of less than 32 weeks. Breastfeeding was associated with greater levels of antibody against tetanus.

Red blood cell transfusions are independently associated with intra-hospital mortality in very low birth weight preterm infants.

OBJECTIVE: To test the hypothesis that red blood cell (RBC) transfusions in preterm infants are associated with increased intra-hospital mortality. STUDY DESIGN: Variables associated with death were studied with Cox regression analysis in a prospective cohort of preterm infants with birth weight <1500 g in the Brazilian Network on Neonatal Research. Intra-hospital death and death after 28 days of life were analyzed as dependent variables. Independent variables were infant demographic and clinical characteristics and RBC transfusions. RESULTS: Of 1077 infants, 574 (53.3%) received at least one RBC transfusion during the hospital stay. The mean number of transfusions per infant was 3.3 ± 3.4, with 2.1 ± 2.1 in the first 28 days of life. Intra-hospital death occurred in 299 neonates (27.8%), and 60 infants (5.6%) died after 28 days of life. After adjusting for confounders, the relative risk of death during hospital stay was 1.49 in infants who received at least one RBC transfusion in the first 28 days of life, compared with infants who did not receive a transfusion. The risk of death after 28 days of life was 1.89 times higher in infants who received more than two RBC transfusions during their hospital stay, compared with infants who received one or two transfusions. CONCLUSION: Transfusion was associated with increased death, and transfusion guidelines should consider risks and benefits of transfusion.

Diphtheria, tetanus, and varicella immunity in health care workers in neonatal units.

BACKGROUND: Susceptible health care workers are at risk of acquiring and transmitting vaccine-preventable diseases to or from patients. The objective of this study was to assess antibody levels against diphtheria, tetanus, and varicella in healthcare workers. METHODS: Antibody levels against diphtheria, tetanus, and varicella were measured in health care professionals in 2 neonatal units at the Federal University of São Paulo, Brazil. RESULTS: Between September and November 2002, 215 of 222 (96.8%) health care workers were studied. Of those, 122 (56.7%) gave oral information regarding their vaccination status against diphtheria and tetanus and only 9 (4.2%) had their vaccination cards. Geometric mean antibody levels against diphtheria, tetanus, and varicella were 0.89 IU/mL (95%CI, 0.73 to 1.08), 0.86 IU/mL (95%CI, 0.68 to 1.07) and 1.10 IU/mL (95%CI, 0.98 to 1.24), respectively. Using internationally accepted definitions, 200 (93.0%) and 182 (84.7%) individuals had full protection against diphtheria and tetanus, respectively. Regarding varicella, 213 (99.1%) individuals were immune and 2 (0.9%) had equivocal immunity against varicella. Of 65 (30.2%) individuals without previous history of the illness, 63 (96.9%) were immune against varicella zoster virus. CONCLUSIONS: Based on serologic screening, most professionals were immune to diphtheria, tetanus, and varicella. Absence of previous history of varicella was an unreliable identifier of susceptibility to varicella zoster virus in the health care workers studied.

Multidimensional pain assessment of preterm newborns at the 1st, 3rd and 7th days of life.

CONTEXT AND OBJECTIVE: It is challenge to assess and treat pain in premature infants. The objective of this study was to compare the multidimensional pain assessment of preterm neonates subjected to an acute pain stimulus at 24 hours, 72 hours and seven days of life. DESIGN AND SETTING: Prospective cohort study, at Universidade Federal de São Paulo. METHODS: Eleven neonates with gestational age less than 37 weeks that needed venepuncture for blood collection were studied. The exclusion criteria were Apgar score < 7 at five minutes, presence of any central nervous system abnormality, and discharge or death before seven days of life. Venepuncture was performed in the dorsum of the hand, and the heart rate, oxygen saturation and pain scales [Neonatal Facial Coding System (NFCS), Neonatal Infant Pain Scale (NIPS), and Premature Infant Pain Profile (PIPP)] were assessed at 24 hours, 72 hours and 7 days of life. NFCS and NIPS were evaluated prior to procedure (Tpre), during venepuncture (T0), and two (T2) and five (T5) minutes after needle withdrawal. Heart rate, O2 saturation and PIPP were measured at Tpre and T0. Mean values were compared by repeated-measurement analysis of variance. RESULTS: The pain parameters did not differ at 24 hours, 72 hours and 7 days of life: heart rate (p = 0.22), oxygen saturation (p = 0.69), NFCS (p = 0.40), NIPS (p = 0.32) and PIPP (p = 0.56). CONCLUSION: Homogeneous pain scores were observed following venepuncture in premature infants during their first week of life.

Factors associated with survival of very-low-birth-weight infants in a Brazilian fee-paying maternity in the 1990s.

This study describes intra-hospital survival rates of very-low-birth-weight infants, as well as factors present at birth associated with survival, during a period of 10 years. This is a Retrospective cohort study performed in a 3rd level nursery at Santa Joana Maternity Hospital, a fee-paying institution in Sao Paulo, Brazil. From January 1991 to December 2000, 963 live-born infants with a birth weight of 500-1499 g, without congenital anomalies, were followed until discharge. Survival was studied according with year of birth, and stratified by birth weight and gestational age. Factors present at birth associated with survival were analyzed by logistic regression. Patient characteristics were: birth weight 500-999 g (38%), gestational ages or=750 g, and gestational age >or=26 weeks.