ABSTRACT
Introducción: El objetivo fue establecer valores de normalidad de antitrombina (AT), la proteína C (PC) y la proteína S (PS) dentro de la primera semana después del nacimiento en el binomio madre-recién nacido, ajustados por factores obstétricos y perinatales, según 2 métodos de laboratorio diferentes. Métodos: Se realizaron determinaciones en 83 neonatos a término sanos y sus madres, con 3 grupos de edad posparto: días 1-2, 3 y 4-7. Resultados :No hubo diferencias para ninguna de las proteínas en los distintos grupos de edad de los neonatos y las madres dentro de la primera semana posparto. El análisis ajustado no mostró ninguna asociación con factores obstétricos o perinatales. Los valores de AT y PC en las madres fueron mayores que en los neonatos (p<0,001), mientras que la PS mostró valores similares. La correlación global de los valores entre los pares madre-recién nacido fue escasa, salvo para la PS libre en los en los siguientes 2 días al parto. Aunque no se encontraron diferencias entre los 2 métodos de laboratorio, los valores absolutos fueron diferentes. (AU)
Introduction: The objective of the study was to establish the normal range for the levels of antithrombin (AT), protein C (PC), and protein S (PS) in the first week post birth in mother-infant dyads, adjusting for obstetric and perinatal factors, based on 2 different laboratory methods. Methods: We took measurements in 83 healthy term neonates and their mothers, establishing 3 postpartum age groups: 1-2 days, 3 days, and 4-7 days. Results: There were no differences in the levels of any of the proteins between the different age groups in neonates or mothers in the first week post birth. The adjusted analysis found no association with obstetric or perinatal factors. The AT and PC levels were higher in mothers compared to infants (P<.001), while the PS levels were similar in both. Overall, the correlation of maternal and infant protein values was poor, except for the levels of free PS in the first 2 days post birth. Although we found no differences based on which of the 2 laboratory methods was applied, the absolute values did differ. (AU)
Subject(s)
Humans , Male , Female , Infant, Newborn , Antithrombins , Protein C , Protein S , Mother-Child Relations , Postpartum PeriodABSTRACT
INTRODUCTION: The objective of the study was to establish the normal range for the levels of antithrombin (AT), protein C (PC), and protein S (PS) in the first week post birth in mother-infant pairings, adjusting for obstetric and perinatal factors, based on 2 different laboratory methods. METHODS: Determinations were carried out in 83 healthy term neonates and their mothers, establishing 3 postpartum age groups: 1-2 days, 3 days, and 4-7 days. RESULTS: There were no differences in the levels of any of the proteins between the different age groups in neonates or mothers in the first week post birth. The adjusted analysis found no association with obstetric or perinatal factors. The AT and PC levels were higher in mothers compared to infants (Pâ¯<â¯.001), while the PS levels were similar in both. Overall, the correlation of maternal and infant protein values was poor, except for the levels of free PS in the first 2 days after delivery. Although we found no differences based on which of the 2 laboratory methods was applied, the absolute values did differ.
Subject(s)
Mothers , Protein C , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Pregnancy , Postpartum Period , Thrombin , Protein S , AntithrombinsABSTRACT
La Sociedad Española de Neonatología estableció en el año 2013 los niveles asistenciales de las unidades neonatales en España. Desde entonces, la natalidad en nuestro país, así como la universalización del conocimiento, de las técnicas y de los dispositivos de tratamiento de los pacientes ha evolucionado significativamente. Esta situación obliga a una redefinición de los actuales niveles asistenciales basándose en criterios de calidad que permitan una mejor comparabilidad entre las unidades y supongan un impulso para la mejora en la atención de nuestros recién nacidos. (AU)
The Spanish Society of Neonatology established in 2013 the care levels of the neonatal units in Spain. Since then, the birth rate in our country, as well as the universalization of knowledge, techniques and patient treatment devices, has evolved significantly. This situation forces a redefinition of the current levels of care based on quality criteria that allow better comparability between the units and represents a challenge to improve the care of our newborns. (AU)
Subject(s)
Humans , Neonatology , Pediatrics , Spain , Societies , Quality of Health CareABSTRACT
The Spanish Society of Neonatology established the care levels of the Neonatal Units in Spain in 2013. Since then, the birth rate in our country, as well as the universalization of knowledge, techniques and patient treatment devices, has evolved significantly. This situation forces a redefinition of the current levels of care based on quality criteria that allow better comparability between the Units and represents a challenge to improve the care of our newborns.
Subject(s)
Neonatology , Infant, Newborn , Humans , SpainABSTRACT
Background: During early skin-to-skin contact (ESSC), alterations in peripheral oxygen saturation (SpO2) and heart rate (HR) have been frequently observed. Objectives: This study aimed to determine the incidence of cardiorespiratory events (CREs) during ESSC in healthy term newborns (HTNs) and estimate the association of maternal and neonatal prognostic factors with the risk of CREs. Methods: A pooled analysis of the cohort from a clinical trial involving healthy mother-child dyads during ESSC was performed. Pulse oximetry was employed to continuously monitor SpO2 and HR within 2 h after birth. The individual and combined prognostic relevance of the demographic and clinical characteristics of dyads for the occurrence of a CRE (SpO2 <91% or HR <111 or >180 bpm) was analyzed through logistic regression models. Results: Of the 254 children assessed, 169 [66.5%; 95% confidence interval (95% CI), 60.5-72.5%] had at least one CRE. The characteristics that increased the risk of CRE were maternal age ≥35 years (odds ratio, 2.21; 95% CI, 1.19-4.09), primiparity (1.96; 1.03-3.72), gestational body mass index (BMI) >25 kg/m2 (1.92; 1.05-3.53), and birth time between 09:00 p.m. and 08:59 a.m. (2.47; 1.02-5.97). Conclusion: CREs were more frequent in HTNs born during nighttime and in HTNs born to first-time mothers, mothers ≥35 years, and mothers with a gestational BMI >25 kg/m2. These predictor variables can be determined during childbirth. Identification of neonates at higher risk of developing CREs would allow for closer surveillance during ESSC.
ABSTRACT
Perinatal Palliative Care is a model of care designed to prevent and treat the physical, spiritual, emotional, and social needs of fetuses and newborn infants with life-threatening or life-limiting conditions. The care extends to the infant's family. It is delivered by an interdisciplinary team to improve the quality of life from the time of diagnosis (possibly in utero) into death and bereavement (days, months or years later). To guarantee the access of this vulnerable population to high quality palliative care, structured programs and protocols need to be further developed in tertiary hospitals that treat highly complex obstetric and neonatal pathologies. Basic training is required for all the professionals involved.
Subject(s)
Bereavement , Palliative Care , Child , Female , Humans , Infant , Infant, Newborn , Perinatal Care , Pregnancy , Quality of LifeABSTRACT
Los cuidados paliativos perinatales son una forma de atención clínica diseñada para anticipar, prevenir y tratar el sufrimiento físico, psicológico, social y espiritual de los fetos y recién nacidos con enfermedades limitantes o amenazantes de la vida, que se extiende a sus familias. Se trata de una atención interdisciplinaria y coordinada que busca ofrecer la mejor calidad de vida posible, desde el diagnóstico (muchas veces intraútero) hasta el fallecimiento y el duelo (días, meses o años después). Los cuidados paliativos perinatales constituyen una prestación de salud básica dirigida a una población particularmente vulnerable. Para garantizar el acceso a una atención de calidad es esencial desarrollar programas estructurados y protocolos clínicos en todos los hospitales terciarios que atienden patología obstétrica y neonatal de alta complejidad. Se requiere también una formación básica de todos los profesionales implicados.(AU)
Perinatal palliative care is a model of care designed to prevent and treat the physical, spiritual, emotional, and social needs of fetuses and newborn infants with life-threatening or life-limiting conditions. The care extends to the infant's family. It is delivered by an interdisciplinary team to improve the quality of life from the time of diagnosis (possibly in utero) into death and bereavement (days, months, or years later). To guarantee the access of this vulnerable population to high quality palliative care, structured programs and protocols need to be further developed in tertiary hospitals that treat highly complex obstetric and neonatal pathologies. Basic training is required for all the professionals involved.(AU)
Subject(s)
Humans , Pregnancy , Infant, Newborn , Pediatrics , Palliative Care , Perinatal Care , Infant, Newborn, Diseases , Quality of Life , SpainABSTRACT
INTRODUCTION: Early skin-to-skin contact (ESSC) is associated with rare, sudden, unexpected postnatal collapse episodes. Placing the newborn in ESSC closer to an upright position may reduce the risk of airway obstruction and improve respiratory mechanics. This study assessed whether a greater inclination of the mother's bed during ESSC would reduce the proportion of healthy term newborns (HTNs) who experienced episodes of pulse oximeter saturation (SpO2) <91%. METHODS: We conducted a multicenter randomized controlled trial comparing the effect of the mother's bed incline, 45° versus 15°, on desaturation in HTNs during ESSC. Before delivery on 1,271 dyads, randomization was conducted, and stringent criteria to select healthy mothers and term newborns were monitored until after birth. Preductal SpO2 was continuously monitored between 10 min and 2 h after birth. The primary outcome was the occurrence of at least one episode of SpO2 <91%. RESULTS: 254 (20%) mother-infant dyads were eligible for analysis (45°, n = 126; 15°, n = 128). Overall, 57% (95% confidence interval [CI]: 51%-63%) of newborns showed episodes of SpO2 <91%. The proportion of infants with SpO2 <91% episodes was 52% in 45° and 62% in 15° (relative risk: 0.80; 95% CI: 0.6-1.07). CONCLUSIONS: We did not show that a high mother bed inclination during ESSC led to significantly fewer HTNs who experienced episodes of SpO2 <91%. Desaturation episodes from 10 min to 2 h after birth occurred in more than half of HTNs.
Subject(s)
Mother-Child Relations , Mothers , Breast Feeding , Female , Humans , Infant , Infant, Newborn , Oxygen , SkinABSTRACT
OBJECTIVE: To develop and test the Neonatal Encephalopathy-Rating Scale (NE-RS), a new rating scale to grade the severity of neonatal encephalopathy (NE) within the first 6 hours after birth. STUDY DESIGN: A 3-phase process was conducted: (1) design of a comprehensive scale that would be specific, sensitive, brief, and unsophisticated; (2) evaluation in a cohort of infants with neonatal encephalopathy and healthy controls; and (3) validation with brain magnetic resonance imaging findings and outcome at 2 years of age. RESULTS: We evaluated the NE-RS in 54 infants with NE and 28 healthy infants. The NE-RS had excellent internal consistency (Cronbach alpha coefficient: 0.93 [95% CI 0.86-0.94]) and reliability (intraclass correlation coefficient in the NE cohort 0.996 [95% CI 0.993-0.998; P < .001]). Alertness, posture, motor response, and spontaneous activity were the top discriminators for degrees of NE. The cut-off value for mild vs moderate NE was 8 points (area under the curve [AUC] 0.99, 95% CI 0.85-1.00) and for moderate vs severe NE, 30 points (AUC 0.93, 95% CI 0.81-0.99). The NE-RS was significantly correlated with the magnetic resonance imaging score (Spearman Rho 0.77, P < .001) and discriminated infants who had an adverse outcome (AUC 0.91, 95% CI 0.83-0.99, sensitivity 0.82, specificity 0.81, positive predictive value 0.87, negative predictive value 0.74). CONCLUSIONS: The NE-RS is reliable and performs well in reflecting the severity of NE within the first 6 hours after birth. This tool could be useful when assessing clinical criteria for therapeutic hypothermia in NE.
Subject(s)
Brain Diseases/diagnosis , Infant, Newborn, Diseases/diagnosis , Severity of Illness Index , Brain/diagnostic imaging , Case-Control Studies , Cohort Studies , Humans , Infant , Infant, Newborn , Magnetic Resonance Imaging , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
BACKGROUND: Early mother-child skin-to-skin contact (SSC) in the first 2 h postpartum is highly beneficial for both mother and child. However, cases have been reported of newborns who have experienced apparently life-threatening events (ALTEs) or sudden death during this procedure. The causes of these events are unknown. Newborn's prone position could influence the onset of these events but there is very little evidence to support any recommendation. We hypothesize that newborns' breathing obstruction episodes increase as mothers lie more horizontally. The main objective of this study is to compare the occurrence of desaturation and bradycardia episodes as a function of mother's bed incline. The study is designed as a randomized, controlled, assessor blind, multicenter, superiority trial with two parallel groups and 1:1 allocation ratio. METHODS: The study participants will be full-term healthy mother-newborn dyads from ten hospitals in Spain. Participants will be randomly assigned to one of two study arms defined by mother's bed inclination (45° or 15°). The planned sample size is 5866. Centralized permuted blocks randomization and assessor blinding will be implemented. The newborns will be monitored remotely with pulse oximetry, from 10 min to 2 h after delivery. We established SO2 and heart rate (HR) limit alarms, as well as an action protocol in the event of alarm activation. The primary outcome is the number of healthy newborns who undergo episodes of SO2 ≤ 90%. Secondary outcomes are the mean SO2 level, the number of newborns who experience episodes of SO2 ≤ 85%, the time to SSC discontinuation due to abnormal SO2 or HR, and episodes of HR < 111 beats per minute (bpm) or > 180 bpm. Subgroups and pooled analysis will be performed to identify if breast-feeding and mother and child positions favor the occurrence of desaturation or bradycardia episodes. DISCUSSION: A simple intervention such as modifying mother's bed angle of inclination while in SSC with her child during the first 2 h postpartum could favor newborn's hemodynamic and respiratory stabilization and thus contribute to reducing the onset of ALTEs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02585492 . Registered on 22nd October 2015. PROTOCOL VERSION: 2 (30th June 2015).
Subject(s)
Mother-Child Relations , Oxygen/metabolism , Randomized Controlled Trials as Topic , Beds , Data Interpretation, Statistical , Female , Heart Rate , Humans , Infant, Newborn , Outcome Assessment, Health Care , Research DesignABSTRACT
The objective of this study was to evaluate the heritability of neonatal arterial ischemic stroke (NAIS) in relation to family history of thromboembolic event, maternal diseases, and thrombophilia in both parents ( F5G1691A, F2G20210A, and MTHFRC677 T mutations). Forty-two consecutive infants ≥36 weeks of gestation <28 days of life with acute symptomatic NAIS and their parents, as well as 129 controls, were prospectively recruited. Information on maternal data (age, body mass index, oral contraception, migraine, epilepsy, hypertension, and immune disease) and a 3-generation pedigree regarding myocardial infarction, pulmonary embolism, cerebrovascular event, and deep vein thrombosis were obtained. Thrombophilia and maternal diseases did not differ between cases and controls, except for the use of oral contraceptives (more frequent in mothers of controls). No differences were found regarding each studied antecedent of thromboembolic event in the families. The NAIS group showed a higher presence of positive family history among second-degree maternal relatives than did the control infants (odds ratio 4.10; 95% confidence interval 1.29-12.99). Our study does not support the hypothesis that common genetic thrombophilia or familial predisposition to thromboembolic events is associated with the occurrence of idiopathic NAIS.
Subject(s)
Brain Ischemia/genetics , Factor V/genetics , Infant, Newborn, Diseases/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Point Mutation , Pregnancy Complications, Hematologic/genetics , Stroke/genetics , Thrombin/genetics , Thrombophilia/genetics , Female , Humans , Infant, Newborn , Male , PregnancySubject(s)
Alleles , Factor V/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Mutation , Prothrombin/genetics , Stroke/genetics , Case-Control Studies , Genetic Association Studies , Genetic Predisposition to Disease , Genotype , Humans , Infant, Newborn , Multicenter Studies as Topic , PhenotypeABSTRACT
OBJECTIVES: The objectives are to 1) determine whether there is a positive correlation between the severity of hypoxic-ischemic encephalopathy and multiple organ dysfunction and 2) evaluate the organ dysfunction pattern in infants with hypoxic-ischemic encephalopathy in the hypothermia era. DESIGN: Retrospective observational study of prospective data collected between April 2009 and December 2012. SETTING: The study took place in the neonatal ICU of Hospital Sant Joan de Déu-Hospital Clínic of Barcelona. PATIENTS: Prospective consecutive newborns with greater than or equal to 36 weeks of gestation, greater than or equal to 1,800 g of weight at birth, and a diagnosis of hypoxic-ischemic encephalopathy was included. INTERVENTIONS: Severity of hypoxic-ischemic encephalopathy was established before starting controlled hypothermia. Six organ systems and 23 clinical and laboratory variables were studied by means of an asymmetrical grading scale. Data were recorded daily during the first 72 hours of life. MEASUREMENTS AND MAIN RESULTS: Seventy-nine patients were studied. All presented with multiple organ dysfunction on day 1. There were differences in the number of affected organs on day 1 according to hypoxic-ischemic encephalopathy stage (p < 0.001). Scale scores correlated positively with the severity of hypoxic-ischemic encephalopathy (area under the curve ranged from 0.77 to 0.87 on every day studied). There were significant differences in the severity of dysfunction of each organ system among the three hypoxic-ischemic encephalopathy stages (p < 0.05). Although the most frequently involved were hepatic and pH and electrolyte imbalance, the most severely affected were the respiratory and cardiovascular systems. CONCLUSIONS: In the hypothermia era, multiple organ dysfunction continues to be almost universal in newborns with hypoxic-ischemic encephalopathy. There is a high correlation between the severity of hypoxic-ischemic encephalopathy and multiple organ dysfunction during the first 3 days of life. A high index of suspicion of relevant multiple organ dysfunction is required in infants admitted with a diagnosis of severe hypoxic-ischemic encephalopathy. Patients with moderate hypoxic-ischemic encephalopathy present wide variability in the severity of multiple organ dysfunction. In the absence of multiple organ dysfunction, a perinatal hypoxic-ischemic origin of acute severe neonatal encephalopathy should be carefully reconsidered.
Subject(s)
Hypothermia, Induced , Hypoxia-Ischemia, Brain/diagnosis , Multiple Organ Failure/etiology , Severity of Illness Index , Female , Humans , Hypoxia-Ischemia, Brain/therapy , Infant, Newborn , Intensive Care Units, Neonatal , Male , Multiple Organ Failure/diagnosis , Prognosis , Retrospective StudiesABSTRACT
BACKGROUND: The notion of Palliative Care (PC) in neonatal and perinatal medicine has largely developed in recent decades. Our aim was to systematically review the literature on this topic, summarise the evolution of care and, based on the available data, suggest a current standard for this type of care. METHODS: Data sources included Medline, the Cochrane Library, CINAHL, and the bibliographies of the papers retrieved. Articles focusing on neonatal/perinatal hospices or PC were included. A qualitative analysis of the content was performed, and data on the lead author, country, year, type of article or design, and direct and indirect subjects were obtained. RESULTS: Among the 1558 articles retrieved, we did not find a single quantitative empirical study. To study the evolution of the model of care, we ultimately included 101 studies, most of which were from the USA. Fifty of these were comments/reflections, and only 30 were classifiable as clinical studies (half of these were case reports). The analysis revealed a gradual conceptual evolution of the model, which includes the notions of family-centered care, comprehensive care (including bereavement) and early and integrative care (also including the antenatal period). A subset of 27 articles that made special mention of antenatal aspects showed a similar distribution. In this subset, the results of the four descriptive clinical studies showed that, in the context of specific programmes, a significant number of couples (between 37 and 87%) opted for PC and to continue with the pregnancy when the foetus has been diagnosed with a lethal illness. CONCLUSIONS: Despite the interest that PC has aroused in perinatal medicine, there are no evidence-based empirical studies to indicate the best model of care for this clinical setting. The very notion of PC has evolved to encompass perinatal PC, which includes, among other things, the idea of comprehensive care, and early and integrative care initiated antenatally.
Subject(s)
Palliative Care , Perinatal Care , Prenatal Care , Comprehensive Health Care , Female , Hospice Care , Humans , Infant, Newborn , Models, Theoretical , PregnancyABSTRACT
OBJECTIVE: Soluble preadipocyte factor 1 (Pref-1) inhibits adipocyte differentiation. We tested whether circulating levels of soluble Pref-1 are higher in smaller fetuses. RESEARCH DESIGN AND METHODS: We performed longitudinal assessments of circulating Pref-1 in infants born appropriate for gestational age (AGA) or small for gestational age (SGA) and also in late-gestational women and in newborns on days 2 and 3. RESULTS: At birth, Pref-1 levels were ~100-fold higher than in adults, being in SGA fetuses ~50% higher than in AGA fetuses. By age 4 months, Pref-1 had reached near-adult levels and the original AGA versus SGA difference had disappeared. Pref-1 levels were low in late-gestational women and were still elevated in newborns. CONCLUSIONS: Pref-1 is abundantly present in the fetus, is higher in SGA than in AGA fetuses, and is likely to be of fetal origin. We speculate that Pref-1 in early life contributes to variation in postnatal adipocyte numbers, in the subsequent expandability of adipose tissue, and thus in the susceptibility to diabetes in later life.
Subject(s)
Infant, Newborn/blood , Intercellular Signaling Peptides and Proteins/blood , Membrane Proteins/blood , Adult , Age Factors , Birth Weight/physiology , Calcium-Binding Proteins , Female , Fetus/metabolism , Follow-Up Studies , Gestational Age , Humans , Infant , Infant, Small for Gestational Age/blood , Intercellular Signaling Peptides and Proteins/analysis , Intercellular Signaling Peptides and Proteins/metabolism , Male , Membrane Proteins/analysis , Membrane Proteins/metabolism , PregnancyABSTRACT
Fundamentos. La encefalopatía hipóxico-isquémica (EHI) perinatal en el recién nacido a término o casi a término es una importante causa de morbimortalidad en el periodo neonatal y de discapacidad ulterior en el niño 1-3. Las implicaciones médicas, sociales y legales que asocia la EHI son importantes y condicionan que ésta constituya un problema de salud pública. Durante todo el siglo XX no se ha dispuesto de ninguna aproximación terapéutica específica para prevenir o aminorar el daño cerebral asociado a esta agresión perinatal. Afortunadamente este panorama ha cambiado, ya que en los últimos años ha tenido lugar un importante avance terapéutico específico para la agresión hipóxico-isquémica del SNC: la hipotermia moderada sostenida. Diversos ensayos clínicos han mostrado que la reducción de la temperatura cerebral en 3-4ºC mediante un enfriamiento corporal total o selectivo del cabeza, iniciado antes de las 6 horas de vida y mantenido durante 72 horas, constituye una intervención eficaz para reducir la mortalidad y la discapacidad mayor en los supervivientes 7-9. Resultado. Este documento presenta las demostraciones que han conducido a que la EHI haya dejado de ser una condición huérfana de intervención terapéutica y examina brevemente los nuevos retos asistenciales que plantea(AU)
Background. Perinatal hypoxic-ischemic encephalopathy (HIE) in the term or near term newborn infant represents a major cause of morbidity and mortality during the neonatal period and subsequent disability in childhood. Medical, social, and legal implications of HIE are important and make this disease a public health problem. During the 20th century, measures aimed at preventing or ameliorating the brain damage associated with this perinatal aggression have been lacking. Fortunately, this situation seems to have changed in recent years with the use of moderate sustained hypothermia. Several clinical trials have shown that a reduction of cerebral temperature by 3-4oC via total body cooling or selective head cooling, initiated within the first 6 hours of life and maintained during 73 hours, is an effective intervention to decrease mortality and major disability among survivors. Result. In this manuscript we review the data that shows how HIE is no longer a disease with no therapeutic options, and we analyze the challenges that this new approach will pose on our healthcare system(AU)
Subject(s)
Humans , Male , Female , Infant, Newborn , Hypothermia, Induced/methods , Hypothermia, Induced , Cryotherapy/methods , Hypoxia, Brain/complications , Hypoxia, Brain/diagnosis , Brain Ischemia/complications , Asphyxia Neonatorum/complications , Asphyxia Neonatorum/diagnosis , Brain Diseases/complications , Brain Diseases/diagnosis , Hypothermia, Induced/trends , Asphyxia Neonatorum/physiopathology , Brain Diseases/physiopathologyABSTRACT
BACKGROUND: A combined Haemophilus influenzae type b and Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib-MenC-TT) may be a convenient alternative to separate Hib and MenC conjugate vaccines. METHODS: Healthy infants randomized in a previous study for priming at 2, 4, and 6 months: Hib-MenC-TT primed group, 3 doses of Hib-MenC-TT + DTPa-HBV-IPV (N = 87); MenC-TT primed group, 2 doses of MenC-TT (NeisVac-C; Baxter Healthcare SA, Zuürich, Switzerland) + 3 doses of DTPa/Hib containing vaccines (N = 178); MenC-CRM primed group, 3 doses of MenC-CRM197(Meningitec; Wyeth Corporation Delaware, Madison, NJ) + DTPa-HBV-IPV/Hib (N = 93). At 13-14 months of age, Hib-MenC-TT and MenC-TT primed groups received a Hib-MenC-TT booster dose and the MenC-CRM primed group a booster dose of DTPa-HBV-IPV/Hib. Blood samples were taken before and at 1 and 18 months postbooster. RESULTS: Before the booster dose, persistence of anti-polyribosyl ribitol phosphate (PRP) antibody concentration > or =0.15 microg/mL in the Hib-MenC-TT (96.4%) and MenC-TT (96.1%) primed groups and of MenC bactericidal titers > or =1:8 in the Hib-MenC-TT primed group (96.3%) was statistically significantly higher than in the MenC-CRM primed group (86.4% and 85.4%, respectively). One month after the Hib-MenC-TT booster, 99.2% subjects in the Hib-MenC-TT primed + MenC-TT primed pooled groups had anti-PRP levels > or =1 microg/mL, and 99.6% had SBA-MenC titers > or =1:128. The Hib-MenC-TT booster tended to be less reactogenic than the DTPa-HBV-IPV/Hib control and no serious adverse events related to vaccination were reported. Eighteen months after boosting with Hib-MenC-TT, SBA-MenC titers > or =1:8 persisted in 92.7% subjects and anti-PRP > or =0.15 microg/mL persisted in 99.4%. CONCLUSIONS: Primary immunization with 3 doses of Hib-MenC-TT coadministered with DTPa-HBV-IPV induced antibodies that persisted up to the second year of life. The Hib-MenC-TT booster administered to primed toddlers induced robust and persistent antibody responses to both the Hib and MenC components and had an acceptable safety profile.
Subject(s)
Antibodies, Bacterial/blood , Haemophilus Vaccines/immunology , Immunization, Secondary , Tetanus Toxoid/immunology , Female , Haemophilus Vaccines/adverse effects , Humans , Infant , Longitudinal Studies , Male , Microbial Viability , Neutralization Tests , Polysaccharides/immunology , Tetanus Toxoid/adverse effects , Time Factors , Vaccines, Conjugate/adverse effects , Vaccines, Conjugate/immunologySubject(s)
Catholicism , Condoms , HIV Infections/prevention & control , Religion and Science , Global Health , HumansABSTRACT
BACKGROUND: This phase II study evaluated the immunogenicity and reactogenicity of primary vaccination with a novel Hib-MenC conjugate vaccine (GlaxoSmithKline [GSK] Biologicals) coadministered with DTPa-HBV-IPV (GSK Biologicals) at 2, 4 and 6 months. METHODS: Healthy infants were randomized to receive Hib-MenC coadministered with DTPa-HBV-IPV (N = 117) or MenC-CRM (Wyeth) coadministered with DTPa-HBV-IPV/Hib (GSK Biologicals; N = 120) at 2, 4 and 6 months. Antibody concentrations were measured before vaccination and after doses 2 and 3. Solicited local and general symptoms, unsolicited symptoms and serious adverse events (SAEs) were recorded. RESULTS: All subjects in the Hib-MenC group had seroprotective titers of anti-PRP antibodies (>or=0.15 microg/mL) and SBA-MenC titers (>or=1:8) 1 month after the third dose. These responses were noninferior to those seen in the control group, in which a 99.1% seroprotection rate was observed for both Hib and MenC. At that time, anti-PRP and SBA-MenC GMTs were significantly higher in the Hib-MenC group (12.8 microg/mL and 2467.1 microg/mL, respectively) than in the control group (3.8 microg/mL and 1833.7 microg/mL). High seroprotection rates were already observed after the second dose of Hib-MenC; 96.4% and 100% of subjects were seroprotected to Hib and MenC, respectively. Immune responses to coadministered antigens were unimpaired; seroprotection/vaccine response rates >or=96.5% were recorded postdose 3 in the Hib-MenC group. No differences in reactogenicity were seen between the 2 study groups. CONCLUSIONS: Coadministration of a Hib-MenC conjugate vaccine with DTPa-HBV-IPV is well tolerated and immunogenic, and does not impair the immune response to any of the coadministered antigens.
Subject(s)
Haemophilus Vaccines/administration & dosage , Meningococcal Vaccines/administration & dosage , Neisseria meningitidis, Serogroup C/immunology , Polysaccharides, Bacterial/administration & dosage , Vaccines, Combined/administration & dosage , Bacterial Capsules , Diphtheria-Tetanus-Pertussis Vaccine , Female , Haemophilus Vaccines/adverse effects , Haemophilus Vaccines/immunology , Hepatitis B Vaccines , Humans , Infant, Newborn , Male , Meningococcal Vaccines/adverse effects , Meningococcal Vaccines/immunology , Poliovirus Vaccine, Inactivated , Polysaccharides, Bacterial/adverse effects , Polysaccharides, Bacterial/immunology , Vaccines, Combined/adverse effects , Vaccines, Combined/immunologyABSTRACT
BACKGROUND: This study evaluated the concurrent use of meningococcal C tetanus conjugate (MenC-TT) vaccine (NeisVac-C) with DTaP-based combinations, according to 2 vaccination schedules, one of which included hepatitis B vaccination at birth (Trial DTaP-HBV-IPV/Hib-097). METHODS: Healthy infants were randomized to receive either DTaP-HBV-IPV/Hib (Infanrix hexa) at 2, 4, and 6 months (N = 115) or HBV at birth followed by DTaP-HBV-IPV/Hib at 2 and 6 months and DTaP-IPV/Hib (Infanrix-IPV Hib) at 4 months (N = 115). In both groups 2 doses of MenC-TT conjugate were coadministered at 2 and 4 months, and compared with 3 doses of MenC-CRM197 conjugate (Meningitec) coadministered at 2, 4, and 6 months with DTaP-HBV-IPV/Hib (N = 120). Antibody concentrations were measured at 2, 6 and 7 months. Solicited local and general symptoms, unsolicited symptoms, and serious adverse events (SAEs) were recorded. RESULTS: All MenC-TT recipients had seroprotective concentrations of anti-PRP antibodies (> or = 0.15 microg/mL) 1 month after the third vaccine dose and all had SBA-MenC titers > or = 1:8 after the second dose of MenC-TT. These responses were noninferior to those seen after 3 doses of DTaP-HBV-IPV/Hib and MenC-CRM. Anti-PRP antibody GMCs were significantly higher in MenC-TT than MenC-CRM vaccinees (7.9, 7.3, 3.8 microg/mL, respectively). Immune responses to all other coadministered antigens were unimpaired, with seroprotection/seropositivity rates > or = 98.1% in MenC-TT vaccinees. All schedules studied were well tolerated, with no differences in reactogenicity between the study groups. CONCLUSIONS: Coadministration of DTaP-HBV-IPV/Hib or DTaP-IPV/Hib with 2 doses of MenC-TT conjugate vaccine is safe, well tolerated, and immunogenic, with no impairment of the response to the coadministered antigens.
