Thesis (PhD)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: Introduction: An association between maternal human immunodeficiency virus (HIV) infection and Necrotizing Enterocolitis (NEC) in preterm infants has been reported. The impact of probiotics in an HIV-exposed very low birth weight (VLBW) infant on the occurrence of NEC is uncertain at present; however it is known that probiotics have protective effects against inflammation and prevent NEC. Postnatal growth restriction is a major issue in preterm, especially extremely-low-birth-weight (ELBW) infants and probiotics have been found to improve feeding tolerance in preterm infants. Human milk oligosaccharides (HMO) also known as the prebiotics of human milk, are known to have bifidogenic and anti-adhesive effects. Infants that receive human milk show a reduced incidence of NEC compared to those who receive infant formula. Very little is known about the composition of breast milk in the HIV-infected mother. Objective: The primary objective of the study was to assess the effect of probiotics on the incidence and severity of NEC in high-risk infants born to HIV-positive and HIV-negative women. The secondary objectives were to assess the effect of probiotic administration on feeding tolerance and growth outcomes of HIV-exposed but uninfected preterm infants, to describe the HMO composition of HIV-infected mothers breast milk and lastly to determine if HMO composition affects the incidence of NEC in HIV-exposed preterm very low birth weight infants. Patients and Methods: A randomized, double blind, placebo controlled trial was conducted for the period July 2011 to August 2012. HIV-exposed and HIV-unexposed premature (<34 weeks gestation) infants with a birth weight of ≥500g and ≤1250g were randomized to receive either a probiotic or a placebo. The probiotic consisted of 1x109 CFU, L. rhamnosus GG and B. infantis per day and was administered for 28 days. NEC was graded according to Bell’s criteria. Anthropometrical parameters and daily intakes were monitored. Breats milk samples were analysed for oligosaccharide content. Results: 74 HIV-exposed and 110 HIV-unexposed infants were enrolled and randomized (mean birth-weight, 987g; mean gestational 28.7 weeks). The incidence of death and NEC did not differ significantly between the HIV-exposed and unexposed groups but a significantly higher NEC incidence was found in the control group. There was no difference in the average daily weight gain for treatment groups or HIV exposure. The HIV-exposed group achieved significantly higher z-scores for length and head circumference at day 28 than the unexposed group (p<0.01 and p=0.03, respectively). There were no differences in the incidence of any signs of feeding intolerance and abdominal distension between the groups. Our results show significantly higher absolute concentrations of 2’-fucosyllactose, laco-N-tetraose and lacto-N-fucopentaose 1 and higher relative abundance of 3’-sialyllactose, difucosyl-lacto-N-tetraose and fucosyl-disialyllacto-N-hexaose in HIV-infected compared to -uninfected Secretor women. DSLNT concentrations were significantly lower in the breast milk of mothers whose infants developed NEC compared to infants without NEC. Conclusion: Probiotic supplementation reduced the incidence of NEC in the premature infants; however results failed to show a lower incidence of NEC in HIV-exposed premature infants. Probiotic supplementation did not affect growth outcomes or the incidence of any signs of feeding intolerance in HIV-exposure. The data confirms previous reports that HIV-infected mothers have higher 3’sialyllactose milk concentrations. Most intriguing though, the data also indicates that low levels of DSLNT in the mother’s milk increase the infant’s risk for NEC, which is in accordance with results from previously published animal studies and warrants further investigation. / AFRIKAANSE OPSOMMING: Inleiding: ʼn Verwantskap tussen moederlike menslike immuniteitsgebreksvirus (MIV) en nekrotiserende enterokolitis (NEK) in premature babas is aangemeld. Die impak van probiotika in ʼn MIV-blootgestelde baie lae geboortemassa (BLGM) baba op die voorkoms van NEK is tans nog onseker, maar dit is wel bekend dat probiotika ʼn beskermende effek het teen inflammasie en die voorkoms van NEK. Nageboortelike groei beperkings is ʼn groot probleem in premature, veral ekstreme lae geboortemassa (ELGM) babas. Daar is gevind dat probiotika voeding toleransie in premature babas kan verbeter. Menslike melk oligosakkariede (MMO), ook bekend as die prebiotika van menslike melk, is bekend om bifidogeniese en anti-kleef effekte te hê. Babas wat moedersmelk ontvang toon ʼn verlaagde voorkoms van NEK in vergelyking met diegene wat baba formule melk ontvang. Baie min inligting is bekend oor die samestelling van borsmelk in die MIV-positiewe moeder. Doel: Die primêre doel van die studie was om die effek van probiotika op die voorkoms en die graad van NEK in hoë risiko babas van MIV-positiewe en MIV-negatiewe vroue te bepaal. Die sekondêre doelwitte was om die effek van probiotika op voeding verdraagsaamheid en groei uitkomste van MIV-blootgestelde, maar nie- geinfekteerde premature babas te evalueer sowel as die MMO samestelling van MIV-positiewe moeders se borsmelk te beskryf en laastens om die invloed van die MMO samestelling op die voorkoms van NEK in baie lae geboortegewig MIV-blootgestelde premature babas te beskryf. Pasiënte en Metodes: ʼn Gerandomiseerde, dubbelblinde, plasebo-beheerde studie is vir die tydperk Julie 2011 tot Augustus 2012 onderneem. MIV-blootgestelde en nie-blootgestelde premature (<34 weke) babas met 'n geboorte gewig van ≥500g en ≤1250g was ewekansig verdeel om probiotika of plasebo te ontvang. Die probiotika het bestaan uit 1x109 kolonie vormende eenhede, L. rhamnosus GG en B. infantis per dag en is toegedien vir 28 dae. NEK is gegradeer volgens Bell se kriteria. Antropometriese parameters en daaglikse inname is gemonitor. Borsmelk monsters is geanaliseer vir oligosakkaried inhoud. Resultate: 74 MIV-blootgestelde en 110 MIV-nie-blootgestelde babas is ingesluit en ewekansig ingedeel (gemiddelde geboorte gewig, 987g, gemiddelde gestasie 28,7 weke). Die voorkoms van die sterftes en NEK het nie beduidend verskil tussen die MIV-blootgestelde en nie-blootgestelde groepe nie, maar 'n beduidende verskil is gevind vir NEK voorkoms tussen die studie en die kontrole groep. Daar was geen verskil in die gemiddelde daaglikse gewigstoename tussen die behandelings groepe of MIV-blootstelling nie. Die MIV-blootgestelde groep het beduidend hoër z-tellings vir lengte en kopomtrek op dag 28 getoon teenoor die nie-blootgestelde groep (p <0.01 en p = 0,03, onderskeidelik). Daar was geen verskille in die voorkoms van voeding onverdraagsaamheid en abdominale distensie tussen die twee groepe nie. Ons resultate dui op aansienlik hoër absolute konsentrasies van 2'-fucosyllactose, laco-N-tetraose en lakto-N-fucopentaose 1 en hoër relatiewe voorkoms van 3'-sialyllactose, difucosyl-lakto-N-tetraose en fucosyl-disialyllacto-N-hexaose in MIV-positiewe vroue in vergelyking met-negatiewe Sekretor vroue. DSLNT konsentrasies was aansienlik laer in die melk van moeders wie se babas NEK ontwikkel het in vergelyking met babas sonder NEK. Gevolgtrekking: Probiotika aanvullings verminder die voorkoms van NEK in premature babas, maar die resultate kon nie ʼn laer voorkoms van NEK in MIV-blootgestelde premature babas bewys nie. Probiotiese aanvulling het geen invloed op groei uitkomste of die voorkoms van voeding onverdraagsaamheid in MIV-blootstelling getoon nie. Die data bevestig vorige verslae wat aandui dat MIV-besmette moeders hoër 3'sialyllactose borsmelk konsentrasies het. ʼn Interessante aspek is dat lae vlakke van DSLNT in die moeder se melk beduidend is van ʼn verhoogde risiko vir NEK, wat in ooreenstemming is met die resultate uit voorheen gepubliseerde dier studies en regverdig verdere ondersoeke.

Esofagite Eosinofílica é uma doença inflamatória crônica restrita ao esôfago e imune mediada por antígenos. Sua prevalência descrita varia desde 0,4%, numa população geral, até 15% em pacientes com sintomas de disfagia. Já se conhece sua associação com doenças atópicas, anafilaxia e alergia alimentar, sendo o leite de vaca um dos principais alimentos envolvidos. Existem relatos recentes de casos em que pacientes foram diagnosticados com esofagite eosinofílica após serem submetidos à imunoterapia oral com o alimento causador de sua alergia alimentar mediada por IgE. Porém, em nenhum destes casos foi avaliado previamente se os mesmos pacientes já não apresentavam eosinofilia esofágica latente e/ou sintomas subjetivos sugestivos da doença. Considerando que, atualmente, um dos tratamentos mais promissores para alergia alimentar é a imunoterapia oral, justificou-se a necessidade de entender se esofagite eosinofílica seria de fato uma complicação do tratamento, ou se seria uma condição pré ou coexistente. Portanto, o objetivo deste trabalho foi avaliar a frequência de eosinofilia esofágica em pacientes com anafilaxia à proteína do leite de vaca. Foram analisados 89 pacientes matriculados no ambulatório de alergia alimentar do HC-FMUSP, com mediana de idade de 8 anos e que apresentavam anafilaxia ao leite de vaca. Todos foram submetidos à endoscopia digestiva alta com biópsias de esôfago, estomago e duodeno. Dados demográficos, comorbidades atópicas, uso de medicações e sintomas gastrointestinais foram analisados e comparados. A frequência de eosinofilia esofágica foi de 38,2% (34 de 89 pacientes). Em 15 dos 34 pacientes com eosinofilia esofágica, foi completada a investigação para esofagite eosinofílica com uso de inibidor de bomba de prótons em dose plena por 8 semanas antes de uma segunda endoscopia. Identificou-se, portanto, cinco pacientes (7,1%) com eosinofilia esofágica responsiva a inibidor de bomba de prótons e 10 pacientes com esofagite eosinofílica (14,2%). No grupo total de pacientes com eosinofilia esofágica (n=34) encontrou-se 29,4% de pacientes com quadro clínico gastrointestinal ausente; 23,5% oligossintomáticos, e apenas 47% com sintomas sugestivos de disfunção esofágica e, destes últimos, nem todos apresentavam sintomas esofágicos persistentes. Pode-se concluir que a frequência de esofagite eosinofílica descrita no grupo estudado foi significativamente superior à estimada na população geral e uma das mais altas descritas em grupos de pacientes com fatores de risco específicos. Também foi observada uma grande parcela de pacientes com eosinofilia esofágica, sendo muitos assintomáticos ou oligossintomáticos, surgindo o questionamento se esta não seria uma doença latente, de início precoce, insidioso e não relacionada diretamente como complicação de tratamentos atuais / Eosinophilic esophagitis is a chronic inflammatory disease, which occurs in the esophagus and is immune mediated by antigens. Its observed prevalence varies between 0.4% in the general population to 15% in patients with dysphagia. Its association with atopic diseases, anaphylaxis and food allergy has already been recognized. Cow\'s milk is one of the main food sources involved. There are recent reports of cases in which patients were diagnosed with eosinophilic esophagitis after being submitted to oral immunotherapy with the food that causes the IgE mediated allergy. However, in none of these cases was it previously determined if the same patients did not already present latent esophageal eosinophilia and/or subjective symptoms suggestive of the disease. Considering that, currently, one of the most promising treatment for food allergy is oral immunotherapy, the need to understand if eosinophilic esophagitis could be a treatment complication, or if it is a coexistent or preexistent condition, is justified. Therefore, the objective of this study was to evaluate esophageal eosinophilia frequency in patients with anaphylaxis to cow\'s milk protein. We analyzed eighty-nine patients registered in the Food Allergy Unit of the HCFMUSP, with a median age of 8 years, who presented cow\'s milk anaphylaxis. All of them were submitted to digestive endoscopy as well as esophagus, stomach, and duodenum biopsies. We also analyzed and compared demographic data, atopic comorbidities, use of medication, and gastrointestinal symptoms. The frequency of esophageal eosinophilia was 38.2% (34 of 89 patients). In 15 of the 34 patients with esophageal eosinophilia, full investigation for the disease was carried out using a proton pump inhibitor at full dose for eight weeks prior to a second endoscopy. From this, five patients (7.1%) had the proton pump inhibitor-responsive esophageal eosinophilia phenotype, and ten patients were diagnosed with eosinophilic esophagitis (14.2%). In the whole group of patients with esophageal eosinophilia (n = 34), it was found 29.4% of patients with an absent gastrointestinal clinical condition, 23.5% were oligosymptomatic, and only 47% had symptoms suggestive of esophagic dysfunction. Of these, not all presented persistent esophagic symptoms. It is possible to conclude that the frequency of eosinophilic esophagitis observed in this group was significantly higher than the estimated for the general population, and one of the highest observed in groups of patients with specific risk factors. A large portion of patients with esophageal eosinophilia were oligosymptomatic or asymptomatic, raising the question if this would not in fact be a latent disease, with a precocious beginning, insidious and not directly related to current treatments complications

O uso de fármacos durante a lactação é uma prática comum; porém, os tratamentos farmacológicos impõem grandes dúvidas tanto aos profissionais quanto às nutrizes sobre a segurança do uso destes durante este período. A amamentação é uma forma de vínculo entre mãe e bebê e está associada a diversos benefícios nutricionais, imunológicos, cognitivos, psicoafetivos, econômicos e sociais. A depressão é um problema clínico importante durante o período pós-parto, e a vulnerabilidade para o início ou recorrência de sintomas depressivos aumenta a possibilidade de uso de psicofármacos enquanto ocorre a lactação. Os antidepressivos inibidores seletivos da recaptação da serotonina são comumente prescritos para o tratamento destes quadros depressivos, entre eles fluoxetina, sertralina, citalopram e paroxetina, sendo que a maioria destes é excretada no leite materno e há grande variabilidade na quantidade de analitos que pode ser recebida pelo lactente. Bupropiona é um fármaco antidepressivo utilizado para o tratamento do tabagismo e quadros depressivos e tem sua excreção ao leite materno relatada em literatura. Métodos bioanalíticos para determinação da excreção de fármacos antidepressivos foram desenvolvidos e validados por cromatografia líquida acoplada a espectrômetro de massas e cromatografia líquida com detecção ultravioleta. Estes métodos demonstraram serem seletivos, lineares, precisos e exatos, com limites de quantificação de 5 ng/mL (fluoxetina, citalopram e bupropiona) e 20 ng/mL (sertralina e paroxetina) para método por LC-MS e de 200 ng/mL para todos os analitos no método por CLAE-UV. As amostras de leite materno foram coletadas em Banco de Leite de mães que declararam utilizar fluoxetina ou sertralina ou paroxetina e analisados. Os dados de concentração encontrados para os fármacos referidos estão dentro da faixa encontrada em literatura confirmando sua excreção no leite materno. Paroxetina apresentou valores abaixo do limite de quantificação. Das concentrações encontradas no leite materno, foram estimadas as doses absolutas e relativas no lactante, sendo que os resultados demonstraram baixos valores em relação a estas estimativas, podendo os fármacos analisados ser considerados seguros para manutenção do uso durante a lactação. Foi também detectada nas análises por LC-MS a presença de norfluoxetina, metabólito da fluoxetina, confirmando sua excreção nesta matriz. / The use of medications during lactation is a common practice; however pharmacological treatments impose serious doubts to both, professionals and nursing mothers, about the safety of drugs use during this period. Breastfeeding is a natural form of bonding between mother and baby and it is associated with many nutritional, immunological, cognitive, psychoemotional, social and economic benefits. Depression is a major clinical problem during the postpartum period and the vulnerability to onset or recurrence of depressive symptoms increases the possibility of psychotropic drug use during lactation. Selective inhibitors of serotonin reuptake are commonly prescribed for the treatment of depressive disorders, including fluoxetine, sertraline, citalopram and paroxetine. Most of these drugs are excreted in breast milk and there is great variability in the amount of analytes that can be received by the infant. Bupropion is an antidepressant used for tabagism treatment and for depression symptoms; it is also described in literature its excretion into breast milk. Bioanalytical methods for determining the excretion of antidepressants were developed and validated by liquid chromatography coupled to mass spectrometry and liquid chromatography with ultraviolet detection. These methods proved to be selective, linear, precise and accurate with quantification limits of 5 ng/mL (fluoxetine, citalopram e bupropion) and 20 ng/mL (sertraline e paroxetine) for LC-MS method and 200 ng/mL for all analytes in the CLAE-UV method. Human milk samples were collected in milk banks from mothers to which the antidepressants fluoxetine or sertraline or paroxetine were administered, and the concentrations in this matrix were verified. Found concentrations were within the range described in the literature confirming their excretion in the breast milk. Paroxetine presented values less than limit of quantification. From the found concentrations, the absolute and relative doses in nursing were estimated. The results showed low values for these estimates and so the analyzed drugs can be considered safe to continue use during lactation. The presence of norfluoxetine, a metabolite of fluoxetine, was also detected by LC-MS, confirming its excretion in this matrix.

Passive exposure of children to drugs is common, but difficult to ascertain as direct studies are in many cases not possible, and currently available indirect measures of drug exposure, such as maternal reports, are likely to be inaccurate. Novel, indirect methods to evaluate drug exposure in the uterus and early life are needed, and may provide risk estimates that can be later correlated with clinical outcomes. In the studies presented here, I have applied novel methods such as measurement of hair drug concentrations and population pharmacokinetics modeling and simulation to evaluate fetal and infant exposure to drugs and potential associated risks. Testing for methamphetamine allowed demonstration, for the first time, that it freely crosses the human placenta. In contrast, analysis of paired maternal–infant hair showed limited cocaine placental transfer, in agreement with animal models. Results of hair tests from children found in marihuana grow houses and other drug operations showed that passive exposure tends to be higher in infants, likely due to higher dependence on, and proximity to care givers. We also demonstrated the importance of measuring drug metabolites to distinguish between systemic exposure to MDMA and simple external hair contamination secondary to drug present in the home environment. Finally, we developed a population pharmacokinetics and simulation approach to accurately estimate drug excretion into breast milk. This novel technique was applied to fluoxetine and to nifurtimox. Use of our approach allowed us to define, for the first time, the limited extent to which fluoxetine and nifurtimox would be expected to cross into breast milk and estimate potential degree of exposure of breastfed infants. In summary, results presented here support the value of these novel methods for the evaluation of fetal and infant drug exposure and suggest a promising value in estimating risks to children passively exposed to drugs.

Passive exposure of children to drugs is common, but difficult to ascertain as direct studies are in many cases not possible, and currently available indirect measures of drug exposure, such as maternal reports, are likely to be inaccurate. Novel, indirect methods to evaluate drug exposure in the uterus and early life are needed, and may provide risk estimates that can be later correlated with clinical outcomes. In the studies presented here, I have applied novel methods such as measurement of hair drug concentrations and population pharmacokinetics modeling and simulation to evaluate fetal and infant exposure to drugs and potential associated risks. Testing for methamphetamine allowed demonstration, for the first time, that it freely crosses the human placenta. In contrast, analysis of paired maternal–infant hair showed limited cocaine placental transfer, in agreement with animal models. Results of hair tests from children found in marihuana grow houses and other drug operations showed that passive exposure tends to be higher in infants, likely due to higher dependence on, and proximity to care givers. We also demonstrated the importance of measuring drug metabolites to distinguish between systemic exposure to MDMA and simple external hair contamination secondary to drug present in the home environment. Finally, we developed a population pharmacokinetics and simulation approach to accurately estimate drug excretion into breast milk. This novel technique was applied to fluoxetine and to nifurtimox. Use of our approach allowed us to define, for the first time, the limited extent to which fluoxetine and nifurtimox would be expected to cross into breast milk and estimate potential degree of exposure of breastfed infants. In summary, results presented here support the value of these novel methods for the evaluation of fetal and infant drug exposure and suggest a promising value in estimating risks to children passively exposed to drugs.

Hintergrund Ein rascher enteraler Nahrungsaufbau bei Frühgeborenen verkürzt die Zeit der parenteralen Ernährung. Somit lassen sich bestimmte Risikofaktoren beeinflussen, die evt. die Morbiditätshäufigkeit der Kinder senken könnten. Mehrere Kohortenstudien zeigten, dass ein standardisierter Nahrungsaufbau mit einer geringeren Komplikationsrate und einem schnelleren Nahrungsaufbau assoziiert ist. Ziel der Studie ist zu überprüfen, ob ein standardisiertes Ernährungsprogramm einen rascheren und komplikationsärmeren enteralen Nahrungsaufbau bei Frühgeborenen ermöglicht. Patienten und Methode In die vorliegende randomisierte, kontrollierte Studie wurden 99 Frühgeborene mit einem Geburtsgewicht von ≤1750 g aufgenommen. In der Gruppe mit standardisierter Ernährung (ST) wurde der enterale Nahrungsaufbau mit Muttermilch oder gespendeter Frauenmilch nach einem speziell ausgearbeiteten Protokoll durchgeführt. In der Gruppe mit der individuellen Ernährungsform (IN) wurde je nach Bedarf und Zustand des Kindes auch semi-elementare Nahrung (Pregomin®) gefüttert. Über die Steigerungsdynamik und Nahrungspausen wurde hier individuell entschieden. Primäres Zielkriterium war die Dauer bis zum Erreichen der vollenteralen Ernährung. Ergebnisse In der ST-Gruppe war die vollständig enterale Ernährung nach 14,93 ± 9,95 (Median 12) Tagen, in der IN-Gruppe nach 16,23 ± 10,86 (Median 14) Tagen möglich. Es konnte kein signifikanter Unterschied gefunden werden. Nur bei hypotrophen Frühgeborenen erwiesen sich die Unterschiede bei der ST-Gruppe gegenüber der IN-Gruppe als statistisch signifikant: 10,20 ± 4,78 (Median 8,5) vs. 16,73 ± 8,57 (Median 15) Tage (p = 0,045). Die Gewichtsentwicklung verlief in beiden Studiengruppen nicht different. Die Kinder in der ST-Gruppe konnten bei einem Gewicht von 116% des Geburtsgewichtes vollständig enteral ernährt werden, in der IN-Gruppe bei einem Gewicht von 122% des Geburtsgewichtes. Die Inzidenz der nekrotisierenden Enterokolitis (4%) und anderer Komplikationen blieb in beiden Studiengruppen niedrig. Die Diagnose „Ernährungsschwierigkeiten“ wurde mit klaren Symptomen definiert und in der IN-Gruppe doppelt so oft gestellt, wie in der ST-Gruppe (14 vs. 7) Schlussfolgerung Das Standardisieren führte unter den Studienbedingungen nicht zu einer Beschleunigung des Nahrungsaufbaus. Anhand unserer Ergebnisse ist es möglich, dass die hypotrophen Frühgeborenen von der standardisierten Ernährung entsprechend des Ernährungsprotokolls profitieren. Diese Hypothese muss in einer neuen Studie überprüft werden. Diese Kinder konnten schneller vollständig enteral ernährt werden, als Frühgeborene, mit individuellem enteralem Nahrungsaufbau. Ein standardisiertes Nahrungsprotokoll ist im klinischen Alltag durchsetzbar, und darauf aufbauend ein enteraler Nahrungsaufbau unter strenger klinischer Beobachtung ohne Komplikationen erfolgreich durchführbar.

Qualitative and quantitative research methods were employed to evaluate the acceptability and feasibility of HIV-1 infected, urban South African mothers being able to feed their infants heat-treated expressed breast milk (HTEBM). Nutritional status assessment of HIV-infected breastfeeding mothers (n=84) indicated that maternal status was not compromised; mean body mass index 26.8 (4.0) kg/m2, triceps skinfold 14.8 (5.50) mm and hemoglobin 11.6 (1.49) g/dL. However, severely immunocompromised mothers (CD4 + &lt; 200 cells/mm3) were more likely to be anemic. Breastmilk viral loads were also higher in mothers with lower CD4+ cell counts. Community based inquiry on the acceptability of HTEBM was accomplished through in-depth interviews of participants (n=31), at the individual (mothers), family (partners, grandparents, mothers-in-law) and at the community level (traditional healers, daycare worker, health care counselors). Although an unfamiliar concept for all interviewed, overall, HTEBM was found to be an acceptable feeding choice regardless of respondents' gender, age, maternal status, family or community role. Further, data indicated mothers rarely received quality infant feeding counseling, consequently mixed feeding, a high risk for HIV transmission, was a common practice. In a pilot longitudinal study, using mixed-methods, the feasibility of mothers successfully implementing a modified breastfeeding intervention (6 months exclusive breastfeeding (EBF), cessation of breastfeeding, followed by use of HTEBM with complementary diet) was evaluated. The majority of mothers (36/66) practiced EBF for 6 months, 42% of whom also used HTEBM, expressing a range of approximately, 65 ml to 600 ml of breastmilk daily, for varying durations (2 weeks to 5 months). Mothers did not experience breast pathology. Home visits were highly enabling as was disclosure of HIV status to a partner. This is the first study to demonstrate that use of HTEBM is a feasible infant feeding option for HIV infected women. HTEBM may offer one solution to reduce vertical transmission of HIV and help maintain nutritional adequacy, as a component of complementary feeding.

Aim: To evaluate the primary health care professionals‘ practice of promoting and supporting breastfeeding in Kaunas city. Objectives: 1.) To evaluate knowledge and breastfeeding practice of mothers who have a baby of age less than 1 year; 2.) To evaluate knowledge and activity of primary health care professionals in promoting breastfeeding; 3.) To compare breastfeeding practice promoted by professionals of primary health care centers with breastfeeding practice of mothers; 4.) To compare the activity of primary health care professionals in informing mothers about breastfeeding with mothers’ evaluation of this activity. Method of assessment: Anonymous questionnaire. 407 questionnaires for mothers were distributed in 26 family clinics, GP’s offices (284 questionnaires returned – 69.8 %) and to all primary health care professionals (84 general practitioners and 52 general practice nurses). 51 questionnaire returned – 60.7 % of GP and 40 questionnaires – 76.9 % of general practice nurses. Data analysis was made with Statistical Package for Social Sciences SPSS (12.0 v.). Microsoft Excel was used for diagrams and tables. Results: Only 62.7 % of questioned mothers were breastfed their babies. Only 42.3 % of mothers were breastfed their babies till their age of 6 months. Only 6 % of mothers were trying to breastfeed their babies more often after reduction of milk in breasts; 8.5 % of mothers were breastfed according regimen; 31 % of mothers were giving pacifiers to their... [to full text]

O uso de fármacos durante a lactação é uma prática comum; porém, os tratamentos farmacológicos impõem grandes dúvidas tanto aos profissionais quanto às nutrizes sobre a segurança do uso destes durante este período. A amamentação é uma forma de vínculo entre mãe e bebê e está associada a diversos benefícios nutricionais, imunológicos, cognitivos, psicoafetivos, econômicos e sociais. A depressão é um problema clínico importante durante o período pós-parto, e a vulnerabilidade para o início ou recorrência de sintomas depressivos aumenta a possibilidade de uso de psicofármacos enquanto ocorre a lactação. Os antidepressivos inibidores seletivos da recaptação da serotonina são comumente prescritos para o tratamento destes quadros depressivos, entre eles fluoxetina, sertralina, citalopram e paroxetina, sendo que a maioria destes é excretada no leite materno e há grande variabilidade na quantidade de analitos que pode ser recebida pelo lactente. Bupropiona é um fármaco antidepressivo utilizado para o tratamento do tabagismo e quadros depressivos e tem sua excreção ao leite materno relatada em literatura. Métodos bioanalíticos para determinação da excreção de fármacos antidepressivos foram desenvolvidos e validados por cromatografia líquida acoplada a espectrômetro de massas e cromatografia líquida com detecção ultravioleta. Estes métodos demonstraram serem seletivos, lineares, precisos e exatos, com limites de quantificação de 5 ng/mL (fluoxetina, citalopram e bupropiona) e 20 ng/mL (sertralina e paroxetina) para método por LC-MS e de 200 ng/mL para todos os analitos no método por CLAE-UV. As amostras de leite materno foram coletadas em Banco de Leite de mães que declararam utilizar fluoxetina ou sertralina ou paroxetina e analisados. Os dados de concentração encontrados para os fármacos referidos estão dentro da faixa encontrada em literatura confirmando sua excreção no leite materno. Paroxetina apresentou valores abaixo do limite de quantificação. Das concentrações encontradas no leite materno, foram estimadas as doses absolutas e relativas no lactante, sendo que os resultados demonstraram baixos valores em relação a estas estimativas, podendo os fármacos analisados ser considerados seguros para manutenção do uso durante a lactação. Foi também detectada nas análises por LC-MS a presença de norfluoxetina, metabólito da fluoxetina, confirmando sua excreção nesta matriz. / The use of medications during lactation is a common practice; however pharmacological treatments impose serious doubts to both, professionals and nursing mothers, about the safety of drugs use during this period. Breastfeeding is a natural form of bonding between mother and baby and it is associated with many nutritional, immunological, cognitive, psychoemotional, social and economic benefits. Depression is a major clinical problem during the postpartum period and the vulnerability to onset or recurrence of depressive symptoms increases the possibility of psychotropic drug use during lactation. Selective inhibitors of serotonin reuptake are commonly prescribed for the treatment of depressive disorders, including fluoxetine, sertraline, citalopram and paroxetine. Most of these drugs are excreted in breast milk and there is great variability in the amount of analytes that can be received by the infant. Bupropion is an antidepressant used for tabagism treatment and for depression symptoms; it is also described in literature its excretion into breast milk. Bioanalytical methods for determining the excretion of antidepressants were developed and validated by liquid chromatography coupled to mass spectrometry and liquid chromatography with ultraviolet detection. These methods proved to be selective, linear, precise and accurate with quantification limits of 5 ng/mL (fluoxetine, citalopram e bupropion) and 20 ng/mL (sertraline e paroxetine) for LC-MS method and 200 ng/mL for all analytes in the CLAE-UV method. Human milk samples were collected in milk banks from mothers to which the antidepressants fluoxetine or sertraline or paroxetine were administered, and the concentrations in this matrix were verified. Found concentrations were within the range described in the literature confirming their excretion in the breast milk. Paroxetine presented values less than limit of quantification. From the found concentrations, the absolute and relative doses in nursing were estimated. The results showed low values for these estimates and so the analyzed drugs can be considered safe to continue use during lactation. The presence of norfluoxetine, a metabolite of fluoxetine, was also detected by LC-MS, confirming its excretion in this matrix.

A Rede Brasileira de Bancos de Leite Humano - rBLH-BR é a primeira rede temática do Serviço Único de Saúde - SUS, decorrente da articulação entre política pública de saúde, integração interinstitucional e atendimento a demandas da sociedade por melhoria da saúde dos lactantes, sendo reconhecida como a maior rede de bancos de leite humano no mundo. A estratégia de bancos de leite no Brasil beneficiou mais de 1,8 milhões de recém-nascidos e teve apoio de 1,3 milhões de doadoras entre 2009 e 2016. Neste contexto, a pesquisa identificou as inovações organizacionais e mercadológicas na rBLH-BR, entre dezembro de 2010 e dezembro de 2015, conforme critérios do Manual de Oslo (2005) e, posteriormente, analisou-se o uso dos canais de difusão pelas inovações identificadas. Metodologicamente a pesquisa adotou estudo de caso como procedimento técnico por meio do uso do método misto numa estratégia incorporada concomitante, envolvendo uma abordagem qualitativa e quantitativa com objetivos exploratórios e descritivos. A pesquisa foi realizada junto ao Centro de Referência Nacional - CRN da rBLH-BR, que é o Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira − IFF/Fiocruz. O estudo foi composto por uma pesquisa documental e entrevistas com especialistas com a finalidade de caracterizar a estrutura da rBLH-BR, identificar as inovações e seus canais de difusão, como também, especificar suas relações. O resultado evidenciou que as inovações organizacionais e mercadológicas seguem padrões. As inovações da dimensão organizacional são caracterizadas por serem desenvolvidas pela própria rede ou em colaboração, por serem inovações no âmbito mundial com grau de impacto radical e com difusão total na rede, que iniciam no CRN, passando pelos Centros de Referência Estaduais - CRE e posteriormente os BLHs, utilizando os meios de comunicação interpessoal como canal de difusão com base em soluções de TIC e web. Outro padrão identificado está relacionado as inovações da dimensão de marketing como novidade no âmbito da organização e de impacto incremental, as quais são desenvolvidas na própria rBLH-BR ou em cooperação, com a difusão partindo do CRN para toda a rede, promovida por meios de comunicação de massa. Portanto, o CRN foi identificado como centro inovador/difusor da rBLH-BR e responsáveis pelas funções de padronização, normatização, planejamento, controle, credenciamento e de estabelecer acordos de cooperação internacional. / Submitted by cmquadros@ucs.br (cmquadros@ucs.br) on 2018-01-30T16:06:23Z No. of bitstreams: 1 Dissertacao Alfonso Augusto Fróes d'Avila.pdf: 1865751 bytes, checksum: 81de714e12faf0bc9f9a27e755d638c7 (MD5) / Made available in DSpace on 2018-01-30T16:06:23Z (GMT). No. of bitstreams: 1 Dissertacao Alfonso Augusto Fróes d'Avila.pdf: 1865751 bytes, checksum: 81de714e12faf0bc9f9a27e755d638c7 (MD5) Previous issue date: 2018-01-30 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES / The Brazilian Network of Human Milk Banks (rBLH-BR) is the first thematic network of the Unified Health System – SUS. The network results from the co-ordination between the public health policy, interinstitutional integration and the need to meet the society`s demands for an improvement in the health of lactating women, and is recognized as the largest network of breast milk banks in the world. The strategy of network of Human milk banks in Brazil has benefited more than 1.8 million newborns and had support from 1.3 million donors between 2009 and 2016. In this context, the research has identified the organizational and marketing innovations at the rBLH-BR from December 2010 and December 2015, according to the criteria of the Oslo Manual (2005). An analysis of the use of the diffusion channels was then conducted through the innovations that have been identified. In the methodological aspect, the research used a case study as technical procedure by means of a mixed method, within a concomitant and integral strategy, developed by means of a qualitative and quantitative approach, the goals of which are exploratory and descriptive. The research was conducted at Centro de Referência Nacional – CRN (National Reference Center) of rBLH-BR, which is the National Institute of Women, Children and Adolescents Health Fernando Figueira – IFF/FioCruz. The study consists of a documental research and interviews with experts with the purpose of characterizing the structure of the rBLH-BR, identify innovations and their channels of diffusion, and specify their relations. The result has shown that organizational and marketing innovations follow patterns. Organizational innovations are developed by the network itself or in collaboration with, since they are innovations at a world level with a radical impact and total diffusion in the network, initiated at the CRN, passing through the State Reference Centers (CRE), and then through the BLHs using interpersonal communications means as a diffusion channel and based on ICT and web solutions. The other pattern – innovations in the marketing dimension as a novelty within the Organization and with an incremental impact - are developed at the rBLH itself or in cooperation with, the diffusion of which starts from the CRN and extends to the entire network, promoted by mass media. Therefore, the CRN has been identified as the innovating and diffusing center of rBLH, responsible for functions such as standardization, planning, control, accreditation and establishment of international cooperation agreements.