Individualized Fortification Based on Measured Macronutrient Content of Human Milk Improves Growth and Body Composition in Infants Born Less than 33 Weeks: A Mixed-Cohort Study.

The optimal method for human milk (HM) fortification has not yet been determined. This study assessed whether fortification relying on measured HM macronutrient content (Miris AB analyzer, Upsala, Sweden) composition is superior to fortification based on assumed HM macronutrient content, to optimize the nutrition support, growth, and body composition in infants born at <33 weeks' gestation. In a mixed-cohort study, 57 infants fed fortified HM based on its measured content were compared with 58 infants fed fortified HM based on its assumed content, for a median of 28 and 23 exposure days, respectively. The ESPGHAN 2010 guidelines for preterm enteral nutrition were followed. Growth assessment was based on body weight, length, and head circumference Δ z-scores, and the respective growth velocities until discharge. Body composition was assessed using air displacement plethysmography. Fortification based on measured HM content provided significantly higher energy, fat, and carbohydrate intakes, although with a lower protein intake in infants weighing ≥ 1 kg and lower protein-to-energy ratio in infants weighing < 1 kg. Infants fed fortified HM based on its measured content were discharged with significantly better weight gain, length, and head growth. These infants had significantly lower adiposity and greater lean mass near term-equivalent age, despite receiving higher in-hospital energy and fat intakes, with a mean fat intake higher than the maximum recommended and a median protein-to-energy ratio intake (in infants weighing < 1 kg) lower than the minimum recommended.

Does Fetal Growth Adequacy Affect the Nutritional Composition of Mothers' Milk?: A Historical Cohort Study.

OBJECTIVE: The study aimed to assess the association between intrauterine growth of preterm infants and energy and macronutrient contents in their mothers' milk. STUDY DESIGN: A historical cohort of mothers of preterm infants was assessed according to offspring's intrauterine growth. Fetal growth restriction (FGR) was defined as small-for-gestational age or appropriate for gestational age with fetal growth deceleration. During the first 4 weeks after delivery, the composition of daily pool samples of mothers' milk was measured by using a mid-infrared human milk analyzer. Explanatory models for milk energy, true protein, total carbohydrate, and fat contents were obtained by generalized additive mixed effects regression models. RESULTS: In total, 127 milk samples were analyzed from 73 mothers who delivered 92 neonates. Energy content was significantly higher in mothers with chronic hypertension (average: +6.28 kcal/dL; 95% confidence interval [CI]: 0.54-12.01; p = 0.034) and for extremely preterm compared with very preterm infants (average: +5.95 kcal/dL; 95% CI: 2.16-9.73; p = 0.003), and weakly associated with single pregnancies (average: +3.38 kcal/dL; 95% CI: 0.07-6.83; p = 0.057). True protein content was significantly higher in mothers with chronic hypertension (average: +0.91 g/dL; 95% CI: 0.63-1.19; p < 0.001) and with hypertension induced by pregnancy (average: +0.25 g/dL, 95% CI: 0.07-0.44; p = 0.007), and for extremely preterm compared with very and moderate preterm infants (average: +0.19; 95% CI: 0.01-0.38; p = 0.043 and +0.28 g/dL; 95% CI: 0.05-0.51; p = 0.017, respectively). Fat content was weakly and negatively associated with FGR, both in SGA infants and AGA infants with fetal growth deceleration (average: -0.44 g/dL; 95% CI: -0.92 to -0.05; p = 0.079 and average: -0.36 g/dL; 95% CI: -0.74 to -0.02; p = 0.066, respectively). CONCLUSION: Energy and macronutrient contents in mothers' milk of preterm infants was significantly and positively associated with the degree of prematurity and hypertension. The hypothesis that the composition of milk is associated with FGR was not demonstrated. KEY POINTS: · Energy and protein are higher for more immature infants.. · Energy and/or protein is higher in hypertension.. · Fat may be lower for infants with intrauterine growth restriction..

Influence of Human Milk on Very Preterms' Gut Microbiota and Alkaline Phosphatase Activity.

The FEEDMI Study (NCT03663556) evaluated the influence of infant feeding (mother's own milk (MOM), donor human milk (DHM) and formula) on the fecal microbiota composition and alkaline phosphatase (ALP) activity in extremely and very preterm infants (≤32 gestational weeks). In this observational study, preterm infants were recruited within the first 24 h after birth. Meconium and fecal samples were collected at four time points (between the 2nd and the 26th postnatal days. Fecal microbiota was analyzed by RT-PCR and by 16S rRNA sequencing. Fecal ALP activity, a proposed specific biomarker of necrotizing enterocolitis (NEC), was evaluated by spectrophotometry at the 26th postnatal day. A total of 389 fecal samples were analyzed from 117 very preterm neonates. Human milk was positively associated with beneficial bacteria, such as Bifidobacterium, Bacteroides ovatus, and Akkermancia muciniphila, as well as bacterial richness. Neonates fed with human milk during the first week of life had increased Bifidobacterium content and fecal ALP activity on the 26th postnatal day. These findings point out the importance of MOM and DHM in the establishment of fecal microbiota on neonates prematurely delivered. Moreover, these results suggest an ALP pathway by which human milk may protect against NEC.

Customized Human Milk Fortification Based on Measured Human Milk Composition to Improve the Quality of Growth in Very Preterm Infants: A Mixed-Cohort Study Protocol.

Adequate nutrition of very preterm infants comprises fortification of human milk (HM), which helps to improve their nutrition and health. Standard HM fortification involves a fixed dose of a multi-nutrient HM fortifier, regardless of the composition of HM. This fortification method requires regular measurements of HM composition and has been suggested to be a more accurate fortification method. This observational study protocol is designed to assess whether the target HM fortification method (contemporary cohort) improves the energy and macronutrient intakes and the quality of growth of very preterm infants, compared with the previously used standard HM fortification (historical cohorts). In the contemporary cohort, a HM multi-nutrient fortifier and modular supplements of protein and fat are used for HM fortification, and the enteral nutrition recommendations of the European Society for Paediatric Gastroenterology Hepatology and Nutrition for preterm infants will be considered. For both cohorts, the composition of HM is assessed using the Miris Human Milk analyzer (Uppsala, Sweden). The quality of growth will be assessed by in-hospital weight, length, and head circumference growth velocities and a single measurement of adiposity (fat mass percentage and fat mass index) performed just after discharge, using the air displacement plethysmography method (Pea Pod, Cosmed, Italy). ClinicalTrials.gov registration number: NCT04400396.

Extremely preterm neonates have more Lactobacillus in meconium than very preterm neonates - the in utero microbial colonization hypothesis.

Growing evidence suggests that maternal microbiota can influence the neonates' gut colonization. However, the mechanisms of vertical bacterial transmission remain poorly defined. We believed that the first colonizers of the newborn come from the mother's gut and vagina during pregnancy and that this is independent of the mode of delivery. We conducted an observational longitudinal study to evaluate the link between the maternal gut microbiota and the meconium's microbiota in extremely and very preterm neonates. Bacterial DNA was extracted from samples and specific bacterial groups were quantified by RT-PCR. In this cohort of 117 preterm neonates, we detected bacterial DNA in 88% of meconium samples. Meconium microbiota of neonates born after 28 gestational weeks (very preterm neonates) showed stronger correlations with their mothers' fecal microbiota. However, neonates born before 28 gestational weeks (extremely preterm neonates) had more Lactobacillus - genus that dominated the vaginal microbiota - than very preterm neonates, regardless of the mode of delivery. Collectively, these data support the hypothesis that maternal bacteria from the gut and vagina can play a role in shaping neonates' gut microbiota and that mother-to-infant bacterial transmission is a controlled and time-specific process. ClinicalTrials.gov Identifier: NCT03663556.

Male sex is an independent risk factor for poor neurodevelopmental outcome at 20 months' corrected age, in human milk-fed very preterm infants: a cohort study.

OBJECTIVE: To determine associations between sex and neurodevelopmental outcomes in human milk-fed very preterm infants, adjusted to early measured nutrient intakes and other neonatal cofactors. METHODS: Consecutive inborn human milk-fed infants, with gestational age <33 weeks, were eligible. In-hospital energy and protein intakes have relied on measured human milk composition. The Bayley Scales of Infant Development II mental and psychomotor developmental indexes were used to assess neurodevelopment at 20 months' corrected age. After univariate analysis, some covariables were used for linear multiple regression. RESULTS: Thirty-two infants were included, with a mean (standard deviation) gestational age of 29.8 (1.8) weeks, and a median birth weight of 1168g (interquartile range 990-1419g). Minimum recommended intakes were achieved in 63.6% and 15.2% of infants for protein and energy, respectively. The mental and psychomotor developmental indexes were within normal limits in 93.8% of infants. The mean mental and psychomotor developmental indexes were significantly lower in males. Only male sex negatively and significantly affected the mental and psychomotor developmental indexes (B=-9.44; 95%CI: -17.64- -1.23; adjusted r2=0.17; p=0.026), adjusted to gestational age and measured energy intake. CONCLUSION: In human milk-fed very preterm infants, males had a significantly lower mental and psychomotor developmental indexes score at 20 months' corrected age, adjusted for gestational age and measured energy intake.

FEEDMI: A Study Protocol to Determine the Influence of Infant-Feeding on Very-Preterm-Infant's Gut Microbiota.

BACKGROUND: Preterm infants are especially vulnerable to gut microbiota disruption and dysbiosis since their early gut microbiota is less abundant and diverse. Several factors may influence infants' gut microbiota, such as the mother's diet, mode of delivery, antibiotic exposure, and type of feeding. OBJECTIVES: This study aims to examine the factors associated with very-preterm neonate's intestinal microbiota, namely: (1) type of infant-feeding (breast milk, donor human milk with or without bovine protein-based fortifier, and preterm formula); (2) maternal diet; and (3) mode of delivery. METHODS: This is an observational study conducted in a cohort of very preterm infants hospitalized in the neonatal intensive care unit of Maternidade Dr. Alfredo da Costa. After delivery, the mothers are asked to collect their own fecal samples and are invited to complete a semiquantitative food frequency questionnaire. The maternal diet will be classified in accordance to the Mediterranean Diet adherence score. Stool samples have been collected from very premature infants every 7 days for 21 days. DNA has been extracted from the fecal samples, and different bacterial genus and species will be quantified by real-time polymerase chain reaction. RESULTS AND CONCLUSIONS: It is hypothesized that significant differences in the microbiota composition and clinical outcomes of very preterm infants will be observed depending on the type of infant feeding. In addition, this study will clarify how pasteurized donor's milk influences the intestinal microbiota colonization of preterm infants. This is a pioneer study developed in collaboration with the country's Human Milk Bank. We also expect to find microbiota alterations in infants according to the mode of delivery and to maternal diet. This study will contribute to increase the evidence on the effects of breast or donor human milk and its fortification with a bovine protein-based fortifier on infant microbiota.

Male sex is an independent risk factor for poor neurodevelopmental outcome at 20 months' corrected age, in human milk-fed very preterm infants: a cohort study / O sexo masculino é fator de risco independente para pior desenvolvimento neurológico na idade corrigida de 20 meses, em lactentes muito prematuros e alimentados com leite humano: estudo de coorte

ABSTRACT Objective: To determine associations between sex and neurodevelopmental outcomes in human milk-fed very preterm infants, adjusted to early measured nutrient intakes and other neonatal cofactors. Methods: Consecutive inborn human milk-fed infants, with gestational age <33 weeks, were eligible. In-hospital energy and protein intakes have relied on measured human milk composition. The Bayley Scales of Infant Development II mental and psychomotor developmental indexes were used to assess neurodevelopment at 20 months' corrected age. After univariate analysis, some covariables were used for linear multiple regression. Results: Thirty-two infants were included, with a mean (standard deviation) gestational age of 29.8 (1.8) weeks, and a median birth weight of 1168g (interquartile range 990-1419g). Minimum recommended intakes were achieved in 63.6% and 15.2% of infants for protein and energy, respectively. The mental and psychomotor developmental indexes were within normal limits in 93.8% of infants. The mean mental and psychomotor developmental indexes were significantly lower in males. Only male sex negatively and significantly affected the mental and psychomotor developmental indexes (B=-9.44; 95%CI: -17.64- -1.23; adjusted r2=0.17; p=0.026), adjusted to gestational age and measured energy intake. Conclusion: In human milk-fed very preterm infants, males had a significantly lower mental and psychomotor developmental indexes score at 20 months' corrected age, adjusted for gestational age and measured energy intake.

RESUMO Objetivo: Determinar a associação entre sexo e desfechos relativos ao neurodesenvolvimento em lactentes muito prematuros e alimentados com leite humano, ajustada para a ingestão de nutrientes medida nos primeiros dias de vida e outros cofatores neonatais. Métodos: Consideramos, para este estudo, lactentes alimentados com leite humano, consecutivamente nascidos em um centro especializado, com idade gestacional <33 semanas. A ingestão intra-hospitalar de energia e proteínas baseou-se na composição medida do leite humano. Os índices de desenvolvimento mental e psicomotor das Bayley Scales of Infant Development II foram usados para avaliar o neurodesenvolvimento na idade corrigida de 20 meses. Após a análise univariada, algumas covariáveis foram usadas para a regressão múltipla linear. Resultados: Incluímos 32 lactentes, com idade gestacional média (desvio padrão) de 29,8 (1,8) semanas e mediana de peso ao nascimento de 1168g (intervalo interquartil: 990-1419g). A ingestão mínima recomendada foi atingida em 63,6% e 15,2% dos lactentes, para proteínas e energia, respectivamente. Os índices de desenvolvimento mental e psicomotor ficaram dentro dos limites normais em 93,8% dos lactentes. A pontuação média nos índices de desenvolvimento mental e psicomotor foi significativamente menor no bebês do sexo masculino. Somente o sexo masculino afetou negativa e significativamente os índices de desenvolvimento mental e psicomotor (B=-9,44; IC95%: -17,64- -1,23; r2 ajustado=0,17; p=0,026), ajustados para idade gestacional e ingestão de energia medida. Conclusão: Em lactentes muito prematuros e alimentados com leite humano, o sexo masculino teve pontuação significativamente mais baixa nos índices de desenvolvimento mental e psicomotor na idade corrigida de 20 meses, ajustada para idade gestacional e ingestão de energia medida.

The fortification method relying on assumed human milk composition overestimates the actual energy and macronutrient intakes in very preterm infants.

BACKGROUND: To achieve recommended nutrient intakes in preterm infants, the target fortification method of human milk (HM) was proposed as an alternative to standard fortification method. We aimed to compare assumed energy and macronutrient intakes based on standard fortified HM with actual intakes relying on measured composition of human milk (HM), in a cohort of HM-fed very preterm infants. METHODS: This study is a secondary retrospective analysis, in which assumed energy and macronutrient contents of daily pools of own mother's milk (OMM) from 33 mothers and donated HM (DHM) delivered to infants were compared with the measured values using a mid-infrared HM analyzer. A fortification method consisting of modular protein and/or fat supplements added to standard fortified HM was used to provide the minimum recommended daily intakes of energy 110 Kcal/kg and protein up to 4.0 g/kg. Assumed nutrient intakes were compared with actual nutrient intakes from full enteral feeding to 35 weeks plus 6 days postmenstrual age, using the Wilcoxon matched-pairs signed ranks test. RESULTS: The composition of 1181 samples of daily pools of HM were measured. For 90.2% of study days, infants were exclusively fed OMM and in remaining days fed OMM plus DHM. Comparing with reported preterm OMM composition, measured protein concentration was significantly lower, and energy and other macronutrient concentrations were lower only from the second to third postnatal week. Using fortified HM, the actual median daily intakes of energy, protein, and fat were significantly lower (113.3 vs. 120.7 Kcal/kg, 4.45 vs. 4.73 g/kg, and 4.96 vs. 5.35 g/kg, respectively) and the actual protein-to-energy ratio (PER) significantly higher than what was assumed (4.2 vs. 4.0), without differences in carbohydrate intake. CONCLUSIONS: When fortifying the HM, we used conservative target intakes trying not to exceed the osmolarity recommended for infant feeds. Actual energy, protein and fat intakes in OMM were significantly lower than assumed. This resulted in inadequate intake using our fortification method, that did not compensate the suboptimal measured energy and macronutrient contents of OMM delivered. Further studies comparing assumed with the gold standard target fortification are needed to determine safe upper limits of assumed fortification.

Associations of Measured Protein and Energy Intakes with Growth and Adiposity in Human Milk-Fed Preterm Infants at Term Postmenstrual Age: A Cohort Study.

OBJECTIVE: To determine the associations of measured protein, energy, and protein-to-energy (PER) intakes with body composition in human milk (HM)-fed preterm infants. STUDY DESIGN: Neonates born at < 33 gestational weeks were eligible. Standard fortification method with modular supplements was used and the HM composition was measured. The weight gain velocity was calculated, and body composition was assessed by air displacement plethysmography at 40 weeks' postmenstrual age (PMA). The fat mass percentage and fat mass index were used as indicators of adiposity, with convenience cut-offs ≤ -1 and ≥ + 1 z-scores for low and high adiposity, respectively. RESULTS: Thirty-three infants were included (median [interquartile range] gestational age: 30 [28-31] weeks; birth weight: 1.175 [1.010-1.408] g); 36.4 and 84.8% did not receive the minimum recommended protein and energy intakes, respectively. Weight gain velocity showed positive weak-to-moderate correlations with nutrient intakes. Overall, no correlations between nutrient intakes and body composition were found. Infants with lower adiposity received lower energy, protein, and PER intakes, while those with higher adiposity received lower energy intake but higher PER intake. CONCLUSION: Overall, no correlations of nutrient intakes with body composition were found; however, differences in nutrient intakes were found between infants with lower and higher adiposity at term PMA.

[Conditions for neonatal resuscitation in Portuguese delivery rooms: a national survey (2009)]. / Condições de assistência ao recém-nascido na sala de partos: inquérito nacional (2009).

INTRODUCTION: In Portugal, since 1989, the rates of maternal, perinatal and neonatal mortality present a significant decrease, after the implemented perinatal network. The continuous assessment of the existing conditions at the different levels of perinatal care is essential to identify deviations from normality and may allow the optimization of quality of care. OBJECTIVES: To obtain information on and to evaluate the conditions and practices of neonatal resuscitation at the Portuguese delivery rooms, in order to propose measures for improvement of neonatal care. MATERIAL AND METHODS: An electronic questionnaire was sent to 35 hospitals with maternity. The survey included questions regarding to human and material resources, characteristics of delivery room practices used in stabilization / resuscitation of the newborn, number of deliveries and number of newborns transferred after birth per year, as well as issues related with the collaboration of obstetric teams. RESULTS: Thirty centres (86%) answered the questionnaire, 16 of the respondents were level III maternities/hospitals. In eight (27%) centres a paediatrician is present at all deliveries, whereas in the remaining centres a paediatrician is available only for risk situations. The material unavailable in some centres include cardio-respiratory monitoring equipment, support device with pressure controlled ventilation, oxygen blender, ventilator, CPAP (continuous positive airway pressure), neonatal transport incubators and equipments for thoracocentesis and paracentesis. The criteria used for prophylactic surfactant and oxygen use are very different among the various centres. All centres reported transferring newborns after birth, either because of lack of differentiation of care or vacant beds. The centres with perinatal support reported less cooperation of the obstetric teams. CONCLUSIONS: The care of the newborn in the national delivery rooms can and should be improved. It is necessary to adapt the equipment and human resources to the needs of each centre. Protocols and practices such as oxygen and "prophylactic" surfactant must be updated, transport after birth must be reduced and the communication with the obstetric teams should be improved.

Respiratory support strategies for the preterm newborn - National survey 2008.

BACKGROUND: Respiratory support strategies for the preterm newborn have been the subject of intense research. AIM: To survey neonatal respiratory support practices in Portugal and to determine whether they reflect evidence from randomised trials. METHODS: Questionnaires were given out to 31 Portuguese neonatal units to determine the types of ventilators, modes of ventilation, lung function monitoring, use of exogenous surfactant, oxygen saturation levels used and the prevalence of chronic lung disease in the preterm newborn. RESULTS: There was a 94% response rate. Draeger babylog was the most frequently used ventilator in neonates. Twelve (41%) units prefer to use early nasal continuous positive airway pressure (NCPAP) whenever possible. Triggered ventilation is the choice of invasive ventilation in 24 (83%) units (SIMV, SIPPV, PSV); four (14%) units have high frequency oscillation ventilation. SIMV is the most frequent (n=13, 45%) weaning mode. Exogenous surfactant is used as prophylactic in 12 (41%) units. All units use lung function measurements to aid choice of ventilator settings and five (17%) units monitor PaCO2 (transcutaneous = 3; capnometry = 2). Seventeen (59%) units allow oxygen saturation levels from 90% to 95% in infants with respiratory distress syndrome and 15 (52%) levels from 85% to 90% in infants with chronic lung disease. Prevalence of chronic lung disease of prematurity ranged from 0% to 75% (median: 10). CONCLUSIONS: Many respiratory strategies for extremely low birth weight infants reflect the result of large randomised trials. More effective methods may be required to encourage the use of early NCPAP preferably with binasal prongs, the use of SIPPV as the main weaning mode, the use of volume targeted ventilation and a more judicious use of exogenous surfactant in order to ensure evidence-based practice.

Intraventricular hemorrhage risk factors in very low birth weight newborns: a case-control study / Fatores de risco para hemorragia intraventricular em recém-nascidos de muito baixo peso: estudo caso-controle

Objective: Identification of variables that affect the risk of severe intraventricular hemorrhage (IVH) in very low birth weight (VLBW) newborns. Methods: Analytic case-control study, in a population consisting of all VLBW newborns admitted to the Neonatal Intensive Care Unit of a maternity hospital, between January 2002 and December 2007. The authors considered as cases all VLBW newborns with severe IVH (grade ? 3), and control all VLBW newborns without IVH. Independent variables included obstetric, perinatal and neonatal diagnosis and therapy. Bivariate analysis and multivariate logistic regression analysis were performed. Results: During this period, of the 864 VLBW newborns admitted to the Neonatal Intensive Care Unit, 9.7% had severe IVH. With bivariate analysis an association between severe IVH, gestational age and birth weight was found. Prenatal care and pre-eclampsia were associated with a decrease in the incidence of severe IVH. Amnionitis, being outborn, vaginal delivery, male gender, intubation in the delivery room, surfactant, hyaline membrane disease, pneumothorax, necrotizing enterocolitis (NEC) perforation and oscillatory high frequency ventilation were associated with an increased incidence of severe IVH. By multivariate logistic regression, the variables associated with increased risk of severe IVH were: pneumothorax (OR = 3.8; 95%CI = 1.7-8.3), NEC with perforation (OR = 8.8; 95%CI = 1.7-45.0), vaginal delivery (OR = 2.0; 95%CI = 1.0-4.1) and high frequency ventilation (OR = 4.8; 95%CI = 1.3-17.3). The following were protective of severe IVH: gestational age (OR = 0.61; 95%CI = 0.52-0.72), patent ductus arteriosus treatment with indomethacin (OR = 0.26; 95%CI = 0.11-0.6) and fertility treatment (OR = 0.24; 95%CI = 0.06-0.94). Conclusion: These data outline the importance of improvement of pre and neonatal care to reduce severe IVH

Objetivo: Identificação de variáveis que influenciem o risco de hemorragia intraventricular (HIV) grave em recém-nascidos de muito baixo peso (RNMBP). Métodos: Efetuou-se um estudo analítico, caso-controle, em uma população constituída por todos os RNMBP admitidos em uma Unidade de Cuidados Intensivos Neonatal (UCIN), no período compreendido entre Janeiro de 2002 e Dezembro de 2007. Consideraram-se casos todos os RNMBP com HIV grave (grau ? 3) e controle todos os RNMBP sem HIV. As variáveis independentes foram dados obstétricos, perinatais, diagnóstico e terapêutica neonatal. Realizou-se análise bivariada e análise de regressão logística multivariada. Resultados: Foram admitidos na Unidade de Cuidados Intensivos Neonatal, neste período, 864 RNMBP, dos quais 9,7% apresentaram HIV grave. Na análise bivariada, verificou-se uma associação entre HIV grave, idade gestacional e peso ao nascer. A atenção pré-natal e pré-eclampsia foram associadas a uma menor incidência de HIV grave. Amnionite, nascimento no exterior, parto vaginal, sexo masculino, intubação na sala de parto, surfactante, doença da membrana hialina, pneumotórax, enterocolite necrotizante (EN) com perfuração e a ventilação de alta frequência oscilatória foram associados a uma maior incidência de HIV grave. No modelo de regressão logística multivariada, as variáveis associadas a um maior risco de HIV grave foram pneumotórax (OR = 3,8; IC95% = 1,7-8,3), EN com perfuração (OR = 8,8; IC95% = 1,7-45,0), parto vaginal (OR = 2,0; IC95% = 1,0-4,1) e ventilação de alta frequência oscilatória (OR = 4,8; IC95% = 1,3-17,3). Foram fatores protetores para HIV grave: idade gestacional (OR = 0,61; IC95% = 0,52-0,72), tratamento da persistência do ducto arterioso com indometacina (OR = 0,26; IC95% = 0,11-0,60) e tratamento de fertilidade (OR = 0,24; IC95% = 0,06-0,94). Conclusão: Os resultados obtidos neste estudo realçam a importância da melhoria da prestação de cuidados pré e neonatais na redução da HIV grave