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..

Burden and severity of children's hospitalizations by respiratory syncytial virus in Portugal, 2015-2018.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection (ALRI) in young children and is of considerable burden on healthcare systems. Our study aimed to evaluate ALRI hospitalizations related to RSV in children in Portugal. METHODS: We reviewed hospitalizations potentially related to RSV in children aged <5 years from 2015 to 2018, using anonymized administrative data covering all public hospital discharges in mainland Portugal. Three case definitions were considered: (a) RSV-specific, (b) (a) plus unspecified acute bronchiolitis (RSV-specific & Bronchiolitis), and (c) (b) plus unspecified ALRI (RSV-specific & ALRI). RESULTS: A total of 9697 RSV-specific hospitalizations were identified from 2015 to 2018-increasing to 26 062 for RSV-specific & ALRI hospitalizations-of which 74.7% were during seasons 2015/2016-2017/2018 (November-March). Mean hospitalization rates per season were, for RSV-specific, RSV-specific & Bronchiolitis, and RSV-specific & ALRI, respectively, 5.6, 9.4, and 11.8 per 1000 children aged <5 years and 13.4, 22.5, and 25.9 in children aged <2 years. Most RSV-specific hospitalizations occurred in healthy children (94.9%) and in children aged <2 years (96.3%). Annual direct costs of €2.4 million were estimated for RSV-specific hospitalizations-rising to €5.1 million for RSV-specific & ALRI-mostly driven by healthy children (87.6%). CONCLUSION: RSV is accountable for a substantial number of hospitalizations in children, especially during their first year of life. Hospitalizations are mainly driven by healthy children. The variability of the potential RSV burden across case definitions highlights the need for a universal RSV surveillance system to guide prevention strategies.

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.

Use of Therapeutic Hypothermia in Sudden Unexpected Postnatal Collapse: A Retrospective Study.

INTRODUCTION: Sudden and unexpected postnatal collapse is a rare event with potentially dramatic consequences. Intervention approaches are limited, but hypothermia has been considered after postnatal collapse. The aim of this study was to analyse sudden and unexpected postnatal collapse cases that underwent therapeutic hypothermia in the five Portuguese hypothermia centres. MATERIAL AND METHODS: In this multicentre, retrospective and descriptive study, clinical, ultrasonography, amplitude-integrated electroencephalography and brain magnetic resonance findings of newborns with postnatal collapse that underwent therapeutic hypothermia are reported (2010 - 2018). Statistical analysis was performed by using IBM SPSS Statistics version 21. RESULTS: Twenty-two cases of sudden and unexpected postnatal collapse were referred for therapeutic hypothermia (82% outborn), all ≥ 36 weeks, with Apgar 5´ ≥ 8. Collapse occurred during the first two hours in 73% (all < 24 hours), 50% during skin-to-skin care, 55% related to feeding and 23% during co-bedding. Moderate-severe encephalopathy and severe acidosis were observed (median: Thompson score 16, pH 6.90, base deficit 22 mmol/L). Amplitude-integrated electroencephalogram was abnormal in 95% and magnetic resonance imaging showed severe brain injury in 46%. The mortality rate was 50%. A possible cause was identified in 27%. DISCUSSION: The incidence rate of 2.7 sudden cases of postnatal collapse per 100 000 births, is possibly under-estimated. All infants suffered the collapse in the first day, mostly within the first two hours, as reported before. Possible causes were identified in less than a third of cases, but multiple predisposing conditions were identified, suggesting that prevention may be possible. Newborn positioning and skin-to-skin care have been the most discussed practices. A significant proportion of infants had poor outcomes. Lower Thompson score, electroencephalogram amplitude normalization and normal magnetic resonance imaging seemed to indicate better outcomes. Although conclusive trials on therapeutic hypothermia after postnatal collapse are not available, its use has been considered individually. No severe adverse effects directly related to hypothermia were registered in this study, but the results do not allow drawing meaningful conclusions. CONCLUSION: In our national sample of 22 infants who suffered sudden and unexpected postnatal collapse and underwent therapeutic hypothermia, a significant proportion had poor outcomes. Absolute conclusions from our experience with hypothermia in postnatal collapse cannot be drawn, but systematic reporting of cases and long-term clinical evaluation would facilitate understanding of the real benefits of hypothermia. As this procedure has not been validated with clinical trials for this indication, its use should be considered on a case-by-case approach. The potentially avoidable nature of unexpected postnatal collapse is evident from its association with certain behaviours and risk factors. Surveillance practices during the first hours should be implemented, whilst the benefits of breastfeeding and skin-to-skin care should continue to be widely promoted.

Introdução: O colapso pós-natal súbito inesperado, apesar de raro, condiciona potenciais consequências dramáticas. As intervenções terapêuticas são limitadas, mas a hipotermia induzida tem sido considerada após estes eventos. O objetivo deste estudo foi analisar os casos de colapso pós-natal súbito inesperado submetidos a hipotermia induzida nos cinco centros portugueses que a realizam. Material e Métodos: Estudo descritivo retrospetivo multicêntrico dos recém-nascidos submetidos a hipotermia induzida após colapso pós-natal entre 2010 e 2018. Foram analisadas as variáveis clínicas, a monitorização por eletroencefalograma de amplitude integrada e imagem por ultrassonografia e a ressonância magnética cerebral. A análise estatística foi efetuada com apoio do IBM SPSS Statistics version 21. Resultados: Foram submetidos a hipotermia terapêutica por colapso súbito 22 recém-nascidos, 82% outborn, todos com 36 ou mais semanas de gestação e Apgar 5´ ≥ 8. A situação ocorreu nas primeiras duas horas de vida em 73% (todos com menos de 24 horas de vida), 50% no contacto pele-a-pele, 55% associados à amamentação e 23% durante partilha de cama. Os recém-nascidos observados apresentaram encefalopatia moderada a grave e acidose grave (mediana: Thompson 16, pH 6,90, défice bases 22 mmol/L). Entre os recém-nascidos, 95% registaram alteração no eletroencefalograma e 46% padrões graves de ressonância cerebral. A taxa de mortalidade foi de 50%. Identificaram-se possíveis causas em 27%. Discussão: Estimou-se uma incidência de 2,7 casos de colapso pós-natal súbito inesperado por cada 100 000 nascimentos, um valor possivelmente subestimado. O colapso ocorreu no primeiro dia em todas as crianças, a maioria nas primeiras duas horas, tal como descrito em publicações anteriores. Identificaram-se possíveis causas em menos de um terço dos casos, mas múltiplas condições predisponentes foram referidas, o que sugere a possibilidade de adoção de medidas preventivas. O posicionamento do recém-nascido e o contacto pele-a-pele têm sido as práticas mais discutidas. Uma proporção significativa das crianças teve uma evolução desfavorável. Um desfecho mais positivo parece ter ocorrido nos casos em que se verificaram valores inferiores na escala de Thompson, normalização do eletroencefalograma de amplitude integrada e ressonância magnética normal. Embora não estejam disponíveis ensaios conclusivos sobre a utilização da hipotermia terapêutica após o colapso pós-natal, o seu uso tem sido considerado individualmente. Nesta revisão não foram observados efeitos adversos diretamente relacionados com o procedimento, mas os resultados não permitem obter conclusões significativas. Conclusão: Na nossa amostra nacional de 22 crianças que sofreram colapso súbito pós-natal e submetidas a hipotermia terapêutica, uma proporção significativa teve uma evolução desfavorável. A nossa experiência e a raridade da entidade clínica não permitem delinear conclusões precisas sobre a aplicação da hipotermia induzida no colapso pós-natal súbito inesperado, pelo que se considera essencial a prevenção. O benefício desta terapêutica poderá ser clarificado através do registo sistemático dos casos e do seguimento a longo prazo das crianças. Embora não existam ensaios clínicos que permitam a sua validação após estes eventos, a hipotermia induzida deve ser uma opção a considerar individualmente. A associação do colapso pós-natal com determinados comportamentos e fatores de risco evidenciam a sua potencial prevenção. Devem ser implementadas estratégias de monitorização nas primeiras horas de vida que permitam simultaneamente a contínua promoção da amamentação e do contacto pele-a-pele.

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.

Vocal responsiveness of preterm infants to maternal infant-directed speaking and singing during skin-to-skin contact (Kangaroo Care) in the NICU.

Vocalizations of full-term newborns occur in a short latency time during the neonatal period. Contingent response time of preterm babies is still unknown. An increase of preterm babies' vocalizations following exposure to parental speech was also observed. Mothers and babies co-modulate their vocalizations in preterm dyads. PURPOSE: To observe temporal features of maternal and infants' vocalizations in speaking and singing conditions in preterm dyads. METHODS: In a NICU mothers (N = 36) were invited to speak and to sing to their preterm infants during Kangaroo Care. Microanalysis of temporal units were performed with ELAN Software. RESULTS AND CONCLUSIONS: Preterm infants vocalize less often while their mothers speak and sing than during baseline and their vocalizations tend to be more alternating in the speaking condition and more overlapping in the singing condition. It is also concluded that preterm infants take more time to respond to maternal speaking than to maternal singing.

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.

Vitamin A in prevention of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) remains one of the most serious challenges in the care of the very preterm infants, affecting approximately one-quarter of infants born < 1500g birth weight and 30% < 1000g. Oxygen toxicity may contribute to its pathogenesis. Vitamin A concentrations are lower in BPD infants which may result in a reduction of the antioxidant protection. It has been found to up regulate genes necessary for fetal lung growth and increase surfactant production in animal models and is also involved in the modulation of immunological and inflammatory responses by regulation of cytokine production. Retinoic acid plays a key role in lung development improving alveolar septation. Evidence exists that vitamin A supplementation for very low birth weight (VLBW) infants, beyond that routinely given in multivitamin preparations, is associated with a reduction in death or BPD. So, parenteral administration of vitamin A to the newborn is one of the current recommended preventive therapies for BPD (number needed to treat 12; 95% CI: 6-94; The information on long-term neurodevelopmental status suggests no evidence of either benefit or harm. Estimates for cerebral palsy range from a number needed to treat of 11 to a number needed to harm of 33. Nowadays, it seems that administration of antenatal vitamin A to the mother in late pregnancy associated with neonatal supplementation can better prevent the development of BPD in areas of endemic vitamin A deficiency. The benefits, in terms of vitamin A status, safety and acceptability of delivering vitamin A in an intravenous emulsion compared with repeat intramuscular injections, the association of vitamin A prenatal and postnatal, as well as the effectiveness and safety of administered high dose vitamin A in ELBW infants await evaluation and should be assessed in further trials.

Vitamin A in Prevention of Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) remains one of the most serious challenges in the care of the very preterm infants, affecting approximately one-quarter of infants born <1500g birth weight and 30% <1000g. Oxygen toxicity may contribute to its pathogenesis. Vitamin A concentrations are lower in BPD infants which may result in a reduction of the antioxidant protection. It has been found to up regulate genes necessary for fetal lung growth and increase surfactant production in animal models and is also involved in the modulation of immunological and inflammatory responses by regulation of cytokine production. Retinoic acid plays a key role in lung development improving alveolar septation. Evidence exists that vitamin A supplementation for very low birth weight (VLBW) infants, beyond that routinely given in multivitamin preparations, is associated with a reduction in death or BPD. So, parenteral administration of vitamin A to the newborn is one of the current recommended preventive therapies for BPD (number needed to treat 12; 95% CI:6-94; The information on long-term neurodevelopmental status suggests no evidence of either benefit or harm. Estimates for cerebral palsy range from a number needed to treat of 11 to a number needed to harm of 33. Nowadays, is seems that administration of antenatal vitamin A to the mother in late pregnancy associated with neonatal supplementation can better prevent the development of BPD in areas of endemic vitamin A deficiency. The benefits, in terms of vitamin A status, safety and acceptability of delivering vitamin A in an intravenous emulsion compared with repeat intramuscular injections, the association of vitamin A prenatal and postnatal, as well as the effectiveness and safety of administered high dose vitamin A in ELBW infants waits evaluation and should be assessed in further trials.

[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.

Neonatal hyperglycaemia: a challenging diagnosis.

Neonatal diabetes mellitus (NDM) is a very rare disorder occurring between 1:400 000 and 1:500 000 live births and, until recently, little was known about this disease. The authors report a case of transient NDM in a 2-day-old female infant admitted in an intensive care unit with a blood glucose level greater than 400 mg/dl, glycosuria, ketonuria and with no evidence of autoimmunity. Treatment with insulin was necessary until the 51st day of life and many difficulties were found in the management of metabolic control because of the need for tiny quantities of insulin. Hyperglycaemia is sometimes routinely treated with insulin by neonatologists but after excluding the common causes of hyperglycaemia, NDM should be considered as a diagnostic possibility with clinical, genetic and therapeutic implications.

Non-steroid anti-inflammatory drugs in the treatment of patent ductus arteriosus in European newborns.

INTRODUCTION: Patent ductus arteriosus (PDA) is a common cause of morbidity and mortality among very low birth weight infants and must be treated on an individual basis. Non-steroid anti-inflammatory drugs (NSAIDs) have been used in the treatment of PDA. However, no general guidelines have been followed. AIM: To know the European reality on NSAIDs in the treatment of PDA in preterm newborns. METHODS: A questionnaire was sent to 24 European Societies of Neonatology and Perinatology to be filled, at least, by two neonatal intensive care units (NICUs) in each country, and to three representatives NICUs in Europe. RESULTS: We received 45 filled forms from 19 countries: 1 (2%) from North, 12 (27%) from East, 6 (13%) from West, and 26 (58%) from South Europe. Intravenous (iv) indomethacin is used in 32 (71%) NICUs (88% use a 30-60 min perfusion), iv ibuprofen in 16 (36%), and oral ibuprofen in 13 (29%). In 45% of NICUs a second course is used; 27% prescribed a third one. Prolonged treatment, 4-6 days, is mentioned by 45% of NICUs, in extremely low birth eight infants and after the failure of 3 courses of treatment. Prophylactic treatment is used in two NICUs, 24% treat no hemodynamically significant PDA, 96% treat with NSAIDs hemodynamically significant PDA and one NICU uses surgical closure as first line treatment. The ibuprofen/indomethacin contra-indications and preferences are similar to the literature. Pedea is the iv ibuprofen solution used and oral ibuprofen is a solution with 20 mg/ml. The choices are influenced by economical reasons in 22% of NICUs. CONCLUSION: Our data show a wide variation among NICUs and countries, regarding the use of NSAIDs to treat PDA, and that no general guidelines are followed. Guidelines or recommendations are necessary to standardize treatment of PDA in Europe, in order to give to all newborns identical health care opportunities.

Neonatal morbi-mortality in very low birth weight in Europe: the Portuguese experience.

The aim of this study was to access evolution in care of very low birth weight (VLBW) infants after the implementation of a regionalization policy in Portugal. The data of the National Portuguese Network of VLBW infants are analyzed concerning mortality, morbidity, and quality of regionalization. A total of 12,826 VLBW infants born from 1 January 1994 to 31 December 2008 were enrolled, with a prevalence of 0.66%-0.99% of all live born. The global mortality was 11%. The major improvement in survival is in the babies more than 1000 g. Since 2004, the threshold of viability is 25 weeks, but the intact survival is around 28 weeks. In the last 10 years with more efficient regionalization more VLBW babies are born in the right place. The improvement in neonatal mortality rate was determinant in the good evolution of perinatal and infant mortalities. After reinforcement of regionalization policies, we found improvements in mortality for VLBW infants. The aims of regionalization were achieved. The reform of perinatal care in Portugal is an example of how a good diagnosis and adequate proposals combined with a strong political will is crucial for changing.