At present, in the EU, there is a specific Legislation on Blood, Tissue and Cells (BTC), but there is a lack of regulation on Donor Human Milk and Human Milk Banks. This legal uncertainty regarding ...the status and handling of Donor Human Milk is a hindrance to the use of human milk in preterm newborns feeding. We are now in the first phase of the Legislative Process for the Revision of the European BTC Legislation that is expected to include Donor Human Milk and human milk banking regulation. The European Milk Bank Association (EMBA) and the other stakeholders are following this process very carefully: we are confident we will have this regulation by the end of 2022 to improve the availability, quality and safety of Donor Human Milk for preterm and sick infants.
Human milk (HM) is a unique nourishment believed to contain biological factors contributing to both short and long-term benefits. Considering that a mother's own milk is often considered the first ...choice for nutrition of neonates, an aspect of increased interest is the possible effect of diabetes on the mammary gland and therefore on breast milk composition. This article aims to review the published literature on this topic, and to offer additional insights on the role of this disease on the composition of HM. This review was performed by searching the MEDLINE, EMBASE, CINHAL and Cochrane Library databases. A total of 50 articles were selected, focused specifically on one of the two types of diabetes: gestational diabetes mellitus (21 studies) and insulin-dependent diabetes mellitus (8 studies). Overall, the findings from the literature suggest that diabetes can alter the composition of HM. Nevertheless, the studies in this field are scarce, and the related protocols present some limitations, e.g., evaluating the variability of just a few specific milk biochemical markers in association with this syndrome.
Postnatal growth restriction is common in preterm infants and is associated with long-term neurodevelopmental impairment. Recent trends in postnatal growth restriction are unclear.
Birth and ...discharge weights from 25,899 Californian very low birthweight infants (birth weight 500-1500 g, gestational age 22-32 weeks) who were born between 2005 and 2012 were converted to age-specific Z-scores and analysed using multivariable modelling.
Birthweight Z-score did not change between 2005 and 2012. However, the adjusted discharge weight Z-score increased significantly by 0.168 Z-scores (0.154, 0.182) over the study period, and the adjusted fall in weight Z-score between birth and discharge decreased significantly between those dates (by 0.016 Z-scores/year). The proportion of infants who were discharged home below the 10th weight-for-age centile or had a fall in weight Z-score between birth and discharge of >1 decreased significantly over time. The comorbidities most associated with poorer postnatal growth were medical or surgical necrotising enterocolitis, isolated gastrointestinal perforation and severe retinopathy of prematurity, which were associated with an adjusted mean reduction in discharge weight Z-score of 0.24, 0.57, 0.46 and 0.32, respectively. Chronic lung disease was not a risk factor after accounting for length of stay.
Postnatal, but not prenatal, growth improved among very low birthweight infants between 2005 and 2012. Neonatal morbidities including necrotising enterocolitis, gastrointestinal perforations and severe retinopathy of prematurity have significant negative effects on postnatal growth.
Summary Background In 2006, WHO produced international growth standards for infants and children up to age 5 years on the basis of recommendations from a WHO expert committee. Using the same methods ...and conceptual approach, the Fetal Growth Longitudinal Study (FGLS), part of the INTERGROWTH-21st Project, aimed to develop international growth and size standards for fetuses. Methods The multicentre, population-based FGLS assessed fetal growth in geographically defined urban populations in eight countries, in which most of the health and nutritional needs of mothers were met and adequate antenatal care was provided. We used ultrasound to take fetal anthropometric measurements prospectively from 14 weeks and 0 days of gestation until birth in a cohort of women with adequate health and nutritional status who were at low risk of intrauterine growth restriction. All women had a reliable estimate of gestational age confirmed by ultrasound measurement of fetal crown–rump length in the first trimester. The five primary ultrasound measures of fetal growth—head circumference, biparietal diameter, occipitofrontal diameter, abdominal circumference, and femur length—were obtained every 5 weeks (within 1 week either side) from 14 weeks to 42 weeks of gestation. The best fitting curves for the five measures were selected using second-degree fractional polynomials and further modelled in a multilevel framework to account for the longitudinal design of the study. Findings We screened 13 108 women commencing antenatal care at less than 14 weeks and 0 days of gestation, of whom 4607 (35%) were eligible. 4321 (94%) eligible women had pregnancies without major complications and delivered live singletons without congenital malformations (the analysis population). We documented very low maternal and perinatal mortality and morbidity, confirming that the participants were at low risk of adverse outcomes. For each of the five fetal growth measures, the mean differences between the observed and smoothed centiles for the 3rd, 50th, and 97th centiles, respectively, were small: 2·25 mm (SD 3·0), 0·02 mm (3·0), and −2·69 mm (3·2) for head circumference; 0·83 mm (0·9), −0·05 mm (0·8), and −0·84 mm (1·0) for biparietal diameter; 0·63 mm (1·2), 0·04 mm (1·1), and −1·05 mm (1·3) for occipitofrontal diameter; 2·99 mm (3·1), 0·25 mm (3·2), and −4·22 mm (3·7) for abdominal circumference; and 0·62 mm (0·8), 0·03 mm (0·8), and −0·65 mm (0·8) for femur length. We calculated the 3rd, 5th 10th, 50th, 90th, 95th and 97th centile curves according to gestational age for these ultrasound measures, representing the international standards for fetal growth. Interpretation We recommend these international fetal growth standards for the clinical interpretation of routinely taken ultrasound measurements and for comparisons across populations. Funding Bill & Melinda Gates Foundation.
It is unclear whether early child development is, like skeletal growth, similar across diverse regions with adequate health and nutrition. We prospectively assessed 1307 healthy, well-nourished ...2-year-old children of educated mothers, enrolled in early pregnancy from urban areas without major socioeconomic or environmental constraints, in Brazil, India, Italy, Kenya and UK. We used a specially developed psychometric tool, WHO motor milestones and visual tests. Similarities across sites were measured using variance components analysis and standardised site differences (SSD). In 14 of the 16 domains, the percentage of total variance explained by between-site differences ranged from 1.3% (cognitive score) to 9.2% (behaviour score). Of the 80 SSD comparisons, only six were >±0.50 units of the pooled SD for the corresponding item. The sequence and timing of attainment of neurodevelopmental milestones and associated behaviours in early childhood are, therefore, likely innate and universal, as long as nutritional and health needs are met.
Large differences exist in size at birth and in rates of impaired fetal growth worldwide. The relative effects of nutrition, disease, the environment, and genetics on these differences are often ...debated. In clinical practice, various references are often used to assess fetal growth and newborn size across populations and ethnic origins, whereas international standards for assessing growth in infants and children have been established. In the INTERGROWTH-21(st) Project, our aim was to assess fetal growth and newborn size in eight geographically defined urban populations in which the health and nutrition needs of mothers were met and adequate antenatal care was provided.
For this study, fetal growth and newborn size were measured in two INTERGROWTH-21(st) component studies using prespecified markers and the same methods, equipment, and selection criteria. In the Fetal Growth Longitudinal Study (FGLS), we studied educated, affluent, healthy women, with adequate nutritional status who were at low risk of intrauterine growth restriction. The primary markers of fetal growth were ultrasound measurements of fetal crown-rump length at less than 14 weeks and 0 days of gestation and fetal head circumference from 14 weeks and 0 days to 40 weeks and 0 days of gestation, and birthlength for newborn size. In the concomitant, population-based Newborn Cross-Sectional Study (NCSS), we measured birthlength in all newborn babies from the eight geographically defined urban populations with the same methods, instruments, and staff as in FGLS. From this large NCSS cohort, we selected an FGLS-like subpopulation to match FGLS with the same eligibility criteria.
Between May 14, 2009, and Aug 2, 2013, we enrolled 4607 women in FGLS and 59 137 women in NCSS. From NCSS, 20 486 (34·6%) women met the FGLS eligibility criteria, and constituted the FGLS-like subpopulation. With variance component analysis, only between 1·9% and 3·5% of the total variability in crown-rump length, fetal head circumference, and newborn birthlength could be attributed to between-site differences. With standardised site effect analysis in 16 gestational age windows from 9 weeks and 0 days of gestation to birth for the three measures (128 comparisons), only one was marginally higher than 0·5 SD of the standardised site difference range. Sensitivity analyses, excluding individual populations in turn from the pooling of all-site centiles across gestational ages, showed no noticeable effect on the 3rd, 50th, and 97th centiles derived from the remaining populations. Our populations were consistent at birth with those in the WHO Multicentre Growth Reference Study (MGRS). The mean birthlength for term newborn babies in that study was 49·5 cm (SD 1·9), which was very similar to that in the FGLS cohort (49·4 cm 1·9) and the NCSS derived FGLS-like subpopulation (49·3 cm 1·8).
Fetal growth and newborn length are similar across diverse geographical settings when mothers' nutritional and health needs are met, and environmental constraints on growth are low. The findings for birthlength are in strong agreement with those of the WHO MGRS. These results provide the conceptual frame to create international standards for growth from conception to newborn baby, which will extend the present infant to childhood WHO MGRS standards.
Bill & Melinda Gates Foundation.
Extrauterine Growth Restriction (EUGR) refers to inadequate growth during hospitalization. Current definitions for EUGR are varied and can be classified as cross-sectional (weight at a given t-time ...<10th centile) or longitudinal (weight loss between birth and a given t-time >1SD). Different t-times are also considered in literature, such as 36 weeks of gestational age (GA) or age at discharge. The aim of this study is to investigate whether EUGR could predict the auxological outcome at 24-30 months, and to evaluate the agreement between cross-sectional and longitudinal definitions. In total, 1589 infants with GA <30 weeks or birthweight ≤ 1500 g and without major congenital anomalies were included in this study. Cross-sectional and longitudinal EUGR were calculated at 36 and 40 weeks of GA, at discharge, and at 28 days. The concordance between the two definitions was estimated by Kappa coefficient. At 24-30 months, 803 infants were measured again. The agreement between the two definitions of EUGR was low. Both EUGR and not-EUGR groups were at lower centiles for weight, but at higher centiles for head circumference at 24-30 months than at birth. Longitudinal EUGR was associated with a poorer growth outcome for weight and height circumference than cross-sectional EUGR. No differences were observed for length. An agreed definition of EUGR is highly desirable in clinical practice to assess medical and nutritional interventions in preterm neonates. Based on the results of this study, we recommend the use of the longitudinal evaluation, that proved to better predict the auxological long-term outcome with respect to the cross-sectional one.
Evidence indicates that human milk (HM) is the best form of nutrition uniquely suited not only to term but also to preterm infants conferring health benefits in both the short and long-term. However, ...HM does not provide sufficient nutrition for the very low birth weight (VLBW) infant when fed at the usual feeding volumes leading to slow growth with the risk of neurocognitive impairment and other poor health outcomes such as retinopathy and bronchopulmonary dysplasia. HM should be supplemented (fortified) with the nutrients in short supply, particularly with protein, calcium, and phosphate to meet the high requirements of this group of babies. In this paper the European Milk Bank Association (EMBA) Working Group on HM Fortification discusses the existing evidence in this field, gives an overview of different fortification approaches and definitions, outlines the gaps in knowledge and gives recommendations for practice and suggestions for future research. EMBA recognizes that "Standard Fortification," which is currently the most utilized regimen in neonatal intensive care units, still falls short in supplying sufficient protein for some VLBW infants. EMBA encourages the use of "Individualized Fortification" to optimize nutrient intake. "Adjustable Fortification" and "Targeted Fortification" are 2 methods of individualized fortification. The quality and source of human milk fortifiers constitute another important topic. There is work looking at human milk derived fortifiers, but it is still too early to draw precise conclusions about their use. The pros and cons are discussed in this Commentary in addition to the evidence around use of fortifiers post discharge.
Long COVID-19 syndrome is a complex of symptoms that occurs after the acute SARS-CoV-2 infection, in the absence of other possible diagnoses. Studies on Long COVID-19 in pediatric population are ...scanty and heterogeneous in design, inclusion criteria, outcomes, and follow-up time. The objective of the present study is to assess the prevalence of Long COVID-19 syndrome in a cohort of Italian pediatric primary care patients, observed for a period of time of 8 to 36 weeks from healing. Prevalence was also assessed in a cohort of pediatric patients hospitalized during acute infection.
Data concerning 629 primary care patients with previous acute SARS-CoV-2 infection were collected by a questionnaire filled in by Primary Care Pediatrician (PCP). The questionnaire was administrated to patients by 18 PCPs based in 8 different Italian regions from June to August 2021. Data concerning 60 hospitalized patients were also collected by consultation of clinical documents.
Cumulative incidence of Long COVID-19 resulted to be 24.3% in primary care patients and 58% in hospitalized patients. The most frequently reported symptoms were abnormal fatigue (7%), neurological (6.8%), and respiratory disorders (6%) for the primary care cohort. Hospitalized patients displayed more frequently psychological symptoms (36.7%), cardiac involvement (23.3%), and respiratory disorders (18.3%). No difference was observed in cumulative incidence in males and females in both cohorts. Previous diseases did not influence the probability to develop Long COVID-19. The prevalence of Long COVID-19 was 46.5% in children who were symptomatic during acute infection and 11.5% in asymptomatic ones. Children aged 0 to 5 years had a greater risk to develop respiratory symptoms, while adolescents (aged 11-16 years) had a greater risk to develop neurological and psychological Long COVID-19 symptoms.
Our study demonstrates that Long COVID-19 is a reality in pediatric age and could involve even patients with mild or no acute symptoms. The results stress the importance of monitoring primary care pediatric patients after acute COVID-19 infection and the relevance of vaccination programs in pediatric population, also in order to avoid the consequences of Long COVID-19 syndrome.
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