Francesca Giuliani

Neonatal Anthropometric Charts: The Italian Neonatal Study Compared With Other European Studies

Background and Objective: This was a nationwide prospective study carried out in Italy between 2005 and 2007, involving 34 centers with a neonatal intensive care unit. The study reports the Italian Neonatal Study charts for weight, length, and head circumference of singletons born between 23 and 42 gestational weeks, comparing them with previous Italian data and with the most recent data from European countries. Patients and Methods: Single live born babies with ultrasound assessment of gestational age within the first trimester, and with both parents of Italian origin. Only fetal hydrops and major congenital anomalies diagnosed at birth were excluded. The reference set consists of 22,087 girls and 23,375 boys. Results: At each gestational age, boys are heavier than girls by about 4%. Later-born neonates are heavier than firstborn neonates by about 3%. The effects of sex and birth order on length and head circumference are milder. No differences were observed between babies born in central-north Italy and southern Italy. A large variability emerged among European neonatal charts, resulting in huge differences in the percentage of Italian Neonatal Study neonates below the 10th centile, which is traditionally used to define small-for-gestational-age babies. In the last 2 decades prominent changes in the distribution of birth weight emerged in Italy and in the rest of Europe, in both term and preterm neonates. Conclusions: The existing European neonatal charts, based on more or less recent data, were found to be inappropriate for Italy. Until an international standard is developed, the use of national updated reference charts is recommended.

Preterm Milk Oligosaccharides During the First Month of Lactation

OBJECTIVE: Oligosaccharides represent one of the main components of human milk, and they have been assigned important biological functions for newborns. Qualitatively and quantitatively, their presence in milk is strictly related to the expression of the mothers Se and/or Le genes, on the basis of which 4 different milk groups have been described. The aim of the study was to provide new data on the oligosaccharide composition of preterm milk in relation to the 4 groups. METHODS: High-pH anion-exchange chromatography was used to quantify levels of 23 oligosaccharides and lactose in 252 milk samples collected from 63 mothers during the first month of lactation and to identify the 4 milk groups. RESULTS: Substantial differences in oligosaccharide contents were found within the groups and were strictly related to the presence or absence of specific fucosyl-oligosaccharides. The highest concentration was found in group 1 (>20 g/L), the lowest level was found in group 4 (∼10 g/L), and intermediate values were observed in groups 2 and 3. No statistically significant differences in lactose concentrations were observed among the groups. CONCLUSIONS: Our data confirm lower lactose concentrations in preterm milk, compared with term milk, and they provide the first detailed characterization of oligosaccharides in preterm milk, demonstrating important differences in oligosaccharide contents in the 4 groups. These differences might exert an influence on several biological functions that are particularly important for preterm infants and currently are attributed to milk oligosaccharides.

Necrotizing enterocolitis: risk factor analysis and role of gastric residuals in very low birth weight infants.

Objective: Necrotizing enterocolitis (NEC) usually occurs in very low birth weight infants and is the most common gastrointestinal emergency in the neonatal intensive care unit. Inasmuch as NEC mortality and morbidity are extremely high, early diagnosis becomes essential. Increased gastric residuals are used to define NEC stage, but studies on qualitative and quantitative residual features as markers of NEC risk are still lacking. The primary goal of this analysis was evaluation of the role of gastric residuals in early identification of patients at risk for NEC. The secondary goal was investigation of NEC risk factors, besides prematurity and birth weight. Methods: In a case-control study, NEC patients were matched with control infants by gestational age and birth weight. Feeding tolerance was assessed by maximum gastric residual volume, maximum residual as percentage of previous feeding, and residual appearance. Mortality and NEC risk factors were also evaluated. Results: In all, 844 very low birth weight infants were admitted to the neonatal intensive care unit during the study period, with an overall mortality before discharge of 14.6%. NEC frequency was 2%. Patent ductus arteriosus was significantly associated with NEC. Mean maximum residual from birth to NEC onset and maximum residual as percentage of the corresponding feed volume were significantly higher in patients than in control infants, as was the percentage of infants with hemorrhagic residuals. Conclusions: Gastric residuals are a marker of feeding intolerance, and bloody residuals seem to be the best predictor for NEC. For early detection of very low birth weight infants at risk for NEC, both gastric residual volumes and bloody residuals represent an early relevant marker.

INTERGROWTH-21st very preterm size at birth reference charts

844 www.thelancet.com Vol 387 February 27, 2016 malformations, or ultrasound evidence of FGR, and 37 because of implausible anthropometric measurements or gestational age estimates. As expected, perinatal events (eg, higher pre-eclampsia, caesarean section, and neonatal mortality rates) for these very preterm babies diff ered from the Newborn Size Standards (appendix). The third, 10th, 50th, 90th, and 97th smoothed centile curves for weight, length, and head circumference at birth according to gestational age and sex, superimposed on the individual data, are shown in the appendix (actual centile values and corresponding equations are provided in the appendix and at the INTERGROWTH-21st website). Values for birthweight and head circumference at 33 weeks’ gestation overlapped perfectly with the original Newborn Size Standards; values for length were complementary at the median level, but less so at the extreme centiles because of the diff erently shaped curves in early and late pregnancy (fi gure). We present very preterm reference charts for newborn baby size at birth using the same underlying population, methods, instruments, standardisation protocols, and statistical analyses as for the Newborn Size Standards, which they complement well. They provide neonatologists with a single way to assess and screen newborn babies from 24 to 42 weeks’ gestation. The head circumference charts are particularly important in view of the urgent need, in the midst of the Zika virus outbreak, to assess the head size of newborn babies with a set of standardised, gestational-age specifi c charts, to avoid over-reporting of cases of microcephaly across all aff ected regions.

The Effect of Holder Pasteurization on Nutrients and Biologically-Active Components in Donor Human Milk: A Review

When a mother’s milk is unavailable, the best alternative is donor milk (DM). Milk delivered to Human Milk Banks should be pasteurized in order to inactivate the microbial agents that may be present. Currently, pasteurization, performed at 62.5 °C for 30 min (Holder Pasteurization, HoP), is recommended for this purpose in international guidelines. Several studies have been performed to investigate the effects of HoP on the properties of DM. The present paper has the aim of reviewing the published papers on this topic, and to provide a comparison of the reported variations of biologically-active DM components before and after HoP. This review was performed by searching the MEDLINE, EMBASE, CINHAL and Cochrane Library databases. Studies that clearly identified the HoP parameters and compared the same DM samples, before and after pasteurization, were focused on. A total of 44 articles satisfied the above criteria, and were therefore selected. The findings from the literature report variable results. A possible explanation for this may be the heterogeneity of the test protocols that were applied. Moreover, the present review spans more than five decades, and modern pasteurizers may be able to modify the degradation kinetics for heat-sensitive substances, compared to older ones. Overall, the data indicate that HoP affects several milk components, although it is difficult to quantify the degradation degree. However, clinical practices demonstrate that many beneficial properties of DM still persist after HoP.

Benefits of donor milk in the feeding of preterm infants.

Mothers own milk is widely recognized as the optimal feeding for term infants, but also provides health benefits that are of vital importance for sick and preterm infants in neonatal intensive care units (NICUs), even though the growth and neurodevelopmental needs of very premature infants are best met by appropriate fortification of human milk (HM). When mothers milk is unavailable or in short supply, donor milk (DM) represents the second best alternative and, although some nutritional elements are inactivated by the pasteurization process, it still has documented advantages compared to formula. Occasionally, the concern that the use of DM might decrease breastfeeding is being raised, but reports exist in literature showing that the use of donor HM in the NICU increases breastfeeding rates at discharge for VLBW infants. The demonstrated benefits of HM highlight the importance of educating health care professionals in breastfeeding support.

Weight growth velocity of very low birth weight infants: role of gender, gestational age and major morbidities

Its well known that VLBWI fail to thrive, however its still unclear how gender, GA and morbidities affect growth pattern: aim of this study is to assess the influence of these factors on weight growth. 262 VLBWI were selected. Weight was recorded daily up to 28 days, weekly up to discharge and during 7 scheduled follow-up visits up to 2 years of corrected age. Individual profiles were fitted with a mathematical function suitable to model selected growth milestones and mean distance and velocity curves were drawn. Effects of gender, GA, major-morbidities, nutritional and respiratory support on individual weight growth milestones were estimated using a multivariate linear model. Each of these variables acts differently on weight growth pattern mainly modifying velocity curves characteristics. In particular, infants with major morbidities weight growth impairment-seen on distance curves at 2 years of corrected age-depends on poor weight velocity during a critical period ending within 4th month of postnatal age, for SGA or BPD infants, starting from 5th month of postnatal for severely neurologically impaired infants. These critical periods could be the most appropriate to identify risk factors for weight growth impairment in VLBWI.

Monitoring human growth and development: a continuum from the womb to the classroom

A comprehensive set of fully integrated anthropometric measures is needed to evaluate human growth from conception to infancy so that consistent judgments can be made about the appropriateness of fetal and infant growth. At present, there are 2 barriers to this strategy. First, descriptive reference charts, which are derived from local, unselected samples with inadequate methods and poor characterization of their putatively healthy populations, commonly are used rather than prescriptive standards. The use of prescriptive standards is justified by the extensive biologic, genetic, and epidemiologic evidence that skeletal growth is similar from conception to childhood across geographic populations, when health, nutrition, environmental, and health care needs are met. Second, clinicians currently screen fetuses, newborn infants, and infants at all levels of care with a wide range of charts and cutoff points, often with limited appreciation of the underlying population or quality of the study that generated the charts. Adding to the confusion, infants are evaluated after birth with a single prescriptive tool: the World Health Organization Child Growth Standards, which were derived from healthy, breastfed newborn infants, infants, and young children from populations that have been exposed to few growth-restricting factors. The International Fetal and Newborn Growth Consortium for the 21st Century Project addressed these issues by providing international standards for gestational age estimation, first-trimester fetal size, fetal growth, newborn size for gestational age, and postnatal growth of preterm infants, all of which complement the World Health Organization Child Growth Standards conceptually, methodologically, and analytically. Hence, growth and development can now, for the first time, be monitored globally across the vital first 1000 days and all the way to 5 years of age. It is clear that an integrative approach to monitoring growth and development from pregnancy to school age is desirable, scientifically supported, and likely to improve care, referral patterns, and reporting systems. Such integration can be achieved only through the use of international growth standards, especially in increasingly diverse, mixed ancestry populations. Resistance to new scientific developments has been hugely problematic in medicine; however, we are confident that the obstetric and neonatal communities will join their pediatric colleagues worldwide in the adoption of this integrative strategy.

Neonatal growth charts.

The ability to recognize abnormal growth at birth and/or an intrauterine malnutrition is of great importance for neonatal care and prognosis. The current gold standard in neonatal auxological evaluation is based on information obtained from both neonatal anthropometric charts and intrauterine growth charts. Numerous charts have been proposed, but they are hardly comparable with each other, due to numerous methodological problems. The Italian Society of Neonatology, the Italian Society of Pediatric Endocrinology and Diabetology and the Italian Society of Medical Statistics and Clinical Epidemiology promoted a multicenter survey with the aim to produce an Italian neonatal anthropometric reference (Italian Neonatal Study [INeS] charts) fulfilling the set of the criteria that a reliable neonatal chart should possess. In clinical practice neonatal charts have some limitations if they are used to monitor postnatal growth of preterm newborns from birth to term. To overcome the problems related to the construction and use of a reference, an international project has recently started a study aiming to create prescriptive standard for the evaluation of postnatal growth of preterm infants (INTERGROWTH-21st). While an international longitudinal standard for evaluating preterm infant postnatal growth is lacking, in Italy the best compromise is likely to be as follows: new INeS charts up to term; International longitudinal charts WHO 2006 or CDC 2002 from term to 2 years; finally, the Italian Society for Pediatric Endocrinology and Diabetes (SIEDP) growth charts could be suitable for monitoring the growth of these infants from 2 years up to 20 years of age.

The antepartum stillbirth syndrome: risk factors and pregnancy conditions identified from the INTERGROWTH-21st Project

To identify risk factors for antepartum stillbirth, including fetal growth restriction, among women with well‐dated pregnancies and access to antenatal care.