Assessing the size of twins at birth using charts developed for singletons may over diagnose small for gestational age in this sub-population. The study aimed to produce international, twin-specific, newborn size normative charts by gestational age and sex. This longitudinal observational study in eight geographically diverse settings prospectively collected data between May 2009 and August 2013 from healthy pregnant women and their newborn twins. The participants were enrolled as part of the INTERGROWTH-21st study, and recruited based on World Health Organization recommendations for evaluation of anthropometric measures. All the women met, in addition to the underlying population characteristics of low perinatal risk, strict individual criteria for a population at low risk of impaired fetal growth. Newborn weight, length and head circumference measures were collected independently in duplicate by two trained anthropometrists within 12 hours of birth using identical equipment and protocols at all sites. From 1034 multiple pregnancies, after exclusions of condition such as smoking, high maternal BMI, and congenital malformations, the final sample was 864 twin newborns. Most of the twins were below the 50th centile of the INTERGROWTH-21st standards for singletons. We present international newborn size normative charts for twins using the same methodological approach adopted to construct the singleton standards.

Twin fetuses show a physiologically slower growth rate in the third trimester compared to singletons. Therefore, it has been suggested that the anthropometric evaluation of twins at birth should be performed using twin-specific charts. To be reliable, anthropometric charts need to fulfil certain methodological criteria to systematically review studies that have developed neonatal twin-specific anthropometric charts and assess their methodological quality. A comprehensive search was conducted across Cinahl, Embase, Global Index Medicus, PubMed, Scopus, Web of Science, Google Scholar, and relevant preprint repositories, followed by a predefined snowballing search. Two reviewers independently screened studies for eligibility, selecting those that have developed cross-sectional anthropometric charts for twins at birth, published since January 1990. Articles were excluded if they did not use anthropometric measurements at birth to construct charts. Two reviewers independently extracted data and performed quality assessment with a 16-item grading system. Sixty-eight studies were included, with all but one constructed reference, not standard, charts. Most studies did not meet the quality criteria: only 9% were prospectively designed, 34% reliably estimated gestational age, 19% reported standardized instruments, 28% described measurement techniques, and 26% did not stratify centiles by sex. This review reveals considerable methodological limitations in existing twin-specific neonatal anthropometric charts.

BACKGROUND: In early 2023, when Omicron was the variant of concern, we showed that vaccinating pregnant women decreased the risk for severe COVID-19-related complications and maternal morbidity and mortality. OBJECTIVE: This study aimed to analyze the impact of COVID-19 during pregnancy on newborns and the effects of maternal COVID-19 vaccination on neonatal outcomes when Omicron was the variant of concern. STUDY DESIGN: INTERCOVID-2022 was a large, prospective, observational study, conducted in 40 hospitals across 18 countries, from November 27, 2021 (the day after the World Health Organization declared Omicron the variant of concern) to June 30, 2022, to assess the effect of COVID-19 in pregnancy on maternal and neonatal outcomes and to assess vaccine effectiveness. Women diagnosed with laboratory-confirmed COVID19 during pregnancy were compared with 2 nondiagnosed, unmatched women recruited concomitantly and consecutively during pregnancy or at delivery. Mother-newborn dyads were followed until hospital discharge. The primary outcomes were a neonatal positive test for COVID-19, severe neonatal morbidity index, severe perinatal morbidity and mortality index, preterm birth, neonatal death, referral to neonatal intensive care unit, and diseases during the neonatal period. Vaccine effectiveness was estimated with adjustment for maternal risk profile. RESULTS: We enrolled 4707 neonates born to 1577 (33.5%) mothers diagnosed with COVID-19 and 3130 (66.5%) nondiagnosed mothers. Among the diagnosed mothers, 642 (40.7%) were not vaccinated, 147 (9.3%) were partially vaccinated, 551 (34.9%) were completely vaccinated, and 237 (15.0%) also had a booster vaccine. Neonates of booster- vaccinated mothers had less than half (relative risk, 0.46; 95% confidence interval, 0.23-0.91) the risk of being diagnosed with COVID-19 when compared with those of unvaccinated mothers; they also had the lowest rates of preterm birth, medically indicated preterm birth, respiratory distress syndrome, and number of days in the neonatal intensive care unit. Newborns of unvaccinated mothers had double the risk for neonatal death (relative risk, 2.06; 95% confidence interval, 1.06-4.00) when compared with those of nondiagnosed mothers. Vaccination was not associated with any congenital malformations. Although all vaccines provided protection against neonatal test positivity, newborns of booster-vaccinated mothers had the highest vaccine effectiveness (64%; 95% confidence interval, 10%-86%). Vaccine effectiveness was not as high for messenger RNA vaccines only. Vaccine effectiveness against moderate or severe neonatal outcomes was much lower, namely 13% in the booster-vaccinated group (all vaccines) and 25% and 28% in the completely and booster-vaccinated groups, respectively (messenger RNA vaccines only). Vaccines were fairly effective in protecting neonates when given to pregnant women <100 days (14 weeks) before birth; thereafter, the risk increased and was much higher after 200 days (29 weeks). Finally, none of the neonatal practices studied, including skin-to-skin contact and direct breastfeeding, increased the risk for infecting newborns. CONCLUSION: When Omicron was the variant of concern, newborns of unvaccinated mothers had an increased risk for neonatal death. Neonates of vaccinated mothers had a decreased risk for preterm birth and adverse neonatal outcomes. Because the protective effect of COVID-19 vaccination decreases with time, to ensure that newborns are maximally protected against COVID-19, mothers should receive a vaccine or booster dose no more than 14 weeks before the expected date of delivery.

AIMS OF THE STUDY: Health equity is a key component of quality of care and an objective for a growing number of quality improvement projects for deontological, ethical, public health and economic reasons. To monitor equity in the delivery of health services in Switzerland, there is a need to implement valid, measurable and actionable equity indicators, along with vulnerability stratifiers such as migrant status, which could lead to differences in quality of care. The aim of this study was to develop a set of healthcare equity indicators and stratifiers targeting inpatient and outpatient populations and to test their feasibility. METHODS: A scoping literature review and inputs from a national interprofessional expert taskforce provided a set of indicators and vulnerability stratifiers. The most valid and measurable indicators and stratifiers were retained using a Delphi process. They were then operationalised, and their implementation tested in three Swiss hospitals from the three language regions. RESULTS: A taskforce of 18 experts, including a patient representative, selected 11 indicators that evaluate structures, processes and outcomes, and five vulnerability stratifiers. Although most indicators and stratifiers could be implemented in all three hospitals, data availability was limited for some variables, including patient satisfaction and access to interpreters for foreign-language patients. CONCLUSIONS: The equity indicators and stratifiers identified by this two-stage process have content validity, wide patient coverage and are focused on inequities in the healthcare system that are actionable through improvement projects. Both the indicators and the project methodology could be replicated in institutions aiming for more equitable care.

Objective: To examine the relationship between etiologically-based preterm birth sub-groups and early postnatal growth according to gestational age at birth. Methods: Prospective, multinational, cohort study involving 15 hospitals that monitored preterm newborns to hospital discharge. Measures/exposures: maternal demographics; etiologically-based preterm birth sub-groups; very, moderate and late preterm categories, and feeding. Primary outcomes: serial anthropometric measures expressed as z-scores of the INTERGROWTH-21st preterm postnatal growth standards. Results: We included 2320 singletons and 1180 twins: very=24.4% (n = 856, including 178 < 28 weeks' gestation); moderate=16.9% (n = 592) and late preterm=58.6% (n = 2052). The median (interquartile range) postmenstrual age at the last measure was 37 (36-38) weeks. The 'no main condition' sub-group percentage increased from early to late preterm; the 'perinatal sepsis' sub-group percentage decreased. 'Perinatal sepsis', 'suspected IUGR' and 'fetal distress' very and late preterm infants had lower postnatal growth patterns than the 'no main condition' reference sub-group. This pattern persisted in late but not very preterm infants when postnatal growth was corrected for weight z-score at birth. Conclusion: The proportional contribution of etiologically-based preterm sub-groups and their postnatal growth trajectories vary by preterm category. Postnatal growth is partially independent of fetal growth in the majority of preterm infants (i.e., those born late preterm).

BACKGROUND: The effect of COVID-19 in pregnancy on maternal outcomes and its association with preeclampsia and gestational diabetes mellitus have been reported; however, a detailed understanding of the effects of maternal positivity, delivery mode, and perinatal practices on fetal and neonatal outcomes is urgently needed. OBJECTIVE: To evaluate the impact of COVID-19 on fetal and neonatal outcomes and the role of mode of delivery, breastfeeding, and early neonatal care practices on the risk of mother-to-child transmission. STUDY DESIGN: In this cohort study that took place from March 2020 to March 2021, involving 43 institutions in 18 countries, 2 unmatched, consecutive, unexposed women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. COVID-19 in pregnancy was determined by laboratory confirmation and/or radiological pulmonary findings or >= 2 predefined COVID-19 symptoms. The outcome measures were indices of neonatal and perinatal morbidity and mortality, neonatal positivity and its correlation with mode of delivery, breastfeeding, and hospital neonatal care practices. RESULTS: A total of 586 neonates born to women with COVID-19 diagnosis and 1535 neonates born to women without COVID-19 diagnosis were enrolled. Women with COVID-19 diagnosis had a higher rate of cesarean delivery (52.8% vs 38.5% for those without COVID-19 diagnosis, P<.01) and pregnancy-related complications, such as hypertensive disorders of pregnancy and fetal distress (all with P<.001), than women without COVID-19 diagnosis. Maternal diagnosis of COVID-19 carried an increased rate of preterm birth (P<.001) and lower neonatal weight (P<.001), length, and head circumference at birth. In mothers with COVID-19 diagnosis, the length of in utero exposure was significantly correlated to the risk of the neonate testing positive (odds ratio, 4.5; 95% confidence interval, 2.2-9.4 for length of in utero exposure >14 days). Among neonates born to mothers with COVID-19 diagnosis, birth via cesarean delivery was a risk factor for testing positive for COVID-19 (odds ratio, 2.4; 95% confidence interval, 1.2-4.7), even when severity of maternal conditions was considered and after multivariable logistic analysis. In the subgroup of neonates born to women with COVID-19 diagnosis, the outcomes worsened when the neonate also tested positive, with higher rates of neonatal intensive care unit admission, fever, gastrointestinal and respiratory symptoms, and death, even after adjusting for prematurity. Breastfeeding by mothers with COVID-19 diagnosis and hospital neonatal care practices, including immediate skin-to-skin contact and rooming-in, were not associated with an increased risk of newborn positivity. CONCLUSION: In this multinational cohort study, COVID-19 in pregnancy was associated with increased maternal and neonatal complications. Cesarean delivery was significantly associated with newborn COVID-19 diagnosis. Vaginal delivery should be considered the safest mode of delivery if obstetrical and health conditions allow it. Mother-to-child skin-to-skin contact, rooming-in, and direct breastfeeding were not risk factors for newborn COVID-19 diagnosis, thus well-established best practices can be continued among women with COVID-19 diagnosis.

We thank Vivanti et al for their interest in our work. The INTERCOVID study started early in 2020 as a rapid, global response to explore the effect of COVID-19 during pregnancy,1Villar J. Ariff S. Gunier R.B. et al.Maternal and neonatal morbidity and mortality among pregnant women with and without COVID-19 infection: the INTERCOVID Multinational Cohort Study.JAMA Pediatr. 2021; 175: 817-826Crossref PubMed Scopus (753) Google Scholar long before the World Health Organization guidelines were published2World Health OrganizationDefinition and categorization of the timing of mother-to-child transmission of SARS-CoV-2. 2021.https://www.who.int/publications/i/item/WHO-2019-nCoV-mother-to-child-transmission-2021.1Google Scholar and before the widespread availability of tests and standardized policies for testing neonates. Hence, we did not undertake multiple sampling in the same baby to determine the timing of mother-to-child transmission. Collecting longitudinal data in a newborn population in the context of a different research study would be expected to yield information about the risk factors for mother-to-child transmission. We reported that cesarean delivery was associated with newborn positivity, though the mechanisms were unexplained.3Giuliani F. Oros D. Gunier R.B. et al.Effects of prenatal exposure to maternal COVID-19 and perinatal care on neonatal outcome: results from the INTERCOVID Multinational Cohort Study.Am J Obstet Gynecol. 2022; 227: 488.e1-488.e17Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar Vivanti et al suggest SARS-CoV-2 placentitis leading to fetal distress could be the cause of the increases in cesarean delivery. We think this is unlikely; although COVID-19 related placentitis has been identified in stillbirths and neonatal deaths,4Schwartz D.A. Avvad-Portari E. Babál P. et al.Placental tissue destruction and insufficiency from COVID-19 causes stillbirth and neonatal death from hypoxic-ischemic injury.Arch Pathol Lab Med. 2022; 146: 660-676Crossref PubMed Scopus (86) Google Scholar it appears too uncommon a complication5Redline R.W. Ravishankar S. Bagby C. Saab S. Zarei S. Diffuse and localized SARS-CoV-2 placentitis: prevalence and pathogenesis of an uncommon complication of COVID-19 infection during pregnancy.Am J Surg Pathol. 2022; 46: 1036-1047Crossref PubMed Scopus (9) Google Scholar to explain such high rates. In addition, as we reported,3Giuliani F. Oros D. Gunier R.B. et al.Effects of prenatal exposure to maternal COVID-19 and perinatal care on neonatal outcome: results from the INTERCOVID Multinational Cohort Study.Am J Obstet Gynecol. 2022; 227: 488.e1-488.e17Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar there were no differences in the indications for cesarean delivery nor in the severity of the maternal condition between the test-positive and negative neonates among test-positive mothers. We have now conducted a series of sensitivity analyses, adding fetal distress to the model as a confounder and removing from the total sample all the neonates with fetal distress (Table). We compared neonates that were positive for SARS-CoV-2 after birth by cesarean delivery to those positive neonates that were not born by cesarean delivery. The odds ratio remained considerably higher and very similar to our original estimates.TableEffect of fetal distress on the relationship between neonatal SARS-CoV-2 positivity and cesarean delivery among COVID-19–diagnosed mothersCasesNeonate SARS-CoV-2-positive cesarean deliveryn/N (%)Neonate SARS-CoV-2-positive noncesarean deliveryn/N (%)AdjustedaModels adjusted for weeks between mother's positive COVID-19 test and delivery and immediate skin-to-skin contact between mother and child. odds ratio (95% confidence interval)All cases—original results from manuscript37/53 (69.8%)16/53 (30.2%)2.4 (1.2–4.7)All cases—adjusting for fetal distress in the model37/53 (69.8%)16/53 (30.2%)2.5 (1.2–4.9)Excluding all neonates with fetal distress28/44 (63.6%)16/44 (36.4%)2.3 (1.1–4.6)Giuliani. Vaginal birth vs cesarean for COVID-19 in pregnancy. Am J Obstet Gynecol 2023.a Models adjusted for weeks between mother's positive COVID-19 test and delivery and immediate skin-to-skin contact between mother and child. Open table in a new tab Giuliani. Vaginal birth vs cesarean for COVID-19 in pregnancy. Am J Obstet Gynecol 2023. We stand by our conclusions that because cesarean delivery does not protect against SARS-CoV-2 transmission to the newborn, vaginal delivery should be the preferred mode of delivery even in symptomatic women as long as there is no indication from an obstetrical or other clinical condition. Cesarean delivery and neonatal SARS-CoV-2 infections: beware of hasty shortcutsAmerican Journal of Obstetrics & GynecologyVol. 228Issue 3PreviewWe read with great interest the article titled "Effects of prenatal exposure to maternal COVID-19 and perinatal care on neonatal outcome: results from the INTERCOVID Multinational Cohort Study." The work reported by the authors of the INTERCOVID study sheds new light on the effects of SARS-CoV-2 in pregnant women and newborns, and they are to be congratulated.1 Full-Text PDF

Background: The aim of this study is to assess the serum values of IL-4, IL-5, IL-10, and IL-13 in a group of infants with non-IgE mediated food allergies treated with a hydrolyzed formula and compare them with a group of healthy peers. Methods: A total of 53 infants aged 1 to 4 months, of which 34 with non-IgE mediated food allergies and 19 healthy infants were enrolled in this study. Infants were eligible if they had gastrointestinal symptoms of food allergy and needed to switch from their initial formula to hydrolyzed formulas with an improvement of symptoms. Controls were fed with either breastmilk or standard formula. Blood samples were taken within one week of a special diet for cases. Interleukinsin in peripheral blood was detected and analyzed using the real-time PCR MAMA method. Fecal calprotectin was evaluated using a quantitative assay. Results: Values of IL-4 and IL-13 were significantly higher in the non-IgE food allergy group compared to the control group (p < 0.05), while IL-5 and IL-10 were significantly lower than the control group (p < 0.05). Fecal calprotectin in the non-IgE food allergy group was significantly higher compared to the control group (p < 0.05). Conclusion: This study provides a theoretical basis that Th2 cytokine expression in infants with a non-IgE mediated food allergy is significantly different than in healthy infants; this finding supports the use of early dietetic treatment with hydrolyzed formulas.

BACKGROUND: It is unclear whether the suggested link between COVID-19 during pregnancy and preeclampsia is an independent association or if these are caused by common risk factors. OBJECTIVE: This study aimed to quantify any independent association between COVID-19 during pregnancy and preeclampsia and to determine the effect of these variables on maternal and neonatal morbidity and mortality. STUDY DESIGN: This was a large, longitudinal, prospective, unmatched diagnosed and not-diagnosed observational study assessing the effect of COVID-19 during pregnancy on mothers and neonates. Two consecutive not diagnosed women were concomitantly enrolled immediately after each diagnosed woman was identified, at any stage during pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed until hospital discharge using the standardized INTERGROWTH-21st protocols and electronic data management system. A total of 43 institutions in 18 countries contributed to the study sample. The independent association between the 2 entities was quantified with the risk factors known to be associated with preeclampsia analyzed in each group. The outcomes were compared among women with COVID-19 alone, preeclampsia alone, both conditions, and those without either of the 2 conditions. RESULTS: We enrolled 2184 pregnant women; of these, 725 (33.2%) were enrolled in the COVID-19 diagnosed and 1459 (66.8%) in the COVID-19 not diagnosed groups. Of these women, 123 had preeclampsia of which 59 of 725 (8.1%) were in the COVID-19 among parous women (risk ratio, 1.64; 95% confidence interval, 0.99-2.73). The risk ratio for preterm birth for all women diagnosed with COVID-19 and preeclampsia was 4.05 (95% confidence interval, 2.99-5.49) and 6.26 (95% confidence interval, 4.35-9.00) for nulliparous women. Compared with women with neither condition diagnosed, the composite adverse perinatal outcome showed a stepwise increase in the risk ratio for COVID-19 without preeclampsia, preeclampsia without COVID-19, and COVID-19 with preeclampsia (risk ratio, 2.16; 95% confidence interval, 1.63-2.86; risk ratio, 2.53; 95% confidence interval, 1.44-4.45; and risk ratio, 2.84; 95% confidence interval, 1.67-4.82, respectively). Similar findings were found for the composite adverse maternal outcome with risk ratios of 1.76 (95% confidence interval, 1.32-2.35), 2.07 (95% confidence interval, 1.20-3.57), and 2.77 (95% confidence interval, 1.66-4.63). The association between COVID-19 and gestational hypertension and the direction of the effects on preterm birth and adverse perinatal and maternal outcomes, were similar to preeclampsia, but confined to nulliparous women with lower risk ratios. CONCLUSION: COVID-19 during pregnancy is strongly associated with preeclampsia, especially among nulliparous women. This association is independent of any risk factors and preexisting conditions. COVID-19 severity does not seem to be a factor in this association. Both conditions are associated independently of and in an additive fashion with preterm birth, severe perinatal morbidity and mortality, and adverse maternal outcomes. Women with preeclampsia should be considered a particularly vulnerable group with regard to the risks posed by COVID-19.

Patient: Female, 1-month-old Final Diagnosis: Intussusception Symptoms: Rectal bleeding Medication: — Clinical Procedure: Ultrasonography Specialty: Pediatrics and Neonatology Objective: Challenging differential diagnosis Background: Intussusception is the most common cause of intestinal obstruction in children, with a peak incidence usually before the second year of age, while in neonates it is a rare entity. We describe a delayed and incidental diagnosis of neonatal intussusception secondary to Meckel’s diverticulum in a neonate with shaken baby syndrome (SBS). This is, to the best of our knowledge, the first reported case of a neonatal intussusception with a Meckel’s diverticulum as a lead point in a neurologically impaired child. Case Report: A term baby presented at 22 days of age at our Emergency Department in severe conditions due to a suspected SBS. Eight days following hospitalization in the Intensive Care Unit, an isolated episode of rectal bleeding occurred, without any worsening of general conditions or abdominal distension. The ultrasonography showed a “doughnut sign” with high suspicion of ileocecal intussusception. A rectal barium contrast enema was performed but was not resolutive. At exploratory laparotomy an ileocecal intussusception with Meckel’s diverticulum acting as a lead point was identified and an intestinal resection was needed due to the ischemic condition of the ileum. The post-operative course was uneventful and the baby recovered well; the residual neurological impairment needed long-term follow-up. Conclusions: Intussusception is a rare entity in neonates and, when severe neurological impairment is present, the diagnosis can be missed because of the compromised condition of the baby and the paucity of gastrointestinal manifestations. In addition, due to the high incidence of lead point in neonatal cases, we recommend reserving non-operative treatment only for selected cases.

Preterm infant growth is a major health indicator and needs to be monitored with an appropriate growth curve to achieve the best developmental and growth potential while avoiding excessive caloric intake that is linked to metabolic syndrome and hypertension later in life. New international standards for size at birth and postnatal growth for preterm infants are available and need implementation in clinical practice. A prospective, single center observational study was conducted to evaluate the in-hospital and long-term growth of 80 preterm infants with a mean gestational age of 33.3 ± 2.2 weeks, 57% males. Size at birth and at discharge were assessed using the INTERGROWTH-21ST standards, at preschool age with World Health Organization (WHO) child growth standards. The employment of INTERGROWTH-21ST Preterm Postnatal longitudinal standards during the in-hospital follow-up significantly reduced the diagnosis of short term extrauterine growth restriction when compared to commonly used cross sectional neonatal charts, with significant lower loss of percentiles between birth and term corrected age (p < 0.0001). The implementation of a package of standards at birth, preterm postnatal growth standards and WHO child growth standards proved to be consistent, with correlation between centile at birth and at follow-up, and therefore effective in monitoring growth in a moderate and late preterm infant cohort without chronic or major morbidities. Infants identified as small for gestational age at birth showed significantly more frequently a need for auxological referral.

Neonatal adrenal hemorrhage (NAH) in newborn infants is a rare event that is associated with specific anatomical and vascular characteristics. It is more common in term infants and occurs more often in neonates who feature perinatal asphyxia. Symptoms that more frequently prompt to diagnosis are prolonged jaundice, detection of an abdominal mass, anemia, scrotal discoloration and/or swelling, hypotonia, lethargy, and hypertension. However, NAH may also occur without symptoms with its detection being occasional. Imaging through ultrasound scans is the cornerstone of diagnosis and follow-up monitoring over time. Here we report on a small NAH case series comprising three full-term, macrosomic infants who were born by vaginal delivery. The first and second ones showed clear signs of birth asphyxia, whereas the third was completely asymptomatic. In all three patients, only the right adrenal gland was involved, in line with what happens in 70% of cases. NAH is usually self-limiting and prone to a progressive resolution in a time ranging between 3 weeks and 6 months and so did in our three patients. Key Points

Background: ExtraUterine Growth Restriction (EUGR) is a common definition for in-hospital growth failure of very preterm infants. Wide heterogeneity is found in definitions and anthropometric charts used to describe EUGR.Aim: We aim to compare two traditional definitions of EUGR with a newly proposed one, based on a longitudinal evaluation, that takes into account the physiological period of fluid loss after birth. We also wish to detect which definition could better predict neurodevelopmental impairment at 24 months of corrected age (CA).Methods: A total of 195 infants with GA < 30 were included. EUGR was calculated both for weight and head circumference (HC). Cross-sectional EUGR was defined as measurements < 10th percentile at discharge; longitudinal EUGR was defined as Δz-score < −1 between birth and discharge measurements. The new longitudinal “post-loss” EUGR definition was proposed as Δz-score < −1 between measurements taken at 14–21 days of life and at discharge. Longitudinal postnatal Intergrowth-21st charts specifically built on preterm infants were used. Association with major and minor neurodevelopmental impairment at 24-month CA was assessed for each definition. K coefficient and ROC curve were evaluated.Results: Longitudinal “post-loss” definition of EUGR for HC is the one predicting minor neurodevelopmental impairment at the multivariate analysis (OR = 3.94), and it is also associated with a worse General Quotient. The chosen cut-off (Δz-score < −1) is the proper one.Conclusion: HC in-hospital growth could be a more accurate tool than weight to predict neurodevelopmental outcomes and especially minor neurological impairment. Longitudinal “post-loss” definition of EUGR assessed on longitudinal charts for preterm infants could be the most appropriate definition from the methodological, clinical, and prognostic point of view.

Objectives To describe the construction of the international INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) standards for child development at 2 years by reporting the cognitive, language, motor and behaviour outcomes in optimally healthy and nourished children in the INTERGROWTH-21st Project. Design Population-based cohort study, the INTERGROWTH-21st Project. Setting Brazil, India, Italy, Kenya and the UK. Participants 1181 children prospectively recruited from early fetal life according to the prescriptive WHO approach, and confirmed to be at low risk of adverse perinatal and postnatal outcomes. Primary measures Scaled INTER-NDA domain scores for cognition, language, fine and gross motor skills and behaviour; vision outcomes measured on the Cardiff tests; attentional problems and emotional reactivity measured on the respective subscales of the preschool Child Behaviour Checklist; and the age of acquisition of the WHO gross motor milestones. Results Scaled INTER-NDA domain scores are presented as centiles, which were constructed according to the prescriptive WHO approach and excluded children born preterm and those with significant postnatal/neurological morbidity. For all domains, except negative behaviour, higher scores reflect better outcomes and the threshold for normality was defined as ≥10th centile. For the INTER-NDA’s cognitive, fine motor, gross motor, language and positive behaviour domains these are ≥38.5, ≥25.7, ≥51.7, ≥17.8 and ≥51.4, respectively. The threshold for normality for the INTER-NDA’s negative behaviour domain is ≤50.0, that is, ≤90th centile. At 22–30 months of age, the cohort overlapped with the WHO motor milestone centiles, showed low postnatal morbidity (<10%), and vision outcomes, attentional problems and emotional reactivity scores within the respective normative ranges. Conclusions From this large, healthy and well-nourished, international cohort, we have constructed, using the WHO prescriptive methodology, international INTER-NDA standards for child development at 2 years of age. Standards, rather than references, are recommended for population-level screening and the identification of children at risk of adverse outcomes.

We studied neurodevelopmental outcomes and behaviours in healthy 2-year old children (N = 1306) from Brazil, India, Italy, Kenya and the UK participating in the INTERGROWTH-21st Project. There was a positive independent relationship of duration of exclusive breastfeeding (EBF) and age at weaning with gross motor development, vision and autonomic physical activities, most evident if children were exclusively breastfed for ≥7 months or weaned at ≥7 months. There was no association with cognition, language or behaviour. Children exclusively breastfed from birth to <5 months or weaned at >6 months had, in a dose-effect pattern, adjusting for confounding factors, higher scores for “emotional reactivity”. The positive effect of EBF and age at weaning on gross motor, running and climbing scores was strongest among children with the highest scores in maternal closeness proxy indicators. EBF, late weaning and maternal closeness, associated with advanced motor and vision maturation, independently influence autonomous behaviours in healthy children.

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.

Background Twins experience altered growth compared to singletons. The primary aim of this study was to compare growth and body composition (BC) of twin and singleton preterm infants from birth to 3 months according to gestational age (GA). Secondary aims were to evaluate the effect of chorionicity and mode of feeding on twins’ BC. Methods Anthropometric measurements and BC were performed at term and 3 months in preterm infants (GA < 37 weeks). Infants were categorized as: extremely, very, moderate and late preterm infants. Chorionicity was assigned as monochorionic, dichorionic or multichorionic. Mode of feeding was recorded as any human milk feeding vs formula feeding. Results Five hundred and seventy-six preterm infants were included (223 twins). Late-preterm twins were lighter and shorter at each study point; fat-free mass (FFM) was lower in these infants at each study point, compared to singletons. No differences were found between twins and singleton on the other category. Multichorionic infants had an FFM deficit compared to monochorionic and dichorionic at term, whereas no differences were found at 3 months. FFM at term was negatively associated with being twin and formula-fed. Conclusions Twins and singletons born before 34 weeks’ GA showed similar anthropometry and BC. Conversely, twin late-preterm infants showed different growth and BC compared to singletons.