Fetal growth velocity standards from the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project.

BACKGROUND: Human growth is susceptible to damage from insults, particularly during periods of rapid growth. Identifying those periods and the normative limits that are compatible with adequate growth and development are the first key steps toward preventing impaired growth. OBJECTIVE: This study aimed to construct international fetal growth velocity increment and conditional velocity standards from 14 to 40 weeks' gestation based on the same cohort that contributed to the INTERGROWTH-21st Fetal Growth Standards. STUDY DESIGN: This study was a prospective, longitudinal study of 4321 low-risk pregnancies from 8 geographically diverse populations in the INTERGROWTH-21st Project with rigorous standardization of all study procedures, equipment, and measurements that were performed by trained ultrasonographers. Gestational age was accurately determined clinically and confirmed by ultrasound measurement of crown-rump length at <14 weeks' gestation. Thereafter, the ultrasonographers, who were masked to the values, measured the fetal head circumference, biparietal diameter, occipitofrontal diameter, abdominal circumference, and femur length in triplicate every 5 weeks (within 1 week either side) using identical ultrasound equipment at each site (4-7 scans per pregnancy). Velocity increments across a range of intervals between measures were modeled using fractional polynomial regression. RESULTS: Peak velocity was observed at a similar gestational age: 16 and 17 weeks' gestation for head circumference (12.2 mm/wk), and 16 weeks' gestation for abdominal circumference (11.8 mm/wk) and femur length (3.2 mm/wk). However, velocity growth slowed down rapidly for head circumference, biparietal diameter, occipitofrontal diameter, and femur length, with an almost linear reduction toward term that was more marked for femur length. Conversely, abdominal circumference velocity remained relatively steady throughout pregnancy. The change in velocity with gestational age was more evident for head circumference, biparietal diameter, occipitofrontal diameter, and femur length than for abdominal circumference when the change was expressed as a percentage of fetal size at 40 weeks' gestation. We have also shown how to obtain accurate conditional fetal velocity based on our previous methodological work. CONCLUSION: The fetal skeleton and abdomen have different velocity growth patterns during intrauterine life. Accordingly, we have produced international Fetal Growth Velocity Increment Standards to complement the INTERGROWTH-21st Fetal Growth Standards so as to monitor fetal well-being comprehensively worldwide. Fetal growth velocity curves may be valuable if one wants to study the pathophysiology of fetal growth. We provide an application that can be used easily in clinical practice to evaluate changes in fetal size as conditional velocity for a more refined assessment of fetal growth than is possible at present (https://lxiao5.shinyapps.io/fetal_growth/). The application is freely available with the other INTERGROWTH-21st tools at https://intergrowth21.tghn.org/standards-tools/.

INTERGROWTH-21st Project international INTER-NDA standards for child development at 2 years of age: an international prospective population-based study.

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.

Late weaning and maternal closeness, associated with advanced motor and visual maturation, reinforce autonomy in healthy, 2-year-old children.

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.

Adherence to the Traditional Mediterranean Diet and Human Milk Composition: Rationale, Design, and Subject Characteristics of the MEDIDIET Study.

Introduction: Knowledge about how a lactating woman's diet influences the composition of her breast milk is still very limited. In particular, no study has evaluated the role of adherence to the Mediterranean diet on human milk characteristics. Aim: We carried out an observational study to investigate the influence of mother adherence to a Mediterranean diet on her breast milk composition. Methods: Between 2012 and 2014, 300 healthy mothers, who exclusively breastfed their babies, were enrolled from five centers across Italy. During a visit to the hospital center 6 weeks after childbirth these women were asked to provide a sample of their freshly expressed breast milk and to answer a series of questions on personal characteristics and lifestyle factors. The application of a validated food frequency questionnaire allowed the collection of detailed dietary habits. Milk was collected and then stored until chemical analyses were performed. The study has been registered (Trial Registration: Dutch Trial register NTR3468). Descriptive analyses on baseline characteristics of mothers and babies were carried out on the participants, overall and stratified by center. Results: The participants had a mean age of 33 years (SD = 4.06), and a pre-pregnancy BMI of 22.3 Kg/m2 (SD = 3.22). Forty-seven percent gave birth to their first child, 40% to the second 13% to the third or subsequent child. Babies had a mean birth weight of 3,324 g (DS = 389), and a mean length of 51 cm (SD = 1.94). Fifty-three percent were males. Conclusion: The present work provides the general description and the characteristics of mothers and babies included in the MediDiet study.

Neurodevelopmental milestones and associated behaviours are similar among healthy children across diverse geographical locations.

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.

Benefits of donor milk in the feeding of preterm infants.

Mother's 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 mother's 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.

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.

Evaluation of postnatal growth of preterm infants.

The past two decades have seen a progressive improvement in the survival rates of preterm infants, especially in neonates <30 weeks of gestational age. These neonates constitute the large majority of the population in neonatal intensive care units. The correct evaluation of postnatal growth of these babies is nowadays of primary concern, although the definition of their optimal postnatal growth pattern is still controversial. Concerns have also been raised about the strategies to monitor their growth, specifically in relation to the charts used. At present the available charts in clinical practice are fetal growth charts, neonatal anthropometric charts and postnatal growth charts for term infants. None of these, for different reasons, is suitable to correctly evaluate preterm infant growth. An international multicentric project has recently started a study aiming at building a prescriptive standard for the evaluation of postnatal growth of preterm infants and it will be available in the next years providing a population that is conceptually as close as possible to the prescriptive approach used for the construction of the WHO infant and child growth standards. At present, while an international longitudinal standard for evaluating preterm infant postnatal growth is lacking, in Italy the best compromise in clinical practice is likely to be as follows: new Italian INeS (Italian Neonatal Study) charts up to term; International longitudinal charts WHO 2006 or CDC 2002 from term to two years; finally the Italian Society for Pediatric Endocrinology and Diabetes (SIEDP) 2006 growth charts could be suitable for monitoring the growth of these infants from two years up to 20 years of age.