- The global, multidisciplinary INTERGROWTH-21st Project showed that babies grow similarly inside the womb and achieve a similar size at birth irrespective of ancestry, nationality or ethnicity, provided mothers are healthy, receive good healthcare, breastfeed, and are not exposed to environmental factors that adversely impact infant growth.
- The project produced international growth standards, which describe how all foetuses and newborns should grow across the world. The standards ensure disturbances in the growth of individual infants can be identified early. At population level, they enable health inequalities within and across countries to be highlighted.
- This report describes how the INTERGROWTH-21st Project led to the production of growth standards that can be used globally to assess infant development.
Growth charts enable parents and healthcare professionals to assess whether a child is growing healthily. The most widely used charts across the globe are international standards, produced by the World Health Organization (WHO), that apply to all children.
The WHO Child Growth Standards are based on the findings of a landmark WHO research study, which showed that breastfed babies, born at term to mothers who are healthy, educated and living in a clean environment, will grow in a similar way from 0 to 5 years of age irrespective of their ethnicity. Thus, the standards describe optimal growth and enable children who are excessively short (stunted) or thin (wasted) to be identified.
The INTERGROWTH-21st Project has produced a comprehensive set of clinical tools for monitoring the growth and development globally of all infants from early pregnancy to 2 years of age.
Multiple factors, many of which are preventable such as poor nutrition and infections, can restrict growth from as early as foetal life. Recognising that growth is affected is vitally important, given that poor growth can lead to a higher risk of health problems in later life, including decreased cognitive development and an increased likelihood of developing cardiovascular and metabolic disorders.
What is INTERGROWTH-21st?
The International Fetal and Newborn Growth Consortium for the 21st Century, or INTERGROWTH-21st, led by Professors Jose Villar, Stephen Kennedy and Aris Papageorghiou, at the University of Oxford, was established to enhance the WHO Child Growth Standards, which do not address the growth of the foetus and only relate to term babies (ie, babies born preterm were not included in the original WHO study).
The need for such standards was recognised as essential because many areas of the world have their own growth charts or references, which can be significantly different from each other. In addition, the studies that generated those charts varied hugely in terms of study design, methodology, and the demographics of the populations recruited. This highlighted the need for high-quality, evidence-based research to define standards for optimal growth, in particular for foetuses and preterm infants. Standards, which describe how children should ideally grow, have considerable advantages over references that simply reflect how children have grown in a limited population at a certain point in time. Standards also allow a consistent approach to monitoring child growth and development worldwide.
The use of the INTERGROWTH-21st postnatal growth standards for preterm infants reduces the risk of overfeeding, which can lead to obesity in later life.
INTERGROWTH-21st, conducted between 2009 and 2016, involved over 300 scientists and clinicians from 18 countries around the world. The project was designed using the same methodological approach as the landmark WHO study, to produce international standards for: 1) foetal growth, based on repeated ultrasound measures throughout pregnancy; 2) newborn size standards, based on the specific gestational age and sex of the baby at birth, and 3) postnatal growth standards for infants born preterm (less than 37 weeks’ gestation).
How were the standards produced?
The INTERGROWTH-21st Project collected longitudinal data, meaning that measures were obtained from the same babies from early pregnancy to 2 years of age. Their mothers were also carefully chosen, as in the original WHO study, to represent healthy, adequately nourished, educated women receiving good healthcare. This meant that any negative environmental impacts on growth were small.
The project recruited nearly 60,000 mothers and babies. Exactly the same methods were used across the eight centres in Brazil, China, India, Italy, Kenya, Oman, UK, and USA. Measurements such as head circumference were taken throughout pregnancy and postnatal life in the same way with rigorous quality controls. Postnatal care was standardised and the use of breast milk was encouraged.
The main finding, which enabled the standards to be produced, was that babies grow similarly inside the womb and achieve a similar size at birth, provided mothers are healthy at the start of pregnancy, have access to evidence-based healthcare, breastfeed, and are not exposed to environmental factors that adversely impact infant growth. In addition, the infants studied remained healthy and followed similar patterns of growth and development until 2 years of age. Crucially, all these similarities were apparent irrespective of ancestry, nationality, or ethnicity.
The international standards produced from the INTERGROWTH-21st research perfectly complement the existing WHO Child Growth Standards, which means that for the first time, human growth can be monitored from foetal life to childhood using tools that were developed in the same way. Thus, the standards were recommended by WHO and the US Centers for Disease Control and Prevention (CDC) to screen for microcephaly (abnormal head and brain development) during the Zika virus outbreak in 2016.
How are the INTERGROWTH-21st standards most impacting the delivery of healthcare?
Many of the reference charts for preterm infants used around the world overestimate poor growth after birth. This can lead to overfeeding when there are fears an infant is not growing as expected. Unfortunately, this can result in an increased likelihood of obesity and other diseases in adulthood.
The evidence-based INTERGROWTH-21st standards describe optimal postnatal development for infants born preterm, which can reduce the risk of overfeeding. The standards also allow evidence-based monitoring and evaluation of the nutritional status of infants and can be used to monitor the impact of interventions designed to improve growth.
How was the project first conceived and what led to its growth on a global scale?
The project was inspired by the original WHO study that produced the WHO Child Growth Standards. That study was based on data obtained from term newborns (ie, those born between 37 and 40 weeks’ gestation) measured from birth to 5 years of age. There was, therefore, a need to produce standards for foetal growth and the growth of a babies born preterm (ie, less than 37 weeks’ gestation). Without the generous support of our funders, it would not have been possible to conduct research at the scale required.
What are the biggest issues with current growth charts?
• Existing growth charts for foetuses and preterm infants are references, not standards. In other words, they merely describe what has happened in a (usually local) population at a particular point in time. They rarely are based on data collected following the same individuals through time and they do not adhere to the WHO recommendation to focus on mothers who are healthy, adequately nourished, educated, receiving evidence-based healthcare, and living in a clean environment to describe optimal growth over time.
• In addition, the data contributing to references are rarely collected with the kind of scientific rigour adopted in both the original WHO study and INTERGROWTH-21st. In particular, studies that have produced references tend to be smaller, utilise routinely collected clinical data rather than data collected prospectively for research, and have not assessed newborns or followed the infants’ growth and development after birth.
• A large number of foetal growth references exist, produced using a variety of methodologies that have generated different results. Thus, a woman can be scanned during pregnancy and told that her foetus is small according to the chart in use in that hospital. She then crosses a national border or into a different region of the city or country and can be told, based on the same measures, that the size is ‘normal’ because another chart was used.
• The use of references normalises poor growth in a disadvantaged population. In other words, if all the babies in a population are small because of, for example, malnourishment then the percentage that will fall beneath the 10th centile (the traditional threshold for defining small) using a reference will be 10%. Re-examination of data from low- to middle-income countries using the INTERGROWTH-21st standards instead of local references has shown that the percentage below the 10th centile can be over 60%, not 10%.
• For child growth, WHO standards only included babies born at term, so it was not possible to assess the growth of preterm infants accurately. INTERGROWTH-21st has created standards to assess: 1) weight at birth starting from 24 weeks gestational age and 2) postnatal growth for children born at each gestational week starting from week 26.
What are the next steps in implementing the INTERGROWTH-21st tools at a global level?
Currently, the use of foetal/newborn/preterm standards varies across countries and region. Some countries, such as Argentina, Brazil, and Uruguay, have fully implemented the INTERGROWTH-21st standards at national level. Other countries, such as France and Nigeria, have medical academies that recommend the use of the INTERGROWTH-21st standards. In the UK and Ghana, as examples, implementation is occurring through a bottom-up approach led by large teaching hospitals. The next steps are for medical academies, health ministries, and leading teaching hospitals globally to review their recommendations so as to change the charts being used.
