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These new results show that race and ethnicity are not the primary factors in a baby's size at birth. What matters more is the educational, health and nutritional status of the mothers, and care provided during pregnancy.

Babies of healthy moms worldwide are similar

Babies' growth in the womb and their size at birth, especially their length, are strikingly similar the world over when born to healthy, well-educated and well-nourished mothers.

That's the finding of a landmark international study, INTERGROWTH-21st, led by Oxford University researchers, which involved almost 60,000 pregnancies in eight defined urban areas in Brazil, China, India, Italy, Kenya, Oman, the UK and USA.

Worldwide there are wide disparities in the average size of babies at birth. This has significant consequences for future health, as small for gestational age babies who are already undernourished at birth often face severe short- and long-term health consequences.

It has previously been suggested that 'race' and 'ethnicity' are largely responsible for differences in the size of babies born in different populations and countries. These new results show that race and ethnicity are not the primary factors. What matters more is the educational, health and nutritional status of the mothers, and care provided during pregnancy.

The researchers carried out ultrasound scans from early pregnancy to delivery to measure babies' bone growth in the womb, using identical methods in all countries and the same ultrasound machines provided by Philips Healthcare. They also measured the length and head circumference of all babies at birth.

They have demonstrated that if mothers' educational, health and nutritional status and care during pregnancy are equally good, babies will have equal chances of healthy growth in the womb and future good health.

The researchers report their findings in The Lancet, Diabetes & Endocrinology. They were funded by the Bill & Melinda Gates Foundation.

"Currently we are not all equal at birth. But we can be.

"We can create a similar start for all by making sure mothers are well educated and nourished, by treating infection and by providing adequate antenatal care.

"Don't tell us nothing can be done. Don't say that women in some parts of the world have small children because they are predestined to do so. It's simply not true."

Jose Villar, lead author, professor the Nuffield Department of Obstetrics & Gynaecology, University of Oxford

The study involved almost 60,000 pregnancies in eight defined urban areas in Brazil, China, India, Italy, Kenya, Oman, the UK and USA.
Babies' bone growth in the womb and their length and head circumference at birth are strikingly similar the world over – when babies are born to educated, healthy and well-nourished mothers.

Overall, no more than 4% of the total difference in fetal growth and birth size could be attributed to differences between the eight populations in the study. Improving the education, health and nutrition of mothers everywhere will boost the health of their babies throughout life within the next generation.

Results are in complete agreement with the previous WHO study using the same methodology from birth to 5 years of age.

In 2010, an estimated 32.4 million babies were born already undernourished in low- and middle-income countries, which represents 27% of all live births globally. This is closely associated with illness and death in infancy and childhood. Small size at birth has an impact on adult health too, with increased risks of diabetes, high blood pressure and cardiovascular disease. Smaller babies also result in substantial costs for health services and a significant economic burden on societies as a whole.

Part of the problem in starting to improve pregnancy outcomes is that fetal growth and newborn size are currently evaluated in clinics around the world using at least 100 different growth charts.

In other words, there are no international standards at present for the fetus and newborn, while such standards do exist for infants and children.

"This is very confusing for doctors and mothers and makes no biological sense. How can a fetus or a newborn be judged small in one clinic or hospital and treated accordingly, only for the mother to go to another city or country, and be told that her baby is growing normally."

Professor Stephen Kennedy, University of Oxford, one of the senior authors of the paper.

The final aim of the INTERGROWTH-21st study is to construct international standards describing optimal growth of a baby in the womb and as a newborn – standards to reflect how a baby should grow when mothers have adequate health, nutrition and socioeconomic status.

The researchers adopted the same approach taken by the WHO's Multicentre Growth Reference Study of healthy infants and children, which established international growth standards from birth to 5 years of age that are now used in more than 140 countries worldwide.

The INTERGROWTH-21st results fit perfectly with the existing WHO standards for infants. The mean length at birth of the newborns in the INTERGROWTH-21st study was 49.4 ± 1.9 cm, compared with 49.5 ±1.9 cm in the WHO infant study.

From now on international standards can be used worldwide to make judgements on growth and size from conception to 5 years. 'Just think, if your cholesterol or your blood pressure are high, they are high regardless of where you live. Why should the same not apply to growth?' said Professor Villar.

Professor Ruyan Pang, from Peking University, China, one of the study's lead investigators, adds: "The INTERGROWTH-21st results fit perfectly with the existing WHO Infant and Child Growth Standards. Having international standards of optimal growth from conception to 5 years of age that everyone in the world can use means it will now be possible to evaluate improvements in health and nutrition using the same yardstick."

"The fact that mothers who are in good health have babies grow in the womb in very similar ways the world over is a tremendously positive message of hope for all women and their families.

"But there is a challenge as well. There are implications in the way we think about public health — about the health and life chances of future citizens everywhere on the planet. All those who are responsible for health care will have to think about providing the best possible maternal and child health."

Zulfiqar Bhutta, Professor, The Aga Khan University, Karachi, Pakistan and the Hospital for Sick Children, Toronto, Canada, Chair of the Steering Committee of this global research team.

Background
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-21st 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.

Methods
For this study, fetal growth and newborn size were measured in two INTERGROWTH-21st 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.

Findings
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]).

Interpretation
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.

Funding
The paper 'The likeness of fetal growth and newborn size across non-isolated populations in the INTERGROWTH-21st Project' is to be published in The Lancet Diabetes & Endocrinology with an embargo of 00:01 UK time on Monday 7 July 2014 / 19:01 US Eastern time on Sunday 6 July 2014.

The study was funded by the Bill & Melinda Gates Foundation.

A number of factors can lead to small babies, such as mothers' poor nutrition and health over a long period, infections, complications during pregnancy, smoking, alcohol, physically demanding work during pregnancy and the baby's premature birth.

Overnutrition is also becoming a problem because of rising rates of obesity that result in more large babies being born.
The scale of the project is unprecedented in this area. It involved the recruitment of almost 60,000 women, the standardisation of clinical practice of 300 health professionals across eight study sites, the careful monitoring of equipment and data to ensure accuracy, and a team of over 200 researchers and clinicians.
As well as the lead authors from Oxford University, the international research team included members from Peking University in China, the Universidade Católica de Pelotas in Brazil, the Aga Khan University in Kenya, the Ministry of Health in Oman, the Università degli Studi di Torino in Italy, the University of Washington School of Medicine and the Swedish Medical Centre, Seattle in the USA, and the Ketkar Hospital in Nagpur, India.

Oxford University's Medical Sciences Division is one of the largest biomedical research centres in Europe, with over 2,500 people involved in research and more than 2,800 students. The University is rated the best in the world for medicine, and it is home to the UK's top-ranked medical school.
From the genetic and molecular basis of disease to the latest advances in neuroscience, Oxford is at the forefront of medical research. It has one of the largest clinical trial portfolios in the UK and great expertise in taking discoveries from the lab into the clinic. Partnerships with the local NHS Trusts enable patients to benefit from close links between medical research and healthcare delivery.

A great strength of Oxford medicine is its long-standing network of clinical research units in Asia and Africa, enabling world-leading research on the most pressing global health challenges such as malaria, TB, HIV/AIDS and flu. Oxford is also renowned for its large-scale studies, which examine the role of factors such as smoking, alcohol and diet on cancer, heart disease and other conditions.

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