The likeness of fetal growth and newborn size across non-isolated populations in the INTERGROWTH-21st Project: the Fetal Growth Longitudinal Study and Newborn Cross-Sectional Study

doi:10.1016/S2213-8587(14)70121-4

The Lancet Diabetes & Endocrinology

Volume 2, Issue 10, October 2014, Pages 781-792

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https://doi.org/10.1016/S2213-8587(14)70121-4 Get rights and content

Summary

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-21^st 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-21^st 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

Bill & Melinda Gates Foundation.

Introduction

Many populations are exposed to adverse environmental conditions and inadequate nutritional intakes that affect fetal growth.¹ Therefore, findings of an increased number of newborn babies small for gestational age in these geographical areas and in immigrants in ethnically heterogeneous populations in developed countries (eg, Netherlands² and the USA³) are not surprising. However, investigators have attributed the high rates of small for gestational age newborn babies reported in certain populations to genetic factors,⁴ despite findings from epidemiological and clinical studies that have consistently shown similar growth patterns across some ethnic groups in infants and children from affluent, well-nourished and geographically diverse backgrounds.5, 6

Up to now, the strongest scientific evidence supporting the notion, first proposed by Habicht and colleagues,⁷ that both infant and child growth are more affected by health, socioeconomic status, and environmental conditions than by ethnic differences, has been provided by the multiethnic WHO Multicentre Growth Reference Study (MGRS) of healthy, breastfed children with minimum environmental, health, and nutrition constraints on growth from six populations in Brazil, Ghana, India, Norway, Oman, and the USA (n=8406).8, 9 Results of the study showed striking similarity in linear growth in children from the six sites,¹⁰ thereby justifying pooling data to construct one international growth standard from birth to 5 years of age, which has since been adopted worldwide.11, 12

Although ample data have contributed to devising international growth standards for infants and children, so far, the data for fetal growth and newborn size have been limited. The conclusions of two recent systematic reviews13, 14 strongly support the need to develop international standards to assess growth patterns in the prenatal and neonatal periods. Therefore, our aim was to assess fetal growth and newborn size across different populations by mapping skeletal growth as a continuous process from after conception to birth in a prospective, population-based project. We used identical methods in eight geographically diverse urban areas in which mothers' health and nutritional needs were met; sanitation practices and the environment were judged not to be constraining growth; and adequate, standardised antenatal care was provided. If the data generated were consistent with the WHO MGRS standards (birth to 5 years), a global set of international fetal and newborn standards could be generated to allow growth to be monitored from the post-conception period to childhood.

Section snippets

Study design and participants

INTERGROWTH-21^st was a multicentre, multi-ethnic, population-based project, done between April 27, 2009, and March 2, 2014, in eight study sites: the cities of Pelotas (Brazil), Turin (Italy), Muscat (Oman), Oxford (UK), and Seattle (USA); Shunyi County, Beijing (China); the central area of Nagpur (India); and the Parklands suburb of Nairobi (Kenya).¹⁵ Its main aim was to study growth, health, nutrition, and neurodevelopment from less than 14 weeks of gestation to 2 years of age, with the same

Results

Between April 27, 2009, and Aug 2, 2013, in FGLS, we screened 13 108 pregnant women attending the study clinics; of these, 4607 (35%) who met the eligibility criteria¹⁵ consented and were enrolled (figure 1). The most common reasons for ineligibility were maternal age younger than 18 years or older than 35 years (915, 11%), maternal height less than 153 cm (1022, 12%; mostly in India and Oman), and BMI of 30 kg/m² or higher (1009, 12%; mostly in the UK and USA). The contribution of each site to

Discussion

We have presented data obtained under rigorously controlled methods, comparing fetal skeletal growth and newborn baby and infant sizes from 9 weeks of gestation to birth, in healthy, well nourished women living in environments with minimal constraints on fetal growth, across eight geographically diverse urban areas worldwide (panel). We selected fat-free mass (ie, skeletal) indicators as the primary measurements to compare fetal growth and newborn size across the study sites. These measurements

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We analyzed data from a cohort of pregnant women and their babies in Sylhet, Bangladesh, assembled between 2011 and 2014. Community health workers visited enrolled babies up to 10 times from birth to age 59 days. Survival status was recorded at each visit. Gestational age was estimated from mother’s reported last menstrual period. Birth weights were measured within 72 hours of delivery. SGA was defined using the INTERGROWTH-21st standard. We estimated unadjusted and adjusted hazard ratios (HRs) and corresponding 95% CIs for babies born preterm and SGA separately for the first and second month of life using bivariate and multivariable weighted Cox regression models.
The analysis included 17 643 singleton live birth babies. Compared with infants born at term-appropriate for gestational age, in both unadjusted and adjusted analyses, infants born preterm-SGA had the greatest risk of death in the first (HR 13.25, 95% CI 8.65-20.31; adjusted HR 12.05, 95% CI 7.82-18.57) and second month of life (HR 4.65, 95% CI 1.93-11.23; adjusted HR 4.1, 95% CI 1.66-10.15), followed by infants born preterm-appropriate for gestational age and term-SGA.
The risk of mortality in infants born preterm and/or SGA is increased and extends through the second month of life. Appropriate interventions to prevent and manage complications caused by prematurity and SGA could improve survival during and beyond the neonatal period.
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To describe differences in the frequency of small-for-gestational age (SGA) and large-for-gestational age (LGA) driven by different birth weight curves in assisted reproductive technology (ART)–conceived pregnancies.
Retrospective cohort study.
Single academic medical center.
Singleton live births between the gestational ages of 36 weeks and 0 days and 42 weeks and 6 days from fresh or frozen embryo transfer (ET).
None.
SGA (<10th percentile) and LGA (>90th percentile) classified by Fenton, INTERGROWTH-21, World Health Organization, Duryea, and Oken curves.
The median birth weight and gestational age at birth among fresh ET pregnancies were 3,289g (interquartile range [IQR], 2,977–3,600g) and 39.4 (IQR, 38.6–40.3) weeks, respectively, and those among frozen ET pregnancies were 3,399g (IQR, 3,065–3,685g) and 39.4 (IQR, 38.7–40.1) weeks, respectively. The frequencies of SGA neonates using each birth weight standard ranged from 5.8% to 13.4% for fresh ET and from 3.5% to 8.7% for frozen ET. Those of LGA neonates ranged from 5.3% to 14.3% for fresh ET and from 6.6% to 21.2% for frozen ET.
The frequency of SGA and LGA neonates among ART-conceived gestations is partially driven by the birth weight standard. Selecting an appropriate standard that best reflects the patient population is critical to quantifying the risk of ART-conceived pregnancies.
Stillbirth risk and smallness for gestational age according to Hadlock, INTERGROWTH-21st, WHO, and GROW fetal weight standards: analysis by maternal ethnicity and body mass index
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This study investigated the performance of 4 internationally used fetal weight standards and their ability to identify stillbirth risk in different ethnic and maternal size groups of a heterogeneous population.
We analyzed routinely collected maternity data from more than 2.2 million pregnancies. Three population-based fetal weight standards (Hadlock, Intergrowth-21st, and World Health Organization) were compared with the customized GROW standard that was adjusted for maternal height, weight, parity, and ethnic origin. Small-for-gestational-age birthweight and stillbirth risk were determined for the 2 largest ethnic groups in our population (British European and South Asian), in 5 body mass index categories, and in 4 maternal size groups with normal body mass index (18.5–25.0 kg/m²). The differences in trend between stillbirth and small-for-gestational-age rates were assessed using the Clogg z test, and differences between stillbirths and body mass index groups were assessed using the chi-square trend test.
Stillbirth rates (per 1000) were higher in South Asian pregnancies (5.51) than British-European pregnancies (3.89) (P<.01) and increased in both groups with increasing body mass index (P<.01). Small-for-gestational-age rates were 2 to 3-fold higher for South Asian babies than British European babies according to the population-average standards (Hadlock: 26.2% vs 12.2%; Intergrowth-21st: 12.1% vs 4.9%; World Health Organization: 32.2% vs 16.0%) but were similar by the customized GROW standard (14.0% vs 13.6%). Despite the wide variation, each standard’s small-for-gestation-age cases had increased stillbirth risk compared with non–small-for-gestation-age cases, with the magnitude of risk inversely proportional to the rate of cases defined as small for gestational age. All standards had similar stillbirth risk when the small-for-gestation-age rate was fixed at 10% by varying their respective thresholds for defining small for gestational age. When analyzed across body mass index subgroups, the small-for-gestation-age rate according to the GROW standard increased with increasing stillbirth rate, whereas small-for-gestation-age rates according to Hadlock, Intergrowth-21st, and World Health Organization fetal weight standards declined with increasing body mass index, showing a difference in trend (P<.01) to stillbirth rates across body mass index groups. In the normal body mass index subgroup, stillbirth rates showed little variation across maternal size groups; this trend was followed by GROW–based small-for-gestation-age rates, whereas small-for-gestation-age rates defined by each population-average standard declined with increasing maternal size.
Comparisons between population-average and customized fetal growth charts require examination of how well each standard identifies pregnancies at risk of adverse outcomes within subgroups of any heterogeneous population. In both ethnic groups studied, increasing maternal body mass index was accompanied by increasing stillbirth risk, and this trend was reflected in more pregnancies being identified as small for gestational age only by the customized standard. In contrast, small-for-gestation-age rates fell according to each population-average standard, thereby hiding the increased stillbirth risk associated with high maternal body mass index.
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ArticlesThe likeness of fetal growth and newborn size across non-isolated populations in the INTERGROWTH-21st Project: the Fetal Growth Longitudinal Study and Newborn Cross-Sectional Study

Summary

Background

Methods

Findings

Interpretation

Funding

Introduction

Section snippets

Study design and participants

Results

Discussion

Lancet

J Clin Epidemiol

Am J Clin Nutr

Ethnic differences in term birthweight: the role of constitutional and environmental factors

Paediatr Perinat Epidemiol

Determinants of low birth weight: methodological assessment and meta-analysis

Bull World Health Organ

The role of genetic susceptibility in the association of low birth weight with type 2 diabetes

Br Med Bull

Growth performance of affluent Indian children is similar to that in developed countries

Bull World Health Organ

Factors associated with unconstrained growth among affluent Ghanaian children

Acta Paediatr

Height and weight standards for preschool children. How relevant are ethnic differences in growth potential?

Lancet

Enrolment and baseline characteristics in the WHO Multicentre Growth Reference Study

Acta Paediatr Suppl

Rationale for developing a new international growth reference

Food Nutr Bull

Assessment of differences in linear growth among populations in the WHO Multicentre Growth Reference Study

Acta Paediatr Suppl

Update on the implementation of the WHO child growth standards

World Rev Nutr Diets

WHO child growth standards

Acta Paediatr

Systematic review of methodology used in ultrasound studies aimed at creating charts of fetal size

BJOG

Pregnancy dating by fetal crown-rump length: systematic review of charts

BJOG

The objectives, design and implementation of the INTERGROWTH-21st project

BJOG

Articles
The likeness of fetal growth and newborn size across non-isolated populations in the INTERGROWTH-21^st Project: the Fetal Growth Longitudinal Study and Newborn Cross-Sectional Study

The objectives, design and implementation of the INTERGROWTH-21^st project