L Cheikh Ismail

The objectives, design and implementation of the INTERGROWTH‐21st Project

Please cite this paper as: Villar J, Altman D, Purwar M, Noble J, Knight H, Ruyan P, Cheikh Ismail L, Barros F, Lambert A, Papageorghiou A, Carvalho M, Jaffer Y, Bertino E, Gravett M, Bhutta Z, Kennedy S, for the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH‐21st). The objectives, design and implementation of the INTERGROWTH‐21st Project. BJOG 2013; 120 (Suppl. 2): 9–26.

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

Please cite this paper as: Villar J, Altman D, Purwar M, Noble J, Knight H, Ruyan P, Cheikh Ismail L, Barros F, Lambert A, Papageorghiou A, Carvalho M, Jaffer Y, Bertino E, Gravett M, Bhutta Z, Kennedy S, for the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH‐21st). The objectives, design and implementation of the INTERGROWTH‐21st Project. BJOG 2013; 120 (Suppl. 2): 9–26.

International standards for early fetal size and pregnancy dating based on ultrasound measurement of crown-rump length in the first trimester of pregnancy.

There are no international standards for relating fetal crown–rump length (CRL) to gestational age (GA), and most existing charts have considerable methodological limitations. The INTERGROWTH‐21st Project aimed to produce the first international standards for early fetal size and ultrasound dating of pregnancy based on CRL measurement.

Conceptual issues related to the construction of prescriptive standards for the evaluation of postnatal growth of preterm infants

Monitoring and interpreting the growth of preterm infants is a major clinical task for neonatologists. The effectiveness of this process depends upon the robustness of the standard selected. Concerns have been raised regarding the nature of the charts currently being used, as well as their appropriateness for present-day neonatal care. To overcome these problems, there is a need for new prescriptive standards based on a population of preterm infants without evidence of impaired fetal growth and born to low-risk women followed up since early pregnancy for precise gestational age dating. Preterm infants contributing to the new standards should be free of congenital malformations and major clinical conditions associated with impaired postnatal growth. These infants should receive standardised, evidence-based clinical care and should follow current feeding recommendations based on exclusive/predominant breastfeeding. This strategy should provide 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. New international standards constructed in this way should contribute to the evidence-based care of these preterm infants.

International estimated fetal weight standards of the INTERGROWTH-21st Project.

Estimated fetal weight (EFW) and fetal biometry are complementary measures used to screen for fetal growth disturbances. Our aim was to provide international EFW standards to complement the INTERGROWTH‐21st Fetal Growth Standards that are available for use worldwide.

Anthropometric standardisation and quality control protocols for the construction of new, international, fetal and newborn growth standards: the INTERGROWTH‐21st Project

The primary aim of the INTERGROWTH‐21st Project is to construct new, prescriptive standards describing optimal fetal and preterm postnatal growth. The anthropometric measurements include the head circumference, recumbent length and weight of the infants, and the stature and weight of the parents. In such a large, international, multicentre project, it is critical that all study sites follow standardised protocols to ensure maximal validity of the growth and nutrition indicators used. This paper describes in detail the anthropometric training, standardisation and quality control procedures used to collect data for these new standards. The initial standardisation session was in Nairobi, Kenya, using newborns, which was followed by similar sessions in the eight participating study sites in Brazil, China, India, Italy, Kenya, Oman, UK and USA. The intraobserver and inter‐observer technical error of measurement values for head circumference range from 0.3 to 0.4 cm, and for recumbent length from 0.3 to 0.5 cm. These standardisation protocols implemented at each study site worldwide ensure that the anthropometric data collected are of the highest quality to construct international growth standards.

The Distribution of Clinical Phenotypes of Preterm Birth Syndrome Implications for Prevention

IMPORTANCE Preterm birth has been difficult to study and prevent because of its complex syndromic nature. OBJECTIVE To identify phenotypes of preterm delivery syndrome in the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project. DESIGN, SETTING, AND PARTICIPANTS A population-based, multiethnic, cross-sectional study conducted at 8 geographically demarcated sites in Brazil, China, India, Italy, Kenya, Oman, the United Kingdom, and the United States. A total of 60,058 births over a 12-month fixed period between April 27, 2009, and March 2, 2014. Of these, 53,871 had an ultrasonography estimate of gestational age, among which 5828 were preterm births (10.8%). Pregnancies were prospectively studied using a standardized data collection and online data management system. Newborns had anthropometric and clinical examinations using standardized methods and identical equipment and were followed up until hospital discharge. MAIN OUTCOMES AND MEASURES The main study outcomes were clusters of preterm phenotypes and for each cluster, we analyzed signs of presentation at hospital admission, admission rates for neonatal intensive care for 7 days or more, and neonatal mortality rates. RESULTS Twelve preterm birth clusters were identified using our conceptual framework. Eleven consisted of combinations of conditions known to be associated with preterm birth, 10 of which were dominated by a single condition. However, the most common single cluster (30.0% of the total preterm cases; n = 1747) was not associated with any severe maternal, fetal, or placental condition that was clinically detectable based on the information available; within this cluster, many cases were caregiver initiated. Only 22% (n = 1284) of all the preterm births occurred spontaneously without any of these severe conditions. Maternal presentation on hospital admission, newborn anthropometry, and risk for death before hospital discharge or admission for 7 or more days to a neonatal intensive care unit, none of which were used to construct the clusters, also differed according to the identified phenotypes. The prevalence of preterm birth ranged from 8.2% in Muscat, Oman, and Oxford, England, to 16.6% in Seattle, Washington. CONCLUSIONS AND RELEVANCE We identified 12 preterm birth phenotypes associated with different patterns of neonatal outcomes. In 22% of all preterm births, parturition started spontaneously and was not associated with any of the phenotypic conditions considered. We believe these results contribute to an improved understanding of this complex syndrome and provide an empirical basis to focus research on a more homogenous set of phenotypes.

Gestational weight gain standards based on women enrolled in the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project: a prospective longitudinal cohort study.

Objective To describe patterns in maternal gestational weight gain (GWG) in healthy pregnancies with good maternal and perinatal outcomes. Design Prospective longitudinal observational study. Setting Eight geographically diverse urban regions in Brazil, China, India, Italy, Kenya, Oman, United Kingdom, and United States, April 2009 to March 2014. Participants Healthy, well nourished, and educated women enrolled in the Fetal Growth Longitudinal Study component of the INTERGROWTH-21st Project, who had a body mass index (BMI) of 18.50-24.99 in the first trimester of pregnancy. Main outcome measures Maternal weight measured with standardised methods and identical equipment every five weeks (plus/minus one week) from the first antenatal visit (<14 weeks’ gestation) to delivery. After confirmation that data from the study sites could be pooled, a multilevel, linear regression analysis accounting for repeated measures, adjusted for gestational age, was applied to produce the GWG values. Results 13 108 pregnant women at <14 weeks’ gestation were screened, and 4607 met the eligibility criteria, provided consent, and were enrolled. The variance within sites (59.6%) was six times higher than the variance between sites (9.6%). The mean GWGs were 1.64 kg, 2.86 kg, 2.86 kg, 2.59 kg, and 2.56 kg for the gestational age windows 14-18+6 weeks, 19-23+6 weeks, 24-28+6 weeks, 29-33+6 weeks, and 34-40+0 weeks, respectively. Total mean weight gain at 40 weeks’ gestation was 13.7 (SD 4.5) kg for 3097 eligible women with a normal BMI in the first trimester. Of all the weight measurements, 71.7% (10 639/14 846) and 94.9% (14 085/14 846) fell within the expected 1 SD and 2 SD thresholds, respectively. Data were used to determine fitted 3rd, 10th, 25th, 50th, 75th, 90th, and 97th smoothed GWG centiles by exact week of gestation, with equations for the mean and standard deviation to calculate any desired centiles according to gestational age in exact weeks. Conclusions Weight gain in pregnancy is similar across the eight populations studied. Therefore, the standards generated in this study of healthy, well nourished women may be used to guide recommendations on optimal gestational weight gain worldwide.

Anthropometric protocols for the construction of new international fetal and newborn growth standards: the INTERGROWTH-21st Project.

The primary aim of the INTERGROWTH‐21st Project is to construct new, prescriptive standards describing optimal fetal and preterm postnatal growth. The anthropometric measurements include the head circumference, recumbent length and weight of the infants, and the stature and weight of the parents. In such a large, international, multicentre project, it is critical that all study sites follow standardised protocols to ensure maximal validity of the growth and nutrition indicators used. This paper describes, in detail, the selection of anthropometric personnel, equipment, and measurement and calibration protocols used to construct the new standards. Implementing these protocols at each study site ensures that the anthropometric data are of the highest quality to construct the international standards.

A rapid questionnaire assessment of environmental exposures to pregnant women in the INTERGROWTH-21st Project.

Impaired fetal growth and preterm birth are the leading causes of neonatal and infant mortality worldwide and there is a growing scientific literature suggesting that environmental exposures during pregnancy may play a causal role in these outcomes. Our purpose was to assess the environmental exposure of the Fetal Growth Longitudinal Study (FGLS) participants in the multinational INTERGROWTH‐21st Project. First, we developed a tool that could be used internationally to screen pregnant women for such exposures and administered it in eight countries on a subsample (n = 987) of the FGLS participants. The FGLS is a study of fetal growth among healthy pregnant women living in relatively affluent areas, at low risk of adverse pregnancy outcomes and environmental exposures. We confirmed that most women were not exposed to major environmental hazards that could affect pregnancy outcomes according to the protocols entry criteria. However, the instrument was able to identify some women that reported various environmental concerns in their homes such as peeling paint, high residential density (>1 person per room), presence of rodents or cockroaches (hence the use of pesticides), noise pollution and safety concerns. This screening tool was therefore useful for the purposes of the project and can be used to ascertain environmental exposures in studies in which the primary aim is not focused on environmental exposures. The instrument can be used to identify subpopulations for more in‐depth assessment, (e.g. environmental and biological laboratory markers) to pinpoint areas requiring education, intervention or policy change.