The satisfactory growth and development at 2 years of age of the INTERGROWTH-21st Fetal Growth Standards cohort support its appropriateness for constructing international standards

Abstract

Background: The World Health Organization recommends that human growth should be monitored with the use of international standards. However, in obstetric practice, we continue to monitor fetal growth using numerous local charts or equations that are based on different populations for each body structure. Consistent with World Health Organization recommendations, the INTERGROWTH-21^st Project has produced the first set of international standards to date pregnancies; to monitor fetal growth, estimated fetal weight, Doppler measures, and brain structures; to measure uterine growth, maternal nutrition, newborn infant size, and body composition; and to assess the postnatal growth of preterm babies. All these standards are based on the same healthy pregnancy cohort. Recognizing the importance of demonstrating that, postnatally, this cohort still adhered to the World Health Organization prescriptive approach, we followed their growth and development to the key milestone of 2 years of age.

Objective: The purpose of this study was to determine whether the babies in the INTERGROWTH-21^st Project maintained optimal growth and development in childhood.

Study design: In the Infant Follow-up Study of the INTERGROWTH-21^st Project, we evaluated postnatal growth, nutrition, morbidity, and motor development up to 2 years of age in the children who contributed data to the construction of the international fetal growth, newborn infant size and body composition at birth, and preterm postnatal growth standards. Clinical care, feeding practices, anthropometric measures, and assessment of morbidity were standardized across study sites and documented at 1 and 2 years of age. Weight, length, and head circumference age- and sex-specific z-scores and percentiles and motor development milestones were estimated with the use of the World Health Organization Child Growth Standards and World Health Organization milestone distributions, respectively. For the preterm infants, corrected age was used. Variance components analysis was used to estimate the percentage variability among individuals within a study site compared with that among study sites.

Results: There were 3711 eligible singleton live births; 3042 children (82%) were evaluated at 2 years of age. There were no substantive differences between the included group and the lost-to-follow up group. Infant mortality rate was 3 per 1000; neonatal mortality rate was 1.6 per 1000. At the 2-year visit, the children included in the INTERGROWTH-21^st Fetal Growth Standards were at the 49th percentile for length, 50th percentile for head circumference, and 58th percentile for weight of the World Health Organization Child Growth Standards. Similar results were seen for the preterm subgroup that was included in the INTERGROWTH-21^st Preterm Postnatal Growth Standards. The cohort overlapped between the 3rd and 97th percentiles of the World Health Organization motor development milestones. We estimated that the variance among study sites explains only 5.5% of the total variability in the length of the children between birth and 2 years of age, although the variance among individuals within a study site explains 42.9% (ie, 8 times the amount explained by the variation among sites). An increase of 8.9 cm in adult height over mean parental height is estimated to occur in the cohort from low-middle income countries, provided that children continue to have adequate health, environmental, and nutritional conditions.

Conclusion: The cohort enrolled in the INTERGROWTH-21^st standards remained healthy with adequate growth and motor development up to 2 years of age, which supports its appropriateness for the construction of international fetal and preterm postnatal growth standards.

Keywords: INTERGROWTH-21(st) fetal growth standards; development; postnatal growth.

Figure 1

Study flow of the INTERGROWTH-21^st Infant Follow-up Study The chart indicates the cohort that contributed data to the construction of the INTERGROWTH-21^st Fetal Growth Standards. CM, congenital malformation; USA, United States of America. Villar et al. Validation of the INTERGROWTH-21^st fetal growth standards. Am J Obstet Gynecol 2018.

Figure 2

Anthropometric measures at 1 and 2 years of age of the children included in the INTERGROWTH-21^st Fetal Growth Standards Data are for children who were included in the INTERGROWTH-21^st Fetal Growth Standards (grey circles) and children who were included in the Preterm Postnatal Growth Standards (red circles). Values are superimposed onto the 3rd, 50th, and 97th percentiles of the World Health Organization Child Growth Standards (girls [pink lines] and boys [blue lines]). For children born preterm, corrected postnatal age was used. Villar et al. Validation of the INTERGROWTH-21^st fetal growth standards. Am J Obstet Gynecol 2018.

Figure 3

Median age of achievement (3rd and 97th percentiles) of 4 gross motor development milestones Data are for children who were included in the INTERGROWTH-21^st Fetal Growth Standards (purple) and children who were included in the INTERGROWTH-21^st Preterm Postnatal Growth Standards (blue). The diamonds represent the use of corrected age for the children who were born preterm. For comparison, the 3rd and 97th percentiles of the World Health Organization windows of achievement for the same milestones are presented in grey (with the median shown as a vertical line). Villar et al. Validation of the INTERGROWTH-21^st fetal growth standards. Am J Obstet Gynecol 2018.

Figure 4

Expected increase from parental height Mean (95% confidence interval) difference between estimated adult height (calculated by doubling infant length at 2 years of age) and mean parental height (calculated as the average of maternal and paternal heights) for children who were included in the INTERGROWTH-21^st Fetal Growth Standards for study sites located in low- and middle-income countries and high-income countries. Villar et al. Validation of the INTERGROWTH-21^st fetal growth standards. Am J Obstet Gynecol 2018.

Supplementary Figure

Study flow of INTERGROWTH-21^st Preterm Postnatal Follow-up at 2 years The chart shows the cohort that contributed data to the construction of the INTERGROWTH-21^st Preterm Postnatal Growth Standards. Villar et al. Validation of the INTERGROWTH-21^st fetal growth standards. Am J Obstet Gynecol 2018.