Monitoring human growth and development: a continuum from the womb to the classroom

A comprehensive set of fully integrated anthropometric measures is needed to evaluate human growth from conception to infancy so that consistent judgments can be made about the appropriateness of fetal and infant growth. At present, there are 2 barriers to this strategy. First, descriptive reference charts, which are derived from local, unselected samples with inadequate methods and poor characterization of their putatively healthy populations, commonly are used rather than prescriptive standards. The use of prescriptive standards is justified by the extensive biologic, genetic, and epidemiologic evidence that skeletal growth is similar from conception to childhood across geographic populations, when health, nutrition, environmental, and health care needs are met. Second, clinicians currently screen fetuses, newborn infants, and infants at all levels of care with a wide range of charts and cutoff points, often with limited appreciation of the underlying population or quality of the study that generated the charts. Adding to the confusion, infants are evaluated after birth with a single prescriptive tool: the World Health Organization Child Growth Standards, which were derived from healthy, breastfed newborn infants, infants, and young children from populations that have been exposed to few growth-restricting factors. The International Fetal and Newborn Growth Consortium for the 21st Century Project addressed these issues by providing international standards for gestational age estimation, first-trimester fetal size, fetal growth, newborn size for gestational age, and postnatal growth of preterm infants, all of which complement the World Health Organization Child Growth Standards conceptually, methodologically, and analytically. Hence, growth and development can now, for the first time, be monitored globally across the vital first 1000 days and all the way to 5 years of age. It is clear that an integrative approach to monitoring growth and development from pregnancy to school age is desirable, scientifically supported, and likely to improve care, referral patterns, and reporting systems. Such integration can be achieved only through the use of international growth standards, especially in increasingly diverse, mixed ancestry populations. Resistance to new scientific developments has been hugely problematic in medicine; however, we are confident that the obstetric and neonatal communities will join their pediatric colleagues worldwide in the adoption of this integrative strategy

Achieving accurate estimates of fetal gestational age and personalised predictions of fetal growth based on data from an international prospective cohort study: a population-based machine learning study.

Background: Preterm birth is a major global health challenge, the leading cause of death in children under 5 years of age, and a key measure of a population's general health and nutritional status. Current clinical methods of estimating fetal gestational age are often inaccurate. For example, between 20 and 30 weeks of gestation, the width of the 95% prediction interval around the actual gestational age is estimated to be 18-36 days, even when the best ultrasound estimates are used. The aims of this study are to improve estimates of fetal gestational age and provide personalised predictions of future growth. Methods: Using ultrasound-derived, fetal biometric data, we developed a machine learning approach to accurately estimate gestational age. The accuracy of the method is determined by reference to exactly known facts pertaining to each fetus-specifically, intervals between ultrasound visits-rather than the date of the mother's last menstrual period. The data stem from a sample of healthy, well-nourished participants in a large, multicentre, population-based study, the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st). The generalisability of the algorithm is shown with data from a different and more heterogeneous population (INTERBIO-21st Fetal Study). Findings: In the context of two large datasets, we estimated gestational age between 20 and 30 weeks of gestation with 95% confidence to within 3 days, using measurements made in a 10-week window spanning the second and third trimesters. Fetal gestational age can thus be estimated in the 20-30 weeks gestational age window with a prediction interval 3-5 times better than with any previous algorithm. This will enable improved management of individual pregnancies. 6-week forecasts of the growth trajectory for a given fetus are accurate to within 7 days. This will help identify at-risk fetuses more accurately than currently possible. At population level, the higher accuracy is expected to improve fetal growth charts and population health assessments. Interpretation: Machine learning can circumvent long-standing limitations in determining fetal gestational age and future growth trajectory, without recourse to often inaccurately known information, such as the date of the mother's last menstrual period. Using this algorithm in clinical practice could facilitate the management of individual pregnancies and improve population-level health. Upon publication of this study, the algorithm for gestational age estimates will be provided for research purposes free of charge via a web portal. Funding: Bill & Melinda Gates Foundation, Office of Science (US Department of Energy), US National Science Foundation, and National Institute for Health Research Oxford Biomedical Research Centre

INTERGROWTH-21st Project international INTER-NDA standards for child development at 2 years of age: an international prospective population-based study.

OBJECTIVES: To describe the construction of the international INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) standards for child development at 2 years by reporting the cognitive, language, motor and behaviour outcomes in optimally healthy and nourished children in the INTERGROWTH-21st Project. DESIGN: Population-based cohort study, the INTERGROWTH-21st Project. SETTING: Brazil, India, Italy, Kenya and the UK. PARTICIPANTS: 1181 children prospectively recruited from early fetal life according to the prescriptive WHO approach, and confirmed to be at low risk of adverse perinatal and postnatal outcomes. PRIMARY MEASURES: Scaled INTER-NDA domain scores for cognition, language, fine and gross motor skills and behaviour; vision outcomes measured on the Cardiff tests; attentional problems and emotional reactivity measured on the respective subscales of the preschool Child Behaviour Checklist; and the age of acquisition of the WHO gross motor milestones. RESULTS: Scaled INTER-NDA domain scores are presented as centiles, which were constructed according to the prescriptive WHO approach and excluded children born preterm and those with significant postnatal/neurological morbidity. For all domains, except negative behaviour, higher scores reflect better outcomes and the threshold for normality was defined as ≥10th centile. For the INTER-NDA's cognitive, fine motor, gross motor, language and positive behaviour domains these are ≥38.5, ≥25.7, ≥51.7, ≥17.8 and ≥51.4, respectively. The threshold for normality for the INTER-NDA's negative behaviour domain is ≤50.0, that is, ≤90th centile. At 22-30 months of age, the cohort overlapped with the WHO motor milestone centiles, showed low postnatal morbidity (<10%), and vision outcomes, attentional problems and emotional reactivity scores within the respective normative ranges. CONCLUSIONS: From this large, healthy and well-nourished, international cohort, we have constructed, using the WHO prescriptive methodology, international INTER-NDA standards for child development at 2 years of age. Standards, rather than references, are recommended for population-level screening and the identification of children at risk of adverse outcomes

Body composition at birth and its relationship with neonatal anthropometric ratios: the newborn body composition study of the INTERGROWTH-21(st) project.

Background We aimed to describe newborn body composition and identify which anthropometric ratio (weight/length; BMI; or ponderal index, PI) best predicts fat mass (FM) and fat-free mass (FFM). Methods Air-displacement plethysmography (PEA POD) was used to estimate FM, FFM, and body fat percentage (BF%). Associations between FFM, FM, and BF% and weight/length, BMI, and PI were evaluated in 1,019 newborns using multivariate regression analysis. Charts for FM, FFM, and BF% were generated using a prescriptive subsample (n=247). Standards for the best-predicting anthropometric ratio were calculated utilizing the same population used for the INTERGROWTH-21(st) Newborn Size Standards (n=20,479). Results FFM and FM increased consistently during late pregnancy. Differential FM, BF%, and FFM patterns were observed for those born preterm (34(+0)-36(+6) weeks' gestation) and with impaired intrauterine growth. Weight/length by gestational age (GA) was a better predictor of FFM and FM (adjusted R(2)=0.92 and 0.71, respectively) than BMI or PI, independent of sex, GA, and timing of measurement. Results were almost identical when only preterm newborns were studied. We present sex-specific centiles for weight/length ratio for GA. Conclusions Weight/length best predicts newborn FFM and FM. There are differential FM, FFM, and BF% patterns by sex, GA, and size at birth

International gestational age-specific centiles for blood pressure in pregnancy from the INTERGROWTH-21st Project in 8 countries: A longitudinal cohort study.

BACKGROUND: Gestational hypertensive and acute hypotensive disorders are associated with maternal morbidity and mortality worldwide. However, physiological blood pressure changes in pregnancy are insufficiently defined. We describe blood pressure changes across healthy pregnancies from the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) Fetal Growth Longitudinal Study (FGLS) to produce international, gestational age-specific, smoothed centiles (third, 10th, 50th, 90th, and 97th) for blood pressure. METHODS AND FINDINGS: Secondary analysis of a prospective, longitudinal, observational cohort study (2009 to 2016) was conducted across 8 diverse urban areas in Brazil, China, India, Italy, Kenya, Oman, the United Kingdom, and the United States of America. We enrolled healthy women at low risk of pregnancy complications. We measured blood pressure using standardised methodology and validated equipment at enrolment at 14 mmHg or diastolic blood pressure by >11 mmHg in fewer than 10% of women at any gestational age. Fewer than 10% of women increased their systolic blood pressure by >24 mmHg or diastolic blood pressure by >18 mmHg at any gestational age. The study's main limitations were the unavailability of prepregnancy blood pressure values and inability to explore circadian effects because time of day was not recorded for the blood pressure measurements. CONCLUSIONS: Our findings provide international, gestational age-specific centiles and limits of acceptable change to facilitate earlier recognition of deteriorating health in pregnant women. These centiles challenge the idea of a clinically significant midpregnancy drop in blood pressure

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.

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-21st 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-21st Project maintained optimal growth and development in childhood. STUDY DESIGN: In the Infant Follow-up Study of the INTERGROWTH-21st 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-21st 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-21st 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-21st 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

Adaptation of the Childbirth Experience Questionnaire (CEQ) in China: A multisite cross-sectional study.

BackgroundThe childbirth experience of women represents a significant aspect of quality care. Due to the lack of a reliable Chinese language tool for assessing childbirth experiences, examples must be adapted from other countries. The aim of this study was to translate an English version of the Childbirth Experience Questionnaire (CEQ) into Chinese and adapt this tool to the Chinese context.MethodsA questionnaire validation study was conducted. A forward-backward translation procedure involving the developer of the CEQ was conducted. The data were collected in postnatal wards at 50 birth facilities in 4 regions of Zhejiang Province, China. Women who gave birth vaginally at the investigated facilities during the study period completed an online questionnaire that included the Chinese version of the CEQ (CEQ-C), demographic information and clinical information. Psychometric analyses were performed to assess the internal and content consistency. After subdividing the sample into subsamples, an exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were applied to examine the structural validity. Known-group comparisons were performed to assess the discriminant validity.ResultsOverall, 1747 women participated in this study. The content validity index (CVI) of the CEQ was 0.92. Based on the comments of the experts combined with the statistical results, we removed 3 items related to pain, sense of control and sense of security and changed 3 items to different dimensions. The CFA supported the four dimensions of the CEQ-C (standard root mean square residual (SRMR) = 0.037, root mean square error of approximation (RMSEA) = 0.036, comparative fit index (CFI) = 0.966, and Tucker-Lewis index (TLI) = 0.959). Cronbach's alpha of the CEQ-C was 0.88, and McDonald's omega value was 0.91. The duration of labor, delivery mode, parity, oxytocin augmentation, pain management, companionship, prenatal education and pain experienced exerted significant effects on the women's childbirth experiences.ConclusionsAlthough some items performed differently in our analysis comparing the English and Chinese versions of the CEQ, the CEQ-C is reliable and valid. Additionally, the CEQ-C is an easy-to-use and promising tool for measuring childbirth experiences among Chinese women in facility settings that can be used to improve the quality of intrapartum care. Efforts are needed to provide women with respectful, evidence-based intrapartum care to facilitate positive childbirth experiences

Alteration of the Nonsystemic Behavior of the Pesticide Ferbam on Tea Leaves by Engineered Gold Nanoparticles

A model system consisting of a nonsystemic pesticide (ferbam), engineered gold nanoparticles (AuNPs) and a plant tissue (tea leaves) was investigated using surface enhanced Raman spectroscopy (SERS). Ferbam has no ability by itself to penetrate into tea leaves. When AuNPs were placed with ferbam onto the surface of tea leaves, however, the SERS signal of the ferbam-AuNPs complex was observed inside of the tea leaves. Within 1 h, the ferbam-AuNPs complex rapidly penetrated into the leaf to a depth of approximately 190 μm, about ¹/₃ to ¹/₂ of the leaf’s thickness. The rate of penetration was dependent on the size of AuNPs, with 30 nm AuNPs-ferbam penetrating more rapidly when compared with complexes made with the 50 and 69 nm AuNPs. These results clearly demonstrated an alteration of the nonsystemic behavior of ferbam in the combined presence with AuNPs. This finding might lead to the development of some new pesticide formulations. Conversely, new toxicity issues may arise as the behaviors and fate of pesticides are altered significantly upon interaction with engineered NPs in the pesticide formulation or environment