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Multiple criteria and growth references have been proposed for extrauterine growth restriction (EUGR). We hypothesized that these may impact the diagnosis of EUGR. The objective was to evaluate the prevalence of EUGR with its different definitions and the concordance according to Fenton, Olsen, and INTERGROWTH-21st in very-low-birthweight (VLBW) infants. This is an observational, retrospective, and multicenter study including VLBW infants from the Spanish SEN1500 Network from 2011 to 2020. Patients with major congenital anomalies, embryopathies, and gestational age less than 24 weeks were excluded. EUGR prevalence was calculated at discharge with cross-sectional, longitudinal, "true" cross-sectional, and "true" longitudinal definitions. Concordance was assessed with Fleiss' kappa coefficient. 23582 VLBW infants from 77 NICUs were included. In total, 50.4% were men with a median of gestational age of 29 (4) weeks. The prevalence of EUGR (cross-sectional, longitudinal, and "true") was variable for weight, length, and head circumference. Overall, the prevalence was higher with Fenton and lower with Olsen (cross-sectional and "true" cross-sectional) and INTERGROWTH-21st (longitudinal and "true" longitudinal). Agreement among the charts by weight was good only for cross-sectional EUGR and moderate for longitudinal, "true" cross-sectional, and "true" longitudinal. Concordance was good or very good for EUGR by length and head circumference. Conclusions: The prevalence of EUGR with the most commonly used definitions was variable in the cohort. Agreement among growth charts was moderate for all the definitions of EUGR by weight except cross-sectional and good or very good for length and head circumference. The choice of reference chart can impact the establishment of the diagnosis of EUGR. What is known: • EUGR has been defined in the literature and daily practice considering weight, length and head circumference with multiple criteria (cross-sectional, longitudinal, and "true" definition) • Different growth charts have been used for EUGR diagnosis What is new: • Prevalence of EUGR is variable depending on the definition and growth chart used in our cohort of VLBW infants • For the most frequently EUGR criteria used, traditionally considering weight, concordance among Fenton, Olsen and INTERGROWTH-21st growth charts is only moderate for all the definitions of EUGR by weight except cross-sectional definition. Concordance among the charts is good or very good for the different criteria of EUGR by head circumference and length [ABSTRACT FROM AUTHOR]

Objectives: The aim of the present study was to compare birth weight (BW) distribution and proportion of BWs below or above specified percentiles in low‐risk singleton pregnancies in healthy South African (SA) women of mixed ancestry with expected values according to four BW references and to determine the physiological factors affecting BW. Methods: This was an ancillary study of a prospective multinational cohort study, involving 7060 women recruited between August 2007 and January 2015 in two townships of Cape Town, characterized by low socioeconomic status, and high levels of drinking and smoking. Detailed information about maternal and pregnancy characteristics, including harmful exposures, was gathered prospectively, allowing us to select healthy women with uncomplicated pregnancies without any known harmful exposures. In this cohort we compared the median BW and the proportion of BWs P90, 95 and 97 according to four reference standards (INTERGROWTH‐21st, customized according to the method described by Mickolajczyk, Fetal Medicine Foundation and revised Fenton reference) with expected values. Appropriate parametric and nonparametric tests were used, and sensitivity analysis was performed for infant sex, first trimester bookings and women of normal body mass index (BMI). Multiple regression was used to explore effects of confounders. Written consent and ethics approval was obtained. Results: The cohort included 739 infants. The INTERGROWTH‐21st standard was closest for the actual BW‐distribution and categories. Below‐expected BW was associated with boys, younger, shorter, leaner women, lower parity and gravidity. Actual BW was significantly influenced by maternal weight, BMI, parity and gestational age. Conclusion: Of the four references assessed in this study, the INTERGROWTH‐21st standard was closest for the actual BW distribution. Maternal variables significantly influence BW. Synopsis: The INTERGROWTH‐21st birth weight standard was the best of four references for this population, but maternal variables affect the actual birth weight (BW) and its deviation from the expected median. [ABSTRACT FROM AUTHOR]

Background and objectives: Variable diagnostic criteria and growth charts have been used for extrauterine growth restriction (EUGR). The objective was to assess the prevalence and concordance of EUGR in extremely-low-birthweight (ELBW) infants with the most frequent diagnostic criteria and growth charts. Materials and methods: An observational, retrospective and multicenter study was conducted from 2011 to 2020 including ELBW infants from the Spanish SEN1500 Network. EUGR prevalence was calculated at discharge using different definitions: cross-sectional (anthropometry less than the 10th centile), longitudinal (decrease of more than 1 SD from birth to discharge), "true" cross-sectional and "true" longitudinal (using the criteria previously described, excluding infants small for gestational age at birth). Concordance among Fenton, Olsen and INTERGROWTH-21st was assessed with Fleiss' Kappa coefficient. Results: The prevalence of EUGR was variable with the different definitions and growth references studied in the 7914 ELBW infants included. Overall, it was higher with Fenton for all the EUGR criteria studied by weight and length. The agreement among growth charts was substantial (κ > 0.6) for all the definitions except for longitudinal EUGR by weight (moderate, κ = 0.578). Conclusions: The prevalence of EUGR was variable in our cohort with the different diagnostic criteria and growth charts. The agreement among charts was good for all the definitions of EUGR except longitudinal EUGR by weight. [ABSTRACT FROM AUTHOR]

Background/Objectives: Extrauterine growth restriction (EUGR) is associated with high mortality and an increased incidence of poor neurodevelopmental outcomes in preterm infants. In this study, we aimed to compare the Intergrowth-21ST (IG-21ST) and Fenton charts in predicting long-term neurodevelopmental and anthropometric outcomes of very low birth weight (VLBW) infants. Methods: Data were collected from 2649 VLBW infants registered in the Korean Neonatal Network born between 240/7 and 316/7 weeks of gestational age from January 2013 to December 2017. Follow-up assessments were conducted at 18–24 months of age, corrected for prematurity. Multiple logistic regression analysis was performed to evaluate the association between EUGR and long-term outcomes. Results: Among the 2649 VLBW infants, 60.0% (1606/2649) and 36.9% (977/2649) were diagnosed as having EUGR defined by the Fenton chart (EUGRF) and by the IG-21ST chart (EUGRIG), respectively. The EUGRIG group exhibited a higher proportion of infants with cerebral palsy, neurodevelopmental impairment (NDI), and growth failure. In multiple logistic regression analysis, adjusted for risk factors for long-term outcome, the EUGRIG group showed higher risk of cerebral palsy (adjusted odds ratio [aOR], 1.66; 95% confidence interval [CI], 1.04–2.65), NDI (aOR, 2.09; 95% CI, 1.71–2.55), and growth failure (aOR, 1.57; 95% CI, 1.16–2.13). Infants with EUGRF tended to develop NDI (aOR, 1.29; 95%CI, 1.03–1.63) and experience growth failure (aOR, 2.44; 95% CI, 1.77–3.40). Conclusions: The IG-21ST chart demonstrated a more effective prediction of long-term neurodevelopmental outcomes, whereas the Fenton chart may be more suitable for predicting growth failure at 18–24 months. [ABSTRACT FROM AUTHOR]

Purpose We prospectively evaluated the association of the insulin resistance of third-trimester Nigerian pregnant women with their newborn infants' insulin resistance and birth size. Pregnancy-associated insulin resistance (IR), often assessed with homeostatic model assessment of IR (HOMA-IR), is associated, especially among women with gestational diabetes (GDM), with abnormal neonatal birth size and body composition, predisposing the baby to metabolic disorders like diabetes and obesity. The associations of maternal IR with neonatal IR, birth size and body composition are less studied in nondiabetic pregnant women, especially in sub-Saharan settings like Nigeria. Methods We originally recruited 401 third trimester, nondiabetic pregnant women to a prospective cohort study, followed up until birth. Blood samples of mothers and babies were obtained, respectively, at recruitment and within 24 hours postbirth for fasting serum glucose (FSG) and insulin (FSI) assays, and HOMA-IR was calculated as [(FSI × FSG)/22.5)]. Results Complete data for 150 mother-baby dyads was analysed: the mothers, with a mean (standard deviation [SD]) age of 31.6 (4.5) years, had live births at a mean (SD) gestational age of 39.2 weeks. The proportions of infants with wasting, stunting, impaired fetal growth (either wasting or stunted), small-for-gestation-age, large-for-gestational-age, low birthweight, and macrosomia were 4.2% (95% confidence interval, 1.1–10.3), 19.7% (12.9–28.0), 23.1% (15.8–31.8), 10.1% (5.3–17.0), 12.6% (7.2–19.9), 0.8% (0.02–4.5), and 5.0% (1.8–10.5), respectively. Maternal HOMA-IR was not associated with neonatal HOMA-IR (p=0.837), birth weight (p=0.416) or body composition measured with weight-length ratio (p=0.524), but birth weight was independently predicted by maternal weight (p=0.006), body mass index (p=0.001), and parity (p=0.012). Conclusions In this nondiabetic/non-GDM cohort, maternal HOMA-IR was not associated with neonatal IR, body size or body composition. Larger studies are required to confirm these findings, with addi-tional inclusion of mothers with hyperglycaemia for comparison.

Purpose: We prospectively evaluated the association of the insulin resistance of third-trimester Nigerian pregnant women with their newborn infants' insulin resistance and birth size. Pregnancy-associated insulin resistance (IR), often assessed with homeostatic model assessment of IR (HOMA-IR), is associated, especially among women with gestational diabetes (GDM), with abnormal neonatal birth size and body composition, predisposing the baby to metabolic disorders like diabetes and obesity. The associations of maternal IR with neonatal IR, birth size and body composition are less studied in nondiabetic pregnant women, especially in sub-Saharan settings like Nigeria. Methods: We originally recruited 401 third trimester, nondiabetic pregnant women to a prospective cohort study, followed up until birth. Blood samples of mothers and babies were obtained, respectively, at recruitment and within 24 hours postbirth for fasting serum glucose (FSG) and insulin (FSI) assays, and HOMA-IR was calculated as [(FSI × FSG)/22.5)]. Results: Complete data for 150 mother-baby dyads was analysed: the mothers, with a mean (standard deviation [SD]) age of 31.6 (4.5) years, had live births at a mean (SD) gestational age of 39.2 weeks. The proportions of infants with wasting, stunting, impaired fetal growth (either wasting or stunted), small-for-gestation-age, largefor-gestational-age, low birthweight, and macrosomia were 4.2% (95% confidence interval, 1.1-10.3), 19.7% (12.9-28.0), 23.1% (15.8-31.8), 10.1% (5.3-17.0), 12.6% (7.2-19.9), 0.8% (0.02-4.5), and 5.0% (1.8-10.5), respectively. Maternal HOMA-IR was not associated with neonatal HOMA-IR (P=0.837), birth weight (P=0.416) or body composition measured with weight-length ratio (P=0.524), but birth weight was independently predicted by maternal weight (P=0.006), body mass index (P=0.001), and parity (P=0.012). Conclusion: In this nondiabetic/non-GDM cohort, maternal HOMA-IR was not associated with neonatal IR, body size or body composition. Larger studies are required to confirm these findings, with addi-tional inclusion of mothers with hyperglycaemia for comparison. [ABSTRACT FROM AUTHOR]

Background and objectives: Variable diagnostic criteria and growth charts have been used for extrauterine growth restriction (EUGR). The objective was to assess the prevalence and concordance of EUGR in extremely-low-birthweight (ELBW) infants with the most frequent diagnostic criteria and growth charts. Materials and methods: An observational, retrospective and multicenter study was conducted from 2011 to 2020 including ELBW infants from the Spanish SEN1500 Network. EUGR prevalence was calculated at discharge using different definitions: cross-sectional (anthropometry less than the 10th centile), longitudinal (decrease of more than 1 SD from birth to discharge), “true” cross-sectional and “true” longitudinal (using the criteria previously described, excluding infants small for gestational age at birth). Concordance among Fenton, Olsen and INTERGROWTH-21st was assessed with Fleiss’ Kappa coefficient. Results: The prevalence of EUGR was variable with the different definitions and growth references studied in the 7914 ELBW infants included. Overall, it was higher with Fenton for all the EUGR criteria studied by weight and length. The agreement among growth charts was substantial (κ > 0.6) for all the definitions except for longitudinal EUGR by weight (moderate, κ = 0.578). Conclusions: The prevalence of EUGR was variable in our cohort with the different diagnostic criteria and growth charts. The agreement among charts was good for all the definitions of EUGR except longitudinal EUGR by weight.

ObjectivesThe aim of this article was to compare the differences between Intergrowth-21st (IG-21) and Fenton growth standards in the classification of intrauterine and extrauterine growth restriction (EUGR) in eastern Chinese preterm infants, and detect which one can better relate to neonatal diseases and predict the physical growth outcomes at 3–5 years old.MethodsPremature infants admitted to a tertiary pediatric hospital in Shanghai, China, from 2016 to 2018 were enrolled. Prenatal information, neonatal diseases during hospitalization, and anthropometric data (weight, height, and head circumference) at birth and at discharge were collected and analyzed. Physical growth outcomes (short stature, thinness, and overweight) were examined by telephone investigations in 2021 at age 3–5 years.ResultsThe medium gestational age and birth weight of the included 1,065 preterm newborns were 33.6 weeks and 1,900 g, respectively. The IG-21 curves diagnosed more newborns with small for gestational age (SGA) (19% vs. 14.7%) and fewer newborns with longitudinal EUGR on height (25.5% vs. 27.9%) and head circumference (17.9% vs. 24.7%) compared to Fenton curves. Concordances between Fenton and IG-21 standards were substantial or almost perfect in the classification of SGA and longitudinal EUGR, but minor in cross-sectional EUGR. EUGR identified by Fenton curves was better related to neonatal diseases than IG-21 curves. There were no statistical significances in the prediction of short stature, thinness, and overweight at 3–5 years old between the two charts.ConclusionsIG-21 growth standards are not superior to Fenton in assessing preterm growth and development in the eastern Chinese population.

Monitoring the growth of neonates in the Neonatal Intensive Care Unit (NICU) using growth charts constitutes an essential part of preterm infant care. Preterm infants are at increased risk for extrauterine growth restriction (EUGR) due to increased energy needs and clinical complications. This retrospective study compares the prevalence of small for gestational age (SGA) at birth and EUGR at discharge in extremely and very preterm neonates hospitalized in the NICU of a tertiary hospital in Greece, using different growth curves, and it examines the associated nutritional and clinical factors. Fenton2013 and INTERGROWTH-21st growth curves were used to calculate z-scores of birth weight (BW) and weight, length, and head circumference at discharge. The study includes 462 newborns with a mean BW of 1341.5 g and mean GA of 29.6 weeks. At birth, 6.3% of neonates were classified as SGA based on Fenton2013 curves compared to 9.3% with INTERGROWTH-21st growth curves. At discharge, 45.9% of neonates were characterized as having EUGR based on the Fenton2013 weight curves and 29.2% were characterized based οn INTERGROWTH-21st curves. Nutritional factors such as the day of initiation, attainment of full enteral feeding, and the duration of parenteral nutrition were associated with EUGR by both curves. The prevalence of SGA and EUGR neonates differs between the two growth references. This shows that further evaluation of these charts is needed to determine the most appropriate way to monitor infant growth. [ABSTRACT FROM AUTHOR]

Objectives. To evaluate the effectiveness of using the international anthropometric standards Intergrowth-21st and WHO Anthro in large for gestational age infants born to mothers with type 1 diabetes mellitus (DM1). Material and methods. 129 full-term children (52 girls, 77 boys) born to mothers with DM1 were examined. Groups of newborns were identified taking into account gender, percentiles and z-scores of body weight, calculated using the Intergrowth-21st and WHO Anthro calculators. Results. Birth weight percentile was 96.0 (81.4-99.5) using Intergrowth-21st standards and 84.0 (58.7-94.1) using WHO Anthro (U=4824.0; p

To systematically review and assess the risk of bias in the literature evaluating the performance of INTERGROWTH-21st estimated fetal weight (EFW) standards to predict maternal, fetal and neonatal adverse outcomes. Searches were performed in seven electronic databases (Scopus, Web of Science, Medline, Embase, Lilacs, Scielo and Google Scholar) using citation tools and keywords (intergrowth AND (standard OR reference OR formula OR model OR curve); all from 2014 to the last search on April 16th, 2021). We included full-text articles investigating the ability of INTERGROWTH-21st EFW standards to predict maternal, fetal or neonatal adverse outcomes in women with a singleton pregnancy who gave birth to infants with no congenital abnormalities. The study was registered on PROSPERO under the number CRD42020115462. Risk of bias was assessed with a customized instrument based on the CHARMS checklist and composed of 9 domains. Meta-analysis was performed using relative risk (RR [95%CI]) and summary ROC curves on outcomes reported by two or more methodologically homogeneous studies. Sixteen studies evaluating fifteen different outcomes were selected. The risk of bias was high (>50% of studies with high risk) for two domains: blindness of assessment (81.3%) and calibration assessment (93.8%). Considering all the outcomes investigated, for 95% of the results, the specificity was above 73.0%, but the sensitivity was below 64.1%. Pooled results demonstrated a higher RR of neonatal small for gestational age (6.71 [5.51–8.17]), Apgar <7 at 5 min (2.17 [1.48–3.18]), and neonatal intensive care unit admission (2.22 [1.76–2.79]) for fetuses classified <10th percentile when compared to those classified above this limit. The limitation of the study is the absence of heterogeneity exploration or publication bias investigation, whereas no outcomes were evaluated by more than five studies. The IG-21 EFW standard has low sensitivity and high specificity for adverse events of pregnancy. Classification <10th percentile identifies a high-risk group for developing maternal, fetal and neonatal adverse outcomes, especially neonatal small for gestational age, Apgar <7 at 5 min, and neonatal intensive care unit admission. Future studies should include blind assessment of outcomes, perform calibration analysis with continuous data, and evaluate alternative cutoff points. [ABSTRACT FROM AUTHOR]

Abstract Objective Our aim was to assess diagnostic accuracy in the prediction of small for gestational age (SGA

No fetal growth standard is currently endorsed for universal use in the United States. Newer standards improve upon the methodologic limitations of older studies; however, before adopting into practice, it is important to know how recent standards perform at identifying fetal undergrowth or overgrowth and at predicting subsequent neonatal morbidity or mortality in US populations. To compare classification of estimated fetal weight that is <5th or 10th percentile or >90th percentile by 6 population-based fetal growth standards and the ability of these standards to predict a composite of neonatal morbidity and mortality. We used data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be cohort, which recruited nulliparous women in the first trimester at 8 US clinical centers (2010–2014). Estimated fetal weight was obtained from ultrasounds at 16 to 21 and 22 to 29 weeks of gestation (N=9534 women). We calculated rates of fetal growth restriction (estimated fetal weight <5th and 10th percentiles; fetal growth restriction<5 and fetal growth restriction<10) and estimated fetal weight >90th percentile (estimated fetal weight>90) from 3 large prospective fetal growth cohorts with similar rigorous methodologies: INTERGROWTH-21, World Health Organization-sex-specific and combined, Eunice Kennedy Shriver National Institute of Child Health and Human Development race-ethnic-specific and unified, and the historic Hadlock reference. To determine whether differential classification of fetal growth restriction or estimated fetal weight >90 among standards was clinically meaningful, we then compared area under the curve and sensitivity of each standard to predict small for gestational age or large for gestational age at birth, composite perinatal morbidity and mortality alone, and small for gestational age or large for gestational age with composite perinatal morbidity and mortality. The standards classified different proportions of fetal growth restriction and estimated fetal weight>90 for ultrasounds at 16 to 21 (visit 2) and 22 to 29 (visit 3) weeks of gestation. At visit 2, the Eunice Kennedy Shriver National Institute of Child Health and Human Development race-ethnic-specific, World Health Organization sex-specific and World Health Organization-combined identified similar rates of fetal growth restriction<10 (8.4%–8.5%) with the other 2 having lower rates, whereas Eunice Kennedy Shriver National Institute of Child Health and Human Development race-ethnic-specific identified the highest rate of fetal growth restriction<5 (5.0%) compared with the other references. At visit 3, World Health Organization sex-specific classified 9.2% of fetuses as fetal growth restriction<10, whereas the other 5 classified a lower proportion as follows: World Health Organization-combined (8.4%), Eunice Kennedy Shriver National Institute of Child Health and Human Development race-ethnic-specific (7.7%), INTERGROWTH (6.2%), Hadlock (6.1%), and Eunice Kennedy Shriver National Institute of Child Health and Human Development unified (5.1%). INTERGROWTH classified the highest (21.3%) as estimated fetal weight>90 whereas Hadlock classified the lowest (8.3%). When predicting composite perinatal morbidity and mortality in the setting of early-onset fetal growth restriction, World Health Organization had the highest area under the curve of 0.53 (95% confidence interval, 0.51–0.53) for fetal growth restriction<10 at 22 to 29 weeks of gestation, but the areas under the curve were similar among standards (0.52). Sensitivity was generally low across standards (22.7%–29.1%). When predicting small for gestational age birthweight with composite neonatal morbidity or mortality, for fetal growth restriction<10 at 22 to 29 weeks of gestation, World Health Organization sex-specific had the highest area under the curve (0.64; 95% confidence interval, 0.60–0.67) and INTERGROWTH had the lowest (area under the curve=0.58; 95% confidence interval 0.55–0.62), though all standards had low sensitivity (7.0%–9.6%). Despite classifying different proportions of fetuses as fetal growth restriction or estimated fetal weight>90, all standards performed similarly in predicting perinatal morbidity and mortality. Classification of different percentages of fetuses as fetal growth restriction or estimated fetal weight>90 among references may have clinical implications in the management of pregnancies, such as increased antenatal monitoring for fetal growth restriction or cesarean delivery for suspected large for gestational age. Our findings highlight the importance of knowing how standards perform in local populations, but more research is needed to determine if any standard performs better at identifying the risk of morbidity or mortality. [ABSTRACT FROM AUTHOR]

ObjectiveEstimated 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.MethodsWomen with an accurate gestational-age assessment, who were enrolled in the prospective, international, multicenter, population-based Fetal Growth Longitudinal Study (FGLS) and INTERBIO-21st Fetal Study (FS), two components of the INTERGROWTH-21st Project, had ultrasound scans every 5 weeks from 9-14 weeks' until 40 weeks' gestation. At each visit, measurements of fetal head circumference (HC), biparietal diameter, occipitofrontal diameter, abdominal circumference (AC) and femur length (FL) were obtained blindly by dedicated research sonographers using standardized methods and identical ultrasound machines. Birth weight was measured within 12 h of delivery by dedicated research anthropometrists using standardized methods and identical electronic scales. Live babies without any congenital abnormality, who were born within 14 days of the last ultrasound scan, were selected for inclusion. As most births occurred at around 40 weeks' gestation, we constructed a bootstrap model selection and estimation procedure based on resampling of the complete dataset under an approximately uniform distribution of birth weight, thus enriching the sample size at extremes of fetal sizes, to achieve consistent estimates across the full range of fetal weight. We constructed reference centiles using second-degree fractional polynomial models.ResultsOf the overall population, 2404 babies were born within 14 days of the last ultrasound scan. Mean time between the last scan and birth was 7.7 (range, 0-14) days and was uniformly distributed. Birth weight was best estimated as a function of AC and HC (without FL) as log(EFW) = 5.084820 - 54.06633 × (AC/100)3  - 95.80076 × (AC/100)3  × log(AC/100) + 3.136370 × (HC/100), where EFW is in g and AC and HC are in cm. All other measures, gestational age, symphysis-fundus height, amniotic fluid indices and interactions between biometric measures and gestational age, were not retained in the selection process because they did not improve the prediction of EFW. Applying the formula to FGLS biometric data (n = 4231) enabled gestational age-specific EFW tables to be constructed. At term, the EFW centiles matched those of the INTERGROWTH-21st Newborn Size Standards but, at

BackgroundThe INTERGROWTH-21st preterm postnatal growth standards (IPPGS) have increasingly been used to evaluate the growth of preterm infants worldwide. However, the validity of IPPGS's application to specific preterm populations remains controversial. This retrospective cohort study aimed to formulate reference growth charts for a preterm cohort in northern China and compare them to the IPPGS.MethodsA total of 1,827 healthy preterm infants with follow-up visits before 70 weeks of postmenstrual age (PMA) were retrospectively sampled from a preterm cohort (N = 2,011) born between 1 January 2011 and 28 February 2021, at the First Affiliated Hospital of Shandong First Medical University. Using the Generalized Additive Models for Location, Scale, and Shape method, 5,539 sets of longitudinal data were used to construct percentile and Z-score charts of length, weight, and head circumference (HC) at 40–64 weeks of PMA. Z-scores of length, weight, and HC (LAZ, WAZ, and HCZ) before 64 weeks were calculated using the IPPGS. Differences in the 50th percentile values between preterm infants and IPPGS (dLength, dWeight, and dHC) were calculated. Z-scores were assigned to six PMA clusters: 40–44, 44–48, 48–52, 52–56, 56–60, and 60–64 weeks for comparison between sexes.ResultsFor eligible infants, the mean PMA and weight at birth were 33.93 weeks and 2.3 kg, respectively. Boys, late preterm infants, twins, and infants with exclusively breastfeeding accounted for 55.8, 70.6, 27.8, and 45.9%, respectively. Compared to IPPGS, preterm infants were longer and heavier, especially for dLength in girls (range, 2.19–2.97 cm), which almost spanned the 50th and 90th percentiles of IPPGS. The dHC tended to narrow with PMA for both sexes. The mean LAZ, WAZ, and HCZ of both sexes at all PMA clusters were >0, especially for LAZ and WAZ (about 1.0 relative to IPPGS), indicating higher levels than the IPPGS at 40–64 weeks. Girls had larger LAZ at each PMA cluster, larger WAZ at 40–44 weeks, and lower HCZ after 56 weeks than boys. HCZ declined with PMA for both sexes.ConclusionPostnatal growth of this preterm cohort was considerably higher than that of the IPPGS at 40–64 weeks of PMA with sex differences.

Objective: Our aim was to assess diagnostic accuracy in the prediction of small for gestational age (SGA <10th centile) and fetal growth restricted (FGR) (SGA <3rd centile) fetuses using three different sonographic methods in pregnancies at increased risk of fetal growth restriction: 1) fetal abdominal circumference (AC) z-scores, 2) estimated fetal weight (EFW) z-scores according to postnatal reference standard; 3) EFW z-scores according to a prenatal reference standard.Methods: Singleton pregnancies at increased risk of fetal growth restriction seen in two university hospitals between 2014 and 2015 were studied retrospectively. EFW was calculated using formulas proposed by the INTERGROWTH-21st project and Hadlock; data derived from publications by the INTEGROWTH-twenty-first century project and Hadlock were used to calculate z-scores (AC and EFW). The accuracy of different methods was calculated and compared.Results: The study group included 406 patients. Prenatal standard EFW z-scores derived from INTERGROWTH-21st project and Hadlock and co-workers performed similarly and were more accurate in identifying SGA infants than using AC z-scores or a postnatal reference standard. The subgroups analysis demonstrated that EFW prenatal standard was more or similarly accurate compared to other methods across all subgroups, defined by gestational age and birth weight.Conclusions: Prenatal standard EFW z-scores derived from either INTERGROWTH-21 st project or Hadlock and co-workers publications demonstrated a statistically significant advantage over other biometric methods in the diagnosis of SGA fetuses. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to assess the predictive ability of the ultrasound estimated percentile weight (EPW) at 35 weeks to predict large for gestational age (LGA) at term delivery according to 6 growth standards, including population, population-customized, and international references. The secondary objectives were to determine its predictive ability to detect adverse perinatal outcomes (APOs) and whether the ultrasound-delivery interval influences the detection rate of LGA newborns.Methods: This was a retrospective cohort study of 9,585 singleton pregnancies. Maternal clinical characteristics, fetal ultrasound data obtained at 35 weeks, and pregnancy and perinatal outcomes were used to calculate EPWs to predict LGAs at delivery according to the customized and the non-customized (NC) Miguel Servet University Hospital (MSUH), the customized Figueras, the NC Fetal Medicine Foundation (FMF), the NC INTERGROWTH-21st, and the NC World Health Organization (WHO) standards.Results: For a 10% false-positive rate, detection rates for total LGAs at delivery ranged from 31.2% with the WHO (area under the curve [AUC] 0.77; 95% confidence interval [CI], 0.76-0.79) to 56.5% with the FMF standard (AUC 0.85; 95% CI, 0.84-0.86). Detection rates and values of AUCs to predict LGAs by ultrasound-delivery interval (range 1-6 weeks) show higher detection rates as the interval decreases. APO detection rates ranged from 2.5% with the WHO to 12.6% with the Figueras standard.Conclusion: The predictive ability of ultrasound estimated fetal weight at 35 weeks to detect LGA infants is significantly greater for FMF and MSUH NC standards. In contrast, the APO detection rate is significantly greater for customized standards. The shorter ultrasound-delivery interval relates to better prediction rates. [ABSTRACT FROM AUTHOR]

Objective: To compare the INTERGROWTH-21st Century growth standard to the Hadlock standard in predicting small for gestational age (SGA) and adverse neonatal outcomes.Method: This is a prospective cohort study on women with singleton gestations referred for fetal growth ultrasound between 26.0 and 36.6 weeks gestational age (GA). The primary outcome is prediction of neonatal SGA. Neonatal SGA was defined as birthweight <10th percentile for GA by Alexander chart. The discriminatory ability of the growth standards was compared using area under receiver operating characteristic curves (AUC).Results: Among 1054 patients who met inclusion criteria, 139 (13.2%) had neonatal SGA. The mean interval between estimated fetal weight and birthweight was 6.7 ± 3.1 weeks. Composite adverse neonatal outcome was seen in 300 (28.4%) patients. The sensitivity for identifying SGA neonates was higher for Hadlock compared with INTERGROWTH-21st standard (41.7 vs. 24.5%); AUC (95% CI) were 0.69 (0.65-0.73) and 0.62 (0.58-0.65), respectively. Both standards were comparable in predicting the composite adverse neonatal outcomes; AUC (95% CI) were 0.52 (0.50-0.53) and 0.52 (0.50-0.54), respectively; p = .28.Conclusions: The Hadlock standard had a moderate but higher discriminatory ability for predicting neonatal SGA compared to the INTERGROWTH-21st project standard. However, the two standards were poor predictors of early adverse neonatal outcomes.Rationale: The Intergrowth-21st project was recently introduced with the goal of providing a universal benchmark for comparing growth across different ethnicity. We performed a prospective cohort study to compare the Intergrowth-21st standard with the commonly used Hadlock standard for predicting pregnancies at risk for neonatal SGA and adverse outcomes. Hadlock fetal growth standard is moderately superior at predicting neonatal SGA compared to the Intergrowth-21st standard. Both standards are poor at predicting adverse neonatal outcomes. These findings, however, need further validation. [ABSTRACT FROM AUTHOR]

Background: Current practice in the UK is to plot premature infant anthropometric measurements on Neonatal and Infant Close Monitoring (NICM) reference charts. These charts have several known limitations. The INTERGROWTH-21st Project has recently produced international ante- and postnatal growth standards. Exact knowledge of growth centiles allows clinicians to accurately assess infant nutritional requirements. Objective: To compare target centile measurements between INTERGROWTH-21st and UK NICM growth charts for premature infants. Method: Anthropometric measurements (weight and head circumference) of a convenience sample of neonates born between 24 and 32 weeks of gestation were analysed retrospectively. Measurements were collected across three time points and plotted on both the NICM and INTERGROWTH-21st growth charts. The respective centiles were compared and analysed by paired-sample t test, Wilcoxon rank test analysis, and multilevel mixed-effect linear regression models. Results: Centiles for weight and head circumference measurements of 96 infants plotted on INTERGROWTH-21st charts were significantly greater than their corresponding UK charts at all three time points. For weight, the average difference between the two charts varied from 9.1 to 16.4 centiles. The difference between the two charts was greater for female than male infants by up to 6.9 centiles (95% CI 10.1–3.8). Conclusion: Existing UK NICM reference charts are significantly different to the growth standards of INTERGROWTH-21st. The choice of which growth chart to adopt in the UK could have important consequences on premature infants' future adult health and therefore requires further prospective observational studies with larger data sets including length measurements and more comprehensive population characteristics. [ABSTRACT FROM AUTHOR]

Objective: To assess the predictive ability of the ultrasound estimated percentile weight (EPW) at 35 weeks of pregnancy to predict adverse perinatal outcomes (APOs) at term delivery according to 5 fetal growth standards, including population, population-customized, and international references.Methods: This was a retrospective cohort study of 9,585 singleton pregnancies. Maternal clinical characteristics, fetal ultrasound data obtained at 35 weeks and pregnancy and perinatal outcomes were used to calculate EPWs to predict APOs according to: the customized and noncustomized (NC) Miguel Servet University Hospital (MSUH), the customized Figueras, the NC INTERGROWTH-21st, and the NC World Health Organization (WHO) international standards. APOs were defined as the occurrence of cesarean or instrumental delivery for nonreassuring fetal status, 5-min Apgar score < 7, arterial cord blood pH <7.10, or stillbirth. The predictive ability of EPW for APOs was analyzed using the area under the curve (AUC), and sensitivities were calculated for different false-positive rates (FPRs).Results: For a 10% FPR, detection rates for total APOs ranged between 12.7% with the customized MSUH (AUC 0.52; 95% CI 0.50-0.55) and 14.4% with the NC MSUH standard (AUC 0.55; 95% CI 0.53-0.57) for EPW by ultrasound; and from 22.0% with the customized MSUH standard (AUC 0.60; 95% CI 0.58-0.63) to 27.8% with the NC WHO (AUC 0.65; 95% CI 0.63-0.68) for EPW at delivery.Conclusions: The predictive capacity of the EPW for APOS is limited and similar, by both ultrasound and at delivery, for the 5 growth standards, without significant differences between customized and NC standards. [ABSTRACT FROM AUTHOR]

Background: A large proportion of pregnant women in lower and middle-income countries (LMIC) seek their first antenatal care after 14 weeks of gestation. While the last menstrual period (LMP) is still the most prevalent method of determining gestational age (GA), ultrasound-based foetal biometry is considered more accurate in the second and third trimesters. In LMIC settings, the Hadlock formula, originally developed using data from a small Caucasian population, is widely used for estimating GA and foetal weight worldwide as the pre-programmed formula in ultrasound machines. This approach can lead to inaccuracies when estimating GA in a diverse population. Therefore, this study aimed to develop a population-specific model for estimating GA in the late trimesters that was as accurate as the GA estimation in the first trimester, using data from GARBH-Ini, a pregnancy cohort in a North Indian district hospital, and subsequently validate the model in an independent cohort in South India., Methods: Data obtained by longitudinal ultrasonography across all trimesters of pregnancy was used to develop and validate GA models for the second and third trimesters. The gold standard for GA estimation in the first trimester was determined using ultrasonography. The Garbhini-GA2, a polynomial regression model, was developed using the genetic algorithm-based method, showcasing the best performance among the models considered. This model incorporated three of the five routinely measured ultrasonographic parameters during the second and third trimesters. To assess its performance, the Garbhini-GA2 model was compared against the Hadlock and INTERGROWTH-21st models using both the TEST set (N = 1493) from the GARBH-Ini cohort and an independent VALIDATION dataset (N = 948) from the Christian Medical College (CMC), Vellore cohort. Evaluation metrics, including root-mean-squared error, bias, and preterm birth (PTB) rates, were utilised to comprehensively assess the model's accuracy and reliability., Findings: With first trimester GA dating as the baseline, Garbhini-GA2 reduced the GA estimation median error by more than three times compared to the Hadlock formula. Further, the PTB rate estimated using Garbhini-GA2 was more accurate when compared to the INTERGROWTH-21st and Hadlock formulae, which overestimated the rate by 22.47% and 58.91%, respectively., Interpretation: The Garbhini-GA2 is the first late-trimester GA estimation model to be developed and validated using Indian population data. Its higher accuracy in GA estimation, comparable to GA estimation in the first trimester and PTB classification, underscores the significance of deploying population-specific GA formulae to enhance antenatal care., Funding: The GARBH-Ini cohort study was funded by the Department of Biotechnology, Government of India (BT/PR9983/MED/97/194/2013). The ultrasound repository was partly supported by the Grand Challenges India-All Children Thriving Program, Biotechnology Industry Research Assistance Council, Department of Biotechnology, Government of India (BIRAC/GCI/0115/03/14-ACT). The research reported in this publication was made possible by a grant (BT/kiData0394/06/18) from the Grand Challenges India at Biotechnology Industry Research Assistance Council (BIRAC), an operating division jointly supported by DBT-BMGF-BIRAC. The external validation study at CMC Vellore was partly supported by a grant (BT/kiData0394/06/18) from the Grand Challenges India at Biotechnology Industry Research Assistance Council (BIRAC), an operating division jointly supported by DBT-BMGF-BIRAC and by Exploratory Research Grant (SB/20-21/0602/BT/RBCX/008481) from Robert Bosch Centre for Data Science and Artificial Intelligence (RBCDSAI), IIT Madras. An alum endowment from Prakash Arunachalam (BIO/18-19/304/ALUM/KARH) partly funded this study at the Centre for Integrative Biology and Systems Medicine, IIT Madras., Competing Interests: The authors declare the following competing interests. HS, RT, and SB are inventors of the Garbhini-GA2 formula (Indian Patent Application no: 202341061748), submitted by the Indian Institute of Technology Madras., (© 2024 The Author(s).)

Objective: To systematically review and assess the risk of bias in the literature evaluating the performance of INTERGROWTH-21 st estimated fetal weight (EFW) standards to predict maternal, fetal and neonatal adverse outcomes., Methods: Searches were performed in seven electronic databases (Scopus, Web of Science, Medline, Embase, Lilacs, Scielo and Google Scholar) using citation tools and keywords (intergrowth AND (standard OR reference OR formula OR model OR curve); all from 2014 to the last search on April 16 th , 2021). We included full-text articles investigating the ability of INTERGROWTH-21 st EFW standards to predict maternal, fetal or neonatal adverse outcomes in women with a singleton pregnancy who gave birth to infants with no congenital abnormalities. The study was registered on PROSPERO under the number CRD42020115462. Risk of bias was assessed with a customized instrument based on the CHARMS checklist and composed of 9 domains. Meta-analysis was performed using relative risk (RR [95%CI]) and summary ROC curves on outcomes reported by two or more methodologically homogeneous studies., Results: Sixteen studies evaluating fifteen different outcomes were selected. The risk of bias was high (>50% of studies with high risk) for two domains: blindness of assessment (81.3%) and calibration assessment (93.8%). Considering all the outcomes investigated, for 95% of the results, the specificity was above 73.0%, but the sensitivity was below 64.1%. Pooled results demonstrated a higher RR of neonatal small for gestational age (6.71 [5.51-8.17]), Apgar <7 at 5 min (2.17 [1.48-3.18]), and neonatal intensive care unit admission (2.22 [1.76-2.79]) for fetuses classified <10 th percentile when compared to those classified above this limit. The limitation of the study is the absence of heterogeneity exploration or publication bias investigation, whereas no outcomes were evaluated by more than five studies., Conclusions: The IG-21 EFW standard has low sensitivity and high specificity for adverse events of pregnancy. Classification <10th percentile identifies a high-risk group for developing maternal, fetal and neonatal adverse outcomes, especially neonatal small for gestational age, Apgar <7 at 5 min, and neonatal intensive care unit admission. Future studies should include blind assessment of outcomes, perform calibration analysis with continuous data, and evaluate alternative cutoff points.

Objectives: To compare a traditional ultrasound (US) method for estimated fetal weight (EFW) calculation and fetal growth restriction diagnosis with 2 newer methods for the prediction of small for gestational age (SGA) at birth. Methods: We reviewed deliveries at our institution from January 1, 2013, to March 31, 2017. Singleton, nonanomalous, well‐dated fetuses with a US examination within 2 weeks of delivery were included. Estimated fetal weights and percentiles were calculated by a traditional method (Hadlock et al; Radiology 1991; 181:129–133) and 2 newer methods: Intergrowth‐21st (INTG; Ultrasound Obstet Gynecol 2017; 49:478–486) and Salomon et al (Ultrasound Obstet Gynecol 2007; 29:550–555). We calculated each method's test characteristics to predict SGA (birth weight < 10th percentile) using both traditional (EFW < 10th percentile) and receiver operating characteristic (ROC)‐derived fetal growth restriction cutoffs. Mean percentile discrepancies between EFW and birth weight measurements were calculated to compare method accuracy. We hypothesized that the INTG and Salomon methods would have superior SGA prediction compared with the Hadlock method. Results: Of 831 pregnancies with a US examination within 2 weeks of delivery, 138 (16.7%) were SGA at birth. Hadlock had the smallest US–birth weight percentile discrepancy (P < .001 versus both INTG and Salomon). When comparing ROC curves, the Hadlock and INTG methods performed comparably, with areas under the curve of 0.91 and 0.90 (P = .08) and optimal EFW cutoffs of the 15th and 22nd percentiles, respectively. The Salomon method performed less well, with an area under the curve of 0.82 (P < .001 versus both Hadlock and INTG methods). Conclusions: In our study cohort, the Hadlock method predicted the birth weight percentile more accurately than the INTG or Salomon methods and performed comparably with INTG to predict SGA when ROC‐derived cutoffs were used. [ABSTRACT FROM AUTHOR]

Background: The Intergrowth-21st (IG) project proposed prescriptive fetal growth standards for global use based on ultrasound measurements from a multicounty study of low-risk pregnancies selected using strict criteria. We examined whether the IG standards are appropriate for fetal growth monitoring in France and whether potential differences could be due to IG criteria for "healthy" pregnancies.Method: We analysed data on femur length and abdominal circumference at the second and/or the third recommended ultrasound examination from 14 607 singleton pregnancies from the Elfe national birth cohort. We compared concordance of centile thresholds using the IG standards and current French references and used restricted cubic splines to plot z-scores by gestational age. A "healthy pregnancy" sub-sample was created based on maternal and pregnancy selection criteria, as specified by IG.Results: Mean gestational age-specific z-scores for femur length and abdominal circumference using French references fluctuated around 0 (-0.2 to 0.1), while those based on IG standards were higher (0.3-0.8). Using IG standards, 2.5% and 5.2% of fetuses at the third ultrasound were <10th centile for femur length and abdominal circumference, respectively, and 31.5% and 16.7% were >90th. Only 34% of pregnancies fulfilled IG low-risk criteria, but sub-analyses yielded very similar results.Conclusion: Intergrowth standards differed from fetal biometric measures in France, including among low-risk pregnancies selected to replicate IG's healthy pregnancy sample. These results challenge the project's assumption that careful constitution of a low-risk population makes it possible to describe normative fetal growth across populations. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this article was to compare the differences between Intergrowth-21st (IG-21) and Fenton growth standards in the classification of intrauterine and extrauterine growth restriction (EUGR) in eastern Chinese preterm infants, and detect which one can better relate to neonatal diseases and predict the physical growth outcomes at 3-5 years old., Methods: Premature infants admitted to a tertiary pediatric hospital in Shanghai, China, from 2016 to 2018 were enrolled. Prenatal information, neonatal diseases during hospitalization, and anthropometric data (weight, height, and head circumference) at birth and at discharge were collected and analyzed. Physical growth outcomes (short stature, thinness, and overweight) were examined by telephone investigations in 2021 at age 3-5 years., Results: The medium gestational age and birth weight of the included 1,065 preterm newborns were 33.6 weeks and 1,900 g, respectively. The IG-21 curves diagnosed more newborns with small for gestational age (SGA) (19% vs. 14.7%) and fewer newborns with longitudinal EUGR on height (25.5% vs. 27.9%) and head circumference (17.9% vs. 24.7%) compared to Fenton curves. Concordances between Fenton and IG-21 standards were substantial or almost perfect in the classification of SGA and longitudinal EUGR, but minor in cross-sectional EUGR. EUGR identified by Fenton curves was better related to neonatal diseases than IG-21 curves. There were no statistical significances in the prediction of short stature, thinness, and overweight at 3-5 years old between the two charts., Conclusions: IG-21 growth standards are not superior to Fenton in assessing preterm growth and development in the eastern Chinese population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Lan, Fu, Zhang, Chen, Pan, Song, Wang and Hong.)

Introduction: The INTERGROWTH-21st project (IG-21) was recently performed aiming to provide a universal benchmark for comparing fetal growth across different ethnicities. Our aim was to compare the IG-21 with a customized standard for predicting pregnancies at risk for neonatal small-for-gestational age (SGA) and adverse outcomes.Material and Methods: This was a prospective cohort study including singleton pregnancies presenting for fetal growth assessment between 26 and 36 weeks of gestation. Fetal growth restriction was defined as estimated fetal weight <10th centile for gestational age using IG-21 and a customized standard. Neonatal SGA was defined as birthweight <10th centile for gestational age by the Alexander chart. Primary outcome was the prediction of neonatal SGA. Secondary outcomes included a composite of adverse neonatal outcomes. The discriminatory ability of each growth standard was compared using area under receiver operating characteristic curves (AUC).Results: Of 1054 pregnancies meeting the inclusion criteria, the incidence of neonatal SGA was 139 (13.2%), and a composite adverse neonatal outcome occurred in 300 (28.4%). The sensitivity of the customized standard (38.8%) was higher than that of IG-21 (24.5%) for predicting neonatal SGA, with AUC (95% CI) of 0.67 (0.63-0.71) for customized vs 0.62 (0.58-0.65) for IG-21; P = .003. Both standards were comparable in predicting the composite adverse neonatal outcomes: AUC (95% CI) 0.52 (0.50-0.55) for customized vs 0.51 (0.50-0.53) for IG-21; P = 0.25.Conclusions: Both growth standards had modest performance in detecting neonatal SGA and were poor at predicting short-term adverse neonatal outcome. [ABSTRACT FROM AUTHOR]

Objectives: To identify risk factors for antepartum stillbirth, including fetal growth restriction, among women with well-dated pregnancies and access to antenatal care.Design: Population-based, prospective, observational study.Setting: Eight international urban populations.Population: Pregnant women and their babies enrolled in the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project.Methods: Cox proportional hazard models were used to compare risks among antepartum stillborn and liveborn babies.Main Outcome Measures: Antepartum stillbirth was defined as any fetal death after 16 weeks' gestation before the onset of labour.Results: Of 60 121 babies, 553 were stillborn (9.2 per 1000 births), of which 445 were antepartum deaths (7.4 per 1000 births). After adjustment for site, risk factors were low socio-economic status, hazard ratio (HR): 1.6 (95% CI, 1.2-2.1); single marital status, HR 2.0 (95% CI, 1.4-2.8); age ≥40 years, HR 2.2 (95% CI, 1.4-3.7); essential hypertension, HR 4.0 (95% CI, 2.7-5.9); HIV/AIDS, HR 4.3 (95% CI, 2.0-9.1); pre-eclampsia, HR 1.6 (95% CI, 1.1-3.8); multiple pregnancy, HR 3.3 (95% CI, 2.0-5.6); and antepartum haemorrhage, HR 3.3 (95% CI, 2.5-4.5). Birth weight <3rd centile was associated with antepartum stillbirth [HR, 4.6 (95% CI, 3.4-6.2)]. The greatest risk was seen in babies not suspected to have been growth restricted antenatally, with an HR of 5.0 (95% CI, 3.6-7.0). The population-attributable risk of antepartum death associated with small-for-gestational-age neonates diagnosed at birth was 11%.Conclusions: Antepartum stillbirth is a complex syndrome associated with several risk factors. Although small babies are at higher risk, current growth restriction detection strategies only modestly reduced the rate of stillbirth.Tweetable Abstract: International stillbirth study finds individual risks poor predictors of death but combinations promising. [ABSTRACT FROM AUTHOR]

Objectives: To assess the suitability of the new INTERGROWTH‐21st and World Health Organization (WHO) estimated fetal weight (EFW) references in a Southern Chinese population. A secondary aim was to determine the accuracy of EFW by assessing the difference between EFW and actual birth weight. Methods: This was a prospective cross‐sectional cohort study. Viable singleton pregnancies at 11–13 weeks' gestation were recruited to undergo a single standardized fetal biometric scan after 20 weeks. The gestational age at which the scan was performed was allocated randomly at the time of recruitment. EFW was predicted using both the Hadlock and INTERGROWTH‐21st weight estimation model formulae. Population‐specific EFW references were constructed. Z‐scores were used to compare these references against the INTERGROWTH‐21st and WHO international size references. Gestational‐age‐adjusted projection was used to assess the difference between EFW on the day of delivery and birth weight for fetuses having biometry scans ≥ 34 weeks. Results: Fetuses of 970 participants had biometry scans. The median number of scans per gestational week was 48 (interquartile range, 43–53). Z‐score comparison indicated that the WHO 10th, 50th and 90th centiles of the EFW reference were consistently higher than the corresponding local centiles, whilst the INTERGROWTH‐21st 10th centile was lower. Fewer than 2% of fetuses scanned at or after 34 weeks would be considered as potentially large‐for‐gestational age, irrespective of which model was used to predict weight. Adopting the WHO international reference would result in approximately one in six fetuses being regarded as potentially small‐for‐gestational age, 50% more than the number determined using a population‐specific reference. Systematic errors of extrapolated EFW were similar, ranging from 5.5% to 7.4%. Conclusions: Centers seeking to use new references, such as the INTERGROWTH‐21st and/or WHO international references, as a means of determining whether a fetus is small‐ or large‐for‐gestational age, would be advised to assess the suitability of these references within their own population using standardized methodology. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To compare the accuracy of the INTERGROWTH-21st (IG-21) with the Italian Society of Ultrasound in Obstetrics and Gynecology (SIEOG) abdominal circumference (AC) standards in the detection of small-for-gestational-age (SGA) fetuses in a high-risk population.Material and Methods: Our study included all pregnant patients with an increased risk of placental insufficiency that were seen in two Italian university hospitals between 2014 and 2015. The accuracy of IG-21 and SIEOG AC standards in the detection of SGA neonates was analyzed by means of the area under the receiver operating characteristic curve (ROC-AUC) at 4 gestational age intervals (24-27, 28-31, 32-35, >35 weeks).Results: We enrolled 428 patients (278 Italians). There was no significant difference between the ROC-AUC of AC according to IG-21 and SIEOG standards for all birthweight thresholds and gestational intervals that were considered. The diagnostic performance was similar in Italian and non-Italian patients. The accuracy was, however, limited, with values of ROC-AUC ranging between 0.80 and 0.89.Conclusions: The IG-21 and SIEOG AC standards are interchangeable for the diagnosis of SGA fetuses. The diagnostic accuracy is, however, limited. We provide figures that can be used to stratify the probability that an infant will be SGA in an obstetric population at increased risk of growth restriction. [ABSTRACT FROM AUTHOR]

Objective: To assess the impact of adopting the INTERGROWTH-21(st) biometry standards in a Chinese population.Design: Retrospective cohort study.Setting: A teaching hospital in Hong Kong.Population: A total of 10 527 Chinese women with a singleton pregnancy having a second- or third-trimester fetal anomaly or growth scan between January 2009 and June 2014.Methods: Z-scores were derived for fetal abdominal circumference (AC), head circumference (HC), and femur length (FL) using the INTERGROWTH-21(st) and Chinese biometry standards. Pregnancies with aneuploidy, structural or skeletal abnormalities, or that developed pre-eclampsia were excluded. Z-scores were stratified as <2.5th, <5th, <10th, >90th, >95th, or >97.5th percentile. Birthweight centile, adjusted for gestation and gender, was categorised as ≤3rd, 3rd to ≤5th, 5th to ≤10th, and >10th. Pairwise comparison and the McNemar test were performed to assess biometry Z-score differences and concordance between the INTERGROWTH-21(st) and Chinese standards.Main Outcome Measures: The sensitivity of both the local and INTERGROWTH-21(st) AC standards to identify pregnancies that were small-for-gestational-age (SGA) was assessed.Results: INTERGROWTH-21(st) AC, HC, and FL Z-scores were significantly lower than those obtained using our local reference for AC, HC, and FL (P < 0.0001 for all). The proportion of fetuses with biometry in the <2.5th, <5th, <10th, >90th, >95th, or >97.5th percentiles was statistically significant (P < 0.01 for all). A total of 1224 (15.5%) of the scans at 18-22 weeks of gestation had AC, HC, or FL below the 3rd percentile of the INTERGROWTH-21(st) standard.Conclusions: Adopting the INTERGROWTH-21(st) standard would lead to a significant number of fetuses being at risk of misdiagnosis for small fetal size, particularly when using HC and FL measures.Tweetable Abstract: INTERGROWTH-21(st) biometry assessment in Chinese leads to fetuses being at risk of misdiagnosis of small fetal size. [ABSTRACT FROM AUTHOR]

The primary aim of the INTERGROWTH-21(st) 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. [ABSTRACT FROM AUTHOR]

The primary aim of the INTERGROWTH-21(st) 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. [ABSTRACT FROM AUTHOR]

The Middle Eastern site in the INTERGROWTH-21(st) Project was Muscat, the capital city of Oman, with approximately 10,500 births per year. The sample for the Newborn Cross-Sectional Study (NCSS) was drawn from two hospitals covering 96% of the region's births. The Fetal Growth Longitudinal Study (FGLS) sample was recruited from four primary health facilities serving Khoula Hospital, using the eligibility criteria in the INTERGROWTH-21(st) protocol. Special activities to encourage participation in this population included local advocacy campaigns to encourage early antenatal booking and ultrasound dating in the population. The major challenges at the site were the recruitment of sufficient numbers of women at an early gestational age, and the timely measurement of all newborns within 12 hours of birth. Many individuals and institutions collaborated effectively over a period of several years on these studies, which required careful planning and close monitoring for their successful implementation. [ABSTRACT FROM AUTHOR]

INTERGROWTH-21(st) is a multicentre, multiethnic, population-based project, being conducted in eight geographical areas (Brazil, China, India, Italy, Kenya, Oman, UK and USA), with technical support from four global specialised units, to study growth, health and nutrition from early pregnancy to infancy. It aims to produce prescriptive growth standards, which conceptually extend the World Health Organization (WHO) Multicentre Growth Reference Study (MGRS) to cover fetal and newborn life. The new international standards will describe: (1) fetal growth assessed by clinical and ultrasound measures; (2) postnatal growth of term and preterm infants up to 2 years of age; and (3) the relationship between birthweight, length and head circumference, gestational age and perinatal outcomes. As the project has selected healthy cohorts with no obvious risk factors for intrauterine growth restriction, these standards will describe how all fetuses and newborns should grow, as opposed to traditional charts that describe how some have grown at a given place and time. These growth patterns will be related to morbidity and mortality to identify levels of perinatal risk. Additional aims include phenotypic characterisation of the preterm and impaired fetal growth syndromes and development of a prediction model, based on multiple ultrasound measurements, to estimate gestational age for use in pregnant women without access to early/frequent antenatal care. [ABSTRACT FROM AUTHOR]

The INTERGROWTH-21(st) Project data management was structured incorporating both a centralised and decentralised system for the eight study centres, which all used the same database and standardised data collection instruments, manuals and processes. Each centre was responsible for the entry and validation of their country-specific data, which were entered onto a centralised system maintained by the Data Coordinating Unit in Oxford. A comprehensive data management system was designed to handle the very large volumes of data. It contained internal validations to prevent incorrect and inconsistent values being captured, and allowed online data entry by local Data Management Units, as well as real-time management of recruitment and data collection by the Data Coordinating Unit in Oxford. To maintain data integrity, only the Data Coordinating Unit in Oxford had access to all the eight centres' data, which were continually monitored. All queries identified were raised with the relevant local data manager for verification and correction, if necessary. The system automatically logged an audit trail of all updates to the database with the date and name of the person who made the changes. These rigorous processes ensured that the data collected in the INTERGROWTH-21(st) Project were of exceptionally high quality. [ABSTRACT FROM AUTHOR]

The South Asian site in the INTERGROWTH-21(st) Project was the city of Nagpur, in Maharashtra State, India, with approximately 4500 births per year among the target population with middle to high socio-economic status. These deliveries are mainly concentrated in 20 small private hospitals, most of which are in the city centre. The sample for the Newborn Cross-Sectional Study (NCSS) was drawn from ten of these hospitals, covering 76% of the target low-risk pregnant population. The Fetal Growth Longitudinal Study (FGLS) sample was recruited from the largest of these institutions, Ketkar Hospital, as well as several ancillary antenatal care clinics. Special activities to encourage participation and raise awareness of the study at this site included translating patient information leaflets into local languages and securing local media interest. Among the unique challenges of the Indian site was the coordination of the large number of hospitals involved in NCSS, a task that required careful planning and organisation by the field teams. [ABSTRACT FROM AUTHOR]

The INTERGROWTH-21st Project presented a complex set of ethical challenges given the involvement of health institutions in geographically and culturally diverse areas of the world, with differing attitudes to pregnancy. This paper addresses how the research team dealt with some of those issues. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Turin, Italy, was one of the two European sites for the INTERGROWTH-21st Project. The sample for the Newborn Cross-Sectional Study (NCSS) was drawn from two obstetric hospitals that together account for 79% of the city's approximately 12 000 births per year. Women were recruited for the Fetal Growth Longitudinal Study ( FGLS) from ten antenatal clinics serving the city's largest obstetric hospital, Azienda Ospedaliera OIRM-S. Anna. Special activities to encourage participation and raise awareness of the project in this population included obtaining an endorsement from the coordinator of the city's antenatal care service, and disseminating information about the project to women through posters and leaflets in antenatal clinics. One of the major challenges at this site was the low recruitment rate in the early phase of FGLS because of the high prevalence of smoking and of women >35 years old in the population. The addition of six extra recruiting clinics served to increase the pool of potentially eligible women who could be screened and led to a marked improvement in the recruitment rate. [ABSTRACT FROM AUTHOR]

Meticulous standardisation and ongoing monitoring of adherence to measurement protocols during data collection are essential to ensure consistency and to minimise systematic error in multicentre studies. Strict ultrasound fetal biometric measurement protocols are used in the INTERGROWTH-21st Project so that data of the highest quality from different centres can be compared and potentially pooled. A central Ultrasound Quality Unit ( USQU) has been set up to oversee this process. After initial training and standardisation, the USQU monitors the performance of all ultrasonographers involved in the project by continuously assessing the quality of the images and the consistency of the measurements produced. Ultrasonographers are identified when they exceed preset maximum allowable differences. Corrective action is then taken in the form of retraining or simply advice regarding changes in practice. This paper describes the procedures used, which can form a model for research settings involving ultrasound measurements. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Carvalho M, Vinayak S, Ochieng R, Choksey V, Musee N, Stones W, Knight H, Cheikh Ismail L, for the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st). Implementation of the INTERGROWTH-21st Project in Kenya. BJOG 2013; 120 (Suppl. 2): 105-110. The African site in the INTERGROWTH-21st Project was Parklands, a wealthy suburb of Nairobi, Kenya, with a largely middle-to-high socio-economic status population. There are three hospitals with obstetric units in Parklands, with approximately 4300 births per year. The Newborn Cross-Sectional Study (NCSS) sample was drawn from all three hospitals, covering 100% of births in this target population. The Fetal Growth Longitudinal Study (FGLS) sample was recruited from antenatal clinics serving these hospitals, using the eligibility criteria in the INTERGROWTH-21st protocol. Special activities to raise awareness of the study included securing media coverage and distributing leaflets in antenatal clinic waiting rooms. FGLS required women to be recruited in the first trimester; therefore, a major challenge at this study site was the high background frequency of first antenatal consultations in the second trimester. The problem was overcome by the study awareness campaign, as a result of which more women started attending antenatal care earlier in pregnancy. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Silveira M, Barros F, Sclowitz I, Domingues M, Mota D, Fonseca S, Mitidieri A, Leston A, Knight H, Cheikh Ismail L, for the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st). Implementation of the INTERGROWTH-21st Project in Brazil. BJOG 2013; 120 (Suppl. 2): 81-86. The Latin American site in the INTERGROWTH-21st Project was Pelotas, Brazil, with approximately 4000 births per year. The sample for the Newborn Cross-Sectional Study (NCSS) was drawn from four hospitals, covering 99% of births in the city. The Fetal Growth Longitudinal Study (FGLS) sample was recruited from one of the largest private ultrasound clinics in the city and 30 smaller, private, antenatal clinics serving middle to high socio-economic status women. Among this site's major challenges was the recruitment of women for FGLS from numerous different clinics. Several public relations activities were conducted to improve collaborative efforts between the research team and obstetricians, paediatricians and community leaders in Pelotas. [ABSTRACT FROM AUTHOR]

The Middle Eastern site in the INTERGROWTH-21st Project was Muscat, the capital city of Oman, with approximately 10 500 births per year. The sample for the Newborn Cross- Sectional Study (NCSS) was drawn from two hospitals covering 96% of the region's births. The Fetal Growth Longitudinal Study (FGLS) sample was recruited from four primary health facilities serving Khoula Hospital, using the eligibility criteria in the INTERGROWTH-21st protocol. Special activities to encourage participation in this population included local advocacy campaigns to encourage early antenatal booking and ultrasound dating in the population. The major challenges at the site were the recruitment of sufficient numbers of women at an early gestational age, and the timely measurement of all newborns within 12 hours of birth. Many individuals and institutions collaborated effectively over a period of several years on these studies, which required careful planning and close monitoring for their successful implementation. [ABSTRACT FROM AUTHOR]

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. INTERGROWTH-2 1st is a multicentre, multiethnic, population-based project, being conducted in eight geographical areas (Brazil, China, India, Italy, Kenya, Oman, UK and USA), with technical support from four global specialised units, to study growth, health and nutrition from early pregnancy to infancy. It aims to produce prescriptive growth standards, which conceptually extend the World Health Organization (WHO) Multicentre Growth Reference Study (MGRS) to cover fetal and newborn life. The new international standards will describe: (1) fetal growth assessed by clinical and ultrasound measures; (2) postnatal growth of term and preterm infants up to 2 years of age; and (3) the relationship between birthweight, length and head circumference, gestational age and perinatal outcomes. As the project has selected healthy cohorts with no obvious risk factors for intrauterine growth restriction, these standards will describe how all fetuses and newborns should grow, as opposed to traditional charts that describe how some have grown at a given place and time. These growth patterns will be related to morbidity and mortality to identify levels of perinatal risk. Additional aims include phenotypic characterisation of the preterm and impaired fetal growth syndromes and development of a prediction model, based on multiple ultrasound measurements, to estimate gestational age for use in pregnant women without access to early/frequent antenatal care. [ABSTRACT FROM AUTHOR]

The South Asian site in the INTERGROWTH-21st Project was the city of Nagpur, in Maharashtra State, India, with approximately 4500 births per year among the target population with middle to high socio-economic status. These deliveries are mainly concentrated in 20 small private hospitals, most of which are in the city centre. The sample for the Newborn Cross- Sectional Study ( NCSS) was drawn from ten of these hospitals, covering 76% of the target low-risk pregnant population. The Fetal Growth Longitudinal Study (FGLS) sample was recruited from the largest of these institutions, Ketkar Hospital, as well as several ancillary antenatal care clinics. Special activities to encourage participation and raise awareness of the study at this site included translating patient information leaflets into local languages and securing local media interest. Among the unique challenges of the Indian site was the coordination of the large number of hospitals involved in NCSS, a task that required careful planning and organisation by the field teams. [ABSTRACT FROM AUTHOR]

The INTERGROWTH-21st Project has in its mandate to develop prescriptive standards for fetal, neonatal and preterm post-neonatal growth. The project comprises three components: the Fetal Growth Longitudinal Study (FGLS), the Preterm Postnatal Follow-up Study (PPFS), and the Newborn Cross-Sectional Study (NCSS). We consider here the statistical aspects of the three components as they relate to the construction of these standards, in particular the sample size, and outline the principles that will guide the planned main analyses. [ABSTRACT FROM AUTHOR]

The INTERGROWTH-21st Project has generated a package of international clinical standards, tools and guidelines. It is now necessary to plan for the next phase of the project: the translation of the research findings into practice through its global dissemination. The plan is to pre-empt barriers to implementation by drawing from the published literature; gathering views and perspectives from policy makers, programmers and practitioners; incorporating input from local 'champions', and collecting and analysing data generated by a monitoring and evaluation system. Working at the global, regional, national and local levels will enable wide dissemination of the package, as well as increase the scope for adaptation and integration in diverse clinical contexts. We seek maximum uptake of the package in policies, guidelines and clinical practice to improve the quality of care offered to mothers and newborns. The strategy will also enhance our understanding of the effectiveness of different approaches to the translation of evidence into practice. [ABSTRACT FROM AUTHOR]