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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.

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]

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).)