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Aims: We aimed to systematically synthesize the current published literature on neonatal growth outcomes associated with antiseizure medication (ASM) use during pregnancy., Methods: We searched seven databases, from inception to 23 March 2022. We investigated small for gestational age (SGA) and low birth weight (LBW) as primary outcomes and birth weight, birth height, cephalization index and head circumference as secondary outcomes. The primary analysis included pregnant people exposed to any ASM compared with unexposed pregnant people. Subgroup analysis included ASM class analysis, within epilepsy group analysis and polytherapy compared to monotherapy., Results: We screened 15 720 citations and included 65 studies in the review. Exposed pregnant people had a significantly increased risk of SGA relative risk (RR) 1.33 (95% CI 1.18 to 1.50, I 2 74%), LBW RR 1.54 (95% CI 1.33 to 1.77, I 2 67%), and decreased birth weight with a mean difference (MD) of -118.87 (95% CI -161.03 to -76.71, I 2 42%) g. A non-significant risk change in birth height and head circumference was observed. In subgroup analysis, ASM polytherapy, within epilepsy and ASM class analysis were also associated with an increased risk of SGA and LBW., Conclusions: This meta-analysis demonstrates that pregnant people exposed to ASMs have a significantly increased risk of adverse fetal growth outcomes including SGA and LBW and decreased birth weight compared to unexposed pregnant people. Polytherapy was associated with higher risks compared to monotherapy. Additional studies are warranted on specific ASM risks., (© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

A minority of children born small for gestational age (SGA) may experience catch-up growth failure and remain short in adulthood. However, the underlying causes and mechanisms of this phenomenon are not yet fully comprehended. We reviewed the present state of research concerning the growth hormone-insulin-like growth factor axis and growth plate in SGA children who fail to achieve catch-up growth. Additionally, we explored the factors influencing catch-up growth in SGA children and potential molecular mechanisms involved. Furthermore, we considered the potential benefits of supplementary nutrition, specific dietary patterns, probiotics and drug therapy in facilitating catch-up growth., (© 2024. The Author(s).)

Introduction: The use of different growth charts can lead to confusion in discussions between professionals. There are obstetric charts (of fetal growth) and neonatal charts (of measurements at birth and of postnatal growth). These charts can be descriptive (derived from an unselected population) or prescriptive (derived from of a population at low risk and with optimal conditions for growth)., Objectives: (1) To describe available charts for infants at birth and in the neonatal period and compare them, and (2) to recommend one or more charts for use in neonatology in France., Methods: Bibliographic research was conducted on MEDLINE and completed by the guidelines of professional societies., Results: Antenatal information about fetal growth restriction or fetuses identified as small-for-gestational-age using Intrauterine charts must be integrated into the identification of newborns at risk, but the use of Intrauterine charts to evaluate birthweight is not recommended to allow consistency with postnatal charts used in neonatal practice. Z-score variations using the updated Fenton postnatal charts are the most appropriate for the assessment of birthweight and postnatal growth for infants born preterm. These charts are sex-specific, include the three measurements (length, weight, and head circumference) and enable longitudinal follow-up of growth up to 50 weeks of corrected age and are linked to the World Health Organization charts at term. The French Audipog charts, although are individualized, accessible online and can be used in maternity units to evaluate birthweight for term infants, but do not allow the follow-up of postnatal growth, while Fenton charts may be used to evaluate birthweight and postnatal growth in the first month for hospitalized term infants., Conclusion: The updated Fenton charts are the neonatal charts that best suit the objectives of pediatricians in France for monitoring the growth of preterm newborns. The use of the Audipog charts at term remains an alternative in maternity wards, while Fenton charts can be used for hospitalized term newborns., (© 2024 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Short stature with IGF-1 receptor (IGF1R) gene alteration is known as small-for-gestational-age (SGA) short stature with elevated serum IGF1 levels. Its prevalence and clinical characteristics remain unclear. No adapted treatment is available for short stature related to IGF1R gene alteration in Japan, and genetic testing is not yet widely accessible. We investigated short stature with IGF1R gene alterations and analyzed the clinical data of 13 patients using the results of questionnaires issued to the Japanese Society for Pediatric Endocrinology. Four cases were caused by a deletion of chromosome 15q26.3, and eight were caused by heterozygous pathogenic variants in the IGF1R gene. Cases with deletions showed a more severe degree of growth impairment (-4.5 ± 0.43 SD) than those caused by pathological variants (-2.71 ± 0.15 SD) and were accompanied by neurodevelopmental delay. However, cases caused by pathological variants lacked distinctive features. Only three of the 12 cases demonstrated serum IGF1 values exceeding +2 SD, and the other three had values below 0 SD. Four patients did not meet the criteria for SGA at birth. Six patients received GH therapy for SGA short stature and showed improvement in growth rate without any side effects or elevated serum IGF1 levels during treatment. Elevated IGF1 levels (over +2 SD) after GH treatment should be considered a suspicious finding. Owing to the lack of distinctive features, there was a possibility of undiagnosed cases of this condition. Promoting genetic testing and clinical trials on GH administration for this condition is recommended.

The aim of this study was to develop a real-time risk prediction model for extrauterine growth retardation (EUGR). A total of 2514 very preterm infants were allocated into a training set and an external validation set. The most appropriate independent variables were screened using univariate analysis and Lasso regression with tenfold cross-validation, while the prediction model was designed using binary multivariate logistic regression. A visualization of the risk variables was created using a nomogram, while the calibration plot and receiver operating characteristic (ROC) curves were used to calibrate the prediction model. Clinical efficacy was assessed using the decision curve analysis (DCA) curves. Eight optimal predictors that namely birth weight, small for gestation age (SGA), hypertensive disease complicating pregnancy (HDCP), gestational diabetes mellitus (GDM), multiple births, cumulative duration of fasting, growth velocity and postnatal corticosteroids were introduced into the logistic regression equation to construct the EUGR prediction model. The area under the ROC curve of the training set and the external verification set was 83.1% and 84.6%, respectively. The calibration curve indicate that the model fits well. The DCA curve shows that the risk threshold for clinical application is 0-95% in both set. Introducing Birth weight, SGA, HDCP, GDM, Multiple births, Cumulative duration of fasting, Growth velocity and Postnatal corticosteroids into the nomogram increased its usefulness for predicting EUGR risk in very preterm infants., (© 2024. The Author(s).)

Adequate nutrition is necessary for achieving optimal growth and neurodevelopment. Growth is a natural and expected process that happens concomitantly with rapid advancements in neurodevelopment. Serial weight, length, and head circumference growth measures are essential for monitoring development, although identifying pathological deviations from normal growth can pose challenges. Appropriate growth assessments require considerations that a range of sizes for length, head circumference, and weight are expected and appropriate. Because of genetic differences and morbidities, there is a considerable overlap between the growth of healthy infants and those with growth alterations. Parents tend to be over-concerned about children who plot low on growth charts and often need reassurance. Thus, the use of terms such as "poor" growth or growth "failure" are discouraged when growth is approximately parallel to growth chart curves even if their size is smaller than specific percentiles. No specific percentile should be set as a growth goal; individual variability should be expected. An infant's size at birth is important information that goes beyond the common use of prognostic predictions of appropriate compared with small or large for gestational age. The lower the birthweight, the lower the nutrient stores and the more important the need for nutrition support. Compared to term infants, preterm infants at term-equivalent age have a higher percentage of body fat, but this diminishes over the next months. Current research findings support expert recommendations that preterm infants should grow, after early postnatal weight loss, similar to the fetus and then term-born infants, which translates to growth approximately parallel to growth chart curves. There is no need for a trade-off between optimum cognition and optimum future health. Each high-risk infant needs individualized nutrition and growth assessments. This review aims to examine infant growth expectations and messaging for parents of preterm and term-born infants within the broader causal framework., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Early life growth trajectories of Indian small for gestational age (SGA) infants are sparse. This study aimed to compare longitudinal growth in appropriate for gestational age (AGA) and SGA infants during their first year of life., Methods: Apparently healthy term infants (52 SGA, 154 AGA) were recruited at birth and followed up till 1 year. Parental, sociodemographic characteristics and feeding patterns were recorded. Anthropometric measurements were assessed at birth, 3, 6, 9 and 12 months of age; Z scores and growth velocity at 3-month intervals were computed. Longitudinal measurements were compared between the two groups, using the two-way Friedmans test. Median regression with mixed effects was used to adjust covariates; p value <0.05 was considered statistically significant., Result: AGA infants had significantly higher median weight (kg) (2.87 (2.67, 3.04) vs 2.39 (2.25, 2.54)) at birth, (7.08 (6.50, 7.54) vs 6.49 (6.13, 6.78)) at 6 months, (8.64 (7.92, 9.14) vs 7.90 (7.36, 8.54)) at 12 months, median length (cm) ((48.10 (47.20, 49.30) vs 46.75 (45.43, 47.50)) at birth, (65.50 (64.23, 66.98) vs 63.33 (62.26, 65.28)) at 6 months, (73.30 (71.58, 74.66) vs 71.55 (70.00, 73.30)) at 12 months. SGA infants had comparable weight velocity at all intervals except 9-12 months (6.62 (6.45, 6.79) vs (6.70 (6.51, 6.85)), being significantly higher than AGA infants. Differences in skinfold thicknesses between groups were observed only at birth. Exclusivity of breast feeding was significantly higher at 3 months in AGA, compared to SGA infants (80.9% vs 57.8%). Length velocity was comparable at all ages between groups. Sexual dimorphism was observed in the growth velocities of both groups., Conclusion: SGA infants grew in parallel to AGA infants, having significantly lower anthropometric measurements at all time points. However, growth velocities were similar; SGA infants had significantly higher weight velocity from 9 to 12 months. Longitudinal studies beyond 1 year of age, using body composition are needed to determine the quality of growth in Indian infants., Competing Interests: Competing interests: None to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Preterm, low-birth weight (LBW) and small-for-gestational age (SGA) newborns have a higher frequency of adverse health outcomes, including linear and ponderal growth impairment., Objective: To describe the growth trajectories and to estimate catch-up growth during the first 5 y of life of small newborns according to 3 vulnerability phenotypes (preterm, LBW, SGA)., Methods: Longitudinal study using linked data from the 100 Million Brazilian Cohort baseline, the Brazilian National Live Birth System (SINASC), and the Food and Nutrition Surveillance System (SISVAN) from 2011 to 2017. We estimated the length/height-for-age (L/HAZ) and weight-for-age z-score (WAZ) trajectories from children of 6-59 mo using the linear mixed model for each vulnerable newborn phenotype. Growth velocity for both L/HAZ and WAZ was calculated considering the change (Δ) in the mean z-score between 2 time points. Catch-up growth was defined as a change in z-score > 0.67 at any time during follow-up., Results: We analyzed 2,021,998 live born children and 8,726,599 observations. The prevalence of at least one of the vulnerable phenotypes was 16.7% and 0.6% were simultaneously preterm, LBW, and SGA. For those born at term, all phenotypes had a period of growth recovery from 12 mo. For preterm infants, the onset of L/HAZ growth recovery started later at 24 mo and the growth trajectories appear to be lower than those born at term, a condition aggravated among children with the 3 phenotypes. Preterm and female infants seem to experience slower growth recovery than those born at term and males. The catch-up growth occurs at 24-59 mo for males preterm: preterm + AGA + NBW (Δ = 0.80), preterm + AGA + LBW (Δ = 0.88), and preterm + SGA + LBW (Δ = 1.08); and among females: term + SGA + NBW (Δ = 0.69), term + AGA + LBW (Δ = 0.72), term + SGA + LBW (Δ = 0.77), preterm + AGA + LBW (Δ = 0.68), and preterm + SGA + LBW (Δ = 0.83)., Conclusions: Children born preterm seem to reach L/HAZ and WAZ growth trajectories lower than those attained by children born at term, a condition aggravated among the most vulnerable., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine the relationship between postnatal foot lengths and estimated gestational age (EGA) in relation to intrauterine growth patterns determined at birth among Nigerian neonates., Design: Hospital-based, cross-sectional., Setting: Olabisi Onabanjo University Teaching Hospital, Sagamu, Nigeria., Participants: 260 neonates with EGA 30- 42 weeks within 48 hours of life., Interventions: Postnatal foot lengths (FL) were measured with Vernier digital calliper in millimetres. The intra-uterine growth pattern was determined using the Lubchenco chart. Pearson correlation and regression analysis tests were performed., Main Outcome Measures: Postnatal foot length in relation to Intra-Uterine Growth Pattern., Results: The mean postnatal FL had a strong positive correlation with the EGA from 30 through 42 weeks (r = 0.855, p < 0.001). The overall mean foot length for preterm neonates was 65.44 (6.92) mm, while that of term neonates was 77.92 (4.24) mm. The linear regression equation was generated as: EGA = 9.43 + (0.37 × FL), p < 0.001. The EGA as measured by FL had the highest positive correlation with Small for Gestational Age (SGA) intra-uterine-growth pattern, followed by Appropriate for Gestational Age (AGA) and least by Large for Gestational Age (LGA) respectively (r = 0.936> 0.861 > 0.666)., Conclusion: The postnatal foot length correlated well with estimated gestational age, and the correlation was best among SGA infants., Funding: None declared., Competing Interests: Conflict of interest: None declared, (Copyright © The Author(s).)

Health related quality of life (HRQoL) is a relevant result when assessing the course of different pathologies and the efficacy of their treatments. HRQoL has been studied previously on adults born small for gestational age (SGA), both in the general population and in patients who had received recombinant human growth hormone (rhGH) treatment, with disparate results. Our study included 50 adults who had received rhGH treatment for the SGA indication in 4 Spanish hospitals. Data have been gathered retrospectively from their clinical records, current weight and height were measured, and patients have been asked to fill out SF-36 and QoLAGHDA quality of life forms, and the Graffar test to evaluate their socio-economical status. Patient's adult height was - 1.2 ± 0.9 SD, lower than their target height of 1 ± 0.8 SD, but gaining 1.7 ± 1 SD from the beginning of the treatment. SF-36 test results showed lower scoring on Mental Health domains than on those related to Physical Health. No correlation was found between HRQoL results and final height, rhGH treatment duration or puberty. Correlation was indeed found between QoLAGHDA and several domains of SF-36, but QoLAGHDA detected fewer patients with low HRQoL than SF-36. Thus, it is concluded that SGA patient's follow-up should include a HRQoL, neuro-cognitive and psychiatric assessment in their transition to adult age. Adult SGA patients without catch up growth have impaired HRQoL, especially in mental health domains., (© 2023. The Author(s).)

Context: Growth hormone (GH) is used to treat short children born small for gestational age (SGA); however, the effects of treatment on pubertal timing and adult height are rarely studied., Objective: To evaluate adult height and peak height velocity in short GH-treated SGA children., Methods: Prospective longitudinal multicenter study. Participants were short children born SGA treated with GH therapy (n = 102). Adult height was reported in 47 children. A reference cohort of Danish children was used. Main outcome measures were adult height, peak height velocity, age at peak height, and pubertal onset. Pubertal onset was converted to SD score (SDS) using Danish reference data., Results: Gain in height SDS from start of treatment until adult height was significant in both girls (0.94 [0.75; 1.53] SDS, P = .02) and boys (1.57 [1.13; 2.15] SDS, P < .001). No difference in adult height between GH dosage groups was observed. Peak height velocity was lower than a reference cohort for girls (6.5 [5.9; 7.6] cm/year vs 7.9 [7.4; 8.5] cm/year, P < .001) and boys (9.5 [8.4; 10.7] cm/year vs 10.1 [9.7; 10.7] cm/year, P = .002), but no difference in age at peak height velocity was seen. Puberty onset was earlier in SGA boys than a reference cohort (1.06 [-0.03; 1.96] SDS vs 0 SDS, P = .002) but not in girls (0.38 [-0.19; 1.05] SDS vs 0 SDS, P = .18)., Conclusion: GH treatment improved adult height. Peak height velocity was reduced, but age at peak height velocity did not differ compared with the reference cohort. SGA boys had an earlier pubertal onset compared with the reference cohort., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Neonatal nutritional supplements may improve early growth for infants born small, but effects on long-term growth are unclear and may differ by sex. We assessed the effects of early macronutrient supplements on later growth. We searched databases and clinical trials registers from inception to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter BMI in childhood (kg/m 2 : adjusted mean difference (aMD) -0.11[95% CI -0.47, 0.25], p = 0.54; 3 trials, n = 333). Supplementation increased length (cm: aMD 0.37[0.01, 0.72], p = 0.04; 18 trials, n = 2008) and bone mineral content (g: aMD 10.22[0.52, 19.92], p = 0.04; 6 trials, n = 313) in infancy, but not at older ages. There were no differences between supplemented and unsupplemented groups for other outcomes. In subgroup analysis, supplementation increased the height z-score in male toddlers (aMD 0.20[0.02, 0.37], p = 0.03; 10 trials, n = 595) but not in females, and no significant sex interaction was observed ( p = 0.21). Macronutrient supplementation for infants born small may not alter BMI in childhood. Supplementation increased growth in infancy, but these effects did not persist in later life. The effects did not differ between boys and girls.

Purpose: Multiple factors influence intrauterine growth and lead to low birth sizes. The impact of genetic alterations on both pre- and post-natal growth is still largely unknown. The aim of this study was to investigate the prevalence of CNVs in an Italian cohort of SGA children with persistent short stature and complex clinical phenotype. rhGH treatment efficacy was evaluated according to the different genotypes., Subjects and Methods: Twenty-four SGA children (10F/14M) with persistent short stature associated with dysmorphic features and/or developmental delay underwent CNV evaluation., Results: CNVs were present in 14/24 (58%) SGA children. Six patients had a microdeletion involving the following regions: 3q24q25.1, 8p21.2p12, 15q26, 19q13.11, 20q11.21q12, 22q11.2. In three females, the same microdeletion involving 17p13.3 region was identified. In two different patients, two microduplications involving 10q21.3 and Xp11.3 region were observed. A further female patient showed both an 11q12.1 and an Xq27.1 microduplication, inherited from her mother and from her father, respectively. In a boy, the presence of a 12p13.33 microdeletion and a 19q13.43 microduplication was found. GH treatment efficacy, expressed by height gain and height velocity in the first 12 months of therapy, was similar in subjects with and without CNVs., Conclusions: These results show that pathogenic CNVs are common in SGA children with short stature associated with additional clinical features. Interestingly, the involvement of 17p13.3 region occurs with a relative high frequency, suggesting that genes located in this region could play a key role in pre- and post-natal growth. rhGH therapy has similar efficacy in the short term whether CNVs are present or not., (© 2021. Italian Society of Endocrinology (SIE).)

Context: Maternal cholesterol is important for fetal development. Whether maternal serum total cholesterol (maternal TC) levels in midpregnancy are associated with small (SGA) or large (LGA) for gestational age independent of prepregnancy body mass index (BMI) and weight gain during pregnancy is inconclusive., Objective: This work aimed to prospectively investigate the association between maternal TC in midpregnancy and SGA or LGA., Methods: The Japan Environment and Children's Study is a nationwide prospective birth cohort study in Japan. Participants in this study included 37 449 nondiabetic, nonhypertensive mothers with singleton birth at term without congenital abnormalities. Birth weight for gestational age less than the 10th percentile and greater than or equal to the 90th percentile were respectively defined as SGA and LGA by the Japanese neonatal anthropometric charts., Results: The mean gestational age at blood sampling was 22.7 ± 4.0 weeks. After adjustment for maternal age, sex of child, parity, weight gain during pregnancy, prepregnancy BMI, smoking, alcohol drinking, blood glucose levels, household income, and study areas, 1-SD decrement of maternal TC was linearly associated with SGA (odds ratio [OR]: 1.20; 95% CI, 1.15-1.25). In contrast, 1-SD increment of maternal TC was linearly associated with LGA (OR: 1.13; 95% CI, 1.09-1.16). Associations did not differ according to prepregnancy BMI and gestational weight gain (P for interaction > .20)., Conclusion: Maternal TC levels in midpregnancy were associated with SGA or LGA in a Japanese cohort. It may help to predict SGA and LGA. Favorable maternal lipid profiles for fetal development must be explored., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Objective: We have shown previously that third-trimester growth in small fetuses (estimated fetal weight (EFW) < 10 th percentile) with birth weight (BW) < 10 th percentile is heterogeneous using individualized growth assessment (IGA). We aimed to test our hypothesis that individual growth patterns in small fetuses with BW > 10 th percentile are also variable but in different ways., Methods: This was a study of 191 cases with EFW < 10 th percentile and BW > 10 th percentile (appropriate-for-gestational-age (AGA) cohort), derived from the PORTO study. Composite size parameters were used to quantify growth pathology at individual third-trimester timepoints (individual composite prenatal growth assessment score (-icPGAS)). The fetal growth pathology score 1 (-FGPS1), calculated cumulatively from serial -icPGAS values, was used to characterize third-trimester growth patterns. Vascular-system evaluation included umbilical artery (UA) and middle cerebral artery (MCA) Doppler velocimetry. Outcome variables were birth age (preterm/term delivery) and BW (expressed as growth potential realization index for weight (GPRI WT ) and percentile). The findings from the AGA cohort were compared with those from small fetuses (EFW < 10 th percentile) with BW < 10 th percentile (small-for-gestational-age (SGA) cohort)., Results: The AGA cohort was found to have 134 fetuses (70%) with normal growth pattern and 57 (30%) with growth restriction based on IGA criteria. Seven growth-restriction -FGPS1 patterns were observed, including the previously defined progressive, late, adaptive and recovering types. The recovering type was the most common growth pattern in the AGA cohort (50.9%). About one-third of fetuses without any evidence of growth restriction had significant unexplained abnormalities in the UA (34%) and MCA (31%) and elevated mean GPRI WT values (113 ± 12.5%). Comparison of the AGA and SGA cohorts indicated a significant difference in the distribution of -FGPS1 growth patterns (P = 0.0001). Compared with the SGA cohort, the AGA cohort had more fetuses with a normal growth pattern (70% vs 38%) and fewer cases with growth restriction (30% vs 62%). While the recovering type was the most common growth-restriction pattern in the AGA cohort (51%), the progressive type was the primary growth-restriction pattern in the SGA cohort (44%). No difference in the incidence of MCA or UA abnormality was found between the SGA and AGA cohorts when comparing subgroups of more than 10 fetuses., Conclusions: Both normal-growth and growth-restriction patterns were observed in the AGA cohort using IGA, as seen previously in the SGA cohort. The seven types of growth restriction defined in the SGA cohort were also identified in AGA cases, but their distribution was significantly different. In one-third of cases without evidence of growth pathology in the AGA cohort, Doppler abnormalities in the UA and MCA were seen. This heterogeneity underscores the difficulty of accurate classification of fetal and neonatal growth status using conventional population-based methods. © 2021 International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 International Society of Ultrasound in Obstetrics and Gynecology.)

A history of preterm or small (SGA) or large (LGA) for gestational age offspring is associated with smoking and unfavorable levels of BMI, blood pressure, glucose and lipids. Whether and to what extent the excess cardiovascular risk observed in women with these pregnancy complications is explained by conventional cardiovascular risk factors (CVRFs) is not known. We examined the association between a history of SGA, LGA or preterm birth and cardiovascular disease among 23,284 parous women and quantified the contribution of individual CVRFs to the excess cardiovascular risk using an inverse odds weighting approach. The hazard ratios (HR) between SGA and LGA offspring and CVD were 1.30 (95% confidence interval (CI) 1.15, 1.48) and 0.89 (95% CI 0.76, 1.03), respectively. Smoking explained 49% and blood pressure may have explained ≈12% of the excess cardiovascular risk in women with SGA offspring. Women with preterm birth had a 24% increased risk of CVD (HR 1.24, 95% CI 1.06, 1.45), but we found no evidence for CVRFs explaining any of this excess cardiovascular risk. While smoking explains a substantial proportion of excess cardiovascular risk in women with SGA offspring and blood pressure may explain a small proportion in these women, we found no evidence that conventional CVRFs explain any of the excess cardiovascular risk in women with preterm birth., (© 2021. The Author(s).)

Fetal growth restriction, previously called intrauterine growth restriction, is a condition in which a fetus does not achieve its full growth potential during pregnancy. Early detection and management of fetal growth restriction are essential because it has significant clinical implications in childhood. It is diagnosed by estimated fetal weight or abdominal circumference below the 10th percentile on formal ultrasonography. Early-onset fetal growth restriction is diagnosed before 32 weeks' gestation and has a higher risk of adverse fetal outcomes. There are no evidence-based measures for preventing fetal growth restriction; however, aspirin used for the prevention of preeclampsia in high-risk pregnancies may reduce the likelihood of developing it. Timing of delivery for pregnancies affected by growth restriction must be adjusted based on the risks of premature birth and ongoing gestation, and it is best determined in consultation with maternal-fetal medicine specialists. Neonates affected by fetal growth restriction are at risk of feeding difficulties, glucose instability, temperature instability, and jaundice. As these children age, they are at risk of abnormal growth patterns, as well as later cardiac, metabolic, neurodevelopmental, reproductive, and psychiatric disorders.

We aimed to evaluate risk factors for growth failure in very low birth weight (VLBW) infants at 18-24 months of corrected age (follow-up1, FU1) and at 36 months of age (follow-up2, FU2). In this prospective cohort study, a total of 2,943 VLBW infants from the Korean Neonatal Network between 2013 and 2015 finished follow-up at FU1. Growth failure was defined as a z-score below -1.28. Multiple logistic regression was used to analyze risk factors for growth failure after dividing the infants into small for gestational age (SGA) and appropriate for gestational age (AGA) groups. Overall, 18.7% of infants were SGA at birth. Growth failure was present in 60.0% at discharge, 20.3% at FU1, and 35.2% at FU2. Among AGA infants, male sex, growth failure at discharge, periventricular leukomalacia, treatment of retinopathy of prematurity, ventriculoperitoneal shunt status and treatment of rehabilitation after discharge were independent risk factors for growth failure at FU1. Among SGA infants, lower birth weight, pregnancy-induced hypertension, and treatment of rehabilitation after discharge were independent risk factors for growth failure at FU1. Mean weight z-score graphs from birth to 36 month of age revealed significant differences between SGA and non-SGA and between VLBW infants and extremely low birth weight infants. Growth failure remains an issue, and VLBW infants with risk factors should be closely checked for growth and nutrition., Competing Interests: The authors have declared that no competing interests exist.

Objective: To examine the longitudinal associations of fetal growth with adverse child growth outcomes and to assess whether maternal metabolic factors modify the associations., Design: Prospective cohort study., Setting: Born in Guangzhou Cohort Study, China., Population: A total of 4818 mother-child pairs., Methods: Fetal growth was assessed according to estimated fetal weight (EFW) from 22 weeks of gestation until birth and the measurement of the birthweight. Fetal growth Z-scores were computed from random effects in the multilevel linear spline models to represent fetal size in early pregnancy (22 weeks of gestation) and growth in mid-pregnancy (22-27 weeks of gestation), early third trimester (28-36 weeks of gestation) and late third trimester (≥37 weeks of gestation)., Main Outcome Measures: Z-scores for childhood stunting, low weight, overweight or obesity, length/height for age (LAZ/HAZ), weight for age (WAZ) and body mass index for age (BMIZ) at the age of 3 years. Adjusted associations were examined using multiple Poisson or linear regression models., Results: Increased Z-scores of fetal size in early pregnancy and growth in mid-pregnancy and early third trimester were associated with a higher risk of childhood overweight or obesity (risk ratios 1.25-1.45). Fetal growth in each period was negatively associated with stunting and low weight, with the strongest associations observed for fetal size in early pregnancy and growth in mid-pregnancy. The results for continuous outcomes (LAZ/HAZ, WAZ and BMIZ) were similar. The associations of fetal growth with overweight or obesity in childhood were stronger among mothers who were underweight and who were overweight or obese than among mothers of normal weight., Conclusions: Accelerated fetal growth before 37 weeks of gestation is associated with children who are overweight or obese, whereas the critical period for stunting and low weight occurs before 28 weeks of gestation., Tweetable Abstract: Fetal growth during different periods is differentially associated with childhood stunting, underweight and overweight or obesity., (© 2021 John Wiley & Sons Ltd.)

Background: Fetal growth restriction (FGR), defined as a fetus failing to reach its genetic growth potential, remains poorly diagnosed antenatally. This study aimed to assess the ability of continuous-wave Doppler ultrasound of the umbilical artery (CWD-UmA) to detect FGR in healthy women with low-risk pregnancies., Methods and Findings: This prospective longitudinal descriptive cohort study enrolled infants born to low-risk mothers who were screened with CWD-UmA between 28-34 weeks' gestation; the resistance index (RI) was classified as normal or abnormal. Infants were assessed at 6, 10, 14 weeks, and 6 months postnatally for anthropometric indicators and body composition using the deuterium dilution method to assess fat-free mass (FFM). Neonates in the abnormal RI group were compared with those in the normal RI group, and neonates classified as small-for-gestational age (SGA) were compared with appropriate-for-gestational age (AGA) neonates. Eighty-one term infants were included. Only 6 of 26 infants (23.1%) with an abnormal RI value would have been classified as SGA. The abnormal RI group had significantly reduced mean FFM and FFM-for-age Z-scores at 6, 10, 14 weeks, and 6 months compared with the normal RI group (P<0.015). The SGA group's FFM did not show this consistent trend when compared to AGA FFM, being significantly different only at 6 months (P = 0.039). The main limitation of the study was the small sample size of the infant follow-up., Conclusions: Abnormal RI obtained from CWD-UmA is able to detect FGR and is considered a useful addition to classifying the neonate only by SGA or AGA at birth., Competing Interests: RP received funding for the South African Medical Research Council (SAMRC) Research Unit and the Council for Scientific and Industrial Research (CSIR) provided the equipment for the study. We have read and understood your journal’s policies, and we believe that neither the manuscript nor the study violates any of these. There are no conflicts of interest to declare.

Purpose: While it is well documented that maternal adverse exposures contribute to a series defects on offspring health according to the Developmental Origins of Health and Disease (DOHaD) theory, paternal evidence is still insufficient. Advanced paternal age is associated with multiple metabolism and psychiatric disorders. Birth weight is the most direct marker to evaluate fetal growth. Therefore, we designed this study to explore the association between paternal age and birth weight among infants born at term and preterm (<37 weeks gestation)., Methods: A large retrospective study was conducted using population-based hospital data from January 2015 to December 2019 that included 69,964 cases of singleton infant births with complete paternal age data. The primary outcome was infant birth weight stratified by sex and gestational age including small for gestational age (SGA, 10th percentile) and large for gestational age (LGA, 90th percentile). Birth weight percentiles by gestational age were based on those published in the INTERGROWTH-21st neonatal weight-for gestational-age standard. Logistic regression analysis and linear regression model were used to estimate the association between paternal age and infant birth weight., Results: Advanced paternal age was associated with a higher risk for a preterm birth [35-44 years: adjusted odds ratio (OR) = 1.13, 95%CI (1.03 to 1.24); >44 years: OR = 1.36, 95%CI (1.09 to 1.70)]. Paternal age exerted an opposite effect on birth weight with an increased risk of SGA among preterm infants (35-44years: OR = 1.85, 95%CI (1.18 to 2.89) and a decreased risk among term infant (35-44years: OR = 0.81, 95%CI (0.68 to 0.98); >44 years: OR = 0.50, 95%CI (0.26 to 0.94). U-shaped associations were found in that LGA risk among term infants was higher in both younger (<25 years) (OR = 1.32; 95%CI, 1.07 to 1.62) and older (35-44 years) (OR = 1.07; 95% CI, 1.01 to 1.14) fathers in comparison to those who were 25 to 34 years old at the time of delivery., Conclusions: Our study found advanced paternal age increased the risk of SGA among preterm infants and for LGA among term infants. These findings likely reflect a pathophysiology etiology and have important preconception care implications and suggest the need for antenatal monitoring., 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., (Copyright © 2021 Mao, Zhang, Wang, Meng, Chen, Dennis, Sheng, Wu and Huang.)

Growth hormone treatment strategies to achieve the goal include the titration of GH doses according to serum insulin-like growth factor I (IGF-I) concentrations. However, IGF-I levels do not always correlate well with the growth response. This study aims to identify the factors affecting the IGF-I concentration and identify the relationship between IGF-I and the treatment response. The data of prepubertal children treated with recombinant human GH for more than one year were obtained from the LG Growth Study (LGS) Database. This study includes patients with idiopathic growth hormone deficiency (IGHD), organic growth hormone deficiency (OGHD), or Turner syndrome (TS) or small for gestational age (SGA). Among 2,021 participants registered in LGS, 366 subjects were selected, 252 had IGHD, 16 had OGHD, 31 had TS, and 67 were SGA. In the IGHD and SGA groups, IGF-I levels had a positive correlation with weight SDS. There was no significant relationship between the pre-treatment IGF-I level and growth response. However, in the IGHD group, the growth response was significantly higher when the change in the IGF-I SDS value was 1 or more (p = 0.0013). Therefore, IGF-I concentrations should be used as an indicator to monitor the treatment compliance rather than for efficacy determination in Korean children of short stature with GH treatment., Competing Interests: The authors have declared that no competing interests exist.

Objective: To explore whether neurosonography can detect differences in cortical development and corpus callosal length in late-onset small fetuses subclassified into small-for-gestational age (SGA) or growth restricted (FGR)., Methods: This was a prospective cohort study in singleton pregnancies, including normally grown fetuses (birth weight between the 10 th and 90 th centiles) and late-onset small fetuses (estimated fetal weight < 10 th centile, diagnosed after 32 weeks of gestation and confirmed by birth weight < 10 th centile). Small fetuses were subclassified into SGA (birth weight between the 3 rd and 9 th centiles and normal fetoplacental Doppler) and FGR (birth weight < 3 rd centile and/or abnormal cerebroplacental ratio and/or abnormal uterine artery Doppler). Neurosonography was performed at 33 ± 1 weeks of gestation to assess the depth of the insula, Sylvian fissure and parieto-occipital sulcus in the axial views and corpus callosal length in the midsagittal plane. Measurements were performed offline using Alma Workstation software and were adjusted by biparietal diameter or cephalic index. Linear regression analysis was used to assess the association between the neurosonographic variables and study group, adjusting for confounding factors such as gender, gestational age at neurosonography, nulliparity and pre-eclampsia., Results: In total, 318 fetuses were included, of which 97 were normally grown and 221 were late-onset small fetuses that were further subdivided into late-onset SGA (n = 67) or late-onset FGR (n = 154). Compared to controls, both SGA and FGR cases showed significantly increased insular depth adjusted for biparietal diameter (median (interquartile range), controls 0.329 (0.312-0.342) vs SGA 0.339 (0.321-0.347) vs FGR 0.336 (0.325-0.349); P = 0.006). A linear tendency to reduced Sylvian fissure depth adjusted for biparietal diameter was also observed across the study groups (mean ± SD, controls 0.148 ± 0.021 vs SGA 0.142 ± 0.025 vs FGR 0.139 ± 0.022; P = 0.003). However, differences were significant only between the FGR and control groups. Corpus callosal length adjusted for cephalic index was significantly reduced in FGR cases compared with both controls and SGA cases, while there was no difference between SGA cases and controls (median (interquartile range), controls 0.500 (0.478-0.531) vs SGA 0.502 (0.487-0.526) vs FGR 0.475 (0.447-0.508); P = 0.005). No differences were found in parieto-occipital sulcus depth between the three study groups., Conclusion: Neurosonography seems to be a sensitive tool to detect subtle structural differences in brain development in late-onset small fetuses. © 2021 International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 International Society of Ultrasound in Obstetrics and Gynecology.)

Introduction: Fatty acids are essential nutrients for the fetus and are supplied by the mother through the placenta. Desaturase and elongase enzymes play an important role in modulating the fatty acid composition of body tissues. We aimed to compare the fatty acid profile and the estimated desaturase and elongase activities in the placenta of appropriate (AGA) versus small-for-gestational-age (SGA), and to determine their relationship with the offspring size at birth., Methods: The placental fatty acid profile was analyzed by gas chromatography in 84 infants (45 AGA and 30 SGA) from a prenatal cohort study. The estimated desaturase and elongase activities were calculated from product-precursor fatty acid ratios. Results were associated with maternal (age, body mass index and weight gain during gestation) and neonatal (gestational age, sex, birth weight and birth length) parameters., Results: Differences in placental fatty acid composition between AGA and SGA infants rather than correlations thereof with neonatal parameters were observed. Placentas from SGA infants contained lower levels of omega-3 (ALA, EPA, DPA, and DHA) and high omega-6/omega-3 ratios (AA/DHA and LA/ALA), as well as low elongase (Elovl5) and high desaturase (D9Dn7 and D5Dn6) activity as compared to AGA infants (all p < 0.0001)., Discussion: Placentas of AGA and SGA infants differed in fatty acids profile as well as in estimated desaturase and elongase activities. A striking feature of SGA placentas was the low availability of omega-3. Hence, omega-3 fatty acid status deserves further attention, as a potential target of prenatal interventions., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Detection of small for gestational age (SGA) fetuses in a third trimester ultrasound could be affected by variation in sonographer performance., Methods: Retrospective analysis of all singleton, non-anomalous ultrasound examinations between 35 +0 -36 +6 weeks gestation, in a single institution where a universal 36-week scan is offered. Screen positive was defined as estimated fetal weight (EFW) <10th centile; SGA was birthweight <10th centile. Individual sonographers' distributions of head circumference (HC), abdominal circumference (AC) and femur length (FL) were used to assess sonographers' screen positive rate (SPR), detection rate (DR) and true positive rate (TPR). Univariate and multivariate regression analysis was performed to assess the association between the sonographers' mean and SD (SD) for HC, AC, FL and their SPR, DR and TPR., Results: There were 27 sonographers performing more than 50 examinations per year, a total of 5691 scans. The mean incidence of SGA was 10.0%. For an overall SPR of 9.4%, the overall DR was 43.8% (95% CI: 39.6% - 48.1%) and the overall TPR was 46.5% (95% CI: 42.9% - 50.2%). Higher AC scatter (SD difference up to 11.6 mm) was associated with higher SPR (P = 0.001). Lower mean FL (difference up to 3.6 mm) was associated with higher SPR (P = 0.003) and higher DR (P = 0.002). As a result, DR varied amongst different sonographers between 14.3% and 85.7% and TPR varied between 8.3% and 100.0%., Conclusions: Monitoring of individual AC and FL distributions is a simple and effective tool for institutional quality assurance., (© 2021 Wiley Periodicals LLC.)

Children born small for gestational age (SGA), and failing to catch-up growth in their early years, are a heterogeneous group, comprising both known and undefined congenital disorders. Care for these children must encompass specific approaches to ensure optimal growth. The use of recombinant human growth hormone (rhGH) is an established therapy, which improves adult height in a proportion of these children, but not with uniform magnitude and not in all of them. This situation is complicated as the underlying cause of growth failure is often diagnosed during or even after rhGH treatment discontinuation with unknown consequences on adult height and long-term safety. This review focuses on the current evidence supporting potential benefits from early genetic screening in short SGA children. The pivotal role that a Next Generation Sequencing panel might play in helping diagnosis and discriminating good responders to rhGH from poor responders is discussed. Information stemming from genetic screening might allow the tailoring of therapy, as well as improving specific follow-up and management of family expectations, especially for those children with increased long-term risks. Finally, the role of national registries in collecting data from the genetic screening and clinical follow-up is considered., Competing Interests: CG received honoraria from Novo Nordisk for consultancies as an expert board member; honoraria from Merck Serono as a medical advisor; honoraria from Ferring for article authorship. CG has no non-financial relationships (personal, political, or professional) that may potentially influence the writing of this manuscript., (Copyright © 2021 Giacomozzi.)

Purpose: To compare the performance of a local estimated fetal weight curve with curves established for other populations to predict small for gestational age (SGA) fetuses., Methods: A retrospective and cross-sectional study involving 231 fetuses in which the performance of a local curve (proposed model) was compared with the Hadlock and Intergrowth-21st curves in the prediction of SGA fetuses, by applying them to a population of high-risk pregnant woman with HIV/AIDS. For each model, a receiver operating characteristic curve was adjusted, considering the SGA classification by the neonatal Intergrowth method as the gold standard, and the area under the curve (AUC) was calculated., Results: The models presented linear correlations with each other. The agreement of the proposed model with Hadlock was very good (kappa = 0.83), whereas the proposed model and Intergrowth-21st had moderate agreement (kappa = 0.44). The SGA fetus detection sensitivities of the proposed model and Hadlock were 61.9% and 57.1%, with specificity of 84.1% and 86.2% and accuracy of 80.1% and 81%, respectively, without statistical difference. The sensitivity of the Intergrowth-21st model was 33.3%, while the accuracy was 85.7% and the specificity was 97.4%. The AUC estimated values for the Hadlock, proposed, and Intergrowth-21st models were 0.834, 0.832, and 0.835, respectively., Conclusion: The proposed model and Hadlock were interchangeable in the prediction of SGA fetuses and superior to the Intergrowth-21st model., (© 2020 Wiley Periodicals LLC.)

Background: Recombinant human growth hormone (rhGH) is approved in Europe as a treatment for short children born small for gestational age (SGA) since 2003. However, no study evaluated the prevalence of SGA children with short stature who qualify for rhGH in Europe so far. This study aimed to investigate in an Italian population the prevalence of children born SGA, of short stature in children born SGA, and of SGA children who qualify for rhGH treatment at 4 years of age., Methods: We conducted a population-based study on primary care pediatricians' databases in Trieste, Italy. Data was collected on 3769 children born between 2004 and 2014. SGA was defined as birth weight and/or birth length ≤ - 2 SDS. Data on height and weight were registered at the closest well-being visit to 1, 2, 3, 4 years of age. Short stature was defined as height ≤ - 2 SDS. Short children born SGA who qualify for rhGH treatment were identified according to Note AIFA #39 criteria (age ≥ 4 years; height ≤ - 2.5 SDS; growth velocity < 50th percentile)., Results: Full data at birth were available for 3250 children. The SGA prevalence was 3.6% (0.8% SGA for weight, 2.2% SGA for length, 0.6% SGA for both weight and length). The prevalence of short stature among SGA children was 9% at 1 year of age, 6% at 2 years (significantly higher in preterm in the first 2 years), 4% at 3 years, 3% at 4 years (all born at term). At 4 years of age, median height SDS was - 0.52. One child born SGA was eligible for GH treatment (0.8% among SGA children)., Conclusions: The prevalence in a general pediatric population of children born SGA who qualify for GH treatment was 1:3250. Although the prevalence of SGA in our population was similar to previous studies, catch-up growth was recorded earlier in our sample compared to previous reports, and term babies had late catch-up. Height SDS of children born SGA at 4 years of age was lower than expected (- 0.52 SDS).

Background: Early postanal growth of preterm infants has many effects on early and late health. However, evidence on growth pattern in Chinese preterm infant population during early life is insufficient. This study aims to describe the growth trajectory, catch-up growth, and risk of overweight of preterm infants during the first 2 years of life in a Chinese community population., Methods: All preterm infants (n = 10,624) received routine childcare in one primary maternal and child healthcare network in 8 years were included. Body weight and length/height at corrected age (CA) 40 weeks, CA 3 months, 6 months, 9 months, 12 months, 18 months, and 24 months were extracted and converted to z-scores based on the World Health Organization (WHO) standards. According to the intrauterine growth status, infants were divided into small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA) infants. Changes of z-score were used to describe the growth velocity. Generalized estimating equation (GEE) model was used to analyze growth trajectory trends over time., Results: Body weight and length/height were overall above the WHO standards during the first 2 years of life. Z-score increased significantly by 0.08 (95% CI: 0.06-0.10) in weight and 0.07 (95% CI: 0.04-0.09) in length/height from CA 40 weeks to 3 months and then levelled off until CA 24 months after adjustment. Almost 90% of AGA and LGA infants achieved growth targets (≥25th percentile of WHO standards), and over 85% of SGA infants achieved catch-up growth (≥10th percentile of WHO standards) before CA 24 months. However, the risk of overweight appeared during this period, with the proportion of infants with the risk of overweight being at the peak at CA 3 months (25.6% of all preterm infants and 39.4% of LGA infants). Growth trajectories of SGA showed increasing trends, but those of LGA showed decreasing trends during the first 2 years., Conclusions: Body weight and length/height of preterm infants are above the WHO standards in the Chinese community population during the first 2 years of life. Catch-up growth is accompanied by risk of overweight as early as CA 3 months. (349 words).

Background: (Epi)genetic disorders associated with small-for-gestational-age with short stature (SGA-SS) include imprinting disorders (IDs). Silver-Russell syndrome (SRS) is a representative ID in SGA-SS and has heterogenous (epi)genetic causes., Subjects and Methods: To clarify the contribution of IDs to SGA-SS and the molecular and phenotypic spectrum of SRS, we recruited 269 patients with SGA-SS, consisting of 103 and 166 patients referred to us for genetic testing for SGA-SS and SRS, respectively. After excluding 20 patients with structural abnormalities detected by comparative genomic hybridization analysis using catalog array, 249 patients were classified into 3 subgroups based on the Netchine-Harbison clinical scoring system (NH-CSS), SRS diagnostic criteria. We screened various IDs by methylation analysis for differentially methylated regions (DMRs) related to known IDs. We also performed clinical analysis., Results: These 249 patients with SGA-SS were classified into the "SRS-compatible group" (n = 148), the "non-SRS with normocephaly or relative macrocephaly at birth group" (non-SRS group) (n = 94), or the "non-SRS with relative microcephaly at birth group" (non-SRS with microcephaly group) (n = 7). The 44.6% of patients in the "SRS-compatible group," 21.3% of patients in the "non-SRS group," and 14.3% in the "non-SRS with microcephaly group" had various IDs. Loss of methylation of the H19/IGF2:intergenic-DMR and uniparental disomy chromosome 7, being major genetic causes of SRS, was detected in 30.4% of patients in the "SRS-compatible group" and in 13.8% of patients in the "non-SRS group.", Conclusion: We clarified the contribution of IDs as (epi)genetic causes of SGA-SS and the molecular and phenotypic spectrum of SRS. Various IDs constitute underlying factors for SGA-SS, including SRS., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society.)

Objective: Catch-up growth (CUG) in small for gestational age (SGA) leads to increased risk of metabolic syndrome and cardiovascular diseases in adults. It remains unclear if microbiota could play an important role in CUG-SGA independent of genetic or nutritional factors. The present study explored the role of gut microbiota in, and its association with, metabolic disorders during CUG-SGA., Methods: An SGA rat model was established by restricting food intake during pregnancy, and the rats were divided into catch-up growth (CUG-SGA) and non-catch-up growth (NCUG-SGA) groups based on body weight and length at the fourth postnatal week. High-throughput sequencing of 16S rRNA was conducted to detect the diversity and composition of the gut microbiota. Fecal short-chain fatty acids (SCFAs) were detected by gas chromatography-mass spectrometry. Transcriptome sequencing of liver tissue was performed and verified using real-time PCR. Concentrations of insulin and total cholesterol were determined using enzyme-linked immunosorbent assay., Results: The composition of gut microbiota in CUG-SGA rats differed from that of NCUG-SGA rats, with reduced abundance of Lactobacillus in the CUG-SGA group. The decrease in Lactobacillus was significantly associated with increased body weight and upregulated insulin and total cholesterol levels. Five SCFAs and two branched chain fatty acids were significantly higher in the CUG-SGA group than in the NCUG-SGA group. Additionally, SCFAs were positively associated with clinical indices such as weight, body mass index, insulin, and total cholesterol. Transcriptomic data revealed that insulin-like growth factor-2 expression was significantly decreased in CUG-SGA rats and was associated with a decrease in Lactobacillus bacteria., Conclusion: Lactobacillus and SCFAs were associated with the metabolic disorders during CUG in SGA. Gut microbiome may play a certain role on metabolic disorders during catch-up growth in small-for-gestational-age., 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., (Copyright © 2021 An, Wang, Guo, Xiao, Lu, Li, Chen, Wang and Dong.)

Objective: To investigate the performance of the machine learning (ML) model in predicting small-for-gestational-age (SGA) at birth, using second-trimester data., Methods: Retrospective data of 347 patients, consisting of maternal demographics and ultrasound parameters collected between the 20th and 25th gestational weeks, were studied. ML models were applied to different combinations of the parameters to predict SGA and severe SGA at birth (defined as 10th and third centile birth weight)., Results: Using second-trimester measurements, ML models achieved an accuracy of 70% and 73% in predicting SGA and severe SGA whereas clinical guidelines had accuracies of 64% and 48%. Uterine PI (Ut PI) was found to be an important predictor, corroborating with existing literature, but surprisingly, so was nuchal fold thickness (NF). Logistic regression showed that Ut PI and NF were significant predictors and statistical comparisons showed that these parameters were significantly different in disease. Further, including NF was found to improve ML model performance, and vice versa., Conclusion: ML could potentially improve the prediction of SGA at birth from second-trimester measurements, and demonstrated reduced NF to be an important predictor. Early prediction of SGA allows closer clinical monitoring, which provides an opportunity to discover any underlying diseases associated with SGA., (© 2021 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Objective: The fetal liver circulation has an important role in fetal growth. The intra-hepatic Umbilical-Porto-Systemic Venous Shunt (IHUPSVS) causes a reduction of the umbilical blood flow to the liver and has been reported to have a restrictive effect on fetal growth. The aim of this study was to evaluate the effect of IHUPSVS on fetal growth., Methods: We conducted a retrospective cohort study of IHUPSVS diagnosed between 2001 and 2019. IHUPSVS was defined as any abnormal communication between any branch of the portal vein and hepatic vein. Pre- and postnatal characteristics were collected from medical files and compared between cases with fetal growth restriction (FGR) and those appropriate for gestational age (AGA)., Results: Twenty-five fetuses were included in the study. Eighteen (72%) had last estimated fetal weight and birth weight below the 10th centile, four (16%) of them between the third and fifth centile, and 11 (44%) below the third centile. Median gestational age at delivery was lower for FGR than AGA fetuses (37 vs. 38 weeks, p = 0.034) and rate of preterm delivery was higher (38.9 vs. 14.3, P = 0.24). Four cases had associated structural anomalies (2 in each group), and two had minor genetic aberrations (1 in each group)., Conclusions: Growth restriction is prevalent in fetuses with IHUPSVS, suggesting that fetal growth should be monitored. In equal measure, in cases with growth restriction, especially without other apparent cause, an intrahepatic shunt should be looked for., (© 2020 John Wiley & Sons Ltd.)

Introduction: Introduction: human growth is the result of an interaction between genetic, hormonal, nutritional, and environmental factors. It is not yet fully understood what is predominant and decisive in determining an individual's weight and height. Objective: the aim of this study was to evaluate the cardiometabolic profile of exclusively breastfed children born small for gestational age (SGA). Methods: this is a prospective cohort study of children born at term who were classified as SGA, and as appropiate for gestational age (AGA), who were followed up to pre-school age. Anthropometric measures and body composition parameters were obtained. Breastfeeding duration was calculated in days, and achievement of catch up of weight was considered an increase in Z-score ≥ 0.67. The cardiometabolic profile was evaluated in the first month of life and repeated at pre-school age. At pre-school age, fasting blood glucose, insulin, HOMA-IR, and blood pressure were measured. Results: twenty SGA and 12 AGA children were studied. The mean duration of exclusive breastfeeding (EBF) was 180 days in both groups. Of SGA children, 85 % had recovery anthropometric parameters for age within the first six months, with a speed of weight gain significantly higher than the that of AGAs (p < 0.001). SGAs continued to be thinner and smaller than AGAs at pre-school age. There was no diagnosis of overweight or obesity in the studied sample, and no differences were foun between groups in laboratory tests. Conclusion: these findings suggest that EBF may confer protection until pre-school age in children born SGA, who are considered at higher risk for chronic non-communicable diseases.

The prevalence of overweight and obesity amongst reproductive women has been increasing worldwide. Our aim was to compare pregnancy outcomes and infant neurocognitive development by different BMI classifications and investigate whether early pregnancy BMI was associated with risks of adverse outcomes in a Southwest Chinese population. We analysed data from 1273 women enrolled in the Complex Lipids in Mothers and Babies (CLIMB) randomized controlled trial in Chongqing, China. Maternal BMI was classified as underweight, normal weight and overweight/obese according to the Chinese, WHO Asian, and WHO European standards. For the adverse pregnancy outcomes, after adjustment for potential confounders, an underweight BMI was associated with increased risk of small for gestational age (SGA) babies, and an overweight/obese BMI was associated with increased risk of maternal gestational diabetes mellitus (GDM), caesarean section (C-section), macrosomia and large for gestational age (LGA) babies. For infant neurocognitive development, 1017 mothers and their children participated; no significant differences were seen in the Mental Development Index (MDI) or the Psychomotor Development Index (PDI) between the three BMI groups. Our findings demonstrate that abnormal early pregnancy BMI were associated with increased risks of adverse pregnancy outcomes in Chinese women, while early pregnancy BMI had no significant influence on the infant neurocognitive development at 12 months of age.

Publication of the Intergrowth-21st and WHO growth charts raises the question of which growth data prenatal providers should use in clinical practice. Is it better to use a universal chart applied globally, or metrics based on local or regional growth patterns? And what about customized charts versus local charts? FIGO has reviewed the different growth charts and studies assessing their reproducibility and predictive values for small- and large-for-gestational age newborns and, where available, adverse fetal outcomes. It concludes that local or regional charts are likely to be best for identifying the 10th percentile of newborns at highest risk. However, international standards for growth may also be used when coupled with locally appropriate thresholds for risk interpretation., (© 2020 International Federation of Gynecology and Obstetrics.)

Background: Offspring of women with type 1 diabetes are at increased risk of fetal growth patterns which are associated with perinatal morbidity. Our aim was to compare rates of large- and small-for-gestational age (LGA; SGA) defined according to different criteria, using data from the Continuous Glucose Monitoring in Type 1 Diabetes Pregnancy Trial (CONCEPTT)., Methods: This was a pre-specified analysis of CONCEPTT involving 225 pregnant women and liveborn infants from 31 international centres ( ClinicalTrials.gov NCT01788527; registered 11/2/2013). Infants were weighed immediately at birth and GROW, INTERGROWTH and WHO centiles were calculated. Relative risk ratios, sensitivity and specificity were used to assess the different growth standards with respect to perinatal outcomes, including neonatal hypoglycaemia, hyperbilirubinaemia, respiratory distress, neonatal intensive care unit (NICU) admission and a composite neonatal outcome., Results: Accelerated fetal growth was common, with mean birthweight percentiles of 82.1, 85.7 and 63.9 and LGA rates of 62, 67 and 30% using GROW, INTERGROWTH and WHO standards respectively. Corresponding rates of SGA were 2.2, 1.3 and 8.9% respectively. LGA defined according to GROW centiles showed stronger associations with preterm delivery, neonatal hypoglycaemia, hyperbilirubinaemia and NICU admission. Infants born > 97.7th centile were at highest risk of complications. SGA defined according to INTERGROWTH centiles showed slightly stronger associations with perinatal outcomes., Conclusions: GROW and INTERGROWTH standards performed similarly and identified similar numbers of neonates with LGA and SGA. GROW-defined LGA and INTERGROWTH-defined SGA had slightly stronger associations with neonatal complications. WHO standards underestimated size in preterm infants and are less applicable for use in type 1 diabetes., Trial Registration: This trial is registered with ClinicalTrials.gov . number NCT01788527 . Trial registered 11/2/2013.

Context: Reduced fertility has been reported for women with congenital adrenal hyperplasia (CAH), especially for those with the salt-losing form. However, data are sparse on reproductive and perinatal outcomes in these women., Objective: To investigate reproductive and perinatal outcomes in women with CAH., Design and Setting: Population-based and nationwide study using the National CAH Register, the Total Population Register, and the Medical Birth Register of Sweden., Participants: A total of 272 women with CAH due to 21-hydroxylase deficiency and 27 200 controls matched by sex, age, and place of birth. The median age was 31 years., Main Outcome Measures: The proportion of CAH women that have given birth, and reproductive and perinatal outcomes., Results: Of the 272 women with CAH, 69 gave birth to at least 1 child (25.4%), which was a lower frequency than for the controls (45.8%) (P < .001). Furthermore, women with CAH had fewer children than controls and were slightly older at birth of their first child. More women with CAH were diagnosed with gestational diabetes than controls, 4.9% versus 1.4% (P < .05), and more women with CAH were delivered through cesarean section, 51.4% versus 12.3% (P < .05). There was no difference in Apgar score or frequency of small-for-gestational age between children born to mothers with CAH and controls., Conclusions: This is, to our knowledge, the largest cohort designed to investigate reproductive and perinatal outcomes in women with CAH. We found the birth rate to be lower in women with CAH; gestational diabetes and cesarean section were more common, but perinatal outcomes were comparable with controls., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: About 8% of children born small for gestational age (SGA) do not reach a final height within the normal range. Recombinant human growth hormone (rhGH) has been shown to be effective in increasing the final height in children born SGA. Our objective was to identify predictive factors of final height in children born SGA treated with rhGH., Materials and Methods: In this retrospective study, conducted in a tertiary pediatric endocrinology referral center, we recruited all patients born SGA (defined as birth length or weight <10th percentile) treated with rhGH for more than 12 months for whom final height data were available. Some patients had received gonadotropin-releasing hormone (GnRH) analog therapy., Results: We included 252 patients with an average birth length of -2.0 ± 0.7 SD and birth weight of -1.7 ± 1.0 SD. After 4.6 ± 2.8 years of rhGH treatment, their height increased from -2.2 ± 0.9 SD to -1.5 ± 0.9 SD. In multivariate analysis, we identified 8 factors that predict 46% of the final height, namely, cause of SGA (p < 0.0001), GnRH analog therapy >2 years (p = 0.006), birth length (p < 0.02), height at the start of rhGH (p < 0.0001), IGF-1 level at the start of rhGH (p = 0.0002), growth velocity during the 1st year of treatment (p = 0.0002), and age and height at the onset of puberty (p < 0.0001, p = 0.0007, respectively)., Conclusion: In this large cohort of SGA patients who had reached their final height, we were able to confirm that growth hormone increases final height in short SGA children. In addition, we identified several factors associated with a better response to growth hormone treatment., (© 2021 S. Karger AG, Basel.)

Background: Children born small for gestational age (SGA) with catch-up growth are at high risk for developing obesity; however, the characteristics of body composition, especially fat distribution, before and after growth hormone (GH) treatment in SGA children without catch-up growth remains largely unknown., Methods: Anthropometric characteristics, body composition by dual-energy X-ray absorption, and fat distribution by computed tomography at the umbilical level were examined in 27 prepubertal short-stature children born SGA before and 1 year after GH treatment., Results: Before GH treatment, short-stature SGA children had lean phenotypes, and both visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were significantly lower than the age- and sex-matched Japanese reference values. Growth hormone treatment significantly increased height standard deviation scores (SDS), without affecting body mass index SDS. Percentage fat mass decreased with GH treatment; however, fat mass was not altered. Both VAT and SAT were significantly lower than the reference values after GH treatment. The ratio of VAT over SAT significantly increased by GH treatment., Conclusions: Both VAT and SAT were within or below the age- and sex-matched Japanese reference values in short-stature children born SGA before and after GH treatment, indicating that GH treatment may not have unfavorable effects on adiposity in short-stature children born SGA, although it may alter fat distribution., (© 2020 Japan Pediatric Society.)

Background: Even though a lot of research has been done on postnatal growth and the occurrence of catch-up growth in small-for-gestational age (SGA) neonates, this phenomenon has not been studied well in appropriate-for-gestational age (AGA) neonates. Postnatal catch-up growth may also occur in AGA neonates indicating a compensatory mechanism for undiagnosed intrauterine growth restriction, especially in AGA neonates with reduced fetal growth velocity., Aims: To describe postnatal growth during the first 5 years of life in SGA and AGA neonates and evaluating the role of fetal growth velocity in catch-up growth., Study Design: Retrospective study in a Dutch tertiary hospital., Subjects: 740 singleton neonates, without congenital anomalies, with ultrasound fetal growth data from 20 weeks and 32 weeks of pregnancy., Outcome Measures: Postnatal growth measurements of height (cm) and weight (kg) from birth until five years of age. Postnatal catch-up growth defined as difference (delta) in both height and weight between 4 weeks and 3 years of age., Results and Conclusions: SGA neonates had a significantly lower height and weight compared to the AGA group for all available measurement moments till 3 years. The catch-up growth between the SGA and AGA groups from 4 weeks up to 3 years after birth was not different between the two groups. However, neonates with reduced fetal growth velocity had a significantly higher risk for catch-up growth in height during the first 3 years after birth. This suggests a role for fetal growth velocity measurement in predicting fetal and subsequent postnatal growth potential., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: We aimed to identify the phenotypic variability of IGF1R defects in a cohort of short children with normal GH secretion gathered through the last decade., Patients and Methods: Fifty children (25 girls) with short stature and a basal/stimulated growth hormone (GH) over 10 ng/ml having either a low birth weight or microcephaly were enrolled. MLPA and then Sanger sequence analysis were performed to detect IGF1R defects. The auxological and metabolic evaluation were carried out in index cases and their first degree family members whenever available., Results: A total of seven (14%) IGF1R defects were detected. Two IGF1R deletions and five heterozygous variants (one frameshift, four missense) were identified. Three (likely) pathogenic, one VUS and one likely benign were classified by using ACMG. All children with IGF1R defects had a height < - 2.5SDS, birth weight < - 1.4SDS, and head circumference < - 1.36SDS. IGF-1 ranged from - 2.44 to 2.13 SDS. One child with a 15q terminal deletion had a normal phenotype and intelligence, whereas low IQ is a finding in a case with missense variant. Two parents who carried IGF1R mutations had diabetes mellitus, hypertension and hyperlipidemia, one of whom also had hypergonadotropic hypogonadism., Conclusion: We found a deletion or variant in IGF1R in 14% of short children. Birth weight, head circumference, intelligence, dysmorphic features, IGF-1 levels and even height are not consistent among patients. Additionally, metabolic and gonadal complications may appear during adulthood, suggesting that patients should be followed into adulthood to monitor for these late complications.

Objectives: Both excessive and restricted fetal growth are associated with changes in cardiac geometry and function at birth. There are significant issues when indexing cardiac parameters for body size in the neonatal period. The aims of this study were to determine to what extent cardiac geometry is dependent on body size in term and preterm neonates with restricted or excessive fetal growth and how this is affected by adiposity., Methods: This was a cross-sectional study of neonates born between 31 and 42 weeks of gestation, divided into three groups: (1) small-for-gestational age (SGA, birth weight > 2 SD below the mean); (2) large-for-gestational age (LGA, birth weight > 2 SD above the mean); and (3) appropriate-for-gestational-age controls (AGA, birth weight ≤ 2 SD from the mean). Cardiac geometry and function were compared between the study groups, adjusting for body size. The potential impact of infant adiposity and maternal disease was assessed., Results: In total, 174 neonates were included, of which 39 were SGA, 45 were LGA and 90 were AGA. Body size was reflected in cardiac dimensions, with differences in cardiac dimensions disappearing between the SGA and AGA groups when indexed for body surface area (BSA) or thoracic circumference. The same was true for the differences in atrial and ventricular areas between the LGA and AGA groups. However, left ventricular inflow and outflow tract dimensions did not follow this trend as, when indexed for BSA, they were associated negatively with adiposity, resulting in diminished dimensions in LGA compared with AGA and SGA neonates. Adiposity was associated positively with left ventricular mass, right ventricular length and area and right atrial area. The SGA group showed increased right ventricular fractional area change, possibly reflecting differences in the systolic function of the right ventricle. We found evidence of altered diastolic function between the groups, with the mitral valve inflow E- to lateral E'-wave peak velocity ratio being increased in the LGA group and decreased in the SGA group., Conclusions: Cardiac geometry is explained by body size in both term and preterm AGA and SGA infants. However, the nature of the relationship between body size and cardiac dimensions may be influenced by adiposity in LGA infants, leading to underestimation of left ventricular inflow and outflow tract dimensions when adjusted for BSA. Adjustments for thoracic circumference provide similar results to those for BSA. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.)

Background The relationship between growth hormone (GH)-replacement therapy and the thyroid axis in GH-deficient (GHD) children remains controversial. Furthermore, there have been few reports regarding non-GHD children. We aimed to determine the effect of GH therapy on thyroid function in GHD and non-GHD children and to assess whether thyrotropin-releasing hormone (TRH) stimulation test is helpful for the identification of central hypothyroidism before GH therapy. Methods We retrospectively analyzed data from patients that started GH therapy between 2005 and 2015. The free thyroxine (FT4) and thyroid-stimulating hormone (TSH) concentrations were measured before and during 24 months of GH therapy. The participants were 149 children appropriate for gestational age with GHD (IGHD: isolated GHD) (group 1), 29 small for gestational age (SGA) children with GHD (group 2), and 25 short SGA children (group 3). Results In groups 1 and 2, but not in group 3, serum FT4 concentration transiently decreased. Two IGHD participants exhibited central hypothyroidism during GH therapy, and required levothyroxine (LT4) replacement. They showed either delayed and/or prolonged responses to TRH stimulation tests before start of GH therapy. Conclusions GH therapy had little pharmacological effect on thyroid function, similar changes in serum FT4 concentrations were not observed in participants with SGA but not GHD cases who were administered GH at a pharmacological dose. However, two IGHD participants showed central hypothyroidism and needed LT4 replacement therapy during GH therapy. TRH stimulation test before GH therapy could identify such patients and provoke careful follow-up evaluation of serum FT4 and TSH concentrations.

Background & Aims: Rapid growth in childhood and obesity are highly prevalent in congenital deficiency infants, but the associations between them remain controversial. This meta-analysis was performed to explore the effects of rapid growth on body mass index (BMI) and percent body fat (PBF), and to clarify potential confounders., Methods: A systematic search was performed using electronic databases including EMBASE (1985 to July 2019) and Medline (1966 to July 2019) for English articles. China National Knowledge Infrastructure Chinese citation database (CNKI) and WANFANG database were used to search articles in Chinese. Reference lists were also screened as supplement. All relevant studies that compare BMI or PBF between rapid group and control group were identified. The definition of rapid growth should be clearly specified. Means and standard deviations/95% confidence intervals (CIs) of BMI and PBF should be available. Relevant information was extracted independently by two reviewers. Study quality was reassessed using the Newcastle-Ottawa Scale. Publication bias and heterogeneity were detected. The random effect model was adopted for combined and stratified analysis., Results: About the effect of rapid growth on BMI, seventeen researches (4473 participants) involving 49 comparisons were included. Pooled analysis showed rapid group had higher BMI of 0.573 (95% CI, 0.355 to 0.791; P < 0.001). Stratified analyses revealed that catch-up weight gain, follow-up age >6 years old, rapid growth duration >2 years, full-term, comparing rapid growth SGA infants with control SGA infants, and from developed and developing countries, would all lead to higher BMI in rapid groups. About the effect of rapid growth on PBF, eleven researches (4594 participants) involving 37 comparisons were included. Pooled analysis showed rapid group had higher PBF of 2.005 (95% CI, 1.581 to 2.429; P < 0.001). Subgroup analyses suggested that catch-up weight gain, follow-up age ≤6 years old, rapid growth duration >2 years, full-term, comparing rapid growth SGA infants with control AGA infants, and participants from developing countries, would lead to increased PBF in rapid groups., Conclusion: Rapid growth has a positive correlation with BMI and PBF. However, stratified analyses show that it is catch-up weight gain that lead to higher BMI and PBF, but not catch-up growth. In addition, rapid growth have long-term effect on BMI and short-term effect on PBF. Rapid growth duration longer than 2 years may increase the risk effect of rapid growth on BMI and PBF. But given that rapid growth would induce multiple health outcomes apart from BMI and PBF, the benefits and risks of rapid growth must be carefully considered and weighted., Competing Interests: Potential conflict of interest None of authors declared a conflict of interest., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)