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Background: Routine Doppler study is a common tool for early diagnosis of Fetal Growth Restriction (FGR) and Small for Gestational Age (SGA) patients. It aimed to determine the role of the Foramen Ovale Pulsatility Index (FOPI) study beside routine Doppler study among patients with FGR and SGA fetuses., Methods: This prospective study was conducted on 35 FGR, 32 SGA, and 33 Appropriate for Gestational Age (AGA) fetuses. Demographic data, amniotic fluid index, neonatal outcome, and Doppler velocimetry, including Umbilical Artery Pulsatility Index (UMAPI), Uterine Artery Pulsatility Index (UTAPI), Middle Cerebral Artery Pulsatility Index (MCAPI), Ductus Venosus Pulsatility Index (DVPI), and FOPI were documented. Kolmogorov-Smirnov normality test, one-way ANOVA, Mann-Whitney U, Kruskal-Wallis, non-parametric pairwise comparisons adjusted for Bonferroni correction, Pearson correlation test, Chi square, Fisher's exact test, and Receiver Operating Characteristic Curve (ROC) analysis with Youden's Index (sensitivity+specificity-1) to estimate cut-off point were used to analyze the data at significance level <0.05 for all tests., Results: FOPI cut-off points were 2.24 (sensitivity=77%, specificity=94%) and 1.15 (sensitivity=90%, specificity=20%) to predict FGR and SGA, respectively. FOPI showed a positive correlation with UMAPI and UTAPI (r=0.52 and r=0.30, P<0.001 and P=0.006, respectively), but not with MCAPI and DVPI (r=0.08 and r=0.12, P=0.50 and P=0.30, respectively). Besides, UMAPI, UTAPI, and FOPI were altered among patients with stages I and II FGR. Umbilical cord potential hydrogen (umbilical cord pH), 1- and 5-min Apgar score significantly increased by Birth weight centile; however, UMAPI, FOPI, and UTAPI significantly decreased., Conclusion: UMAPI is recommended to predict short-term neonatal morbidities and demonstrate the early or late onset FGR. Besides, FOPI is suggested as the first-line Doppler study to detect abnormal growth velocity. More studies are warranted, especially considering long-term neonatal morbidities., Competing Interests: None declared., (Copyright: © Iranian Journal of Medical Sciences.)

Purpose: We aimed to evaluate several quantitative methods to describe the diastolic notch (DN) and compare their performance in the prediction of fetal growth restriction., Materials and Methods: Patients who underwent a placental scan at 16-26 weeks of gestation and delivered between Jan 2016 and Dec 2020 were included. The uterine artery pulsatility index was measured for all of the patients. In patients with a DN, it was quantified using the notch index and notch depth index. Odds ratios for small for gestational age neonates (defined as birth weight <10th and <5th percentile) were calculated. Predictive values of uterine artery pulsatility, notch, and notch depth index for fetal growth restriction were calculated., Results: Overall, 514 patients were included, with 69 (13.4%) of them delivering a small for gestational age neonate (birth weight<10th percentile). Of these, 20 (20.9%) had a mean uterine artery pulsatility index >95th percentile, 13 (18.8%) had a unilateral notch, and 11 (15.9%) had a bilateral notch. 16 patients (23.2%) had both a high uterine artery pulsatility index (>95th percentile) and a diastolic notch. Comparison of the performance between uterine artery pulsatility, notch, and notch depth index using receiver operating characteristic curves to predict fetal growth restriction <10th percentile found area under the curve values of 0.659, 0.679, and 0.704, respectively, with overlapping confidence intervals., Conclusion: Quantifying the diastolic notch at 16-26 weeks of gestation did not provide any added benefit in terms of prediction of neonatal birth weight below the 10th or 5th percentile for gestational age, compared with uterine artery pulsatility index., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Objective: To compare maternal vascular indices and hemodynamic parameters at 35-37 weeks' gestation in pregnancies complicated by delivery of a small-for-gestational-age (SGA) or growth-restricted (FGR) neonate., Methods: This was a prospective observational study of women with a singleton pregnancy attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. The visit included recording of maternal demographic characteristics, medical history, vascular indices and hemodynamic parameters, which were obtained using a non-invasive operator-independent device and included pulse-wave velocity, augmentation index, cardiac output, stroke volume, central systolic and diastolic blood pressure, total peripheral resistance and heart rate. Women with hypertensive disorders of pregnancy were excluded. SGA was diagnosed if birth weight was < 10 th percentile. FGR was diagnosed if, in addition to birth weight < 10 th percentile, at the 35-37-week scan, uterine artery or umbilical artery pulsatility index (PI) was > 95 th percentile or fetal middle cerebral artery PI was < 5 th percentile., Results: Among the 6413 women included in the study, there were 605 (9.4%) cases of SGA, 133 (2.1%) cases of FGR and 5675 (88.5%) cases that were unaffected by SGA or FGR. Women with SGA or FGR, compared to unaffected pregnancies, had increased peripheral vascular resistance and reduced cardiac output. Central systolic and diastolic blood pressure were increased in the FGR group compared with the unaffected group. Aortic stiffness, as assessed by pulse-wave velocity, and augmentation index did not differ between affected and unaffected pregnancies. In the FGR group, compared with the SGA group, central systolic and diastolic blood pressure were higher, whereas heart rate was lower., Conclusions: SGA and FGR pregnancies exhibit deranged maternal hemodynamic responses compared with unaffected pregnancies. Pregnancies with FGR have higher central blood pressure compared to those with SGA, but it remains unclear whether these differences are driven by the size of the fetus or pathological fetal growth. © 2024 International Society of Ultrasound in Obstetrics and Gynecology., (© 2024 International Society of Ultrasound in Obstetrics and Gynecology.)

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.)

Objective: To describe the short- and long-term outcomes of infants with early-onset fetal growth restriction (FGR) and umbilical artery absent or reversed end-diastolic flow (AREDF), delivered before 30 weeks' gestation and managed proactively., Methods: This was a retrospective cohort study of fetuses delivered for fetal indication before 30 completed weeks' gestation that had early-onset FGR (defined as estimated fetal weight more than 2 SD below the mean) with AREDF in the umbilical artery (FGR group), at the level-3 perinatal unit in Lund, Sweden, between 1998 and 2015. Perinatal outcome and neurodevelopment at ≥ 2 years of age in surviving infants were compared with those of a group of infants without small-for-gestational-age birth weight or any known fetal Doppler changes delivered before 30 weeks in Lund during the corresponding time period (non-FGR group). In the FGR group, the main indication for delivery was the Doppler finding of AREDF in the umbilical artery., Results: There were 139 fetuses (of which 26% were a twin/triplet) in the FGR group and 946 fetuses (of which 28% were a twin/triplet) in the non-FGR group. The FGR infants had a median birth weight of 630 g (range, 340-1165 g) and gestational age at birth of 187 days (range, 164-209 days), as compared with 950 g (range, 470-2194 g) and 185 days (range, 154-209 days), respectively, in the non-FGR group. The rate of fetal mortality did not differ between the two groups (5.0% and 5.4% in the FGR and non-FGR groups, respectively). All seven intrauterine deaths in the FGR group occurred before 26 weeks' gestation. In the FGR group compared with the non-FGR group, severe intraventricular hemorrhage was less frequent and bronchopulmonary dysplasia and septicemia were more frequent (P = 0.008, P < 0.001 and P = 0.017, respectively). In the FGR group, the survival rate at 2 years (83% of liveborn infants) and the rate of cerebral palsy (7%) did not differ significantly from those in the non-FGR group (82% and 8%, respectively). The rate of survival without neurodevelopmental impairment was higher in the non-FGR group (83%) than in the FGR group (62%) (P < 0.001), as well as in infants in the FGR group delivered at or after 26 weeks (72%) compared with those delivered before 26 weeks (40%) (P = 0.003). Within the FGR group, outcomes were similar between twins and singletons and, in those who survived beyond 2 years, outcomes were similar between fetuses with absent and those with reversed end-diastolic flow in the umbilical artery., Conclusions: Infants delivered very preterm after severe FGR with AREDF in the umbilical artery had a similar rate of survival as did non-FGR infants of corresponding gestational age; however, they were at higher risk of neurodevelopmental impairment, the risk being most pronounced following birth before 26 weeks. Gestational age remains an important factor associated with the prognosis of early-onset FGR; nevertheless, the present results support the hypothesis, which should be tested prospectively, that fetuses with early-onset FGR and umbilical artery AREDF may benefit from early intervention rather than expectant management, and that umbilical artery Doppler findings could be incorporated into clinical protocols for cases very early in gestation. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Background: Pregnancies with small-for-gestational-age fetuses are at increased risk of adverse maternal-fetal outcomes. Previous studies examining the relationship between maternal hemodynamics and fetal growth were mainly focused on high-risk pregnancies and those with fetuses with extreme birthweights, such as less than the 3rd or 10th percentile and assumed a similar growth pattern in fetuses above the 10th percentile throughout gestation., Objective: This study aimed to evaluate the trends in maternal cardiac function, fetal growth, and oxygenation with advancing gestational age in a routine obstetrical population and all ranges of birthweight percentiles., Study Design: This was a prospective, longitudinal study assessing maternal cardiac output and peripheral vascular resistance by bioreactance at 11 +0 to 13 +6 , 19 +0 to 24 +0 , 30 +0 to 34 +0 , and 35 +0 to 37 +0 weeks' gestation, sonographic estimated fetal weight in the last 3 visits and the ratio of the middle cerebral artery by umbilical artery pulsatility indices or cerebroplacental ratio in the last 2 visits. Women were divided into the following 5 groups according to birthweight percentile: group 1, <10th percentile (n=261); group 2, 10 to 19.9 percentile (n=180); group 3, 20 to 29.9 percentile (n=189); group 4, 30 to 69.9 percentile (n=651); and group 5, ≥70th percentile (n=508). The multilevel linear mixed-effects model was performed to compare the repeated measures of hemodynamic variables and z scores of the estimated fetal weight and cerebroplacental ratio., Results: In visit 2, compared with visit 1, in all groups, cardiac output increased, and peripheral vascular resistance decreased. At visit 3, groups 1, 2, and 3, compared with 4 and 5, demonstrated an abrupt decrease in cardiac output and increase in peripheral vascular resistance. From visit 2, group 1 had a constant decline in estimated fetal weight, coinciding with the steepest decline in maternal cardiac output and rise in peripheral vascular resistance. In contrast, in groups 4 and 5, the estimated fetal weight had a stable or accelerative pattern, coinciding with the greatest increase in cardiac output and lowest peripheral vascular resistance. Groups 2 and 3 showed a stable growth pattern with intermediate cardiac output and peripheral vascular resistance. Increasing birthweight was associated with higher cerebroplacental ratio. Groups 3, 4, and 5 had stable cerebroplacental ratio across visits 3 and 4, whereas groups 1 and 2 demonstrated a significant decline (P<.001)., Conclusion: In a general obstetrical population, maternal cardiac adaptation at 32 weeks' gestation parallels the pattern of fetal growth and oxygenation; babies with birthweight<20th percentile have progressive decline in fetal cerebroplacental ratio, decline in maternal cardiac output, and increase in peripheral vascular resistance., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

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.)

Abnormal maternal serum biomarkers (AMSB), identified through the aneuploidy screening programme, are frequent incidental findings in pregnancy. They are associated with fetal growth restriction (FGR), but previous studies have not examined whether this association is with early-onset (< 34 weeks) or late-onset (> 34 weeks) FGR; as a result there is no consensus on management. The aims of this study were to determine the prevalence and phenotype of FGR in women with AMSB and test the predictive value of placental sonographic screening to predict early-onset FGR. 1196 pregnant women with AMSB underwent a 21-24 week "placental screen" comprising fetal and placental size, and uterine artery Doppler. Multivariable regression was used to calculate a predictive model for early-onset FGR (birthweight centile < 3rd/< 10th with absent umbilical end-diastolic flow, < 34 weeks). FGR prevalence was high (10.3%), however early-onset FGR was uncommon (2.3%). Placental screening effectively identified early-onset (area under the curve (AUC) 0.93, 95% confidence interval (CI) 0.87-1.00), but not late-onset FGR (AUC 0.70, 95% CI 0.64-0.75). Internal validation demonstrated robust performance for detection/exclusion of early-onset FGR. In this cohort, utilisation of our proposed algorithm with targeted fetal growth and Doppler surveillance, compared with universal comprehensive surveillance would have avoided 1044 scans, potentiating significant cost-saving for maternity services.

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.)

Importance: The magnitude of the association of intrauterine growth restriction (IUGR) and small for gestational age (SGA) status with cognitive outcomes in preterm and term-born children has not been established., Objective: To examine cognitive outcomes of preterm and term-born children who had IUGR and were SGA compared with children who were appropriate for gestational age (AGA) during the first 12 years of life., Data Sources: For this systematic review and meta-analysis, the Scopus, PubMed, Web of Science, Science Direct, PsycInfo, and ERIC databases were searched for English-language, peer-reviewed literature published between January 1, 2000, and February 20, 2020. The following Medical Subject Heading terms for IUGR and SGA and cognitive outcomes were used: intrauterine growth restriction, intrauterine growth retardation, small for gestational age AND neurodevelopment, neurodevelopmental outcome, developmental outcomes, and cognitive development., Study Selection: Inclusion criteria were assessment of cognitive outcomes (full-scale IQ or a cognitive subscale), inclusion of an AGA group as comparison group, and inclusion of gestational age at birth and completion of cognitive assessment up to 12 years of age., Data Extraction and Synthesis: The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines were followed. Data were double screened for full-text articles, and a subset were independently coded by 2 authors. Standardized mean differences (SMDs) and odd ratios from individual studies were pooled by applying random-effects models., Main Outcomes and Measures: Cognitive outcomes, defined as mental, cognitive, or IQ scores, estimated with standardized practitioner-based cognitive tests or as borderline intellectual impairment (BII), defined as mental, cognitive, or IQ scores at least 1 SD below the mean cognitive score., Results: In this study of 89 samples from 60 studies including 52 822 children, children who had IUGR and were SGA had significantly poorer cognitive outcomes (eg, cognitive scores and BII) than children with AGA in childhood. For cognitive scores, associations are consistent for preterm (SMD, -0.27; 95% CI, -0.38 to -0.17) and term-born children (SMD, -0.39; 95% CI, -0.50 to -0.28), with higher effect sizes reported for term-born IUGR and AGA group comparisons (SMD, -0.58; 95% CI, -0.82 to -0.35). Analyses on BII revealed a significantly increased risk in the preterm children who had IUGR and were SGA (odds ratio, 1.57; 95% CI, 1.40-1.77) compared with the children with AGA., Conclusions and Relevance: Growth vulnerabilities assessed antenatally (IUGR) and at the time of birth (SGA) are significantly associated with lower childhood cognitive outcomes in preterm and term-born children compared with children with AGA. These findings highlight the need to develop interventions that boost cognitive functions in these high-risk groups.

Background: Delayed brain function development in small-gestational-age (SGA) infants has been reported. We aimed to quantify rates of immature neonatal EEG patterns and their association with neurodevelopment in SGA full-term neonates., Methods: Using a cohort design, 50 SGA (birthweight <10th percentile) and 44 appropriate-gestational-age (AGA) term neonates underwent continuous video-EEG recordings lasting >3 h. Seventy-three of them were assessed at 2-years-old using Bayley-III-Scales. For EEG analysis, several segments of discontinuous/alternating EEG tracings were selected., Main Outcomes Measured: (1) Visual analysis (patterns of EEG maturity); (2) Power spectrum in δ, θ, α and β frequency bands; and (3) scores in motor, cognitive and language development., Results: (1) SGA infants, compared to AGA, showed: (a) higher percentages of discontinuous EEG, both asynchrony and interhemispheric asymmetry, and bursts with delta-brushes, longer interburst-interval duration and more transients/hour; (b) lower relative power spectrum in δ and higher in α; and (c) lower scores on motor, language and cognitive neurodevelopment. (2) Asymmetry >5%, interburst-interval >5 s, discontinuity >11%, and bursts with delta-brushes >11% were associated with lower scores on Bayley-III., Conclusions: In this prospective study, SGA full-term neonates showed high rates of immature EEG patterns. Low-birthweight and immaturity EEG were both correlated with low development scores.

Intrauterine growth restriction (IUGR) is a clinical definition applied to neonates born with clinical features of malnutrition and in-utero growth retardation irrespective of their birth weight percentile. This study was aimed to determine the frequency of pulmonary hypertension (PH) in neonates with IUGR. In this descriptive cross-sectional study, we followed 96 neonates with IUGR (≤28 days) and 38 neonates without IUGR born in the department of the neonatal intensive care unit children hospital complex Multan, Pakistan. We analyzed certain factors such as gender, gestational age (GA) (weeks), birth weight (BW in kg), weight percentile (WP) for GA, meconium aspiration syndrome (MAS), birth asphyxia (BA) and respiratory distress syndrome (RDS) for pulmonary hypertension (PH) in IUGR and non-IUGR group. GA was measured by the Ballard scoring system. Echocardiography was performed for all patients by the pediatric cardiologist to measure pulmonary arterial (PA) pressure using Bernoulli's equation. Out of total 96 IUGR neonates, 33.3% (n = 32) suffered from PH, of which 65.3% (n = 18) were male and 43.7% (n = 14) were female. The percentages of IUGR neonates with BA, MAS and RDS were 34.4%, 18.8% and 22.9% respectively. The data were analyzed using the SPSS-16 software to test the statistical significance of the results. A p-value less than 0.05 was considered significant. When the chi-square test was applied, it depicted that MAS was significantly associated with PH in IUGR neonates (p = 0.0001) compared to non-IUGR neonates. Our findings suggested an increased chance of PH in IUGR neonates and MAS may be a strong factor.

Numerous studies have investigated the risk of developing asthma due to early-life experiences and environmental exposures. However, the influence of intrauterine growth restriction and postnatal undernutrition on childhood wheezing/asthma remains unclear. Thus, we examined the effects of both small for gestational age (SGA) and postnatal stunted growth on ever asthma among children in the rural areas in Bangladesh.Multiple follow-up studies were conducted in a cohort of randomized clinical trial of nutrition interventions during pregnancy (the MINIMat trial). Overall, 1208 and 1697 children were followed-up for asthma at 4.5 and 10 years, respectively. Anthropometric measurements were obtained at various intervals from birth to 10 years of age. Ever asthma was identified using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire.Results showed that SGA was significantly associated with increased risk of ever asthma at 4.5 and 10 years after adjusting for sex, body mass index, socioeconomic status, family history of asthma, gestational age at birth, mother's parity, mother's age at birth and intervention trial arm [odds ratio (OR)=1.97 (95% confidence interval (CI): 1.34-2.90) and 1.86 (95% CI: 1.18-2.72)]. For the postnatal effect of undernutrition, stunting at 1 and 2 years was significantly associated with ever asthma at 4.5 and 10 years [1 year: OR=1.77 (95% CI: 1.22-2.57) and OR=1.72 (95% CI: 1.16-2.56), 2 years: OR=1.49 (95% CI: 1.06-2.10) and OR=1.41 (95% CI: 1.02-1.96)].In conclusion, SGA and undernutrition during infancy has an influence on childhood asthma among children in Bangladesh, indicating the need for nutritional interventions early in life.

Background: Small for gestational age (SGA) is frequently used to define fetal growth restriction (FGR). However, FGR describes a slowdown in fetal growth and is not synonymous with SGA, which may introduce misclassification. We investigated the effect of both on delivery and childhood outcomes., Methods: From a prospective population-based cohort study we included 7959 live singleton births with data available on second trimester estimated fetal weight (EFW) and birth weight. We used a decrease in growth of > 40 percentiles between second trimester EFW and birthweight to define a deceleration in growth. SGA was defined as birthweight

Objective: To demonstrate the differences in intrauterine fetal deaths and neonatal deaths between small for date (SFD) and Non-SFD neonates by applying a novel classification from both Z scores of placental weight (PW) and fetal/placental weight ratio (F/P) to small for gestational age (SGA) neonates. Methods: From 93,034 placentas/infants of mothers who vaginally delivered a singleton infant (Japan Perinatal Registry Network database 2013), SGA (n=7,780) was chosen according to the reference to Japanese neonatal growth chart. They were divided into two subgroups: SFD (body weight and height less than the 10 th percentile, n=3,379) and Non-SFD (only body weight less than the 10 th percentile, n=4,401). Z scores of PW and F/P based on the standard curves for sex-, parity-, and gestational-age-specific PW and F/P were calculated. The population was classified into 9 groups according to the combination of 'low vs. middle vs. high' i) PW Z score and ii) F/P Z score. In both i) and ii), ± 1.28 standard deviations in the Z scores were used for classifying low vs. middle vs. high, with 3×3 making 9 groups. From top-left to bottom-right, we labeled the groups as Group A to Group I. Results: SFD and Non-SFD neonates distributed in the same 6 groups (A, D, E, G, H, I). In group E, which was considered to be balanced placental and infant growth, the incidence of intrauterine fetal death was significantly higher in Non-SFD neonates than in SFD neonates. In group D, which was considered to be small placenta and balanced infant growth, the incidence of neonatal death was significantly higher in SFD neonates than in Non-SFD neonates. Conclusion: Assessment of SGA neonates by dividing them into SFD and Non-SFD neonates and application of a 9-group classification by PW and F/P Z scores were informative to understand the pathophysiological involvement of an imbalance between placental and fetal sizes., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: Infants born small for gestational age because of pathologic placenta-mediated fetal growth restriction can be difficult to distinguish from those who are constitutionally small. Additionally, even among fetal growth-restricted pregnancies with evident placental disease, considerable heterogeneity in clinical outcomes and long-term consequences has been observed. Gene expression studies of fetal growth-restricted placentas also have limited consistency in their findings, which is likely due to the presence of different molecular subtypes of disease. In our previous study on preeclampsia, another heterogeneous placenta-centric disorder of pregnancy, we found that, by clustering placentas based only on their gene expression profiles, multiple subtypes of preeclampsia, including several with co-occurring suspected fetal growth restriction, could be identified., Objective: The purpose of this study was to discover placental subtypes of normotensive small-for-gestational-age pregnancies with suspected fetal growth restriction through the use of unsupervised clustering of placental gene expression data and to investigate their relationships with hypertensive suspected fetal growth-restricted placental subtypes., Study Design: A new dataset of 20 placentas from normotensive small-for-gestational-age pregnancies (birthweight <10th percentile for gestational age and sex) with suspected fetal growth restriction (ultrasound features of placental insufficiency) underwent genome-wide messenger RNA expression assessment and blinded detailed histopathologic evaluation. These samples were then combined with a subset of samples from our previously published preeclampsia cohort (n=77) to form an aggregate fetal growth-focused cohort (n=97) of placentas from normotensive small-for-gestational-age, hypertensive (preeclampsia and chronic hypertensive) small-for-gestational-age, and normotensive average-for-gestational-age pregnancies. Gene expression data were subjected to unsupervised clustering, and clinical and histopathologic features were correlated to the identified sample clusters., Results: Clustering of the aggregate dataset revealed 3 transcriptional subtypes of placentas from normotensive small-for-gestational-age/suspected fetal growth-restricted pregnancies, with differential enrichment of clinical and histopathologic findings. The first subtype exhibited either no placental disease or mild maternal vascular malperfusion lesions, and, co-clustered with the healthy average-for-gestational-age control subjects; the second subtype showed more severe evidence of hypoxic damage and lesions of maternal vascular malperfusion, and the third subtype demonstrated an immune/inflammatory response and histologic features of a maternal-fetal interface disturbance. Furthermore, all 3 of these normotensive small-for-gestational-age subtypes co-clustered with a group of placentas from hypertensive small-for-gestational-age pregnancies with more severe clinical outcomes, but very comparable transcriptional and histologic placental profiles., Conclusion: Overall, this study provides evidence for at least 2 pathologic placental causes of normotensive small-for-gestational-age, likely representing true fetal growth restriction. These subtypes also show considerable similarity in gene expression and histopathology to our previously identified "canonical" and "immunologic" preeclampsia placental subtypes. Furthermore, we discovered a subtype of normotensive small-for-gestational-age (with suspected fetal growth restriction) with minimal placental disease that may represent both constitutionally small infants and mild fetal growth restriction, although these cannot be distinguished with the currently available data. Future work that focuses on the identification of etiology-driven biomarkers and therapeutic interventions for each subtype of fetal growth restriction is warranted., (Copyright © 2018. Published by Elsevier Inc.)

Background: Pregnancies complicated with small for gestational age (SGA) neonates are reported with maternal circulatory maladaptations., Objectives: We aimed to understand the pathophysiology of the maternal circulation in normotensive SGA pregnancies and to point out the trimestral differences from those with appropriate-to-large (non-SGA [NGA]) neonates., Methods: An observational study was conducted in 3 trimestral cohorts of normotensive pregnancies, categorized after birth according to neonatal birth weight percentile (BW%) as SGA (BW% ≤10, n = 158) or NGA (BW% > 10, n = 1,038). Standardized electrocardiogram-Doppler ultrasound, impedance cardiography, and bio-impedance were used to assess the maternal heart, arteries, veins, and fluid., Results: Diastolic blood pressure and mean arterial pressure were not significantly different, unless in the third trimester. In SGA compared to NGA pregnancies, total peripheral resistance (TPR) was higher and total arterial compliance, cardiac output (CO), and total body water (TBW) were lower throughout pregnancy. Venous return-enhancing functions were activated. In NGA but not SGA pregnancies, a positive correlation was found between BW% and CO + TBW and a negative correlation between BW% and TPR., Conclusions: SGA pregnancies are characterized by lower maternal body fluid volume and CO, while normal blood pressures are maintained via increased TPR already from the first trimester onwards. Pregnancy-induced hemodynamic changes are superimposed on these characteristics., (© 2019 S. Karger AG, Basel.)

Objectives: To evaluate body water volumes and cardiac output in each trimester of pregnancies complicated with hypertension and/or poor fetal growth, relative to uncomplicated pregnancy., Methods: In this semi-longitudinal cohort study, a standardised non-invasive maternal hemodynamics assessment in first, second or third trimester was performed in 1068 women with uncomplicated pregnancy (UP), 75 with early onset (EPE) and 117 with late onset preeclampsia (LPE), 139 with gestational hypertension (GH), 129 with small for gestational age (SGA) neonates and 43 with essential hypertension (EH). Women with hypertension or SGA were included prior to onset of symptoms or at diagnosis of disease; 46% of women (758/1631) were assessed in ≥ 2 trimesters. Impedance cardiography and spectrum analysis were used to measure cardiac output, total body water (TBW), extracellular (ECW) and intracellular water (ICW). A linear mixed model was used for inter-trimestrial comparison of parity-, age- and BMI-corrected values within and between groups., Results: For all pregnancies, TBW is higher in each consecutive trimester, mainly due to increasing fraction of ECW (ECW%). Compared to first trimester UP, ECW and ECW% are higher in EPE whereas TBW, ECW and ICW are lower in SGA. Compared to inter-trimestrial differences in UP, abnormal changes for body water volumes are observed in GH, EPE and LPE and for CO in EPE and LPE. Changes in EH are not different from UP., Conclusions: This study is the first to show that concomitant gestational changes of ECW and CO are different from UP already in preclinical stages of pregnancies complicated with hypertension and/or poor fetal growth, except EH. This finding highlights the relevance of early gestational assessment of maternal body fluid status in pregnancies at risk for hypertension or poor fetal growth., Competing Interests: The authors have declared that no competing interests exist.

Background: Preterm birth and low birth weight are associated with reduced nephron numbers and increased risk of hypertension and kidney disease in later life., Aims: We tested the hypothesis that extremely preterm birth and intrauterine growth restriction is associated with decreased renal function in mid childhood., Methods: At 11 years of age the following measures were obtained in a regional cohort of children born extremely premature (EP, i.e. < 28 weeks gestational age-GA) or with extremely low birth weight (ELBW, i.e. BW < 1000 grams) and in matched controls born at term with appropriate BW (AGA): Height, weight, abdominal circumference, triceps and subscapular skin fold thicknesses, blood pressure, plasma levels of creatinine, cystatin C and symmetric dimethyl arginine (SDMA). Small for gestational age (SGA) was defined as a BW < 10th percentile for GA. Glomerular filtration rate (GFR) was estimated according to the equations by Schwartz, Zappitelli and Gao., Results: Fifty-seven of 61 eligible EP/ELBW children, 20 (35%) born SGA, and 54 controls, were assessed. Estimated GFR decreased while plasma SDMA increased from the children born AGA at term through those born preterm AGA to preterm SGA. Systolic BP was correlated to fat mass indices (p<0.03), but not to renal function (p>0.2) and did not differ between the groups., Conclusions: Children born EP/ELBW, particularly those born SGA, had impaired renal function at age 11 years as judged from estimated GFRs and plasma levels of SDMA. Since reduced renal function is associated with an increased risk of later disease, these children should be followed in order to minimize additional risk factors., Competing Interests: Bevital A/S provided financial support in the form of salaries for KM and ØM, and research materials. This does not alter our adherence to the PLOS ONE policies on sharing data and materials.

Objective: To investigate whether abdominal circumference growth velocity (ACGV) improves the prediction of perinatal outcome in small-for-gestational-age (SGA) fetuses beyond that afforded by estimated fetal weight (EFW) and cerebroplacental ratio (CPR)., Methods: A cohort of 235 singleton SGA fetuses at 36-38 weeks' gestation was examined. ACGV, EFW and CPR centiles were calculated. ACGV centile was determined using data from a large database of 19-21- and 36-38-week scans in an unselected population. Binary variables of ACGV < 10 th , EFW < 3 rd and CPR < 5 th centiles were defined as abnormal. Two composite adverse outcomes (CAO) were explored: CAO-1 defined as at least one of umbilical artery pH < 7.10, 5-min Apgar score < 7 or neonatal unit admission, and CAO-2 that included in addition hypoglycemia, intrapartum fetal distress and perinatal death. Univariate and multivariate logistic regression analyses were performed to analyze the relationship between the three risk factors and their predictive value for CAO. The change in screening performance afforded by adding ACGV to EFW and CPR was assessed and receiver-operating characteristics (ROC) curves were calculated., Results: ACGV < 10 th centile was an independent risk factor for CAO. The sensitivity, specificity, positive and negative likelihood ratios of a predictive model based on EFW < 3 rd centile and CPR < 5 th centile were, respectively, 51%, 70%, 1.71 and 0.69 for CAO-1 and 41%, 70%, 1.39 and 0.83 for CAO-2. After addition of ACGV < 10 th centile to the model, the respective values were 82%, 46%, 1.54 and 0.38 for CAO-1 and 71%, 47%, 1.34 and 0.62 for CAO-2. Using continuous variables, the areas under the ROC curves improved marginally from 0.669 (95% CI, 0.604-0.729) to 0.741 (95% CI, 0.677-0.798) for CAO-1 and from 0.646 (95% CI, 0.580-0.707) to 0.700 (95% CI, 0.633-0.759) for CAO-2 after addition of ACGV to the model., Conclusions: ACGV is a risk factor for adverse neonatal outcome that is independent of EFW and of CPR, although any improvement in the prediction of adverse outcome is not statistically significant. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To evaluate the impact of serum insulin-like growth factor-1 (IGF-1) levels on cardiac function in small for gestational age (SGA) infants., Study Design: This is a prospective, observational study. Serum IGF-1 levels at birth and echocardiography measurements at 1 week of age were compared between SGA and appropriate for gestational age (AGA) infants., Results: Thirty-one SGA infants and 27 AGA infants were enrolled. Serum IGF-1 levels were lower in the SGA infants than in the AGA infants. SGA infants had lower mitral lateral annular systolic (S') and early diastolic (E') tissue Doppler imaging velocities compared with AGA infants (S', 5.1 ± 0.9 vs 5.7 ± 1.2 cm/s; E', 6.1 ± 1.5 cm/s vs 7.1 ± 1.3 cm/s; p  < 0.05). Serum IGF-1 levels positively correlated with E' velocity in the entire population ( r  = 0.44, p  < 0.001) and in SGA infants ( r  = 0.39, p  < 0.05). In multivariate linear regression analysis, serum IGF-1 and S' velocity were independently associated with E' velocity in the entire population and in SGA infants., Conclusion: Decreased serum IGF-I levels could account for cardiac diastolic dysfunction in SGA infants., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

We explored whether there was a relationship between the sFlt-1/PlGF ratio in early-late and late-onset SGA patients and whether it is associated with neonatal birth weight., Material/methods: 110 patients who were diagnosed with a fetal weight below the 10th percentile for gestational age and who at the same time delivered neonates with a birth weight below the 10th percentile for gestational age. For each of the patients sFlt-1, PlGF and the sFlt-1/PlGF ratio were studied and uterine artery (UtA) and umbilical artery (UA) Doppler were performed., Results: sFlt-1/PlGF ratios and neonatal birth weight which showed significant negative correlation across the entire population studied (R = -0.46, p < 0.001). In late-onset SGA patients this negative correlation was observed, as well (R = -0.54, p < 0.001) In the group of patients with pregnancies older than 34 weeks and an sFlt-1/PlGF ratio ≥38, we observed a significantly lower neonatal birth weight when compared to the same gestational age group with an sFlt-1/PlGF ratio <38 (2045 g vs 2405 g, p < 0.001)., Conclusion: Late-onset SGA syndromes are characterized by lower sFlt-1/PlGF ratios, which indicates a lower degree of placental function impairment. The sFlt-1/PlGF ratio can be a predictor of more significant growth disorders and a lower neonatal birth weight. The sFlt-1/PlGF ratio can be helpful in distinguishing between disordered angiogenesis-dependent and other causes of late-onset SGA cases., (Copyright © 2018 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Fetal growth restriction increases the risk of poor childhood growth and development and chronic disease in adulthood. Yet, little is known about biological pathways that mediate the long-lasting effects of suboptimal intrauterine growth. We explored the plasma proteome in a cohort of 500 Nepalese children 6-8 years of age to identify plasma proteins associated with multiple anthropometric size indicators at birth. Among 982 proteins analyzed, no proteins differed by birth weight, length, or weight-for-length indicators. However, 25 proteins were differentially abundant in children with a small vs normal head circumference at birth (<-2 vs. ≥-2 z-scores of the WHO growth standards). Angiopoietin-like 6 was 19.4% more abundant and the other 24 proteins were 7-21% less abundant in children with a small vs normal head circumference at birth, adjusted for potential confounders. The less abundant proteins included actins, actin filament organizing proteins (α-actinin, talin, filamin, cofilin, profilin, and vinculin), proteins involved in muscle contraction, and glycolytic enzymes, which were all positively correlated with each other. A novel cluster of childhood plasma proteins involved in angiogenesis and cytoskeleton dynamics was associated with a small head size at birth. The prognostic value of an altered proteomic phenotype remains to be investigated.

Objectives: To investigate the risks of delivering small-for-gestational-age (SGA) and large-for-gestational-age (LGA) infants in women with early- (delivered before 34weeks of gestation) and late-onset (delivered at or after 34weeks of gestation) preeclampsia., Study Design: We conducted a retrospective cohort study of 29,494 singleton deliveries after 24weeks' gestation, excluding pregnancies complicated by fetal anomalies, stillbirths, and prepregnancy diabetes mellitus. Univariate and multivariate logistic analyses adjusted for potential confounding factors, including prepregnancy body mass index (BMI), gestational weight gain (GWG), and gestational diabetes mellitus (GDM), were performed., Results: Among women who delivered before 34weeks, significantly more women with preeclampsia delivered SGA infants than women without preeclampsia (50.6% vs. 7.0%; adjusted odds ratio [OR] 16.3; 95% confidence interval [CI] 8.1-32.9). Among women who delivered at or after 34weeks, women with preeclampsia had higher rates of delivering SGA (25.5% vs. 7.0%) and LGA (13.7% vs. 9.9%) infants than women without preeclampsia. After adjustment for confounding factors, preeclampsia remained a significant risk factor for delivering SGA infants (adjusted OR 5.7; 95% CI 4.6-7.1), but the association between preeclampsia and the delivery of LGA infants was diminished (adjusted OR 0.8; 95% CI 0.6-1.1)., Conclusions: Our results confirm that preeclampsia is associated with SGA and that the association is stronger with early-onset disease. Although women with late-onset preeclampsia had a higher rate of delivering LGA infants, the association between late-onset preeclampsia and LGA is due to confounding factors, such as high prepregnancy BMI, excessive GWG, and GDM, related to maternal metabolic abnormalities., (Copyright © 2017 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Objective: To assess the clinical utility of the fetal myocardial performance index (MPI) in assessment and management of the small-for-gestational-age (SGA) fetus/growth-restricted fetus (FGR)., Methods: This was a prospective cohort study in metropolitan Australia of patients referred in the period June 2012 to March 2015 to fetal medicine services at 24-38 weeks' gestation for suspected singleton SGA/FGR (estimated fetal weight (EFW) < 10 th centile with or without abnormal umbilical artery (UA) Doppler) pregnancy. Patients had MPI assessed in addition to routine measures, and were followed through to birth. We compared MPI values against those of a local reference population and gestational age-matched controls, and assessed the correlation with perinatal outcome and other Doppler measures., Results: Fifty-two cases were included, 38 diagnosed < 32 weeks and 14 diagnosed ≥ 32 weeks. None demonstrated significantly elevated left, right or delta MPI compared with the reference population or with gestational age-matched controls at the time of first MPI evaluation. There were no consistent longitudinal patterns in MPI that would suggest its clinical utility. The mean ± SD gestational age at delivery was 34.6 ± 3.8 weeks and birth weight was 1.7 ± 0.6 kg, and the median neonatal hospital admission time was 27 days, confirming a pathological cohort. There were no significant correlations between left, right or delta-MPI and perinatal outcome, although there were significant correlations between UA, middle cerebral artery (MCA) and ductus venosus (DV) Doppler and perinatal outcome (birth weight, gestational age at birth and length of neonatal hospital stay). Exploratory subgroup comparisons (EFW < 3 rd vs 3 rd -10 th centile; early- vs late-onset; abnormal vs normal UA Doppler) found only minor differences in MPI, reaching statistical, but not clinical, significance, only in the EFW < 3 rd vs 3 rd -10 th centile comparison., Conclusions: MPI did not demonstrate clinical utility in either triage or longitudinal follow-up of an SGA/FGR cohort presenting to fetal medicine services. Given that prior research suggesting its utility originates from single-center cohorts, while multicenter, large cohorts have suggested little utility or no additional utility if routine UA/MCA/DV Doppler is performed, publication bias may have affected previous reports. It seems unlikely that MPI has clinical utility in assessment and management of SGA/FGR fetuses. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Intrauterine growth restriction (IUGR) represents a rate of fetal growth that is less than average for the population and the growth potential of a specific infant. IUGR produces infants who are small for gestational age (SGA) but also appropriate for gestational age (AGA). It refers to growth less than expected for gestational age and is most often under 10th percentiles for age. It develops during the late second and third trimesters of gestation. The etiology of IUGR is multifactorial. One of the most important factors which leads to IUGR is a decrease of nutrients and oxygen delivered to the fetus by the placenta. The growth of adipose tissue and skeletal muscle is limited by the declined fetal nutrient supply later in gestation. IUGR affects about 24% of babies born in developing countries. Worldwide, IUGR is the second cause of perinatal morbidity and mortality behind the premature birth and a major predisposing factor to metabolic disorders throughout postnatal life, even at adult age. Skeletal muscle represents about 35-40% of the body mass and plays an essential role in metabolic homeostasis, being responsible for 65% of fetal glucose consumption. A reduction in skeletal muscle growth characterizes IUGR fetuses compared to normal weight neonates. The decrease in muscle mass is not compensated after birth and persists until adulthood. This is a review of the literature, a neonatological, clinical point of view on the effects of IUGR on striated muscles. The available studies on this subject are currently the results of experimental research on animals, and information about the human fetus and newborn are scarce.

Objective: To investigate whether fetal growth restriction (FGR) diagnosis, based on pathological prenatal fetal Doppler velocimetry, is associated with bronchopulmonary dysplasia (BPD) independently of being small for gestational age (SGA) per se at birth among very preterm infants., Design: Prospective, observational study. FGR was defined as failing fetal growth in utero and fetal Doppler velocimetry abnormalities., Setting: Policlinico Universitario Agostino Gemelli, Roma, Italy., Patients: Preterm newborns with gestational age ≤30 weeks and birth weight (BW) ≤1250 g., Main Outcome Measures: Bronchopulmonary dysplasia., Results: In the study period, 178 newborns were eligible for the study. Thirty-nine infants (22%) were considered fetal growth-restricted infants. Among the 154 survived babies at 36 weeks postmenstrual age, 12 out of 36 (33%) of the FGR group developed BPD versus 8 out of 118 (7%) of the NO-FGR group (p<0.001). BPD rate was sixfold higher among the SGA-FGR infants compared with the SGA-NO-FGR infants. In a multivariable model, FGR was significantly associated with BPD risk (OR 5.1, CI 1.4 to 18.8, p=0.01), independently from BW z-score that still remains a strong risk factor (OR 0.5, CI 0.3 to 0.9, p=0.01)., Conclusion: Among SGA preterm infants, BPD risk dramatically increases when placenta dysfunction is the surrounding cause of low BW. Antenatal fetal Doppler surveillance could be a useful tool for studying placenta wellness and predicting BPD risk among preterm babies. Further research is needed to better understand how FGR affects lung development., Competing Interests: Competing interests: There is no potential conflict of interest, real or perceived in: (1) study design; (2) the collection,analysis and interpretation of data; (3) the writing of the report and (4) the decision to submit the paper for publication., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To investigate the renal function of small-for-gestational-age (SGA) infants at the early stage after birth., Methods: A total of 40 preterm SGA infants, 33 full-term SGA infants, 80 preterm appropriate-for-gestational-age (AGA) infants, and 33 full-term AGA infants were included in this study. The following indices were compared between the SGA infants and AGA infants within 48 hours after admission: blood urea nitrogen (BUN), serum creatinine (SCr), estimated glomerular filtration rate (eGFR), blood pressure, urine volume per body weight, and proteinuria., Results: The preterm SGA group had a significantly lower BUN level than the preterm AGA group (P<0.05). However, there were no significant differences in SCr level, eGFR, and blood pressure between the two groups (P>0.05). The full-term SGA group had a significantly higher SCr level and a significantly lower eGFR than the full-term AGA group (P<0.05). However, there were no significant differences in BUN level and blood pressure between the two groups (P>0.05). There was no significant difference in urine volume per body weight between the preterm SGA and preterm AGA groups (P>0.05) and between the full-term SGA and full-term AGA groups (P>0.05). There was no significant difference in the incidence of proteinuria between the preterm SGA and preterm AGA groups (P>0.05). Proteinuria was not present in the SGA full-term and AGA full-term groups., Conclusions: SCr and eGFR can be used as the diagnostic indices for early renal damage of SGA infants. The renal function is worse in full-term SGA infants than in full-term AGA infants.

Objective: To estimate whether pregnancy outcomes in women with severe preeclampsia (sPE) with small for gestational age (SGA) fetuses differ from those with sPE without SGA or isolated SGA., Study Design: We conducted a retrospective cohort study of consecutive non-anomalous, livebirths in a single tertiary care institution from 2004 to 2008. We compared pregnancy outcomes in women who had sPE with SGA (birthweight<10th percentile), and sPE without SGA to those with isolated SGA as reference. The primary outcome was a neonatal composite score including low 5-min APGAR, NICU admission and neonatal death. Secondary outcomes were components of the composite as well as placental abruption and cesarean delivery. Analysis was repeated with SGA defined as birthweight<5th percentile. Multivariable logistic regression was used to adjust for confounders., Results: 1905 women met inclusion criteria: 156 sPE with SGA, 746 sPE without SGA, 1003 isolated SGA. The risk of the neonatal composite score was higher for sPE with SGA (adjusted odds ratio [aOR] 2.29; 95% confidence interval [CI] 1.39-3.79) and sPE without SGA (aOR 3.66; 95% CI 2.71-4.93) compared to isolated SGA. The risk of abruption and cesarean were similarly increased in women with sPE with SGA and sPE without SGA compared to those with isolated SGA., Conclusion: Similar to women with sPE without SGA fetus, women who have sPE with SGA are at a higher risk for several adverse maternal and neonatal outcomes compared to isolated SGA. These findings suggest that women with preeclampsia and SGA should be managed as sPE rather than as isolated SGA., (Copyright © 2017 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Background: Intrauterine growth restriction is associated with arterial hypertension in adulthood; however, the underlying mechanism is unclear., Objectives: We hypothesized that serum insulin-like growth factor-1 (IGF-1) levels affect central aortic elastic properties and structure in small-for-gestational-age (SGA) infants., Methods: Eighteen SGA infants and 22 appropriate-for-gestational-age (AGA) infants were enrolled in this study. The serum IGF-1 level within 1 h of birth and abdominal aortic echo parameters at 1 week of age were retrospectively compared., Results: In the SGA infants, IGF-1 levels (27.6 ± 17.7 vs. 42.6 ± 15 ng/ml, p = 0.006), aortic strain (10.2 ± 3.1 vs. 12.8 ± 3.1%, p = 0.01), and aortic distensibility (0.73 ± 0.19 vs. 0.92 ± 0.34 cm2/dyn × 10-4, p = 0.05) were significantly lower compared with AGA infants. By contrast, blood pressure, aortic intima-media thickness (aIMT) in relation to body weight (383 ± 163 vs. 256 ± 43 μm/kg, p < 0.001), aortic stiffness index in relation to body weight (2.0 ± 1.7 vs. 1.1 ± 0.4, p = 0.005), and arterial pressure-strain elastic modulus (293 ± 72 vs. 242 ± 78 mm Hg, p = 0.04) were higher compared with AGA infants. In the SGA infants, IGF-1 levels were significantly correlated with aortic strain (r = 0.49, p = 0.04), aIMT in relation to body weight (r = -0.61, p = 0.007), and aortic stiffness index in relation to body weight (r = -0.63, p = 0.005)., Conclusions: Decreased serum IGF-1 levels in SGA infants may affect the vascular compliance and structure of the central aorta., (© 2016 S. Karger AG, Basel.)

Objectives: To assess the value of single and serial fetal biometry for the prediction of small- (SGA) and large-for-gestational-age (LGA) neonates delivered preterm or at term., Methods: A cohort study of 3,971 women with singleton pregnancies was conducted from the first trimester until delivery with 3,440 pregnancies (17,334 scans) meeting the following inclusion criteria: 1) delivery of a live neonate after 33 gestational weeks and 2) two or more ultrasound examinations with fetal biometry parameters obtained at ≤36 weeks. Primary outcomes were SGA (<5th centile) and LGA (>95th centile) at birth based on INTERGROWTH-21st gender-specific standards. Fetus-specific estimated fetal weight (EFW) trajectories were calculated by linear mixed-effects models using data up to a fixed gestational age (GA) cutoff (28, 32, or 36 weeks) for fetuses having two or more measurements before the GA cutoff and not already delivered. A screen test positive for single biometry was based on Z-scores of EFW at the last scan before each GA cut-off so that the false positive rate (FPR) was 10%. Similarly, a screen test positive for the longitudinal analysis was based on the projected (extrapolated) EFW at 40 weeks from all available measurements before each cutoff for each fetus., Results: Fetal abdominal and head circumference measurements, as well as birth weights in the Detroit population, matched well to the INTERGROWTH-21st standards, yet this was not the case for biparietal diameter (BPD) and femur length (FL) (up to 9% and 10% discrepancy for mean and confidence intervals, respectively), mainly due to differences in the measurement technique. Single biometry based on EFW at the last scan at ≤32 weeks (GA IQR: 27.4-30.9 weeks) had a sensitivity of 50% and 53% (FPR = 10%) to detect preterm and term SGA and LGA neonates, respectively (AUC of 82% both). For the detection of LGA using data up to 32- and 36-week cutoffs, single biometry analysis had higher sensitivity than longitudinal analysis (52% vs 46% and 62% vs 52%, respectively; both p<0.05). Restricting the analysis to subjects with the last observation taken within two weeks from the cutoff, the sensitivity for detection of LGA, but not SGA, increased to 65% and 72% for single biometry at the 32- and 36-week cutoffs, respectively. SGA screening performance was higher for preterm (<37 weeks) than for term cases (73% vs 46% sensitivity; p<0.05) for single biometry at ≤32 weeks., Conclusions: When growth abnormalities are defined based on birth weight, growth velocity (captured in the longitudinal analysis) does not provide additional information when compared to the last measurement for predicting SGA and LGA neonates, with both approaches detecting one-half of the neonates (FPR = 10%) from data collected at ≤32 weeks. Unlike for SGA, LGA detection can be improved if ultrasound scans are scheduled as close as possible to the gestational-age cutoff when a decision regarding the clinical management of the patient needs to be made. Screening performance for SGA is higher for neonates that will be delivered preterm., Competing Interests: The authors have declared that no competing interests exist.

Background: The purpose of this study was to clarify cardiovascular structure and function in small for gestational age (SGA) infants across a range of intrauterine growth restriction (IUGR) severity., Methods and results: This prospective study included 38 SGA infants and 30 appropriate for gestational age (AGA) infants. SGA infants were subclassified into severe and mild SGA according to the degree of IUGR. Cardiovascular structure and function were evaluated using echocardiography at 1 week of age. Compared with the AGA infants, both the severe and mild SGA infants showed increased left ventricular diastolic dimensions (severe SGA 10.2±2.4, mild SGA 8.2±1.3, and AGA 7.3±0.7 mm/kg, P<0.05 for all) and decreased global longitudinal strain (severe -21.1±1.6, mild -22.5±1.8, and AGA -23.8±1.8%, P<0.05 for all). Severe SGA infants showed a decreased mitral annular early diastolic velocity (severe 5.6±1.4 vs. AGA 7.0±1.3 cm/s, P<0.01) and increased isovolumic relaxation time (severe 51.3±9.2 vs. AGA 42.7±8.2 ms, P<0.01). Weight-adjusted aortic intima-media thickness and arterial wall stiffness were significantly greater in both SGA infant groups. These cardiovascular parameters tended to deteriorate with increasing IUGR severity., Conclusions: SGA infants, including those with mild SGA, showed cardiovascular remodeling and dysfunction, which increased with IUGR severity. (Circ J 2016; 80: 2212-2220).

Background: Restriction in fetal growth is associated with cardiovascular disease in adulthood. It is unclear whether abnormal intrauterine growth influences arterial morphology during the fetal or neonatal stage. The objective was to study the regional arterial morphology with respect to gestational age and abnormal fetal body size., Methods and Results: We studied body anthropometrics and arterial morphology and physiology in 174 neonates born between 31 and 42 weeks of gestation, including neonates with birth weights appropriate, small, and large for age, with very high resolution vascular ultrasound (35-55 MHz). In simple linear regressions, parameters of body size (body weight, body surface area, and organ circumference) and gestational age were statistically significantly associated with common carotid, brachial, femoral arterial parameters (lumen diameter [LD], wall layer thickness [intima-media thickness and intima-media-adventitia thickness], and carotid artery wall stress [CAWS]). Male sex was statistically significantly associated with LD and CAWS. In multiple linear regression models, body size, gestational age, and sex explained a large proportion of the arterial variance (R( 2) range, 0.37-0.47 for LD; 0.09-0.35 for intima-media thickness; 0.21-0.41 for intima-media-adventitia thickness; and 0.23 for CAWS; all models P<0.001). Arterial wall layer thickness, LDs, and CAWS were independently and strongly predicted by body size, and no effect of maternal disease was observed when added to the models. Gestational age and male sex were also independently but more weakly associated with arterial LDs and CAWS (P<0.01), but not with arterial wall layers., Conclusions: These results indicate that the intrauterine growth of fetal arterial LD and wall layer thickness are primarily attributed to body growth overall. LD and CAWS show weaker association with gestational age and sex., (© 2016 American Heart Association, Inc.)

Objective: To investigate the effect of fetal growth restriction and gender on cerebral oxygenation in preterm neonates during the first 3 days of life., Design: Case-control study., Setting: Neonatal Intensive Care Unit of the Wilhelmina Children's Hospital, The Netherlands., Patients: 68 (41 males) small for gestational age (SGA) (birth weight <10th percentile) and 136 (82 males) appropriate for gestational age (AGA) (birth weight 20th-80th percentile) neonates, matched for gender, gestational age, ventilatory and blood pressure support., Methods: Regional cerebral oxygen saturation (rScO2) and cerebral fractional tissue oxygen extraction (cFTOE) as measured by near-infrared spectroscopy throughout the first 72 h of life were compared between SGA and AGA neonates. The effect of gender was also explored within these comparisons., Results: SGA neonates demonstrated higher rScO2 (71% SEM 0.2 vs 68% SEM 0.2) and lower cFTOE (0.25 SEM 0.002 vs 0.29 SEM 0.002) than AGA neonates. There was an independent effect of gender on rScO2 and cFTOE, resulting in the finding that SGA males displayed highest rScO2 and lowest cFTOE (73% SEM 0.3 respectively 0.24 SEM 0.003). AGA males and SGA females showed comparable rScO2 (69% SEM 0.2 vs 69% SEM 0.4) and cFTOE (0.28 SEM 0.002 vs 0.28 SEM 0.004). AGA females showed lowest rScO2 and highest cFTOE (66% SEM 0.2 respectively 0.30 SEM 0.002)., Conclusions: Growth restriction and gender influence cerebral oxygenation and oxygen extraction in preterm neonates throughout the first 3 days of life., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Brainstem auditory function in small-for-gestational age (SGA) babies born at 30 and less weeks of gestation is poorly understood. We recorded and analysed brainstem auditory evoked response (BAER) at term in babies born at 26-30 weeks of gestation with a birthweight <3rd centile. Compared with normal term appropriate-for-gestational age (AGA) babies, the preterm SGA babies showed a significant increase in all BAER wave latencies at all click rates of 21-91/s (p < 0.05-0.001). The I-V and III-V interpeak intervals were also increased (p < 0.01-0.001), while the I-III interval was marginally decreased at 91/s (p < 0.05). No significant abnormalities were seen in wave amplitudes. Compared with age-matched preterm AGA babies, the SGA preterm babies showed an increase in wave I latency and a decrease in I-III interval at 51 and 91/s (all p < 0.05). No major and consistent differences were found in the two groups of babies in BAER wave amplitude variables. The increased I-V interval in the preterm SGA babies was correlated inversely with occipito-frontal head circumference at time of testing., Conclusion: Brainstem auditory function is deviant from the normal in SGA babies born at 30 and less weeks of gestation. There is delayed brainstem neural maturation, which is associated with a small head size, and slightly precocial maturation in the more peripheral brainstem auditory regions., What Is Known: Intrauterine growth retardation has a subtle degree of adverse effect on central brainstem auditory pathway in preterm babies born at 31-36 weeks of gestation., What Is New: Brainstem neural maturation is delayed, with slightly precocial maturation in the more peripheral brainstem auditory regions, in SGA babies born at 30 and less weeks of gestation.

Numerous conditions, including placental vascular compromise, can lead to small-for-gestational-age (SGA) infants. As few studies have investigated primarily term placentas from SGA infants, we compared placentas from 67 SGA infants to placentas from 67 infants with appropriate weights for gestational age (AGA) in this population, matched for gestational age and gender. Placental histology was reviewed and electronic records were queried for maternal and fetal birth data, infant morbidities, and infant follow-up weights. Comparison of these 2 cohorts showed that placentas from SGA infants were more likely to have smaller weights and thinner umbilical cords than those from AGA infants. SGA placentas had a significant increase in another uteroplacental malperfusion feature: single and multiple infarctions. Rates of preeclampsia, infant cardiac anomalies, and infant genetic abnormalities were not statistically different between groups. Fetal and maternal inflammatory responses, nongestational diabetes, and gestational hypertension were more common in the controls, but these are common indications for placental examination. No statistical differences were present for decidual vasculopathy, chronic villitis, intervillous thrombi, or meconium. More SGA neonates had hypoglycemia compared to their AGA counterparts. SGA infants tended to have decreased weights up to 7 months of age; however, the low number of infants with follow-up limited the statistical significance. This study confirms that small placental size and select features of uteroplacental malperfusion are more common in SGA versus AGA term placentas. The lack of other significant differences may be due to the inclusion of only term infants, with more severe pathology leading to preterm delivery.

Objectives: To review systematically the evidence on impact of cerebral redistribution, as assessed by fetal middle cerebral artery (MCA) Doppler, on neurological outcomes in small-for-gestational-age (SGA) or growth-restricted fetuses., Methods: For this systematic review, MEDLINE was searched for all controlled studies reporting neurological outcomes in SGA or growth-restricted babies with cerebral redistribution based on MCA Doppler indices, from inception to September 2013. We used relative risk or odds ratios, with 95% CI, to identify the association of cerebral redistribution with neurological outcomes., Results: The search yielded 1180 possible citations, of which nine studies were included in the review, with a total of 1198 fetuses. Definitions of SGA and cerebral redistribution were variable, as was study quality. Data could not be synthesized in meta-analyses because of heterogeneity in outcome reporting. Cerebral redistribution was not associated with increased risk of intraventricular hemorrhage in neonates (five studies; n = 806). When present in preterm fetuses, cerebral redistribution was associated with normal Neonatal Behavioral Assessment Scale (NBAS) scores at 40 weeks (one study; n = 62) but abnormal psychomotor development at 1 year of age on the Bayley scale (one study; n = 172). When present in term SGA fetuses, cerebral redistribution was associated with increased risk of motor and state organizational problems on NBAS (two studies; n = 158), and lower mean percentile scores in communication and problem solving at 2 years of age on the Ages and Stages Questionnaire (one study; n = 125)., Conclusions: SGA fetuses with cerebral redistribution may be at higher risk of neurodevelopmental problems. More data are needed from adequately controlled studies with long-term follow-up before conclusions can be drawn. If these findings are true, there is a need to re-evaluate timing of delivery in the management of SGA fetuses, particularly when cerebral redistribution is found at term gestation., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: Among late-onset small fetuses, a combination of estimated fetal weight (EFW), cerebroplacental ratio (CPR) and mean uterine artery (UtA) pulsatility index (PI) can predict a subgroup of fetuses with poor perinatal outcome; however, the association of these criteria with fetal cardiac structure and function is unknown. Our aim was to determine the presence and severity of signs indicating cardiac dysfunction in small fetuses, classified as intrauterine growth-restricted (IUGR) or small-for-gestational age (SGA), according to EFW, CPR and UtA-PI., Methods: A cohort of 209 late-onset small fetuses that were delivered > 34 weeks of gestation was divided in two categories: SGA (n = 59) if EFW was between the 3(rd) and 9(th) centiles with normal CPR and UtA-PI; and IUGR (n = 150) if EFW was < 3(rd) centile, or < 10(th) centile with a CPR < 5(th) centile and/or UtA-PI > 95(th) centile. The small population was compared with 150 appropriately grown fetuses (controls). Fetal cardiac morphometry and function were assessed by echocardiography using two-dimensional M-mode, conventional and tissue Doppler., Results: Compared with controls, both IUGR and SGA fetuses showed larger and more globular hearts (mean left sphericity index ± SD: controls, 1.8 ± 0.3; SGA, 1.5 ± 0.2; and IUGR, 1.6 ± 0.3; P < 0.01) and showed signs of systolic and diastolic dysfunction, including decreased tricuspid annular plane systolic excursion (mean ± SD: controls, 8.2 ± 1.1; SGA, 7.4 ± 1.2; and IUGR, 6.9 ± 1.1; P < 0.001) and increased left myocardial performance index (mean ± SD: controls, 0.45 ± 0.14; SGA, 0.51 ± 0.08; and IUGR, 0.57 ± 0.1; P < 0.001)., Conclusions: Despite a perinatal outcome comparable to that of normal fetuses, the population of so-defined SGA fetuses showed signs of prenatal cardiac dysfunction. This supports the concept that at least a proportion of them are not 'constitutionally small' and that further research is needed., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To investigate the potential value of uterine artery (UtA) pulsatility index (PI) and mean arterial pressure (MAP) at 19-24 weeks' gestation, in combination with maternal characteristics and medical history and fetal biometry in the prediction of delivery of small-for-gestational-age (SGA) neonates in the absence of pre-eclampsia (PE) and to examine the potential value of such assessment in deciding whether the third-trimester scan should be performed at 32 and/or 36 weeks' gestation., Methods: This was a screening study in 63 975 singleton pregnancies, including 3702 (5.8%) that delivered SGA neonates with birth weight < 5(th) percentile (SGA < 5(th) ) in the absence of PE. Multivariable logistic regression analysis was used to determine if screening by a combination of maternal factors, fetal head circumference (HC), abdominal circumference (AC), femur length (FL), UtA-PI and MAP had significant contribution in predicting SGA neonates. A model was developed to select gestational age for the third-trimester assessment, at 32 and/or 36 weeks, based on the results of screening at 19-24 weeks., Results: The detection rates (DRs) of combined screening by maternal factors, fetal biometry and UtA-PI at 19-24 weeks were 90%, 68% and 44% for SGA < 5(th) delivering < 32, 32-36 and ≥ 37 weeks' gestation, respectively, at a false-positive rate (FPR) of 10%. The performance of screening was not improved by the addition of MAP. The DR of SGA < 5(th) delivering at 32-36 weeks improved from 68% to 90% with screening at 32 rather than at 19-24 weeks. Similarly, the DR of SGA < 5(th) delivering ≥ 37 weeks improved from 44% with screening at 19-24 weeks to 59% and 76% when screening at 32 and 36 weeks, respectively. In a hypothetical model, it was estimated that if the desired objective of prenatal screening is to predict about 80% of the cases of SGA < 5(th) , it would be necessary to select 17% of the population at the 19-24-week assessment to be reassessed at 32 weeks and 38% to be reassessed at 36 weeks; 62% would not require a third-trimester scan., Conclusion: Prenatal prediction of a high proportion of SGA neonates necessitates the undertaking of screening in the third trimester of pregnancy in addition to assessment in the second trimester, and the timing of such screening, at 32 and/or 36 weeks, should be contingent on the results of the assessment at 19-24 weeks., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: Fetal magnetoencephalography records fetal brain activity non-invasively. Delayed brain responses were reported for fetuses weighing below the tenth percentile. To investigate whether this delay indicates delayed brain maturation resulting from placental insufficiency, this study distinguished two groups of fetuses below the tenth percentile: growth-restricted fetuses with abnormal umbilical artery Doppler velocity (IUGR) and constitutionally small-for-gestational-age fetuses with normal umbilical artery Doppler findings (SGA) were compared with fetuses of adequate weight for gestational age (AGA), matched for age and behavioural state., Design: A case-control study of matched pairs., Setting: Fetal magnetoencephalography-Center at the University Hospital of Tuebingen., Population: Fourteen IUGR fetuses and 23 SGA fetuses were matched for gestational age and fetal behavioural state with 37 healthy, normal-sized fetuses., Methods: A 156-channel fetal magentoencephalography system was used to record fetal brain activity. Light flashes as visual stimulation were applied to the fetus. The Student's t-test for paired groups was performed., Main Outcome Measure: Latency of fetal visual evoked magnetic responses (VER)., Results: The IUGR fetuses showed delayed VERs compared with controls (IUGR, 233.1 ms; controls, 184.6 ms; P = 0.032). SGA fetuses had similar evoked response latencies compared with controls (SGA, 216.1 ms; controls, 219.9 ms; P = 0.828). Behavioural states were similarly distributed., Conclusion: Visual evoked responses are delayed in IUGR fetuses, but not in SGA. Fetal behavioural state as an influencing factor of brain response latency was accounted for in the comparison. This reinforces that delayed brain maturation is the result of placental insufficiency., (© 2015 Royal College of Obstetricians and Gynaecologists.)

Objectives: To assess the diagnostic accuracy of placental growth factor (PlGF) and ultrasound parameters to predict delivery of a small-for-gestational-age (SGA) infant in women presenting with reduced symphysis-fundus height (SFH)., Methods: This was a multicenter prospective observational study recruiting 601 women with a singleton pregnancy and reduced SFH between 24 and 37 weeks' gestation across 11 sites in the UK and Canada. Plasma PlGF concentration < 5(th) centile, estimated fetal weight (EFW) < 10(th) centile, umbilical artery Doppler pulsatility index > 95(th) centile and oligohydramnios (amniotic fluid index < 5 cm) were compared as predictors for a SGA infant < 3(rd) customized birth-weight centile and adverse perinatal outcome. Test performance statistics were calculated for all parameters in isolation and in combination., Results: Of the 601 women recruited, 592 were analyzed. For predicting delivery of SGA < 3(rd) centile (n = 78), EFW < 10(th) centile had 58% sensitivity (95% CI, 46-69%) and 93% negative predictive value (NPV) (95% CI, 90-95%), PlGF had 37% sensitivity (95% CI, 27-49%) and 90% NPV (95% CI, 87-93%); in combination, PlGF and EFW < 10(th) centile had 69% sensitivity (95% CI, 55-81%) and 93% NPV (95% CI, 89-96%). The equivalent receiver-operating characteristics (ROC) curve areas were 0.79 (95% CI, 0.74-0.84) for EFW < 10(th) centile, 0.70 (95% CI, 0.63-0.77) for low PlGF and 0.82 (95% CI, 0.77-0.86) in combination., Conclusions: For women presenting with reduced SFH, ultrasound parameters had modest test performance for predicting delivery of SGA < 3(rd) centile. PlGF performed no better than EFW < 10(th) centile in determining delivery of a SGA infant., (© 2015 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the international society of ultrasound in obstetrics and gynecology.)

The cerebroplacental ratio (CPR) is emerging as an important predictor of adverse pregnancy outcome, and this has implications for the assessment of fetal well-being in fetuses diagnosed as small for gestational age (SGA) and those appropriate for gestational age close to term. Interest in this assessment tool has been rekindled because of recent reports associating an abnormal ratio with adverse perinatal events and associated postnatal neurological outcome. Fetuses with an abnormal CPR that are appropriate for gestational age or have late-onset SGA (>34 weeks of gestation) have a higher incidence of fetal distress in labor requiring emergency cesarean delivery, a lower cord pH, and an increased admission rate to the newborn intensive care unit when compared with fetuses with a normal CPR. Fetuses with early-onset SGA (<34 weeks of gestation) with an abnormal CPR have a higher incidence of the following when compared with fetuses with a normal CPR: (1) lower gestational age at birth, (2) lower mean birthweight, (3) lower birthweight centile, (4) birthweight less than the 10th centile, (5) higher rate of cesarean delivery for fetal distress in labor, (6) higher rate of Apgar scores less than 7 at 5 minutes, (7) an increased rate of neonatal acidosis, (8) an increased rate of newborn intensive care unit admissions, (9) higher rate of adverse neonatal outcome, and (10) a greater incidence of perinatal death. The CPR is also an earlier predictor of adverse outcome than the biophysical profile, umbilical artery, or middle cerebral artery. In conclusion, the CPR should be considered as an assessment tool in fetuses undergoing third-trimester ultrasound examination, irrespective of the findings of the individual umbilical artery and middle cerebral artery measurements. A CPR calculator is available at http://www.ajog.org/pb/assets/raw/Health%20Advance/journals/ymob/CPR/index.htm., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We investigated the association between maternal zinc level during pregnancy and the risks of low birth weight (LBW) and small for gestational age (SGA) infants in a large population-based birth cohort study. In this study, 3187 pregnant women were recruited. For serum zinc level, 2940 pregnant women were sufficient (≥56 μg/dL) and 247 deficient (<56 μg/dL). Of interest, 7.3% newborns were with LBW among subjects with low zinc level (RR: 3.48; 95% CI: 2.03, 5.96; P < 0.001). Adjusted RR for LBW was 3.41 (95% CI: 1.97, 5.91; P < 0.001) among subjects with low zinc level. Moreover, 15.0% newborns were with SGA among subjects with low zinc level (RR: 1.98; 95% CI: 1.36, 2.88; P < 0.001). Adjusted RR for SGA was 1.93 (95% CI: 1.32, 2.82; P < 0.001) among subjects with low zinc level. A nested case-control study within above cohort showed that maternal serum zinc level was lower in SGA cases as compared with controls. By contrast, maternal serum C-reactive protein, TNF-α and IL-8 levels were significantly higher in SGA cases than that of controls. Moreover, nuclear NF-κB p65 was significantly up-regulated in placentas of SGA cases as compared with controls. Taken together, maternal zinc deficiency during pregnancy elevates the risks of LBW and SGA infants.

Objective: To determine the association between isolated mid-trimester short fetal femur length and adverse perinatal outcome., Methods: This is a retrospective cohort study of patients with singleton gestations routinely assessed by second trimester ultrasound examination during 2006-2013. A fetal isolated short femur was defined as a femur length (FL) below the 5th percentile in a fetus with an abdominal circumference greater than the 10th percentile. Cases of aneuploidy, skeletal dysplasia and major anomalies were excluded. Primary outcomes of interest included the risk of small for gestational age neonates, low birth weight and preterm birth (PTB). Secondary outcome parameters were a 5-min Apgar score less than 7 and a neonatal intensive care unit admission. A control group of 200 fetuses with FL ≥ 5th percentile was used to compare primary and secondary outcome parameters within both groups. Chi-square and Student's t-tests were used where appropriate., Results: Out of 608 eligible patients with a short FL, 117 met the inclusion criteria. Isolated short FL was associated with an increased risk for small for gestational age (19.7% versus 8.0%, p = 0.002) neonates, low birth weight (23.9% versus 8.5%, p<0.001), PTB (19.7% versus 6.0%, p<0.001) and neonatal intensive care unit admissions (13.7% versus 3.5%, p = 0.001). The incidence of a 5-min Apgar score less than 7 was similar in both groups., Conclusion: Isolated short FL is associated with a subsequent delivery of small for gestational age and Low birth weight neonates as well as an increased risk for PTB. This information should be considered when counseling patients after mid-trimester isolated short FL is diagnosed.

Objective: The objective of this study is to measure aortic intima-media thickness (aIMT) and aortic diameter (AD) in appropriate for gestational age (AGA) fetuses, small for gestational age (SGA) fetuses, and intrauterine growth restricted (IUGR) fetuses., Methods: Case-control study performed between June 2011 and June 2012. Forty-nine AGA fetuses, 40 SGA fetuses, and 35 IUGR fetuses underwent concomitant measurement of aIMT and AD at a mean gestational age of 34.4 weeks., Results: Median aIMT was higher in fetuses with IUGR (0.504 mm [95%CI: 0.477-0.530 mm]), than in SGA fetuses (0.466 mm [95% CI: 0.447-0.485 mm]), and AGA fetuses (0.471 mm [95% CI: 0.454-0.488 mm]) (p = 0.023). Mean AD was significantly lower in fetuses with IUGR (4.451 mm [95% CI: 4.258-4.655 mm]), than in AGA fetuses (4.74 mm [95% CI: 4.63-4.843 mm]) (p = 0.028)., Conclusions: Growth restricted fetuses have a thicker aortic wall than AGA and SGA fetuses, which possibly represents preclinical atherosclerosis and a predisposition to later cardiovascular disease.

Objective: To evaluate the impact of late 3rd trimester fetal growth cessation on anatomical birth characteristic predictions used in classifying SGA neonates., Methods: A prospective longitudinal study was performed in 119 pregnancies with normal neonatal growth outcomes. Seven biometric parameters were measured at 3-4 weeks intervals using 3D ultrasonography. Rossavik size models were determined to predict birth characteristics at different ages. Percent Differences (% Diff) were calculated from predicted and measured birth characteristics. Growth Cessation Ages (GCA) were identified when no systematic change in % Diff values occurred after specified prediction ages. Systematic and random prediction errors were compared using different assumptions about the GCA. Predicted and measured size parameters were used to determine six new Growth Potential Realization Index (GPRI) reference ranges. Five were used to sub-classify 34 SGA neonates (weight < 10th percentile) based on the number of abnormal GPRI values., Results: Growth cessation ages were 38 weeks for HC, AC, mid-thigh circumference, estimated weight and mid-arm circumference. Crown-heel length GCA was 38.5 weeks. At GCA, birth characteristics had prediction errors that varied from 0.08 ± 3.4% to 15.7 ± 9.1% and zero % Diff slopes after 38 weeks. Assuming growth to delivery gave increased systematic and random prediction errors as well as positive % Diff slopes after 38 weeks, MA. Seventeen of the SGA neonates had 0 or 1 abnormal GPRI values [Subgroup 1] and 17 others had 2 or more abnormal values [Subgroup 2]. In Subgroup 1, 4/85 (4.7%) of GPRI's were abnormal while in Subgroup 2, 43/85 (50.6%) were abnormal. Use of only one type of GPRI for SGA subclassification resulted in substantial false negative and some false positive rates when compared to subclassification based on all five GPRI values., Conclusions: Growth cessation occurred at approximately 38 weeks for all six birth characteristics studied. SGA neonates can be separated into normal and growth restricted subgroups based on the frequency of abnormal GPRI values (GPRI Profile Classification).

Objectives: To compare uterine artery pulsatility index (PI) obtained at 11 + 0 to 13 + 6 weeks of gestation in singleton and twin pregnancies and to evaluate changes in PI values of twin pregnancies developing pre-eclampsia (PE) or small-for-gestational age (SGA) of either one or both fetuses., Methods: Uterine artery PI was measured in 421 twin pregnancies (384 dichorionic and 37 monochorionic) and in 500 singleton pregnancies. The measured mean and lowest uterine artery PI values were converted to multiples of the expected normal median (MoM) after correction for maternal body mass index, ethnicity and gestational age. The median PI-MoM values of twins were compared with those of singleton pregnancies. In twin pregnancies, PI-MoM values were analyzed according to chorionicity, development of early-onset (< 34 weeks) or late-onset (≥ 34 weeks) PE and SGA of one or both twins., Results: Uterine artery PI-MoM was significantly lower in twin compared with singleton pregnancies (mean K = 174.31, P < 0.0001, lowest K = 139.27, P < 0.0001). However, there were no significant differences in the uterine artery PI-MoM values between monochorionic and dichorionic twins. The uterine artery PI in twin pregnancies that developed early-onset PE (P < 0.001) and SGA of both twins (P < 0.05) was higher than the uterine artery PI in uncomplicated twin pregnancies, whereas no differences were found for late PE or SGA of one twin., Conclusions: First-trimester placental impedance to flow, as assessed by uterine artery Doppler examination, is reduced in twin pregnancies, with no differences related to chorionicity. The relative increase of uterine artery PI found in twin pregnancies that developed early PE and SGA of both twins suggests that first-trimester uterine artery assessment may be useful in identifying such complications., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To test if serum YKL-40 is increased in women developing preeclampsia or small-for-gestational age fetuses. We also assessed the association between uterine artery pulsatility index, notching and serum YKL-40 levels., Design: Prospective cohort study., Setting: A primary referral unit for obstetric ultrasound., Population: A total of 1214 unselected pregnant women enrolled at nuchal translucency examination between 11(+3) and 13(+6)  weeks of gestation., Methods: All women had ultrasound and blood sample collection at the nuchal translucency scan, a 20-week malformation scan and 25-week and 32-week fetal growth examinations. Uterine artery Doppler was assessed and outcome was registered from medical records., Main Outcome Measures: Preeclampsia, hypertension, small-for-gestational age., Results: Serum YKL-40 was associated with increasing maternal age (p < 0.0001), body mass index (p = 0.0002), primiparity (p = 0.0003), and hypertension (p = 0.015). Serum YKL-40 increased from 12 to 20 weeks and decreased from 20-25 and 25-32 weeks of gestation. No association was found between preeclampsia and serum YKL-40. Small-for-gestational-age at birth was significantly associated with a 5.4% increase in serum YKL-40 at 32 weeks of gestation (95% CI 1.5-9.3, p = 0.005). An association was found between uterine artery pulsatility index at 32 weeks and small-for-gestational age (p = 0.0015) but not between YKL-40 and uterine artery notching (p = 0.83)., Conclusions: Serum YKL-40 was not associated with preeclampsia. Increasing serum YKL-40 was related to maternal age, body mass index and small-for-gestational age and may reflect an exaggerated inflammatory response., (© 2014 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: To assess carotid and aortic intima-media thickness (IMT) in term small-for-gestational-age (SGA) newborns with and without prenatal signs of severity., Methods: This prospective study comprised 67 cases diagnosed prenatally and 134 normally grown newborns. Cases were subclassified into SGA with no signs of severity and those with signs of severity, defined as a birth weight below the 3(rd) percentile or abnormal uterine artery Doppler or cerebroplacental ratio. Blood pressure and vascular IMT were evaluated., Results: SGA newborns showed a non-significant trend for higher values of blood pressure. IMT values were significantly increased in SGA newborns, with and without signs of severity, compared with controls. The magnitude of the increase was higher in SGA newborns with signs of severity., Conclusions: Vascular IMT was increased in SGA newborns, irrespective of the presence or absence of prenatal signs of severity. This finding challenges the notion of 'constitutionally small' SGA, and supports the premise that the majority of SGA newborns have true growth restriction and suffer fetal cardiovascular programming., (Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.)