Appropriate For Gestational Age Fetuses Research Articles

Comparison Between Fetal Abdominal Subcutaneous Tissue Thickness and Abdominal Circumference to Predict Large for Gestational Age Neonate in Gestational Diabetes

Objective: Increased subcutaneous fat deposition in abdomen in large for gestational age (LGA) fetuses of mothers with gestational diabetes mellitus can be measured by fetal abdominal subcutaneous tissue thickness (FASTT) using ultrasound. The current study aimed to evaluate the correlation between FASTT and birth weight and compare FASTT and abdominal circumference (AC) for prediction of LGA babies in gestational diabetes. Materials and methods: 150 term GDM women were enrolled into the study. FASTT was measured weekly. Birth weight was measured immediately after delivery and categorized into SGA, AGA and LGA according to International growth charts. The last FASTT and AC values were recorded for analysis. Correlation statistics was used to determine the relation between FASTT with birth weight and ROC curves were used to compare FASTT and AC for prediction of LGA fetuses. Results: There was weak positive correlation between FASTT and birth weight with Pearson’s co-efficient (r) of 0.375. The cut-off value for FASTT to predict LGA fetuses obtained by ROC curve was ≥8.05 mm with sensitivity and specificity of 68.8% and 68.7%. The mean values of FASTT for small for gestational age (SGA), appropriate for gestational age (AGA) and LGA fetuses were significantly different. AUC for FASTT was 0.692 and for AC was 0.755. Conclusion: FASTT had a positive but weak correlation with birth weight. The utility of FASTT as a screening tool may not be impressive. FASTT can discriminate between SGA, AGA and LGA fetuses. AC is a better predictor than FASTT for LGA neonates.

Measurement of Calprotectin and PTH in the Amniotic Fluid of Early Second Trimester Pregnancies and Their Impact on Fetuses with Growth Disorders: Are Their Levels Related to Oxidative Stress?

Background: During the early stages of human fetal development, the fetal skeleton system is chiefly made up of cartilage, which is gradually replaced by bone. Fetal bone development is mainly regulated by the parathyroid hormone parathormone (PTH) and PTH-related protein, with specific calprotectin playing a substantial role in cell adhesion and chemotaxis while exhibiting antimicrobial activity during the inflammatory osteogenesis process. The aim of our study was to measure the levels of PTH and calprotectin in early second trimester amniotic fluid and to carry out a comparison between the levels observed among normal full-term pregnancies (control group) and those of the groups of embryos exhibiting impaired or enhanced growth. Methods: For the present prospective study, we collected amniotic fluid samples from pregnancies that underwent amniocentesis at 15 to 22 weeks of gestational age during the period 2021–2023. Subsequently, we followed up on all pregnancies closely until delivery. Having recorded fetal birthweights, we then divided the neonates into three groups: small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). Results: In total, 64 pregnancies, including 14 SGA, 10 LGA, and 40 AGA fetuses, were included in our study. Both substances were detected in early second trimester amniotic fluid in both groups. Concentrations of calprotectin differed significantly among the three groups (p = 0.033). AGA fetuses had a lower mean value of 4.195 (2.415–6.425) IU/mL, whereas LGA fetuses had a higher mean value of 6.055 (4.887–13.950) IU/mL, while SGA fetuses had a mean value of 5.475 (3.400–9.177) IU/mL. Further analysis revealed that only LGA fetuses had significantly higher calprotectin concentrations compared to AGA fetuses (p = 0.018). PTH concentration was similar between the groups, with LGA fetuses having a mean value of 13.18 (9.51–15.52) IU/mL, while SGA fetuses had a mean value of 14.18 (9.02–16.00) IU/mL, and AGA fetuses had similar concentrations of 13.35 (9.05–15.81) IU/mL. The differences in PTH concentration among the three groups were not statistically significant (p = 0.513). Conclusions: Calprotectin values in the amniotic fluid in the early second trimester were higher in LGA fetuses compared to those in the SGA and AGA categories. LGA fetuses can possibly be in a state of low-grade chronic inflammation due to excessive fat deposition, causing oxidative stress in LGA fetuses and, eventually, the release of calprotectin. Moreover, PTH concentrations in the amniotic fluid of early second trimester pregnancies were not found to be statistically correlated with fetal growth abnormalities in either LGA or SGA fetuses. However, the early time of collection and the small number of patients in our study should be taken into account.

Midline structures and cortical development in fetuses with late growth restriction according to Doppler status: prospective study.

Fetuses with late growth restriction (FGR) have a higher risk of sub-optimal neurocognitive performance after birth. Previous studies have reported that impaired brain and cortical development can start in utero. The primary aim of this study was to report midline structures and cortical development in fetuses with late growth restriction according to its severity; the secondary aim was to elucidate whether the severity of FGR, as defined by the presence of abnormal Doppler findings, plays a role in affecting brain growth and maturation. Prospective cross-sectional study including fetuses with late FGR undergoing neurosonography between 32 and 34 weeks of gestation. Midline structures (corpus callosum (CC) and cerebellar vermis (CV) length) and cortical development, including the depth of Sylvian (SF), parieto-occipital (POF) and calcarine (CF) were compared between FGR, small (SGA) and appropriate for gestational age (AGA) fetuses, defined upon the Delphi criteria. Sub-group analysis according to the severity of FGR (normal vs abnormal fetal Dopplers) was also performed. Univariate analysis was used to analyze the data. 52 FGR with normal, 60 with abnormal Dopplers, 64 SGA and 100 AGA fetuses were included in the analysis. SGA and FGR fetuses showed significant differences in absolute values of CC (median (interquartile range) control 43.47 (28.9-56.05), vs SGA 41.85 (27.82-51.79), vs FGR ND 38.54 (29.12-50.53), vs FGR AD 31.72 (23.8-40.19) K= 26.68; p<0.0001), CV (control 24.85 (17.55-29.21), SGA K=16.71; p=0.0008), SF (control 14.52 (10.65-16.76) vs SGA 12.71 (9.8-15.10) vs FGR ND 11.93 (9.12-13.43) VS FGR A 8.30 (6.72-10.33) K=75.82; p<0.0001), POF (control 8.56 (6.31-11.09) vs SGA 8.11 (5.58-10.43) vs FGR ND 7.81 (6.14-9.29) vs FGR AD 6.56 (4.22-7.99), K=45.06; p<0.0001) and CF ( control 9.27 (6.70-11.45) vs SGA 8.23 (5.67-10.65) vs FGR ND 7.68 (5.22-9.41) vs FGR AD 6.26 (4.48-7.19) K=46.14; p<0.0001) when compared to AGA controls with a progressive reduction across groups. When neurosonographic variables were corrected for fetal HC values, significant difference in the length of CC, SF, POF and CF but CV were observed only in FGR fetuses with abnormal Doppler when compared to AGA controls. Late onset small fetuses showed shorter CC length and a delayed cortical development when compared to control. After controlling for HC size these differences remain significant only in FGR fetuses with abnormal Dopplers. These findings support the existence of a link between brain development and impaired placental function. This article is protected by copyright. All rights reserved.

Evaluation of the type of fetal umblical-portal anastomosis in late-onset fetal growth restriction: A case-control study.

To evaluate the type of umbilical-portal anastomosis in late-onset fetal growth restriction (LO-FGR) and appropriate for gestational age (AGA) fetuses. To investigate the impact of the type of umbilical-portal anastomosis on the adverse outcomes in LO-FGR. This study observed 150 pregnancies with AGA fetuses and 62 pregnancies with fetuses with LO-FGR. In each case, the point of reference for measuring the abdominal circumference was established. The type of umbilical-portal anastomosis was evaluated as T-shaped, X-shaped, and H-shaped according to the shape of main portal vein and portal sinus. Incidences of the type of umbilical-portal anastomosis in AGA and LO-FGR fetuses were evaluated. T-shaped anastomosis was the most common (56.7%) in the AGA group and X-shaped (66.1%) in the LO-FGR group. In LO-FGR, T-shape anastomosis was significantly lower and X-shape anastomosis was significantly higher than AGA (p < 0.001). X-shaped anastomosis was associated with LO-FGR and the RR was 2.3 (95% CI 1.5-3.6; p < 0.001). Incidences of admission to NICU and emergency C/S for fetal distress were higher in fetuses with X -shaped anastomosis in the LO-FGR (p < 0.05). X-shaped umbilical-portal anastomosis have a prognostic significance in LO-FGR fetuses.

Placental growth factor and fetoplacental Doppler indices in combination predict preterm birth reliably in pregnancies complicated by fetal growth restriction.

To assess the association between placental biomarkers (placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1)/PlGF ratio) and fetoplacental Doppler indices (umbilical artery (UA) pulsatility index (PI) and uterine artery (UtA) PI) in various combinations for predicting preterm birth (PTB) in pregnancies complicated by fetal growth restriction (FGR). This was a prospective observational cohort study, performed at Mater Mother's Hospital in Brisbane, Queensland, Australia, from May 2022 to June 2023, of pregnancies complicated by FGR and appropriate-for-gestational-age (AGA) pregnancies. Maternal serum PlGF levels, sFlt-1/PlGF ratio, UA-PI and UtA-PI were measured at 2-4-weekly intervals from recruitment until delivery. Harrell's concordance statistic (Harrell's C) was used to evaluate multivariable Cox proportional hazards regression models featuring various combinations of placental biomarkers and fetoplacental Doppler indices to ascertain the best combination to predict PTB (< 37 weeks). Multivariable Cox regression models were used with biomarkers as time-varying covariates. The study cohort included 320 singleton pregnancies, comprising 179 (55.9%) affected by FGR, defined according to a Delphi consensus, and 141 (44.1%) with an AGA fetus. In the FGR cohort, both low PlGF levels and elevated sFlt-1/PlGF ratio were associated with significantly shorter time to PTB. Low PlGF was a better predictor of PTB than was either sFlt-1/PlGF ratio or a combination of PlGF and sFlt-1/PlGF ratio (Harrell's C, 0.81, 0.78 and 0.79, respectively). Although both Doppler indices were significantly associated with time to PTB, in combination they were better predictors of PTB than was either UA-PI > 95th centile or UtA-PI > 95th centile alone (Harrell's C, 0.82, 0.75 and 0.76, respectively). Predictive utility for PTB was best when PlGF < 100 ng/L, UA-PI > 95th centile and UtA-PI > 95th centile were combined (Harrell's C, 0.88) (hazard ratio, 32.99; 95% CI, 10.74-101.32). Low maternal serum PlGF level (< 100 ng/L) and abnormal fetoplacental Doppler indices (UA-PI > 95th centile and UtA-PI > 95th centile) in combination have the greatest predictive utility for PTB in pregnancies complicated by FGR. Their assessment may help guide clinical management of these complex pregnancies. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Reduced adipose tissue in growth-restricted fetuses using quantitative analysis of magnetic resonance images.

Fat-water MRI can be used to quantify tissues' lipid content. We aimed to quantify fetal third trimester normal whole-body subcutaneous lipid deposition and explore differences between appropriate for gestational age (AGA), fetal growth restriction (FGR), and small for gestational age fetuses (SGAs). We prospectively recruited women with FGR and SGA-complicated pregnancies and retrospectively recruited the AGA cohort (sonographic estimated fetal weight [EFW] ≥ 10th centile). FGR was defined using the accepted Delphi criteria, and fetuses with an EFW < 10th centile that did not meet the Delphi criteria were defined as SGA. Fat-water and anatomical images were acquired in 3T MRI scanners. The entire fetal subcutaneous fat was semi-automatically segmented. Three adiposity parameters were calculated: fat signal fraction (FSF) and two novel parameters, i.e., fat-to-body volume ratio (FBVR) and estimated total lipid content (ETLC = FSF*FBVR). Normal lipid deposition with gestation and differences between groups were assessed. Thirty-seven AGA, 18 FGR, and 9 SGA pregnancies were included. All three adiposity parameters increased between 30 and 39weeks (p < 0.001). All three adiposity parameters were significantly lower in FGR compared with AGA (p ≤ 0.001). Only ETLC and FSF were significantly lower in SGA compared with AGA using regression analysis (p = 0.018-0.036, respectively). Compared with SGA, FGR had a significantly lower FBVR (p = 0.011) with no significant differences in FSF and ETLC (p ≥ 0.053). Whole-body subcutaneous lipid accretion increased throughout the third trimester. Reduced lipid deposition is predominant in FGR and may be used to differentiate FGR from SGA, assess FGR severity, and study other malnourishment pathologies. Fetuses with growth restriction have reduced lipid deposition than appropriately developing fetuses measured using MRI. Reduced fat accretion is linked with worse outcomes and may be used for growth restriction risk stratification. • Fat-water MRI can be used to assess the fetal nutritional status quantitatively. • Lipid deposition increased throughout the third trimester in AGA fetuses. • FGR and SGA have reduced lipid deposition compared with AGA fetuses, more predominant in FGR.

Detection and Quantification of Neurotrophin-3 (NT-3) and Nerve Growth Factor (NGF) Levels in Early Second Trimester Amniotic Fluid: Investigation into a Possible Correlation with Abnormal Fetal Growth Velocity Patterns.

Abnormal fetal growth is associated with adverse perinatal and long-term outcomes. The pathophysiological mechanisms underlying these conditions are still to be clarified. Nerve growth factor (NGF) and neurotrophin-3 (NT-3) are two neurotrophins that are mainly involved in the neuroprotection process, namely promotion of growth and differentiation, maintenance, and survival of neurons. During pregnancy, they have been correlated with placental development and fetal growth. In this study, we aimed to determine the early 2nd trimester amniotic fluid levels of NGF and NT-3 and to investigate their association with fetal growth. This is a prospective observational study. A total of 51 amniotic fluid samples were collected from women undergoing amniocentesis early in the second trimester and were stored at -80 °C. Pregnancies were followed up until delivery and birth weight was recorded. Based on birth weight, the amniotic fluid samples were divided into three groups: appropriate for gestational age (AGA), small for gestational age (SGA), and large for gestational age (LGA). NGF and NT-3 levels were determined by using Elisa kits. NGF concentrations were similar between the studied groups; median values were 10.15 pg/mL, 10.15 pg/mL, and 9.14 pg/mL in SGA, LGA, and AGA fetuses, respectively. Regarding NT-3, a trend was observed towards increased NT-3 levels as fetal growth velocity decreased; median concentrations were 11.87 pg/mL, 15.9 pg/mL, and 23.5 pg/mL in SGA, AGA, and LGA fetuses, respectively, although the differences among the three groups were not statistically significant. Our findings suggest that fetal growth disturbances do not induce increased or decreased production of NGF and NT-3 in early second trimester amniotic fluid. The trend observed towards increased NT-3 levels as fetal growth velocity decreased shows that there may be a compensatory mechanism in place that operates in conjunction with the brain-sparing effect. Further associations between these two neurotrophins and fetal growth disturbances are discussed.

Longitudinal Behavior of Left-Ventricular Strain in Fetal Growth Restriction

Fetal growth restriction (FGR) is associated with an increased risk of adverse outcomes resulting from adaptive cardiovascular changes in conditions of placental insufficiency, leading to cardiac deformation and dysfunction, which can be evaluated with 2D speckle tracking echocardiography (2D-STE). The aim of the present study was to evaluate whether reduced fetal growth is associated with cardiac left-ventricle (LV) dysfunction, using 2D-STE software widely used in postnatal echocardiography. A prospective longitudinal cohort study was performed, and global (GLO) and segmental LV longitudinal strain was measured offline and compared between FGR and appropriate-for-gestational-age (AGA) fetuses throughout gestation. All cases of FGR fetuses were paired 1:2 to AGA fetuses, and linear mixed model analysis was performed to compare behavior differences between groups throughout pregnancy. Our study shows LV fetal longitudinal strain in FGR and AGA fetuses differed upon diagnosis and behaved differently throughout gestation. FGR fetuses had lower LV strain values, both global and segmental, in comparison to AGA, suggesting subclinical cardiac dysfunction. Our study provides more data regarding fetal cardiac function in cases of placental dysfunction, as well as highlights the potential use of 2D-STE in the follow-up of cardiac function in these fetuses.

Risk of Stillbirth in Pregnancies Complicated by Diabetes, Stratified by Fetal Growth.

To compare stillbirth rates per week of expectant management stratified by birth weight in pregnancies complicated by gestational diabetes mellitus (GDM) or pregestational diabetes mellitus. A national population-based retrospective cohort study of singleton, nonanomalous pregnancies complicated by pregestational diabetes or GDM was performed using national birth and death certificate data from 2014 to 2017. Stillbirth rates per 10,000 patients (stillbirth incidence at gestational age week/ongoing pregnancies-[0.5×live births at gestational age week]) were determined for each week of pregnancy from 34 to 39 completed weeks of gestation. Pregnancies were stratified by birth weight, categorized as having small-for-gestational-age (SGA), appropriate-for-gestational-age (AGA), or large-for-gestational-age (LGA) fetuses, assigned by sex-based Fenton criteria. Relative risk (RR) and 95% CI for stillbirth were calculated for each gestational age week compared with the GDM-related AGA group. We included 834,631 pregnancies complicated by either GDM (86.9%) or pregestational diabetes (13.1%) in the analysis, with a total of 3,033 stillbirths. Stillbirth rates increased with advancing gestational age for pregnancies complicated by both GDM and pregestational diabetes regardless of birth weight. Compared with pregnancies with AGA fetuses, those with both SGA and LGA fetuses were significantly associated with an increased risk of stillbirth at all gestational ages. Ongoing pregnancies at 37 weeks of gestation complicated by pregestational diabetes with LGA or SGA fetuses had respective stillbirth rates of 64.9 and 40.1 per 10,000 patients. Pregnancies complicated by pregestational diabetes had an RR of stillbirth of 21.8 (95% CI 17.4-27.2) for LGA fetuses and 13.5 (95% CI 8.5-21.2) for SGA fetuses compared with GDM-related AGA at 37 weeks of gestation. The greatest absolute risk of stillbirth was in pregnancies complicated by pregestational diabetes at 39 weeks of gestation with LGA fetuses (97/10,000). Pregnancies complicated by both GDM and pregestational diabetes affected by pathologic fetal growth have an increased risk of stillbirth with advancing gestational age. This risk is significantly higher with pregestational diabetes, especially pregestational diabetes with LGA fetuses.

Maternal Blood Fatty Acid Levels in Fetal Growth Restriction.

To assess the maternal blood levels of fatty acids (FAs) in pregnancies with fetal growth restriction (FGR). This prospective cross-sectional study included pregnant women with gestational age between 26 and 37 + 6 weeks with FGR and appropriate for gestational age (AGA) fetuses. The levels of saturated, trans, monounsaturated, and polyunsaturated FAs were measured using centrifugation and liquid chromatography. The Student's t-test, Mann-Whitney test, and general linear model, with gestational age and maternal weight as covariants, were used to compare FA levels and the FGR and AGA groups. The Chi-square was used to evaluate the association between groups and studied variables. Maternal blood sample was collected from 64 pregnant women, being 24 FGR and 40 AGA. A weak positive correlation was found between the palmitoleic acid level and maternal weight (r = 0.285, p = 0.036). A weak negative correlation was found between the gamma-linoleic acid level and gestational age (r = - 0.277, p = 0.026). The median of the elaidic acid level (2.3 vs. 4.7 ng/ml, p = 0.045) and gamma-linoleic acid (6.3 vs. 6.6 ng/ml, p = 0.024) was significantly lower in the FGR than the AGA group. The palmitoleic acid level was significantly higher in the FGR than AGA group (50.5 vs. 47.6 ng/ml, p = 0.033). Pregnant women with FGR had lower elaidic acid and gamma-linoleic acid levels and higher palmitoleic acid levels than AGA fetuses.

Exploration on appropriate fetal weight of twin pregnancies at different gestational weeks and pregnancy complications and outcomes

Objective: To explore the appropriate fetal weight of twin pregnancies at different gestational weeks and the association with pregnancy complications and outcomes. Methods: Fetal weight at different gestational weeks and related pregnancy complications and outcomes from 1 225 twin pregnancies, who gave birth at Peking University First Hospital from January 2004 to December 2020, were analyzed in this study, including hypertensive disorders in pregnancy, gestational diabetes mellitus (GDM), fetal growth restriction (FGR), fetal distress, preterm birth and neonatal asphyxia. The appropriate fetal weight of twin pregnancies at different gestational weeks were analysed based on the information from 616 twin pregnancies without complications (except preterm birth), and were expressed as P10~P90. The chi-square test was used to compare the risk of pregnancy complications and adverse outcomes in large for gestational age (LGA), appropriate for gestational age (AGA) and small for gestational age (SGA) twin pregnancies and the difference in incidence of pregnancy complications and adverse outcomes in different years. Results: The appropriate fetal weights of normal twin pregnancies at 28 to 37 weeks and 38-40 weeks of gestation were 910-1 255 g, 996-1 518 g, 1 105-1 785 g, 1 295-1 825 g, 1 336-2 000 g, 1 754-2 321 g, 1 842-2 591 g, 1 913-2 615 g, 2 150-2 847 g, 2 350-3 130 g and 2 450-3 250 g, respectively. The incidences of hypertensive disorders in pregnancy, FGR, fetal distress and neonatal asphyxia related to SGA twin pregnancies were significantly higher than AGA twin pregnancies (all P<0.05). The incidence of GDM in twin pregnant from 2017 to 2020 was higher than that from 2004 to 2009 or from 2010 to 2016, but the incidence of fetal distress and neonatal asphyxia were lower than those from 2010 to 2016, and the differences were statistically significant (all P<0.05). Conclusions: The appropriate weights of twin fetuses at different gestational weeks are different from singleton. The incidence of pregnancy complications and adverse outcomes in AGA fetuses is significantly lower than that in SGA fetuses under the specific weight standard for twin fetuses, which could provide a practical basis for clinical management of twin pregnancy.

The importance of the cerebroplacental ratio for the prognosis of neonatal outcome in AGA fetuses

PurposeAs a Doppler sonographic parameter, the cerebroplacental ratio (CPR) provides information about fetal hemodynamics and the redistribution of fetal blood volume in response to a metabolic change. The present study was undertaken to determine the extent to which CPR can be used as a valid parameter in routine obstetric assessment. We investigated whether CPR can be used to assess the neonatal outcome in appropriate for gestational age (AGA) fetuses and its association with secondary cesarean section due to fetal distress.MethodsIn this retrospective analysis 1739 pregnant women were admitted to the University Women‘s Clinic Magdeburg, Germany, between January 2016 and December 2017. Of them, 710 AGA fetuses were eligible for analysis. SGA fetuses with an estimated fetal weight < 10th percentile were excluded from the study. The AGA fetuses were divided in two groups based on the CPR: 669 fetuses showed a normal CPR ≥ 1.08; 41 fetuses showed a decreased CPR < 1.08.ResultsIn our study cohort decreased CPR in AGA fetuses was associated with threefold increased rate of cesarean sections due to fetal distress (p < 0.001). Our data suggested that low CPR is a reliable predictor of an impaired neonatal outcome in AGA fetuses in terms of a lower birth weight, transfer to neonatology, longer length of hospitalization, and the presence of severe morbidity.ConclusionDecreased CPR in AGA fetuses correlated with impaired neonatal outcome and secondary cesarean section due to fetal distress. The potential role of CPR for obstetric screening should be investigated in further studies.

Fetal neurosonography at 31-35 weeks reveals altered cortical development in pre-eclampsia with and without small-for-gestational-age fetus.

To explore the pattern of fetal cortical development in pregnancies complicated by pre-eclampsia (PE), with and without a small-for-gestational-age (SGA) fetus, compared to uncomplicated pregnancies. This was a prospective observational study including singleton pregnancies complicated by normotensive SGA (birth weight < 10th centile) (n = 77), PE with an appropriate-for-gestational-age (AGA) fetus (n = 76) or PE with a SGA fetus (n = 67), and 128 uncomplicated pregnancies (normotensive AGA) matched by gestational age at ultrasound. All pregnancies underwent detailed neurosonography, using a transabdominal and transvaginal approach, at 31-35 weeks' gestation to assess the depth of the insula, Sylvian fissure, parieto-occipital sulcus, cingulate sulcus and calcarine sulcus. All measurements were adjusted for biparietal diameter (BPD). In addition, a grading score of cortical development was assigned to each brain structure, ranging from Grade 0 (no development) to Grade 5 (maximum development). Univariate and multiple regression analyses were conducted. Similar to findings in previous studies, normotensive pregnancies with a SGA fetus showed significant differences in cortical development compared with controls, with reduced Sylvian fissure depth adjusted for BPD (14.5 ± 2.4 vs 16.6 ± 2.3; P < 0.001) and increased insula depth adjusted for BPD (33.2 ± 2.0 vs 31.8 ± 2.0; P < 0.001). Interestingly, a similar cortical development pattern was observed in PE pregnancies with a SGA fetus and in PE pregnancies with an AGA fetus, manifested by reduced Sylvian fissure depth adjusted for BPD (14.2 ± 2.3 and 14.3 ± 2.3 vs 16.6 ± 2.3; P < 0.001 for both) and greater insula depth adjusted for BPD (33.2 ± 2.1 and 32.8 ± 1.7 vs 31.8 ± 2.0; P < 0.001 for both) compared with controls. No significant differences were observed in parieto-occipital, cingulate sulcus or calcarine sulcus depth across the study groups. The Sylvian fissure was scored as Grade 4 in significantly more (93.2% vs 59.5%) and as Grade 5 in significantly fewer (2.7% vs 37.3%) PE pregnancies with an AGA fetus compared with controls (P < 0.05 for both). These differences remained significant even after statistical adjustment for potential confounders, including ethnicity, low socioeconomic status, nulliparity, chronic hypertension, pregestational diabetes, assisted reproductive technologies, smoking and fetal gender, with the application of Benjamini-Hochberg procedure for multiple comparisons. PE with or without SGA is associated with a differential fetal cortical development pattern which is similar to that described previously in small fetuses. Future research is warranted to elucidate better the mechanism(s) underlying these changes. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Umbilical Venous Volume Flow in Late-Onset Fetal Growth Restriction.

Umbilical vein flow (UVF) is reduced in fetal growth restriction (FGR). We compared absolute and size-adjusted UVF (estimated fetal weight [EFW] and abdominal circumference [AC]) and rates of abnormal UVF parameters (<10th percentile) among FGR fetuses meeting Delphi criteria (FGR-D) against small for gestational age (SGA) fetuses and appropriate for gestational age (AGA) controls. Absolute UVF, UVF/EFW, and UVF/AC were compared between 73 FGR pregnancies (35 FGR-D, 38 SGA) and 108 AGA controls. Rates of abnormal UVF were compared to abnormal umbilical artery pulsatility index (UAPI). Independent samples t-tests, Mann-Whitney U, odds ratio (OR), chi-squared, and Fisher's exact tests were used as appropriate. Mean absolute UVF was significantly decreased in FGR-D compared to AGA (P=.0147), but not between SGA and AGA fetuses. The incidence of both abnormal absolute UVF and UVF/AC values (<10th centile) was higher among late-onset FGR fetuses versus AGA fetuses (UVF: OR 2.7, confidence interval [CI] 1.37-5.4; UVF/AC: OR 2.73, CI 1.37-5.4). UVF was more frequently abnormal than UAPI and in only two fetuses were both Doppler values abnormal. Absolute UVF is altered in late-onset FGR, and most pronounced among FGR-D. UVF may provide additional insight into fetal compromise in those affected by growth restriction.

Brain-Derived Neurotrophic Factor Levels in Cord Blood from Growth Restricted Fetuses with Doppler Alteration Compared to Adequate for Gestational Age Fetuses.

Background and Objectives: Fetal growth restriction (FGR) is a severe obstetric disease characterized by a low fetal size entailing a set of undesired consequences. For instance, previous studies have noticed a worrisome association between FGR with an abnormal neurodevelopment. However, the precise link between FGR and neurodevelopmental alterations are not yet fully understood yet. Brain-derived neurotrophic factor (BDNF) is a critical neurotrophin strongly implicated in neurodevelopmental and other neurological processes. In addition, serum levels of BDNF appears to be an interesting indicator of pathological pregnancies, being correlated with the neonatal brain levels. Therefore, the aim of this study is to analyze the blood levels of BDNF in the cord blood from fetuses with FGR in comparison to those with weight appropriate for gestational age (AGA). Materials and Methods: In this study, 130 subjects were recruited: 91 in group A (AGA fetuses); 39 in group B (16 FGR fetuses with exclusively middle cerebral artery (MCA) pulsatility index (PI) < 5th percentile and 23 with umbilical artery (UA) PI > 95th percentile). Serum levels of BDNF were determined through ELISA reactions in these groups. Results: Our results show a significant decrease in cord blood levels of BDNF in FGR and more prominently in those with UA PI >95th percentile in comparison to AGA. FGR fetuses with exclusively decreased MCA PI below the 5th percentile also show reduced levels of BDNF than AGA, although this difference was not statistically significant. Conclusions: Overall, our study reports a potential pathophysiological link between reduced levels of BDNF and neurodevelopmental alterations in fetuses with FGR. However, further studies should be conducted in those FGR subjects with MCA PI < 5th percentile in order to understand the possible implications of BDNF in this group.

Fetal cardiac alterations in the late-onset growth-restricted fetuses: A prospective case-control study.

Fetal growth restriction (FGR) has significant consequences on cardiac functions. This study aims to evaluate cardiac functional parameters in late-onset (FGR) fetuses and compare those appropriate for gestational age (AGA) fetuses. Fifty-six singleton pregnancies were involved in this prospective case-control study. Delphi consensus was used to define late-onset FGR. We compared the E/A ratio, left myocardial performance index (MPI) and tricuspid annular plane systolic excursion (TAPSE) in late-onset FGR cases and gestational age-matched AGA fetuses. Twenty-eight late-onset FGR and 28 AGA fetuses were enrolled. The mean gestational age in the late-onset FGR group was 34.1 ± 2.3 weeks and 34.4 ± 2.1 in controls. The E/A ratio was 0.88 ± 0.09 in AGA fetuses, 0.79 ± 0.11 in the late-onset FGR group, and significantly lower in late-onset FGR fetuses (p: 0.012). Left MPI was 0.51 ± 0.09 in AGA and 0.62 ± 0.11 in the late-onset FGR group. Left MPI was markedly higher in late-onset FGR fetuses (p: 0.024). TAPSE was 7.4 ± 2.9 mm in controls and 5.2 ± 1.8 in the late-onset FGR group, and it was significantly shorter in the late-onset FGR fetuses (p: 0.016). Late-onset FGR is associated with cardiac remodeling and dysfunction. Fetal echocardiography may be beneficial to detect those subtle cardiac changes.

The Assessment of Vitamin D Levels in Pregnant Women is not Associated to Fetal Growth Restriction: A Cross Sectional Study.

To assess maternal serum levels of vitamin D in fetuses appropriate for gestational age (AGA), small for gestational age (SGA), and with fetal growth restriction (FGR) according to estimated fetal weight (EFW). This cross-sectional study included 87 pregnant women between 26 and 36 weeks of gestation: 38 in the AGA group, 24 in the SGA group, and 25 in the FGR group. Maternal serum vitamin D levels were assessed using the chemiluminescence method. The Fisher exact test was used to compare the results between the groups. The mean ± standard deviation (SD) of maternal age (years) and body mass index (kg/m2) in the AGA, SGA, and FGR groups were 25.26 ± 8.40 / 26.57 ± 4.37; 25.04 ± 8.44 / 26.09 ± 3.94; and 25.48 ± 7.52 / 26.24 ± 4.66, respectively (p > 0.05). The maternal serum vitamin D levels (mean ± SD) of the AGA, SGA, and FGR groups were 22.47 ± 8.35 ng/mL, 24.80 ± 10.76 ng/mL, and 23.61 ± 9.98 ng/mL, respectively, but without significant differences between the groups (p = 0.672). Maternal serum vitamin D levels did not present significant differences among pregnant women with AGA, SGA, or FGR fetuses between 26 and 36 weeks of gestation according to EFW.

Intrapartum Fetal Electrocardiogram in Small- and Large-for-Gestational Age Fetuses.

This study aimed to evaluate whether intrapartum fetal electrocardiogram (ECG) tracings with ST-elevation or depression occur more frequently in each stage of labor in small-for-gestational age (SGA) or large-for-gestational age (LGA), as compared with appropriate-for-gestational age (AGA) fetuses. We conducted a secondary analysis of a large, multicenter trial in which laboring patients underwent fetal ECG waveform-analysis. We excluded participants with diabetes mellitus and major fetal anomalies. Birth weight was categorized as SGA (<10th percentile), LGA (>90th percentile), or AGA (10-90th percentile) by using a gender and race/ethnicity specific nomogram. In adjusted analyses, the frequency of ECG tracings with ST-depression or ST-elevation without depression was compared according to birthweight categories and labor stage. Our study included 4,971 laboring patients in the first stage and 4,074 in the second stage. During the first stage of labor, there were no differences in the frequency of ST-depression in SGA fetuses compared with AGA fetuses (6.7 vs. 5.5%; adjusted odds ratio [aOR]: 1.41, 95% confidence interval [CI]: 0.93-2.13), or in ST-elevation without depression (35.8 vs. 34.1%; aOR: 1.17, 95% CI: 0.94-1.46). During the second stage, there were no differences in the frequency of ST-depression in SGA fetuses compared with AGA fetuses (1.6 vs. 2.0%; aOR: 0.69, 95% CI: 0.27-1.73), or in ST-elevation without depression (16.2 vs. 18.1%; aOR: 0.90, 95% CI: 0.67-1.22). During the first stage of labor, there were no differences in the frequency of ST-depression in LGA fetuses compared with AGA fetuses (6.3 vs. 5.5%; aOR: 0.97, 95% CI: 0.60-1.57), or in ST-elevation without depression (33.1 vs. 34.1%; aOR: 0.80, 95% CI: 0.62-1.03); during the second stage of labor, the frequency of ST-depression in LGA compared with AGA fetuses (2.5 vs. 2.0%, aOR: 1.36, 95% CI: 0.61-3.03), and in ST-elevation without depression (15.5 vs. 18.1%; aOR: 0.83, 95% CI: 0.58-1.18) were similar as well. The frequency of intrapartum fetal ECG tracings with ST-events is similar among SGA, AGA, and LGA fetuses. · SGA and LGA neonates are at increased risk of cardiac dysfunction.. · Fetal ECG has been used to evaluate fetal response to hypoxia.. · Fetal ST-elevation and ST-depression occur during hypoxia.. · Frequency of intrapartum ST-events is similar among SGA, AGA and LGA fetuses..

Growth Velocity and Doppler Evaluation to Predict Nonreassuring Fetal Heart Rate at Birth in Low-Risk Women: A Prospective, Longitudinal Study

Introduction: This study investigated whether fetal growth deceleration in term, appropriate-for-gestational-age (AGA) fetuses is associated with placental insufficiency and nonreassuring fetal heart rate (NRFHR) at birth. Methods: In this prospective study, 246 low-risk, singleton pregnancies at term with AGA fetuses were recruited. Correlation between decreased growth velocity (decline in estimated fetal weight [EFW] percentile), low EFW (EFW^Q1 = latest EFW between 11 and 25% percentiles), umbilical artery (UA) pulsatility index (PI), middle cerebral artery (MCA) PI, and cerebro-placental ratio (CPR) with cesarean and instrumental deliveries due to NRFHR were tested. Results: The median change between fetal weight estimates (percentiles/week) was +0.49% (95% CI: −4 to +5%). Ten percent had decreased EFW percentile >3.5%/week. Fetal growth velocity/week was associated with MCA (r = 0.21, p < 0.001) and CPR (r = 0.24, p < 0.001) and inversely correlated with UA PI (r = −0.28, p < 0.001). NRFHR and cesarean section (CS) rates due to NRFHR were associated with decreased growth velocity, EFW^Q1, and low CPR. The combination of abnormal CPR with decreased growth velocity occurred in 12 pregnancies, of which 5 (42%) had urgent CS due to NRFHR. The combination of abnormal CPR with EFW^Q1 occurred in 9 pregnancies, of which 4 (44%) had urgent CS due to NRFHR. These combinations increased the likelihood ratio of CS due to NRFHR two-fold (8.41; 2.54–24.5) but did not significantly alter the number needed to treat by elective CS (3.78–4.68). Conclusion: Fetal growth velocity, EFW between 10 and 25th percentiles (EFW^Q1), and abnormal CPR improves prediction of unplanned CS due to NRFHR among term AGA fetuses. This should be considered when counseling about the delivery method.

Novel metabolic marker Afamin: A predictive factor for Large-for-Gestational-Age (LGA) fetus estimation in pregnancies with gestational diabetes mellitus?

Gestational diabetes mellitus (GDM) affects both maternal and fetal/infant outcomes during and after pregnancy. The reason for the high incidence of large-for-gestational-age (LGA) infants in GDM patients despite close monitorization of glucose levels with early detection of the disease remains unclear to date. Our study aims to investigate the levels of the third-trimester novel marker afamin in GDM versus non-GDM pregnancies in terms of glycemic control status and their utility in the prediction of LGA fetuses. This prospective case-control study analysis involved 49 pregnant women with GDM diagnosed using the 75-g oral glucose tolerance test (75-g OGTT) and 40 randomly selected women with a similar body mass index (BMI) and gestational age (GA). Blood samples were collected in the third trimester of pregnancy. The afamin level was determined using a human afamin ELISA kit according to the manufacturer's procedure. There was no significant difference found in BMI or GA of patients. Third-trimester afamin levels were 93.91 mg/L and 83.87 mg/L in the GDM and non-GDM groups, respectively (p=0.625). Afamin values of patients were not correlated with age, BMI, GA, HgA1c, 75-g OGTT fasting and 75-g OGTT 1-hour, or 75-g OGTT 2-hour values (p>0.05). GDM patients with LGA fetuses had significantly higher afamin values than patients with appropriate-for-gestational-age (AGA) fetuses (120.8 mg/L versus 91.26 mg/L, respectively). Between GDM patients with either LGA or AGA fetuses, there was no statistically significant difference found for age, BMI, GAs, insulin dose, 75-g OGTT results, or HgA1c values. Our findings conclude that novel marker afamin levels could predict the risk of LGA infants independently of glycemic control status and provide insight into the pathogenesis of LGA fetuses, thus helping to reduce the risk of associated complications.