Late-onset Fetal Growth Restriction Research Articles

The genetics and clinical outcomes in 151 cases of fetal growth restriction: A Chinese single-center study

ObjectiveTo determine the detection rate of chromosomal abnormalities and pregnancy outcomes in fetuses with intrauterine growth restriction.Study designA total of 151 fetal samples with intrauterine growth restriction were were divided into the isolated fetal growth restriction (FGR) group, FGR group with structural malformation, and FGR group with non-structural malformation, according to ultrasound abnormalities. The enrolled patients were divided into an early onset FGR group (<32 weeks) and a late-onset FGR group (≥32 weeks). Chromosomal karyotype and microarray analyses were performed and pregnancy outcomes were monitored.ResultsThe karyotypes of 122 patients were analyzed. Four patients exhibited abnormal chromosome numbers or structures. Variations in copy number were detected in 151 cases; 19 cases were found to have chromosomal abnormalities, with a positivity rate of 12.6 %. There was one trisomy in 18 cases, one trisomy in 21 cases, eight pathogenic copy number variations (CNVs), and nine CNVs of unknown clinical significance. The detection rate of FGR combined with structural malformation was significantly higher than that of isolated FGR group. The detection rate of FGR with structural malformations was significantly higher than that with non-structural malformations. The positive detection rate in the FGR group was similar to that in the FGR group with non-structural malformations, with no statistical significance. Chromosomal abnormalities were detected in 17 patients with early onset FGR, with a positivity rate of 13.8 %. Two cases of chromosomal abnormalities were detected in the late-onset FGR group, with a positive rate of 7.1 %, with no statistical significance. A total of 151 fetuses with FGR were followed up for pregnancy outcomes, resulting in 36 cases of pregnancy termination and 13 cases of loss to follow-up. Among the 102 delivered fetuses, six exhibited delayed growth and development, one presented with hypospadias, and another failed the hearing screening. The remaining 94 fetuses demonstrated normal growth and development.ConclusionsThis study confirms the value of CNV detection in fetuses and dynamic ultrasound monitoring for fetuses with intrauterine growth restriction.

Etiologic evaluation and pregnancy outcomes of fetal growth restriction (FGR) associated with structural malformations

This study aimed to evaluate the etiology and pregnancy outcomes of fetuses underwent invasive prenatal diagnosis for fetal growth restriction (FGR) accompanied by structural malformations. Data from 130 pregnancies referred for prenatal diagnosis for FGR accompanied by structural malformations were obtained between July 2011 and July 2023. Traditional karyotyping was conducted for all the subjects. A total of 37 (28.5%) cases of chromosomal abnormalities were detected by karyotyping, including 30 cases of numerical anomalies and seven cases of unbalanced structural anomalies. Trisomy 18 was the most common abnormalities, accounting for 51.4%, significantly higher than any other chromosomal abnormality. The cohort was predominantly comprised of early-onset FGR (88.5%) compared to late-onset FGR (11.5%). The incidences of chromosomal abnormalities in this two groups were 29.6% (34/115) and 20.0% (3/15), respectively (p > 0.05). The majority (74.6%, 97/130) of the cohort were affected by a single system malformation, with chromosomal abnormalities found in 19.6% (19/97) of cases. In pregnancies of structural malformations involving two and multiple systems, the frequencies were 56.5% (13/23), and 50.0% (5/10), respectively. Single nucleotide polymorphism array (SNP array) was performed in parallel for 65 cases, revealing additional 7.7% cases of copy number variants (CNVs) compared to karyotyping. Polymerase chain reaction (PCR) was used for detection of cytomegalovirus (CMV) DNA in 92 cases. All fetuses with FGR associated with two or more system malformations were either terminated or stillborn, irrespective of chromosomal aberrations. Conversely, 71.8% of pregnancies with a single-system malformation and normal genetic testing results resulted in live births. Furthermore, two (2.2%) cases tested positive for CMV DNA, leading to one termination and one case of serious developmental disorder after birth. Our study suggests that structural malformations associated with FGR are more likely to affect a single organ system. When multiple systems are involved, the incidence of chromosomal abnormalities and termination rates are notably high. We advocate for the use of CMA and CMV DNA examinations in FGR cases undergo invasive prenatal diagnosis, as these tests can provide valuable insights for etiological exploration and pregnancy management guidance.

Evaluation of systemic immune-inflammation index for predicting late-onset fetal growth restriction.

To determine a cut-off value for systemic immune-inflammation index (SII) (neutrophil × platelet/lymphocyte) in the prediction of fetal growth restriction (FGR). This case-control study was conducted retrospectively at the Obstetrics-Gynecology and Perinatology Clinics of Etlik Zubeyde Hanim Women's Health Education and Training Hospital. Singleton pregnant women with late-onset FGR who were followed up in outpatient clinics or hospitalized and whose pregnancy resulted at our hospital were included in the study group (group I). Healthy early and full-term singleton pregnant women with spontaneous labor who were followed up in the same hospital and whose pregnancy resulted at the same hospital were included in the control group (group II). Receiver-operating characteristic curves were used to assess the performance of SII value in predicting FGR. We recruited 79 cases (pregnant with late-onset fetal growth restriction) and 79 controls (healthy pregnant), matched for age, body mass index, and parity. ΔSII was statistically significantly higher in the pregnant with late-onset FGR compared with healthy pregnant (123 vs -65; p = 0.039). The values in ROC curves with the best balance of sensitivity/specificity were > 152 109/L (49% sensitivity, 70% specificity) and > 586 109/L (27% sensitivity, 90% specificity) for late-onset FGR. Higher ΔSII levels in maternal blood indicate an inflammatory process causing FGR. The cut-off value for ΔSII (> 586 109/L) at 90% specificity can be used as a screening test. In the presence of ΔSII levels > 586 109/L (27% sensitivity and 90% specificity), the physicians should be more cautious about risk for FGR. Therefore, pregnant women at risk for FGR should be checked more frequently and monitored closely. However, further studies are needed to confirm our findings.

Fetal Femoral Artery Doppler Evaluation in Late-Onset Fetal Growth Restriction: A Case-Control Study

Objective: To compare the femoral artery and other ultrasonographic Doppler measurements between fetuses with late-onset fetal growth restriction and uncomplicated fetuses.&#x0D; Material and method: This prospective cohort study was conducted with 168 patients, including 83 pregnancies presenting with late-onset fetal growth restriction and 85 uncomplicated control pregnancies at similar gestational weeks. The study group was further divided into two according to the neonatal intensive care unit requirements. Demographic characteristics, obstetric characteristics, femoral artery and other ultrasonographic Doppler measurements, and pregnancy outcomes were compared between the groups.&#x0D; Results: Uterine artery pulsatility index, umbilical artery systolic/diastolic ratio, and peak systolic velocity of the middle cerebral artery were similar between the study and control groups. However, while the middle cerebral artery pulsatility index was significantly lower in the study group, the femoral artery pulsatility index value was significantly higher (p

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.

Clinical significance of three-dimensional power Doppler combined with two-dimensional Doppler ultrasonography for evaluating fetal growth restriction

Objectives To assess the predictive accuracy of three-dimensional (3D) power Doppler combined with two-dimensional (2D) Doppler ultrasonography in detecting fetal growth restriction (FGR). Methods The study was conducted on singleton pregnancies presenting for growth ultrasound examinations between 20 and 40 weeks of gestation. 63 patients with FGR were enrolled and matched 1:1.8 for gestational age with normal fetuses. Both groups were further divided into subgroups, with 32 weeks as the threshold—early-onset and late-onset FGR groups, and corresponding control groups. Conventional 2D Doppler parameters and standardized 3D power Doppler measurements of the placenta, including vascularization index (VI), flow index (FI), and vascularization-flow index (VFI) were obtained for each patient. Results (1) The average gestational weeks of delivery and birth weight of newborns in early-onset and late-onset FGR case groups were lower than those in control groups, while the incidence of placenta previa and adverse pregnancy outcomes were higher than those in control groups. (2) The biparietal diameter, head circumference, abdominal circumference, femur length, estimated fetal weight, middle cerebral artery systolic/diastolic velocity ratio (S/D), pulsatility index (PI), resistance index (RI), and placental blood perfusion indices of vascular index (VI), flow index (FI), vascular flow index (VFI), and cerebro-placental ratio (CPR) of the early-onset and late-onset FGR case groups were all lower than those of the control group. Moreover, the S/D, PI, and RI of the umbilical and uterine arteries were higher than those of the corresponding control group. (3) For early-onset FGR, the area under the curve (AUC) of the umbilical artery PI was the largest (0.861), exhibiting the highest predictive value. When combined with the placental blood perfusion index, the AUC was 0.789. For late-onset FGR, the AUC of the CPR was 0.861. After integrating the placental blood perfusion index, the AUC increased to 0.877. The positive likelihood ratio (PLR) of combined 2D Doppler indexes (21.938) and negative likelihood ratio (NLR) of VFI (0.565) were the highest in the early-onset FGR group. The PLR of combined 3D Doppler indexes (8.536) and NLR of VFI (0.557) were the highest in the late-onset FGR group. Conclusions The combination of 3D Doppler indices with 2D Doppler ultrasonography demonstrated superior predictive value in diagnosing late-onset FGR compared to other conventional indicators. The 3D Dower index, VFI, has a good true-negative predictive value for both early- and late-onset FGR.

Effects of uterine Doppler on midbrain growth and cortical development in late onset fetal growth restricted fetuses: a prospective cross-sectional study

Objective To investigate midbrain growth, including corpus callusum (CC), cerebellar vermis (CV) and cortical development in late fetal growth restriction (FGR) depending on uterine artery (UtA) Pulsatility Index (PI) values. Methods This was a prospective study including singleton fetuses with late FGR characterized by abnormal cerebral placental ratio (CPR). According to UtA PI values, the FGR fetuses were subdivided into normal ≤95th centile) and abnormal (>95th centile). Neurosonography was performed at 33–44 weeks of gestations to assess CC and CV lengths and the depth of Sylvian fissure (SF), parieto-occipital (POF) and calcarine fissures (CF). Neurosonographic variables were normalized for fetal head circumference size. Results The study cohort included 60 fetuses with late FGR, 39 with normal UtA PI and 21 with abnormal PI values. The latter group showed significant differences in CC (median (interquartile range) normal 35.9 (28.49–45.53) vs abnormal UtA PI 25.31(19.76–35.13) mm; p < 0.0022), CV (normal 25.78 (18.19–29.35) abnormal UtA PI 17.03 (14.07–24.16)mm; p = 0.0067); SF (normal 10.58 (8.99–11.97)vs abnormal UtA PI 7.44 (6.23–8.46) mm; p < 0.0001), POF (normal 6.85 (6.35–8.14) vs abnormal UtA PI 4.82 (3.46–7.75) mm; p < = 0.0184) and CF (normal 04.157 (2.85–5.41) vs abnormal UtA PI 2.33 (2.49–4.01)); p < 0.0382). Conclusions Late onset FGR fetuses with abnormal UtA PI showed shorter CC and CV length and delayed cortical development compared to those with normal uterine PI. These findings support the existence of a link between abnormal brain development and changes in utero placental circulation.

Single-cell RNA sequencing reveals association of aberrant placental trophoblasts and FN1 reduction in late-onset fetal growth restriction

IntroductionFetal growth restriction (FGR) can lead to fetal mental development abnormalities, malformations, and even intrauterine death. Defects in the trophoblasts at the maternal-fetal interface may contribute to FGR. However, the impact of trophoblasts on FGR is still not well understood. Therefore, the objective of this study is to characterize the heterogeneity of placental cells at the single-cell level and investigate the role of trophoblast subtypes in the pathogenesis of FGR at the cellular and molecular levels. MethodsSingle-cell RNA sequencing was performed on the maternal side of placentas from two normal pregnant women and two pregnant women with FGR. Lentivirus transfection was used to establish a FN1 knockout model in trophoblast HTR-8-Svneo cells. The effect of FN1 knockout on cell migration and invasion of HTR-8-Svneo cells was assessed through wound healing and transwell assays. ResultsNine cell types were annotated in 39,161 cells derived from single-cell RNA sequencing. The FGR group exhibited a decrease in the percentage of trophoblasts, especially in subtype of extravillous trophoblasts (EVTs). The expression of FN1 was reduced in trophoblasts and EVTs. Furthermore, the protein expression levels of FN1 in the placentas of FGR patients were significantly lower than those of normal pregnant women. The cell migration and invasion ability of HTR-8-Svneo cells were inhibited after the knockdown of FN1. DiscussionThe dysregulation of the trophoblast subtype-EVTs is involved in placental dysplasia related to FGR. The association between aberrant placental trophoblasts and reduced FN1 expression may contribute to insufficient remodeling of spiral arteries and the formation of FGR.

Does Amnioumbilicocerebral Ratio Better Predict Adverse Neonatal Outcomes in Comparison to Other Doppler Parameters in Late-Onset Fetal Growth Restriction?

Does Amnioumbilicocerebral Ratio Better Predict Adverse Neonatal Outcomes in Comparison to Other Doppler Parameters in Late-Onset Fetal Growth Restriction?

Evaluation of carotid artery Doppler measurements in late-onset fetal growth restriction: a cross-sectional study

Background/Aim: It has been reported that both the internal carotid artery (ICA) and the common carotid artery (CCA) are associated with hypoxia, also observed in late-onset fetal growth restriction (FGR). However, it has not yet been investigated whether these Doppler measurements differ in cases of late-onset FGR. This study evaluated the ICA and the CCA Doppler parameters in late-onset FGR fetuses and compared these measurements with those of healthy fetuses. Methods: This cross-sectional observational study comprised 75 singleton pregnancies diagnosed with late-onset FGR between the 32nd and 37th weeks of gestation, alongside 75 healthy fetuses paired 1:1 based on obstetric history and gestational age between June 2022 and May 2023. The Delphi consensus of 2016 was used for the definition of late-onset FGR. The exclusion criteria were congenital anomalies, presence of any additional disease, maternal body mass index over 35 kg/m2, abdominal scars hindering ultrasound visualization, use of medications such as antenatal steroids, sympathomimetics, and indomethacin that affect vascular function, drug use, smoking during pregnancy, concurrent preeclampsia, and multiple pregnancies. Upon the patients' admission to the hospital, their demographic characteristics were documented, and ultrasonographic examinations and Doppler measurements were subsequently performed. The Doppler velocimetry of the umbilical artery (UA) encompassed measurements of the systolic to diastolic ratio (S/D), pulsatility index (PI), and peak systolic velocity (PSV). The carotid artery Doppler velocimetry of the middle cerebral artery (MCA), ICA, and CCA encompassed measurements of the PI, resistance index (RI), and PSV. We assessed the diagnostic performance of Doppler measurements for late-onset FGR through receiver operating characteristic (ROC) analysis. Results: In the late-onset FGR group, the mean UA-SD was higher (2.7 [0.6] vs. 2.5 [0.5], P=0.006), and the mean UA-PI (0.8 [0.2] vs. 0.9 [0.2], P=0.011) and mean PSV (35.6 [8.2] vs. 41.1 [7.1], P&lt;0.001) were lower compared to the control group. In the late-onset FGR group, carotid Doppler measurements were more pronounced than UA Doppler measurements. Moreover, ICA Doppler measurements exhibited superior diagnostic performance in predicting late-onset FGR compared to other Doppler measurements (Area under the curve [AUC]=0.777, P&lt;0.001 for ICA-PI; AUC=0.751, P&lt;0.001 for ICA-RI; AUC=0.749, P&lt;0.001 for ICA-PSV). Conclusion: In fetuses with late-onset FGR, UA Doppler measurements showed minimal differences compared to healthy fetuses, but differences in carotid Doppler measurements, especially in the ICA, were more pronounced. Therefore, in the management of fetuses suspected of having late-onset FGR, a more detailed Doppler examination might be required.

Effect of low-molecular-weight heparin on placenta-mediated fetal growth restriction in a tertiary referral hospital: A 7-year retrospective cohort study.

To investigate the effect of low-molecular-weight heparin (LMWH) on placenta-mediated fetal growth restriction (FGR). A cohort of 570 pregnant women diagnosed with placenta-mediated FGR were enrolled from January 1, 2015 through to December 31, 2021. A birth database, including demographic data, antenatal complications, and detailed delivery and newborn data, was created to collect variables from the Hospital Information System (HIS) Database. The unique personal registration number, assigned to each patient on first registration with HIS in the West China Second University Hospital, was used to link these patients. LMWH use was defined as at least 1-week prescription from diagnosis of placenta-mediated FGR. Pregnant women received LMWH (Enoxaparin 4000 IU/day) by self-administered subcutaneous injection only when they agreed and signed informed consent. Primary outcome was intrauterine fetal death after 20 weeks of pregnancy. Secondary outcomes included preterm birth (PB), Apgar score less than 7 at 1 min, admission to neonatal intensive care unit (NICU), and birth weight. Logistic regression analysis was conducted to compute adjusted odds ratio (aOR) with 95% confidence intervals (CI) for outcomes. After controlling for confounders, LMWH use was associated with a decreased risk of intrauterine fetal death (aOR 2.49, 95% CI 1.35-4.57, P = 0.003), PB before 37 weeks of pregnancy (aOR 3.35, 95% CI 2.14-5.23, P < 0.001), PB before 34 weeks of pregnancy (aOR 2.25, 95% CI 1.36-3.74, P = 0.002), Apgar score less than 7 at 1 min (aOR 2.25, 95% CI 1.36-3.74, P = 0.002), NICU admission (aOR 2.29, 95% CI 1.48-3.55, P < 0.001). Using LMWH increased the mean birth weight in PB before 32 weeks of pregnancy (mean ± standard deviation [SD] 1126.4 ± 520.0 g, P = 0.020), PB before 37 weeks of pregnancy (mean ± SD 1563.9 ± 502.7 g, P = 0.019), early-onset FGR (mean ± SD 2125.2 ± 665.7 g, P < 0.001), late-onset FGR (mean ± SD 2343.4 ± 507.9, P < 0.001), and non-severe FGR (mean ± SD 2231.1 ± 607.2 g, P < 0.001). Use of LMWH can significantly improve the fetal and neonatal outcomes among pregnant women with placenta-mediated FGR, particularly reducing the risk of intrauterine fetal death.

Placental pathology in early-onset fetal growth restriction: insights into fetal growth restriction mechanisms.

Early-onset fetal growth restriction (FGR), an identifiable variant of FGR, exhibits divergences in its severity, management, and placental pathologies when juxtaposed with late-onset FGR. The objective of this cross-sectional investigation was to scrutinize placental pathologies in pregnancies afflicted by early-onset FGR, emphasizing a comparative analysis between cohorts with and without preeclampsia (PE). The study encompassed a cohort of 85 expectant mothers who received a diagnosis of early-onset FGR. Rigorous histopathological (HP) and immunohistochemical (IHC) assessments were conducted on the placentas. Comparative analyses were performed, distinguishing between individuals diagnosed with both PE and early-onset FGR, and those presenting normotensive early-onset FGR. HP analysis unveiled a multitude of shared placental lesions, encompassing retroplacental hemorrhage, expedited villous maturation, infarctions, and calcification-associated fibrin deposits. IHC investigations displayed affirmative immunoreactivity for anti-hypoxia-inducible factor (HIF) and anti-vascular endothelial growth factor (VEGF) antibodies within the placental infarcted villitis. Moreover, noteworthy variances in placental measurements and distinctive lesions were discerned when comparing the PE and early-onset FGR cohort with the normotensive group. Maternal malperfusion emerged as a pivotal determinant linked to placental lesions in pregnancies affected by early-onset FGR. Remarkably, the occurrence of infarctions, specifically delayed infarctions, exhibited a noteworthy correlation with PE. These findings accentuate the significance of pursuing additional research endeavors aimed at unraveling the intricate mechanisms governing maternal malperfusion and its consequential influence on placental health in the context of early-onset FGR, with particular attention to the interplay with PE.

Relationship between kisspeptin levels in the third trimester and late-onset fetal growth restriction: A case-control study

IntroductionWe aimed to investigate whether maternal serum kisspeptin levels are associated with late-onset FGR and contribute to adverse perinatal outcomes. MethodIn this case-control study, a total of 90 pregnant women admitted to the perinatology clinic were enrolled. Forty-five of them were diagnosed with FGR and 45 women with healthy pregnancies formed the control group. Maternal serum levels of kisspeptin 1 were compared. ResultsMedian kisspeptin1 serum levels were higher in the group of patients with FGR according to gestational age than in the control group [79.4(3.9–230.2) pg/mL vs. 39.8(0.4–188.3) pg/mL; p = 0.001]. The optimal cut-off value for kisspeptin1 was 30.32 pg/mL, with a positive predictive value of 64.6% (95% CI; 0.54–0.86), negative predictive value of 87.5% (95% CI; 0.44–0.72), positive likelihood ratio 1.75 (95% CI; 1.31–2.32), negative likelihood ratio 0.14 (95% CI; 0.04–0.44). DiscussionKisspeptin1 differed significantly in late-onset FGR compared with the control group. This difference from the control group can be used to estimate late-onset FGR.

Assessment of late on-set fetal growth restriction using SMI (superb microvascular imaging) Doppler.

The identification of late-onset fetal growth restriction (FGR) fetuses remains a challenge, given the difficulty to distinguish them from healthy small for gestational age (SGA) fetuses. Given the limitations of conventional Doppler for the identification of placental insufficiency, the appearance of superb microvascular imaging (SMI) Doppler seems promising. Our main objective was to evaluate the diagnostic capability of SMI Doppler for the detection of placental insufficiency findings. A prospective observational study was conducted at a tertiary care center, including 51 patients who had been diagnosed with late on-set SGA or FGR. A placental ultrasonographic evaluation was carried out using SMI Doppler. Patients were sorted into two groups attending to the histologic evaluation of the placentas after delivery: Group 1 (21 cases), Normal group; and Group 2 (30 cases), FGR group. Placentas in the FGR group had lower peak systolic velocity (PV) values of the chorionic plate. The PV of the other vessels were consistently lower in the FGR group that in the normal group, although without reaching statistical significance. The PV of the chorionic plate measured with SMI Doppler, have the capacity to identify placental insufficiency findings. Ultrasonographic placental assessment using SMI Doppler appears to be a useful technique for the evaluation of suspected late on-set placental insufficiency.

Management of late-onset fetal growth restriction: pragmatic approach.

There is limited prospective evidence to guide the management of late-onset fetal growth restriction (FGR) and its differentiation from small-for-gestational age. The aim of this study was to assess prospectively a novel protocol in which ultrasound criteria were used to classify women with suspected late FGR into two groups: those at low risk, who were managed expectantly until the anticipated date of delivery, and those at high risk, who were delivered soon after 37 weeks of gestation. We also compared the outcome of this prospective cohort with that of a historical cohort of women presenting similarly with suspected late FGR, in order to evaluate the impact of the new protocol. This was a prospective study of women with a non-anomalous singleton pregnancy at ≥ 32 weeks' gestation attending a tertiary hospital in London, UK, between February 2018 and September 2019, with estimated fetal weight (EFW) ≤ 10th centile, or EFW > 10th centile in addition to a decrease in fetal abdominal circumference of ≥ 50 centiles compared with a previous scan, umbilical artery Doppler pulsatility index > 95th centile or cerebroplacental ratio < 5th centile. Women were classified as low or high risk based on ultrasound and Doppler criteria. Women in the low-risk group were delivered by 41 weeks of gestation, unless they subsequently met high-risk criteria, whereas women in the high-risk group (EFW < 3rd centile, umbilical artery Doppler pulsatility index > 95th centile or EFW between 3rd and 10th centiles (inclusive) with abdominal circumference drop or abnormal Dopplers) were delivered at or soon after 37 weeks. The primary outcome was adverse neonatal outcome and included hypothermia, hypoglycemia, neonatal unit admission, jaundice requiring treatment, suspected infection, feeding difficulties, 1-min Apgar score < 7, hospital readmission and any severe adverse neonatal outcome (perinatal death, resuscitation using inotropes or mechanical ventilation, 5-min Apgar score < 7, metabolic acidosis, sepsis, and cerebral, cardiac or respiratory morbidity). Secondary outcomes were adverse maternal outcome (operative delivery for abnormal fetal heart rate) and severe adverse neonatal outcome. Women managed according to the new protocol were compared with a historical cohort of 323 women delivered prior to the implementation of the new protocol, for whom management was guided by individual clinician expertise. Over 18 months, 321 women were recruited to the prospective cohort, of whom 156 were classified as low risk and 165 were high risk. Adverse neonatal outcome was significantly less common in the low-risk compared with the high-risk group (45% vs 58%; adjusted odds ratio (aOR), 0.6 (95% CI, 0.4-0.9); P = 0.022). There was no significant difference in the rate of adverse maternal outcome (18% vs 24%; aOR, 0.7 (95% CI, 0.4-1.2); P = 0.142) or severe adverse neonatal outcome (3.8% vs 8.5%; aOR, 0.5 (95% CI, 0.2-1.3); P = 0.153) between the low- and high-risk groups. Compared with women in the historical cohort classified retrospectively as low risk, low-risk women managed under the new protocol had a lower rate of adverse neonatal outcome (45% vs 58%; aOR, 0.6 (95% CI, 0.4-0.9); P = 0.026). Appropriate risk stratification to guide management of late FGR was associated with a reduced rate of adverse neonatal outcome in low-risk pregnancies. In clinical practice, a policy of expectantly managing women with a low-risk late-onset FGR pregnancy at term could improve neonatal and long-term development. Randomized controlled trials are needed to assess the effect of an evidence-based conservative management protocol for late FGR on perinatal morbidity and mortality and long-term neurodevelopment. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Correlations of Placental Histopathology, Neonatal Outcome, and Cardiotocogram Baseline Variability and Acceleration Patterns in the Growth Restricted Preterm Population.

To evaluate the possible connections of cardiotocography (CTG) signs with neonatal outcome and placental histopathology between growth restricted preterms. Placental slides, baseline variability, and acceleration patterns of cardiotocograms, and neonatal parameters were studied retrospectively. Placental histopathological changes were diagnosed according to the Amsterdam criteria; percentage of intact terminal villi and capillarization of villi were also studied. 50 cases were analyzed: 24 were early-onset fetal growth restriction (FGR), 26 were late-onset FGR. Reduced baseline variability was related to poor neonatal outcome; lack of accelerations similarly had associations with poor outcomes. Maternal vascular malperfusion, avascular villi, VUE, and chorangiosis were more common in the background of reduced baseline variability and absence of accelerations. Lower percentage of intact terminal villi was significantly associated with lower umbilical artery pH, higher lactate levels, and reduced baseline variability on CTG; absence of accelerations was correlated with decreased capillarization of terminal villi. Baseline variability and absence of accelerations seem to be useful and reliable markers in predicting poor neonatal outcome. Maternal and fetal vascular malperfusion signs, decreased capillarization, and lower percentage of intact villi in placenta could contribute to pathologic CTG signs and poor prognosis.

Prenatal Predictors of Neurobehavioral Outcome in Children with Fetal Growth Restriction at 6 Years of Age: A Retrospective Cohort Study

(1) Background: Fetal growth restriction (FGR) increases the risk of adverse neurodevelopmental outcomes, especially in preterm newborns. This study aims to describe the behavioral results of FGR at 6 years of age and to demonstrate the relationship of certain predictive factors with this development. (2) Methods: This retrospective cohort study included 70 children born in 2015 at the University Hospital Carlos Haya, Málaga, Spain who had been exposed to FGR during pregnancy; neonatal and infant data were recorded retrospectively. Children were assessed prospectively at 6 years of age by means of a strengths and difficulties questionnaire (SDQ) to study behavioral outcomes. (3) Results: We demonstrated that there are higher behavioral disability rates in children exposed to FGR during pregnancy and, in particular, high rates of hyperactivity or conduct problems. We also proved a negative relationship between the birth weight percentile and the total behavioral scale score, along with a positive correlation between hyperactivity and the emotional and behavioral scales. Learning difficulties were more frequent in early-onset FGR than in late-onset FGR. (4) Conclusions: Our study of behavioral development has demonstrated higher behavioral disability rates in children with FGR at 6 years of age; specifically, high rates of hyperactivity or conduct problems. At the same time, we have proved a negative relationship between the birth weight percentile and the total behavioral scale score.

The role of different Doppler parameters in predicting adverse neonatal outcomes in fetuses with late-onset fetal growth restriction.

The aim of this study is to clarify the role of different Doppler parameters such as umbilicocerebral ratio (UCR), cerebroplacentouterine ratio (CPUR), aortic isthmus, renal artery, and umbilical vein flow Doppler in predicting adverse neonatal outcomes in fetuses with late -onset fetal growth restriction. The study included all patients diagnosed with fetal growth restriction at 32-39 weeks' gestation between 01/02/2020 and 01/02/2022 and treated at the Department of Obstetrics and Gynecology, Inonu University School of Medicine. Patients included in the study had a median gestational week at delivery of 37 (minimum 33+0-maximum 39+0), median CPR of 1.42 (minimum-maximum 0.43-3.57), and median UCR of 0.7 (minimum-maximum 0.28-2.3). Receiver operating characteristic analysis was performed to determine the performance of the measured obstetric Doppler parameters in predicting the development of adverse neonatal outcomes. Umbilical venous blood flow showed the best performance in predicting adverse neonatal outcomes [area under the curve 0.952, 95% confidence interval (CI) 0.902-0.981, p<0.001]. Multivariate logistic regression analysis showed that fetuses with abnormal CPUR had a 4.5-fold (95% CI 0.084-0.583, p=0.02) increased risk of adverse neonatal outcome, whereas fetuses with abnormal umbilical venous flow had a 1.07-fold (95% CI 0.903-0.968, p<0.001) increased risk of adverse neonatal outcome. The results of this study demonstrate that the use of UCR, CPUR, umbilical venous flow, and aortic isthmus PI Doppler parameters along with umbilical artery PI and CPR are effective in predicting adverse neonatal outcomes in fetuses with late -onset fetal growth restriction.

Diastolic deceleration area in the fetal MCA: a new Doppler parameter

Objective Doppler velocimetry has been widely used throughout the years as a valuable tool in the follow-up and prognosis of various pregnancy complications. Numerous Doppler indices have been introduced to qualitatively describe fetal blood flow. Currently, the Pulsatility index (PI) is the most widely used index for this purpose. In current clinical practice, middle cerebral artery (MCA) PI measurement is commonly used to assess fetal well-being, especially in late-onset fetal growth restriction (FGR). However, existing evidence suggests that MCA PI alone is inferior to the ratio between MCA and umbilical artery (UA) pulsatility indices in predicting adverse perinatal and neonatal outcomes. When comparing normal and abnormal MCA Doppler waveforms, it is evident that most changes appear in the diastolic part of the heart cycle. Therefore, the PI, which contains elements from both systole (peak systolic velocity–PSV) and diastole (end-diastolic velocity), may not be the most effective tool for quantifying fetal brain sparing (BS). Methods We hypothesize that another measurement modality that focuses predominantly on the diastole could be more efficient for evaluating the amount of vasodilatation. In ultrasound velocimetry of larger blood vessels, there is a well-known phenomenon called “dicrotic notch” (DN), which appears on the declining part of each Doppler waveform and can be used to precisely pinpoint the end of systole and the start of diastole. We hypothesized that the extent of cerebral vasodilation can be more accurately assessed by measuring the area between the dicrotic notch (DN) and the end-diastolic velocity (which we refer to as the “diastolic deceleration area–DDA”). In this study, we introduced a new Doppler parameter along with a rationale for DDA measurement in the fetal MCA. We also defined third-trimester nomograms and provided a preliminary assessment of the correlation between DDA and fetal oxygen deficiency. Results Our findings suggest that the DDA may serve as an independent instrument for identifying hypoxia during late pregnancy, either on its own or in conjunction with other Doppler and cardiotocography modalities. Conclusion However, before incorporating DDA into clinical practice, it is crucial to conduct further research and validation studies with larger sample sizes and more diverse populations. This would help assess the generalizability of the results and establish optimal cutoff points for DDA in various clinical settings. It is also important to prospectively study the role of DDA in early- and late-onset fetal growth restriction (FGR), Rh-isoimmunization/anemia, preeclampsia, gestational diabetes, and other pregnancy complications. In fact, we believe that the concept of measuring specific areas in arterial Doppler velocimetry indices could have significant implications not only in fetal medicine and obstetrics, but also in other areas of human and veterinary medicine.

Role of global sphericity index in evaluation of fetal cardiac remodeling in late onset fetal growth restriction and small for gestational age fetuses

Fetal growth restriction (FGR) fetuses develop cardiovascular remodeling and dysfunction and, in this process, heart first compensates by changing its shape from ellipsoid to spherical and then cardiac dysfunction follows. Our aim was to evaluate global sphericity index (GSI) after 32 weeks of gestation to evaluate this change in cardiac shape and correlate GSI changes associated with fetal growth abnormalities. This was a prospective study conducted at 32-38 weeks of gestation. Women were classified into three groups-Appropriate for gestational age (AGA), small for gestational age (SGA), late onset FGR (LO FGR) and GSI was measured and perinatal outcome studied. Out of 217 women, 131 were of AGA, 31 were SGA, 55 were of late onset FGR. SGA and late onset FGR groups had low GSI compared to AGA group. There was no significant difference in mean GSI between late onset FGR and SGA groups. Neonatal morbidity, adverse perinatal outcomes did not significantly differ with GSI in SGA and late onset FGR groups. This study showed that late gestation small fetuses develop early stages of cardiovascular remodeling as shown by GSI changes. These changes were independent of Doppler changes. This supports the concept that atleast a proportion of them are not constitutionally small but are true forms of FGR.