Expression levels and clinical significance of autophagy related proteins in placenta tissues of pregnant women with fetal growth restriction / 基础医学与临床

Objective To explore the expression and clinical significance of autophagy related proteins Beclin-1,microtubule-associated protein 1 light chain 3(LC3)in placenta tissues of pregnant women with fetal growth restric-tion(FGR).Methods A total of 40 pregnant women undergoing delivery due to FGR and 40 pregnant women un-dergoing normal delivery in the Second Affiliated Hospital of Zhengzhou University were enrolled as FGR group and healthy group between August 2022 and August 2023.The general clinical data in the two groups were collected.The levels of Beclin-1 and LC3 mRNA in placenta tissues were detected by PCR,and expressions of Beclin-1 and LC3 proteins were detected by immunohistochemistry.The differences in positive of Beclin-1 and LC3 proteins among patients with different clinical data were analyzed.Results The placental thickness,placental mass and neonatal weight in FGR group were lower than those in healthy group(P＜0.05).The mRNA levels of Beclin-1 and LC3 in FGR group were higher than those in healthy group(P＜0.05)and positive expression rates of Beclin-1 and LC3 proteins were significantly higher than those in healthy group(P＜0.05).There was significant difference in positive expression profile of Beclin-1 and LC3 proteins among patients with different placental thickness,placental mass and neonatal weight(P＜0.05).Conclusions The positive expressions of autophagy genes(Beclin-1 and LC3)are related to FGR,and their specific expression levels are closely related to fetal growth and development.

Clinical application status and research progress in fetal growth standards / 复旦学报（医学版）

Ultrasound measurement of fetal biological parameters is an important indicator for evaluating fetal intrauterine growth and development,and its corresponding fetal growth standards are important criteria for determining whether the measurement parameters are normal or have fetal growth restriction.There are classic regional standards of prenatal ultrasonic measurement that have been used for many years,as well as international standards that have received widespread attention in recent years.However,there is no unified global standard.This paper reviewed the development process and clinical application status of fetal growth standards,explore future research trends,with a view to providing reference value for clinical practice.

The Role of Cerebral-Placenta-Uterine Ratio in Predicting Late-Onset Fetal Growth Restriction / 实用妇产科杂志

Objective:To evaluate the efficacy of cerebral-placental-uterine ratio(CPUR)in predicting late-on-set fetal growth restriction(FGR).Methods:From May 2020 to May 2021,1255 women with singleton pregnancy who underwent prenatal examinations at the University of Hong Kong Shenzhen Hospital were selected for fetal growth and Doppler measurements at 35-37 +6 weeks of gestation.Pregnant women with birth weight of newbo-rns＜the 10th percentile were the FGR group.The pulsatility index(PI)of uterine artery(UtA),umbilical artery(UA)and fetal middle cerebral artery(MCA)were analyzed separately and in combination.ROC curve was used to analyze the cerebral-placental-uterine ratio(CPUR),cerebral-placental ratio(CPR),cerebral-uterine ratio(C-UtA)for predicting late-onset FGR;and to evaluate the sensitivity,positive and negative predictive value and of CPUR in the prediction of late-onset FGR.Results:The area under the curve(AUC)of CPUR,CPR,C-UtA and mean UtA-PI for FGR grope were 0.88,0.86,0.84 and 0.72.Under certain cut-off values and 87% specificity,the specificity of CPUR,CPR,C-UtA and mean UtA-Pifor predicting FGR group was 43.2%,46.6%,39.8% and 23.9%,respectively.The positive predictive values of CPUR,CPR,C-UtA and mean UtA-PI,UA-PI for predicting FGR group were 90.5%,71.9%,83.3%,63.6%and 5.2%,respectively.Conclusions:CPUR is more effective in predicting late onset FGR than CPR,C-UtA and mean UtA-PI.It can effectively increase the detection rate of fetal growth restrictionand reduce the FGR risk.

The predictive value of serum hs-CRP and sFlt-1 levels for fetal growth restriction in patients with ges-tational hypertension / 现代医院

Objective To investigate the changes in the levels of serum high-sensitivity C-reactive protein(hs-CRP)and soluble fms-like tyrosine kinase-1(sFlt-1)in hypertensive disorder of pregnancy(HDP)patients with fetal growth restriction(FGR),and to evaluate their predictive value for FGR.Methods A total of 137 HDP patients admitted to the Obstetrics De-partment of Ganzhou Maternal and Child Health Hospital from December 2021 to May 2023 were selected as the study subjects.According to whether their fetuses had growth restriction,they were divided into the restricted group(n=46)and the non-re-stricted group(n=91).The general information and serum levels of hs-CRP and sFlt-1 were collected and analyzed.Multiple lo-gistic regression analysis was used to identify the influencing factors for fetal growth restriction in HDP patients,and receiver oper-ating characteristic(ROC)curve was plotted to evaluate the predictive value of serum hs-CRP and sFlt-1 levels for fetal growth restriction in HDP patients.Results Univariate analysis showed that the serum levels of folic acid(FA),vitamin B12(VitB12),and placental growth factor(PIGF)in the restricted group were lower than those in the non-restricted group,while the serum lev-els of hs-CRP and sFlt-1 were higher than those in the non-restricted group,with statistically significant differences(P＜0.05).Multivariate analysis showed that serum hs-CRP,sFlt-1,and PIGF levels were independent risk factors for fetal growth restriction in HDP patients.The H-L test of the model showedx2=7.014,P=0.535,indicating a good fit.The area under the ROC curve(AUC)was 0.932,with a 95％CI of 0.889-0.975(P＜0.05),a sensitivity of 93.50％,and a specificity of 89.00％.Conclusion Serum hs-CRP and sFlt-1 levels are upregulated in HDP patients with fetal growth restriction,indicating their good predictive value for the occurrence of fetal growth restriction.

Evaluation of maternal serum fibroblast growth factor-23 levels in fetal growth restriction and gestational hypertensive disease

SUMMARY OBJECTIVE: The objective of this study was to determine serum fibroblast growth factor-23 levels in preeclampsia, eclampsia, gestational hypertension, and the presence of fetal growth restriction subgroups. METHODS: A total of 55 pregnant women with planned cesarean section were included in this cross-sectional study. They were divided into two groups, namely, control (25) and gestational hypertensive disease (30). The gestational hypertensive disease group was evaluated by dividing it into three subgroups (preeclampsia, eclampsia, and gestational hypertension) according to the clinical and laboratory findings of the disease and two subgroups (presence of fetal growth restriction and absence of fetal growth restriction) according to the birth weight percentile. Demographic parameters, obstetric history, physical examination findings, and laboratory values were evaluated. RESULTS: Demographic parameters and obstetric history were similar between the two groups, while gestational week of delivery was lower in the gestational hypertensive disease group (p=0.002). Laboratory parameters and serum fibroblast growth factor-23 (pg/mL) values were similar between the two groups. In the subgroup analysis for gestational hypertension, preeclampsia, and eclampsia, there was no statistically significant difference in serum fibroblast growth factor-23 levels between gestational hypertension, preeclampsia, eclampsia, and control groups. In the subgroup analysis based on the presence of fetal growth restriction, serum fibroblast growth factor-23 levels were similar to the control group in the gestational hypertensive disease absence of fetal growth restriction, while serum fibroblast growth factor-23 levels and serum calcium levels were statistically significantly lower in the gestational hypertensive disease with the presence of fetal growth restriction (p=0.044 and p<0.001, respectively). Conclusion: Serum fibroblast growth factor-23 levels are similar between pregnancies complicated with gestational hypertensive disease and normotensive pregnancies. However, serum fibroblast growth factor-23 levels were found to be lower in pregnancies complicated with gestational hypertensive disease with the presence of fetal growth restriction.

PREDICTION OF PREECLAMPSIA BY UTERINE ARTERY DOPPLER

Objective: To evaluate the role of mean pulsatility index by first trimester uterine artery doppler in prediction of preeclampsia. A prospective observational study was conducted in a tertiary c Methodology: are center. Of 200 women screened, 136 women met eligible criteria and 130 consented for participation in the study. In addition to nuchal translucency and crown-rump length, mean uterine artery pulsatility index (PI) was measured at 11–13+6 weeks, and women were followed up till delivery to observe the development of gestational hypertension, preeclampsia and fetal growth restriction (FGR). Categorical variables were analyzed using ROC curve, and P?0.05 (5%) was used to calculate significance. Among 130 women followed t Results: ill delivery, 9 (6.92%) had mean PI >95% and 121 (93.08%) had normal Doppler. A significantly higher number of women with PI ?95% had preeclampsia (55.55%) (p < 0.001), and the sensitivity of PI in prediction of preeclampsia was 55.55% with specificity of 98.80%. No association was found between PI and FGR (p = 0.228). Conclusion: This study showed a positive association with the development of preeclampsia . The predictive accuracy of first trimester uterine artery Doppler using PI with cutoff of >95% has low sensitivity in prediction of preeclampsia (55.55%) but it has high specificity(98.80%) for prediction of PE(Preeclampsia).

Maternal Blood Fatty Acid Levels in Fetal Growth Restriction / Níveis sanguíneos maternos de ácidos graxos na restrição do crescimento fetal

Abstract Objective: To assess the maternal blood levels of fatty acids (FAs) in pregnancies with fetal growth restriction (FGR). Methods: 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. Results: 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. 4.7ng/ml, p = 0.045) and gamma-linoleic acid (6.3 vs. 6.6ng/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. 47.6ng/ml, p = 0.033). Conclusion: Pregnant women with FGR had lower elaidic acid and gamma-linoleic acid levels and higher palmitoleic acid levels than AGA fetuses.

Resumo Objetivo: Avaliar os níveis sanguíneos maternos de ácidos graxos (AGs) em gestações com restrição de crescimento fetal (RCF). Métodos: Este estudo prospectivo transversal incluiu gestantes com idade gestacional entre 26 e 37 semanas e 6 dias com RCF e fetos adequados para a idade gestacional (AIG). Os níveis de ácidos graxos saturados, trans, monoinsaturados e poliinsaturados foram medidos usando centrifugação e cromatografia líquida. O teste t-Student, o teste de Mann-Whitney e o modelo linear geral, com idade gestacional e peso materno como covariantes, foram utilizados para comparar os níveis de AGs e os grupos RCF e AIG. O teste Qui-quadrado foi utilizado para avaliar a associação entre os grupos e as variáveis estudadas. Resultados: Amostra de sangue materno foi coletada de 64 gestantes, sendo 24 RCF e 40 AIG. Uma correlação positiva fraca foi encontrada entre o nível de ácido palmitoleico e o peso materno (r = 0,285, p = 0,036). Uma correlação negativa fraca foi encontrada entre o nível de ácido gama-linoleico ea idade gestacional (r = −0,277, p = 0,026). A mediana do nível de ácido elaídico (2,3 vs. 4,7 ng/ml, p = 0,045) e ácido gama-linoleico (6,3 vs. 6,6 ng/ml, p = 0,024) foram significativamente menores no grupo RCF do que no grupo AIG. O nível de ácido palmitoleico foi significativamente maior no grupo RCF do que no grupo AIG (50,5 vs. 47,6 ng/ml, p = 0,033). Conclusão: Gestantes com RCF apresentaram níveis mais baixos de ácido elaídico e ácido gama-linoleico e níveis mais elevados de ácido palmitoleico do que os fetos AIG.

Comparison between Protocols for Management of Fetal Growth Restriction / Comparação entre protocolos de acompanhamento da restrição de crescimento fetal

Abstract This comprehensive review compares clinical protocols of important entities regarding the management of fetal growth restriction (FGR), published since 2015. Five protocols were chosen for data extraction. There were no relevant differences regarding the diagnosis and classification of FGR between the protocols. In general, all protocols suggest that the assessment of fetal vitality must be performed in a multimodally, associating biophysical parameters (such as cardiotocography and fetal biophysical profile) with the Doppler velocimetry parameters of the umbilical artery, middle cerebral artery, and ductus venosus. All protocols reinforce that the more severe the fetal condition, the more frequent this assessment should be made. The timely gestational age and mode of delivery to terminate the pregnancy in these cases can vary much between the protocols. Therefore, this paper presents, in a didactic way, the particularities of different protocols for monitoring FGR, in order to help obstetricians to better manage the cases.

Resumo Esta revisão compreensiva compara protocolos clínicos de entidades importantes em relação ao manejo da restrição de crescimento fetal (RCF), publicados desde 2015. Cinco protocolos foram escolhidos para a extração de dados. Não houve diferenças relevantes quanto ao diagnóstico e classificação da RCF entre os protocolos. Em geral, todos os protocolos sugerem que a avaliação da vitalidade fetal deve ser realizada de forma multimodal, associando parâmetros biofísicos (como cardiotocografia e perfil biofísico fetal) aos parâmetros dopplervelocimétricos da artéria umbilical, artéria cerebral média e ducto venoso. Todos os protocolos reforçam que quanto mais grave a condição fetal, mais frequente essa avaliação deve ser feita. A idade gestacional oportuna e o modo de parto para interromper a gravidez nesses casos podem variar muito entre os protocolos. Portanto, este trabalho apresenta, de forma didática, as particularidades de diferentes protocolos de acompanhamento de RCF, a fim de auxiliar os obstetras no melhor manejo dos casos.

Fetal thymus in growth-restricted fetuses due to placental insufficiency

SUMMARY OBJECTIVE: The aim of this study was to assess fetal thymus size by ultrasound in growth-restricted fetuses due to placental insufficiency and compare to high-risk and low-risk pregnancy fetuses with normal placental function. METHODS: This is a nested case-control study of pregnant women followed up at a university hospital (July 2012 to July 2013). In all, 30 pregnant women presenting small fetuses for gestational age (estimated fetal weight <p10) due to placental insufficiency (umbilical artery Doppler >p95) were compared to 30 high-risk and 30 low-risk pregnancies presenting normal Doppler indices. The thymus transverse diameter and perimeter were converted into zeta score according to the normal values for gestational age. Head circumference and femur length were used to calculate ratios. RESULTS: Fetal thymus were significantly lower in pregnancies with placental insufficiency when compared to high-risk and low-risk pregnancies presenting, respectively, transverse diameter zeta score (-0.69±0.83 vs. 0.49±1.13 vs. 0.83±0.85, p<0.001) and P zeta score (-0.73±0.68 vs. 0.45±0.96 vs. 0.26±0.89, p<0.001). There was also a significant difference (p<0.05) in the ratios among the groups: pregnancies with placental insufficiency (TD/HC=0.10, P/FL=1.32, and P/HC=0.26), high-risk pregnancies (TD/HC=0.11, P/FL=1.40, and P/HC=0.30), and control group (DT/HC=0.11, P/FL=1.45, and P/HC=0.31). CONCLUSION: Fetal thymus size is reduced in growth-restricted fetuses due to placental insufficiency, suggesting fetal response as a consequence of the adverse environment.

Determination of the ideal timing of delivery among growth- restricted fetuses at less than 32 weeks age of gestation using a stage-based doppler protocol for admitted patients at the Philippine Children’s Medical Center

OBJECTIVES@#Early onset fetal growth restriction substantially contributes to neonatal mor-bidities and mortalities. The main dilemma lies on the timing of delivery, especially for pre- and peri-viable fetuses, due to the challenge in creating an ideal balance of minimized in-utero hy- poxia-induced fetal injury or death versus the risks of iatrogenic preterm delivery. We wished to determine the ideal timing of delivery among growth-restricted fetuses <32 weeks gestation us- ing a stage-based doppler protocol.@*MATERIALS AND METHODS@#A retrospective-cohort study of 67 singleton-pregnant wom- en with growth restriction at <32 weeks gestation and hospitalized from January 2010 to Sep- tember 2021 was conducted. Medical records were reviewed, and the outcomes were extracted. The primary outcomes were arterial pH at birth and mortality, while secondary outcomes includ- ed neonatal morbidities.@*RESULTS@#Fetal growth restriction progressed by an average of 3 stages (41.79%) within a 2- to 3.5-week period. More than half had arterial pH <7.20, which was lowest at Stage II FGR (50.00%). The prevalence of neonatal mortality was 16.42% and was lowest at Stage I (8.70%) and Stage II FGR (18.75%).@*CONCLUSION@#Doppler studies may be conducted weekly for Stage I, biweekly for Stage II, every 1-2 days for Stage III and every 12 hours for Stage IV. Delivery is ideal at Stage II as this resulted in the least number of acidosis and neonatal mortalities.