Resolvin D1 level during different trimesters of pregnancy for predicting the risk of fetal growth retardation in elderly pregnancy.

Resolvin D1 (RvD1) is potentially associated with fetal growth retardation (FGR) through alleviating maternal inflammation and its linkage with several pregnancy complications. Thus, this study detected RvD1 levels at different trimesters of pregnancy, aiming to investigate its role in predicting FGR risk of elderly pregnant women. This prospective, observational cohort study enrolled 165 elderly pregnant women aged ≥35 years. Serum RvD1 was detected at 10-13 weeks (early pregnancy), 20-23 weeks (middle pregnancy), and 30-33 weeks (late pregnancy) of gestational week by enzyme-linked immunosorbent assay. RvD1 was varied among different trimesters of pregnancy in elderly pregnant women (p < 0.001). FGR occurred in 25 (15.2%) women in this study. RvD1 at early (p = 0.009), middle (p = 0.002), and late (p = 0.003) pregnancy was decreased in women with FGR versus those without. By multivariate analysis, RvD1 at middle pregnancy (odds ratio (OR): 0.477, p < 0.001), pre-pregnancy body mass index (OR: 0.763, p = 0.025), and gestational diabetes mellitus (yes versus no) (OR: 0.071, p = 0.031) were independently correlated with declined FGR risk. While age (OR: 1.382, p = 0.009) was independently associated with elevated risk of FGR. Furthermore, the combination of these independent factors as a predictive model exhibited a good potential for assessing FGR risk (area under the curve: 0.802, 95% confidence interval: 0.711-0.894). In conclusion, RvD1 at different trimesters of pregnancy is negatively linked with the risk of FGR, whose level at middle pregnancy serves as an independent factor for FGR risk in elderly pregnant women.

Causal Pathways Between the Acute Experience of Violence During Pregnancy and Fetal Intrauterine Growth Restriction: A Cohort Study.

Introduction: Violence during pregnancy (VDP) is a prevalent global issue with dire consequences for the mother and the developing fetus. These consequences include prematurity, low birthweight, and intrauterine growth restriction (IUGR), but its pathways remain elusive. This study investigated the causal pathways between VDP and IUGR using mediation analysis. Methods: A prospective population-based birth cohort was followed from the beginning of the third gestational trimester to the second year of life. IUGR was defined by the Kramer index, and information on VDP was collected using the WHO-Violence Against Women (WHO VAW) questionnaire. Cases were considered positive only when no other life episodes were reported. Ten different mediators were analyzed as possible pathways based on previous research. Path analysis was conducted to evaluate these relationships. Results: The path analysis model included 755 dyads and presented an adequate fit. Violence during pregnancy showed a direct effect (ß = -0.195, p = 0.041) and a total effect (ß = -0.276, p = 0.003) on IUGR. Violence was associated with gestational depression or anxiety, tobacco and alcohol consumption, changes in blood pressure, and the need for emergency care, but these did not constitute mediators of its effect on IUGR. The sum of the indirect effects, however, showed a significant association with IUGR (ß = -0.081, p = 0.011). Conclusion: The acute experience of violence during pregnancy was associated with IUGR, primarily via a direct pathway. An indirect effect was also present but not mediated through the variables analyzed in this study. The robust strength of these associations underscores the negative health consequences of violence against women for the succeeding generation.

A liquid chromatographic-mass spectrometric procedure for analysis of pentaerythrityl tetranitrate metabolites - Development, validation and application to ovine serum and human plasma samples.

Pentaerythrityl tetranitrate (PETN) is an established drug in the treatment of coronary heart disease and heart failure. It is assumed, that the vasodilative and vasoprotective effects of PETN also have a positive impact on pregnant patients with impaired placental perfusion and studies evaluating the effect of PETN in risk pregnancies have been carried out. In the context of these clinical trials, measuring of serum levels of PETN and its metabolites pentaerythrityl trinitrate (PETriN), pentaerythrityl dinitrate (PEDN), pentaerythrityl mononitrate (PEMN) and pentaerythritol (PE) were required. To evaluate the transfer of PETN and its metabolites (PEXN) from the mother to the fetus using samples from a human clinical trial and animal study, the present work aimed to develop a rapid and simple method to simultaneously analyze PEXN in human and ovine samples. A method employing a rapid and simple liquid-liquid extraction followed by reversed-phase (C18) liquid chromatography coupled to high-resolution mass spectrometry with negative electrospray ionization was developed and validated for the detection of PETN and PEXN in human and ovine samples. PE could only be qualitatively detected at higher concenrations. Method validation requirements, including accuracy, repeatability and intermediate precision were fulfilled in ovine and human samples for all other PEXN with exception PETriN in human samples. The recovery (RE) in ovine samples was 76.7 % ± 12 % for PEMN, 98 % ± 23 % for PEDN, 94 % ± 22 % for PETriN, in human samples RE was 59 % ± 16 % for PEMN, 67 % ± 19 % for PEDN, 71 % ± 17 %. The matrix effects (ME) in ovine samples were 90 % ± 11 % for PEMN, 70 % ± 30 % for PEDN, 107 % ± 17 % for PETriN, in human samples the ME were 93 % ± 13 % for PEMN, 84 % ± 17 % for PEDN, 98 % ± 16 % for PETriN. The limits of quantification (LOQ) in ovine samples were 1.0 ng/mL for PETriN and 0.1 ng/mL for PEMN and PEDN. The LOQs in human samples were 5.0 ng/mL for PETriN and 0.3 ng/mL for PEMN und PEDN. The newly developed method was used to analyze 184 ovine serum samples and 18 human plasma samples. In ovine maternal samples, the highest observed PEDN concentration was 3.5 ng/mL and the highest PEMN concentration was 10 ng/mL, the respective concentrations in fetal serum samples were 4.9 ng/mL for PEDN and 5.4 ng/mL for PEMN. PETriN was only detected in traces in maternal and fetal samples, whereas PETN could not be detected at all. In human maternal samples, the highest concentration for PEDN was 27 ng/mL and for PEMN 150 ng/mL. In umbilical cord plasma, concentrations of 2.3 ng/mL for PEDN and 73 ng/mL for PEMN were detected. Although the PEMN and PEDN concentrations in the human samples were several times higher than in ovine samples, neither PETN nor PETriN signals could be detected. These results demonstrated that the metabolites were transferred from mother to fetus with a slight time delay.

Fetal aortic isthmus Doppler assessment to predict the adverse perinatal outcomes associated with fetal growth restriction: systematic review and meta-analysis.

PURPOSE: Fetal growth restriction (FGR) management and delivery planning is based on a multimodal approach. This meta-analysis aimed to evaluate the prognostic accuracies of the aortic isthmus Doppler to predict adverse perinatal outcomes in singleton pregnancies with FGR. METHODS: PubMed, EMBASE, the Cochrane Library, ClinicalTrials.gov and Google scholar were searched from inception to May 2021, for studies on the prognostic accuracy of anterograde aortic isthmus flow compared with retrograde aortic isthmus flow in singleton pregnancy with FGR. The meta-analysis was registered on PROSPERO and was assessed according to PRISMA and Newcastle-Ottawa Scale. DerSimonian and Laird's random-effect model was used for relative risks, Freeman-Tukey Double Arcsine for pooled estimates and exact method to stabilize variances and CIs. Heterogeneity was quantified using I2 statistics. RESULTS: A total of 2933 articles were identified through the electronic search, of which 6 studies (involving 240 women) were included. The quality evaluation of studies revealed an overall acceptable score for study group selection and comparability and substantial heterogeneity. The risk of perinatal death was significantly greater in fetuses with retrograde Aortic Isthmus blood flow, with a RR of 5.17 (p value 0.00001). Similarly, the stillbirth rate was found to have a RR of 5.39 (p value 0.00001). Respiratory distress syndrome had a RR of 2.64 (p value = 0.03) in the group of fetuses with retrograde Aortic Isthmus blood flow. CONCLUSION: Aortic Isthmus Doppler study may add information for FGR management. However, additional clinical trial are required to assess its applicability in clinical practice.

Performance of fetal ultrasound and magnetic resonance imaging in predicting birthweight according to the test-to-delivery interval: A cohort study.

OBJECTIVE: To assess the influence of the test-to-delivery interval (TDI) on the performance of ultrasound (US) and magnetic resonance imaging (MRI) for predicting birthweight (BW). STUDY DESIGN: This is a secondary analysis of a prospective, single center, blinded cohort study that compared MRI and US for the prediction of BW ≥ 95th percentile in singleton pregnancies. Patients that were included in the initial study underwent US and MRI for estimation of fetal weight between 36 + 0/7 and 36 + 6/7 weeks of gestation (WG). The primary outcome of the current study was to report the changes of US and MRI sensitivity and specificity in the prediction of BW > 95th percentile, BW > 90th percentile, BW < 10th percentile, and BW < 5th percentile, according to the TDI. The secondary outcome was to represent the performance of both tools in the prediction of BW > 90th percentile when TDI is<2 weeks, between 2 and 4 weeks, and>4 weeks. Receiver operating characteristic (ROC) curves were constructed accordingly. RESULTS: 2378 patients were eligible for final analysis. For the prediction of BW > 95th or 90th percentile, the sensitivity of MRI remains high until 2 weeks, and it decreases slowly between 2 and 4 weeks, in contrast to the sensitivity of US which decreases rapidly 2 weeks after examination (p < 0.001). For the prediction of BW < 10th or 5th percentile, the sensitivity of both tools decreases in parallel between 1 and 2 weeks. The specificities of both tools remain high from examination till delivery. These findings are reproducible with the use of the antenatal customized and the postnatal national growth charts. CONCLUSION: The performance of MRI in the prediction of BW, especially in large-for-gestational age, is maximal when delivery occurs within two weeks of the examination, decreasing slightly thereafter, in contrast with the performance of US which decreases drastically over time.

Associação entre as condições de nascimento e a densidade mineral óssea de adultos das coortes de nascimentos de 1982 e 1993 de Pelotas, Rio Grande do Sul, Brasil / Association between birth conditions and bone mineral density in adults from the 1982 and 1993 birth cohorts in Pelotas, Rio Grande do Sul State, Brazil / Asociación entre las condiciones de nacimiento y la densidad mineral ósea de adultos de las cohortes de nacimiento de 1982 y 1993 en Pelotas, Rio Grande do Sul, Brasil

Resumo: Este estudo avaliou a associação do peso ao nascer, idade gestacional e crescimento intrauterino com a densidade mineral óssea (DMO) aos 22 e 30 anos, nas coortes de nascimentos de 1982 e 1993 de Pelotas, Rio Grande do Sul, Brasil. A DMO foi medida por absorciometria por raios X com dupla energia (DXA), a associação foi avaliada usando análise de variância e a regressão linear múltipla para o controle de confundimento por: sexo, renda familiar ao nascer, tabagismo materno na gestação, escolaridade materna, cor da pele materna e índice de massa corporal pré-gestacional. Foi testado se a gordura corporal na vida adulta era mediadora da associação analisada, por meio da G-computation Formula. Foram avaliados 6.803 participantes das coortes de 1982 e 1993, aos 30 e 22 anos, respectivamente. O peso ao nascer teve associação com a DMO em todos os sítios, com maior diferença no colo femoral. Os nascidos com menos de 2.000g apresentaram, em média, -0,036g/cm2 (IC95%: -0,064; -0,008) de DMO no colo femoral em comparação àqueles com mais de 3.500g. Aqueles com escore-z de crescimento intrauterino com pelo menos 1,28 desvio padrão abaixo da média apresentaram, em média, -0,013g/cm2 (IC95%: -0,024; -0,002) de DMO na coluna lombar, em relação aos com escore-z acima da média. A análise de mediação mostrou que gordura corporal na idade adulta não mediou a associação. As condições de nascimento foram associadas com a densidade mineral óssea na vida adulta, e a identificação dos fatores precoces relacionados à perda de DMO é essencial devido à inversão demográfica em progresso em países de média e baixa renda.

Abstract: This study assessed the association of birth weight, gestational age, and intrauterine growth with bone mineral density (BMD) at 22 and 30 years of age in the 1982 and 1993 birth cohorts in Pelotas, Rio Grande do Sul State, Brazil. BMD was measured by dual-energy X-ray absorptiometry (DXA) and the association was assessed using analysis of variance. Multiple linear regression was used to control for confounding factors: sex; household income at birth; maternal smoking during pregnancy; maternal schooling; maternal ethnicity/skin color; and pre-pregnancy body mass index. The study tested whether body fat in adulthood was a mediator of the association analyzed, using the G-computation Formula. A total of 6,803 participants from the 1982 and 1993 cohorts were evaluated at 30 and 22 years of age, respectively. Birth weight was associated with BMD at all sites, with a greater difference at the femoral neck. Individuals born weighing less than 2,000g had on average -0.036g/cm2 (95%CI: -0.064; -0.008) of BMD in the femoral neck than individuals weighing more than 3,500g. Individuals with an intrauterine growth z-score at least 1.28 standard deviation below the mean had an average of -0.013g/cm2 (95%CI: -0.024; -0.002) of BMD in the lumbar spine compared with individuals with an above-average z-score. The mediation analysis showed that body fat in adulthood did not mediate the association. Birth conditions have been associated with BMD in adulthood and the identification of early factors related to bone loss is essential due to the demographic inversion that has been taking place in low- and middle-income countries.

Resumen: Este estudio evaluó la asociación del peso al nacer, la edad gestacional y el crecimiento intrauterino con la densidad mineral ósea (DMO) a los 22 y 30 años de edad, en las Cohortes de Nacimiento de 1982 y 1993 de Pelotas, Rio Grande do Sul, Brasil. La DMO se midió mediante absorciometría de rayos X de doble emisión (DXA), y la asociación se evaluó mediante ANOVA y regresión lineal múltiple para controlar la confusión por sexo, ingresos familiares al nacer, tabaquismo materno durante el embarazo, escolaridad materna, color de piel materno e índice de masa corporal antes del embarazo. Se comprobó si la grasa corporal en la edad adulta era un mediador de la asociación analizada, utilizando G-computation Formula. Se evaluaron 6.803 participantes de las cohortes 82 y 93, de 30 y 22 años, respectivamente. El peso al nacer se asoció con la DMO en todos los sitios, con la mayor diferencia en el cuello femoral. Los nacidos con un peso inferior a 2.000g tuvieron una media de -0,036g/cm2 (IC95%: -0,064; -0,008) de DMO en el cuello femoral, que aquellos con más de 3.500g. Aquellos con una puntuación z de crecimiento intrauterino de al menos 1,28 desviaciones estándar por debajo de la media presentaron un promedio de -0,013g/cm2 (IC95%: -0,024; -0,002) de DMO en la columna lumbar, con relación a aquellos con un puntaje z superior a la media. El análisis de mediación mostró que la grasa corporal en la edad adulta no medió la asociación. Las condiciones de nacimiento se asociaron con la DMO en la edad adulta, y la identificación temprana de factores relacionados con la pérdida de DMO es esencial debido a la inversión demográfica que ha estado ocurriendo en los países de ingresos medios y bajos.

PREGNANT WOMEN WITH COVID-19 AND PLACENTA ANGIOGENESIS.

OBJECTIVE: Aim of our research was to conduct a clinical and laboratory analysis of the impact of COVID-19 on pregnancy and the condition of the fetus. PATIENTS AND METHODS: Materials and Methods: At the first stage, we conducted a retrospective examination of 50 pregnant women treated at Ternopil Municipal Hospital No.2 (Ukraine) between November 2020 and January 2022 with the history of COVID-19, confirmed by PCR test, and 25 pregnant COVID-19 negative pregnant women (control group). At the second stage, we performed prospective cohort study and involved 40 pregnant women treated with the history of COVID-19, confirmed by PCR, and 10 pregnant COVID-19 negative women with a physiological course of pregnancy as a control group.Women were divided into the following groups: group I -10 women diagnosed with COVID-19 during the first trimester of pregnancy: group II-15 women diagnosed during the second trimester; group III-15 women diagnosed during the third trimester. Ultrasound examination and cardiotocograms were performed to assess fetus status. Blood samples were collected at delivery. To determine whether COVID-19 could alter placental angiogenesis, vascular endothelial growth factor A (VEGFA), PlGF and interleuin-32-α were assessed. RESULTS: Results: We identified that concentration of VEGFA was 95.30±5.65 pg/ml in control group. In women who had COVID-19 in first trimester, this index was 1.3 times higher, in second trimester 1.63 times higher and in third trimester by 2 times compared to control group. PlGF concentration was only 27,4 percent in group I, 16 percent in group II and 30 percent in group III,compared to control group. Concentration of interleuin-32-α was 67.27±5.63 pg/ml in control group and increased to 167 percent in group I, by 2.8 times in group II and by 6.3 times in group III compared to control group. CONCLUSION: Conclusions: COVID-19 has a negative impact on placental angiogenesis, including VEGFA and PlGF. Fetal post-COVID-19 syndrome requires timely diagnosis of disorders and further study. Post-COVID-19 syndrome is an immune-dependent pathology in which the processes of protracted cytokine activation occur in the body of a pregnant woman.

La suplementación con zinc favorece el crecimiento intrauterino en fetos de ratas diabéticas / Zinc supplementation favours intrauterine growth in diabetic rat fetuses

La deficiencia de zinc puede ser un factor mediador en los trastornos del crecimiento fetal en la descendencia de la gestante diabética. Se persiguió como objetivo determinar la influencia de un suplemento con zinc sobre la morfometría externa corporal y craneofacial en fetos de ratas diabéticas con hiperglucemias moderadas. Durante la gestación, ratas diabéticas y controles fueron suplementadas por vía oral con sulfato de zinc (50 mg/kg-pc) o no recibieron tratamiento. Los fetos descendientes del grupo diabético suplementado presentaron niveles similares a los controles en las variables de crecimiento somático determinadas. La suplementación con zinc a ratas diabéticas favoreció el crecimiento intrauterino en los fetos. Los resultados de esta investigación constituyen aportes para dilucidar los requerimientos de zinc que permitan prevenir los trastornos del crecimiento fetal en la descendencia de gestantes diabéticas.

Zinc deficiency may be a mediating factor in fetal growth disorders in the offspring of diabetic pregnant women. The objective was to determine the influence of a zinc supplement on external body and craniofacial morphometry in diabetic rat fetuses with moderate hyperglycemia. During gestation, diabetic and control rats were orally supplemented with zinc sulphate (50 mg/kg bw) or received no treatment. The fetuses descendants of the supplemented diabetic group had levels similar to the control ones in the determined somatic growth variables. Zinc supplementation to diabetic rats favoured intrauterine growth in fetuses. The results of this research constitute a contribution to elucidate zinc requirements that allow preventing fetal growth disorders in the offspring of diabetic pregnant women.

Mitochondrial Network: Electric Cable and More.

Mitochondria in a cell can unite and organize complex, extended structures that occupy the entire cellular volume, providing an equal supply with energy in the form of ATP synthesized in mitochondria. In accordance with the chemiosmotic concept, the oxidation energy of respiratory substrates is largely stored in the form of an electrical potential difference on the inner membrane of mitochondria. The theory of the functioning of extended mitochondrial structures as intracellular electrical wires suggests that mitochondria provide the fastest delivery of electrical energy through the cellular volume, followed by the use of this energy for the synthesis of ATP, thereby accelerating the process of ATP delivery compared to the rather slow diffusion of ATP in the cell. This analytical review gives the history of the cable theory, lists unsolved critical problems, describes the restructuring of the mitochondrial network and the role of oxidative stress in this process. In addition to the already proven functioning of extended mitochondrial structures as electrical cables, a number of additional functions are proposed, in particular, the hypothesis is put forth that mitochondrial networks maintain the redox potential in the cellular volume, which may vary depending on the physiological state, as a result of changes in the three-dimensional organization of the mitochondrial network (fragmentation/fission-fusion). A number of pathologies accompanied by a violation of the redox status and the participation of mitochondria in them are considered.

Prenatal prediction of adverse outcome using different charts and definitions of fetal growth restriction.

OBJECTIVE: Fetal growth assessment by ultrasound aims to identify small babies that are at higher risk of perinatal morbidity and mortality. The current study explores if the association between suboptimal fetal growth and adverse perinatal outcome varies with different definitions of fetal growth restriction and weight charts/standards. METHODS: This was a retrospective cohort study of 17261 singleton non-anomalous pregnancies from 24+0 weeks' gestation at a tertiary referral hospital. Estimated fetal weight (EFW) and Doppler indices were converted into gestational age specific centiles using a growth reference standard (Intergrowth-21) and various reference charts (Hadlock, Fetal Medicine Foundation [FMF] and Swedish). Test characteristics were assessed using definitions of FGR according to the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), Society of Maternal and Fetal Medicine (SMFM) and Swedish criteria. Adverse perinatal outcome was defined as perinatal death, admission to the neonatal intensive care (NICU) at term, 5' Apgar score < 7, and therapeutic cooling for neonatal encephalopathy. The association between FGR according to different definitions and adverse perinatal outcome was compared. Multivariate logistic regression was used to investigate the strength of the associations between ultrasound parameters and adverse perinatal outcome. Ultrasound parameters were also tested for correlation. RESULTS: Intergrowth-21 (IG-21), Hadlock and FMF fetal size references classified 1.47%, 3.55% and 4.5% fetuses respectively as FGR using the ISUOG definition and 2.87%, 8.82% and 10.6% fetuses respectively using the SMFM definition. The sensitivity of each of the definition/chart combinations for adverse perinatal outcome varied from 4.4% (ISUOG definition with IG-21 charts) to 13.2% (SMFM definition with FMF charts). The concomitant specificity also varied from 89.4% (SMFM definition with FMF charts) to 98.6% (ISUOG definition with IG-21 charts). ISUOG and Swedish criteria showed the highest specificity, positive predictive value, and positive likelihood ratio in detecting adverse outcomes irrespective of which fetal size reference charts/standards were used. Conversely, the SMFM definition had the highest sensitivity across all investigated growth charts. Low estimated fetal weight, elevated uterine artery mean PI, abnormal umbilical artery PI and abnormal cerebro-placental ratio were all significantly associated with adverse perinatal outcome and there was positive correlation between the covariates. Multivariate logistic regression showed that uterine artery Doppler mean PI and smallness (EFW below the 5th centile) were the only parameters to be consistently associated with adverse outcome irrespective of definitions or fetal size growth charts used. CONCLUSIONS: The prevalence of FGR is variable based on the specific definition as well as the fetal size reference chart used to diagnose FGR. Irrespective of the method of classification, the sensitivity for the identification of adverse perinatal outcome remains low. Estimated fetal weight, uterine artery and fetal Dopplers are all significant predictors of adverse perinatal outcome. As these indices are correlated to each other, a prediction algorithm is advocated to overcome the limitations of using them in isolation. This article is protected by copyright. All rights reserved.

Resultados perinatales del crecimiento intrauterino restringido. Cienfuegos, 2022

Fundamento: el crecimiento intrauterino restringido necesita un manejo intensivo prenatal para determinar el estado fetal y el tiempo del parto. Objetivo: describir los resultados perinatales del crecimiento intrauterino restringido. Métodos: estudio de serie de casos desarrollado en el Hospital de Cienfuegos, en el 2022. Se estudiaron las variables: tipo de crecimiento intrauterino retardado, resultados del ultrasonido Doppler en vasos maternos y fetales, enfermedades que complicaron el embarazo, tipo de parto, peso y tiempo gestacional al parto, resultados adversos perinatales. Se comparó la distribución de variables de importancia en la clínica con los resultados adversos perinatales. Resultados: el crecimiento restringido afectó al 4,7 % de los partos, el 25 % fue de inicio precoz; el 17,3 % presentó preeclampsia, el 41,3 % tuvo IPM ArUt >95 p. El 14,4 % de los fetos presentó alteraciones en los flujos del Doppler (ICP<5 p con 42 %); el 98 % tuvo crecimiento restringido grado I. El 19 % de las gestantes necesitó interrupción del embarazo en semana 34 o antes. Se realizó cesárea al 44,6 % y el 18,7 % de los recién nacidos vivos necesitó ingreso en UCIN; hubo tres muertes neonatales y dos muertes fetales tardías. Los resultados adversos perinatales fueron más frecuentes en fetos con ICP<5 p, el parto antes de las 34 semanas y el peso al nacer menor de 1500 g (p<0,05). Conclusiones: la alteración del índice cerebro placentario en el feto, nacer antes de las 34 semanas y peso inferior a 1500 g al nacer, eleva el riesgo adverso perinatal en los fetos/neonatos con crecimiento intrauterino restringido.

Foundation: restricted intrauterine growth requires intensive prenatal management to determine fetal status and delivery time. Objective: To describe the perinatal outcomes of restricted intrauterine growth. Methods: case series study developed at the Cienfuegos Hospital in 2022. The studied variables were: type of delayed intrauterine growth, results of Doppler ultrasound in maternal and fetal vessels, diseases that complicated the pregnancy, type of delivery, weight and gestational time to delivery, adverse perinatal outcomes. The distribution of clinically important variables was compared with adverse perinatal outcomes. Results: delayed growth affected 4.7% of births, 25% had early onset; 17.3% had preeclampsia, 41.3% had MPI ArUt >95 p. 14.4% of fetuses presented alterations in Doppler flows (ICP<5 p with 42%); 98% had restricted growth grade I. 19% of pregnant women needed termination of pregnancy at week 34 or before. A cesarean section was performed in 44.6% and 18.7% of live newborns required admission to the NICU; there were three neonatal deaths and two late fetal deaths. Adverse perinatal outcomes were more frequent in fetuses with ICP<5 p, delivery before 34 weeks and birth weight less than 1500 g (p<0.05). Conclusions: the alteration of the cerebroplacental index in the fetus, birth before 34 weeks and weight less than 1500 g at birth, increases the adverse perinatal risk in fetuses/neonates with restricted intrauterine growth.

Maternal, obstetric, and fetal Doppler characteristics in a high-risk population: prediction of adverse perinatal outcomes and of cesarean section due to intrapartum fetal compromise.

Objective: To evaluate the capacity of fetal Doppler, maternal, and obstetric characteristics for the prediction of cesarean section due to intrapartum fetal compromise (IFC), a 5-min Apgar score < 7, and an adverse perinatal outcome (APO), in a high-risk population. Materials and Methods: This was a prospective cohort study involving 613 singleton pregnant women, admitted for labor induction or at the beginning of spontaneous labor, who underwent Doppler ultrasound within the last 72 h before delivery. The outcome measures were cesarean section due to IFC, a 5-min Apgar score < 7, and any APO. Results: We found that maternal characteristics were neither associated with nor predictors of an APO. Abnormal umbilical artery (UA) resistance index (RI) and the need for intrauterine resuscitation were found to be significant risk factors for cesarean section due to IFC (p = 0.03 and p < 0.0001, respectively). A UA RI > the 95th percentile and a cerebroplacental ratio (CPR) < 0.98 were also found to be predictors of cesarean section due to IFC. Gestational age and a UA RI > 0.84 were found to be predictors of a 5-min Apgar score < 7 for newborns at < 29 and ≥ 29 weeks, respectively. The UA RI and CPR presented moderate accuracy in predicting an APO, with areas under the ROC curve of 0.76 and 0.72, respectively. Conclusion: A high UA RI appears to be a significant predictor of an APO. The CPR seems to be predictive of cesarean section due to IFC and of an APO in late preterm and term newborns.

Objetivo: Avaliar a capacidade do Doppler fetal e características materno-obstétricas na predição de cesariana por comprometimento fetal intraparto (CFI), índice de Apgar de 5º min < 7 e desfecho perinatal adverso (DPA) em uma população de alto risco. Materiais e Métodos: Estudo de coorte prospectivo envolvendo 613 parturientes admitidas para indução ou em início de trabalho de parto espontâneo que realizaram ultrassonografia Doppler nas 72 horas anteriores ao parto. Os desfechos foram cesariana por CFI, índice de Apgar de 5º min < 7 e DPA. Resultados: As características maternas não foram associadas nem preditoras de DPA. Índice de resistência (IR) da artéria umbilical (AU) anormal (p = 0,03) e necessidade de medidas de ressuscitação intrauterina (p < 0,0001) permaneceram como fatores de risco significativos para cesariana por CFI. IR AU > 95º e razão cerebroplacentária (RCP) < 0,98 foram preditores de cesariana. Idade gestacional e IR AU > 0,84 foram os preditores de índice de Apgar de 5º min < 7 para recém-nascidos < 29 e ≥ 29 semanas, respectivamente. IR AU e RCP apresentaram acurácia moderada na predição de DPA (área sob a curva ROC de 0,76 e 0,72, respectivamente). Conclusão: IR UA mostrou-se preditor significativo de DPA. RCP revelou-se possível preditora de cesariana por CFI e DPA em recémnascidos prematuros tardios e a termo.

Fetal brain volumes and neurodevelopmental outcome of intrauterine growth restricted fetuses.

OBJECTIVE: This study aims to investigate the correlation of MRI measured fetal brain volumetrics with long-term neurodevelopmental outcome, among intrauterine growth restricted (IUGR) and apparently healthy fetuses. STUDY DESIGN: A historical cohort study at a single tertiary referral medical center during 6 years period, of fetuses diagnosed with IUGR due to placental insufficiency, and apparently healthy fetuses, who had fetal brain MRI scan. The volumes of the supratentorial brain region, both hemispheres and the cerebellum were measured by 3D MRI semi-automated volume measurements. The cerebellar to supratentorial ratio (CER/ST) was calculated. Volumes were plotted on normal growth curves. 17 IUGR fetuses, and 53 apparently healthy fetuses adhered to participate in the VABS-II questionnaire, evaluating neurodevelopmental outcome. RESULTS: 70 patients (mean age at conducting VABS-II questionnaire 4.4 ± 2.1 years, 38 males) were evaluated. Among fetuses born in a gestational age of 36 weeks or later, IUGR fetuses demonstrated a significantly larger number of abnormal results in the VABS-II communication domain (p =.049). No significant differences were found in other domains or in overall neurodevelopmental outcome. The CER/ST ratio correlated with the overall neurodevelopmental outcome of the total study population (r = 0.40, p <.001), and of the IUGR group separately (ρ = 0.58, p =.02). CONCLUSION: CER/ST ratio measured using fetal brain MRI was found to be correlated with long term neurodevelopmental outcome. This result may aid in clinical interpretation of biometric data obtained by fetal brain MRI, linking it with long term neurodevelopmental outcome.

Guideline No. 442: Fetal Growth Restriction: Screening, Diagnosis, and Management in Singleton Pregnancies.

OBJECTIVE: Fetal growth restriction is a common obstetrical complication that affects up to 10% of pregnancies in the general population and is most commonly due to underlying placental diseases. The purpose of this guideline is to provide summary statements and recommendations to support a clinical framework for effective screening, diagnosis, and management of pregnancies that are either at risk of or affected by fetal growth restriction. TARGET POPULATION: All pregnant patients with a singleton pregnancy. BENEFITS, HARMS, AND COSTS: Implementation of the recommendations in this guideline should increase clinician competency to detect fetal growth restriction and provide appropriate interventions. EVIDENCE: Published literature in English was retrieved through searches of PubMed or MEDLINE, CINAHL, and The Cochrane Library through to September 2022 using appropriate controlled vocabulary via MeSH terms (fetal growth retardation and small for gestational age) and key words (fetal growth, restriction, growth retardation, IUGR, FGR, low birth weight, small for gestational age, Doppler, placenta, pathology). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. Grey literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Table A1 for definitions and Table A2 for interpretations of strong and conditional [weak] recommendations). INTENDED AUDIENCE: Obstetricians, family physicians, nurses, midwives, maternal-fetal medicine specialists, radiologists, and other health care providers who care for pregnant patients. TWEETABLE ABSTRACT: Updated guidelines on screening, diagnosis, and management of pregnancies at risk of or affected by FGR. SUMMARY STATEMENTS: RECOMMENDATIONS: Prediction of FGR Prevention of FGR Detection of FGR Investigations in Pregnancies with Suspected Fetal Growth Restriction Management of Early-Onset Fetal Growth Restriction Management of Late-Onset FGR Postpartum management and preconception counselling.

Placental Mesenchymal Dysplasia Associated with Severe Intrauterine Growth Restriction: A Case Report.

Placental mesenchymal dysplasia (PMD) is an uncommon placental lesion, which may mimic molar pregnancy at gross and microscopic examination. PMD can be associated with fetal growth restriction, Beckwith-Wiedemann syndrome, intrauterine fetal death, and preterm delivery. Nonetheless, it may also be associated with a normal appearing fetus. We aimed to emphasize that clinicians, radiologists, and pathologists should be aware of PMD as one of the etiologies of intrauterine growth restriction (IUGR). We presented the case of a 27-year-old gravida 1, para 1 woman who was admitted to Ayatollah Rouhani hospital, in Babol, Iran, at 30 weeks of gestation due to severe IUGR and fetal tachycardia. Ultrasound examination showed uteroplacental insufficiency and increased resistive index (RI) of umbilical artery. At last, a normal female fetus (1320 g) with no definitive anomalies was delivered by cesarean section. Pathological examination revealed cystically dilated stem villi with peripherally located thick-walled muscular stem vessels, and also stromal fibroblasts overgrowth in some stem villi. None of the examined sections revealed trophoblastic proliferation or stromal trophoblastic inclusion. The findings confirmed the diagnosis of PMD. Careful radiological and pathological examination should be performed in the case of IUGR for ruling out the rare placental abnormalities, including PMD.

Assessing the Impact of Uterine Artery Doppler and Low-Dose Aspirin on Fetomaternal Outcome: A Prospective Study in Low-Risk Pregnant Women in Western Part of India.

Introduction Fetal growth restriction (FGR) and pregnancy-induced hypertension (PIH) are significant and clinically relevant complications observed in many pregnancies. Early prediction of these complications may be possible through the assessment of the umbilical artery pulsatility index (UAPI). However, its utility in routine practice for otherwise normal pregnancy needs further exploration in India. Objectives This study aimed to evaluate the potential benefits of incorporating UAPI for the timely use of low-dose aspirin in preventing FGR and PIH in a tertiary care hospital in the western part of India. Methodology A prospective study was conducted involving 64 low-risk (i.e., not having any feature of high-risk pregnancy) pregnant women selected from routine antenatal care outpatient departments over a period of two years. All women underwent uterine artery Doppler examination during the 11-13+6 weeks of pregnancy and those who had high UAPI received low-dose (150 mg) aspirin till the 35th week. The incidence of FGR and PIH was analyzed and compared between high UAPI and normal UAPI pregnancy. Results A total of 64 pregnant women with a mean age of 27.11±4 years participated in the study. Among the women, eight (12.5%) were found to have high UAPI and were put on aspirin. Among those eight women, two developed PIH. In the normal UAPI group, nine (16.07%) developed PIH (p-value = 0.62). FGR was found in one case among the eight who received aspirin and in eight cases among the 56 who had normal UAPI (p-value > 0.99). Conclusion The study concluded that despite having normal UAPI, women categorized as low-risk may develop PIH and FGR. Hence, the routine use of UAPI should be investigated in further cohort studies using a large sample to draw a generalizable conclusion for the Indian population.

First Report of a Derivative Chromosome 13 with a Duplicated 11p15 Locus Associated with Silver-Russell Syndrome.

Silver-Russell Syndrome (SRS) is a disorder that is primarily characterised by intrauterine growth restriction which may occur asymmetrically or in whole, leading to a fetus being small relative to its gestational age. We present a female infant (proband) born in 2018 at a tertiary hospital in Muscat, Oman, with severe congenital anomalies. The proband carried a >25Mb duplication of the chromosomal 11p15-11pter locus of chromosome 13; creating a derivative chromosome 13 (der[13]) and was reported as 46,XX,der(13)add(11p15-11pter). A methylation-sensitive assay confirmed a diagnosis of SRS. Although the prognosis for SRS patients is generally good, the proband presented with a clinically severe phenotype culminating in death at the age of nine months. To the best of the authors' knowledge, this is the first report of a derivative chromosome 13 with a duplicated 11p15 locus in a patient with SRS.

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

OBJECTIVES: 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). METHODS: 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 3 T 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. RESULTS: Thirty-seven AGA, 18 FGR, and 9 SGA pregnancies were included. All three adiposity parameters increased between 30 and 39 weeks (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). CONCLUSIONS: 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. CLINICAL RELEVANCE STATEMENT: 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. KEY POINTS: • 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.

Acupuncture on intrauterine growth restriction associated brain injury: case study including use of magnetic resonance imaging.

Brain injury due to intrauterine growth restriction (IUGR) is a thorny clinical problem that often leads to permanent neurological deficits such as cerebral palsy. Few practical therapies can treat an IUGR-associated brain injury. We employed acupuncture to treat a 6-month-old male patient with severe hypoxic-ischemic encephalopathy (HIE) due to IUGR, as confirmed by magnetic resonance imaging (MRI). Three courses of acupuncture treatment significantly improved some of the patient's clinical characteristics, such as his insensitive responsiveness and motor deficits, with remarkably reversed HIE features on MRI at 1-year of age. This case suggests that acupuncture is a potential treatment option for an IUGR-associated brain injury and warrants further investigation.

Prediction of Perinatal and Neurodevelopmental Outcomes in Newborns with a Birth Weight below the 3rd Percentile: Performance of Two International Curves - Prospective Cohort from a Brazilian City / Predição de resultados perinatais e de neurodesenvolvimento em recém-nascidos com peso ao nascer abaixo do percentil 3: Desempenho de duas curvas internacionais - coorte prospectiva de uma cidade brasileira

Abstract Objectives To evaluate the performance of Intergrowth-21 st (INT) and Fetal Medicine Foundation (FMF) curves in predicting perinatal and neurodevelopmental outcomes in newborns weighing below the 3rd percentile. Methods Pregnant women with a single fetus aged less than 20 weeks from a general population in non-hospital health units were included. Their children were evaluated at birth and in the second or third years of life. Newborns (NB) had their weight percentiles calculated for both curves. Sensitivity, specificity, positive (PPV) and negative predictive value (NPV), and area under the ROC curve (ROC-AUC) for perinatal outcomes and neurodevelopmental delay were calculated using birth weight < 3rd percentile as the cutoff. Results A total of 967 children were evaluated. Gestational age at birth was 39.3 (± 3.6) weeks and birth weight was 3,215.0 (± 588.0) g. INT and FMF classified 19 (2.4%) and 49 (5.7%) newborns below the 3rd percentile, respectively. The prevalence of preterm birth, tracheal intubation >24 hours in the first three months of life, 5th minute Apgar <7, admission to a neonatal care unit (NICU admission), cesarean section rate, and the neurodevelopmental delay was 9.3%, 3.3%, 1.3%, 5.9%, 38.9%, and 7.3% respectively. In general, the 3rd percentile of both curves showed low sensitivity and PPV and high specificity and NPV. The 3rd percentile of FMF showed superior sensitivity for preterm birth, NICU admission, and cesarean section rate. INT was more specific for all outcomes and presented a higher PPV for the neurodevelopmental delay. However, except for a slight difference in the prediction of preterm birth in favor of INT, the ROC curves showed no differences in the prediction of perinatal and neurodevelopmental outcomes. Conclusion Birth weight below the 3rd percentile according to INT or FMF alone was insufficient for a good diagnostic performance of perinatal and neurodevelopmental outcomes. The analyzes performed could not show that one curve is better than the other in our population. INT may have an advantage in resource contingency scenarios as it discriminates fewer NB below the 3rd percentile without increasing adverse outcomes.

Resumo Objetivos Avaliar o desempenho das curvas de Intergrowth-21 st (INT) e Fetal Medicine Foundation (FMF) na predição de resultados perinatais e de neurodesenvolvimento de recém-nascidos com peso abaixo do percentil 3. Métodos Foram incluídas gestantes de feto único com idade inferior a 20 semanas de uma população geral em unidades de saúde não hospitalares. Seus filhos foram avaliados ao nascimento e no segundo ou terceiro anos de vida. Os recém-nascidos tiveram seus percentis de peso calculados para ambas as curvas. Sensibilidade, especificidade, valor preditivo positivo (VPP) e negativo (VPN) e área sob a curva ROC (ROC-AUC) foram calculados para desfechos perinatais e atraso de neurodesenvolvimento considerando o peso ao nascimento menor que o percentil 3 como ponto de corte. Resultados Um total de 967 crianças foram avaliadas ao nascimento e no segundo ou terceiro anos de vida. A idade gestacional ao nascer foi de 39,3 (±3,6) semanas e o peso ao nascimento foi de 3.215,0 (±588,0) g. INT e FMF classificaram 19 (2,4%) e49 (5,7%) recém-nascidos abaixo do percentil 3, respectivamente. A prevalência de parto prétermo, intubação traqueal > 24 horas nos primeiros três meses de vida, Apgar de 5° minuto < 7, internação em unidade de terapia intensiva neonatal (internação em UTIN), taxa de cesariana e atraso de neurodesenvolvimento foi 9,3%, 3,3%, 1,3%, 5,9%, 38,9% e 7,3% respectivamente. Em geral, o percentil 3 de ambas as curvas apresentou baixa sensibilidade e VPP e alta especificidade e VPN. O percentil 3 de FMF mostrou sensibilidade superior para parto prematuro, internação em UTIN e taxa de cesariana. INT foi mais específico para todos os desfechos e apresentou maior VPP para o atraso do neurodesenvolvimento. Entretanto, exceto por uma pequena diferença na predição de parto pré-termo em favor de INT, as curvas ROC não mostraram diferenças na predição de resultados perinatais e de desenvolvimento neurológico. Conclusão O peso ao nascer abaixo do percentil 3 segundo INT ou FMF isoladamente foi insuficiente para um bom desempenho diagnóstico de desfechos perinatais e de neurodesenvolvimento. As análises realizadas não puderam mostrar que uma curva é melhor que a outra em nossa população. INT pode ter vantagem em cenários de contingência de recursos, pois discrimina menos recém-nascidos abaixo do percentil 3 sem aumentar os desfechos adversos.