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.

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).

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.

Effectiveness of Scutellaria baicalensis Georgi root in pregnancy-related diseases: A review / 中西医结合学报

The root of Scutellaria baicalensis Georgi, also called Huangqin, is frequently used in traditional Chinese medicine. In ancient China, S. baicalensis root was used to clear heat, protect the fetus, and avoid a miscarriage for thousands of years. In modern times, pregnancy-related diseases can seriously affect maternal and fetal health, but few systematic studies have explored the mechanisms and potential targets of S. baicalensis root in the treatment of pregnancy-related diseases. Flavonoids (baicalein, wogonin and oroxylin A) and flavonoid glycosides (baicalin and wogonoside) are the main chemical components in the root of S. baicalensis. This study presents the current understanding of the major chemical components in the root of S. baicalensis, focusing on their traditional uses, potential therapeutic effects and ethnopharmacological relevance to pregnancy-related disorders. The mechanisms, potential targets and experimental models of S. baicalensis root for ameliorating pregnancy-related diseases, such as recurrent spontaneous abortion, preeclampsia, preterm birth, fetal growth restriction and gestational diabetes mellitus, are highlighted.

Screening of ultrasound markers for predicting selective fetal growth restriction in monochorionic twins at 11-13 + 6 weeks / 中华超声影像学杂志

Objective:To screen the ultrasound markers of predictive value at 11-13 + 6 weeks for selective fetal growth restriction (sFGR) in monochorionic (MC) twins. Methods:A retrospective analysis of MC twin pregnancies collected prospectively from June 2020 to December 2021 at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, with standardized ultrasound examinations performed at 11-13 + 6 weeks.According to the expert consensus on the diagnostic criteria for sFGR, collected MC twin pregnancies were divided into sFGR group and control group (normal MC twin group). Maternal age, maternal history, mode of conception, the incidence of increased nuchal translucency (NT) thickness, NT discordance, crown-rump length (CRL) discordance, abnormal ductus venous Doppler waveform and abnormal umbilical cord insertion position were compared between the two groups, and those markers that differed between groups were further analyzed for screening early ultrasound markers that could be used to predict sFGR. Results:A total of 106 cases were included in the analysis, 30 cases in sFGR group and 76 cases in control group. ①Compared with control group, sFGR group had a higher incidence of low fetal birth weight (below the 10th and 3rd percentile) in both surviving cases, large birth weight discordance and a higher incidence of birth weight inconsistency (difference >25%) ( P<0.001). ②Compared with control group, the CRL discordance was larger in sFGR group [7.8% (3.8%, 9.2%) versus 3.8% (1.5%, 7.2%)] and the incidence of abnormal cord insertion position (33.3% versus 6.6%) was higher, the differences were statistically significant ( P=0.004 and <0.001, respectively), whereas the differences of NT discordance, incidence of increased NT and abnormal ductus venous Doppler waveform were not statistically significant (all P values >0.05). ③CRL discordance was a risk factor for sFGR ( OR=1.136, 95% CI=1.021-1.264), with an area under the ROC curve of 0.682 (95% CI=0.576-0.787) for predicting sFGR, the sensitivity and specificity were 0.567 and 0.737 at a cut-off value of 6.5%. Abnormal umbilical cord insertion position was a risk factor for sFGR ( OR=7.100, 95% CI=2.176-23.167) with a sensitivity of 0.333 and specificity of 0.934 for predicting sFGR. Conclusions:CRL discordance and abnormal cord insertion position are risk factors for the development of sFGR and are of value in predicting sFGR in MC twins.

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.

Utilidad de la ecografía Doppler en el diagnóstico, el pronóstico y el manejo de la restricción del crecimiento fetal: situación en Chile / Usefulness of Doppler ultrasound for the diagnosis, prognosis and management of fetal growth restriction: situation in Chile

INTRODUCCIÓN: La restricción del crecimiento fetal (RCF) se define como la disminución patológica de la tasa de crecimiento fetal, generalmente asociada a insuficiencia placentaria. Se diagnostica mediante ultrasonografía obstétrica y velocimetría Doppler, pero no existe un consenso global respecto a los parámetros referenciados. OBJETIVO: Brindar una revisión actualizada de la aproximación clínica de la RCF en Chile, enfocada en el uso de la ultrasonografía Doppler como herramienta fundamental para el diagnóstico, el pronóstico y el manejo de esta patología, y realizar una comparativa con respecto a otros países. MÉTODO: Se realizó una revisión con palabras clave en las bases de datos PubMed y SciELO. RESULTADOS: Se obtuvieron 89 referencias bibliográficas, logrando una revisión de datos actualizados del uso del Doppler en la RCF tanto en el mundo como en Chile. CONCLUSIONES: La Guía Perinatal 2015 publicada en Chile carece de actualización con los conocimientos y la evidencia científica más recientes. Sin embargo, concuerda en gran parte con los lineamientos y las pautas generales de manejo de la RCF de las diferentes guías clínicas analizadas. Las discrepancias entre las guías revisadas podrían explicarse por la gran variabilidad de la evidencia de los estudios científico-clínicos, los cuales es importante unificar a través de una guía que promueva una estandarización de la atención de la RCF en el país.

INTRODUCTION: Fetal growth restriction (FGR) is the pathological decrease in the fetal growth rate generally associated with placental insufficiency. Diagnosis is made by obstetric ultrasonography and Doppler velocimetry, assessing different biometric and hemodynamic parameters. However, there is no global consensus regarding the parameters to be referenced. OBJECTIVE: To provide an updated review of the FGR clinical approach in Chile, focused on the use of Doppler ultrasonography as a fundamental tool in the diagnosis, prognosis, and management of this pathology and to compare with other countries. METHOD: A literature search was conducted in the PubMed and SciELO databases, including relevant and updated articles. RESULTS: The search included 89 bibliographic references under which it was possible to make a review of the most current data on the use of Doppler in FGR both worldwide and in Chile. CONCLUSIONS: The 2015 Perinatal Guidelines published in Chile is not updated with the latest scientific evidence and knowledge. However, it largely agrees with international guidelines for FGR management. The discrepancies between the revised guidelines could be explained due to the variability of evidence from scientific-clinical studies, which are essential to unify for standardized care of FGR in the country.

Decoding placental pathology: Usage of a comprehensive checklist and scoring system for reporting of placentas in the hypertensive disorders of pregnancy

Introduction/Context: Hypertensive disorders of pregnancy (HDP) are major complications of pregnancy and seen in about 5% to 10% of all pregnancies. Among these, pre-eclampsia is a leading cause of perinatal and fetal morbidity and mortality. It is a multifactorial and multisystemic disorder that results in a variety of histomorphologic features, some of which may be missed if a diligent examination is not performed. Aims and Objectives: The present study aimed to propose a checklist and novel scoring system to ensure comprehensive placental examination. We also aimed to evaluate the correlation, if any, between histopathological and morphometric findings in HDP and with fetal growth. Materials and Methods: A total of 100 placentas of women diagnosed with hypertensive disorders of pregnancy were included in our cross-sectional, observational study. Morphometric features and histological features that are known to be seen in HDP were analyzed, and each of them was given a numerical score based on their severity. Statistical Analysis Used: Pearson correlation coefficient test was applied to correlate these findings, and ANOVA test was used to assess the correlation of these findings with fetal growth restriction (FGR). Results: More than 50% of the placentas studied recorded maximum scores for weight and volume. At least 25% of the placentas showed the presence of all histo-pathological features under study. The association of total morphometric and histological scores was not found to be statistically significant (P-value = 0.239). We found a significant difference between means of morphometric scores of cases with normal fetal growth and cases showing FGR (P-value = 0.008). Conclusion: Uneven distribution and presentation of the lesions in these cases may lead to the absence of correlation between morphometry and histopathology, as seen in our study. Morphometric derangements in the placenta correlate with FGR. Our proposed checklist and scoring system can be utilized to standardize reporting of placental specimens in the evaluation of placentas with HDP, in order to facilitate and standardize the placental reporting.

Desempeño predictivo de los criterios diagnósticos de restricción de crecimiento fetal para resultados adversos perinatales en un hospital de Popayán, Colombia / Predictive performance of fetal growth restriction criteria for adverse perinatal outcomes in a hospital in Popayán, Colombia

Objetivos: determinar el desempeño predictivo de la definición de retardo de crecimiento fetal (RCF) de ultrasonografía de la Sociedad de Medicina Materno Fetal (SMMF), consenso Delphi (CD) y Medicina Fetal de Barcelona (MFB) respecto a resultados adversos perinatales en cada una, e identificar si hay asociación entre diagnóstico de RCF y resultados adversos perinatales. Materiales y métodos: se realizó un estudio de cohorte retrospectiva. Se incluyeron gestantes con embarazo único de 24 a 36 semanas con 6 días, quienes fueron atendidas en la unidad de medicina materna fetal con evaluación ecográfica de crecimiento fetal y atención de parto en una institución hospitalaria pública de referencia ubicada en Popayán, Colombia. Se excluyeron embarazos con hallazgos ecográficos de anomalías congénitas. Muestreo por conveniencia. Se midieron variables sociodemográficas y clínicas de las gestantes al ingreso, la edad gestacional, el diagnóstico de RCF y el resultado adverso perinatal compuesto. Se analizó la capacidad predictiva de tres criterios diagnósticos de restricción de crecimiento fetal para malos resultados perinatales y la asociación entre el diagnóstico de RCF y mal resultado periantal. Resultados: se incluyeron 228 gestantes, cuya edad media fue de 26,8 años, la prevalencia de RCF según los tres criterios fue de 3,95 %, 16,6 % y 21,9 % para CD, MFB y SMMF respectivamente. Ningún criterio aportó área bajo la curva aceptable para predicción de resultado neonatal adverso compuesto, el diagnóstico de RCF por CD y SMMF se asoció a resultados adversos perinatales con RR de 2,6 (IC 95 %: 1,5-4,3) y 1,57 (IC 95 %: 1,01-2,44), respectivamente. No se encontró asociación por MFB RR: 1,32 (IC 95 %: 0,8-2,1). Conclusiones: ante un resultado positivo para RCF, el método Delphi se asocia de manera más importante a los resultados perinatales adversos.Los tres métodos tienen una muy alta proporción de falsos negativos en la predicción de mal resultado perinatal. Se requieren estudios prospectivos que reduzcan los sesgos de medición y datos ausentes.

Objectives: To determine the predictive performance of fetal growth restriction by Maternal Fetal Medicine Society (MFMS) definition of ultrasound, the Delphi consensus (DC) and the Barcelona Fetal Medicine (BFM) criteria for adverse perinatal outcomes, and to identify whether there is an association between the diagnosis of fetal growth restriction (FGR) and adverse perinatal outcomes. Material and methods: A retrospective cohort study was conducted including women with singleton pregnancies between 24 and 36 weeks of gestation seen at the maternal fetal medicine unit for ultrasound assessment of fetal growth and delivery care in a public referral hospital in Popayán, Colombia. Pregnancies with ultrasound findings of congenital abnormalities were excluded. Convenience sampling was used. Sociodemographic and clinical variables were measured on admission; additional variables were gestational age, FGR diagnosis and adverse composite perinatal outcome. The predictive ability of three fetal growth restriction diagnostic criteria for poor perinatal outcomes was analyzed and asociation between FGR and adverse perinatlal outcomes. Results: Overall, 228 pregnant women with a mean age of 26.8 years were included; FGR prevalence according to the three criteria was 3.95 %, 16.6 % and 21.9 % for DC, BFM and MFMS, respectively. None of the criteria resulted in an acceptable area under the curve for the prediction of the composite adverse neonatal outcome; FGR diagnosis by DC and MFMS were associated with adverse perinatal outcomes with a RR of 2.6 (95 % CI: 1.5-4.3) and 1.57 (95 % CI: 1.01-2.44) respectively. No association was found for BFM RR: 1.32 (95 % CI: 0.8-2.1). Conclusions: Given a positive result for FGR, the Delphi method is significantly associated with adverse perinatal outcomes. The proportion of false negative results for a poor perinatal outcome is high for the three methods. Prospective studies that reduce measurement and attrition bias are required.

The Role of High Concentrations of Homocysteine for the Development of Fetal Growth Restriction / O papel de altas concentrações de homocisteína para o desenvolvimento da restrição de crescimento fetal

Abstract Objective To assess homocysteine (Hcy) levels in the three trimesters of pregnancy in women with fetal growth restriction (FGR) and to evaluate the role of Hcy as a possible predictor of FGR. Methods A total of 315 singleton pregnant women were included in the present prospective cohort study and were monitored since the 1st trimester of pregnancy before delivery. Newborns were monitored for the first 7 days of life. Patients who had risk factors for FGR were excluded. Fetal growth restriction was defined according to uterine fundal height (< 10 percentile), ultrasound fetometry (< 5 percentile), and anthropometry of newborns (<5 percentile). The concentrations of Hcy were detected at between 10 and 14, between 20 and 24, and between 30 and 34 weeks of pregnancy by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristics (ROC) curve test and diagnostic odds ratio (DOR) were performed to evaluate the results of ELISA. Results The concentration of Hcy in patients with FGR was 19.65 umol/L at between 10 and 14 weeks, compared with 9.28 umol/L in patients with normal fetal growth (p<0.0001). The optimal cut-off level for Hcy in the 1st trimester of pregnancy was>13.9 umol/L with AUC 0.788, sensitivity of 75%, specificity of 83.6%, and DOR of 15.2. Conclusion Assessment of serum Hcy concentration may be used as a predictor of FGR, with the highest diagnostic utility in the 1st trimester of pregnancy.

Resumo Objetivo Avaliar os níveis de homocisteína (Hcy) em três trimestres da gravidez em mulheres com restrição de crescimento fetal (FGR, na sigla em inglês) e avaliar o papel da Hcy como possível preditor de FGR. Métodos Um total de 315 gestantes solteiras foram incluídas no presente estudo de coorte prospectivo e monitoradas desde o 1° trimestre de gravidez antes do parto. Os recém-nascidos foram acompanhados durante os primeiros 7 dias de vida. Pacientes que apresentam fatores de risco para FGR foram excluídos. A FGR foi definida de acordo com a altura do fundo do útero (< percentil 10), ultrassonografia fetometria (< percentil 5) e antropometria dos recém-nascidos (< percentil 5). As concentrações de Hcy foram detectadas entre 10 e 14, entre 20 e 24 e entre 30 e 34 semanas de gravidez por ensaio de imunoabsorção enzimática (ELISA, na sigla em inglês). O teste da curva das características de operação do receptor (ROC, na sigla em inglês) e a razão de chances de diagnóstico (DOR, na sigla em inglês) foram realizados para avaliar os resultados do ELISA. Resultados A concentração de Hcy em pacientes com FGR foi de 19,65 umol/L entre 10 e 14 semanas, em comparação com 9,28 umol/L em pacientes com crescimento fetal normal (p<0,0001). O nível de corte ideal para Hcy no 1° trimestre da gravidez foi>13,9 umol/L com AUC 0,788, sensibilidade de 75%, especificidade de 83,6%, e DOR 15,2. Conclusão A avaliação da concentração sérica de Hcy pode ser usada como um preditor de FGR, com maior utilidade diagnóstica no 1° trimestre de gravidez.

A Critical Assessment of Stillbirths at a Tertiary Care Hospital

Background: Globally in 2015, 2.6 million stillbirths occurred with estimated stillbirth rate (SBR) of 18.4/1000 births. India is the world capital of stillbirth accounting for 22.6% of world’s stillbirths. Objectives: The objective of the study is to study the demographic profile of women experiencing stillbirth, to understand the risk factors for stillbirth in low resource settings, and to find the etiology of stillbirth so as to facilitate designing of a stillbirth prevention strategy. Methods: This was a cross?sectional observational study done at a tertiary care hospital of Delhi from June 2017 to December 2019. All babies delivered after 20 weeks of gestation showing no sign of life after birth were considered stillborn. Prestructured proforma was filled for each case and data were analyzed. Results: A total of 50,461 births took place during the study period, out of which 1824 were stillborn, making SBR of 36.15/1000 births of our institution. Most of the women belonged to age group 21–25 years and more than 50% of women were illiterate. Twenty?nine percent of women were completely unbooked, 48% were referred from other centers and 23% were registered at our hospital. Placental causes accounted for 22%, hypertension for 23%, and labor complications for 9% of cases while in 22% cases, cause could not be found. Conclusion: Stillbirth remains a neglected issue. A significant proportion of stillbirths are preventable by adequate antenatal care. Notification of stillbirths will give us the exact figures and realization of the seriousness of the problem which will help us work towards the solutions.

Tratamiento farmacológico en la restricción del crecimiento fetal: revisión de la bibliografía / Pharmacological management for fetal growth restriction: literature review

Resumen OBJETIVO: Explorar las diferentes estrategias de tratamiento farmacológico de la restricción del crecimiento fetal propuestas a lo largo del tiempo. METODOLOGÍA: Revisión cuasi-sistemática de la evidencia científica histórica disponible acerca del tratamiento médico descrito para la atención de mujeres embarazadas con restricción del crecimiento fetal. RESULTADOS: Entre los tratamientos médicos descritos para tratar la restricción del crecimiento fetal, los donadores de óxido nítrico, las estatinas y la aspirina asociada con omega 3, han tenido desenlaces no consistentes en estudios con limitado tamaño de muestra. Por lo que se refiere a los inhibidores de la 5-fosfodiesterasa, el sildenafilo no se ha asociado con un aumento de la velocidad de crecimiento fetal pero sí con alarmas respecto de su seguridad debidas al incremento de los casos de hipertensión pulmonar fetal y mortalidad perinatal. Por su parte, el tadalafilo ha mostrado desenlaces iniciales favorables y se esperan estudios con mayor tamaño de muestra que permitan emitir recomendaciones claras con respecto a su indicación. También se esperan los desenlaces de estudios clínicos en curso, para definir la indicación de la heparina de bajo peso molecular en este escenario en virtud de sus prometedores resultados iniciales. Los procedimientos más invasivos, como la inyección de factor de crecimiento endotelial vascular y la plasmaféresis, permanecen en estudio como propuestas terapéuticas por los resultados de estudios preclínicos y clínicos con pocos pacientes. CONCLUSIÓN: Por ahora, ninguna estrategia farmacológica propuesta ha conseguido generar recomendaciones fuertes para su indicación; sin embargo, se esperan nuevos estudios con alta calidad metodológica que generen evidencia científica lo suficientemente contundente para recomendar su indicación.

Abstract OBJECTIVE: To explore the different pharmacological treatment strategies for fetal growth restriction proposed over time. METHODOLOGY: Quasi-systematic review of the available historical scientific evidence on the medical treatment described for the care of pregnant women with fetal growth restriction. RESULTS: Among the medical treatments described to treat fetal growth restriction, nitric oxide donors, statins, and aspirin associated with omega-3 have had inconsistent outcomes in studies with limited sample size. As for 5-phosphodiesterase inhibitors, sildenafil has not been associated with an increase in fetal growth velocity, but there have been alarms regarding its safety due to the increase in cases of fetal pulmonary hypertension and perinatal mortality. On the other hand, tadalafil has shown favorable initial outcomes and studies with a larger sample size are awaited to issue clear recommendations regarding its indication. The results of ongoing clinical studies are also awaited to define the indication of low molecular weight heparin in this setting, given its promising initial results. More invasive procedures, such as vascular endothelial growth factor injection and plasmapheresis, remain under study as therapeutic proposals due to the results of preclinical and clinical studies with few patients. CONCLUSION: For now, no proposed pharmacological strategy has managed to generate strong recommendations for its indication; however, new studies with high methodological quality are expected to generate scientific evidence strong enough to recommend its indication.

Displasia mesenquimal placentaria asociada con restricción del crecimiento intrauterino de inicio temprano: reporte de un caso / Placental mesenchymal dysplasia associated with early onset intrauterine growth restriction: a case report

Resumen ANTECEDENTES: La displasia mesenquimal placentaria es una anomalía de la vasculatura y del tejido conectivo placentario que altera la estructura y la función de las vellosidades, se asocia con un desenlace perinatal adverso. CASO CLÍNICO: Paciente de 21 años, primigesta, con 15.2 semanas de embarazo establecidas por fetometría, con placenta corporal anterior, de morfología anormal, con múltiples imágenes hipoecogénicas que semejan racimos de uvas, sin flujo vascular en el Doppler color. La valoración ecográfica de las 33 semanas reportó fetometría para 27.2 semanas, anhidramnios y placentomagelia, con alteración en los parámetros de la flujometría Doppler. En la prueba sin estrés se diagnosticó restricción del crecimiento intrauterino estadio IV. La imagen del feto fue heterogénea en el flanco derecho de 4.7 x 4.1 cm. El embarazo finalizó por cesárea con una recién nacida con Apgar 8-9, de 930 gramos, placenta agrandada con vellosidades hidrópicas. El estudio histopatológico reportó: displasia mesenquimal placentaria. La resección del tumor abdominal fue electiva, por vía laparoscópica, al cuarto mes de vida, con diagnóstico histopatológico de hamartoma mesenquimal hepático. CONCLUSIÓN: La displasia mesenquimal placentaria es una anomalía placentaria benigna, relacionada con restricción del crecimiento intrauterino de inicio temprano que puede evolucionar, incluso, a la muerte del feto por hipoxia crónica debido a las anomalías en la vasculatura microscópica que afectan el desarrollo de las vellosidades terminales e interfiere en el intercambio de gases, nutrientes y electrolitos en el espacio intervelloso.

Abstract BACKGROUND: Placental mesenchymal dysplasia is an anomaly of the vasculature and placental connective tissue which alters the structure and function of the villi, being associated with an adverse perinatal outcome. CLINICAL CASE: Patient 21 years old, primigestation, with 15.2 weeks of pregnancy established by fetometry, with anterior body placenta, abnormal morphology, with multiple hypoechogenic images resembling clusters of grapes, without vascular flow in color Doppler. Ultrasound evaluation at 33 weeks, reporting fetometry for 27.2 weeks, anhydramnios and placentomagelia, with alteration in Doppler parameters, as well as in a non-stress test diagnosing fetal growth restriction stage IV. Fetus with heterogeneous image on the right flank of 4.7 x 4.1 cm. Abdominal pregnancy interruption was decided, obtaining a live female newborn, Apgar 8/9, weight 930 grams, enlarged placenta with hydropic villi. The histopathology study reports placental mesenchymal dysplasia. Abdominal tumor resection was performed electively by laparoscopy at 4 months of age with a histopathological diagnosis of hepatic mesenchymal hamartoma. CONCLUSION: Placental mesenchymal dysplasia is a benign placental anomaly, related to early-onset intrauterine growth restriction that can even progress to fetal death by chronic hypoxia due to abnormalities in the microscopic vasculature that affect the development of the terminal villi and interfere with the exchange of gases, nutrients and electrolytes in the intervillous space.

The Assessment of Vitamin D Levels in Pregnant Women is not Associated to Fetal Growth Restriction: A Cross Sectional Study / A avaliação dos níveis de vitamina D em gestantes não está associada à restrição do crescimento fetal: um estudo transversal

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

Resumo Objetivo Avaliar o nível sérico materno de vitamina D em fetos adequados para idade gestacional (AIG), pequenos para idade gestacional (PIG) e com restrição de crescimento (RCF) de acordo com a estimativa de peso fetal (EPF). Métodos Realizou-se um estudo transversal envolvendo 87 gestantes entre 26 e 36 semanas, sendo: 38 do grupo AIG, 24 do grupo PIG e 25 do grupo RCF. A dosagem sérica materna de vitamina D foi realizada pelo método de quimiluminescência. Para as comparações entre os grupos, utilizou-se o teste exato de Fisher. Resultados A média ± desvio-padrão (DP) da idade materna (anos) e do índice de massa corporal (kg/m2) nos grupos AIG, PIG e RCF foram 25,26 ± 8,40 / 26,57 ± 4,37; 25,04 ± 8,44 / 26,09 ± 3,94; e 25,48 ± 7,52 / 26,24 ± 4,66, respectivamente (p>0,05). A concentração sérica materna de vitamina D (médias ± desvios-padrão) dos grupos AIG, PG e RCF foram 22,47±8,35 ng/ml; 24,80_10,76 ng/ml; e 23,61 ± 9,98 ng/ml, respectivamente, contudo, sem diferenças significativas entre os grupos (p=0,672). Conclusão A concentração sérica materna de vitamina D não apresentou diferenças significantes entre gestantes com fetos AIG, PIG ou RCF entre 26 e 36 semanas de acordo com a EPF.

Restricción del crecimiento fetal y trombofilia / Fetal growth restriction and thrombophilia / Restrição de crescimento fetal e trombofilia

Resumen: La restricción del crecimiento fetal es una patología obstétrica frecuente, multifactorial, con elevada morbimortalidad perinatal, que debe ser abordada por un equipo multidisciplinario. Se define como la incapacidad para lograr el máximo potencial de crecimiento fetal. En Uruguay se recomienda para los criterios diagnósticos los establecidos en 2016 por la International Society of Ultrasound in Obstetric and Gynecology (ISUOG), destacando que la realización del seguimiento del crecimiento ecográfico no debe realizarse en un plazo menor a 2 semanas. Se describen causas maternas, fetales y ovulares Dentro de las probables causas maternas se describen en la literatura las trombofilias, fundamentalmente las adquiridas.

Abstract: Fetal growth restriction is a frequent, multifactorial obstetric pathology with high perinatal morbidity and mortality, which must be addressed by a multidisciplinary team. It is defined as the inability to achieve the maximum potential for fetal growth. In Uruguay, the diagnostic criteria established in 2016 by the International Society of Ultrasound in Obstetric and Gynecology (ISUOG) are recommended for diagnostic criteria, highlighting that ultrasound growth monitoring should not be performed in less than 2 weeks. Maternal, fetal and ovular causes are described. Among the probable maternal causes, thrombophilias, mainly acquired ones, are described in the literature.

Resumo: A restrição do crescimento fetal é uma patologia obstétrica multifatorial frequente, com elevada morbimortalidade perinatal, que deve ser tratada por equipe multidisciplinar. É definida como a incapacidade de atingir o potencial máximo de crescimento fetal. No Uruguai, os critérios diagnósticos estabelecidos em 2016 pela Sociedade Internacional de Ultrassom em Obstetrícia e Ginecologia (ISUOG) são recomendados como critérios diagnósticos, destacando-se que o monitoramento ultrassonográfico do crescimento não deve ser realizado em menos de 2 semanas. São descritas as causas maternas, fetais e ovulares, e dentre as prováveis causas maternas, as trombofilias, principalmente adquiridas, são descritas na literatura.

Prenatal Ultrasound Diagnosis of Biometric changes in the Brain of Growth Restricted Fetuses. A Systematic Review of Literature / Diagnóstico ecográfico de alterações biométricas no cérebro de fetos comrestrição do crescimento fetal. Uma revisão sistemática da literatura

Abstract Fetal growth restriction (FGR) occurswhen the fetus does not reach its intrauterine potential for growth and development as a result of compromise in placental function. It is a condition that affects 5 to 10% of pregnancies and is the second most common cause of perinatal morbidity and mortality. Children born with FGR are at risk of impaired neurological and cognitive development and cardiovascular or endocrine diseases in adulthood. The purpose of the present revision is to perform a literature search for evidence on the detection and assessment by ultrasound of brain injury linked to FGR during fetal life. Using a systematic approach and quantitative evaluation as study methodology, we reviewed ultrasound studies of the fetal brain structure of growth-restricted fetuses with objective quality measures. A total of eight studies were identified. High quality studies were identified for measurement of brain volumes; corpus callosum; brain fissure depth measurements, and cavum septi pellucidi width measurement. A low-quality study was available for transverse cerebellar diameter measurement in FGR. Further prospective randomized studies are needed to understand the changes that occur in the brain of fetuseswith restricted growth, as well as their correlation with the changes in cognitive development observed.

Resumo A restrição do crescimento fetal (RCF) ocorre quando umfeto não consegue atingir seu potencial de crescimento intrauterino, na maioria das vezes por compromisso da função placentária. É uma condição que afeta de 5 a 10% das gravidezes e é a segunda causa mais comum de morbidade e mortalidade perinatal. Crianças nascidas com RCF incorrem em maior risco de atraso no desenvolvimento neurológico e cognitivo, bem como de doenças cardiovasculares e/ou endócrinas, na idade adulta. O objetivo desta revisão foi o de pesquisar na literatura evidência sobre o diagnóstico pré-natal por ecografia de lesões cerebrais relacionadas com a RCF. Utilizando uma abordagem sistemática, avaliamos de forma quantitativa a metodologia dos oito estudos que preencheram os critérios de inclusão e foram, assim, incluídos nesta revisão. Foram identificados estudos de alta qualidade para a medição dos volumes cerebrais;medição do corpo caloso; medição da profundidade das incisuras cerebrais emedição do cavum do septo pelúcido. Os autores identificaram um estudo de qualidade inferior sobre a medição transversal do diâmetro transcerebelar em fetos com RCF. Mais estudos prospectivos randomizados são necessários para perceber quais as alterações que ocorrem no cerébro dos fetos com restrição do seu crescimento, bem como, a sua correlação com as alterações do desenvolvimento cognitivo observadas.

Doppler de arteria umbilical en fetos con síndrome de Down / Umbilical artery Doppler in fetuses with Down syndrome

INTRODUCCIÓN: La aneuploidía más común entre los recién nacidos vivos es el síndrome de Down (SD). En estos niños el crecimiento está disminuido, con una frecuencia del 25% de restricción del crecimiento intrauterino, pero no se ha establecido el papel de la insuficiencia placentaria. El objetivo es estudiar la resistencia placentaria a través del Doppler de arteria umbilical con índice de pulsatilidad (IP) y el tiempo medio de desaceleración (t/2), y el posible efecto de la insuficiencia placentaria en fetos con SD. MÉTODO: Se realizó Doppler en la arteria umbilical en 78 fetos con SD, se midieron el IP y el t/2, y se compararon los resultados con los pesos de nacimiento. RESULTADOS: Se estudiaron 78 fetos con SD con 214 mediciones Doppler. El t/2 y el IP estaban alterados en el 71,5% y el 65% de las mediciones, respectivamente. La incidencia de t/2 alterado aumenta con la edad gestacional desde un 28,6% a las 15-20 semanas hasta un 89,3% sobre las 36 semanas (p < 0,01); cifras similares se observan para el IP. La clasificación de los pesos fue: 64% adecuados, 12% grandes y 24% pequeños para la edad gestacional. La última medición de t/2 antes del parto era normal en el 17% y estaba alterada en el 83%. En el caso del IP, los valores fueron normales en el 27% y anormales en el 73%. El peso de nacimiento, la edad gestacional y el porcentaje de niños adecuados para la edad gestacional eran significativamente mayores en el grupo con Doppler normal que en el grupo con Doppler alterado. El z-score del t/2 estaba marcadamente alterado (−2.23), pero el del peso de nacimiento solo estaba algo disminuido (−0,39). La mortalidad perinatal fue del 10%, significativamente mayor cuando el flujo diastólico era ausente o reverso. CONCLUSIONES: El estudio demuestra que los fetos con SD tienen una alta incidencia de alteración del Doppler umbilical para el IP y el t/2, lo cual sugiere una insuficiencia placentaria grave. Este deterioro parece iniciarse hacia el final del segundo trimestre y aumenta con la edad gestacional. Sin embargo, en estos fetos, la insuficiencia placentaria produce una ligera caída en el crecimiento fetal. Como hipótesis general pensamos que en los fetos con SD hay datos claros de insuficiencia placentaria, pero habría algún factor que les protegería de una restricción grave del crecimiento.

INTRODUCTION: The most common aneuploidy in live newborns is Down syndrome (DS), in these children growth is decreased, with a frequency of 25-36% of fetal growth restriction (FGR); however, it is not established the role of placental insufficiency. The objective is to study the Doppler of the umbilical artery with pulsatility index (PI) and half peak systolic velocity (hPSV) deceleration time and the possible role of placental insufficiency in fetuses with DS. METHOD: Doppler was performed in fetuses with DS, the umbilical artery and IP and hPSV were measured, and the results were compared with birth weights. RESULTS: 78 fetuses with DS were studied with 214 Doppler measurements. hPSV and the IP were altered in 71.5% and 65% of the measurements; the incidence of abnormal hPSV increases with gestational age from 28.6% between 15 to 20 weeks, to 89.3% over 36 weeks (p < 0.01), similar figures are observed with respect to the PI. The weight classification was: 24% of FGR, 12% of great for age and 64% of adequate for gestational age (AGA). The last measurement of hPSV before delivery was normal in 17% of the fetuses and was abnormal in 83%, in the case of PI the normal and abnormal values were 27 and 73%, respectively. Birth weight, gestational age, and the percentage of AGA children were significantly higher in the normal Doppler group than in the abnormal Doppler group. The hPSV z-score was markedly altered (−2.23), but the birth weight z-score is slightly decreased (−0.39). Perinatal mortality is 10% and is significantly higher when diastolic flow is absent or reverse. CONCLUSIONS: The study shows that DS fetuses have a high incidence of abnormal umbilical Doppler measured with IP and hPSV, which suggests severe placental insufficiency, this deterioration seems to start towards the end of the second trimester and increases with gestational age. However, in these fetuses, placental insufficiency causes a discrete drop in fetal growth. As a general hypothesis, we think that there is clear evidence of placental insufficiency in fetuses with DS, but there would be some factor that would protect these fetuses from severe growth restriction.

Outcome of twin fetuses with selective fetal growth restriction / 中华围产医学杂志

Selective fetal growth restriction (sFGR) occurs in about 10% to 15% of monochorionic twins with a high incidence of intrauterine fetal death and low gestational age at birth. sFGR is associated with multisystem adverse prognosis, including brain injury, myocardial hypertrophy, right ventricular outflow tract obstruction, intestinal perforation, and abnormal insulin secretion. sFGR can be classified into three types based on the umbilical artery Doppler waveforms under ultrasound. The clinical characteristics and prognosis vary with the different types. There are few reported studies on the sFGR population, and comprehensive, long-term follow-up is needed.

The value of microvascular flow imaging method for the evaluation of placenta perfusion and prediction of fetal growth restriction: a pilot study / 中华超声影像学杂志

Objective:To evaluate the placental micro-vascular circulation by microvascular flowing imaging (MVFI) method, and to explore the clinical value of microvascular index (MVI) for the diagnosis of fetal growth restriction (FGR).Methods:A total of 21 fetuses at 24-34 weeks of gestation at the Peking Union Medical College Hospital from October to November 2019 were enrolled in this study, including 7 fetal growth restriction (FGR) fetuses, and 14 normal fetuses as control group. The fetuses of the two groups were matched according to the gestational weeks at the ratio of 1∶2. Fetal biometry parameters were measured and the placenta was observed by two-dimensional ultrasound.Uterine artery pulse index (UtA-PI), middle cerebral artery pulse index (MCA-PI), and umbilical artery S/D ratio were evaluated by color and pulse-wave Doppler. The placenta mico-circulation was displayed by the MVFI method and MVI was measured.Results:The study included 14 normal fetuses and 7 FGR fetuses. Compared with the control group, more placenta in the FGR group manifested as thickened and heterogeneous with decreased MVI and increased UtA-PI. There was statistically significant difference in placental mean MVI between two groups ( P=0.044). Besides, a trend towards significant negative correlation was observed between MVI and placenta thickness, although this was not statistically significant ( rs=-0.35, P=0.065). MVI had a higher specificity (100%) in the prediction of FGR. Conclusions:MVFI can display the micro-circulation of the placenta, and provide a direct and quantitative assessment method for placental perfusion.