Antibiotic therapy in patients with amniotic fluid sludge and risk of preterm birth: a meta-analysis.

PURPOSE: Amniotic Fluid Sludge (AFS) has been theorized to be sonographic evidence of an underlying infection/inflammation and studies have concluded that approximately 10% of the patients who show signs of preterm labor with intact membranes have an underlying intraamniotic infection, mostly subclinical, carrying an increased risk for preterm birth with its subsequent neonatal and maternal complications. The purpose of the present systematic review is to evaluate the impact of antibiotic therapy on preterm birth rates of women diagnosed with AFS. METHODS: We searched Medline, Scopus, the Cochrane Central Register of Controlled Trials CENTRAL, Google Scholar, and Clinicaltrials.gov databases for relevant articles published until the 30th of September 2022. Observational studies (prospective and retrospective) that evaluated the impact of antibiotics on preterm delivery rates of patients with AFS were considered eligible for inclusion. Statistical meta-analysis was performed with RStudio and we calculated pooled risk ratios (OR) and 95% confidence intervals (CI). To evaluate the information size, we performed trial sequential analysis (TSA) and the methodological quality of the included studies was assessed using RoBINS tools. RESULTS: Overall, four retrospective cohort studies were included in the present systematic review and 369 women were enrolled. We demonstrated that preterm delivery prior to 34, 32 and 28 weeks of gestational age was comparable among the groups of women that had antibiotics and those that did not (OR: 0.34, 95% CI 0.05, 2.14, 0.40 [0.09, 1.66], 0.35 [0.08, 1.58], respectively) but the statistical heterogenicity of the studies included was high for every gestational period that was examined. CONCLUSIONS: According to our study, we cannot conclude that the use of antibiotics in women with amniotic fluid sludge benefit the prognostic risk to deliver prematurely. It is quite clear that data from larger sample sizes and more well adjusted and designed studies are needed.

Ophthalmic artery Doppler at 19-23 weeks' gestation in pregnancies that deliver small-for-gestational-age neonates.

OBJECTIVES: First, to explore hemodynamic differences between pregnancies delivering a small-for-gestational-age (SGA) neonate in the absence of hypertensive disorders and those that develop pre-eclampsia (PE) or gestational hypertension (GH), by comparing the ophthalmic artery peak systolic velocity (PSV) ratio and first (PSV1) and second (PSV2) PSV at 19-23 weeks' gestation, and second, to compare these pregnancies for markers of placental perfusion and function. METHODS: This was a prospective observational study in women attending for a routine hospital visit at 19 + 1 to 23 + 3 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, ultrasound examination for assessment of fetal anatomy and growth, and measurement of maternal ophthalmic artery PSV ratio, PSV1, PSV2, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF). The values of PSV ratio, PSV1, PSV2, MAP, UtA-PI and PlGF were converted to multiples of the median (MoM) or deltas. Mean MoMs or deltas of these biomarkers in the SGA, PE and GH groups were compared with those in the unaffected group. The definition of SGA was birth weight below the 10th percentile in the absence of PE or GH. RESULTS: The study population of 5214 pregnancies contained 4375 (83.9%) that were unaffected by SGA, PE or GH, 563 (10.8%) complicated by SGA, 157 (3.0%) with PE and 119 (2.3%) with GH. There were three main findings of the study. First, in the SGA, PE and GH groups, compared with unaffected pregnancies, the PSV ratio delta, PSV2 MoM, MAP MoM and UtA-PI MoM were increased and PlGF MoM was decreased; however, the magnitude of most changes was smaller in the SGA group than in PE and GH groups. Second, in the PE and GH groups, but not in the SGA group, PSV1 MoM was increased. Third, in general, in the pathological pregnancies, the magnitude of deviation of biomarkers from unaffected pregnancies was greater for those delivering at < 37 than at ≥ 37 weeks' gestation. CONCLUSION: In mid-gestation, pregnancies that subsequently develop hypertensive disorders and those delivering a SGA neonate, compared with unaffected pregnancies, have abnormal uteroplacental measurements and increased maternal ophthalmic artery PSV ratio. These data suggest similar pathophysiology in the two conditions, with evidence of placental dysfunction and increased peripheral vascular resistance, but the magnitude of abnormalities is greater in hypertensive disorders. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Relationship between ophthalmic artery Doppler and maternal cardiovascular function.

OBJECTIVE: In mid-gestation, the finding of an increase in the ophthalmic artery second to first peak of systolic velocity ratio (PSV ratio) provides useful prediction of subsequent development of pre-eclampsia (PE). The objective of this study of an unselected population at 19-23 weeks' gestation was to gain a better understanding of the factors that influence ophthalmic artery Doppler by examining the possible association between the PSV ratio and maternal cardiovascular function. METHODS: This was a prospective observational study in women attending for a routine hospital visit at 19 + 1 to 23 + 3 weeks' gestation. This visit included assessment of flow velocity waveforms from the maternal ophthalmic arteries and assessment of maternal cardiovascular function. The following nine cardiovascular indices were examined: E/A ratio; E/e' ratio; myocardial performance index; global longitudinal systolic strain; left ventricular ejection fraction; peripheral vascular resistance; left ventricular cardiac output; left ventricular mass indexed for body surface area; and mean arterial pressure. The ophthalmic artery PSV ratio and the nine cardiovascular indices were converted to either log10 multiples of the median (MoM) values or deviations from the median (deltas) values after adjustment for maternal characteristics and elements of medical history. Regression analysis was then used to examine the significance of the association between PSV ratio delta and MoM or delta values of each cardiovascular index in the total population and in the subgroup that developed PE. RESULTS: The study population of 2853 pregnancies contained 76 (2.7%) that developed PE. In the total population, there were significant but weak associations between the PSV ratio and most of the cardiovascular indices, with r-values of < 0.1, except for mean arterial pressure with r = 0.178. In the subgroup that developed PE, a moderately strong association between the PSV ratio and left ventricular mass indexed for body surface area was noted (r = 0.308). CONCLUSIONS: The findings of this study suggest that Doppler assessment of PSV ratio in the ophthalmic artery provides information about peripheral vascular status. The increase in PSV ratio in women who develop PE is associated with increased afterload and an increase in left ventricular thickness. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Ophthalmic artery Doppler in combination with other biomarkers in prediction of pre-eclampsia at 35-37 weeks' gestation.

OBJECTIVE: To examine the potential value of maternal ophthalmic artery Doppler at 35-37 weeks' gestation in combination with the established biomarkers of pre-eclampsia (PE), including mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1), in the prediction of subsequent development of PE. METHODS: This was a prospective observational study in women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, ultrasound examination for fetal anatomy and growth, assessment of flow velocity waveforms from the maternal ophthalmic arteries, and measurement of MAP, UtA-PI, serum PlGF and serum sFlt-1. The competing-risks model was used to estimate the individual patient-specific risks of delivery with PE at any time and at < 3 weeks after assessment by a combination of maternal demographic characteristics and medical history with biomarkers. The area under the receiver-operating-characteristics curve and detection rate (DR) of delivery with PE, at a 10% false-positive rate (FPR), in screening by combinations of maternal factors with ophthalmic artery second to first peak of systolic velocity ratio (PSV ratio), MAP, UtA-PI, serum PlGF and serum sFlt-1 were determined. The modeled performance of screening for PE was also estimated. RESULTS: The study population of 2287 pregnancies contained 60 (2.6%) that developed PE, including 19 (0.8%) that delivered with PE at < 3 weeks after assessment. The PSV ratio improved the prediction of PE with delivery at any stage after assessment provided by maternal factors alone (from 25.4% to 50.6%), maternal factors and MAP (54.3% to 62.7%), maternal factors, MAP and PlGF (68.3% to 70.8%) and maternal factors, MAP, PlGF and sFlt-1 (75.7% to 76.7%), at a FPR of 10%. The PSV ratio also improved the prediction of PE with delivery at < 3 weeks after assessment provided by maternal factors alone (from 31.0% to 69.4%), maternal factors and MAP (74.1% to 83.4%), maternal factors, MAP and UtA-PI (77.1% to 85.0%) and maternal factors, MAP and PlGF (84.8% to 88.6%). The empirical results for DR at a 10% FPR were consistent with the modeled results. Screening by a combination of maternal factors with MAP and PSV ratio also detected 59.4% (95% CI, 58.6-82.5%) of cases of gestational hypertension with delivery at any stage after assessment, and 86.7% (95% CI, 82.4-100%) of those with delivery at < 3 weeks after assessment. CONCLUSION: Ophthalmic artery Doppler could potentially improve the performance of screening for PE at 35-37 weeks, especially imminent PE with delivery within 3 weeks after assessment, but further studies are needed to validate this finding. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Ophthalmic artery Doppler in combination with other biomarkers in prediction of pre-eclampsia at 19-23 weeks' gestation.

OBJECTIVE: To examine the potential value of maternal ophthalmic artery Doppler at 19-23 weeks' gestation on its own and in combination with the established biomarkers of pre-eclampsia (PE), including uterine artery (UtA) pulsatility index (PI), mean arterial pressure (MAP), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1), in the prediction of subsequent development of PE. METHODS: This was a prospective observational study of women attending for a routine hospital visit at 19 + 1 to 23 + 3 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, ultrasound examination for fetal anatomy and growth, assessment of flow velocity waveforms from the maternal ophthalmic arteries, and measurement of MAP, UtA-PI, serum PlGF and serum sFlt-1. Waveforms were obtained from the ophthalmic arteries in sequence from the right eye, left eye and again from the right and then left eye. We recorded the average of the four measurements, two from each eye, for the following four indices: first peak of systolic velocity; second peak of systolic velocity; PI; and the ratio of the second to first peak of systolic velocity (PSV ratio). The measurements of the four indices were standardized to remove the effects of maternal characteristics and elements from the medical history. The competing-risks model was used to estimate the individual patient-specific risks of delivery with PE at < 37 and ≥ 37 weeks' gestation and to determine the area under the receiver-operating-characteristics curve (AUC) and detection rate (DR), at a 10% false-positive rate (FPR), in screening by a combination of maternal demographic characteristics and medical history with biomarkers. The modeled performance of screening for PE was also estimated. RESULTS: The study population of 2853 pregnancies contained 76 (2.7%) that developed PE, including 18 (0.6%) that delivered with PE at < 37 weeks' gestation. The ophthalmic artery PSV ratio was significantly increased in PE pregnancies, and the PE effect depended on gestational age at delivery; the deviation from normal was greater for early than late PE. The second peak of systolic velocity was also increased in PE pregnancies, but the effect did not depend on gestational age at delivery. The other two ophthalmic artery indices of first peak of systolic velocity and PI were not significantly affected by PE. The PSV ratio improved the prediction of preterm PE provided by maternal factors alone (from 56.1% to 80.2%), maternal factors, MAP and UtA-PI (80.7% to 87.9%), maternal factors, MAP, UtA-PI and PlGF (85.5% to 90.3%) and maternal factors, MAP, UtA-PI, PlGF and sFlt-1 (84.9% to 89.8%), at a FPR of 10%. The PSV ratio also improved the prediction of term PE provided by maternal factors alone (from 33.8% to 46.0%), maternal factors, MAP and UtA-PI (46.6% to 54.2%), maternal factors, MAP, UtA-PI and PlGF (45.2% to 53.4%) and maternal factors, MAP, UtA-PI, PlGF and sFlt-1 (43.0% to 51.2%), at a FPR of 10%. The empirical results for DR at a 10% FPR were consistent with the modeled results. The second peak of systolic velocity did not improve the prediction of either preterm or term PE provided by maternal factors alone. CONCLUSION: Ophthalmic artery PSV ratio at 19-23 weeks' gestation, both on its own and in combination with other biomarkers, is potentially useful for prediction of subsequent development of PE, especially preterm PE, but larger studies are needed to validate this finding. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Doppler de la arteria oftálmica en combinación con otros biomarcadores para la predicción de la preeclampsia a las 19-23 semanas de gestación OBJETIVOS: Estudiar el valor potencial del Doppler de la arteria oftálmica materna a las 19-23 semanas de gestación, tanto por sí solo como en combinación con los biomarcadores establecidos de la preeclampsia (PE), a saber, el índice de pulsatilidad (IP) de la arteria uterina (AUt), la presión arterial media (PAM), el factor de crecimiento placentario (FCPl) sérico y la tirosina quinasa-1 (sFlt-1) tipo fms soluble en suero, en la predicción del desarrollo posterior de la PE. MÉTODOS: Este fue un estudio prospectivo de observación a mujeres que acudieron al hospital a una consulta de rutina entre las 19+1 y las 23+3 semanas de gestación. Esta consulta incluyó el registro de las características demográficas y el historial médico de la madre, el examen ecográfico de la anatomía y el crecimiento del feto, la evaluación de la forma de onda de velocidad de flujo de las arterias oftálmicas maternas, y la medición de la PAM, el IP-AUt, el FCPl sérico y la sFlt-1 sérica. La forma de onda se obtuvo de las arterias oftálmicas consecutivamente del ojo derecho, el ojo izquierdo y de nuevo del ojo derecho y luego del izquierdo. Se registró el promedio de las cuatro mediciones, dos de cada ojo, para los siguientes cuatro índices: primer pico de velocidad sistólica; segundo pico de velocidad sistólica; IP; y el cociente entre el segundo y el primer pico de velocidad sistólica (cociente PVS). Las mediciones de los cuatro índices se estandarizaron, a fin de eliminar los efectos de las características y los elementos maternos del historial clínico. Se utilizó el modelo de riesgos en competencia para estimar los riesgos específicos de cada paciente en el parto en cuanto a la PE a <37 y ≥37 semanas de gestación y para determinar el área bajo la curva de la característica operativa del receptor (ABC) y la tasa de detección (TD), con una tasa de falsos positivos (TFP) del 10%, en la detección mediante una combinación de características demográficas maternas e historial médico con biomarcadores. También se estimó el rendimiento del modelo de la detección de la PE. RESULTADOS: La población de estudio de 2853 embarazos contenía 76 (2.7%) mujeres que desarrollaron PE, entre ellas 18 (0.6%) que dieron a luz con PE a <37 semanas de gestación. El cociente de PVS de la arteria oftálmica aumentó significativamente en los embarazos con PE, y el efecto de la PE dependió de la edad gestacional en el momento del parto; la desviación de la curva normal fue mayor en el caso de la PE temprana que en el de la tardía. El segundo pico de velocidad sistólica también aumentó en los embarazos con PE, pero el efecto no dependió de la edad gestacional en el momento del parto. Los otros dos índices de la arteria oftálmica del primer pico de velocidad sistólica e IP no se vieron afectados significativamente por la PE. El cociente de PVS mejoró la predicción de la PE pretérmino proporcionada exclusivamente por los factores maternos (del 56,1% al 80,2%), los factores maternos, la PAM y el IP-AUt (del 80,7% al 87,9%), los factores maternos, la PAM, el IP-AUt y el FCPl (del 85,5% al 90,3%) y los factores maternos, la PAM, el IP-AUt, el FCPl y la sFlt-1 (del 84,9% al 89,8%), con una TFP del 10%. La tasa de PVS también mejoró la predicción de la PE a término proporcionada exclusivamente por los factores maternos (del 33,8% al 46,0%), los factores maternos, la PAM y el IP-AUt (del 46,6% al 54,2%), los factores maternos, la PAM, el IP-AUt y el FCPl (del 45,2% al 53,4%) y los factores maternos, la PAM, el IP-AUt, el FCPl y la sFlt-1 (del 43,0% al 51,2%), con una TFP del 10%. Los resultados empíricos de la TD con una TFP del 10% concordaron con los resultados del modelo. El segundo pico de velocidad sistólica no mejoró la predicción de la PE pretérmino o a término proporcionada exclusivamente por los factores maternos. CONCLUSIÓN: La proporción de PVS de la arteria oftálmica a las 19-23 semanas de gestación, tanto por sí sola como en combinación con otros biomarcadores, es potencialmente útil para la predicción del desarrollo posterior de la PE, especialmente la PE pretérmino, pero se necesitan estudios más amplios para validar este hallazgo.

Ophthalmic artery Doppler in prediction of pre-eclampsia at 35-37 weeks' gestation.

OBJECTIVES: First, to examine the potential value of maternal ophthalmic artery Doppler at 35-37 weeks' gestation in the prediction of subsequent development of pre-eclampsia (PE), and, second, to examine the variability between repeat measurements in the same eye and variability in measurements between the two eyes. METHODS: This was a prospective observational study in women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. The visit included recording of maternal demographic characteristics and medical history and assessment of flow velocity waveforms from the maternal ophthalmic artery. Waveforms were obtained in sequence from the right eye, left eye and again from the right and then left eye. We recorded the average of the four measurements, two from each eye, for the following four indices: first peak of systolic velocity; second peak of systolic velocity; pulsatility index; and the ratio of the second to first peak of systolic velocity (PSV ratio). The measurements of the four indices were standardized to remove the effects of maternal characteristics and elements from the medical history. The competing-risks model was used to determine the detection rate (DR) of delivery with PE at any time and at < 3 weeks after assessment, at a 10% false-positive rate (FPR), in screening by maternal factors alone and a combination of maternal factors and the adjusted value of each of the four ophthalmic artery indices. RESULTS: The study population of 2287 pregnancies contained 60 (2.6%) that developed PE, including 19 (0.8%) that delivered with PE at < 3 weeks after assessment. The DR, at 10% FPR, of delivery with PE at any time after assessment by maternal factors was 25.0% (95% CI, 14.7-37.9%), and this increased by 25 percentage points to 50.0% (95% CI, 36.8-63.2%) with the addition of the adjusted PSV ratio (P = 0.005); the respective values for delivery with PE at < 3 weeks after assessment were 31.6% (95% CI, 12.6-56.6%) and 57.9% (95% CI, 33.5-79.8%). The other ophthalmic artery indices did not improve the prediction provided by maternal factors alone. There was good correlation between the first and second measurements of PSV ratio from the same eye (right eye r = 0.823, left eye r = 0.840), but poorer correlation in the first and second measurements between the two eyes (first measurement r = 0.690, second measurement r = 0.682). In screening by maternal factors and PSV ratio for PE with delivery at any stage after assessment, the estimated DR, at 10% FPR, was 50.0% when the average of four measurements was used (two from each eye), 49.1% when the average of one measurement from each eye was used, 47.3% when the average of two measurements from the same eye was used, and 45.8% when only one measurement was used. CONCLUSIONS: Ophthalmic artery PSV ratio at 35-37 weeks' gestation can predict subsequent delivery with PE, especially if this occurs within 3 weeks after assessment. In the assessment of ophthalmic artery Doppler, it is necessary to use the average of one measurement from each eye to minimize variability of measurements. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Intertwin discordance in fetal size at 11-13 weeks' gestation and pregnancy outcome.

OBJECTIVE: To investigate the value of intertwin discordance in fetal crown-rump length (CRL) at the 11-13-week scan in the prediction of adverse outcome in dichorionic (DC), monochorionic diamniotic (MCDA) and monochorionic monoamniotic (MCMA) twin pregnancies. METHODS: This was a retrospective analysis of prospectively collected data on twin pregnancies undergoing routine ultrasound examination at 11-13 weeks' gestation between 2002 and 2019. In pregnancies with no major abnormalities, we examined the value of intertwin discordance in fetal CRL in DC, MCDA and MCMA twins in the prediction of fetal loss at < 20 and < 24 weeks' gestation, perinatal death at ≥ 24 weeks, preterm delivery at < 32 and < 37 weeks, birth of at least one small-for-gestational-age (SGA) neonate with birth weight < 5th percentile and intertwin birth-weight discordance of ≥ 20% and ≥ 25%. RESULTS: First, the study population of 6225 twin pregnancies included 4896 (78.7%) DC, 1274 (20.4%) MCDA and 55 (0.9%) MCMA twin pregnancies. Second, median CRL discordance in DC twin pregnancies (3.2%; interquartile range (IQR), 1.4-5.8%) was lower than in MCDA twins (3.6%; IQR, 1.6-6.2%; P = 0.0008), but was not significantly different from that in MCMA twins (2.9%; IQR, 1.2-5.1%; P = 0.269). Third, compared to CRL discordance in DC twin pregnancies with two non-SGA live births at ≥ 37 weeks' gestation, there was significantly larger CRL discordance in both DC and MCDA twin pregnancies complicated by fetal death at < 20 and < 24 weeks' gestation, perinatal death at ≥ 24 weeks, preterm birth at < 32 and < 37 weeks, birth of at least one SGA neonate and birth-weight discordance ≥ 20% and ≥ 25%, and in MCDA twin pregnancies undergoing endoscopic laser surgery. Fourth, the predictive performance of CRL discordance for each adverse pregnancy outcome was poor, with areas under the receiver-operating-characteristics curves ranging from 0.533 to 0.624. However, in both DC and MCDA twin pregnancies with large CRL discordance, there was a high risk of fetal loss. Fifth, in DC twin pregnancies, the overall rate of fetal loss at < 20 weeks' gestation was 1.3% but, in the small subgroup with CRL discordance of ≥ 15%, which constituted 1.9% of the total, the rate increased to 5.3%. Sixth, in MCDA twin pregnancies, the rate of fetal loss or endoscopic laser surgery at < 20 weeks was about 11%, but, in the small subgroups with CRL discordance of ≥ 10%, ≥ 15% and ≥ 20%, which constituted 9%, < 3% and < 1% of the total, the risk was increased to about 32%, 49% and 70%, respectively. Seventh, in MCMA twin pregnancies, there were no significant differences in CRL discordance for any of the adverse outcome measures, but this may be the consequence of the small number of cases in the study population. CONCLUSIONS: In both DC and MCDA twin pregnancies, increased CRL discordance is associated with an increased risk of fetal death at < 20 and < 24 weeks' gestation, perinatal death at ≥ 24 weeks, preterm birth at < 37 and < 32 weeks, birth of at least one SGA neonate and birth-weight discordance ≥ 20% and ≥ 25%, but CRL discordance is a poor screening test for adverse pregnancy outcome. However, in DC twins, CRL discordance of ≥ 15% is associated with an increased risk of fetal loss at < 20 and < 24 weeks' gestation and, in MCDA twins, CRL discordance of ≥ 10%, and more so discordance of ≥ 15% and ≥ 20%, is associated with a very high risk of fetal loss or endoscopic laser surgery at < 20 and < 24 weeks and this information is useful in counseling women and defining the timing for subsequent assessment and possible intervention. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.