Severe smallness as predictor of adverse perinatal outcome in suspected late small-for-gestational-age fetuses: systematic review and meta-analysis.

OBJECTIVE: To investigate the performance of severe smallness in the prediction of adverse perinatal outcome among fetuses with suspected late-onset small-for-gestational age (SGA). METHODS: A systematic search was performed to identify relevant studies in PubMed, Web of Science and Scopus. Late-onset SGA was defined as estimated fetal weight (EFW) or abdominal circumference (AC) < 10th percentile diagnosed at or after 32 weeks' gestation, while severe SGA was defined as EFW or AC < 3rd percentile or < 2 SD. Random-effects modeling was used to generate hierarchical summary receiver-operating-characteristics (HSROC) curves. The performance of severe SGA (as a presumptive diagnosis) in predicting adverse perinatal outcome among singleton pregnancies with suspected late-onset SGA was expressed as area under the HSROC curve (AUC), sensitivity, specificity and positive/negative likelihood ratios. The association between suspected severe SGA and adverse perinatal outcome was also assessed by random-effects modeling using the Mantel-Haenszel method and presented as odds ratio (OR). The non-exposed group was defined as non-severe SGA (EFW ≥ 3rd centile). RESULTS: Twelve cohort studies were included in this systematic review and meta-analysis. The studies included a total of 3639 fetuses with suspected late-onset SGA, of which 1246 had suspected severe SGA. Significant associations were found between suspected severe SGA and composite adverse perinatal outcome (OR, 1.97 (95% CI, 1.33-2.92)), neonatal intensive care unit admission (OR, 2.87 (95% CI, 1.84-4.47)) and perinatal death (OR, 4.26 (95% CI, 1.07-16.93)). However, summary ROC curves showed limited performance of suspected severe SGA in predicting perinatal outcomes, with AUCs of 60.9%, 66.9%, 53.6%, 57.2%, 54.6% and 64.9% for composite adverse perinatal outcome, neonatal intensive care unit admission, neonatal acidosis, Cesarean section for intrapartum fetal compromise, low Apgar score and perinatal death, respectively. CONCLUSION: Although suspected severe SGA was associated with a higher risk of perinatal complications, it performed poorly as a standalone parameter in predicting adverse perinatal outcome. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Third-trimester uterine artery Doppler for prediction of adverse outcome in late small-for-gestational-age fetuses: systematic review and meta-analysis.

OBJECTIVE: To investigate the predictive ability for adverse perinatal outcome of abnormal third-trimester uterine artery Doppler in late small-for-gestational-age (SGA) fetuses. METHODS: A systematic search was performed to identify relevant observational studies and randomized controlled trials evaluating the performance of abnormal third-trimester uterine artery Doppler for the prediction of adverse perinatal outcome in suspected SGA fetuses and SGA neonates. Abnormal uterine artery Doppler was defined as uterine artery pulsatility index > 95th percentile or ≥ 2 SD above the mean, or bilateral uterine artery notching. Hierarchical summary receiver-operating-characteristics (ROC) curves were constructed using random-effects modeling. Bayesian analysis was used to calculate the posterior probability of adverse perinatal outcome following an abnormal or normal uterine artery Doppler assessment. RESULTS: Seventeen observational studies (including 7552 fetuses either diagnosed with suspected SGA (n = 3461) or later diagnosed as a SGA neonate (n = 4091)) met the inclusion criteria; no randomized-controlled trials met the inclusion criteria. Summary ROC curves showed that, among suspected SGA fetuses, the best predictive accuracy of abnormal third-trimester uterine artery Doppler was for perinatal mortality and the worst was for composite adverse perinatal outcome, with areas under the summary ROC curves of 0.90 and 0.66, respectively. The corresponding positive and negative likelihood ratios were 16.5 and 0.6 for perinatal mortality and 2.82 and 0.65 for composite adverse perinatal outcome, respectively. Following an abnormal vs normal uterine artery Doppler assessment, the posterior risks for composite adverse perinatal outcome, admission to the neonatal intensive care unit, Cesarean section for intrapartum fetal compromise, 5-min Apgar score < 7, neonatal acidosis and perinatal death were: 52.3% vs 20.2%, 48.6% vs 18.7%, 23.1% vs 15.2%, 3.59% vs 1.32%, 9.15% vs 5.12% and 31.4% vs 1.64%, respectively. CONCLUSION: Abnormal uterine artery Doppler in the third trimester appears to be moderately useful in predicting perinatal death in pregnancies with suspected SGA. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Doppler uterino en el tercer trimestre para la predicción de resultados adversos en fetos pequeños para la edad gestacional: revisión sistemática y metaanálisis OBJETIVO: Investigar la capacidad de predicción de resultados perinatales adversos del Doppler uterino anómalo en el tercer trimestre en fetos pequeños para la edad gestacional (PEG). MÉTODOS: Se realizó una búsqueda sistemática para identificar estudios observacionales pertinentes y ensayos controlados aleatorizados que hubieran evaluado el comportamiento del Doppler uterino anómalo en el tercer trimestre para la predicción de resultados perinatales adversos en fetos con sospecha de ser PEG y en neonatos PEG. El Doppler uterino anómalo se definió como el índice de pulsatilidad de la arteria uterina >95 percentil o DE ≥2 por encima de la media, o escotadura bilateral de la arteria uterina. Se elaboraron modelos de efectos aleatorizados para la elaboración de una curva jerárquica resumen de las características operativas del receptor (ROC, por sus siglas en inglés). Se utilizó el análisis bayesiano para calcular la probabilidad a posteriori de un resultado perinatal adverso después de una evaluación de Doppler uterino anómalo o normal. RESULTADOS: Diecisiete estudios observacionales (incluidos 7552 fetos diagnosticados como sospechosos de ser PEG (n=3461) o diagnosticados posteriormente como neonatos PEG (n=4091)) cumplieron los criterios de inclusión; ningún ensayo controlado aleatorizado cumplió los criterios de inclusión. Las curvas resumen ROC mostraron que, entre los fetos sospechosos de ser PEG, la mayor precisión predictiva del Doppler uterino anómalo en el tercer trimestre fue para la muerte perinatal y la peor fue para el resultado perinatal adverso compuesto, con áreas por debajo de las curvas resumen ROC de 0,90 y 0,66, respectivamente. Los cocientes de verosimilitud correspondientes, positivo y negativo, fueron de 16,5 y 0,6 para la mortalidad perinatal y de 2,82 y 0,65 para el resultado perinatal adverso compuesto, respectivamente. Los riesgos posteriores a una evaluación de Doppler uterino anómalo vs normal, para el resultado perinatal adverso compuesto, la admisión en la unidad de cuidados intensivos para neonatos, la cesárea por deterioro fetal durante el parto, el test de Apgar a los 5 minutos <7, la acidosis neonatal y la muerte perinatal, fueron: 52,3% vs 20,2%, 48,6% vs 18,7%, 23,1% vs 15,2%, 3,59% vs 1,32%, 9,15% vs 5,12% y 31,4% vs 1,64%, respectivamente. CONCLUSIÓN: El Doppler uterino anómalo en el tercer trimestre parece ser moderadamente útil para predecir la muerte perinatal en embarazos con sospecha de ser PEG.

Added value of cerebro-placental ratio and uterine artery Doppler at routine third trimester screening as a predictor of SGA and FGR in non-selected pregnancies.

OBJECTIVES: The objective of this study is to determine the added value of cerebroplacental ratio (CPR) and uterine Doppler velocimetry at third trimester scan in an unselected obstetric population to predict smallness and growth restriction. METHODS: We constructed a prospective cohort study of women with singleton pregnancies attended for routine third trimester screening (32+0-34+6 weeks). Fetal biometry and fetal-maternal Doppler ultrasound examinations were performed by certified sonographers. The CPR was calculated as a ratio of the middle cerebral artery to the umbilical artery pulsatility indices. Both attending professionals and patients were blinded to the results, except in cases of estimated fetal weight < p10. The association between third trimester Doppler parameters and small for gestational age (SGA) (birth weight <10th centile) and fetal growth restriction (FGR) (birth weight below the third centile) was assessed by logistic regression, where the basal comparison was a model comprising maternal characteristics and estimated fetal weight (EFW). RESULTS: A total of 1030 pregnancies were included. The mean gestational age at scan was 33 weeks (SD 0.6). The addition of CPR and uterine Doppler to maternal characteristics plus EFW improved the explained uncertainty of the predicting models for SGA (15 versus 10%, p < .001) and FGR (12 versus 8%, p = .03). However, the addition of CPR and uterine Doppler to maternal characteristics plus EFW only marginally improved the detection rates for SGA (38 versus 34% for a 10% of false positives) and did not change the predictive performance for FGR. CONCLUSIONS: The added value of CPR and uterine Doppler at 33 weeks of gestation for detecting defective growth is poor.

Should phenotype of previous preterm birth influence management of women with short cervix in subsequent pregnancy? Comparison of vaginal progesterone and Arabin pessary.

OBJECTIVE: To investigate whether the classification of a previous spontaneous preterm birth (sPTB) as preterm labor (PTL) with intact membranes (IM) or as preterm prelabor rupture of membranes (PPROM) impacts the efficacy of cervical pessary or vaginal progesterone for prevention of sPTB in pregnant women with short cervix on transvaginal ultrasound. METHODS: This was a retrospective cohort study of asymptomatic high-risk singleton pregnancies with a short cervix and history of sPTB, treated using Arabin pessary or vaginal progesterone for primary PTB prevention, conducted at four European hospitals. A log-rank test on Kaplan-Meier curves was used to assess the difference in performance of pessary and progesterone, according to history of PTL-IM or PPROM. Linear regression analysis was used to evaluate significant predictors of gestational age at delivery. RESULTS: Between 2008 and 2015, 170 women were treated with a pessary and 88 with vaginal progesterone. In women treated with a pessary, rate of sPTB < 34 weeks was 16% in those with a history of PTL-IM and 55% in those with a history of PPROM. In women treated with progesterone, rate of sPTB < 34 weeks was 13% in those with a history of PTL-IM and 21% in those with a history of PPROM. Treatment with a pessary resulted in earlier delivery in women with previous PPROM than in any other subgroup (P < 0.0001). Linear regression analysis showed a clear effect of PPROM history (P < 0.0001), combination of PPROM history and treatment (P = 0.0003) and cervical length (P = 0.0004) on gestational age at birth. CONCLUSIONS: Cervical pessary may be a less efficacious treatment option for women with previous PPROM; however, these results require prospective validation before change in practice is recommended. Phenotype of previous preterm birth may be an important risk predictor and treatment effect modifier; this information should be reported in future clinical trials. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Longitudinal growth assessment for prediction of adverse perinatal outcome in fetuses suspected to be small-for-gestational age.

OBJECTIVE: Fetal growth restriction (FGR) is associated with an increased risk of adverse perinatal outcome. However, distinguishing this condition from small-for-gestational age (SGA) remains elusive. A set of criteria has been proposed recently for such a purpose, including the degree of smallness, Doppler parameters and growth velocity. The aim of this study was to establish whether the use of growth velocity adds value to Doppler assessment in predicting adverse perinatal outcome among SGA-suspected fetuses. METHODS: This was a prospective cohort study of consecutive singleton pregnancies with late (diagnosis ≥ 32.0 weeks) SGA (estimated fetal weight (EFW) < 10th centile). Longitudinal growth assessment was performed by calculation of EFW z-velocity between diagnosis and last scan before delivery. Improvement in the association with and predictive performance of EFW z-velocity for adverse perinatal outcome was compared against standard criteria of FGR evaluated before delivery (EFW < 3rd centile, abnormal uterine Doppler or abnormal cerebroplacental ratio). RESULT: A total of 472 patients were evaluated prospectively for suspected SGA. Of these, 231 (48.9%) qualified as late FGR. Univariate analysis showed a significant trend towards higher frequency (14.5% vs 8.2%; P = 0.041) of EFW z-velocity in the lowest decile in pregnancies with adverse perinatal outcome. Nonetheless, the addition of EFW z-velocity improved neither the association with nor the predictive performance of standard criteria of FGR for adverse perinatal outcome. CONCLUSIONS: Longitudinal assessment of fetal growth by means of EFW z-velocity did not have any independent predictive value for adverse perinatal outcome when used in combination with Doppler in SGA-suspected fetuses. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Second- to third-trimester longitudinal growth assessment for prediction of small-for-gestational age and late fetal growth restriction.

OBJECTIVE: Detection of fetal growth restriction (FGR) remains poor and most screening strategies rely on cross-sectional evaluation of fetal size during the third trimester. A longitudinal and individualized approach has been proposed as an alternative method of evaluation. The aim of this study was to compare second- to third-trimester longitudinal growth assessment to cross-sectional evaluation in the third trimester for the prediction of small-for-gestational age (SGA) and late FGR in low-risk singleton pregnancy. METHODS: This was a prospective cohort study of 2696 unselected consecutive low-risk singleton pregnancies scanned at 21 ± 2 and 32 ± 2 weeks. For cross-sectional growth assessment, abdominal circumference (AC) measurements were transformed to z-values according the 21st-INTERGROWTH standards. Longitudinal growth assessment was performed by calculating the AC z-velocity and the second- to third-trimester AC conditional growth centile. Longitudinal assessment was compared with cross-sectional assessment at 32 weeks. Association of cross-sectional and longitudinal evaluations with SGA and late FGR was assessed by logistic regression analysis. Predictive performance was determined by receiver-operating characteristics curve analysis. RESULT: In total, 210 (7.8%) newborns were classified as SGA and 103 (3.8%) as late FGR. Neither longitudinal measurement improved the association with SGA or late FGR provided by cross-sectional evaluation of AC z-score at 32 weeks. Areas under the curves of AC z-velocity and conditional AC growth were significantly smaller than those of cross-sectional AC z-scores (P < 0.001), although AC z-velocity performed significantly better than did conditional AC growth (P < 0.001). CONCLUSION: Longitudinal assessment of fetal growth from the second to third trimester has a low predictive capacity for SGA and late FGR in low-risk singleton pregnancy compared with cross-sectional growth evaluation. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Risk of fetal death in growth-restricted fetuses with umbilical and/or ductus venosus absent or reversed end-diastolic velocities before 34 weeks of gestation: a systematic review and meta-analysis.

OBJECTIVE: The objective of the study was to establish the risk of fetal death in early-onset growth-restricted fetuses with absent or reversed end-diastolic velocities in the umbilical artery or ductus venosus. DATA SOURCES: A systematic search was performed to identify relevant studies published in English, Spanish, French, Italian, or German using the databases PubMed, ISI Web of Science, and SCOPUS, without publication time restrictions. STUDY ELIGIBILITY CRITERIA: The study criteria included observational cohort studies and randomized controlled trials of early-onset growth-restricted fetuses (diagnosed before 34 weeks of gestation), with information on the rate of fetal death occurring before 34 weeks of gestation and absent or reversed end-diastolic velocities in the umbilical artery and/or ductus venosus. STUDY APPRAISAL AND SYNTHESIS METHODS: For quality assessment, 2 reviewers independently assessed the risk of bias using the Newcastle-Ottawa Scale for observational studies and the Cochrane Collaboration's tool for randomized trials. For the meta-analysis, odds ratio for both fixed and random-effects models (weighting by inverse of variance) were used. Heterogeneity between studies was assessed using tau2, χ2 (Cochrane Q), and I2 statistics. Publication bias was assessed by a funnel plot for meta-analyses and quantified by the Egger method. RESULTS: A total of 31 studies were included in this meta-analysis. The odds ratios for fetal death (random-effects models) were 3.59 (95% confidence interval, 2.3-5.6), 7.27 (95% confidence interval, 4.6-11.4), and 11.6 (95% confidence interval, 6.3-19.7) for growth-restricted fetuses with umbilical artery absent end-diastolic velocities, umbilical artery reversed end-diastolic velocities, and ductus venosus absent or reversed end-diastolic velocities, respectively. There was no substantial heterogeneity among studies for any of the analyses. CONCLUSION: Early-onset growth-restricted fetuses with either umbilical artery or ductus venosus absent or reserved end-diastolic velocities are at a substantially increased risk for fetal death.

Fetal and neonatal alloimmune thrombocytopenia.

Fetomaternal alloimmune thrombocytopenia (FMAIT) is a relatively uncommon disease, but is the leading cause of severe thrombocytopenia in the newborn. It can cause severe complications and long-term disabilities. The main objective of screening is to reduce both the morbidity and mortality associated with FMAIT, primarily by preventing intracranial hemorrhage. However, controversy surrounds both pre- and antenatal management. This article discusses pathogenesis, screening, diagnosis, and both pre- and neonatal management of FMAIT.