Mortality and severe neurological morbidity in extremely preterm growth-restricted fetuses.

OBJECTIVE: To develop a model for the prediction of adverse perinatal outcome in growth-restricted fetuses requiring delivery before 28 weeks in order to provide individualized patient counseling. METHODS: This was a retrospective multicenter cohort study of singleton pregnancies with antenatal suspicion of fetal growth restriction requiring delivery before 28 weeks' gestation between January 2010 and January 2020 in six tertiary public hospitals in the Barcelona area, Spain. Separate predictive models for mortality only and mortality or severe neurological morbidity were created using logistic regression from variables available antenatally. For each model, predictive performance was evaluated using receiver-operating-characteristics (ROC)-curve analysis. Predictive models were validated externally in an additional cohort of growth-restricted fetuses from another public tertiary hospital with the same inclusion and exclusion criteria. RESULTS: A total of 110 cases were included. The neonatal mortality rate was 37.3% and, among the survivors, the rate of severe neurological morbidity was 21.7%. The following factors were retained in the multivariate analysis as significant predictors of mortality: magnesium sulfate neuroprotection, gestational age at birth, estimated fetal weight, male sex and Doppler stage. This model had a significantly higher area under the ROC curve (AUC) compared with a model including only gestational age at birth (0.810 (95% CI, 0.730-0.889) vs 0.695 (95% CI, 0.594-0.795); P = 0.016). At a 20% false-positive rate, the model showed a sensitivity, negative predictive value and positive predictive value of 66%, 80% and 66%, respectively. For the prediction of the composite adverse outcome (mortality or severe neurological morbidity), the model included: gestational age at birth, male sex and Doppler stage. This model had a significantly higher AUC compared with a model including only gestational age at birth (0.810 (95% CI, 0.731-0.892) vs 0.689 (95% CI, 0.588-0.799); P = 0.017). At a 20% false-positive rate, the model showed a sensitivity, negative predictive value and positive predictive value of 55%, 63% and 74%, respectively. External validation of both models yielded similar AUCs that did not differ significantly from those obtained in the original sample. CONCLUSIONS: Estimated fetal weight, fetal sex and Doppler stage can be combined with gestational age to improve the prediction of death or severe neurological sequelae in growth-restricted fetuses requiring delivery before 28 weeks. This approach may be useful for parental counseling and decision-making. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Postnatal genetic and neurodevelopmental assessment in infants born at term with severely low birth weight of non-placental origin.

OBJECTIVE: To determine the frequency of genetic syndromes and childhood neurodevelopmental impairment in non-malformed infants born at term with severely low birth weight and no evidence of placental insufficiency. METHODS: This case series was constructed from the data of infants delivered at term between 2013 and 2018 with severely low birth weight, defined as birth weight more than 2.5 SD below the mean, with normal maternal and fetal Doppler (umbilical artery, fetal middle cerebral artery, cerebroplacental ratio and uterine artery) and no maternal hypertensive disorder during pregnancy or fetal structural anomaly on prenatal ultrasound examination. Clinical exome sequencing and copy number variation (CNV) analysis were performed using DNA extracted from the children's saliva. Cognitive and psychomotor development was evaluated using the Bayley Scales of Infant and Toddler Development, 3rd edition or the Wechsler Intelligence Scale for Children, 5th edition tests, according to the child's age at testing. RESULTS: Among the 36 405 infants born within the study period, 274 (0.75%) had a birth weight below -2.5 SD, of whom 98 met the inclusion criteria. Among the 63 families contacted, seven (11%) reported a postnatal diagnosis of a genetic syndrome and a further 18 consented to participate in the study. Median gestational age at delivery was 38.0 (interquartile range (IQR), 37.3-38.5) weeks and median birth weight was 2020 (IQR, 1908-2248) g. All 18 children showed a normal result on clinical exome sequencing and CNV analysis, but six (33%) obtained a low score on neurodevelopmental testing. CONCLUSION: Non-malformed severely small term infants with no clinical or Doppler signs of placental insufficiency present a high rate of genetic syndromes and neurodevelopmental impairment during childhood. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

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.

Ten-year experience of protocol-based management of small-for-gestational-age fetuses: perinatal outcome in late-pregnancy cases diagnosed after 32 weeks.

OBJECTIVE: To report our 10-year experience of protocol-based management of small-for-gestational-age (SGA) fetuses, based on standardized clinical and Doppler criteria, in late-pregnancy cases. METHODS: A retrospective cohort was constructed of consecutive singleton pregnancies referred for late-onset (> 32 weeks) SGA (defined as estimated fetal weight (EFW) < 10th centile) that were classified as fetal growth restriction (FGR) or low-risk SGA, based on the severity of smallness (EFW < 3rd centile) and the presence of Doppler abnormalities (uterine artery pulsatility index (UtA-PI) ≥ 95th centile or cerebroplacental ratio (CPR) < 5th centile). Low-risk SGA pregnancies were followed at 2-week intervals and delivered electively at 40 weeks. FGR pregnancies were followed at 1-week intervals, or more frequently if there were signs of fetal deterioration, and were delivered electively after 37 + 0 weeks' gestation. The occurrence of stillbirth and composite adverse outcome (CAO; defined as neonatal death, metabolic acidosis, need for endotracheal intubation or need for admission to the neonatal intensive care unit) was analyzed in low-risk SGA and FGR pregnancies. RESULTS: A total of 1197 pregnancies with EFW < 10th centile were identified and classified at diagnosis as low-risk SGA (n = 619; 51.7%) or FGR (n = 578; 48.3%). Of these, 160 were delivered before 37 weeks' gestation; for obstetric reasons in 93 (58.1%) cases, severe pre-eclampsia in 33 (20.6%), FGR with severe hypoxia in 47 (29.4%) and stillbirth in four (2.5%) (indications are non-exclusive). During follow-up, 52/574 (9.1%) low-risk SGA pregnancies were reclassified as FGR, whereas 22/463 (4.8%) FGR pregnancies were reclassified as low-risk SGA. Overall, there were no stillbirths in the low-risk SGA group and four in the FGR group, all of which occurred before 37 weeks. There were no instances of neonatal death in pregnancies delivered ≥ 37 weeks. The risk of CAO was higher in those meeting antenatal criteria for FGR at 37 weeks than in those classified as low-risk SGA (32/493 (6.5%) vs 15/544 (2.8%); odds ratio, 2.5 (95% CI, 1.3-4.6)). In FGR pregnancies, the adjusted odds ratio (95% CI) for CAO was 6.3 (1.8-21.1) in those with EFW < 3rd centile, while it was 3.2 (1.5-6.8) and 4.2 (1.9-8.9) in those with UtA-PI ≥ 95th centile and CPR < 5th centile, respectively, as compared to FGR pregnancies without each of these criteria. CONCLUSION: Protocol-based risk stratification with different management and monitoring schemes for late pregnancy with a suspected SGA baby, based on clinical and Doppler criteria, enables identification and tailored assessment of high-risk FGR, while allowing expectant management with safe perinatal outcome for low-risk SGA fetuses. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Guía de actuación para el manejo de la infección por COVID-19 durante en el embarazo / A clinical management protocol for COVID-19 infection in pregnant women

La infección causada por el nuevo coronavirus SARS-CoV-2 (COVID-19) representa actualmente una de las mayores emergencias sanitarias a nivel mundial. La aparición de una nueva infección potencialmente grave y la situación de pandemia actual ha implicado importantes ajustes en la práctica clínica en medicina materno-fetal. Aunque no parece existir una mayor afectación o susceptibilidad al virus de las mujeres embarazadas respecto la población general, existen aspectos específicos ligados a la gestación que deben tenerse en cuenta de cara al diagnóstico y manejo de la COVID-19 en pacientes embarazadas. En el siguiente documento se exponen las recomendaciones y el protocolo de actuación ante la infección por COVID-19 durante el embarazo desarrollado en nuestro centro, basado en la evidencia científica disponible hasta la fecha y las principales recomendaciones internacionales

The severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) disease (COVID-19) has caused a large global outbreak and has had a major impact on health systems and societies worldwide. The generation of knowledge about the disease has occurred almost as fast as its global expansion. Very few studies have reported on the effects of the infection on maternal health, since its onset. The mother and foetus do not seem to be at particularly high risk. Nevertheless, obstetrics and maternal-foetal medicine practice have made profound changes in order to adapt to the pandemic. In addition, there are aspects specific to COVID-19 and gestation that should be known by specialists. In this review an evidenced-based protocol is presented for the management of COVID-19 in pregnancy

[A clinical management protocol for COVID-19 infection in pregnant women]. / Guía de actuación para el manejo de la infección por COVID-19 durante en el embarazo.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has caused a large global outbreak and has had a major impact on health systems and societies worldwide. The generation of knowledge about the disease has occurred almost as fast as its global expansion. Very few studies have reported on the effects of the infection on maternal health, since its onset. The mother and foetus do not seem to be at particularly high risk. Nevertheless, obstetrics and maternal-foetal medicine practice have made profound changes in order to adapt to the pandemic. In addition, there are aspects specific to COVID-19 and gestation that should be known by specialists. In this review an evidenced-based protocol is presented for the management of COVID-19 in pregnancy.

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.

Maternal fasting glycemia and adverse pregnancy outcomes in a Mediterranean population.

AIMS: The hyperglycemia and adverse pregnancy outcome study demonstrated a continuous association between fasting plasma glucose (FPG) levels below those diagnostic of diabetes and adverse neonatal outcomes. We aimed to investigate whether the same association was found in a Mediterranean population. METHODS: A retrospective analysis of singleton pregnancies attended at our Hospital between 2008 and 2015 (n = 5203). FPG was evaluated in the second trimester, and it was divided into 7 categories (1 < 75, 2 75-79, 3 80-84, 4 85-89, 5 90-94, 6 95-99 and 7 100-124 mg/dL). Pregnancy outcomes included elective cesarean delivery, gestational hypertensive disorders (GHD), large for gestational age (LGA), small for gestational age (SGA), macrosomia, prematurity, severe prematurity and APGAR at 1 min <7. RESULTS: Maternal age was 33.8 ± 3.8 years, and BMI at first antenatal visit was 22.9 ± 3.5 kg/m2; mean FPG was 79 ± 7 mg/dL. A positive association was observed between FPG and LGA (p < 0.001), GHD (p = 0.004) and prematurity both <37 and <34 weeks of gestation (p = 0.001 and p = 0.004). FPG and SGA were inversely related (p = 0,038). FPG was not significantly related to rate of C-section or APGAR. Adjusted odds ratios associated with 1 standard deviation increase in the fasting plasma glucose (7 mg/dL) were 1.26 (1.15 to 1.37) for LGA, 1.28 (1.09 to 1.49) for GHD and 0.83 (0.74-0.93) for SGA. In a multivariate analysis controlling for confounders, FPG remained associated with LGA. CONCLUSIONS: We found an association between FPG levels, below those diagnostic of gestational diabetes according to our guidelines, and adverse maternal and neonatal outcomes in a Mediterranean population.

Impact of aspirin on trophoblastic invasion in women with abnormal uterine artery Doppler at 11-14 weeks: a randomized controlled study.

OBJECTIVE: Defective trophoblastic invasion is a key feature in many cases of pre-eclampsia (PE). Uterine artery (UtA) Doppler is a validated non-invasive proxy for trophoblastic invasion. The aim of this study was to explore whether low-dose aspirin, administered from the first trimester, improves trophoblastic invasion, evaluated by UtA Doppler during the second and third trimesters in women defined as high risk by abnormal first-trimester UtA Doppler. METHODS: This randomized Phase-II study had a triple-blind, parallel-arm, controlled design. Singleton pregnancies with abnormal mean UtA Doppler at 11-14 weeks and absence of other major risk factors for PE received 150 mg extended-release aspirin or identical-appearing placebo tablets from study inclusion to 28 weeks. Main outcome measure was UtA pulsatility index (PI) at 28 weeks' gestation. Secondary outcomes included frequency of development of PE and growth restriction/small-for-gestational age (SGA). RESULTS: A total of 155 women completed the follow-up and were analyzed. No difference in mean UtA-PI was found between women in the aspirin and placebo groups at 28 weeks (mean UtA-PI Z-score (mean ± SD), 0.99 ± 1.48 vs 0.85 ± 1.25; P = 0.52). Seven women developed PE: four (5%) in the aspirin group and three (4%) in the placebo group. There was a trend toward lower incidence of SGA in the aspirin group (8.8% vs 17.3%; P = 0.11). CONCLUSION: In women with defective trophoblastic invasion, as reflected by abnormal UtA Doppler, low-dose aspirin started in the first trimester does not have a significant effect on UtA impedance as pregnancy progresses; however, the study was underpowered to detect potential small effects . Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

First-trimester screening for early and late small-for-gestational-age neonates using maternal serum biochemistry, blood pressure and uterine artery Doppler.

OBJECTIVE: To assess the effectiveness of first-trimester screening for early and late small-for-gestational-age (SGA) neonates using maternal serum biochemistry, blood pressure and uterine artery Doppler. METHODS: This was a prospective study of 4970 women with a singleton pregnancy who underwent routine first-trimester screening between 2009 and 2011. A logistic regression-based predictive model for SGA, defined as birth weight < 10(th) percentile, divided into early- or late-onset based on gestational age at delivery before or after 34 weeks' gestation, was constructed. The model included maternal baseline characteristics: serum levels of pregnancy-associated plasma protein-A and free ß-human chorionic gonadotropin at 8-12 weeks and blood pressure and uterine artery Doppler at 11 + 0 to 13 + 6 weeks. RESULTS: The prevalence of early and late SGA was 0.6% and 7.9%, respectively. Association with pre-eclampsia was 67% and 8%, respectively. At a false-positive rate of 15%, the detection rate for early SGA was 73%; however it differed substantially for cases with and without pre-eclampsia (90% vs 40%). For late SGA, at false-positive rates of 15 and 50%, detection rates were 32% and 70%, respectively, and did not substantially differ between cases with and without pre-eclampsia. CONCLUSIONS: First-trimester screening predicts early SGA mainly because of its strong association with pre-eclampsia. Although prediction of late SGA was poorer, at a high false-positive rate it might be considered as part of a first-trimester strategy to select women requiring ultrasound assessment in the third trimester.

Increased nuchal translucency and normal karyotype: perinatal and pediatric outcomes at 2 years of age.

OBJECTIVE: To assess the perinatal and pediatric outcomes up to 2 years of age in singleton karyotypically normal fetuses with increased nuchal translucency (NT) above the 99(th) percentile. METHODS: Singleton fetuses with NT above the 99(th) percentile and normal karyotype scanned in our center from 2002 to 2006 were included. Work-up included first- and second-trimester anomaly scan, first- and second-trimester fetal echocardiography, and in selected cases infection screening and genetic testing. Among survivors, a pediatric follow-up up to 2 years of age was undertaken. RESULTS: During this 4-year period, 171 singleton fetuses with NT above the 99(th) percentile and normal karyotype were included in the study. There were seven spontaneous fetal losses, 38 terminations of pregnancy and two postnatal deaths. Among the 124 (72.5%) survivors, 12 (9.7%) were born with structural abnormalities. Neurodevelopmental follow-up was completed in 108 (87.1%) of the 124 survivors and four (3.7%) showed moderate to severe impairment. Overall, a structural abnormality or genetic syndrome was diagnosed in 50 fetuses/newborns. Prenatal diagnosis was achieved for 83.8% (31/37) of the structural abnormalities and 69.2% (9/13) of the genetic syndromes. Interestingly, a single umbilical artery was found in six fetuses with no structural defects at birth, five of which had a long-term favorable outcome (4.5%), and in one 22q11 microdeletion syndrome was diagnosed at 2 years of age. CONCLUSION: Singleton fetuses with an increased NT above the 99(th) percentile and normal karyotype showed a 63% intact survival. Long-term neurodevelopmental outcome among survivors did not appear to differ from that reported for the general population.

Longitudinal changes in uterine, umbilical and fetal cerebral Doppler indices in late-onset small-for-gestational age fetuses.

OBJECTIVES: To determine the longitudinal trends and rates of conversion of normal to abnormal uterine (UtA), umbilical (UA) and middle cerebral artery (MCA) Doppler velocimetry throughout the third trimester in late-onset small-for-gestational-age (SGA) fetuses. METHODS: UtA, UA and MCA Doppler velocimetry was serially performed in a cohort of singleton consecutive late-onset SGA fetuses with normal Doppler values at diagnosis. The rate of conversion of normal to abnormal Doppler values was evaluated by survival analysis. Longitudinal trends were modeled by means of multilevel analysis. RESULTS: A total of 616 scans were performed on 171 SGA fetuses. Mean gestational age at inclusion and at delivery was 34.1 (SD 1.6) and 38.7 (SD 1.7) weeks, respectively. The proportions of abnormal UtA (2.3 vs. 4.1%) and UA (2.3 vs. 2.9%) pulsatility index (PI) were not significantly different between 37 weeks and before delivery. On the other hand, the proportions of abnormal MCA-PI (4.1 vs. 13.5%) and cerebroplacental ratio (CPR) (7 vs. 22.8%) were significantly different between these two examinations. The remaining proportion of cases with normal UtA-, UA- and MCA-PIs and CPR at 40 weeks were 98.6, 94.5, 85 and 49.6%, respectively. Whereas a slight increasing trend was observed for the UtA-PI (ß = 0.002) and UA-PI (ß = 0.01), MCA-PI (ß = 0.044) and CPR (ß = 0.124) showed a progressive decrease until delivery. CONCLUSIONS: Late-onset SGA fetuses with normal Doppler velocimetry upon diagnosis show progression from 37 weeks' gestation with worsening CPR followed by a decrease in MCA-PI.

Learning curve for Doppler measurement of fetal modified myocardial performance index.

OBJECTIVE: To assess the learning curve for measurement of the fetal modified myocardial performance index (MPI). METHODS: Three trainees with the theoretical knowledge of but without prior experience in performing MPI measurement were selected. Each trainee and one experienced examiner measured MPI in a cohort of 90 consecutive fetuses. The average difference between the three trainees and the expert in the MPI measurements was calculated; a difference below 10% was considered to indicate an accurate measurement. Individual and averaged learning curves were delineated using cumulative sum analysis (CUSUM). RESULTS: The gestational age at evaluation ranged from 20 + 4 to 41 + 4 (mean, 33 + 3) weeks. The CUSUM plots demonstrated that, on average, competence in performing fetal MPI measurement was achieved by 65 cases. The average number of attempts to achieve competence were 42, 77 and 83 for the ejection time, isovolumetric contraction time and isovolumetric relaxation time, respectively. CONCLUSIONS: Evaluation of fetal MPI by an inexperienced trainee requires on average 65 measurements to achieve competence.

Middle versus anterior cerebral artery Doppler for the prediction of perinatal outcome and neonatal neurobehavior in term small-for-gestational-age fetuses with normal umbilical artery Doppler.

OBJECTIVE: To evaluate whether anterior cerebral artery (ACA) Doppler ultrasonography is superior to middle cerebral artery (MCA) Doppler in the prediction of perinatal outcome and neonatal neurobehavior in term small-for-gestational-age (SGA) fetuses with normal umbilical artery (UA) Doppler. METHODS: MCA and ACA Doppler ultrasonography was performed in a cohort of SGA term fetuses with normal UA Doppler. Perinatal outcome and neonatal neurobehavioral performance were compared with a group of term appropriate-for-gestational age (AGA) infants. Neurobehavior was evaluated at 40 ( +/- 1) weeks of corrected age with the Neonatal Behavioral Assessment Scale. Differences between the study groups were adjusted for potential confounding variables by multiple linear or logistic regression analyis. RESULTS: A total of 199 newborns (98 SGA and 101 AGA) were included. Among the SGA fetuses, 28.6 and 17% had MCA and ACA redistribution, respectively. Cases with either type of redistribution had an increased risk for adverse outcome, with no differences in predictive performance between the two parameters. SGA fetuses with MCA redistribution compared with controls had an increased risk for abnormal neurobehavioral performance in motor (36 vs. 20%; adjusted P = 0.02) and state organization (25 vs. 17.5%; adjusted P = 0.03) areas. SGA fetuses with ACA redistribution had only an increased risk for abnormal neurobehavioral performance area in state organization compared with controls (30 vs. 17.5%; adjusted P = 0.021). CONCLUSION: In term SGA newborns with no signs of brain-sparing, ACA Doppler investigation does not provide any benefit over MCA in terms of the prediction of adverse perinatal outcome.

Prevalence and perinatal outcome of dichorionic and monochorionic twins with nuchal translucency above the 99(th) percentile and normal karyotype.

OBJECTIVE: To evaluate the prevalence of and perinatal outcome associated with increased nuchal translucency thickness (NT) > 99(th) percentile in dichorionic and monochorionic twins with normal karyotype. METHODS: Two hundred and six consecutive twin pregnancies (166 dichorionic and 40 monochorionic) underwent an NT scan during a 4-year period. In those with NT > 99(th) percentile and normal karyotype, we performed first- and second-trimester anomaly scans, fetal echocardiography at 14-16 and 20-22 weeks, maternal serology and, in monochorionic pregnancies, serial ultrasound examinations every other week. Perinatal outcome was recorded. RESULTS: There were 10 (4.95%) pregnancies in which one of the fetuses had NT > 99(th) percentile and normal karyotype, including five fetuses (1.5%) in dichorionic and five (6.25%) in monochorionic pregnancies. During the same period the prevalence of NT > 99(th) percentile and normal karyotype in singleton pregnancies studied in our center was 2.6%. Among the 10 twins affected, six (60%) were diagnosed with structural abnormalities (three dichorionic and three monochorionic), and two intrauterine fetal demises occurred (one dichorionic and one monochorionic). Thus, the perinatal outcome was normal in only two of the pregnancies, one dichorionic and one monochorionic. CONCLUSIONS: The prevalence of NT > 99(th) percentile in dichorionic twins with a normal karyotype is similar to that in singletons. In monochorionic twins we confirmed previous studies reporting an increased prevalence compared with singletons. NT > 99(th) percentile with a normal karyotype in twins was associated with a high rate of fetal abnormalities and/or fetal demise (overall 80%) irrespective of chorionicity.

Neurodevelopmental outcome in 2-year-old infants who were small-for-gestational age term fetuses with cerebral blood flow redistribution.

OBJECTIVE: To assess the neurodevelopmental outcome at 2 years of age of children who had been small-for-gestational-age (SGA) term babies with cerebral blood flow redistribution. METHODS: Perinatal outcome was assessed in a cohort of 97 term singleton appropriate-for-gestational-age and 125 term singleton SGA fetuses with normal umbilical artery Doppler, stratified according to the presence of cerebral blood flow redistribution. Neurodevelopmental outcome was assessed prospectively at 2 years of age by means of the 24-month Age & Stage Questionnaire (ASQ). RESULTS: Of the 125 SGA fetuses, 25 had redistribution of the cerebral blood flow, and 100 did not. There were no significant differences in perinatal outcome between these two SGA groups. At 2 years of age, children who had been SGA fetuses with middle cerebral artery (MCA) pulsatility index (PI) < 5(th) centile had a higher incidence of suboptimal neurodevelopmental outcome compared with those with normal MCA-PI (52% vs. 31%; P = 0.049) and a lower mean centile in communication (53.1 vs. 67.4; P = 0.006) and problem-solving (39.7 vs. 47.4; P = 0.04) areas. CONCLUSION: SGA fetuses with cerebral blood flow redistribution have a higher risk of subtle neurodevelopmental deficits at 2 years of age. This challenges the concept that fetal cerebral redistribution is an entirely protective mechanism and suggests MCA-PI as a risk stratifying factor for adverse neurodevelopmental outcome.

Association of smoking during pregnancy and fetal growth restriction: subgroups of higher susceptibility.

OBJECTIVE: To analyze the association between maternal smoking and fetal growth restriction, defined as a failure to achieve the growth potential, and to define subgroups of higher susceptibility for this association. STUDY DESIGN: A definition of growth restriction by customized birthweight standards applied to 13,661 non-malformed singleton deliveries. Customization was performed by maternal ethnic origin, height, booking weight, parity, gestational age at delivery and fetal gender. The adjusted risk of smoking for customized smallness-for-gestational age and the identification of subgroups with higher susceptibility were assessed by logistic regression. RESULTS: Overall, the adjusted odds ratio of smoking (all levels of exposure grouped) for the occurrence of growth restriction was 1.9 (95% confidence interval: 1.69-2.13). Smoking was etiologically responsible for 13.9% (95% confidence interval: 11.2-16.5) of the cases of growth restriction occurring in the population. Smoking resulted in an increasingly greater risk of growth restriction with progressive levels of cigarette consumption. The risk of smoking for fetal growth restriction was significantly greater in older women and those with a previous history of spontaneous preterm delivery. CONCLUSIONS: Smoking is associated with a higher risk for growth restriction. In addition, older pregnant women and those with a previous history of preterm delivery have an increased susceptibility.