Natural history and mid-term neurodevelopmental outcome of fetuses with isolated mild ventriculomegaly diagnosed in the second half of pregnancy.

INTRODUCTION: Prenatal diagnosis and counseling of isolated ventriculomegaly (VM) represent a considerable challenge. We aimed to analyze the intrauterine evolution, associated anomalies, and neurodevelopmental outcome using the Battelle Development Inventory (BDI) of fetuses with an initial diagnosis of isolated mild VM. MATERIAL AND METHODS: Retrospective cohort study of fetuses diagnosed with mild isolated VM (10 -12 mm) between 2012 and 2016 in a tertiary hospital. In 2018, parents were invited to complete the structured BDI test for the neurodevelopmental evaluation of their children in five domains (personal-social skills, adaptive behavior, psychomotor ability, communication, and cognition). Results exceeding two standard deviations were considered abnormal and referred to an expert neuropediatrician. RESULTS: We identified 43 cases of mild isolated VM. In 5 (11%), structural abnormalities were detected during prenatal follow-up, being related to non-regressive forms (p = .01) and bilateral VM (p = .04). The BDI test was completed by 19/43 (44%). The global score was abnormal in 10/19 (53%). Of them, the neuropediatrician confirmed a neurodevelopmental delay solely in 3 cases that had already been diagnosed with neurological disorders. The most affected domains were gross motor skills (63%), personal-social (63%), and adaptive domains (47%). Communicative and cognitive areas were abnormal in 26% of cases. CONCLUSION: In fetuses with isolated mild VM detected in the second half of pregnancy, 53% had an abnormal BDI test at 2-6 years, but a neurological disorder was only confirmed in the 30% of them.

Prenatal diagnosis of isolated coronary artery fistula: systematic review, analysis of perinatal prognostic factors and case report.

BACKGROUND: Isolated coronary artery fistula (CAF) is a rare entity in which evidence for both prognosis and need for perinatal treatment is lacking. We aim to evaluate the characteristics, evolution and perinatal outcomes of reported cases, including one from our center. MATERIAL AND METHODS: We performed a systematic review in Medline, Pubmed, and Embase databases for cohort studies or case series related to prenatally diagnosed isolated congenital CAF according to PRISMA guidelines. The search was restricted to articles published until January 2022, including a case report from our center. A descriptive analysis was performed, and perinatal characteristics were dichotomized by outcome (development of symptoms, as well as the need for surgery during the neonatal period). Strength of association between prenatal variables and outcome was evaluated through Odds Ratio. RESULTS: Only 27 cases of prenatal diagnosis of isolated CAF have been published, including our patient. Most had their origin in the right coronary artery (63%) and drained in the right ventricle (55.6%). Most cases (72%) developed progressive intrauterine dilation of the fistulous tract, which was usually associated with symptoms of cardiac overload, such as cardiomegaly (57.7%). Up to two-thirds of prenatally diagnosed patients developed heart failure symptoms in the neonatal period, and 84% required postnatal intervention. Prenatal diagnosis of both cardiomegaly and diastolic steal is associated with an OR of 52 and 41 of developing postnatal symptoms. CONCLUSION: Prenatal diagnosis of isolated CAF can be achieved with adequate tools and trained sonographers. The development of cardiomegaly and diastolic steal significantly increases the risk of developing postnatal symptoms.

Longitudinal changes in angiogenesis biomarkers within 72 h of diagnosis and time-to-delivery in early-onset preeclampsia.

OBJECTIVES: To evaluate the association between the increment of the sFlt-1/PlGF ratio within the first 72 h after the diagnosis of early-onset preeclampsia (PE) and the time-to-delivery. Secondarily we aimed to test its predictive value for maternal adverse outcomes. STUDY DESIGN: Retrospective cohort study of 155 women with early-onset PE and measurement of sFlt-1/PlGF at diagnosis and delivery from which the expected distributions of the daily increment (Δ) of sFlt-1/PlGF ratio, sFlt-1 and PlGF were obtained. Of them, in 110 a short-term evaluation at 72 +/- 24 h was available and Δ72h were calculated and compared to the expected distributions. The high-risk groups were those with Δ72h sFlt-1/PlGF and Δ72h sFlt-1 > 3rd expected quartile or Δ72h PlGF < 1st expected quartile. The low-risk groups were those with Δ72h ≤ 0 for sFlt-1/PlGF and sFlt-1 or Δ72h PlGF ≥ 0. The rest were considered intermediate risk. MAIN OUTCOME MEASURES: Time-to-delivery and maternal adverse outcomes were compared between the three groups. RESULTS: Δ72h sFlt-1/PlGF and sFlt-1 > 3rd quartile had a significant reduction of time-to-delivery when compared to increments < 3rd quartile or ≤ 0 (5 vs 11 vs 14 days, p < 0.01) and (6 vs 8 vs 15 days, p < 0.01), respectively. Both were limited for the prediction of maternal adverse outcomes. Δ72h PlGF showed no significant relation with time-to-deliver but all abruptio placentae had PlGF < 70 pg/mL at diagnosis. CONCLUSION: High Δ72h sFlt-1/PlGF and sFlt-1 are associated to a shorter time-to-delivery while low PlGF at diagnosis is associated to abruptio placentae.

Predictors of adverse perinatal outcome up to 34 weeks, a multivariable analysis study.

The objective was to evaluate the best predictors of adverse perinatal outcome (APO) in foetuses examined up to 34 weeks and delivered by spontaneous or induced labour. This was a retrospective study of 129 pregnancies that underwent an ultrasound Doppler examination at 23-34 weeks and entered into labour within 30 days. Cerebroplacental ratio (CPR) and mean uterine artery pulsatility index (mUtA PI) were converted into multiples of the median (MoM) and estimated foetal weight (EFW) into centiles to adjust for gestational age (GA). Sonographic and clinical parameters were evaluated using logistic regression analysis.The multivariable model for the prediction of APO presented a notable accuracy: Detection rate (DR) was 39.5% for a false positive rate (FPR) of 5% and 56.8% for a FPR of 10%, AUC 0.82, p < .0001. Significant predictors were GA, EFW centile, and CPR MoM, but not mUtA PI MoM. Moreover, the type of labour onset did not exert any influence on APO. In conclusion, up to 34 weeks, prediction of APO after spontaneous or induced labour may be done measuring CPR and EFW.IMPACT STATEMENTWhat is already known on this subject? Earlier in pregnancy, foetal growth restriction is caused by placental disease causing progressive hemodynamic changes. These changes have been exhaustively described. Conversely, information about the best predictors of adverse outcome is scarce.What do the results of this study add? The findings of this study show that prior to 34 weeks and up to 1 month before labour, labour outcome might be predicted by gestational age, foetal cerebroplacental ratio (CPR) and estimated foetal weight (EFW).What are the implications of these findings for clinical practice and/or further research? If CPR behaves as a good marker of outcome not only at the end of pregnancy but also earlier in gestation, it might be interrogated along with EFW in foetuses attempting vaginal delivery to determine the risk of adverse outcome.

Correlation of Kryptor and Elecsys® immunoassay sFlt-1/PlGF ratio on early diagnosis of preeclampsia and fetal growth restriction: A case-control study.

OBJECTIVES: The measurement of the soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1/PlGF) ratio on automated platforms has improved the detection of preeclampsia and fetal growth restriction (PE/FGR). The cut-off points of >38 and ≥85 has been defined for "rule in" and "aid in diagnosis", respectively, using the Elecsys® platform. We aimed to compare the performance of these cut-offs between the Elecsys® and Kryptor platforms at 24-28 weeks. STUDY DESIGN: Observational case-control study of singleton pregnancies at high risk for PE/FGR and sFlt-1/PlGF measurement at 24-28 weeks' gestation: 21 cases (9 early PE/FGR with delivery <32 weeks) were 1:1 matched for body mass index and parity with 21 controls. Correlations of the sFlt-1, PlGF and sFlt-1/PlGF values and diagnostic accuracy of the >38 and ≥85 cutoffs for early and late PE/FGR using Elecsys® and Kryptor assays were evaluated. MAIN OUTCOME MEASURES: PE/FGR cases showed significantly higher median (IQR) sFlt-1/PlGF values at 24-28 weeks vs. controls, using both Elecsys® and Kryptor platforms: 55 (13-254) and 97 (13-530) vs. 4.1 (2.0-6.5) and 3.9 (1.8-7.7), respectively. The sFlt-1/PlGF correlation between both methods was excellent (r2 = 0.95) although lower PlGF and higher sFlt-1/PlGF values were observed with Kryptor. The higher diagnostic accuracy was obtained for early PE/FGR with the ≥85 cutoff (95.2%; 95%CI: 83.8-99.4%) in both platforms. CONCLUSION: sFlt-1/PlGF measurements correlates well between Elecsys® and Kryptor platforms, and the cutoffs of >38 and ≥85 exhibit high diagnostic accuracy for assessing early PE/FGR at 24-28 weeks with both methods.

Prognostic Factors of Successful Cervical Ripening and Labor Induction in Late-Onset Fetal Growth Restriction.

OBJECTIVE: The aim of this work was to identify independent risk factors influencing the achievement of vaginal delivery among women undergoing labor induction for late-onset fetal growth restriction (FGR). METHODS: This was a retrospective cohort study of 201 singleton pregnancies with late-onset FGR (diagnosed >32 + 0 weeks) that required labor induction with cervical ripening from 37 + 0 weeks, either with dinoprostone (from 2014 to 2015) or Foley balloon (from 2016 to 2018). Independent factors for successful vaginal delivery were identified. A prediction model of vaginal delivery with the identified factors was made using logistic regression and bootstrapping with 1,000 re-samples performed for bias correction. RESULTS: Perinatal results were more favorable in the vaginal delivery group, with significantly lower neonatal admission rates (4.0 vs. 13.7%) and lower composite neonatal morbidity (4.0 vs. 15.7%). The labor induction method (Foley balloon), higher cerebro-placental ratio, lower pre-gestational BMI, and absence of pre-eclampsia were identified as independent factors associated to vaginal delivery. The area under the curve of the model was of 0.75 (95% CI 0.70-0.79). CONCLUSIONS: The use of a Foley balloon is the only modifiable risk factor to improve the chances of vaginal delivery when attempting induction of labor in singleton pregnancies with late-onset FGR.

Prognostic value of the aortic isthmus Doppler assessment on late onset fetal growth restriction.

Background As conflicting results have been reported about the association of reversed flow on the aortic isthmus (AoI) and adverse perinatal results in fetal growth restriction (FGR), we aim to compare perinatal outcomes (including tolerance to labor induction) of late-onset FGR between those with anterograde and reversed AoI flow. Methods This was an observational retrospective cohort study on 148 singleton gestations diagnosed with late-onset FGR (diagnosis ≥32+0 weeks), with an estimated fetal weight (EFW) <10th centile and mild fetal Doppler alteration: umbilical artery (UA) pulsatility index (PI) >95th centile, middle cerebral artery (MCA)-PI <5th centile or cerebral-placental ratio <5th centile. Anterograde AoI flow was present in n=79 and reversed AoI flow in n=69. Delivery was recommended from 37 weeks in both groups. Perinatal results were compared between the groups. Results The global percentage of vaginal delivery of fetuses with anterograde and reversed blood flow was 55.7% vs. 66.7% (P=0.18) and the percentage of cesarean section (C-section) for non-reassuring fetal status was 12.7% vs. 15.9% (P=0.29), respectively. When evaluating those that underwent labor induction, the vaginal delivery rate was 67.9% vs. 77.2% (P=0.17), respectively. There were no significant differences regarding any other perinatal variables and there were no cases of severe morbidity or mortality. Conclusion We observed that the presence of reversed AoI flow does not worsen perinatal outcomes on fetuses with late-onset growth restriction with mild Doppler alterations. Attempt of labor induction is feasible in these fetuses regardless of the direction of AoI flow.

Labor Induction in Late-Onset Fetal Growth Restriction: Foley Balloon versus Vaginal Dinoprostone.

OBJECTIVE: To compare vaginal delivery rate and perinatal outcomes of fetuses with late-onset fetal growth restriction (FGR) undergoing labor induction, depending on the method for cervical ripening (dinoprostone vs. Foley balloon). MATERIAL AND METHODS: We conducted a retrospective cohort study of 148 consecutive singleton gestations diagnosed with stage I late-onset FGR and Bishop score < 7, in which labor induction was indicated at ≥37 + 0 weeks. Before January 2016, cervical ripening was achieved with 10 mg of vaginal dinoprostone (n = 77) and afterwards with Fo-ley balloon (n = 71). Logistic regression analysis was used to estimate the association between mode of delivery and induction method. RESULTS: Foley balloon had lower percentages of uterine tachysystole with fetal repercussion (4.2 vs. 16.9%, p = 0.01) and cesarean sections for suspected fetal distress (7.0 vs. 26.0%, p < 0.01) when compared to dino-prostone. Lower percentages of cesarean sections were found in the Foley balloon group (15.5 vs. 37.7%, p < 0.01). The odds ratio and adjusted odds ratio of cesarean section with dinoprostone were of 3.3 and 4.4, respectively. Perinatal mortality and severe morbidity were null in both groups. CONCLUSION: The use of Foley balloon resulted in a higher percentage of vaginal delivery compared to dinoprostone, with a favorable safety profile in both groups.

Fetal Biometry and Doppler Study for the Assessment of Perinatal Outcome in Stage I Late-Onset Fetal Growth Restriction.

OBJECTIVE: To compare perinatal outcomes on fetuses classified as stage I late-onset fetal growth restriction (FGR) depending on the estimated fetal weight (EFW) centile category and the fetal and maternal Doppler study. MATERIAL AND METHODS: Retrospective cohort study on 131 cases of stage I late-onset FGR (diagnosis ≥32+0 weeks), defined as: EFW < 3rd centile and normal Doppler (G1) or EFW < 10th centile and mean uterine artery pulsatility index (PI) > 95th centile (G2) or EFW < 10th centile and mild fetal Doppler alteration: umbilical artery PI > 95th centile, middle cerebral artery PI < 5th centile, or cerebroplacental ratio < 5th centile (G3). All groups were compared to their perinatal results. RESULTS: There were 37, 30, and 64 cases in G1, G2, and G3, respectively. G1 and G2 showed lower percentages of cesarean section when compared with G3 (18.4, 22.5, and 45.3% (p < 0.01), respectively), being attributable to an excess of cesarean sections for non-reassuring fetal status. These differences remained when definitive birth weight centile was above that considered to define FGR, being 5.9, 12.5, and 41.8% (p < 0.01), respectively. DISCUSSION: In stage I late-onset FGR fetuses, abnormal fetal Doppler is associated with a poorer tolerance to vaginal delivery, even when the birth weight is > 10th centile.

Angiogenesis-related biomarkers (sFlt-1/PlGF) in placental mesenchymal dysplasia.

Determination of the soluble fms-like tyrosine kinase-1 to placental growth factor ratio (sFlt-1/PlGF) in the maternal serum is expected to aid in the monitoring and decision-making process of women at risk for placental dysfunction. We report two cases of placental mesenchymal dysplasia (PMD) with sFlt-1/PlGF correlation. The first case is a dichorionic twin pregnancy with one fetus affected by PMD and Beckwith-Wiedemann syndrome in which a high value of sFlt-1/PlGF was found, coinciding with acute maternal and fetal wellbeing decline at 31 weeks. The second case corresponds to a singleton pregnancy diagnosed of PMD with normal sFlt-1/PlGF and favorable outcome.

Angiogenesis-Related Biomarkers (sFlt-1/PLGF) in the Prediction and Diagnosis of Placental Dysfunction: An Approach for Clinical Integration.

Placental dysfunction is involved in a group of obstetrical conditions including preeclampsia, intrauterine growth restriction, and placental abruption. Their timely and accurate recognition is often a challenge since diagnostic criteria are still based on nonspecific signs and symptoms. The discovering of the role of angiogenic-related factors (sFlt-1/PlGF) in the underlying pathophysiology of placental dysfunction, taking into account that angiogenesis-related biomarkers are not specific to any particular placental insufficiency-related disease, has marked an important step for improving their early diagnosis and prognosis assessment. However, sFlt-1/PlGF has not been yet established as a part of most guidelines. We will review the current evidence on the clinical utility of sFlt-1/PlGF and propose a new protocol for its clinical integration.

Gestational age-specific scoring systems for the prediction of coarctation of the aorta.

OBJECTIVES: To determine which combination of cardiac parameters provides the best prenatal prediction of coarctation of aorta (CoAo). METHODS: We selected all cases of simple cardiac asymmetry prenatally diagnosed in 2003-2013. Logistic regression was used to select the best predictors of CoAo. RESULTS: The study population included 115 fetuses. CoAo was confirmed in 52 neonates (45%). The sample was divided in two groups according to the gestational age (GA) at diagnosis: early group (EG) ≤28 weeks (n = 57), and late group (LG) >28 weeks (n = 58). CoAo was confirmed in 75% and 16% of cases, respectively. GA-specific scoring systems with maximum two parameters were made, and the pairwise combination with the best diagnostic performance for each group was selected. In EG, the z-score of ascending aorta (AAo) and aortic isthmus (three vessels and trachea view) showed the best diagnostic accuracy [area under receiver-operating curve (AUC) 0.98, 95% confidence interval (CI) 0.94-1.00]. In the LG, the best results were provided by the tricuspid valve/mitral valve ratio with the main pulmonary artery/AAo ratio (AUC 0.84, 95% CI 0.67-1.00). CONCLUSIONS: Gestational age-specific scoring systems combining size-based cardiac parameters may improve the accuracy of fetal echocardiography to stratify the risk of CoAo. The objectivity and simplicity of its components may facilitate its implementation in fetal cardiology units.

Mid-term neurodevelopmental outcome in isolated mild ventriculomegaly diagnosed in fetal life.

OBJECTIVE: To analyze mid-term neurodevelopment outcome in children with isolated mild ventriculomegaly (VM) ≤12 mm diagnosed in fetal life, using the Battelle Developmental Inventory Screening Test (BDIST). METHODS: 86 cases of mild VM were identified. 68 were excluded due to: other cerebral anomalies (n = 40), extra-cerebral anomalies (n = 3), chromosomal defects (n = 4), dysmorphic syndromes (n = 4), congenital infections (n = 2), termination of pregnancy (n = 9), stillbirth (n = 2) and incomplete follow-up (n = 4). 18 cases (range 1-8 years) of isolated mild VM were included for analysis. Seven neurodevelopment domains were assessed by BDIST. RESULTS: Routine neuropediatrical evaluation detected neurological disorders in five children (28%; 3 with language impairment, one left hemiparesis and one intellectual retardation). BDIST showed some degree of neurodevelopmental delay in higher proportions: 66% in social-personal skills, 56% in gross motor skills, 39% in adaptive behavior and 28% in fine motor skills. Communicative and cognitive areas were the least affected (11 and 22% had moderate-to-severe involvement, respectively). A general trend towards worse outcomes was observed in the group of ≥4 years, although significant differences were only found for gross motor skills. CONCLUSION: Subtle neurological delays may appear during the infant period in fetuses prenatally diagnosed of isolated mild VM. In consequence, adequate measures should be established for early detection and treatment.