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Objective: To determine the prevalence of pulmonary hypertension (PAH) in left-sided congenital diaphragmatic hernia (CDH); how we could predict it; and how PAH contributed to the model for mortality prediction.Study Design: Retrospective analysis in three European centers. The primary outcome was the presence of PAH on postnatal day (d) 1, 7, and at discharge. Studied predictors of PAH were: observed/expected-lung/head-ratio (o/e LHR), liver-herniation, fetoscopic endoluminal tracheal occlusion (FETO), and gestational age (GA) at delivery. The combined effect of pre- and postnatal variables on mortality was modeled by Cox regression.Results: Of the 197 neonates, 56 (28.4%) died. At d1, 67.5% (133/197) had PAH and 61.9% (101/163) by d7. Overall, 6.4% (9/141) had PAH at discharge. At d1, o/e LHR (odds ratio (OR) 0.96) and FETO (OR 2.99) independently correlated to PAH (areas under the curve [AUC]: 0.74). At d7, PAH significantly correlated only with the use of FETO (OR 3.9; AUC: 0.65). None were significant for PAH at discharge. Combining the occurrence of PAH with antenatal biomarkers improved mortality prediction (p = 0.02), in a model including o/e LHR (HR: 0.94), FETO (HR: 0.35), liver herniation (HR: 16.78), and PAH (HR: 15.95).Conclusions: Antenatal prediction of PAH was only moderate. The postnatal occurrence of PAH further increases the risk of death. Whereas this may be used to counsel parents in the postnatal period, our study demonstrates there is a need to find more accurate antenatal predictors for PAH. [ABSTRACT FROM AUTHOR]

Congenital diaphragmatic hernia can be diagnosed in the prenatal period and its severity can be measured by fetal imaging. There is now level I evidence that, in selected cases, Fetoscopic Endoluminal Tracheal Occlusion with a balloon increases survival to discharge from the neonatal unit as well as the risk for prematurity. Both effects are dependent on the time point of tracheal occlusion. Fetoscopic Endoluminal Tracheal Occlusion may also lead to iatrogenic death when the balloon cannot be timely retrieved. The implementation of the findings from our clinical studies, may also vary based on local conditions. These may be different in terms of available skill set, access to fetal therapy, as well as outcome based on local neonatal management. We encourage prior benchmarking of local outcomes with optimal postnatal management, based on large enough numbers and using identical criteria as in the recent trials. We propose to work further on prenatal prediction methods, and the improvement of fetal intervention. In this manuscript, we describe a research agenda from a fetal medicine perspective. This research should be in parallel with innovation in neonatal and pediatric (surgical) management of this condition. [ABSTRACT FROM AUTHOR]

Objective: Children with congenital diaphragmatic hernia (CDH) are at risk for neurodevelopmental delay. Herein we report on prenatal changes in biometry and brain perfusion in fetuses with isolated CDH. Study Design: This retrospective study evaluated fetuses with isolated, left‐sided CDH in three European referral centers. Abdominal circumference (AC), femur length (FL), head circumference (HC), transcerebellar diameter (TCD), middle cerebral artery (MCA) Doppler, and ventricular width (VW) were assessed during four gestational periods (<24 weeks, 25–28 weeks, 29–32 weeks, >33 weeks). Z‐scores were calculated, and growth curves were created based on longitudinal data. Results: In 367 fetuses, HC, AC and FL were within normal ranges throughout gestation. The TCD diminished with advancing gestational age to fall below the fifth percentile after 32 weeks. A less pronounced but similar trend was seen in VW. The peak systolic velocity of the MCA was consistently approximately 10% lower than normal. Disease severity was correlated to TCD (p = 0.002) and MCA doppler values (p = 0.002). There were no differences between fetuses treated with FETO and those managed expectantly. Conclusion: Fetuses with isolated left‐sided CDH have a small cerebellum and reduced MCA peak systolic velocity. Follow up studies are necessary to determine the impact of these changes on neurodevelopment. Key points: What's already known about this topic? Children with congenital diaphragmatic hernia (CDH) are at increased risk for neurodevelopmental problems. It remains uncertain if brain development is already impaired prenatally What does this study add?Fetuses with isolated CDH have a smaller than average cerebellum but normal sized head, which may indicate an altered prenatal brain development in CDHThis study is the first to report on biometry and cerebellar and ventricular growth curves and brain blood flow in fetuses with CDH [ABSTRACT FROM AUTHOR]

Objective: Adverse event (AE) monitoring is central to assessing therapeutic safety. The lack of a comprehensive framework to define and grade maternal and fetal AEs in pregnancy trials severely limits understanding risks in pregnant women. We created AE terminology to improve safety monitoring for developing pregnancy drugs, devices and interventions. Method: Existing severity grading for pregnant AEs and definitions/indicators of 'severe' and 'life‐threatening' conditions relevant to maternal and fetal clinical trials were identified through a literature search. An international multidisciplinary group identified and filled gaps in definitions and severity grading using Medical Dictionary for Regulatory Activities (MedDRA) terms and severity grading criteria based on Common Terminology Criteria for Adverse Event (CTCAE) generic structure. The draft criteria underwent two rounds of a modified Delphi process with international fetal therapy, obstetric, neonatal, industry experts, patients and patient representatives. Results: Fetal AEs were defined as being diagnosable in utero with potential to harm the fetus, and were integrated into MedDRA. AE severity was graded independently for the pregnant woman and her fetus. Maternal (n = 12) and fetal (n = 19) AE definitions and severity grading criteria were developed and ratified by consensus. Conclusions: This Maternal and Fetal AE Terminology version 1.0 allows systematic consistent AE assessment in pregnancy trials to improve safety. Key points: What's already known about this topic? Adverse event (AE) monitoring is central to assessing therapeutic safety. The lack of a comprehensive AE framework in pregnancy trials severely limits understanding risks in pregnant women What does this study add? Through international consensus we systematically developed definitions and severity grading for maternal and foetal AEs: Maternal and Fetal AE Terminology Version 1.0. New fetal AE definitions were adopted by the Medical Dictionary for Regulatory Activities. This terminology should be used to monitor safety in pregnancy trials [ABSTRACT FROM AUTHOR]

Intrauterine growth restriction (IUGR) is an obstetric complication characterised by placental insufficiency and secondary cardiovascular remodelling that can lead to cardiomyopathy in adulthood. Despite its aetiology and potential therapeutics are poorly understood, bioenergetic deficits have been demonstrated in adverse foetal and cardiac development. We aimed to evaluate the role of mitochondria in human pregnancies with IUGR. In a single‐site, cross‐sectional and observational study, we included placenta and maternal peripheral and neonatal cord blood mononuclear cells (PBMC and CBMC) from 14 IUGR and 22 control pregnancies. The following mitochondrial measurements were assessed: enzymatic activities of mitochondrial respiratory chain (MRC) complexes I, II, IV, I + III and II + III, oxygen consumption (cell and complex I‐stimulated respiration), mitochondrial content (citrate synthase [CS] activity and mitochondrial DNA copy number), total ATP levels and lipid peroxidation. Sirtuin3 expression was evaluated as a potential regulator of bioenergetic imbalance. Intrauterine growth restriction placental tissue showed a significant decrease of MRC CI enzymatic activity (P < 0.05) and CI‐stimulated oxygen consumption (P < 0.05) accompanied by a significant increase of Sirtuin3/β‐actin protein levels (P < 0.05). Maternal PBMC and neonatal CBMC from IUGR patients presented a not significant decrease in oxygen consumption (cell and CI‐stimulated respiration) and MRC enzymatic activities (CII and CIV). Moreover, CS activity was significantly reduced in IUGR new‐borns (P < 0.05). Total ATP levels and lipid peroxidation were preserved in all the studied tissues. Altered mitochondrial function of IUGR is especially present at placental and neonatal level, conveying potential targets to modulate obstetric outcome through dietary interventions aimed to regulate Sirtuin3 function. [ABSTRACT FROM AUTHOR]

Objectives: To compare the robustness of several methods based on quantitative ultrasound (US) texture analysis to evaluate its feasibility for extracting features from US images to use as a clinical diagnostic tool. Methods: We compared, ranked, and validated the robustness of 5 texture‐based methods for extracting textural features from US images acquired under different conditions. For comparison and ranking purposes, we used 13,171 non‐US images from widely known available databases (OUTEX [University of Oulu, Oulu, Finland] and PHOTEX [Texture Lab, Heriot‐Watt University, Edinburgh, Scotland]), which were specifically acquired under different controlled parameters (illumination, resolution, and rotation) from 103 textures. The robustness of those methods with better results from the non‐US images was validated by using 666 fetal lung US images acquired from singleton pregnancies. In this study, 2 similarity measurements (correlation and Chebyshev distances) were used to evaluate the repeatability of the features extracted from the same tissue images. Results: Three of the 5 methods (gray‐level co‐occurrence matrix, local binary patterns, and rotation‐invariant local phase quantization) had favorably robust performance when using the non‐US database. In fact, these methods showed similarity values close to 0 for the acquisition variations and delineations. Results from the US database confirmed robustness for all of the evaluated methods (gray‐level co‐occurrence matrix, local binary patterns, and rotation‐invariant local phase quantization) when comparing the same texture obtained from different regions of the image (proximal/distal lungs and US machine brand stratification). Conclusions: Our results confirmed that texture analysis can be robust (high similarity for different condition acquisitions) with potential to be included as a clinical tool. [ABSTRACT FROM AUTHOR]

Background: Congenital diaphragmatic hernia (CDH) is characterized by a defective closure of the diaphragm occurring as an isolated defect in 60% of cases. Lung size, liver herniation, and pulmonary circulation are major prognostic indices. Isolated CDH genetics is heterogeneous and poorly understood. Whether genetic lesions are also outcome determinants has never been explored.Objectives: To identify isolated CDH genetic causes, to fine map the mutational burden, and to search for a correlation between the genotype and the disease severity and outcome.Methods: Targeted massively parallel sequencing of 143 human and mouse CDH causative and candidate genes in a cohort of 120 fetuses with isolated CDH and detailed outcome measures.Results: Pathogenic and likely pathogenic variants were identified in 10% of the cohort. These variants affect both known CDH causative genes, namely, ZFPM2, GATA4, and NR2F2, and new genes, namely, TBX1, TBX5, GATA5, and PBX1. In addition, mutation burden analysis identified LBR, CTBP2, NSD1, MMP14, MYOD1, and EYA1 as candidate genes with enrichment in rare but predicted deleterious variants. No obvious correlation between the genotype and the phenotype or short-term outcome has been found.Conclusion: Targeted resequencing identifies a genetic cause in 10% of isolated CDH and identifies new candidate genes. [ABSTRACT FROM AUTHOR]

Aim: To compare macronutrient and fibre intake by pre-school children born with intra-uterine growth restriction (IUGR) or as appropriate for gestational age (AGA) and to compare their intake with paediatric nutritional recommendations for identification of potential areas of modification during early life.Methods: A parental 3-day dietary record was obtained for children of age 1-6 years, born at Hospital Clinic, Barcelona, Spain (2002-2007) with IUGR (n = 37) or AGA (n = 53). Mean nutrient intake (adjusted for body mass index), nutrient adequacy ratios (NAR) and percentage of energy intake (EI%) were compared.Results: Macronutrient and fibre intake of the two groups did not differ significantly. However, IUGR children showed significantly higher than the recommended levels of protein EI% (18 (95% confidence interval (CI) 16-19)), NAR for saturated fatty acids (SFAs) (1.2 (95% CI 1.1-1.5)) and NAR for carbohydrate (1.4 (95% CI 1.2-1.6)) and significantly lower than the recommended levels of NAR for unsaturated fatty acids (UFAs) (0.6 (95% CI 0.5-0.8)) and for fibre (0.6 (95% CI 0.5-0.8)). Likewise, children born with AGA showed similar pattern compared to the recommended levels for protein EI% (17 (95% CI 16-18)), NAR for SFAs (1.3 (95% CI 1.2-1.4)), NAR for UFAs (0.6 (95% CI 0.5-0.7)) and NAR for fibre (0.8 (95% CI 0.7-0.9)).Conclusion: Spanish pre-school children consume proteins and SFAs in abundance and UFAs and fibre in moderation. Reinforcement of healthy eating is recommended for long-term health benefits, especially for at-risk children born with IUGR, whose consumption of carbohydrate is additionally greater than that recommended. [ABSTRACT FROM AUTHOR]

Objectives: To perform a comprehensive assessment of cortical development in fetuses with isolated nonsevere ventriculomegaly (INSVM) by neurosonography.Methods: We prospectively included 40 fetuses with INSVM and 40 controls. INSVM was defined as atrial width between 10.0 and 14.9 mm without associated malformation, infection, or chromosomal abnormality. Cortical development was assessed by neurosonography at 26 and 30 weeks of gestation measuring depth of selected sulci and applying a maturation scale from 0 (no appearance) to 5 (maximally developed) of main sulci and areas.Results: INSVM showed underdeveloped calcarine and parieto-occipital sulci. In addition, significant delayed maturation pattern was also observed in regions distant to ventricular system including Insula depth (controls 30.8 mm [SD 1.7] vs INSVM 31.7 mm [1.8]; P = .04), Sylvian fissure grading (>2 at 26 weeks: controls 87.5% vs INSVM 50%, P = .01), mesial area grading (>2 at 30 weeks: controls 95% vs INSVM 62.5%; P = .03), and cingulate sulcus grading (>2 at 30 weeks: controls 100% vs INSVM 80.5%; P = .01).Conclusions: Fetuses with INSVM showed underdeveloped cortical maturation including also regions, where effect of ventricular dilatation is unlikely. These results suggest that in a proportion of fetuses with INSVM, ventricular dilation might be related with altered cortical architecture. [ABSTRACT FROM AUTHOR]

We reviewed data from a cohort of fetuses with ureterocele diagnosed and operated prenatally in four fetal therapy centers. Inclusion criteria were (1) ureterocele confirmed on detailed fetal ultrasound examination, (2) absence of additional fetal malformations, and (3) fetal intervention to decompress the ureterocele with local institutional review boards' approval. Data on sonographic follow-up, obstetrical, neonatal outcome, and postnatal evaluation were collected. Ten cases of prenatally treated ureterocele are described. Six cases benefited from a fetoscopy for laser incision and decompression, two cases had an ultrasound guided puncture before resorting to a fetoscopy with laser incision, one case had a balloon catheterization under ultrasound guidance, and one case had an ultrasound-guided opening of the ureterocele with a laser fiber passed through a 20-gauge needle. Mean gestational age at diagnosis was 21.6 GW. Two cases underwent termination of pregnancy. The remaining eight cases recovered normal amniotic fluid volume and delivered a liveborn child at a mean gestational age of 38.6 GW with normal creatinine levels during the first week of life. Prenatal incision provided complete treatment of severely obstructive ureteroceles in 80% of the cases and allowed improvement of urinary electrolytes, renal size and echogenicity, bladder filling in all survivors, and recollection of normal amniotic fluid volume, in case of oligoanhydramnios. © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

To assess the impact of HIV-infection and highly active anti-retroviral treatment in mitochondria and apoptotic activation of caspases during pregnancy and their association with adverse perinatal outcome. Changes of mitochondrial parameters and apoptotic caspase activation in maternal peripheral blood mononuclear cells were compared at first trimester of pregnancy and delivery in 27 HIV-infected and -treated pregnant women versus 24 uninfected pregnant controls. We correlated immunovirological, therapeutic and perinatal outcome with experimental findings: mitochondrial DNA (mt DNA) content, mitochondrial protein synthesis, mitochondrial function and apoptotic caspase activation. The HIV pregnancies showed increased adverse perinatal outcome ( OR: 4.81 [1.14-20.16]; P < 0.05) and decreased mt DNA content (42.66 ± 5.94%, P < 0.01) compared to controls, even higher in naïve participants. This depletion caused a correlated decrease in mitochondrial protein synthesis (12.82 ± 5.73%, P < 0.01) and function (20.50 ± 10.14%, P < 0.001), not observed in controls. Along pregnancy, apoptotic caspase-3 activation increased 63.64 ± 45.45% in controls ( P < 0.001) and 100.00 ± 47.37% in HIV-pregnancies ( P < 0.001), in correlation with longer exposure to nucleoside analogues. HIV-infected women showed increased obstetric problems and declined genetic and functional mitochondrial parameters during pregnancy, especially those firstly exposed to anti-retrovirals. The apoptotic activation of caspases along pregnancy is emphasized in HIV pregnancies promoted by nucleoside analogues. However, we could not demonstrate direct mitochondrial or apoptotic implication in adverse obstetric outcome probably because of the reduced sample size. [ABSTRACT FROM AUTHOR]

Fetal growth restriction (FGR) is among the obstetrical entities with the greatest variation in clinical practice. The first clinically relevant step in the management of FGR is the distinction of 'true' FGR, associated with signs of abnormal feto-placental function and poorer perinatal outcome, from small for gestational age fetuses, which do not present abnormal Doppler and have near normal perinatal outcome. Such distinction should not be only relied on umbilical artery Doppler, as this parameter identifies only severe, early-onset, forms of placental insufficiency. Instead, FGR should be diagnosed in the presence of any of the factors associated with a poorer perinatal outcome, including Doppler cerebroplacental ratio and uterine artery Doppler, a growth centile below the third centile. Upon diagnosis, differentiating into early-onset and late-onset FGR is useful to distinguish two clear phenotypes, with differences in severity, association with preeclampsia, and sequence of fetal deterioration. Finally, management of FGR aims at an optimal balance between minimizing fetal injury or death versus the risks of iatrogenic preterm delivery. We propose a protocol that integrates current evidence to classify stages of fetal deterioration, and establishes follow-up intervals and optimal delivery timings, which may facilitate decision-making and minimize variability in the clinical management. [ABSTRACT FROM AUTHOR]

Objective This study aimed to describe the distribution of placental growth factor (PlGF) plasma levels in pregnancies complicated by preeclampsia (PE) according to the gestational age at clinical onset and to assess PlGF's predictive role for maternal complications. Methods A total of 84 women whose pregnancies were complicated by PE before 37 weeks' gestation were enrolled. According to gestational age at onset, three groups were defined: group I, <28 weeks; group II, 28 to 31+6 weeks; and group III, 32 to 36+6 weeks. PlGF plasma levels were measured at diagnosis, and their association with maternal complications was investigated. Plasma PlGF levels below 12 pg/mL were designated as very low. Results PlGF levels were very low in seven (87.5%) of eight women diagnosed before 28 weeks' gestation, 29 (78.4%) of 37 patients diagnosed between 28 and 32 weeks' gestation, and 16 (41%) of 39 cases diagnosed after 32 weeks' gestation. The sensitivity of very low PlGF values for predicting maternal complications was 76.9%, but the false positive rate was 65.5%. Positive and negative predictive values were 34.5% and 76.9%, respectively. Conclusion The predictive role of a low PlGF level in predicting maternal complications in very early PE is limited because of both its low specificity and low positive predictive value. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective To evaluate Doppler parameters of the two segments of the posterior cerebral artery (PCA) in normally grown and growth restricted (IUGR) fetuses. Methods Normal reference values of the pulsatility index (PI), peak systolic velocity, end-diastolic velocity, and time-averaged maximum velocity from the two segments of the PCA (segment one, PCA-S1; segment two, PCA-S2) were constructed in 350 pregnant women from 20 to 40 weeks of gestation. The association of the two PCA segments with the middle cerebral artery (MCA), and with the umbilical artery was evaluated in 50 IUGR fetuses. Results In normal fetuses, Doppler parameters from PCA-S1 and PCA-S2 showed similar behavior throughout gestation. In IUGR fetuses, the PI of the two PCA segments was significantly reduced with no differences between them. PCA-S2 PI showed a higher correlation with the MCA-PI ( r = 0.73) than PCA-S1 PI ( r = 0.63; p = 0.001). IUGR fetuses showed vasodilatation in the PCA earlier than in the MCA disregarding the umbilical artery-PI value. Conclusion In IUGR fetuses, the two segments of the PCA show signs of vasodilatation earlier than the MCA. As IUGR fetuses deteriorate, the two segments of the PCA and the MCA behave similarly. © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT Measuring the stiffness of the cervix might be useful in the prediction of preterm delivery or successful induction of labor. For that purpose, a variety of methods for quantitative determination of physical properties of the pregnant cervix have been developed. Herein, we review studies on the clinical application of these new techniques. They are based on the quantification of mechanical, optical, or electrical properties associated with increased hydration and loss of organization in collagen structure. Quasi-static elastography determines relative values of stiffness; hence, it can identify differences in deformability. Quasi-static elastography unfortunately cannot quantify in absolute terms the stiffness of the cervix. Also, the current clinical studies did not demonstrate the ability to predict the time point of delivery. In contrast, measurement of maximum deformability of the cervix (e.g. quantified with the cervical consistency index) provided meaningful results, showing an increase in compliance with gestational age. These findings are consistent with aspiration measurements on the pregnant ectocervix, indicating a progressive decrease of stiffness along gestation. Cervical consistency index and aspiration measurements therefore represent promising techniques for quantitative assessment of the biomechanical properties of the cervix. © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective The aim of this study is to evaluate the independent and combined value of gestational age, fetal weight, fetoplacental Doppler, and myocardial performance index for the prediction of individual risk of early (≤7 days) intrauterine fetal death (IUFD) after laser therapy in twin-to-twin transfusion syndrome (TTTS). Material and Methods A consecutive series of 215 cases of TTTS treated with laser therapy in three centers was prospectively studied. Ultrasound evaluation within 24 h of surgery included estimated fetal weight discordance, umbilical artery, pulsatility index (PI) and diastolic flow evaluation, middle cerebral artery PI and middle cerebral artery peak systolic velocity, ductus venosus PI and atrial flow assessment, and modified myocardial performance index. Logistic regression analysis was used to explore the association of preoperative parameters with IUFD. Results Intrauterine fetal death occurred in 17 (7.9%) of the recipients and 33 (15.3%) donors ( p = 0.016). The only independent predictors of IUFD in recipients was the middle cerebral artery peak systolic velocity >1.5 MoM (OR = 22, p = 0.015), but this event was present in only 3% of recipients. In donors, reverse end diastolic flow in the umbilical artery (OR = 14.748, p = 0.033), estimated fetal weight discordance (OR = 1.054, p = 0.036), and gestational age (OR = 0.757, p = 0.046) were independent predictors. Conclusion In TTTS, preoperative fetal assessment can identify independent risk factors for early post-operative IUFD, particularly in donors. © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective We aimed to measure whether website-provided information about congenital diaphragmatic hernia (CDH) and fetal therapy for severe cases provides added value compared with clinical counseling of parents. Methods This is a single center study in 102 couples who earlier opted for fetoscopic endoluminal tracheal occlusion (FETO) because of isolated severe CDH. They were asked to fill out an anonymized web-based survey of 12 questions. Then, they were offered access to information on the web pages of the randomized Tracheal Occlusion to Accelerate Lung Growth (TOTAL) trial. One week later, their appreciation was measured again by a second questionnaire. Results Eighty-two (80%) parents completed the first questionnaire, and 48 (47%) completed the entire survey. Several items became more clear to the parents after reading the website, such as the length of hospital stay (23.2% prior to web information, 60.4% after; P = 0.004), maternal risk, or the requirement of fetal anesthesia for FETO (43.9% resp. 79.2%; P = <0.001). Conclusion Complementing prenatal counseling on CDH and FETO by standardized information via website is perceived by parents as of added value. Maternal risks and the need for fetal medication need more clarification during the verbal counseling prior to prenatal interventions. © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective To evaluate the fetal cardiac function by modified myocardial performance index (Mod-MPI) in pregnant diabetic patients. Methods Modified myocardial performance index was measured in fetuses of patients with diabetes (DM) between 30 and 40 weeks of gestation. The isovolumetric contraction time, isovolumetric relaxation time and ejection time were measured. Mod-MPI was calculated as (isovolumetric contraction time + isovolumetric relaxation time)/ejection time. Results were analyzed by using one-way analysis of variance (post hoc Bonferroni correction), Chi-square and Student's test. Results Modified myocardial performance index values of fetuses from DM mothers were significantly higher than controls (0.43 vs 0.37, P < 0.0001), and it was not different between gestational versus pregestational DM (0.42 vs 0.45, P = 0.18). Mod-MPI was also higher in the presence of polyhydramnios (0.49 vs 0.41, P < 0.0001), insulin use (0.46 vs 0.40, P < 0.05), and large for gestational age fetuses (0.49 vs 0.40, P < 0.0001). There were no significant differences in Mod-MPI between newborns with versus without neonatal complications such as hypoglycemia or polycythemia. Conclusions In fetuses of DM mothers, evaluation of the Mod-MPI identifies those with worse maternal disease and large fetal size. © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective To assess the predictive value of fetal nuchal translucency (NT) measurement in the prenatal diagnosis of single-gene disorders. Methods From January 1996 to December 2006, fetal NT was prospectively measured before chorionic villi sampling in 169 pregnancies at high risk for a single-gene disorder at 11 to 13 weeks of pregnancy. Results No differences were found between the 63 affected and 116 nonaffected fetuses in pregnancy demographic characteristics, in mean NT measurements, expressed either in millimetres [1.8 (95% CI:1.6-1.9) vs 1.7 (95% CI:1.6-1.8)] or in multiples of the median [1.19 (95%CI: 1.04-1.35) vs 1.14 (95%CI: 1.05-1.23)], or in median NT. The percentage of increased NT above the 95th percentile was similar for affected (9.5%) and nonaffected (11.2%) fetuses. Conclusion Not all single-gene disorders are associated with enlarged NT, therefore NT cannot be regarded as a generic marker for single-gene disorder but only for a limited number of these conditions. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective Congenital diaphragmatic hernia (CDH) is a congenital birth defect affecting around 1/3000 births. We propose that a significant number of isolated CDH cases have an underlying genetic cause, and that a subset of these result from copy number variations (CNVs) identifiable by array CGH. Methodology We have designed a custom array targeted at genes and genomic loci associated with CDH. A total of 79 isolated CDH patients were screened using this targeted array. Results In three patients, we detected genomic imbalances associated with the observed diaphragmatic hernia; a deletion of 8p22-p23.3, 14.2 Mb in size, a 340 kb duplication of Xq13.1 including the ephrin-B1 gene ( EFNB1), and mosaicism for trisomy 2. Conclusion Using this approach, we detected genomic imbalances associated with CDH in 3/79 (4%) isolated CDH patients. Our findings further implicate 8p deletions as being associated with CDH. The duplication of EFNB1 further highlights this gene as a potential candidate involved in diaphragm development. Mosaicism for trisomy 2 is a rare event and unlikely to be a common cause of CDH. Further investigations of isolated CDH patients by array CGH will continue to identify novel submicroscopic loci and refine genomic regions associated with CDH. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Fetal diagnosis prompts the question for fetal therapy in highly selected cases. Some conditions are suitable for in utero surgical intervention. This paper reviews historically important steps in the development of fetal surgery. The first invasive fetal intervention in 1963 was an intra-uterine blood transfusion. It took another 20 years to understand the pathophysiology of other candidate fetal conditions and to develop safe anaesthetic and surgical techniques before the team at the University of California at San Francisco performed its first urinary diversion through hysterotomy. This procedure would be abandoned as renal and pulmonary function could be just as effectively salvaged by ultrasound-guided insertion of a bladder shunt. Fetoscopy is another method for direct access to the feto-placental unit. It was historically used for fetal visualisation to guide biopsies or for vascular access but was also abandoned following the introduction of high-resolution ultrasound. Miniaturisation revived fetoscopy in the 1990s, since when it has been successfully used to operate on the placenta and umbilical cord. Today, it is also used in fetuses with congenital diaphragmatic hernia (CDH), in whom lung growth is triggered by percutaneous tracheal occlusion. It can also be used to diagnose and treat urinary obstruction. Many fetal interventions remain investigational but for a number of conditions randomised trials have established the role of in utero surgery, making fetal surgery a clinical reality in a number of fetal therapy programmes. The safety of fetal surgery is such that even non-lethal conditions, such as myelomeningocoele repair, are at this moment considered a potential indication. This, as well as fetal intervention for CDH, is currently being investigated in randomised trials. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objectives To assess the intra- and interobserver reliability of the umbilical vein (UV) diameter, time-averaged maximum velocity (TAMX) and umbilical vein blood flow (BF). Methods Sixty-three consecutive singleton pregnancies between 24 and 42 weeks were evaluated by two independent operators. UV diameter and TAMX were measured. UV flow was calculated as UV area × 60 × TAMX × 0.5. Reliability analyses were performed by means of the intraclass correlation coefficient (ICC) for agreement. Differences between and within observers were explored and agreement limits calculated by means of the Bland-Altman test. Results Satisfactory Doppler parameters were successfully obtained from all fetuses. The intraobserver ICCs for UV diameter, TAMX, and BF were 0.7, 0.59, and 0.55, respectively, whereas the interobserver ICCs were 0.65, 0.46, and 0.60, respectively. The 95% confidence intervals of the intraobserver differences were (+0.15, − 0.14), (+8.0, − 7.9), and (+150, − 138.7), respectively. The 95% confidence intervals of the interobserver differences were (+0.16, − 0.16), (+8.5, − 8.2), and (+138.8, − 141.9), respectively. Conclusions Noninvasive Doppler calculation of umbilical vein blood flow and its components are reliable enough for clinical use. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aim: To compare the prevalence of transient periventricular echodensities (TPE), periventricular leukomalacia (PVL) and haemorrhagic brain lesions (HBL) in singleton intrauterine growth-restricted (IUGR) infants and in those appropriate for gestational age (AGA). Methods: Thirty-five IUGR and 35 AGA singleton infants born between 24- and 34-week gestational age were studied. The presence of TPE, PVL and HBL was assessed with ultrasound (US) at day 3 (US-I), 2 weeks (US-II) after delivery and at term-equivalent age (US-III). Results: IUGR neonates had an increased prevalence of TPE at US-I (18/35 vs. 8/35, p= 0.02) and an increased prevalence of PVL at US-II (8/32 vs. 1/31, p = 0.03) and US-III (8/29 vs. 1/29, p = 0.02). No significant differences in the prevalence of HBL were found between the two groups. Conclusions: IUGR is associated with an increased prevalence of white matter damage on US brain scans in preterm neonates. [ABSTRACT FROM AUTHOR]

Objective: To assess the intra- and interobserver reliability of the fetal ductus venosus (DV) blood flow measurements at 11-14 weeks' gestation in a high-risk population for chromosomal defects. Methods: Thirty-five consecutive singleton pregnancies at high risk for chromosomal or genetic anomalies were included. DV end-diastolic velocity (EDV) and the pulsatility index for veins (PIV) were determined by manual tracing in three sets of waveforms by a single sonographist to assess intraobserver reliability using transvaginal ultrasound. Subsequently, the EDV and the PIV were also determined in a further set by a second sonographist to assess interobserver reliability. Reliability was evaluated by means of the Intraclass Correlation Coefficient (ICC). The degree of agreement was also examined using the limits of agreement method. Results: The intraobserver reliability was 0.81 (95% C.I. 0.69-0.89) for EDV and 0.91 (95% C.I. 0.85-0.95) for the PIV, both corresponding to almost perfect reliability. The interobserver reliability was 0.50 (95% C.I. 0.20-0.70) for EDV, and 0.74 (95% C.I. 0.54-0.86) for PIV, corresponding respectively to moderate and substantial reliabilities. The 95% interval of the EDV differences (cm/s) within and between observers were (+6.1, - 4.6) and (+13.6, - 9.7), respectively. The 95% interval of the PIV differences within and between observers were (+0.32, - 0.36) and (+0.7, - 0.67), respectively. Conclusions: Interobserver reliability for EDV is only moderate, whereas for the PIV is substantial, allowing its use for clinical purposes in a high-risk population. [ABSTRACT FROM AUTHOR]