Objective
To report a recent update on fetuses with right‐sided congenital diaphragmatic hernia (RCDH) in the era of fetal surgery.
Design
Retrospective review of prospectively collected data.
...Setting
Fetal treatment centres in Leuven and Barcelona.
Population
Consecutive cases of RCDH between 2002 and 2012.
Methods
Data on prenatal imaging, genetic testing, pregnancy and neonatal outcomes were extracted from our databases, including structural and genetic anomalies, candidate outcome predictors such as lung size, liver herniation ratio, polyhydramnios, cervical length, preterm prelabour rupture of membranes and gestational age at birth.
Main outcome measures
Survival and oxygen dependency at discharge.
Results
Ten out of 86 fetuses with RCDH had associated abnormalities. Of 76 isolated pregnancies, eight women opted for termination of pregnancy, most with severe hypoplasia and one was lost to follow up. Nineteen pregnancies were expectantly managed and delivered at a mean gestational age of 36.0 ± 3.0 weeks. Survival at discharge was 53% (10/19), one being oxygen dependent. In the fetal surgery group (n = 48), mean gestational age at delivery was 34.5 ± 3.0 weeks. In our recent experience not previously published (n = 23) survival rate was 52 and 39% were oxygen dependent at discharge. Pooling these data with earlier reported observations by our group we observed a 42% survival rate in 57 fetuses. Lung size on magnetic resonance imaging and an interval of >24 hours between reversal of tracheal occlusion and delivery were predictors of outcome.
Conclusions
Right‐sided CDH seems to have a poorer outcome than that reported for fetuses with left‐sided CDH with similar lung size before birth. Survival rates after expectant management with observed/expected lung‐to‐head ratio values ≤45 and ≤30% were 17 and 0%, respectively. In those undergoing fetal surgery (observed/expected lung‐to‐head ratio ≤45%) there was an apparent increase (42%).
Fetuses with isolated nonsevere ventriculomegaly (INSVM) are at risk of presenting neurodevelopmental delay. However, the currently used clinical parameters are insufficient to select cases with high ...risk and determine whether subtle changes in brain development are present and might be a risk factor. The aim of this study was to perform a comprehensive evaluation of cortical development in INSVM by magnetic resonance (MR) imaging and assess its association with neonatal neurobehavior.
Thirty-two INSVM fetuses and 29 healthy controls between 26-28 weeks of gestation were evaluated using MR imaging. We compared sulci and fissure depth, cortical maturation grading of specific areas and sulci and volumes of different brain regions obtained from 3D brain reconstruction of cases and controls. Neonatal outcome was assessed by using the Neonatal Behavioral Assessment Scale at a mean of 4 ± 2 weeks after birth.
Fetuses with INSVM showed less profound and underdeveloped sulcation, including the Sylvian fissure (mean depth: controls 16.8 ± 1.9 mm, versus INSVM 16.0 ± 1.6 mm;
= .01), and reduced global cortical grading (mean score: controls 42.9 ± 10.2 mm, versus INSVM: 37.8 ± 9.9 mm;
= .01). Fetuses with isolated nonsevere ventriculomegaly showed a mean global increase of gray matter volume (controls, 276.8 ± 46.0 ×10 mm
, versus INSVM 277.5 ± 49.3 ×10 mm
,
= .01), but decreased mean cortical volume in the frontal lobe (left: controls, 53.2 ± 8.8 ×10 mm
, versus INSVM 52.4 ± 5.4 ×10 mm
;
= < .01). Sulcal depth and brain volumes were significantly associated with the Neonatal Behavioral Assessment Scale severity (
= .005, Nagelkerke R
= 0.732).
INSVM fetuses showed differences in cortical development, including regions far from the lateral ventricles, that are associated with neonatal neurobehavior. These results suggest the possible use of these parameters to identify cases at higher risk of altered neurodevelopment.
Objective
To determine whether a novel therapy for placental insufficiency could achieve orphan drug status by estimating the annual incidence of placental insufficiency, defined as an estimated ...fetal weight below the 10th centile in the presence of abnormal umbilical artery Doppler velocimetry, per 10 000 European Union (EU) population as part of an application for European Medicines Agency (EMA) orphan designation.
Design
Incidence estimation based on literature review and published national and EU statistics.
Setting and population
European Union.
Methods
Data were drawn from published literature, including national and international guidelines, international consensus statements, cohort studies and randomised controlled trials, and published national and EU statistics, including birth rates and stillbirth rates. Rare disease databases were also searched.
Results
The proportion of affected pregnancies was estimated as 3.17% (95% CI 2.93–3.43%), using a weighted average of the results from two cohort studies. Using birth rates from 2012 and adjusting for a pregnancy loss rate of 1/100 gave an estimated annual incidence of 3.33 per 10 000 EU population (95% CI 3.07–3.60 per 10 000 EU population). This fell below the EMA threshold of 5 per 10 000 EU population.
Conclusions
Maternal vascular endothelial growth factor gene therapy for placental insufficiency was granted EMA orphan status in 2015 after we demonstrated that it is a rare, life‐threatening or chronically debilitating and currently untreatable disease. Developers of other potential obstetric therapies should consider applying for orphan designation, which provides financial and regulatory benefits.
Tweetable
Placental insufficiency meets the European Medicines Agency requirements for orphan disease designation.
Tweetable
Placental insufficiency meets the European Medicines Agency requirements for orphan disease designation.
Monochorionic (MC) twins represent a significant proportion of perinatal morbidity and mortality. Overall, 1 of 3 MC twin pregnancies will develop complications in relation to the MC placenta and the ...presence of interfetal placental anastomoses. From a clinical standpoint, these complications can be grouped into four main types of clinical problems: chronic transfusion, acute transfusion, growth discordance, and discordant malformation. Differential diagnosis of MC twin complications is still challenging due to frequent overlap of their clinical signs and the complex relationships between them. Clinical experience demonstrates that most instances of wrong management derive from failure to comply with a basic set of rules for diagnosis and management. In this review, we propose a simplified approach to the understanding of MC twin pregnancy, its potential complications, and the key concepts allowing adequate differential diagnosis and targeted management.
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