FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2058711521> ?p ?o ?g. }

• W2058711521 endingPage "111" @default.
• W2058711521 startingPage "108" @default.
• W2058711521 abstract "The human lung is a complex and highly specialized organ with over 40 differentiated cell types. Optimal lung function is determined prenatally and an in utero adverse event may interfere with the delicate lung development process and lead to variable degrees of pulmonary hypoplasia1. Disturbances in the pseudoglandular period (7–16 weeks) interfere with bronchial and arterial branching. When lung development is hampered during the cannalicular phase (16–26 weeks), complexity of the respiratory acinus is reduced and lung maturation may be impaired. Pulmonary effects thus differ according to the underlying disease and a few typical examples immediately come to mind. Renal agenesis simply causes lethal pulmonary hypoplasia. Oligohydramnios due to ruptured membranes prior to 25 weeks will cause pulmonary hypoplasia in 85% of cases, half of them dying from respiratory failure in the neonatal period. Congenital diaphragmatic hernia (CDH) is lethal in 40% of newborns due to neonatal ventilatory problems as well as pulmonary hypertension. CDH is present as early as 9 weeks and interferes with airway and vascular development from that point onwards, leading to progressively more complex lung pathology than that resulting from premature rupture of membrane, which occurs later in gestation. Today, thanks to screening programs and high-resolution ultrasound equipment, lung developmental problems are readily diagnosed. However, diagnosis is only the start. Given the variable consequences of these conditions, reliable methods are required to quantify the extent of disturbance of lung development. Prospective parents expect us to predict the level of morbidity as well as mortality associated with what we have diagnosed. Furthermore, we associate clinical consequences with a certain diagnosis and prognosis. Optimal perinatal care involving in utero referral can be planned or, in cases of lethal forms, termination or antenatal intervention may be considered. The prenatal examination thus evolves from a diagnostic to a prognostic process. Diagnostic tests need to be highly accurate, reproducible, and wherever possible technically and economically acceptable and non-invasive. In this and the following issue of the White Journal, there are several articles dedicated to different aspects of antenatal evaluation of lung problems. We would like to take this opportunity to discuss the potential and limitations of prenatal lung assessment. First, we would like to draw your attention to some generic issues related to the validation of a predictive test for lung hypoplasia. Any prenatal imaging test considered will have inherent limitations as such tests measure tissue features, and their accuracy relies on good spatial resolution of that imaging technique. Resolution differs between imaging methods and will no doubt improve as technology advances over time. Any measurement used in the test will be prone to intra- and interobserver variability, and what may be efficient under certain circumstances may no longer be so when applied on a larger scale. However, even if the reliability of the measurement technique has been established it is very likely that measurements, hence the test, will be most accurate late in gestation. Early in gestation, observed changes may be so minimally different from what is expected in normal subjects, that overlap of normal and lethal is unavoidable. In other words, a predictive test may only become highly accurate so late in gestation that its clinical implications are minimal or even nil. There are also limitations imposed by, and unique to, the particular pathology under investigation. Each lung developmental condition has its own, yet usually ill-defined natural history. This is in part due to their rarity and the paucity of reliable data. Reported numbers are prone to observation bias that is present in the pathological, obstetric, neonatological or pediatric surgery literature. The discrepancy in mortality rates, according to whether they are quoted by prenatal or postnatal specialists, explains what is known as ‘hidden mortality’2. Today, many studies in the obstetric literature should be considered as interventional because termination of pregnancy (TOP) is an option. TOP is more likely to be offered to those patients with what is perceived to be a dismal prognosis, based precisely on the parameters that are to be validated. Furthermore, lung development diseases may cover a heterogeneous spectrum, with large variability. Both lungs may not be affected similarly and the time course of effects on the lung may change throughout gestation. For instance, lung hypoplasia in CDH is worse on the ipsilateral side, and the disease has been shown to be progressive throughout pregnancy. This means that predictive tests will need different cut-off values for variable gestational ages3. Finally, with advances in neonatal care these diseases are ‘moving targets’ and what is lethal today may no longer be so tomorrow. Despite all these limitations, predicting prognosis is a clinical need. The first goal of a lung assessment method should be to predict viability. Definitions of pulmonary hypoplasia come from the dark rooms of the department of pathology dealing only with non-survivors. Lung development is typically quantified by assessing lung weight as a proportion of total body weight4. Microscopic definitions, based on morphometric evaluation of the distal airways, or molecular assessments based on DNA content, have also been proposed. Regardless of the type, all these tests are, of course, unusable by the fetal medicine specialist. Gas exchange does not occur during fetal life, hence respiratory function or failure cannot truly be tested prenatally. Therefore, prenatal imaging techniques logically try to mimic what is done postnatally, i.e. quantify the lung anatomically. Pulmonary hypoplasia is principally an anatomical rather than a functional concept. We started measuring fetal (two-dimensional (2D)) biometric indices or using the relationship of lung or thorax dimensions to biometric parameters not affected by the condition. Widely used are thoracic over abdominal circumference (for oligohydramnios)5 or the lung-to-head ratio (LHR) (for CDH)6. Besides ‘anatomical’ assessment of the lung itself, 2D ultrasound may also be used to detect other variables predicting outcome. Amniotic fluid volume can be accurately measured in cases of oligohydramnios. For CDH, the presence of liver herniation, polyhydramnios, and a whole series of other epiphenomena, are claimed to relate to neonatal outcome. Combining parameters (such as LHR and liver herniation in the case of CDH7 or biometric indices and clinical parameters in the case of preterm premature rupture of membranes (PPROM)5) can improve predictive values as shown in larger series. 2D ultrasound is cheap, non-invasive, widely available, and with appropriate training reliable measurements can be made8. Moeglin et al. conclude in this issue that 2D ultrasound remains clinically valuable, certainly in longitudinal follow-up9 and we continue to use these ‘anatomical’ variables when counseling patients10. The study by Heling et al. in this issue, however, arrives at a different conclusion11. The authors should certainly be credited for prospectively gathering data from a single center involving one observer. They also looked at morbidity indicators, as previously done in the nineties when Japanese investigators related biometric variables to postnatal arterial-alveolar oxygen diffusion gradients and other aspects of mechanical ventilation12. However, on closer scrutiny of their data, we urge caution in abandoning anatomical variables such as LHR in clinical management, which meanwhile seem to be validated elsewhere in many cases7, 10, 13. The Heling study falls into some of the typical traps mentioned earlier. Information is lacking on cases in which termination was performed (25% of the population) and who are likely to be those with the poorest prognostic factors. Data from left- and right-sided lesions, which have different prognoses, as well from different gestational ages, are mixed. Only half (n = 10) of the cases have measurements obtained within the clinically relevant time frame of between the second and third trimesters and only six cases had a LHR < 1.0. Applying statistics to such a small group becomes difficult, and simply looking at a slightly different cut-off value of < 0.9, as earlier proposed by Harrison et al.13, puts their patient collective and their outcomes in a different perspective. All these considerations should not prevent us from questioning, with them, the currently proposed (anatomical) criteria of a dismal prognosis. It is very likely that the complexity of lung function cannot be captured in a few anatomical 2D features. It seems, therefore, logical to attempt to measure lung volume directly in three dimensions. That technology is now available and several studies have published nomograms for multiplanar and rotational volume acquisitions. In this issue, Moeglin et al. demonstrate that these two three-dimensional (3D) techniques are interchangeable9. Far fewer data are available on 3D volumetry in patients at risk for lung hypoplasia14, 15. Just as for 2D measurements, we need more non-interventional studies in homogeneous populations at high risk for pulmonary hypoplasia, documenting cases either prior to 26 weeks, and/or studying them longitudinally. Ultrasound examination can look further than the fetal lung contour and can study pulmonary vascularization as more modern means become available. Although only indirectly related to hypoplasia, Ruano et al. in this issue underscore the performance of 3D power Doppler in the anatomical study of (abnormal) vascularization of pulmonary sequestration16. As far as hypoplasia is concerned, fetal echocardiography is able to assess the repercussions of pulmonary hypoplasia on right and left ventricular proportions and can measure branch pulmonary artery diameters, which are correlated to lung mass. In CDH, a larger contralateral diameter and discrepancy between contra- and ipsilateral diameters, have been shown to predict neonatal death and morbidity indicators such as later oxygen requirements3. However, the value of fetal echocardiography and Doppler lies deeper than measuring size or diameter. Doppler interrogation at different sites within the venous and arterial pulmonary circulations or ductus arteriosus is a proxy of vascular resistance, and thus function. Pulmonary vascular resistance is indirectly related to hypoplasia in some diseases17. In the study by Tchirikov et al., which at the time of writing is available from the online version of the White Journal, this technology was used to study the effects of experimental prenatal tracheal occlusion to trigger lung growth18. Pulmonary growth was shown, without changes in flow velocity profiles in the pulmonary arteries. This was, however, performed in fetal sheep without hypoplastic lungs at the onset of the experiment and conclusions may be different in hypoplastic lungs. Although they represent a first step to functional evaluation, our expectations of Doppler studies are not high. Again, these tests need to demonstrate very small changes in peak systolic and end-diastolic velocities, which are already minimal during pregnancy. Limitations in the accurate performance of such studies include the difficulty associated with achieving an optimal angle of insonation in the presence of abnormal anatomy, and the variability of the waveform according to whether it is derived from the proximal or distal vasculature. An interesting functional test is the so-called prenatal oxygenation test. Similar to what happens at birth, increasing oxygen levels (obtained through maternal hyperoxygenation) will, in a normal lung, cause a dramatic drop in pulmonary arterial resistance. The fetus is used as its own control and resistances before and during hyperoxygenation are compared. A decrease of less than 20% had a negative predictive value of 93% and positive predictive value of 79% in a population at risk for pulmonary hypoplasia19. The test relies on the reaction of arterial smooth muscle cells to circulating nitric oxide. Unfortunately, this can only be expected to be measured meaningfully and consistently beyond 30 weeks of gestation. As the bulk of the smooth muscle cell mass in resistance arteries is only laid down later in gestation, the test cannot and will not be usable between 20–26 weeks, which of course is the crucial stage for decision-making. The next logical step is to use fetal magnetic resonance imaging (fetMRI). Since MRI is physically a static imaging technique, in its dawn, fetMRI was hampered by significant fetal motion artifacts. Faster acquisition times have overcome this limitation, but resolution can still be improved, which is particularly relevant to early gestation and to cases of pathology. New developments in hardware, ultrafast gradient systems and parallel imaging continue to decrease image blurring, and increase resolution and spatial detail, and even open the door for real-time imaging (albeit the real-time potential is unlikely to reach that of ultrasound). From a theoretical point of view, fetMRI is the ideal instrument for fetal lung volume and lung-to-body volume measurements. The amount of lung fluid, which directly relates to functional residual capacity, can be accurately measured by fetMRI. Several morphological and volumetric studies in fetuses with normal and hypoplastic lungs are already available20-22, but have been mainly conducted in late pregnancy. Again, as for 3D ultrasound, fetMRI volumetry needs validation in non-interventional studies, and in patients with pulmonary hypoplasia prior to 26 weeks. In an experimental study by Jani et al. in the next issue, the accuracy of fetMRI volumetry was tested in mid-gestational sheep with CDH23. Measurements of fetal lung volume were most accurate in the axial plane, probably because volume is calculated on a greater number of slices (as compared to the sagittal plane). Accuracy was only half as good for measurements of anomalous as compared to normal lungs. This underscores the need for further clinical validation in the target population before implementation. In the future, we can expect fetMRI to yield other non-morphological but functional information by applying specific magnetic gradients and tissue properties such as perfusion or free water diffusion. fetMRI can document lung maturation, which is information that cannot be obtained by ultrasound24. In summary, it seems very unlikely that a test studying a single antenatal feature will enable us to predict postnatal lung function. New 3D methods measuring more accurately anatomical variables need to be properly evaluated, and the combination of different variables may further improve prediction. However, any cut-off values will need continual validation, as changes in pre- and postnatal therapy might modify the equation over time. Furthermore, these tests will always remain far from a functional evaluation of the prenatal lung, and for this reason we should continue to look for alternative methods to do better." @default.
• W2058711521 created "2016-06-24" @default.
• W2058711521 creator A5010005177 @default.
• W2058711521 creator A5018476377 @default.
• W2058711521 creator A5040620270 @default.
• W2058711521 creator A5077355483 @default.
• W2058711521 creator A5081192617 @default.
• W2058711521 creator A5087565405 @default.
• W2058711521 creator A5089387072 @default.
• W2058711521 date "2005-01-31" @default.
• W2058711521 modified "2023-10-09" @default.
• W2058711521 title "Progress in intrauterine assessment of the fetal lung and prediction of neonatal function" @default.
• W2058711521 cites W1969853930 @default.
• W2058711521 cites W1970977340 @default.
• W2058711521 cites W1989186280 @default.
• W2058711521 cites W1992503867 @default.
• W2058711521 cites W1999405232 @default.
• W2058711521 cites W2012755473 @default.
• W2058711521 cites W2012831790 @default.
• W2058711521 cites W2016195836 @default.
• W2058711521 cites W2021080784 @default.
• W2058711521 cites W2021814629 @default.
• W2058711521 cites W2039967758 @default.
• W2058711521 cites W2043421635 @default.
• W2058711521 cites W2065152377 @default.
• W2058711521 cites W2067154676 @default.
• W2058711521 cites W2072415190 @default.
• W2058711521 cites W2072417312 @default.
• W2058711521 cites W2082057581 @default.
• W2058711521 cites W2083951407 @default.
• W2058711521 cites W2085810828 @default.
• W2058711521 cites W2090292516 @default.
• W2058711521 cites W2091142227 @default.
• W2058711521 cites W2093630864 @default.
• W2058711521 cites W2167107449 @default.
• W2058711521 cites W2395633806 @default.
• W2058711521 doi "https://doi.org/10.1002/uog.1845" @default.
• W2058711521 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15685667" @default.
• W2058711521 hasPublicationYear "2005" @default.
• W2058711521 type Work @default.
• W2058711521 sameAs 2058711521 @default.
• W2058711521 citedByCount "20" @default.
• W2058711521 countsByYear W20587115212018 @default.
• W2058711521 crossrefType "journal-article" @default.
• W2058711521 hasAuthorship W2058711521A5010005177 @default.
• W2058711521 hasAuthorship W2058711521A5018476377 @default.
• W2058711521 hasAuthorship W2058711521A5040620270 @default.
• W2058711521 hasAuthorship W2058711521A5077355483 @default.
• W2058711521 hasAuthorship W2058711521A5081192617 @default.
• W2058711521 hasAuthorship W2058711521A5087565405 @default.
• W2058711521 hasAuthorship W2058711521A5089387072 @default.
• W2058711521 hasBestOaLocation W20587115211 @default.
• W2058711521 hasConcept C126322002 @default.
• W2058711521 hasConcept C131872663 @default.
• W2058711521 hasConcept C172680121 @default.
• W2058711521 hasConcept C177713679 @default.
• W2058711521 hasConcept C2777714996 @default.
• W2058711521 hasConcept C2779234561 @default.
• W2058711521 hasConcept C3018587741 @default.
• W2058711521 hasConcept C54355233 @default.
• W2058711521 hasConcept C71924100 @default.
• W2058711521 hasConcept C86803240 @default.
• W2058711521 hasConceptScore W2058711521C126322002 @default.
• W2058711521 hasConceptScore W2058711521C131872663 @default.
• W2058711521 hasConceptScore W2058711521C172680121 @default.
• W2058711521 hasConceptScore W2058711521C177713679 @default.
• W2058711521 hasConceptScore W2058711521C2777714996 @default.
• W2058711521 hasConceptScore W2058711521C2779234561 @default.
• W2058711521 hasConceptScore W2058711521C3018587741 @default.
• W2058711521 hasConceptScore W2058711521C54355233 @default.
• W2058711521 hasConceptScore W2058711521C71924100 @default.
• W2058711521 hasConceptScore W2058711521C86803240 @default.
• W2058711521 hasIssue "2" @default.
• W2058711521 hasLocation W20587115211 @default.
• W2058711521 hasLocation W20587115212 @default.
• W2058711521 hasOpenAccess W2058711521 @default.
• W2058711521 hasPrimaryLocation W20587115211 @default.
• W2058711521 hasRelatedWork W1963927723 @default.
• W2058711521 hasRelatedWork W1968596735 @default.
• W2058711521 hasRelatedWork W1980685318 @default.
• W2058711521 hasRelatedWork W1991426134 @default.
• W2058711521 hasRelatedWork W2009219090 @default.
• W2058711521 hasRelatedWork W2028067405 @default.
• W2058711521 hasRelatedWork W2052576884 @default.
• W2058711521 hasRelatedWork W2074270357 @default.
• W2058711521 hasRelatedWork W22971176 @default.
• W2058711521 hasRelatedWork W3111777359 @default.
• W2058711521 hasVolume "25" @default.
• W2058711521 isParatext "false" @default.
• W2058711521 isRetracted "false" @default.
• W2058711521 magId "2058711521" @default.
• W2058711521 workType "article" @default.