Fetal pulmonary hypoplasia, anuria, and oligohydramnios: clinicopathologic observations and review of the literature

The pathology of the lungs was studied in infants dying perinatally with urinary tract malformations. Fetal pulmonary hypoplasia was found in association with anuria and oligohydramnios; however, when renal function was present, pulmonary hypoplasia was absent. Pulmonary hypoplasia appears not to be related genetically or teratologically to the various urinary tract malformations but rather to be secondary to fetal anuria and oligohydramnios. The presence of minimal amounts of amniotic fluid is probably necessary for normal development of the fetal lung.     

Fetal serum ss2-microglobulin and cystatin C in the prediction of post-natal renal function in bilateral hypoplasia and hyperechogenic enlarged kidneys

OBJECTIVES: To evaluate fetal serum ss2-microglobulin and cystatin C in the prediction of post-natal renal function in bilateral hypoplasia and hyperechogenic enlarged kidneys. Predicting post-natal renal function is crucial to the prenatal evaluation of fetal nephropathies. Prenatal ultrasound can identify terminal renal failure, but is not sensitive enough to identify infants whose post-natal renal function will be impaired. Fetal serum ss2-microglobulin and cystatin C are potential predictors of post-natal renal function. METHODS: Fifty-four prenatally diagnosed cases of bilateral nephropathy were retrospectively reviewed. Final diagnosis was established using histological or post-natal findings: renal hypoplasia (n = 7), cystic dysplasia (n = 9), autosomal dominant polycystic kidney disease (ADPKD; n = 8) or autosomal recessive polycystic kidney disease (ARPKD; n = 22) and transient sonographic abnormalities (n = 8). Fetal serum ss2-microglobulin and cystatin C were assayed respectively in 54 and 38 cases. The prognostic value of these markers was assessed in terms of the post-natal outcome. RESULTS: In bilateral kidney hypoplasia and cystic dysplasia, ss2-microglobulin and cystatin C were significantly (p < 0.0001 and p < 0.02 respectively) higher than in the normal control group. In hyperechogenic fetal kidneys (ARPKD, ADPKD and transient sonographic abnormalities), these markers were not different from controls. However, whereas normal values cannot exclude renal failure, abnormal values predict post-natal renal failure. CONCLUSIONS: In bilateral renal hypoplasia and dysplasia, fetal serum ss2-microglobulin and cystatin C are good markers for post-natal renal function. However, in bilateral renal hyperechogenic enlargement, abnormal values are associated with poor post-natal renal function, but normal values cannot preclude renal failure.     

Treatment of congenital pulmonary airway malformation induced hydrops fetalis via percutaneous sclerotherapy

Large type II and III congenital pulmonary airway malformations (CPAMs) can cause pulmonary hypoplasia, non-immune hydrops fetalis and fetal demise. Fetal intervention is indicated if hydrops fetalis develops. In this report, we describe three cases of type II and III CPAMs complicated by hydrops and treated with percutaneous sclerotherapy by ethanolamine injection into the tumor. All 3 cases demonstrated reduction in size of the CPAM and resolution of the hydrops with subsequent delivery at term. We believe that fetal percutaneous sclerotherapy can be used as a minimally invasive palliative strategy to treat CPAM-induced hydrops fetalis. Further studies are needed to delineate the risks of this novel technique.     

Pulmonary balloon valvuloplasty in a fetus with critical pulmonary stenosis/atresia with intact ventricular septum and heart failure

Outcome of fetuses with critical pulmonary stenosis (critical PS) or atresia of the pulmonary valve (PA) with intact ventricular septum (IVS) is closely related with right ventricle hypoplasia and its consequent hemodynamics. Fetal echocardiography not only allows early detection of this condition but also monitors its normally unfavorable evolution. These cases may benefit from intrauterine intervention relieving outflow tract obstruction in order to achieve a biventricular circulation. Successful valvuloplasty of the pulmonary valve was performed in a fetus with critical PS-IVS and heart failure at 25 weeks. After the procedure there was a significant improvement in fetal hemodynamics. Follow-up scans at 34 weeks detected a significant restenosis with signs of circulatory failure leading to premature delivery of the baby. An immediate postnatal valvuloplasty successfully completed the ultimate objective of biventricular repair. Fetal pulmonary valvuloplasty is feasible and may change the natural history of the disease in fetuses with critical PS-IVS.     

Two-dimensional and three-dimensional ultrasound of fetal anasarca: the glass baby

Fetal edema was recognized in the past as a complication of alloimmune disease. More recently, fetal edema is frequently seen in conditions that cause non-immune fetal hydrops with increased soft tissue thickness. Classically there is a halo pattern around fetal head, neck, thorax, and abdomen. Fetal edema is associated with karyotype abnormalities, with multiple congenital anomalies, and with certain fetal infections like parvovirus B19 that cause severe fetal anemia. In the present case there was no evidence of infection or karyotype abnormality, but there was hypoplasia of umbilical cord vessels, pulmonary hypoplasia, and pericardial effusion. The etiology of fetal hydrops may remain unknown in up to 30% of cases.     

Fetoscopic transuterine release of posterior urethral valves: a new technique

Fetal urinary tract obstruction with oligohydramnios produces pulmonary hypoplasia and renal dysplasia. Decompression of the obstructed urinary tract may restore amniotic fluid and allow lung growth, but transabdominal catheter shunt decompression is often inadequate and does not allow for cycling of the bladder, while open procedures cause significant maternal morbidity. Disruption of the anatomic obstruction, usually posterior urethral valves in a male fetus, would be ideal but has proven technically difficult. Here we describe a new technique of percutaneous fetal cystoscopy and disruption of posterior urethral valves, and the case report of our first application of this technique. We pre-sent a case of a 17-week male fetus with posterior urethral valves which underwent fetal cystoscopy for mechanical disruption of posterior urethral valves. This minimally invasive approach to disruption of posterior urethral valves in a fetus is a novel method for decompressing the urinary tract. The technique offers a minimal degree of maternal morbidity and, if instituted early enough, can restore amniotic fluid volume, avert fatal pulmonary hypoplasia and may preserve renal function.     

Fetal magnetic resonance imaging

PURPOSE OF REVIEW: Fetal magnetic resonance imaging is becoming more used in the evaluation of complex fetal abnormalities. Rapid advances in the technology and application of fetal magnetic resonance imaging necessitate a review of this subject. RECENT FINDINGS: Diffusion-weighted imaging, magnetic resonance spectroscopy and functional magnetic resonance imaging may allow assessment of fetal brain even before anatomical abnormalities are demonstrated. We discuss the uses of fetal magnetic resonance imaging in better assessment of pulmonary hypoplasia, congenital diaphragmatic hernia and renal anomalies. SUMMARY: The additional information from fetal magnetic resonance imaging, beyond that obtained by ultrasound, is invaluable in prenatal counseling, delivery planning and planning for pre- or postnatal intervention. As intrauterine and neonatal surgery evolve, so will the utilization of fetal magnetic resonance imaging.     

Fetal lung volume measurement by magnetic resonance imaging in congenital diaphragmatic hernia

Objective To study the potential for prenatal magnetic resonance imaging to predict pulmonary hypoplasia in congenital diaphragmatic hernia.
Design Prospective observational study.
Setting Tertiary care centre.
Participants Thirteen cases of congenital diaphragmatic hernia (11 left, 2 right) without associated anomalies and 74 controls.
Methods Measurements by magnetic resonance imaging of fetal lung volume were achieved. In the control fetuses, a regression analysis was performed to associate fetal lung volume with gestational age. This yielded a formula allowing calculation of the expected fetal lung volume as a function of gestational age. In the cases with congenital diaphragmatic hernia, the observed/expected fetal lung volume ratio was compared with perinatal outcome.
Main outcome measures Neonatal mortality and pulmonary hypoplasia, which was defined as lung/body weight ratios less than 0.012.
Results The expected fetal lung volume was derived from the following formula: Fetal lung volume (mL) = exp (1.24722 + 0.08939 × gestational age in weeks). The observed/expected fetal lung volume ratio was significantly lower in congenital diaphragmatic hernia (median: 0.31, range: 0.06–0.63), than in controls (median: 0.99, range: 0.42–1.94). This ratio was significantly less in the infants with congenital diaphragmatic hernia who died (median: 0.26, range: 0.06–0.63) compared with those who survived (median: 0.46, range: 0.35–0.56). The observed: expected fetal lung volume ratio was significantly correlated with the post mortem lung: body weight ratio.
Conclusion In isolated congenital diaphragmatic hernia, fetal lung volume measurement by magnetic resonance imaging is a potential predictor of pulmonary hypoplasia and postnatal outcome. Further studies are required to establish the clinical value of magnetic resonance imaging for the prenatal assessment of fetal lungs.     

Congenital diaphragmatic hernia: Treatment and outcomes

Congenital diaphragmatic hernia (CDH) is a congenital defect in the diaphragm that allows herniation of abdominal contents into the fetal chest and leads to varying degrees of pulmonary hypoplasia and pulmonary hypertension. Advances in prenatal diagnosis and the institution of standardized delivery and postnatal care protocols have led to improved survival. Fetal endoscopic tracheal occlusion shows early promise for patients with the most severe CDH, but prospective randomized data is still required. CDH survivors have a variety of associated morbidities that require long-term follow-up and early intervention strategies for optimal care.     

Fetal surgery for severe lower urinary tract obstruction

Fetal interventions have been proposed for treatment of severe lower urinary tract obstruction (LUTO), as this condition is associated with high rates of perinatal mortality and postnatal renal impairment. The rationale for in utero treatment for those cases is based on the possibility of relieving the obstruction, improving the amniotic fluid volume, and preventing renal and bladder damage. Candidates for fetal intervention should be rigorously selected based on the confirmation of severe LUTO (dilated bladder and bilateral hydronephrosis), oligohydramnios or anyhydramnios and 'favorable' fetal urinalysis (dependent on gestational age). Nowadays there are two different therapeutic options with specific technical approaches. Vesico-amniotic shunting is an easier procedure, but with a higher frequency of related complications. Fetal cystoscopy can be used for diagnostic purpose and for treatment of posterior urethral valves, with suggestive advantage of allowing a more physiological release of the obstruction. According to the literature, estimated survival rates and postnatal normal renal function frequencies are approximately 40 and 50% after vesico-amniotic shunting and 75 and 65% after fetal cystoscopy, respectively.     

Antenatal diagnosis of pulmonary sequestration: a review.

The prenatal diagnosis of pulmonary sequestration has been demonstrated in 17 published reports, including a new case report presented here. In 11 cases (65 per cent), the definitive diagnosis was not appreciated until after birth, although a fetal mass was recognized on ultrasonographic study in the antenatal period. Seventy-five per cent of cases were thoracic sequestrations, and 25 per cent were abdominal lesions. Fetal hydrops, found in 35 per cent of cases, was universally associated with stillbirth or neonatal death. Polyhydramnios, pleural effusions, mediastinal shifts, pulmonary hypoplasia, and preterm labor were not uncommon findings. The high incidence of related malformations, well described in the postnatal literature, was remarkably absent in this antepartum series. Although the perinatal outcome for abdominal lung sequestrations is reasonably good, the prognosis in cases of thoracic sequestration remains guarded. Aggressive respiratory support after birth will not salvage those infants with underlying severe pulmonary hypoplasia. Early in utero catheter drainage may provide the best treatment for the pleural effusions associated with thoracic sequestrations, although this therapy remains under investigation.     

Three-dimensional ultrasonographic assessment of fetal lung volume as prognostic factor in isolated congenital diaphragmatic hernia

OBJECTIVE: To evaluate the potential of three-dimensional ultrasound to predict outcome in congenital diaphragmatic hernia. DESIGN: Prospective observational study. SETTING: Tertiary care centre. POPULATION: Twelve cases of isolated congenital diaphragmatic hernia (11 left-sided, 1 right-sided) and 109 controls. METHODS: Fetal lung volume was assessed by three-dimensional ultrasound using the technique of rotation of the multiplanar imaging. In the control fetuses, a logistic transformation was performed to correlate fetal lung volume with gestational age, and the confidence interval was obtained with a bootstrap resampling. A mathematical equation was then obtained allowing calculation of the expected fetal lung volume as a function of gestational age. In fetuses with congenital diaphragmatic hernia, the observed/expected lung volume ratio was compared with postnatal outcome. MAIN OUTCOME MEASURES: Neonatal mortality and pulmonary hypoplasia, which was defined as lung/body weight ratios less than 0.012. RESULTS: The expected fetal lung volume was derived from the mathematical equation: Fetal lung volume (mL) = exp (4.72/(1 + exp ((20.32 - gestational age in weeks)/6.05))). The observed/expected fetal lung volume ratio was significantly lower in the congenital diaphragmatic hernia group (median: 0.34, range: 0.16-0.66), than in the control group (median: 1.02, range: 0.62-1.97, P < 0.0001). The distribution of this ratio was significantly downshifted in the infants with congenital diaphragmatic hernia who died (median: 0.19, range: 0.18-0.66) compared with survivors (median: 0.44, range: 0.36-0.66, P= 0.04). The observed/expected fetal lung volume ratio was also correlated with the postmortem lung/body weight ratio. CONCLUSION: In isolated congenital diaphragmatic hernia, fetal lung volume measurement by three-dimensional ultrasound is a potential predictor for pulmonary hypoplasia and postnatal outcome.     

Prenatal diagnosis of atelosteogenesis type I at 21 weeks' gestation

We describe prenatal diagnosis in a male fetus at 21 weeks of gestation with atelosteogenesis type I (AO I). Fetal ultrasonography (US) revealed absent or deficient ossification of the posterior neural arches of the thoracic spine, humeri, radii, ulnae, fibulae, and short tubular bones other than the distal phalanges, in addition to extremely short, thick femora. Fetal magnetic resonance imaging (MRI) using an ultrafast imaging sequence depicted dysmorphic features, pulmonary hypoplasia, and large cisterna magna. Postmortem radiographs warranted a diagnosis of AO I. Autopsy corroborated not only pulmonary hypoplasia but also laryngeal stenosis. The chondro-osseous histological findings were consistent with those of AO I. Meticulous evaluation using fetal US and MRI permits a definitive prenatal diagnosis of AO I to be made.     

Sonographic detection of fetal urinary-tract anomalies

The diagnosis of urinary-tract anomalies in the fetus can frequently be made with antenatal ultrasound imaging. This report details 19 cases of fetal urinary-tract malformation diagnosed during a 30-month period. Early onset and more complete urinary-tract obstruction, oligohydramnios, renal dysplasia, and pulmonary hypoplasia occur frequently in cases where urinary-tract anomalies were detected in utero. The frequent association of other major structural anomalies, severe renal damage, and irreversible pulmonary hypoplasia make imperative an intensive evaluation of the fetus before considering invasive surgical procedures.     

Prenatal diagnosis and management of congenital cystic adenomatoid malformation of the lung

OBJECTIVE: Our purpose was to review the management and outcome of pregnancies with a prenatal diagnosis of fetal congenital cystic adenomatoid malformation of the lung (CCAM). STUDY DESIGN: A retrospective review was performed of all cases since 1995 with a prenatal diagnosis of fetal CCAM from the sole tertiary perinatal referral center in Western Australia. RESULTS: Twenty-one pregnancies with CCAM were identified. The gestational age at diagnosis was <22 weeks in 86% of cases. Macrocysts were seen in 76% of cases during ultrasound examination. Seventeen pregnancies continued until term. Regression of the sonographic appearances was observed in 19% of cases. Fetal hydrops complicated two cases. One neonate died within 24 hours of delivery because of pulmonary hypoplasia. Twelve children have required pulmonary lobectomies. No adverse sequelae are evident in surviving children. CONCLUSION: Most cases of prenatally diagnosed CCAM have had a good outcome. This review has positively influenced the counseling of women with this diagnosis.     

Heterogeneity in fetal akinesia deformation sequence (FADS): autopsy confirmation in three 20-21-week fetuses.

Fetal akinesia deformation sequence (FADS) is a rare condition characterized by intrauterine growth retardation (IUGR), congenital limb contractures, pulmonary hypoplasia, hydramnios and craniofacial abnormalities. The present report comprises an autopsy study of three fetuses to illustrate the variable clinical manifestations and neuropathological findings. Fetus 1 had arthrogryposis and no movement on fetal ultrasound examination. Aborted at 21 weeks, the fetus showed micrognathia, bilateral joint contracture with pterygia at the elbow and axilla. Growth retardation and pulmonary hypoplasia were not major features. Neuropathologic examination revealed anterior horn cell loss and lateral corticospinal tract degeneration in spinal cord, with marked muscular atrophy. Fetus 2, 20 weeks' gestation, had fetal akinesia, nuchal thickening, left pleural effusion, and Dandy-Walker malformation on ultrasound examination. Autopsy showed low-set ears, ocular hypertelorism, cleft palate, flexion contractures with pterygia over axilla, elbow and groin, pulmonary hypoplasia, Dandy-Walker malformation, unremarkable spinal cord and skeletal muscle. Fetus 3, 21 weeks' gestation, was aborted for fetal akinesia, neck and limb webbing and severe arthrogryposis. At autopsy, similar facial abnormalities, contracture and pterygia in neck and multiple major joints were found. Borderline pulmonary hypoplasia and severe lumbar scoliosis were also present. The brain, spinal cord and muscle were unremarkable. In these three fetuses, the prenatal ultrasound and autopsy findings were characteristic of FADS. Neurogenic spinal muscular atrophy was the basis of fetal akinesia in Case 1. Dandy-Walker malformation was present in Case 2, but the pathogenetic mechanism of fetal akinesia was not clear as spinal cord and muscle histology appeared normal. The etiology of akinesia was undetermined in Case 3; no extrinsic or intrinsic cause was identified.     

Ductus arteriosus flow velocity modulation by fetal breathing movements as a measure of fetal lung development

A test is needed that would accurately predict favorable neonatal lung performance in the presence of prolonged severe oligohydramnios caused by ruptured membranes so that optimal obstetric care can be provided. We propose such a test that is based on the degree of modulation of fetal ductal blood flow velocity by fetal breathing movements after maternal glucose loading. In a prospective cross-sectional study of 49 normal pregnancies (50 fetuses) between 25 and 38 weeks an exponential increase in breathing-related ductal blood flow velocity modulation was observed with advancing gestational age, reflecting the developing pulmonary vascular bed. Fetal ductal flow velocity waveforms were also recorded in 13 cases of prolonged severe oligohydramnios after ruptured membranes before 28 weeks' gestation. Normal ductal blood flow velocity modulation values were associated with normal neonatal lung performance, whereas reduced ductal blood flow velocity modulation values were associated with pulmonary hypoplasia. Fetal breathing-related ductal flow velocity modulation appears to be a promising predictor of neonatal lung performance.     

Fetal intervention in obstructive uropathy: prognostic indicators and efficacy of intervention

Management of the fetus with bilateral hydronephrosis is controversial; ability to predict outcome and efficacy of prenatal intervention are unknown. We studied 40 fetuses referred for ultrasonography, examination of fetal urine, and possible therapy. We retrospectively assigned fetuses to a good prognosis group if fetal urine was hypotonic (sodium less than 100 mEq/L, chloride less than 90 mEq/L, osmolarity less than 210 mOsm/L) and there was no ultrasonographic evidence of dysplasia; we assigned fetuses to a poor prognosis group if even one criterion was abnormal. Survival was greater in the good prognosis group than in the poor prognosis group (81% vs 12.5%; 87% vs 30%, excluding abortions) (p less than 0.005). We then attempted to assess the efficacy of prenatal urinary decompression by comparing outcome within the good and poor prognosis groups. Survival with intervention was greater in both the good prognosis group and the poor prognosis group (89% vs 70% and 30% vs 0%). In 6 of the 8 survivors in the good prognosis group, severe oligohydramnios was reversed by decompression. We conclude the fetal urine electrolyte levels and ultrasonographic appear helpful in predicting residual fetal renal function and neonatal outcome and that prenatal decompression may prevent the development of fatal pulmonary hypoplasia.     

Altérations du système rénine-angiotensine (SRA) fœtal : entre génétique et toxicité médicamenteuse

Renal tubular dysgenesis (RTD) and angiotensin 2 receptor blockers (ARB) fetopathy are severe disorders of renal development with fetal anuria and oligohydramnios. Hypocalvaria, Potter sequence, pulmonary hypoplasia, fetal or perinatal death can be associated. This common phenotype highlights that a functional renin-angiotensin system (RAS) is essential in maintaining renal blood flow during fetal life. Gene mutations in its components can cause RTD. Strong recommendations must also be made to avoid the use of drugs interfering with fetal RAS, such as ARB or angiotensin-converting enzyme inhibitors.     

In utero therapy for lower urinary tract obstruction.

Lower urinary tract obstruction has a significant impact on neonatal and child health. Pulmonary hyperplasia and renal impairment could be direct or indirect consequences of this condition leading to significant morbidity and mortality. Evaluation of fetuses with suspected lower urinary tract obstruction is performed not only to confirm the diagnosis but also to assess renal prognosis. Ultrasound examination and urinary analysis aid in the evaluation of these fetuses. The decision to perform fetal intervention in these cases is a difficult one. Vesico-amniotic fetal shunting, open fetal surgery and more recently endoscopic fetal surgery for this condition are available as possible modalities of fetal intervention. Case selection for fetal intervention is extremely important in order to both avoid unnecessary intervention in those unlikely to survive, and also to avoid procedure related complications in fetuses likely to do well without intervention. Vesico-amniotic shunting has the advantage of bypassing the obstruction, however it is often associated with complications. Open fetal surgery is not usually recommended because of the complications and high fetal loss rate. Endoscopic surgery to visualise and treat the cause of lower urinary tract obstruction has been tried. Fetal endoscopic surgery is in its infancy and endoscopic procedures are limited to a few groups. This current review addresses evaluation, case selection and therapeutic options for lower urinary tract obstruction in utero. It also discusses the limited data against which the efficacy of the various options can be assessed. The current state of fetal intervention is detailed in the present review.