Since the first case of fetal urothelial malformation was diagnosed in 1970 , with the advances in imaging, especially the use of ultrasound prenatal screening, the number of fetal and neonatal hydronephrosis detected has increased significantly. This requires clinical workers to take timely and appropriate treatment measures for fetal and neonatal hydrocele to preserve the kidney function of the affected children. However, a significant portion of fetal and neonatal hydrocele can be eliminated naturally, i.e., physiological hydrocele, so it is necessary to understand the criteria for the diagnosis of fetal and neonatal hydrocele and to deal with fetal and neonatal hydrocele correctly and timely. It seems very necessary, and the current research is reviewed as follows.
I. The pathological evolution of fetal hydronephrosis
Fetal hydronephrosis refers to a significant separation of the renal pelvic collecting system during fetal life. Most fetal hydronephrosis is physiological in nature. Differences in renal vascular resistance, glomerular filtration rate (GFR) and tubular concentrating capacity before and after birth result in four to eight times higher prenatal urine flow than postnatal urine flow in the fetus, and this high urine flow may lead to ureteral dilatation without significant obstruction. On the other hand, the deposition and arrangement of elastic fibers, collagen fibers, and some other matrix of the fetal ureter are different from those of the postnatal ureter, and their compliance is higher, thus making the fetal ureter easily tortuous and dilated; finally, some partial or temporary anatomical or functional obstructions that can be improved during postnatal development can also lead to dilatation of the adjacent urinary tract. All of these conditions can manifest as fetal hydronephrosis, but this hydronephrosis often changes with fetal development, renal physiology and ureteral histology, and spontaneously resolves before the end of pregnancy or during the first year of life, without further intervention.
Fetal hydronephrosis due to truly obstructive factors, on the other hand, is pathologic and can have serious consequences. Complete obstruction of the upper urinary tract during embryonic development will result in a non-functioning kidney with severe cystic dysplasia, an impairment with similar results to congenital anencephaly. Obvious indications of poor prognosis in these cases include early onset of renal parenchymal changes, low amniotic fluid, severe congenital renal malformations, and bladder output tract obstruction. In animal models of severe urinary tract obstruction, rapid and progressive decreases in renal blood flow (RBF) and glomerular filtration rate (GFR) occur, which are not recovered, and tubular function (e.g., potassium and phosphate secretion) is significantly reduced. Because of the short and straight renal tubules in fetuses and neonates, the same degree of obstruction affects fetuses more than adults. chevvalier et al [6] studied neonatal rats with complete unilateral urinary tract obstruction (UUO) and showed that renal function in the developing kidney decreases linearly with the duration of ureteral obstruction. This suggests that only early resolution of the obstruction may maximize the preservation of the function of the affected kidney. Josephson made a model of mild to moderate ureteral obstruction in neonatal rats and observed that renal blood flow (RBF), glomerular filtration rate (GFR) and potassium secretion could decrease to about 30%. The affected renal function is largely compensated by the corresponding increase in renal function on the healthy side, and only early release of the obstruction can reverse the loss of glomerular function on the affected side.
Prevalence of fetal hydronephrosis
Hydronephrosis is one of the most common congenital malformations detected by prenatal screening. Large studies have shown that urethral dilatation is visible in one in every hundred pregnancies. A large Swedish prenatal screening showed a 0.17% incidence of fetal hydronephrosis, while a prospective prenatal ultrasound survey study in the UK found 0.76%. However, a significant proportion of these cases were eventually identified as physiologic hydronephrosis; the difficulty in detecting clinically significant, pathologic hydronephrosis lies in the high incidence of physiologic hydronephrosis and the limitations of current diagnostic criteria for determining pathologic urinary tract dilatation. Follow-up studies have shown that the number of fetal hydronephrosis requiring prenatal or postnatal intervention is approximately 1 in 500.
III. Diagnosis of fetal hydronephrosis
(i) Prenatal diagnosis
Ultrasound has been widely used in the diagnosis of fetal urethral anomalies. Factors to be considered in the diagnosis of fetal hydronephrosis by ultrasound include: the gestational week at the time of diagnosis, the site of urethral lesion involvement, the extent of hydronephrosis, and evidence of pathological obstruction.
Distinguishing between physiologic pelvic dilatation and meaningful or pathologic hydronephrosis is critical for prenatal screening and for possible interventions. Up to 18% of normal fetuses examined after 24 weeks of gestation may have a dilated renal pelvis between 3 and 11 mm. Several studies have evaluated clinically meaningful diagnostic criteria for fetal hydronephrosis. For most cases, persistent postnatal renal anomalies occur in those presenting with: anterior-posterior renal pelvis > 6mm at < 20 weeks of gestation; anterior-posterior renal pelvis > 8mm at 20-30 weeks of gestation; anterior-posterior renal pelvis > 10mm at > 30 weeks of gestation; Grignon et al. classified prenatal hydronephrosis after 20 weeks of gestation into five classes: class I: dilated renal pelvis Less than 1 cm, normal renal calyces; Grade 2: pelvis dilated 1-1.5 cm, normal renal calyces; Grade 3: pelvis dilated > 1.5 cm, mildly dilated renal calyces; Grade 4: pelvis dilated > 1.5 cm, moderately dilated renal calyces; Grade 5: pelvis dilated > 1.5 cm, severely dilated renal calyces, thinning of renal parenchyma. The simplified grading method: mild hydronephrosis, pelvis dilated < 1.5 cm, calyces normal; moderate hydronephrosis, calyces dilated > 1.5 cm, calyces dilated; severe hydronephrosis, pelvis > 1.5 cm, calyces dilated, renal parenchyma thinning. The classification established by the Fetal Urological Society in 1988 is: after excluding vesicoureteral reflux, hydronephrosis is classified into four grades: grade zero, no hydronephrosis; grade one, mild separation of the renal pelvis; grade two, dilatation of one or several renal calyces in addition to the dilated pelvis; grade three, dilatation of all renal calyces; grade four, dilatation of the renal calyces and thinning of the renal parenchyma. In China, Wang Changlin et al. classified it into three types: type A, simple pelvis dilatation in the range of 1.0-1.5 cm; type B, pelvis dilatation less than 1.5 cm and parenchymal dilatation; type C, pelvis significantly dilated more than 1.5 cm and parenchymal thinning.
Ultrasonography can observe the severity of fetal hydronephrosis, lateral differentiation, the presence of ureteral dilatation, renal parenchymal changes and abnormalities in the size, wall thickness and emptying of the bladder, which are important in determining physiologic or pathologic hydronephrosis. Low amniotic fluid is an important indicator of poor prognosis.
Ultrasonography can also indicate the etiology. The most common causes of fetal hydronephrosis are: obstruction of the ureteropelvic junction, ectopic ureteral cysts, and vesicoureteral reflux. Pelvic ureteral junction (PUJ) obstruction is the most common cause of fetal hydronephrosis. It is characterized by varying degrees of pelvic dilatation, dilated calyces, no ipsilateral ureteral dilatation, normal bladder, and normal amniotic fluid volume. When pelvic calyx dilatation is accompanied by ureteral dilatation, the most common etiology found postnatally is vesicoureteral reflux (VUR), giant ureter, posterior ureteral valve (PUV), and Megan’s ventral brown ensemble sign. Because ureteral dilatation is often not seen, many nonspecific hydronephrosis are often due to VUR or giant ureter. Vesicoureteral reflux accounts for 25-35% of nonspecific fetal hydronephrosis. A male fetus presenting with significant hydronephrosis of the renal pelvis and ureter, with dilated bladder and thinning walls, and normal renal structure and amniotic fluid volume, suggests a high probability of severe vesicoureteral reflux, a condition defined as megacystismegaureterassociation. Renal duplication anomalies should be considered when asymmetric dilatation of the upper collecting system of the ipsilateral kidney is seen or when ureteral cysts are seen in the bladder. Posterior ureteral valves (PUV) in male fetuses are characterized by unilateral or bilateral ureteral and renal hydrops, thickening of the bladder wall with trabecular formation and sometimes dilatation, dilatation of the posterior ureter, changes in the renal parenchyma (e.g., hyperechoic areas or subcortical cysts), and varying degrees of amniotic fluid reduction. The Meconium Brown syndrome is characterized by a significantly more dilated ureter than the renal pelvis, a dilated bladder with an umbilical ureteral malformation, and the presence of a giant urethra, with normal amniotic fluid volume in most cases.
(ii) Postnatal diagnosis
More than half a century of research has led urologists to recognize that hydronephrosis does not necessarily equal obstruction. Several studies have shown that many newborns with severe hydronephrosis do not have pathologic obstruction. Even though some had an initial decline in renal function, further follow-up revealed no deterioration in renal function, no progression of hydronephrosis, and no compensatory hypertrophy of the contralateral kidney in these kidneys. However, on the other hand, missed diagnosis of a truly obstructed kidney can lead to severe or even irreversible renal function impairment, so the debate in the management of neonatal hydronephrosis is to determine when pathologically significant obstruction is present. All standard diagnostic tests used to evaluate hydronephrosis in this age group, such as IVP, US, nephrogram and Whittaker’s test, are inaccurate. The diagnosis in most cases can only rely on changes in indicators during repeated examinations and long-term follow-up.
(1) Morphologic changes in the dilated renal pelvis demonstrated by IVU and USIVU or US can also confirm the diagnosis of neonatal renal obstruction. However, serial findings of progressive hydronephrosis may suggest the presence of obstruction. koff et al. determined whether compensatory changes occurred by applying US to the size of the normal kidney contralateral to the infant with unilateral hydronephrosis as a diagnostic method to determine the presence of obstruction, and showed that the kidney contralateral to unilateral obstructive hydronephrosis tended to be compensatingly enlarged. They suggested that a renal growth chart could be created by measuring the length of a series of normal kidneys, which could facilitate the diagnosis of obstructive neonatal hydronephrosis. This idea was recently supported by Chevalier et al. with experimental studies showing that the developing kidney of the neonatal rat exhibits an extremely sensitive renal compensatory balance in the presence of complete unilateral urinary tract obstruction.
In 1989, Platt et al. described the potential use of the obstruction coefficient (RI, resistive ludes) obtained by Doppler ultrasound (DUS). The non-invasive nature of renal RI measurement makes it of great potential use in pediatric obstructive uropathy. with RI = 0.07 as the upper limit of normal in adults, more work is needed to determine normal or abnormal criteria for renal RI in children. the RI is age-dependent, especially in infants, and in healthy pediatric patients in the first year of life, the RI is generally greater than 0.07. in addition, saline instillation and the application of tachypnea can greatly improve the accuracy of RI in diagnosing obstructive hydronephrosis in children.
(2) Diuretic renogram (diuretic renogram) post-frusemide drainage curve (post-frusemide drainage curve) and half-time drainage (T1/2) are influenced by many factors; therefore, they cannot be used as criteria for the diagnosis of obstruction. Hydration status, renal function, pelvic volume and contractility, position of the child, degree of bladder filling, duration of diuretic application, dose and type of radiopharmaceutical can affect the results. Individual renal function measurements, which are used to determine the presence of obstruction, vary from 30% to 40% of the individual renal function threshold for determining obstruction in different studies [24], and the presence of obstruction is considered when renal function is less than 40%. One way to improve the quality of the diuretic nephrogram is to do the test with maximum diuresis: intravenous application of hypotonic saline at a dose of 2L/1.73m2 body surface area within 2 hours after drinking 20 ml of water/per kg of body weight. This method may improve the specificity and sensitivity for the diagnosis of PUJO. However, its use in neonates has not been seen.
(3) Whether VCUG should be done in fetal hydronephrosis that has been diagnosed is controversial. the general practice is that VCUG is recommended if the fetal renal pelvis is greater than 8 mm in diameter and dilated calyces or dilated ureters are present. other investigators have done VCUG also in neonates with hydronephrosis that showed significant remission on postnatal ultrasound. hollowell et al. reported that in 147 children who underwent pyeloplasty Therefore, they suggested that VCUG should be one of the routine evaluation methods for children with suspected diagnosis of PUVG.
Treatment of fetal hydronephrosis
(I) Intervention in the fetal period
After the diagnosis of fetal hydronephrosis, the management becomes controversial. In most cases, the diagnosis is made between the fourth and sixth trimester, and another ultrasound should be performed before full term. In the case of bilateral ureterorenal hydrops with dilated bladder, ultrasound should be performed every four weeks after the diagnosis. Other diagnostic methods to evaluate fetal status include, amniocentesis, umbilical cord blood sampling, and chorionic villus sampling. Umbilical cord blood sampling has become the standard method for rapid fetal sampling at 14-16 weeks of gestation. The advantage of chorionic villus sampling is that it allows chromosomal analysis to be done at 8 to 10 weeks of gestation.
Only a small percentage of hydronephrosis requires prenatal intervention and should be performed by an experienced provider with a consent form. Including long-term fetal bladder drainage, the most appropriate clinical indication for the intervention is a male fetus between 4 and 6 months of gestation presenting with severe bilateral ureterorenal hydrops, urine indicators meeting criteria, and progressive amniotic fluid reduction. The rationale for fetal urinary drainage is that severe early obstruction will lead to renal developmental damage and that bypassing the obstructed urinary system by shunting urine directly into the amniotic sac will reduce intrarenal pressure sufficiently to prevent irreversible damage and prevent renal dysplasia associated with hypohydramnios. Percutaneous ureterostomy and cystostomy have been reported in a few cases, and there are no prognostic data for a large sample of renal outcomes after intrauterine intervention. However complications such as shunt obstruction or dislocation and intestinal herniation along the needle tract have been reported. In addition, the intervention may lead to fetal injury, maternal infection, preterm delivery, and miscarriage, which can be harmful to future pregnancies.
(II) Postnatal treatment
(1) Initial evaluation: A confirmatory ultrasound examination is performed two to three days after birth, and if bilateral hydronephrosis or a severe urinary tract anomaly (e.g., posterior urethral valves or isolated renal obstruction) is suspected, further diagnosis may be delayed until one month after delivery. Because neonatal oliguria can mask moderate obstruction, ultrasonography performed in the first days after birth may have missed the diagnosis.
(2) Therapeutic measures: In infants with postnatally confirmed hydronephrosis, although infection in combination with ureteral obstruction is thought to cause significant renal damage, there are no data to suggest a good outcome with prophylactic antibiotics. Therefore, some authors recommend prophylactic antibiotics for all newborns with prenatally detected, postnatally confirmed hydronephrosis, while other institutions apply antibiotics only for those with a severely dilated renal collecting system such as a renal pelvis larger than 10 mm. The usual daily oral penicillin G is 20 KIU/kg, amoxicillin 15 mg/kg or methotrexate 2 mg/kg.
When the initial evaluation reveals bilateral hydronephrosis or isolated hydronephrosis, ultrasound or excretory cystourethrography should be performed immediately, and if PUV is diagnosed, resection or drainage surgery should be performed. If VUR or obstructive giant ureter is found, prophylactic antibiotics are started.
The current management of newborns with a confirmed diagnosis of PUJO is varied. Many investigators support immediate pyeloplasty based on the theory that obstruction in the neonatal period leads to decreased renal function, and that in some patients renal function is not restored even if the obstruction is removed, and that early surgery may prevent loss of renal function. However, this theory is not supported by objective indicators, and it is not possible to determine whether the improvement in renal function is the result of early pyeloplasty or a natural increase in renal function in the early postpartum period.
In addition, some investigators have suggested that a decrease in renal function represents an obstruction requiring surgery. The theory is that in the presence of significant obstruction, renal filtration will be compromised and renal function will decline progressively, whereas in the absence of persistent obstruction, renal function will be approximately stable, and if renal function is greater than 35% in the early phase, then the kidney can be safely observed. However, there is also the question of how much damage to renal function would be caused if the affected kidney underwent a relatively delayed pyeloplasty after a period of conservative management. There are no clear criteria to predict early which kidneys will eventually require surgical intervention. Some follow-up studies have shown that some mature kidneys do not fully recover their lost function after pyeloplasty. This view is supported by Subramaniam et al, whose recent study showed that kidneys delayed in pyeloplasty had poorer improvements in renal function than those who underwent pyeloplasty earlier.
Since all studies on the role of early surgery are retrospective, the exact role of prophylactic surgery cannot yet be demonstrated. Some recent reports suggest that those with anterior and posterior pelvic diameters greater than 2 cm should undergo surgery early, regardless of renal function, and whether early pyeloplasty is ultimately beneficial can only be determined by further randomized controlled studies.
Primary neonatal megaureter is a dilated distal ureter that may not be associated with loss of renal function, and the dilatation may resolve significantly during serial follow-up. In one study of 34 hydronephrosis associated with primary obstructive giant ureter detected by prenatal ultrasound, only 2 cases were treated surgically due to progressive renal function loss, and most of the dilatation gradually decreased during subsequent development. Therefore, the lack of clinical signs suggests surgery when reduced renal function (less than 30%) is detected.
Other causes: ureteral cysts, the best early treatment is transendoscopic resection. For obstructive ectopic ureter, there are several treatment options depending on the function of the renal segment involved, the size of the ureter and the presence of vesicoureteral reflux. In cases of hydronephrosis associated with neurogenic bladder or Megan’s belly syndrome, it is important to ensure that the bladder is sufficiently empty and surgery is usually not required. Early prophylactic antibiotics should be applied in the presence of vesicoureteral reflux, whereas polycystic kidneys require serial ultrasound and prophylactic antibiotics do not work.
In conclusion, there are still many pressing issues in the diagnosis and management of fetal and neonatal hydronephrosis that require further observation and research.