Beatiz Bañuelos Marco1
Ricardo González
Barbara Ludwikowski
Anja Lingnau- 1Department of Urology, Charité Medical University of Berlin, Berlin, Germany
- 2Pediatric Surgery and Urology, Kinder- und Jugendkrankenhaus AUF DER BULT, Hanover, Germany
We reviewed the literature addressing outcomes of fetal intervention of conditions that require post-natal urological management including lower urinary tract obstruction, hydrometrocolpos, congenital adrenal hyperplasia, and myelomeningocele. Despite several decades of fetal intervention for these conditions, benefits remain elusive in part because of the enormous difficulty of conducting prospective randomized studies. In this review, we reached the following conclusions:
1. Prenatal intervention in lower urinary tract obstruction (LUTO) improves survival in the worst cases by improving pulmonary function and it may be advantageous for renal function, particularly in patients with adverse urine parameters.
2. Prenatal treatment of female fetuses at risk of having congenital adrenal hyperplasia (CAH) reduces virilization. Non-invasive fetal DNA analysis allows earlier diagnosis, reducing the risk of treating with dexamethasone males and non-affected fetuses.
3. Fetal treatment of myelomeningocele (MMC) is gaining momentum. Prospective studies including standardized urologic evaluation will determine if the encouraging results reported by some hold on the long term follow-up.
Introduction
The purpose of this minireview is to present current knowledge of the effectiveness and impact of prenatal intervention in fetuses with congenital anomalies which have urological consequences in postnatal life. Prenatal detection of genito-urinary tract anomalies has been possible for about 50 years and prenatal surgical interventions for lower urinary tract obstruction (LUTO) date back to the 1980s (1). Significant technical improvements in ultrasonography (US) technology and the addition of fetal MRI have led to significant refinements in prenatal diagnosis. In addition, fetal genetic testing has allowed the prenatal diagnosis of many diseases, among them congenital adrenal hyperplasia (CAH) the prenatal treatment of which impacts postnatal management and outcome. Nevertheless, prenatal treatment of many conditions diagnosed prenatally remains controversial. Here we briefly summarize the current literature regarding prenatal management of fetal lower urinary obstruction, hydronephrosis, hydrocolpos, congenital adrenal hyperplasia, and myelomeningocele.
Method
Literature review searching PubMed, Cochrane, and Embase databases using pertinent key words for each subject of this review. Articles from the last 10 years were preferentially included for this review. Older articles were included if considered important.
Results
Lower Urinary Tract Obstruction (LUTO)
Fetal LUTO refers to the combination of bilateral hydroureteronephrosis and a persistently distended bladder (2). It occurs in 2.2/10,000 pregnancies (2). Fetal LUTO in the second trimester of gestation can lead to postnatal renal failure as well as early respiratory insufficiency due to pulmonary hypoplasia resulting from diminished or absent amniotic fluid. The principal causes of LUTO are posterior urethral valves, Eagle Barret syndrome (prune belly syndrome or PBS) and urethral atresia (3). The mortality of fetus with bilateral hydronephrosis, a distended bladder and oligo- or anhydramnios in the second trimester of life approaches 100% without intervention. End stage renal insufficiency will affect a high proportion of surviving fetuses leading to dialysis and the need of a transplant at the age of 5 years (4).
In the course of the last 4 decades studies tend to demonstrate an early survival advantage by placing a percutaneous shunt between the bladder and the amniotic cavity (VAS) (5). Although VAS is the most common treatment to restore the amniotic fluid volume and alleviate the obstruction, the rate of complications is still very high, 40% (4), and the long term renal function remains uncertain. Anecdotal cases of survival and even good renal function in cases of early bladder decompression are published (6, 7) but prospective series are rare. Survival is improved on the perinatal period, but at 6 months and 2 years follow up there is no evidence of neither a better survival rate nor renal function. Oligohydramnios on the 16–24 weeks of pregnancy can cause irreversible pulmonary hypoplasia (4, 8).
A recent publication by Ruano et al. proposed a new, standardized approach to the selection of patients with LUTO based on multiple criteria including amniotic fluid levels, renal appearance, and fetal urinary electrolyte assessment. The biochemistry and ultrasound characteristics of the fetal kidneys are important to estimate fetal renal function (9).
However, the evaluation of the fetal renal function is difficult since sonographic parameters are not sensible enough and according to some authors biochemical parameters have poor clinical accuracy in the selection of those patients that could benefit from the procedure (10). However, non-favorable results in the biochemistry analysis of the fetal urine correlate with irreversible histological changes in the fetal kidney and aid in identifying fetuses which will not benefit from intervention (11). In a recent publication including 89 patients with prenatally detected posterior urethral valves followed, 20% of the patients were followed for at least 20 years. The authors report that postnatal glomerular filtration rate was >60 mL/min/1.73 m2 in 67.4% of the cases and <30 mL/min/1.73 m2 in 17%. A combination of β2-microglobulin and chloride had the best prognostic value (93% sensitivity and 71% specificity). They concluded that fetal urine parameters predicted long-term postnatal renal function (12) confirming earlier more preliminary observations (13).
Posterior Urethral Valves (PUV) Are the Most Common Cause of LUTO
More than one third of the boys with PUV have a lifetime risk for end-stage renal disease (14). Conversely, PUV accounts for 18% of the pediatric end-stage renal disease. In fetal ultrasonography in the second trimester, the keyhole sign (appearance of a distended bladder and prostatic urethra is the most common sign of PUV (1–3).
Urethral atresia (UA) is seen in 0.3/10,000 births. In the absence of spontaneous decompression of the bladder or prenatal intervention, the condition is invariably fatal.
Prune Belly Syndrome (PBS), also known as the triad syndrome or Eagle Barret syndrome in seen in 1/30,000–40,000. The association of PBS with urethral obstruction (which may no longer be present at the time of diagnosis) is no longer disputed (15, 16).
Prenatal Treatment of LUTO
Prenatal treatment of LUTO dates back more than 3 decades (17). From initial open vesicostomy, treatment have evolved to percutaneous placement of vesicoamniotic shunts to fetoscopic surgery. While open bladder decompression has been abandoned, debate continues regarding the superiority of shunting vs. a fetoscopic approach.
Vesicoamniotic Shunt (VAS)
In 1986, International Fetal Surgery Registry reported 41% survival after VAS placement (18). With current techniques and patient selection survival is now approaching 70% in the first year (19).
Nassr et al. published meteanalysis which included 9 articles of fetal VAS placement with a follow up to 2 years and better defined diagnosis of LUTO (4). One-hundred-twelve fetuses were shunted and 134 fetuses treated conservatively. Shunted fetuses had statistically better survival in the first 6 months of life (57% VAS vs. 39% observed), but it didn't impact survival between 6 and 12 months. Also there wasn't any evidence that VAS placement improved postnatal renal function. However, it should be noted that the effect of VAS placement was less evident in those patient with better prognosis based on favorable fetal urinary chemistry. In contrast those with poor prognostic features benefitted from VAS placement. Ruano et al. also reported better survival after shunting (8). Historically, Freedman et al. reported series of 55 fetuses with LUTO who received VAS and concluded that: “When evaluated by specific diagnosis, intervention appears to provide outcomes in these high risk fetuses that are comparable to those for disease detected post-natally” (3). A recent meta-analysis also suggests that VAS may improve renal function (20). Unfortunately, until today the rate of complications of VAS reaches almost a 40% including shunt migration, obstruction, and displacement (9).
Fetal Cystoscopy
Fetal cystoscopy was reported to aid in making an accurate diagnosis at the time of prenatal intervention (21). Cystoscopy permits simultaneous evaluation of the bladder and urethra and even laser ablation of posterior urethral valves (22–25) but after more than 20 years of attempting such treatment the risk of creating fistulas remains high.
In the retrospective study from Ruano et al. (9, 26), 111 fetuses with severe LUTO were evaluated between 1990 and 2013. In 34 fetuses cystoscopy was performed, in 16 VAS was placed and nothing was performed in 16. The overall survival was higher in the group of patients who underwent any kind of treatment; being 43.8% in the VAS group, 38.2% in the fetal cystoscopy group and 19.7% in the group who did not undergo treatment. The 6 months survival rate show no statistically difference between the fetal cystoscopy group and the VAS group. The evaluation of the renal function showed that compared with no treatment fetal cystoscopy significantly improved the renal function, an improvement that could not be demonstrated on the VAS group. After performing multivariate analysis and adjusting for all variables including gestational age at diagnosis of LUTO, type of fetal intervention given, postnatal diagnosis of the cause of LUTO and fetal center location, as well as considering termination of pregnancy, fetal cystoscopy was associated with a significant improvement in the 6 months survival rate and a not significant trend toward normal renal function. Fetal VAS did not show a significant improvement in renal function. Also in this study, complications of those patients undergoing cystoscopy and intervention was high: fistula in 8.8%, and recurrence of LUTO 5.9% which leaded to preterm delivery and death after birth. Complications of VAS, mainly obstruction or migration, occurred in 31.3%.
Other Urinary Tract Anomalies
In cases of mild upper tract dilatation there is a 11.9% risk of pathological findings, and 1/10 fetuses presenting mild hydronephrosis has a serious condition (27). Ureteroceles may cause bladder outlet obstruction with similar consequences as other cases of LUO. Prenatal detection and fetoscopic treatment has been reported (28, 29).
Thus, prenatal intervention in LUTO improves survival in the worst cases by improving pulmonary function and it may be advantageous for renal function, particularly in patients with adverse urine parameters.
Hydrocolpos and Cloaca
A retrovesical cystic mass in a female fetus usually represent a Mullerian structure filled with fluid. Mallman et al. reported 20 cases which illustrate the spectrum of differential diagnoses, associated malformations and possible course of action (30). Most of the cases were detected in the late ultrasound screening, and only one in the second semester screening (median gestational age at diagnosis 30 weeks). Intra-abdominal cystic masses present a difficult differential diagnosis which may include hydronephrosis, fetal ovarian cysts, anterior cystic teratoma, cloacal malformation, intra-abdominal teratoma, anterior meningocele, and hydrocolpos. Most of the fetuses presenting hydrocolpos will prove to have a severe malformation. Final diagnoses in this series included anorectal malformation in 13, anal atresia, cloacal malformation, cloacal exstrophy intra-abdominal teratoma, vaginal atresia or duplication, persistent urogenital sinus or cardiac malformations. Two of twenty parents opted for termination of pregnancy, three suffered intrauterine fetal death. Fifteen were born at median gestational age of 35 weeks and underwent postnatal reconstructive procedures. Of interest is that the association with ascites indicated a severe associated malformation such as a cloacal malformation (31). Persistent urogenital sinus with hydrometrocolpos is a potentially treatable malformation but the fetal survival depends on the other associated anomalies and the time of prenatal diagnosis. Prenatal decompression may be used in selected cases (32).
Prenatal detection of hydrometrocolpos rarely leads to prenatal intervention but allows improved family counseling.
Congenital Adrenal Hyperplasia (CAH)
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is an autosomal recessive disorder caused by mutations in the CYP21A2 gene. The incidence of the classic form varies between 1/15,000 and 1/24,000, more common in Asians and Caucasians than in Africans. In the classic form synthesis of cortisol and aldosterone are impaired which may result in adrenal insufficiency and salt wasting and in females, virilized genitalia (33).
Genetic studies reveal a mutation in the CYP21A2 gene. Although numerous mutations have been reported, 10 are found in the majority of cases. Prenatal genetic studies allow early detection of the mutation in subsequent pregnancies.
Prenatal diagnosis is recommended in pregnancies when both parents are carriers of the disorder, one parent has a clinical manifestations of CAH or there an affected family member (34). German guidelines recommend prenatal diagnosis in the following cases: (1) Families with one affected child (index case) with classic CAH (CYP21A2); (2) Known parental heterozygosity for classic CAH (no index case) (3) New relationship of a parent of a child with classic CAH if the new partner is known to be a carrier for classic CAH; (4) Homozygosity or compound heterozygosity for classic CAH of one parent when the other parent is a heterozygous gene carrier for classic CAH (35).
As recently as 2015 prenatal treatment of fetuses at risk of virilization was considered experimental in Germany. Part of the reason for this reservation was that for the treatment with dexamethasone to be effective, it had to be initiated before the diagnosis could be confirmed by chorionic villous sampling which expose non-affected fetuses to unnecessary treatment. New developments in the diagnosis by non-invasive methods performing genetic testing of fetal DNA extracted from maternal blood might make the treatment more acceptable (36).
The aim of the prenatal treatment is to avoid virilization of the female fetus. The treatment with dexamethasone was introduced in 1978 by Forest in France and in 1986 in the U.S. Although highly effective if used consistently before the 8 week of those pregnancies at risk, it is not absent of controversies due to animal studies showing effects on brain development (37) but the issue remains controversial (38). With older invasive diagnostic methods (chorionic villus sampling), the sex of the child is determined between 12th and 14th weeks, treatment is suspended if the child is a male or a non-affected female which meant unnecessarily treating 7 of 8 fetuses (37). Non-invasive DNA analysis may overcome these objections (36, 39).
Nevertheless, other potential adverse effects on the cardiovascular, renal and metabolic functions are likely but not yet well-understood (40).
Prenatal treatment of female fetuses at risk of having CAH reduces virilization. Non-invasive fetal DNA analysis allow earlier diagnosis, reducing the risk of treating with dexamethasone males and non-affected fetuses.
Myelomeningocele
Myelomeningocele (MMC) is a life altering birth defect, which results from an incomplete closure of the neural tube during the fourth week of gestation. It affects 5 of 10,000 births (41). Prenatal closure of the myelomeningocele aims at reducing the noxious effect of the amniotic fluid on the exposed spinal cord (42). Fetal repair of has been done by open surgery, fetoscopic surgery, or a combination of both.
The MOMS trial (43) was a multicenter study comprising 183 fetuses of which 158 were evaluated at 12 month of age that demonstrated that, within the period of the follow-up the incidence of ventriculo-peritoneal shunt placement were reduced from 82% in the group operated after birth to 40% in the prenatally operated group. Other potential benefits of prenatal closure included better mental development and motor function. Disadvantages of fetal closure included an increased risk of preterm delivery and uterine rupture at delivery.
Since first MMC closure 1998 (44), nine reports of urological outcomes on 291 cases have been published worldwide (45–52). Most reports that compared early bladder function of MMC patients treated pre- or post-natally failed to show nay advantages. However, there are two encouraging reports. Carr, based on interviews with 54 patients or families who had prenatal closure of MMC, reported that 10 children (18.5%) were toilet-trained, two patients had stool continence, and one was continent of urine but required bowel management, suggesting better outcomes than expected with postnatal closure (53).
Horst et al. reported urodynamic outcomes in 8 of 30 children with 2 year follow-up whose MMC was closed prenatally and compared them with a group with conventional treatment (51). Although they report that bladder function was normal in half of the patients. However, given the difficulties of evaluating bladder function before toilet training the results must be interpreted with caution. Bladder wall thickness was significantly more frequent in prenatally treated patients. This may be the result of better neurological outcome or sphincter denervation as reported by others (47).
Fetal treatment of MMC is gaining momentum. Prospective studies including standardized urologic evaluation will determine if the encouraging results reported by some hold on the long term follow-up.
Conclusions
1. Prenatal intervention in LUTO improves survival in the worst cases by improving pulmonary function and it may be advantageous for renal function, particularly in patients with adverse urine parameters. Development of better instrumentation would improve the success of fetal cystoscopy and reduce complications.
2. Prenatal treatment of female fetuses at risk of having CAH reduces virilization. Non-invasive fetal DNA analysis allow earlier diagnosis, reducing the risk of treating with dexamethasone males and non-affected fetuses.
3. Fetal treatment of MMC is gaining momentum. Prospective studies including standardized urologic evaluation will determine if the encouraging results reported by some hold on the long term follow-up.
Author Contributions
All authors contributed to the conception of this review. BB and RG conducted the review of the literature and wrote the manuscript. AL and BL contributed substantially to the preparation of the manuscript.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
References
1. Harrison M, Golbus M, Filly R, Nakayama D, Callen P, de Lorimier A, et al. Management of the fetus with congenital hydronephrosis. J Pediatr Surg. (1982) 17:728–42. doi: 10.1016/S0022-3468(82)80437-5
2. Pinette M, Blackstone J, Wax J, Cartin A. Enlarged fetal bladder: differential diagnosis and outcomes. J Clin Ultrasound. (2003) 31:328–34. doi: 10.1002/jcu.10179
3. Freedman A, Bukowski T, Smith C, Evans M, Johnson M, González R. Fetal therapy for obstructive uropathy: diagnosis specific outcomes. J Urol. (1996) 156(Pt. 2):720–3. doi: 10.1097/00005392-199608001-00042
4. Nassr A, Shazly S, Abdelmagied A, Araujo Júnior E, Tonni G, Kilby MD, et al. Effectiveness of vesicoamniotic shunt in fetuses with congenital lower urinary tract obstruction: an updated systematic review and meta-analysis. Ultrasound Obstet Gynecol. (2017) 49:696–703. doi: 10.1002/uog.15988
5. Clayton D, Brock J. Current state of fetal intervention for lower urinary tract obstruction. Curr Urol Rep. (2018) 19:12. doi: 10.1007/s11934-018-0760-9
6. Stalberg K, González R. Urethral atresia and anhydramnios at 18 weeks of gestation can result in normal development. J Pediatr Urol. (2012) 8:e33–5. doi: 10.1016/j.jpurol.2011.11.007
7. González R, De Filippo R, Jednak R, Barthold J. Urethral atresia: long-term outcome in 6 children who survived the neonatal period. J Urol. (2001) 165(Pt. 2):2241–4. doi: 10.1016/S0022-5347(05)66174-5
8. Ruano R, Sananes N, Wilson C, Au J, Koh C, Gargollo P, et al. Fetal lower urinary tract obstruction: proposal for standardized multidisciplinary prenatal management based on disease severity. Ultrasound Obstet Gynecol. (2016) 48:476–82. doi: 10.1002/uog.15844
9. Ruano R, Sananes N, Sangi-Haghpeykar H, Hernandez-Ruano S, Moog R, Becmeur F, et al. Fetal intervention for severe lower urinary tract obstruction: a multicenter case-control study comparing fetal cystoscopy with vesicoamniotic shunting. Ultrasound Obstet Gynecol. (2015) 45:452–8. doi: 10.1002/uog.14652
10. Morris R, Quinlan-Jones E, Kilby M, Khan K. Systematic review of accuracy of fetal urine analysis to predict poor postnatal renal function in cases of congenital urinary tract obstruction. Prenat Diagn. (2007) 27:900–11. doi: 10.1002/pd.1810
11. Qureshi F, Jacques S, Seifman B, Quintero R, Evans M, Smith C, et al. In utero fetal urine analysis and renal histology correlate with the outcome in fetal obstructive uropathies. Fetal Diagn Ther. (1996) 11:306–12. doi: 10.1159/000264329
12. Dreux S, Rosenblatt J, Moussy-Durandy A, Patin F, Favre R, Lortat-Jacob S, et al. Urine biochemistry to predict long-term outcomes in fetuses with posterior urethral valves. Prenat Diagn. (2018) 38:964–70. doi: 10.1002/pd.5359
13. Freedman A, Bukowski T, Smith C, Evans M, Berry S, Gonzalez R, et al. Use of urinary beta-2-microglobulin to predict severe renal damage in fetal obstructive uropathy. Fetal Diagn Ther. (1997) 12:1–6. doi: 10.1159/000264415
14. Berte N, Vrillon I, Larmure O, Gomola V, Ayav C, Mazeaud C, et al. Long-term renal outcome in infants with congenital lower urinary tract obstruction. Prog Urol. (2018) 28:596–602. doi: 10.1016/j.purol.2018.06.005
15. González R. Urethral obstruction sequence or prune belly. In: González R, Ludwikowski B, editors. Handbook of Urological Diseases in Children. Singapore: World Scientific Publishing Co (2011). p. 431–8.
16. Pagon R, Smith D, Shepard T. Urethral obstruction malformation complex: a cause of abdominal muscle deficiency and the “prune belly”. J Pediatr. (1979) 94:900–6. doi: 10.1016/S0022-3476(79)80210-3
17. Glick P, Harrison M, Golbus M, Adzick N, Filly R, Callen P, et al. Management of the fetus with congenital hydronephrosis II: prognostic criteria and selection for treatment. J Pediatr Surg. (1985) 20:376–87. doi: 10.1016/S0022-3468(85)80223-2
18. Manning F, Harrison M, Rodeck C. Catheter shunts for fetal hydronephrosis and hydrocephalus. Report of the International Fetal Surgery Registry. N Engl J Med. (1986) 315:336–40. doi: 10.1056/NEJM198607313150532
19. Jeong B, Won H, Lee M. Perinatal outcomes of fetal lower urinary tract obstruction after vesicoamniotic shunting using a double-basket catheter. J Ultrasound Med. (2018) 37:2147–56. doi: 10.1002/jum.14565
20. Saccone G, D'Alessandro P, Escolino M, Esposito R, Arduino B, Vitagliano A, et al. Antenatal intervention for congenital fetal lower urinary tract obstruction (LUTO): a systematic review and meta-analysis. J Matern Fetal Neonatal Med. (2018) 2 1–161. doi: 10.1080/14767058.2018.1519543
21. Sananes N, Cruz-Martinez R, Favre R, Ordorica-Flores R, Moog R, Zaloszy A, et al. Two-year outcomes after diagnostic and therapeutic fetal cystoscopy for lower urinary tract obstruction. Prenat Diagn. (2016) 36:297–303. doi: 10.1002/pd.4771
22. Martínez J, Masoller N, Devlieger R, Passchyn E, Gómez O, Rodo J, et al. Laser ablation of posterior urethral valves by fetal cystoscopy. Fetal Diagn Ther. (2015) 37:267–73. doi: 10.1159/000367805
23. Quintero R, Johnson M, Romero R, Smith C, Arias F, Guevara-Zuloaga F, et al. In-utero percutaneous cystoscopy in the management of fetal lower obstructive uropathy. Lancet. (1995) 26:537–40. doi: 10.1016/S0140-6736(95)91381-5
24. Sananes N, Favre R, Koh C, Zaloszyc A, Braun M, Roth D, et al. Urological fistulas after fetal cystoscopic laser ablation of posterior urethral valves: surgical technical aspects. Ultrasound Obstet Gynecol. (2015) 45:183–9. doi: 10.1002/uog.13405
25. Quintero R, Shukla A, Homsy Y, Bukkapatnam R. Successful In utero endoscopic ablation of posterior urethral valves: a new dimension in fetal urology. Urology. (2000) 55:774. doi: 10.1016/S0090-4295(00)00500-8
26. Luks F. Re: Fetal intervention for severe lower urinary tract obstruction: a multicenter case-control study comparing fetal cystoscopy with vesicoamniotic shunting. R. Ruano, N. Sananes, H. Sangi-Haghpeykar, S. Hernandez-Ruano, R. Moog, F. Becmeur, A. Zaloszyc, A. M. Giron, B. Morin and R. Favre. Ultrasound Obstet Gynecol 2015; 45:452-458. Ultrasound Obstet Gynecol. (2015) 45:375–6. doi: 10.1002/uog.14823
27. Nguyen H, Herndon C, Cooper C, Gatti J, Kirsch A, Kokorowski P, et al. The Society for Fetal Urology consensus statement on the evaluation and management of antenatal hydronephrosis. J Pediatr Urol. (2010) 6:212–31. doi: 10.1016/j.jpurol.2010.02.205
28. Quintero R, Homsy Y, Bornick P, Allen M, Johnson P. In-utero treatment of fetal bladder-outlet obstruction by a ureterocele. Lancet. (2001) 357:1947–8. doi: 10.1016/S0140-6736(00)05084-4
29. Chalouhi G, Morency A, De Vlieger R, Martinez J, Blanc T, Hodges R, et al. Prenatal incision of ureterocele causing bladder outlet obstruction: a multicenter case series. Prenat Diagn. (2017) 37:968–74. doi: 10.1002/pd.5091
30. Mallmann M, Reutter H, Mack-Detlefsen B, Gottschalk I, Geipel A, Berg C, et al. Prenatal diagnosis of hydro(metro)colpos: a series of 20 cases. Fetal Diagn Ther. (2019) 45:62–8. doi: 10.1159/000486781
31. Nigam A, Kumar M, Gulati S. Fetal ascites and hydrometrocolpos due to persistent urogenital sinus and cloaca: a rare congenital anomaly and review of literature. BMJ Case Rep. (2014) 2014:bcr2013202231. doi: 10.1136/bcr-2013-202231
32. Chen C, Liu F, Jan S, Chang P, Lin Y, Lan C. Ultrasound-guided fluid aspiration and prenatal diagnosis of duplicated hydrometrocolpos with uterus didelphys and septate vagina. Prenat Diagn. (1996) 16:572–6.
33. Witchel S. Congenital adrenal hyperplasia. J Pediatr Adolesc Gynecol. (2017) 30:520–34. doi: 10.1016/j.jpag.2017.04.001
34. Rodríguez A, Ezquieta B, Labarta J, Clemente M, Espino R, Rodriguez A, et al. [Recommendations for the diagnosis and treatment of classic forms of 21-hydroxylase-deficient congenital adrenal hyperplasia]. An Pediatr. (2017) 87:116.e1–10. doi: 10.1016/j.anpedi.2016.12.002
35. Dörr H, Binder G, Reisch N, Gembruch U, Oppelt P, Wieacker P, et al. Experts' opinion on the prenatal therapy of Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency - guideline of DGKED in cooperation with DGGG (S1-Level, AWMF Registry No. 174/013, July 2015). Geburtshilfe Frauenheilkd. (2015) 75:1232–8. doi: 10.1055/s-0041-109717
36. Kazmi D, Bailey J, Yau M, Abu-Amer W, Kumar A, Low M, et al. New developments in prenatal diagnosis of congenital adrenal hyperplasia. J Steroid Biochem Mol Biol. (2017) 165:121–3. doi: 10.1016/j.jsbmb.2016.06.016
37. Meyer-Bahlburg H, Dolezal C, Haggerty R, Silverman M, New M. Cognitive outcome of offspring from dexamethasone-treated pregnancies at risk for congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Eur J Endocrinol. (2012) 167:103–10. doi: 10.1530/EJE-11-0789
38. Maryniak A, Ginalska-Malinowska M, Bielawska A, Ondruch A. Cognitive and social function in girls with congenital adrenal hyperplasia – influence of prenatally administered dexamethasone. Child Neuropsychol. (2014) 20:60–70. doi: 10.1080/09297049.2012.745495
39. Cernat A, De Freitas C, Majid U, Trivedi F, Higgins C, Vanstone M. Facilitating informed choice about non-invasive prenatal testing (NIPT): a systematic review and qualitative meta-synthesis of women's experiences. BMC Pregnancy Childbirth. (2019) 19:27. doi: 10.1186/s12884-018-2168-4
40. Lajic S, Karlsson L, Nordenström A. Prenatal treatment of congenital adrenal hyperplasia: long-term effects of excess glucocorticoid exposure. Horm Res Paediatr. 89:362–71. doi: 10.1159/000485100
41. Bennett K, Carroll M, Shannon C, Braun S, Dabrowiak M, Crum A, et al. Reducing perinatal complications and preterm delivery for patients undergoing In utero closure of fetal myelomeningocele: further modifications to the multidisciplinary surgical technique. J Neurosurg Pediatr. (2014) 14:108–14. doi: 10.3171/2014.3.PEDS13266
42. Meuli M, Meuli-Simmen C, Yingling C, Hutchins G, Hoffman K, Harrison M, et al. Creation of myelomeningocele In utero: a model of functional damage from spinal cord exposure in fetal sheep. J Pediatr Surg. (1995) 30:1028–32. doi: 10.1016/0022-3468(95)90335-6
43. Adzick N, Thom E, Spong C, Brock Jr, Burrows P, Johnson M, et al. A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med. (2011) 364:993–1004. doi: 10.1056/NEJMoa1014379
44. Tulipan N, Bruner J. Myelomeningocele repair In utero: a report of three cases. Pediatr Neurosurg. (1998) 28:177–80. doi: 10.1159/000028645
45. Holzbeierlein J, Pope JI, Adams M, Bruner J, Tulipan N, Brock Jr. The urodynamic profile of myelodysplasia in childhood with spinal closure during gestation. J Urol. (2000) 164:1336–9. doi: 10.1016/S0022-5347(05)67191-1
46. Holmes N, Nguyen H, Harrison M, Farmer D, Baskin L. Fetal intervention for myelomeningocele: effect on postnatal bladder function. J Urol. (2001) 166:2383–6. doi: 10.1016/S0022-5347(05)65596-6
47. Koh C, DeFilippo R, Borer J, Khoshbin S, Bauer S. Bladder and external urethral sphincter function after prenatal closure of myelomeningocele. J Urol. (2006) 176:2232–6. doi: 10.1016/j.juro.2006.07.077
48. Clayton D, Brock Jr. In utero intervention for urologic diseases. Nat Rev Urol. (2012) 21:207–17. doi: 10.1038/nrurol.2012.9
49. Lee N, Gomez P, Uberoi V, Kokorowski P, Khoshbin S, Bauer S, et al. In utero closure of myelomeningocele does not improve lower urinary tract function. J Urol. (2012) 188(Suppl. 4):1567–71. doi: 10.1016/j.juro.2012.06.034
50. Leal da Cruz M, Liguori R, Garrone G, Leslie B, Ottoni S, Carvalheiro S, et al. Categorization of bladder dynamics and treatment after fetal myelomeningocele repair: first 50 cases prospectively assessed. J Urol. (2015) 193(Suppl. 5):1808–11. doi: 10.1016/j.juro.2014.10.118
51. Horst M, Mazzone L, Schraner T, Bodmer C, Möhrlen U, Meuli M, et al. Prenatal myelomeningocele repair: do bladders better? Neurourol Urodyn. (2017) 36:1651–8. doi: 10.1002/nau.23174
52. Macedo AJ, Ottoni S, Garrone G, Liguori R, Cavalheiro S, Moron A, et al. In utero myelomeningocoele repair and urological outcomes: the first 100 cases of a prospective analysis. Is there an improvement in bladder function? BJU Int. (2018) 123:676–81. doi: 10.1111/bju.14639
Keywords: LUTO, congenital adrenal hyperplasia (CAH), vesicoamniotic shunt, myelomeningocele, fetal therapy, posterior urethral valves
Citation: Bañuelos Marco B, González R, Ludwikowski B and Lingnau A (2019) Effectiveness of Prenatal Intervention on the Outcome of Diseases That Have a Postnatal Urological Impact. Front. Pediatr. 7:118. doi: 10.3389/fped.2019.00118
Received: 30 January 2019; Accepted: 11 March 2019;
Published: 02 April 2019.
Edited by:
Luis Henrique Braga, McMaster University, CanadaReviewed by:
Sadaf Aba Umer Kodwavwala, Sindh Institute of Urology and Transplantation, PakistanAndres Gomez Fraile, Hospital Universitario 12 De Octubre, Spain
Copyright © 2019 Bañuelos Marco, González, Ludwikowski and Lingnau. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Ricardo González, ricardo_gonzalez33154@yahoo.com