Use of Corticosteroids in Prenatal Treatment of Congenital Pulmonary Adenomatoid Malformation: Integrative Review

Fortes, Isadora Macedo Lins Parentes; Bennini Junior, João Renato

doi:10.1055/s-0041-1741517

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Revista Brasileira de Ginecologia e Obstetrícia

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Sumário

Review Article • Rev. Bras. Ginecol. Obstet. 44 (3) • Mar 2022 • https://doi.org/10.1055/s-0041-1741517 copy

Use of Corticosteroids in Prenatal Treatment of Congenital Pulmonary Adenomatoid Malformation: Integrative Review

Uso de corticosteroides no tratamento pré-natal da malformação adenomatoide pulmonar congênita:Revisão integrativa

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective

To review data on the use of corticosteroids for the treatment of fetuses with high-risk congenital pulmonary adenomatoid malformation (CPAM).

Methods

Integrative review based on the literature available onMEDLINE and LILACS, including articles published until November, 2020.

Results

The initial search resulted in 87 articles, 4 of which were selected for analysis, with all of them being retrospective descriptive observational studies. In the group of fetuses that received only a single corticosteroid cycle, the hydrops resolution rate was 70%, and the survival rate was 83.8%. In fetuses treated with 2 or more cycles of corticosteroids, there was an improvement in the condition of hydrops or edema in a single body compartment in 47%, and survival of 81.8% of the fetuses.

Conclusion

The use of corticosteroids for the prenatal treatment of high-risk CPAM appears to be associated with an improvement in perinatal outcomes.

Keywords:
congenital pulmonary adenomatoid malformation; fetal treatment; corticosteroid; betamethasone; hydrops

Article	Type of article	Study objective	Place of study	Studied population	Number of individuals	Main results
Morris et al.¹³13 Morris LM, Lim FY, Livingston JC, Polzin WJ, Crombleholme TM. High-risk fetal congenital pulmonary airway malformations have a variable response to steroids. J Pediatr Surg. 2009;44(01):60-65. Doi: 10.1016/j.jpedsurg.2008.10.012 https://doi.org/10.1016/j.jpedsurg.2008....	Retrospective review	Review the experience with CPAMs to determine the fetal response to steroid therapy	Cincinnati, OH, USA	Fetuses diagnosed with high-risk CPAM and treated with at least one course of betamethasone	44 with CPAM, of which 15 were selected to receive at least one dose of corticosteroids	● Thirteen were hydropic and 2 were nonhydropic. ● Seven of the 13 hydropic fetuses (54%) shown an initial response to steroid administration, whereas the 2 nonhydropic high-risk fetuses progressed to birth without developing hydrops. ● Seven of 15 patients, however, resulted in the fetal demise or early postnatal death, giving a survival rate of 53%.
Curran et al.¹⁴14 Curran PF, Jelin EB, Rand L, Hirose S, Feldstein VA, Goldstein RB, et al. Prenatal steroids for microcystic congenital cystic adenomatoid malformations. J Pediatr Surg. 2010;45(01):145-150. Doi: 10.1016/j.jpedsurg.2009.10.025 https://doi.org/10.1016/j.jpedsurg.2009....	Retrospective review	Evaluate the effect of prenatal steroid treatment in fetuses with sonographically diagnosed CPAM	San Francisco, CA,USA	Patients with a diagnosis of fetal CPAM with a predominatelymicrocystic lesion and not submitted to a fetal surgical intervention for CPA and who received maternal administration of a single course ofprenatal steroids	Sixteen pregnancies with predominately microcysticCPAM treated with a single course of prenatal steroids (3 were excluded because of lack of follow-up information.	● All 13 fetuses survived to delivery and 11 survived to neonatal discharge. ● At the time of steroid administration, all patients had CVR greater than 1,6, and 9 of them also had nonimmune hydrops fetalis. ● After a course of steroids, CVR decreased in 8 of the 13 patients, and hydrops resolved in 7 of the 9 patients with hydrops.● The 2 patients whose hydrops did not resolve with steroid treatment did not survive to discharge.
Peranteau et al.¹⁵15 Peranteau WH, Boelig MM, Khalek N, Moldenhauer JS, Martinez-Poyer J, Hedrick HL, et al. Effect of single and multiple courses of maternal betamethasone on prenatal congenital lung lesion growth and fetal survival. J Pediatr Surg. 2016;51(01):28-32. Doi: 10.1016/j.jpedsurg.2015.10.018 https://doi.org/10.1016/j.jpedsurg.2015....	Retrospective review	Present theexperience with the management fetuses with large congenital lunglesions receiving multiple courses of maternal BMZ and provide anupdate on the response of those receiving a single course.	Philadelphia, PA,USA	Fetuses with congenital lung lesions managed with maternal BMZ	Forty-three patients were managed with prenatal steroids (28 with single course and 15 with multiple courses)	● Single course recipients demonstrated a reduction in lesion size and resolution of hydrops in 82% and 88% of patients respectively compared with 47% and 56% in recipients of multiple steroid courses. ● Survival of multiple course patients (86%) was comparable to that of single course patients (93%) and improved compared with non-treated historical controls. ● Multiple course recipients demonstrated an increased need for open fetal surgery and postnatal surgery at a younger age.
Derderian et al.¹⁶16 Derderian SC, Coleman AM, Jeanty C, Lim FY, Shaaban AM, Farrell JA, et al. Favorable outcomes in high-risk congenital pulmonary airway malformations treated with multiple courses of maternal betamethasone. J Pediatr Surg. 2015;50(04):515-518. Doi: 10.1016/j.jpedsurg.2014.08.019 https://doi.org/10.1016/j.jpedsurg.2014....	Retrospective review	Review treatment approaches and outcomes of fetuses who received multiple courses of maternal betamethasone at two tertiary fetal treatment centers.	Cincinnati, OH, and San Francisco, CA,USA	Patients treated with multiple courses of prenatal steroids for high-risk CPAMs	Eight patients with high-risk CPAM	● All patients (9) but one either had an increased CVR or number of fluid-containing compartments involved after a single course of antenatal betamethasone, prompting additional courses. ● Four patients stabilized, three improved and two progressed after the second course. ● The two cases with disease progression underwent an in utero resection. ● There were one in utero fetal demise and two deaths within the delivery room. Both fetuses that underwent a fetal resection died. ● All but one mother who delivered a viable fetus had complications of pregnancy.

Article	Number of fetuses treated	Corticosteroid used*	Number of cycles	Type of lung injury	Fetuses with hydrops	Fetuses without hydrops	Mediastinal shift	Average gestational age (weeks)	Average CVR before treatment
Morris et al.¹³13 Morris LM, Lim FY, Livingston JC, Polzin WJ, Crombleholme TM. High-risk fetal congenital pulmonary airway malformations have a variable response to steroids. J Pediatr Surg. 2009;44(01):60-65. Doi: 10.1016/j.jpedsurg.2008.10.012 https://doi.org/10.1016/j.jpedsurg.2008....	15	Betamethasone 12.5 mg 02 doses	1	Macrocystic (n = 7)Microcystic (n = 7)Hybrid (n = 1)	13	2	NA	24 ± 4.1	2.62 ± 1.51
Curran et al.¹⁴14 Curran PF, Jelin EB, Rand L, Hirose S, Feldstein VA, Goldstein RB, et al. Prenatal steroids for microcystic congenital cystic adenomatoid malformations. J Pediatr Surg. 2010;45(01):145-150. Doi: 10.1016/j.jpedsurg.2009.10.025 https://doi.org/10.1016/j.jpedsurg.2009....	13	Betamethasone 12 mg 02 doses	1	Predominantly microcystic	9	2 with ascites2 without edema	100%	24.55 ± 1.53	2.72 ± 0.92
Peranteau et al.¹⁵15 Peranteau WH, Boelig MM, Khalek N, Moldenhauer JS, Martinez-Poyer J, Hedrick HL, et al. Effect of single and multiple courses of maternal betamethasone on prenatal congenital lung lesion growth and fetal survival. J Pediatr Surg. 2016;51(01):28-32. Doi: 10.1016/j.jpedsurg.2015.10.018 https://doi.org/10.1016/j.jpedsurg.2015....	43 #	Betamethasone 12 mg 02 doses	1	Macrocystic and microcystic	18	25	43	23.4 ± 2.2	2 ± 0.6
			2	Macrocystic and microcystic				24 ± 2	2.6 ± 0.7
			3	Macrocystic andmicrocystic				25.3 ± 0.3	2.5 ± 0.4
Derderian et al.¹⁶16 Derderian SC, Coleman AM, Jeanty C, Lim FY, Shaaban AM, Farrell JA, et al. Favorable outcomes in high-risk congenital pulmonary airway malformations treated with multiple courses of maternal betamethasone. J Pediatr Surg. 2015;50(04):515-518. Doi: 10.1016/j.jpedsurg.2014.08.019 https://doi.org/10.1016/j.jpedsurg.2014....	8	Betamethasone 12.5 mg 02 doses	2	Predominantly microcystic	5	3 with ascites	NA	First cycle: 22Second cycle: 25	2.8

Article	Regression of hydrops	Interval between treatment and resolution of hydrops	Regression of CVR	Resolution of mediastinal shift	Survival rate	Mean gestational age of childbirth (weeks)
Morris et al.¹³13 Morris LM, Lim FY, Livingston JC, Polzin WJ, Crombleholme TM. High-risk fetal congenital pulmonary airway malformations have a variable response to steroids. J Pediatr Surg. 2009;44(01):60-65. Doi: 10.1016/j.jpedsurg.2008.10.012 https://doi.org/10.1016/j.jpedsurg.2008....	54%^a a 3 fetuses needed complementary surgery after corticosteroid therapy.	NA	NA	NA	53%	NA
Curran et al.¹⁴14 Curran PF, Jelin EB, Rand L, Hirose S, Feldstein VA, Goldstein RB, et al. Prenatal steroids for microcystic congenital cystic adenomatoid malformations. J Pediatr Surg. 2010;45(01):145-150. Doi: 10.1016/j.jpedsurg.2009.10.025 https://doi.org/10.1016/j.jpedsurg.2009....	77.8% of hydrops100% of those with ascites	29.9 days	61.5%	100%	100%^b b 84.6% survived hospital discharge.	35.6
Peranteau et al.¹⁵15 Peranteau WH, Boelig MM, Khalek N, Moldenhauer JS, Martinez-Poyer J, Hedrick HL, et al. Effect of single and multiple courses of maternal betamethasone on prenatal congenital lung lesion growth and fetal survival. J Pediatr Surg. 2016;51(01):28-32. Doi: 10.1016/j.jpedsurg.2015.10.018 https://doi.org/10.1016/j.jpedsurg.2015....	Single cycle: 88%Multiples cycles: 56%General: 71%	NA	Single cycle: 82%Multiples cycles: 47%	Single cycle: 57%Multiples cycles: 40%General: 51%	Single cycle: 93%Multiples cycles: 86%General: 98%	NA
Derderian et al.¹⁶16 Derderian SC, Coleman AM, Jeanty C, Lim FY, Shaaban AM, Farrell JA, et al. Favorable outcomes in high-risk congenital pulmonary airway malformations treated with multiple courses of maternal betamethasone. J Pediatr Surg. 2015;50(04):515-518. Doi: 10.1016/j.jpedsurg.2014.08.019 https://doi.org/10.1016/j.jpedsurg.2014....	First cycle: 12.8% with improvement	NA	First cycle:62.5% with stabilization	NA	75%	34
	Second cycle:37.5% with improvement37.5% with stabilization		Second cycle:25% with improvement50% with stabilization

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[1] Address for correspondence
Professor João Renato Bennini Junior, MD, PhD, Cidade Universitária Zeferino Vaz, 13083-970, Barão Geraldo, Campinas, SP, Brazil (e-mail: bennini@unicamp.br).