Skip to main content
SpringerLink
Log in

Alport syndrome and pregnancy: a case series and literature review

  • Maternal-Fetal Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

To assess pregnancy outcome in women with Alport syndrome and the impact of pregnancy on the disease progression.

Methods

We describe one of the largest series of pregnancies in Alport syndrome. Seven pregnancies of six women were monitored by a multidisciplinary team of nephrologists and gynecologists. After delivery, patients were followed for at least 3 years. We compare our results with those in the literature.

Results

Pregnancy course was uneventful in the patient with isolated microscopic hematuria. In the other cases, all presenting mild proteinuria at conception, some complications occurred. Proteinuria worsened during the last trimester, reaching nephrotic ranges in five out of six pregnancies and was associated with fluid overload leading to hospitalizations and early delivery. The majority of the newborns had a low birth weight. The two patients with arterial hypertension at conception and twin pregnancy developed pre-eclampsia and renal function deterioration persisted after delivery. The one with pre-pregnancy renal dysfunction reached end-stage renal disease. In the other patients, in which renal function and blood pressure were and remained normal, proteinuria improved after delivery and no signs of disease progression were recorded at last observation.

Conclusions

Our observations suggest that Alport syndrome should be considered a potential risk factor for pregnancy in proteinuric patients due to the development of pre-eclampsia, renal function deterioration, and/or full-blown nephrotic syndrome that results in anasarca, slowing of fetal growth and pre-term delivery. Thus, all women with Alport syndrome should receive pre-conceptional counseling and be kept in close follow-up during pregnancy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Savige J, Colville D, Rheault M, Gear S, Lennon R, Lagas S, Finlay M, Flinter F (2016) Alport syndrome in women and girls. Clin J Am Soc Nephrol 11:1713–1720

    Article  PubMed  PubMed Central  Google Scholar 

  2. Cosgrove D, Liu S (2017) Collagen IV diseases: a focus on the glomerular basement membrane in Alport syndrome. Matrix Biol 57–58:45–54

    Article  PubMed  Google Scholar 

  3. Hudson BG, Tryggvason K, Sundaramoorthy M, Neilson EG (2003) Alport’s syndrome, Goodpasture’s syndrome, and type IV collagen. New Engl J Med 348:2543–2556

    Article  CAS  PubMed  Google Scholar 

  4. Kashtan CE (2001) Alport syndrome and thin basement membrane nephropathy (last updated 2015 Nov 25) gene reviews. University of Washington, Seattle

    Google Scholar 

  5. Morinière V, Dahan K, Hilbert P, Lison M, Lebbah S, Topa A, Bole-Feysot C, Pruvost S, Nitschke P, Plaisier E, Knebelmann B, Macher MA, Noel LH, Gubler MC, Antignac C, Heidet L (2014) Improving mutation screening in familial hematuric nephropathies through next generation sequencing. J Am Soc Nephrol 25:2740–2751

    Article  PubMed  PubMed Central  Google Scholar 

  6. Fallerini C, Dosa L, Tita R, Del Prete D, Feriozzi S, Gai G, Clementi M, La Manna A, Miglietti N, Mancini R, Mandrile G, Ghiggeri GM, Piaggio G, Brancati F, Diano L, Frate E, Pinciaroli AR, Giani M, Castorina P, Bresin E, Giachino D, De Marchi M, Mari F, Bruttini M, Renieri A, Ariani F (2014) Unbiased next generation sequencing analysis confirms the existence of autosomal dominant Alport syndrome in a relevant fraction of cases. Clin Genet 86:252–257

    Article  CAS  PubMed  Google Scholar 

  7. Jais JP, Knebelmann B, Giatras I, De Marchi M, Rizzoni G, Renieri A, Weber M, Gross O, Netzer K-O, Flinter F, Pirson Y, Verellen C, Wieslander JR, Persson U, Tryggvason K, Martin P, Hertz JM, Schroder C, Sanak M, Krejcova S, Carvalho MF, Saus J, Antignac C, Smeets H, Gubler MC (2000) X-linked Alport syndrome: natural history in 195 families and genotype- phenotype correlations in males. J Am Soc Nephrol 11:649–657

    CAS  PubMed  Google Scholar 

  8. Bekheirnia MR, Reed B, Gregory MC (2010) Genotype-phenotype correlation in X-linked Alport syndrome. J Am Soc Nephrol 21:876–883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Rheault MN (2012) Women and Alport syndrome. Pediatr Nephrol 27:41–46

    Article  PubMed  Google Scholar 

  10. Jais JP, Knebelmann B, Giatras I, De Marchi M, Rizzoni G, Renieri A, Weber M, Gross O, Netzer K-O, Flinter F, Pirson Y, Dahan K, Wieslander JR, Persson U, Tryggvason K, Martin P, Hertz JM, Schroder C, Sanak M, Carvalho MF, Saus J, Antignac C, Smeets H, Gubler MC (2003) X-linked Alport syndrome: natural history and genotype-phenotype correlations in girls and women belonging to 195 families: a “European Community Alport Syndrome Concerted Action” study. J Am Soc Nephrol 14:2603–2610

    Article  PubMed  Google Scholar 

  11. Yefet E, Tovbin D, Nachum Z (2016) Pregnancy outcomes in patients with Alport syndrome. Arch Gynaecol Obstet 293:739–747

    Article  CAS  Google Scholar 

  12. Crovetto F, Moroni G, Zaina B, Acaia B, Ossola MW, Fedele L (2013) Pregnancy in women with Alport syndrome. Int Urol Nephrol 45:1223–1227

    Article  PubMed  Google Scholar 

  13. Nevis IF, Reitsma A, Dominic A, McDonald S, Thabane L, Akl EA, Hladunewich M, Akbari A, Joseph G, Sia W, Iansavichus AV, Garg AX (2011) Pregnancy outcomes in women with chronic kidney disease: a systematic review. Clin J Am Soc Nephrol 6:2587–2598

    Article  PubMed  PubMed Central  Google Scholar 

  14. Bramham K, Parnell B, Nelson-Piercy C, Seed PT, Poston L, Chappell LC (2014) Chronic hypertension and pregnancy outcomes: systematic review and meta-analysis. BMJ 348:g2301

    Article  PubMed  PubMed Central  Google Scholar 

  15. Cabiddu G, Castellino S, Gernone G, Moroni G, Giannattasio M, Gregorini G, Giacchino F, Attini R, Loi V, Limardo M, Gammaro L, Todros T, Piccoli GB (2016) A best practice position statement on pregnancy in chronic kidney disease: the Italian Study Group on kidney and pregnancy. J Nephrol 29:277–303

    Article  PubMed  PubMed Central  Google Scholar 

  16. Matsuo K, Tudor EL, Baschat AA (2007) Alport syndrome and pregnancy. Obstet Gynecol 109:531–532

    Article  PubMed  Google Scholar 

  17. Mehta S, Saifan C, Abdellah M, Choueiry R, Nasr R, El-Sayegh S (2013) Alport’s syndrome in pregnancy. Case Rep Med. https://doi.org/10.1155/2013/374020

    PubMed  PubMed Central  Google Scholar 

  18. Kitanovska BG, Gerasimovska V, Livrinova V (2016) Two pregnancies with a different outcome in a patient with Alport syndrome. Open Access Maced J Med Sci 4(3):439–442

    Article  PubMed  PubMed Central  Google Scholar 

  19. Alessi M, Fabris A, Zambon A, Cremasco D, Murar o E, Dosa L (2014) Pregnancy in Alport syndrome: a report of two differently-evolving cases. J Obstet Gynaecol 34(1):98–100

    Article  CAS  PubMed  Google Scholar 

  20. Nishizawa Y, Takei T, Miyaoka T, Kamei D, Mochizuki T, Nitta K (2016) Alport syndrome and pregnancy: good obstetric and nephrological outcomes in a pregnant woman with homozygous autosomal recessive Alport syndrome. J Obstet Gynaecol Res 42(3):331–335

    Article  PubMed  Google Scholar 

  21. Matsubara S, Ueda Y, Takahashi H, Nagai T, Kuwata T, Muto S, Yamaguchi T, Takizawa T, Suzuki M (2009) Pregnancy complicated with Alport syndrome: a good obstetric outcome and failure to diagnose an infant born to a mother with Alport syndrome by umbilical cord immunofluorescence staining. J Obstet Gynaecol Res 35(6):1109–1114

    Article  PubMed  Google Scholar 

  22. Matsubara S, Muto S (2012) Good obstetric outcome of consecutive pregnancies in a woman with Alport syndrome. Arch Gynecol Obstet 286:261–262

    Article  PubMed  Google Scholar 

  23. Bramham K, Lightstone L (2012) Pre-pregnancy counseling for women with chronic kidney disease. J Nephrol 25(04):450–459

    Article  PubMed  Google Scholar 

  24. Helal I, Fick-Brosnahan GM, Reed-Gitomer B, Schrier RW (2012) Glomerular hyperfiltration: definitions, mechanisms and clinical implications. Nat Rev Nephrol 8:293–300

    Article  CAS  PubMed  Google Scholar 

  25. Sibai BM, Villar MA, Mabie BC (1990) Acute renal failure in hypertensive disorders of pregnancy: pregnancy outcome and remote prognosis in thirty-one consecutive cases. Am J Obstet Gynecol 162:777–783

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

No supplemental funding was provided for this research.

Author information

Authors and Affiliations

  1. Nephrology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Francesca Brunini, Davide Gianfreda, Piergiorgio Messa & Gabriella Moroni

  2. Department of Obstetrics and Gynecology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Barbara Zaina, Wally Ossola & Luigi Fedele

  3. Pediatric Nephrology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Marisa Giani

Authors
  1. Francesca Brunini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Barbara Zaina
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Davide Gianfreda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wally Ossola
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marisa Giani
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Luigi Fedele
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Piergiorgio Messa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gabriella Moroni
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

FB data collection, data analysis, and manuscript writing/editing. BZ clinical assessment of mothers and fetus during pregnancy and patient follow-up. DG data collection. WO clinical assessment of mothers and fetus during pregnancy and patient follow-up. MG patient follow-up at diagnosis. LF paper assessment. PGM paper assessment. GM project development; clinical assessment of mothers and fetus during pregnancy and patient follow-up; data analysis and manuscript writing/editing.

Corresponding author

Correspondence to Francesca Brunini.

Ethics declarations

Conflict of interest

The authors report no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the IRCCS Ca’ Granda Ospedale Maggiore Policlinico ethics committee-Milano area B- and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

Informed consent

Data were collected retrospectively in an anonymous database without interfering with the best clinical practice at any time during patients’ follow-up. Due to the retrospective nature of the study, neither written nor verbal informed consent was necessary, according to the ethical standards of the institutional Ethics Committee.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Brunini, F., Zaina, B., Gianfreda, D. et al. Alport syndrome and pregnancy: a case series and literature review. Arch Gynecol Obstet 297, 1421–1431 (2018). https://doi.org/10.1007/s00404-018-4720-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-018-4720-x

Keywords

Search

Navigation