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Advances in Chronic Kidney Disease, Vol 14, No 2 (April), 2007: pp 199-205 199
200 Blowey and Warady
Table 1. Stages of Chronic Kidney Disease Accordingly, a PubMed search for articles re-
Stage GFR (mL/min/1.73 m ) 2 lated to neonatal outcome in women with
CKD, transplantation, or dialysis was com-
1 ⬎90 pleted. Publications dating 1980 forward were
2 60-89
3 30-59 reviewed for applicability, and the bibliogra-
4 15-29 phy was searched for articles not noted in the
5 ⬍15 PubMed search.
Table 2. Summary of the Studies Assessing Neonatal Outcome in Pregnancies Associated with Chronic
Kidney Disease and End-Stage Renal Disease
General Population Transplant Dialysis CKD
Preterm (⬍37 weeks) 12.3% 50%-54% 67% 16%-59%
SGA — 33%-45% 37% 7%-37%
Neonatal mortality 0.68% 1%-3% 10%-11% 3%-10%
BW ⬍2,500 g 8% 46%-50% 94% 37%
Abbreviations: BW, birth weight; CKD, chronic kidney disease; SGA, small for gestational age.
Outcome of Infants Born to Women with CKD 201
in the absence of hypertension. They are pre- 9 months to 18 years). Of the 48 infants in the
scribed for patients with all stages of CKD, in survey, 94% were considered to be in good
kidney transplant recipients, and in dialysis general health, 95% had a normal physical
patients as a means to control blood pressure examination (1 child with cerebral palsy and 1
and help preserve residual kidney function. child with a claw-hand deformity), and 98%
These agents are contraindicated in preg- were considered developmentally normal. As
nancy because of the well-characterized feto- no formal developmental testing was done,
toxic effects of ACE inhibitors. ACE inhibitor subtle developmental abnormalities could not
fetopathy, characterized by fetal hypotension, be excluded. In a much smaller study of chil-
anuria-oliogohydramnios, growth restriction, dren who underwent a more detailed assess-
pulmonary hypoplasia, renal tubular dyspla- ment of development, all 6 children (aged 1 to
sia, and hypocalvaria, may occur with second- 6 years) born to mothers with a functioning
trimester or third-trimester exposure to ACE kidney transplant were considered to have
inhibitors.32-35 The neonatal mortality for in- normal development.39 Although these data
fants with ACE-inhibitor fetopathy may be as do not suggest any severe health challenges,
high as 25%.33 Historically, first-trimester ex- one must keep in mind, as mentioned previ-
posure to ACE inhibitors has not been per- ously, that children born to mothers with
ceived as a risk for adverse birth outcomes; ESRD or CKD are more likely to be born pre-
however, a recent study suggests that first- mature and that extremely low-birth-weight
trimester exposure to ACE inhibitors does in- babies (eg, ⬍1,000 g) have considerable long-
crease the risk of major congenital malforma- term health and educational needs and can
tions.36 have significant neurodevelopment impair-
ment.40,41 Fortunately, although babies born
Developmental Outcome to mothers with ESRD or CKD tend to be
premature, most infants are apparently born
The long-term cognitive, developmental, and after 32 weeks of gestational age and do not
functional outcome of infants born to mothers incur the same neurodevelopmental risks as
with CKD is of importance to the parents, as extremely low-birth-weight infants.
well as to the medical community that must
provide the appropriate support services. Un-
fortunately, very little information is available
Summary
on the developmental outcome of children
born to mothers with CKD, to those receiving The ability to provide an accurate assessment
dialysis, or to those with a functioning kidney of neonatal outcome of infants born to women
transplant. An exploratory phone survey of with CKD is made difficult by the lack of good
women registered in the NTPR found that data. Currently, we are aware that pregnancy
16% of children born to transplant recipients in women with CKD and ESRD is associated
receiving cyclosporine had developmental de- with high rate of preterm birth and SGA in-
lays or required educational support.37 Al- fants with resultant increased risk of neonatal
though no formal developmental or control mortality. Whether the risks are caused by the
group testing was conducted, the study high- specific underlying maternal kidney disease,
lights the potential for subtle developmental factors unique to kidney transplantation or
abnormalities and the need for further explo- dialysis, or one of the many comorbid condi-
ration. Willis et al.38 completed a cross-sec- tions or required medications is not clear and
tional prevalence survey on the general health requires further investigation. Although an
and developmental state of 48 children born increased risk of congenital anomalies does
to kidney transplant recipients. The survey not appear to occur in this population, the
included a basic physical and developmental information should be viewed with caution
assessment, the latter of which consisted of an until more specific studies can be done to
assessment of the attainment of developmen- assess the short-term impact of the newer
tal milestones and academic achievement. The immunosuppressive regimens and the com-
median age of follow-up was 5.2 years (range: pletion of long-term studies to assessing the
204 Blowey and Warady
potential for developmental anomalies and 17. Clausson B, Cnattingius S, Axelsson O: Preterm and
delayed toxicity. term births of small for gestational age infants: A
population-based study of risk factors among nullip-
arous women. Br J Obstet Gynaecol 105:1011-1017,
1998
References 18. Armenti VT, Stefanosky EV, Cater JR, et al: Pregnancy
in transplant recipients. J Transplant Coordination
1. K/DOQI: Clinical practice guidelines for chronic kid- 5:130-136, 1995
ney disease: Evaluation, classification, and stratifica- 19. Armenti VT, Ahlswede KM, Ahlswede BA, et al:
tion. Am J Kidney Dis 39:S1-S266, 2002 (suppl 1) National Transplantation Pregnancy Registry: Out-
2. National Institutes of Health: U.S. Renal Data System, comes of 154 pregnancies in cyclosporine-treated fe-
USRDS 2005 Annual Data Report: Atlas of End-Stage male kidney transplant recipients. Transplantation
Renal Disease in the United States. Bethesda, MD. 57:502-506, 1994
2005. Available at: URL: http://www.usrds.org
20. Armenti VT, Radomski JS, Moritz MJ, et al: Report
3. Rizzoni G, Ehrich JHH, Broyer M, et al: Successful
from the National Transplantation Pregnancy Regis-
pregnancies in women on renal replacement therapy:
try (NTPR): Outcomes of pregnancy after transplan-
Report from the EDTA registry. Nephol Dial Trans-
tation. Clin Transpl 103-114, 2004
plant 7:279-287, 1992
21. Ehrich JHH, Loirat C, Davison JM, et al: Repeated
4. Hou SH: Pregnancy in women on haemodialysis and
successful pregnancies after kidney transplantation in
peritoneal dialysis. Bailliers Clin Obstet Gynaecol
8:481-500, 1994 102 women (report by the EDTA registry). Nephol
5. McKay DB, Josephson MA: Pregnancy in recipients of Dial Transplant 11:1314-1317, 1996
solid organs— effects on mother and child. N Engl 22. Sibanda N, Briggs J, Davison J, et al: Outcomes of
J Med 354:1281-1293, 2006 pregnancies after renal transplantation: A report of
6. Rey E, Couturier A: The prognosis of pregnancy in the UK transplant pregnancy registry. Hypertens
women with chronic hypertension. Am J Obstet Gy- Pregnancy 23:136, 2004 (suppl 1)
necol 171:410-416, 1994 23. Wong KM, Bailey RR, Lynn KL, et al: Pregnancy in
7. Imbasciati E, Pardi G, Capetta P, et al: Pregnancy in renal transplant recipients: The Christchurch experi-
women with chronic renal failure. Am J Nephrol 6:193- ence. NZ Med J 108:190-192, 1995
198, 1986 24. Thompson BC, Kingdon EJ, Tuck SM, et al: Pregnancy
8. Cunningham FG, Cox SM, Harstad TW, et al: Chronic in renal transplant recipients: The Royal Free Hospital
renal disease and pregnancy outcome. Am J Obstet experience. QJM 96:837-844, 2003
Gynecol 163:453-459, 1990 25. Hou SH: Pregnancy in continuous ambulatory perito-
9. Jungers P, Houillier P, Chauveau D, et al: Pregnancy neal dialysis (CAPD) patients. Perit Dial Int 10:201-204,
in women with reflux nephropathy. Kidney Int 50: 1990
593-599, 1996 26. Chao AS, Huang JY, Lien R, et al: Pregnancy in
10. Chapman AB, Johnson AM, Gabow PA: Pregnancy women who undergo long-term hemodialysis. Am J
outcome and its relationship to progression of renal Obstet Gynecol 187:152-156, 2002
failure in autosomal dominant polycystic kidney dis- 27. Jones DC, Hayslett JP: Outcome of pregnancy in
ease. J Am Soc Nephrol 5:1178-1185, 1994 women with moderate or severe renal insufficiency.
11. Surian M, Imbasciati E, Cosci P, et al: Glomerular N Engl J Med 335:226-232, 1996
disease and pregnancy: A study of 123 pregnancies in 28. Katz AI, Davison JM, Hayslett JP, et al: Pregnancy in
patients with primary and secondary glomerular dis- women with kidney disease. Kidney Int 18:192-206,
eases. Nephron 36:101-105, 1984
1980
12. Stettler RW, Cunningham FG: Natural history of
29. Abe S, Amagasaki Y, Konishi K, et al: The influence of
chronic proteinuria complicating pregnancy. Am J
antecedent renal disease on pregnancy. Am J Obstet
Obstet Gynecol 167:1219-1224, 1992
Gynecol 153:508-514, 1985
13. Gordon M, Landon MB, Samuels P, et al: Perinatal
30. Horbar JD, Badger GJ, Carpenter JH, et al: Trends in
outcome and long-term follow-up associated with
mortality and morbidity for very low birth weight
modern management of diabetic nephropathy. Obstet
Gynecol 87:401-409, 1996 infants, 1991-1999. Pediatrics 110:143-151, 2002
14. Barcelo P, Lopez-Lillo J, Cabero L, et al: Successful 31. Wilson-Costello D, Friedman H, Minich N, et al: Im-
pregnancy in primary glomerular disease. Kidney Int proved survival rates with increased neurodevelop-
30:914-919, 1986 mental disability for extremely low birth weight in-
15. Matthew T, MacDorman M: Infant Mortality Statistics fants in the 1990s. Pediatrics 115:997-1003, 2005
form the 2003 Period Linked Birth/Infant Death Data 32. Piper JM, Ray WA, Rosa FW: Pregnancy outcome
Set. National Vital Statistics Report, Volume 54, Num- following exposure to angiotensin-converting en-
ber 16. 2006. Hyattsville, MD, National Center for zyme inhibitors. Obstet Gynecol 80:429-432, 1992
Health Statistics 33. Sedman AB, Kershaw DB, Bunchman TE: Recogni-
16. Koops BL, Morgan LJ, Battaglia FC: Neonatal mortal- tion and management of angiotensin converting
ity risk in relation to birth weight and gestational age: enzyme inhibitor fetopathy. Pediatr Nephrol 9:382-
Update. J Pediatr 101:969-977, 1982 385, 1995
Outcome of Infants Born to Women with CKD 205
34. Hulton SA, Thomson PD, Cooper PA, et al: Angioten- 38. Willis FR, Findlay CA, Gorrie MJ, et al: Children of
sin-converting enzyme inhibitors in pregnancy may renal transplant recipient mothers. J Paediatr Child
result in neonatal renal failure. S Afr Med J 78:673- Health 36:230-235, 2000
676, 1990 39. Korsch BM, Klein JD, Negrete VF, et al: Physical and
35. Pryde PG, Sedman AB, Nugent CE, et al: Angioten- psychological follow-up on offspring of renal allo-
sin-converting enzyme inhibitor fetopathy. J Am Soc graft recipients. Pediatrics 65:275-283, 1980
Nephrol 3:1575-1582, 1993 40. Hack M, Taylor HG, Drotar D, et al. Chronic condi-
36. Cooper WO, Hernandez-Diaz S, Arbogast PG, et al: tions, functional limitations, and special health care
Major congenital malformations after first-trimester needs of school-aged children born with extremely
exposure to ACE inhibitors. N Engl J Med 354:2443- low-birth-weight in the 1990s. JAMA 294:318-325,
2451, 2006 2005
37. Stanley CW, Gottlieb R, Zager R, et al: Developmental 41. Marlow N, Wolke D, Bracewell MA, et al: Neuro-
well-being in offspring of women receiving cyclo- logic and developmental disability at six years of
sporine post-renal transplant. Transplant Proc 31:241- age after extremely preterm birth. N Engl J Med
242, 1999 352:9-19, 2005