Across all stages of kidney disease, the risk for adverse pregnancy outcomes increases, according to a prospective observational study published online March 12 in the Journal of the American Society of Nephrology. Yet the data also indicate that good maternal–fetal outcomes are possible even in the presence of advanced disease.

These findings may be useful for counseling and monitoring affected women during pregnancy, note researchers led by nephrologist Giorgina Piccoli, MD, from San Luigi University Hospital, University of Turin, Italy.
The Torino-Cagliari Observational Study (TOCOS) compared pregnancy outcomes in 504 women with chronic kidney disease (CKD) with those in 836 well-matched low-risk women. The mean age of mothers with CKD in Turin and Cagliari was 31.9 years, and the mean age of the controls in both centers was 29.9 years. The majority of participants were white, and more than half of patients and control participants were nulliparous (56.2% and 58.1%, respectively).

Baseline assessments included hypertension, proteinuria (>1 g/day), systemic disease, and CKD stage at referral. The researchers followed the women, noting adverse outcomes including caesarean section, preterm delivery (<37 weeks), early preterm delivery (<34 weeks), small size for gestational age (SGA), neonatal intensive care unit (NICU) use, new onset of maternal hypertension, new onset or doubling of proteinuria, and CKD stage shift. In addition, they assessed the pregnancies for general combined outcome (preterm delivery, NICU, SGA) and severe combined outcome (early preterm delivery, NICU, SGA).

The risk for adverse outcomes increased in stepwise fashion across all disease stages. For stage 1 vs stages 4 to 5, the general combined outcome was 34.1% vs 90.0%; the severe combined outcome was 21.4% vs 80.0% (P < .001).

In stage 1 CKD, preterm delivery was associated with baseline hypertension, systemic disease, and proteinuria. However, even after adjusting for these classic risks, stage 1 CKD remained associated with adverse pregnancy outcomes even in women without baseline hypertension, proteinuria, or systemic disease (odds ratio, 1.88; 95% confidence interval, 1.27 – 2.79) compared with women in control group.

In terms of specific maternal–fetal outcomes, in women with stage 1 CKD, the rate of caesarean section was 48.4% vs 70.1% for stage 2, 78.4% for stage 3, and 70.0% for stages 4 to 5 (P < .001). Preterm delivery rate was 23.5% for stage 1 vs 50.6% for stage 2, 78.4% for stage 3, and 88.9% for stages 4 to 5 (P < .001). NICU rates by stage were 10.3%, 27.6%, 44.4%, and 70.0% (P < .001). SGA (<10%) by stage was 13.3%, 17.9%, 18.9%, and 50.0% (P = .023). General combined outcome ranged from 34.1% to 90.0% (P < .001), and severe combined outcome from 21.4% 80.0% (P < .001).
New-onset maternal hypertension ranged from 7.9% in stage 1 to 50.0% in stages 4 to 5 (P < .001). New-onset or doubling of proteinuria was 20.5% in stage 1 and 70.0% in stages 4 to 5 (P < .001).

The risk for intrauterine death did not differ between patients and controls.

“Renal function matters, and its effect is likely to be continuous: considering only the cases with a live-born baby, our data confirm a stepwise increase in pregnancy-related risks from stage 1 to stage 4-5,” the authors write. “Interestingly, there is a significant increase in risk from stage 1 to stage 2 CKD, which represents a sort of ‘gray’ area with regard to kidney function.”

The authors also note that the TOCOS data contrast with the data from a 2009 population-based study that found no additional risk with a mild reduction in glomerular filtration rate, thus suggesting that the clinical definition of CKD is more complex than the mere evaluation of glomerular filtration rate.

They recommend that clinicians take special care when treating pregnant women with CKD, even in the absence of known risk factors.

Commenting in an American Society of Nephrology press release, lead author Dr Piccoli said, “The findings indicate that any kidney disease — even the least severe, such as a kidney scar [from] a previous episode of kidney infection, with normal kidney function — has to be regarded as relevant in pregnancy, and all patients should undergo a particularly careful follow-up.” She added that “a good outcome was possible in patients with advanced CKD, who are often discouraged to pursue pregnancy.”