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Association of prior pregnancy with 24-hour urine composition and stone risk.
Vivian Paredes Bhushan, MS1, Marie-Therese Valovska, MD1, Vernon M. Pais, Jr., MD2.
1Dartmouth Geisel School of Medicine, Hanover, NH, 2Dartmouth-Hitchcock Medical Center, Lebanon, NH.

BACKGROUND: Pregnancy is associated with increased lifetime prevalence of nephrolithiasis. During pregnancy, purported changes in urinary milieu include hypercalciuria and alkaline urine, which may predispose to calcium phosphate urolithiasis. Postpartum, it is unknown whether the cumulative number of pregnancies is associated with increased risk of these findings and calcium phosphate stone formation. We studied the effect of prior pregnancies on the urinary milieu and stone composition in a cohort of female stone formers.
METHODS: With IRB approval, we performed a single-center retrospective review of stone patients treated between 2007 and 2017. We identified non-cystinuric, living female patients with complete 24-hour urinalyses and stone analyses who consented to a pregnancy history questionnaire. Linear regression was used to assess the association of pregnancy with urinary calcium, calcium phosphate supersaturation (SSCaP), and pH, comparing nongravid (G0) and previously gravid women. Pure stones were assigned to their respective category. Mixed stones were assigned to the category corresponding to their predominant crystal species. We additionally categorized stones containing >10% calcium phosphate as “calcium phosphate-containing stones”. Age, body mass index (BMI), and diabetes were adjusted for in the multivariate analysis.
RESULTS: Of 116 who met inclusion criteria, 22 (19%) were G0 and 97 (81%) were previously gravid. Of those previously gravid, 15 (12.9%) were primigravid (G1), 26 (22.4%) secundigravid (G2), and 53 (45.7%) had three or more pregnancies (G3+). Mean age was 54.3 years, and did not differ significantly by history of pregnancy (p=0.9). Mean years since last pregnancy was 24.6. Mean BMI at time of 24 hour urine was 29.6 kg/m2. Previously gravid women were more likely to exhibit hypercalciuria than G0 women (50% vs 22.7%, p< 0.05). Mean urine calcium was increased in G3+ women compared to G0 women (211.9 mg vs 153.2 mg, p < 0.05). On multivariate analysis, both SSCaP and urine calcium remained elevated in G3+ compared to G0 women (+0.049 and +49 mg/d, respectively, p < 0.05). Prior gravidity did not impart significant effect on most recent urine pH. There was no difference in the odds of calcium oxalate stone formation among G0 women and previously gravid women, across all number of pregnancies. There was no difference observed in the odds of predominantly calcium phosphate stone formation of greater than 50% composition among G0 women and previously gravid women. However, compared with G3+ women, nulligravids were significantly less likely to have any calcium phosphate-containing stones (OR:0.296; p =0.034; 95%CI [0.096-0.912]).
CONCLUSIONS: Women with multiple pregnancies were more likely than G0 women to have hypercalciuria and elevated SSCaP, even decades after their last pregnancy. While these findings are suggestive of lasting effects, there was no proclivity in the formation of predominantly calcium phosphate stones, suggesting that pregnancy is only one of many factors contributing to nephrolithiasis.


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