Kidney Dysfunction Before Pregnancy Linked to Preterm Birth

Pregnant women with kidney dysfunction prior to conception were more likely to have preterm birth, according to a population-based cohort study.

For women with creatinine measures taken in the 10 weeks prior to the estimated data of conception, the adjusted relative risk for delivery before 37 weeks was 1.23 (95% CI 1.09-1.38) in those with abnormally high levels (>77 μmol/L) versus mothers with healthy kidney function, reported Ziv Harel, MD, MSc, of St. Michael's Hospital in Toronto, and colleagues.

The risk of early preterm birth (before 32 weeks' gestation) was doubled in women with pre-existing kidney dysfunction, the team also noted in the study appearing online in CMAJ, the Canadian Medical Association journal.

The findings appeared to be driven by increased likelihood of induced birth before 37 weeks (aRR 1.30, 95% CI 1.11-1.52) -- risk of spontaneous preterm birth was not significantly increased with high levels of creatinine before conception.

"In the current study, elevated serum creatinine was notably associated with an increased risk for outcomes of a fetus severely small for gestational age and preeclampsia," Harel and co-authors said, noting that this may explain the increased risk for a provider-initiated preterm birth, but not spontaneous preterm birth.

"Given that measurement of serum creatinine is a readily available and inexpensive blood test, there may be a role for screening potentially high-risk women for kidney dysfunction either before conception or in the first half of pregnancy," the researchers added.

Asked for her perspective, Kjersti Aagaard, MD, PhD, a maternal-fetal medicine specialist at Baylor College of Medicine in Houston, who was not involved in this research, told MedPage Today that this is the largest, most robust study to quantify the risk of preterm birth in women with elevated levels of creatinine.

"But it's not spontaneous preterm birth in women who have these elevated creatinine levels," Aagaard said. "It's very specifically indicated preterm birth."

She said the risk is significant for patients who have a provider-initiated preterm delivery, for reasons such as development of preeclampsia or worsened renal failure. The ability to counsel patients and test those who may be high-risk are important clinical implications, Aagaard added.

"I think this underscores that mild renal dysfunction is a big problem in pregnancy," said Kathryn Drennan, MD, a maternal-fetal medicine provider at the University of Rochester Medical Center in New York, who was also not involved with the study. "It really helps to emphasize the fact that even women with creatinines that are 'normal' but are at the higher end of that range, represent a population at increased risk for poor outcomes of pregnancy," she told MedPage Today.

Drennan explained that the results might look even more pronounced in a U.S. population, which typically has more patients with diabetes and hypertensive disorders.

While the association between pre-pregnancy kidney dysfunction and preterm delivery has been defined in smaller studies and case series, the relationship is not well understood, Harel and colleagues noted, explaining that they aimed to quantify the risk of preterm delivery in this population using population-defined cut points of pregnancy serum creatinine.

For the study, the investigators assessed hospital births in Ontario between 2007 and 2016. Women ages 16 to 50 were included, all of whom had their serum creatinine measured 10 weeks before estimated conception.

Women with multifetal pregnancies, end-stage renal disease, or a kidney transplant right before conception were not included in the study, and neither were maternal deaths during pregnancy, ectopic pregnancies, and abortions before 20 weeks.

The primary outcome was preterm birth before 37 weeks' gestation. The researchers defined serum creatinine as a level above the 95th percentile (>77 μmol/L), and they adjusted for confounders including maternal age, rural residence, residential income, world region of origin, as well as diabetes, chronic hypertension, and tobacco and drug use. The group also performed a subgroup analysis of women with chronic kidney disease.

Of approximately 56,000 pregnancies, preterm birth occurred in 7%. The average maternal age was 31, and nearly half of participants were nulliparous. More than half of all preterm births were initiated by a provider.

Aside from the association between renal dysfunction and preterm birth, women with abnormally high levels of serum creatinine also had a greater risk of stillbirth (aRR 1.57, 95% CI 1.04-2.37).

In a subgroup analysis of 9,800 women with chronic kidney disease, associations were stronger for preterm birth with concomitant preeclampsia (aRR 2.52, 95% CI 1.68-3.77), and stillbirth (aRR 3.14, 95% CI 1.76-5.61).

Study limitations, Harel and colleagues said, included that they could not account for medications used to manage renal function. In addition the group said that using creatinine levels as the single measurement of kidney dysfunction may limit the results, and that criteria used to distinguish women with healthy renal function from those with chronic kidney disease may have resulted in misclassification.

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