Fetal renal artery impedance as assessed by Doppler ultrasound in pregnancies complicated by intraamniotic inflammation and preterm birth

Abstract

Objective: The objective of the study was to evaluate the fetal renal artery impedance in the context of inflammation-associated preterm birth.

Study design: We conducted a prospective Doppler assessment of the fetal renal artery impedance in 70 singleton fetuses. The study group consisted of 56 premature fetuses (median, 28.1 [interquartile range, 25.3-30.6] weeks at enrollment). Gestational age (GA) reference ranges were generated based on fetuses with uncomplicated pregnancies (n = 14). Doppler studies included renal artery pulsatility index (PI), resistance index (RI), systolic/diastolic (S/D) ratio, and presence or absence of end-diastolic blood flow. Proteomic profiling (surface-enhanced laser desorption ionization time-of-flight) was used for assessment of intraamniotic inflammation and biomarker peak corresponding to beta2-microglubin. Data were interpreted in relationship to amniotic fluid index (AFI), cord blood interleukin (IL)-6 and erythropoietin (EPO) levels. The cardiovascular and metabolic profiles of the neonates were investigated in the first 24 hours of life.

Results: Fetuses delivered by mothers with intraamniotic inflammation had higher cord blood IL-6 but not EPO levels. Fetal inflammation did not affect either renal artery PI, RI, S/D ratio, or end-diastolic blood flow. Neonates delivered in the context of intraamniotic inflammation had higher serum blood urea nitrogen levels, which correlated significantly with AF IL-6 levels. The renal artery RI and SD ratio were inversely correlated with the AFI independent of GA, cord blood IL-6, and status of the membranes.

Conclusion: The fetus is capable of sustaining normal renal artery impedance despite inflammation. Resistance in the renal vascular bed affects urine output independent of inflammation.

Figure 1. Enrollment flowchart of patients assigned to the study and control groups

* Demise prior to admission to Newborn Special Care Unit (NBSCU).

Figure 2. Representative SELDI-TOF mass spectrometry profiles of the amniotic fluid of a woman without and one with intra-amniotic inflammation [Mass Restricted (MR) score = 3 or 4]

The MR score ranges from 0 to 4, depending upon the presence or absence of each of the 4 protein biomarkers (defensin 2, 1 and calgranulin C and A). A value of 1 was assigned if a biomarker peak was present and 0 if absent. MR score 0 (zero) indicates “no” inflammation. MR score 3-4 indicates “severe” inflammation. Biomarkers: P1= defensin 2 [3,377 Da], P2= defensin 1 [3,448 Da], P3= calgranulin C [10,443 Da], P4= calgranulin A [10,834 Da], R = beta2 microglobulin [11,731 Da]. The R peak is not part of the MR score. IAI= intra-amniotic inflammation; Da = Daltons

Figure 3. Technique for evaluation and assessment of the fetal renal artery blood flow

(A) A frontal plane image of the fetal abdomen to allow identification of the abdominal aorta and its bifurcation at the level of the fetal kidneys. Renal artery blood flow was sampled within the lumen of the renal artery away from the aorta and before any emergent branches. The velocity waveform was recorded at fast speed with a low pass filter. (B) Representative Doppler flow tracing of the renal artery in a patient with intra-amniotic inflammation.

Figure 4. Relationship of amniotic fluid interleukin-6 (IL-6) and neonatal blood urea nitrogen (BUN)

Distribution of amniotic fluid IL-6 levels in logarithmic format (y axis) versus the neonatal serum blood urea nitrogen (BUN) (x axis) in the neonates admitted to New Born Special Care Unit who had an evaluation of the serum blood urea nitrogen (BUN, n=40) in the first day of life. The regression line and 95% confidence and prediction intervals (dotted lines) are also shown.

Figure 5. Relationships of amniotic fluid amniotic fluid index (AFI) and renal artery Doppler indices in the Study group (n=56)

(A) Distribution of amniotic fluid index (y axis) versus the resistance index (RI) (x axis) (B) Distribution of amniotic fluid index (y axis) versus the systolic/diastolic (S/D) ratio (x axis). The regression line and 95% confidence and prediction intervals (dotted lines) are also shown.