Objective
Pregnancy is associated with substantial changes in the maternal circulatory physiology. Our aim was to investigate maternal cerebral blood flow (CBF) during normal pregnancies.
Study Design
We prospectively measured maternal CBF in 210 low-risk pregnant women at different gestational ages, and in 15 nonpregnant women. CBF was assessed by measuring blood flow volume in the internal carotid artery (ICA) by dual-beam angle-independent digital Doppler ultrasound.
Results
ICA blood flow volume increased during pregnancy from 318 mL/min ± 40.6 mL/min in the first trimester to 382.1 mL/min ± 50.0 mL/min during the third trimester, corresponding to CBF values of 44.4 and 51.8 mL/min –1 /100 g –1 , respectively ( P < .0001). CBF changes were associated with progressive decrease in cerebral vascular resistance and moderate increase in ICA diameter.
Conclusion
Maternal CBF is gradually increasing during normal pregnancy. Vasorelaxing impact of estrogens and other factors on cerebral vessels may explain the changes in CBF during pregnancy.
During the course of human pregnancy, several significant changes in systemic hemodynamics appear. Among them, cardiac output elevation up to 49% has been extensively reported and is currently thought to be related to reduction in peripheral vascular resistance that is induced by nitric oxide (NO) and to blood volume expansion. In contrast, little is known on the maternal cerebral hemodynamics during the course of pregnancy. In one report, maternal cerebral blood flow (CBF) was measured by single-photon emission computerized tomography (SPECT) and found to be increased during the first trimester in comparison to CBF postpregnancy termination. Other studies have advocated the use of transcranial Doppler (TCD) for the measurements of maternal middle cerebral artery (MCA) blood flow velocities as a correlate for CBF. Unfortunately, the results of these studies are of limited value since the correlation between MCA flow velocities and CBF is not linear, especially during pregnancy where vascular tone is lower than in nonpregnant women. In an attempt to cope with the shortcomings of TCD technology, Belfort et al investigated an algorithm aiming at the estimation of the cerebral perfusion pressure (CPP) relying on TCD during pregnancy and found that CPP was increased during the course of pregnancy. Assuming some correlation between CPP and CBF, the authors hypothesized that CBF increases significantly during the course of pregnancy although CBF was not directly measured. Several studies, however, have disputed the correlation between CPP and CBF and thus no firm conclusion can be drawn from MCA flow velocities, especially when taking into consideration that CPP was not actually measured but calculated. Obviously, the choice of TCD for CBF evaluation in these studies found its origin in evident difficulties in measuring CBF during pregnancy, by means of SPECT, positron emission tomography, stable xenon computerized tomography, or xenon 133 clearance techniques, which all represent gold standards for CBF measurements. Recently, increasing attention has been drawn to the potential use of Doppler ultrasound for the measurement of blood flow volume (BFV) in the internal carotid artery (ICA) as a correlate for CBF in the corresponding hemisphere in clinical and experimental studies. Recent reports have shown that the combination of angle-independent dual-beam ultrasound with digital Doppler technology results in high accuracy in CBF assessment in comparison with xenon clearance technique.
In the present study, we aimed to characterize maternal hemispheric CBF during the course of pregnancy by measuring ICA BFV.
Materials and Methods
The study was approved by the local research ethics board and all participants gave written informed consent. Maternal ICA blood flow was measured prospectively in 229 women with a singleton pregnancy, and in 15 nonpregnant healthy women who were selected to provide sufficient data for having a 95% confidence interval. The study design was cross-sectional and each woman was examined only once. The investigated women’s age range was between 17 and 44 years (mean age, 28.2 ± 5.9 years). Participants were healthy pregnant women, who attended the obstetrics clinics during this period for routine pregnancy care, and healthy nonpregnant women. Exclusion criteria were anemia with hemoglobin <10 g/dL, smoking, hypertension, cardiac or cerebral vascular disease, use of drugs affecting cardiovascular system, and diabetes or gestational diabetes. Gestational age was calculated from the last menstrual period and verified with first-trimester ultrasound measurements.
Patients were studied in a semidarkened room after resting for 10 minutes in a 15-degrees left lateral recumbent position. BFV in both ICAs was measured using an angle-independent dual-beam flow Doppler system (Quantix ND; Cardiosonix, Raanana, Israel) according to a technique previously described. Briefly, angle-independent dual-beam flow is based on simultaneous interrogation using 2 ultrasound beams with known geometric configuration. Using dedicated digital Doppler technology, hundreds of sample volumes (or gates) of <200 μm in length are simultaneously sampled along the course of each ultrasonic beam at successive depths. Each sample volume is subjected to fast Fourier transform analysis, and an original algorithm is employed for real-time calculation of flow velocities in each set of successive gates. Further processing of the large number of small sample volumes enables determination of the pulsatile flow velocity profile and the vessel diameter. Volume blood flow can then be obtained through integration of the velocity profile over the vascular cross-sectional area. Additionally, the device uses a dedicated algorithm that averages changes in both vessel diameter and flow velocity profile during 4 sequential cardiac cycles, therefore taking into account temporal and spatial variations. Blood pressure (BP) was measured by an automated BP monitor (BP-1001S; Colin Electronics, Komaki, Japan). Cerebral vascular resistance (CVR) was calculated according to the following formula: CVR = mean BP (mm Hg)/BFV (mL/min), in which BFV is the cumulated BFV in both ICAs. Data from both ICA BFV were then used to calculate global CBF using an algorithm developed by linear correlation analysis between ICA BFV and hemispheric CBF measured by xenon 133 clearance technique (global CBF = total volume blood flow × 0.108 + 10.5).
Statistical analyses were performed using SAS statistical package (SAS Institute, Cary, NC).
Linear regression analyses were carried out to investigate the relationship among variables of interest (ICA flow, global CBF, CVR, vessel diameter) over time. The relationship was described using the parameter estimate (beta) as well as the P value with P value of .05 taken to denote statistical significance. Statistical analyses calculations for the various variables were adjusted for maternal age. Fixed effect models were used since the sample size at each week was not suitable for random effect models. Additionally, continuous data from each trimester were analyzed by 1-way analysis of variance followed by post hoc Bonferroni multiple comparison tests and categorical data were calculated by χ 2 test.
Results
Clinical characteristics of participating women including age, weight, parity, and gestational age are presented in Table 1 . The gestational age distribution of the recruited women is depicted in Table 1 . The mean age of participating women was not different across trimesters ( Table 1 ). ICA BFV measurements could be obtained in 210 of the pregnant women (91.7%) and in all nonpregnant subjects. Bilateral ICA flow volume was measured and there was no significant difference between the 2 sides.
| Characteristic | Nonpregnant (n = 15) | First trimester (n = 31) | Second trimester (n = 50) | Third trimester (n = 129) | P a |
|---|---|---|---|---|---|
| Age, y | 31.1 (28.7–33.5) | 27.3 (24.2–30.5) | 28.3 (26.5–30.0) | 28.4 (27.4–29.4) | NS |
| Weight, kg | 62.6 (54.9–70.2) | 63.7 (58.4–68.9) | 68.8 (66.0–71.6) | 72.3 (69.8–74.7) |
|
| Primiparous, n | 15 | 13 | 18 | 51 | |
| Multiparous, n | 0 | 18 | 32 | 78 |
|
| Gestational age, wk | 0 | 9.9 (9.0–10.8) | 22.5 (21.4–23.4) | 34.8 (34.2–35.4) | < .05 for all |
a 0 = Nonpregnant; 1 = First trimester; 2 = Second trimester; 3 = Third trimester.
Blood flow in the ICA increased continuously during the course of pregnancy from a nonpregnant value of 294.2 (95% confidence interval [CI], 264.9–323.4) to 382.1 (95% CI, 372.9–391.7) mL/min during the third trimester ( P < .0001) ( Figure 1 , A, and Table 2 ). Using a linear regression model we calculated that ICA flow increased by 2.5 mL/min during each week of gestation.
