A Systematic Review and Meta-Analysis of Physiologic Variables in Sheep Fetuses

Abstract

The fetal sheep model has been widely used in fetal therapy research. However, there is a significant degree of variability among published normal values. Our study aimed to evaluate the literature available on normal values for hemodynamics, blood gases, and acid-base status in the sheep fetus and to determine the best possible estimation of such physiologic values. We conducted a systematic review with a comprehensive search of several databases. We included 189 articles in the database and over 2,800 sheep fetuses. Analysis revealed a mean umbilical blood flow of 202 mL/kg/min (95% CI: 182 to 223); mean arterial pCO2 of 49.8 mm Hg (95% CI: 49.2 to 50.3); mean arterial pO2 of 22.3 mm Hg (95% CI: 21.9 to 22.7); mean arterial pH of 7.35 (95% CI: 7.3487 to 7.3562); and mean arterial oxygen saturation of 59.8 (95% CI; 58 to 61.7). Our findings were punctuated by a high heterogeneity, for which we conducted several subanalyses. The results showed high heterogeneity and small study effect in the literature available and provided our best assessment of relevant variables on normal hemodynamics, blood gases, and acid-base status in the fetus after using strategies to mitigate the risk of bias present in the literature.

Figure 1.

Strategy listing all search terms used and how they were combined.

Figure 2.

PRISMA flow diagram. A flow diagram showing the process of eliminating studies that did not meet inclusion criteria.

Figure 3.

Funnel plot of oxygen saturation values. Each study included is represented as a dot, y-axis is a measure of precision (SE), and x-axis is the mean. The dotted lines forming a triangle represent the 95% CI within which studies are expected to fall. The lighter vertical line corresponds to no intervention effect.

Figure 4.

Funnel plot of arterial pCO₂ values. Each study included is represented as a dot, y-axis is a measure of precision (SE), and x-axis is the mean. The dotted lines forming a triangle represent the 95% CI within which studies are expected to fall. The lighter vertical line corresponds to no intervention effect.

Figure 5.

Funnel plot of arterial pO₂. Each study included is represented as a dot, y-axis is a measure of precision (SE), and x-axis is the mean. The dotted lines forming a triangle represent the 95% CI within which studies are expected to fall. The lighter vertical line corresponds to no intervention effect.

Figure 6.

Funnel plot of arterial pH values. Each study included is represented as a dot, y-axis is a measure of precision (SE), and x-axis is the mean. The dotted lines forming a triangle represent the 95% CI within which studies are expected to fall. The lighter vertical line corresponds to no intervention effect.

Figure 7.

Funnel plot umbilical blood flow. Each study included is represented as a dot, y-axis is a measure of precision (SE), and x-axis is the mean. The dotted lines forming a triangle represent the 95% CI within which studies are expected to fall. The lighter vertical line corresponds to no intervention effect.