Infants' Blood Volume in a Controlled Trial of Placental Transfusion at Preterm Delivery

METHODS

RESULTS

The mean blood volume of infants delivered with DCC (74.4 mL/kg; range: 45–103 mL/kg) was significantly greater than that for the ECC group (62.7 mL/kg; range: 47–77 mL/kg; P < .001). The mean blood volume of infants delivered vaginally with DCC (80.5 mL/kg) was significantly greater than that for the ECC group (61.3 mL/kg; P < .001). The infants delivered through cesarean section with DCC had greater blood volume (mean: 70.4 mL/kg; range: 45–83 mL/kg) than did the ECC group (mean: 64.0 mL/kg; range: 48–77 mL/kg), but this difference was not significant (P = .1) (Table 1).

For the gestational ages of 27[0/7] to 29[6/7] weeks and 30[0/7] to 32[6/7] weeks, infants delivered with DCC had significantly greater blood volumes than did those in the ECC group (P < .001 and P = .01, respectively). The infants in the group with gestational ages of 24[0/7] to 26[6/7] weeks on average had greater blood volume after DCC (mean: 78.0 mL/kg) than after ECC (mean: 57.9 mL/kg), but this was not analyzed statistically because the sample size was small (Table 1).

Figure 1 illustrates the blood volumes and actual cord-clamping times. The median cord-clamping times were 90 seconds for the DCC group and 10 seconds for the ECC group. The blood volume increased with the delay in cord clamping, especially for vaginal deliveries. Delaying the cord clamping from 60 seconds to 90 seconds (Fig 1) did not lead to a difference in measured blood volumes. The mean hematocrit level for the DCC group (0.53; SD: 0.9) was not significantly different from that for the ECC group (0.49; SD: 0.8; P = .10; 95% CI for advantage: 1 to 10).

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FIGURE 1

Blood volume and time to cord clamping, according to mode of delivery. The circled observations are those that were randomized to delay clamping but were actually clamped early.

When the analysis for all cases was repeated by using the actual cord-clamping status, rather than the intended/assigned status, the 95% CI for the average gain in blood volume with DCC versus ECC (95% CI: 8.0–19.3) showed only a minimal change, compared with that based on the intention to treat (95% CI: 5.8–17.5). There were no complications for infants or mothers during the placental transfusion procedures. We did not analyze clinical outcomes for this study.

DISCUSSION

By measuring blood volumes, we have demonstrated the possibility of achieving partial placental transfusion for preterm infants at 24 to 32 weeks of gestation. Placental transfusion was achieved by delaying cord clamping, gravity, adequate expansion of the lungs when necessary, and intravenous oxytocin treatment to stimulate uterine contraction after cesarean section delivery. The measured blood volumes ranged from 45 to 103 mL/kg in this study. Our infants were nursed in humidified, double-shield incubators to minimize insensible water loss; cumulative blood sampling losses before red blood cell volume measurements were added to the final blood volume.

Mollison et al³⁰ determined blood volume values of 68 to 100 mL/kg (mean: 84.7 mL/kg) by measuring both red blood cell volumes and plasma volumes (“albumin space”) separately for 28 healthy term infants with varied times of cord clamping. Mean blood volumes of 70.3 ± 2.3 mL/kg (ECC after a 5-second delay) and 83.9 ± 2.7 mL/kg (DCC at ≥1 minute) were determined for term infants with the ¹²⁵I-labeled serum albumin dilution method.³ Saigal et al⁴ found mean blood volumes of 79.7 mL/kg (ECC) and 89.6 mL/kg (1-minute DCC) for more-mature preterm infants (28–36 weeks; mean: 33.5 weeks) delivered vaginally. Strauss et al²⁷ measured red blood cell volumes for 35 infants born at <36 weeks of gestation and reported significant increases among neonates who underwent DCC (42.1 ± 7.8 mL/kg), compared with ECC (36.8 ± 6.3 mL/kg). For 2 infants of <30 weeks of gestation, a reinfusion of autologous, processed, placental blood was given to mimic placental transfusion.

There are several possible explanations for the differences between actual blood volume findings in the present study and those reported by Saigal et al.⁴ The discrepancies could be attributable to methodologic differences in blood volume measurements, differences in mode of delivery, and differences in gestational ages of the infants studied. Saigal et al⁴ reported blood volumes for infants born through the vaginal route at 28 to 36 weeks of gestation, and the blood volume estimations at 4 hours of age were based on plasma volume measurements with the ¹²⁵I-labeled human serum albumin dilution method. We studied infants born through both the cesarean section and vaginal routes at 24 to 32 weeks of gestation, and the blood volume was estimated by measuring the red blood cell volume at 4 hours of age. We did not use any correction factor for the venous/arterial hematocrit values, whereas the previous study used a correction factor of 0.87 to obtain total-body hematocrit values for calculation of blood volumes. Calculating the blood volume from the measured plasma volume overestimates the actual blood volume, because the labeled albumin method estimates the albumin space rather than the true plasma volume for sick patients with capillary leaks.^31,32

The placental transfusion seems to have been more pronounced in the groups with lower gestational ages (24[0/7] to 26[6/7] weeks and 27[0/7] to 29[6/7] weeks) and after vaginal delivery, although the number of infants in the group born at 24 to 26 weeks of gestation was too small for statistical confidence. Most of the published data on placental transfusion, for both term and preterm infants, are from vaginal deliveries; data on cesarean delivery cases are limited. The safety and feasibility of DCC treatment for preterm infants delivered through cesarean section were demonstrated.^18,19,26,27 Strauss et al²⁷ reported no difference in mean measured red blood cell volumes for preterm infants delivered through cesarean section with DCC (37.2 ± 8.2 mL/kg) versus ECC (36.8 ± 7.8 mL/kg). The present study confirmed the possibility not only of delaying cord clamping but also of achieving placental transfusion for infants delivered both vaginally and through cesarean section. All 3 infants who were assigned randomly to DCC but actually received ECC (Fig 1) were delivered through cesarean section. When the data were reanalyzed with exclusion of these 3 infants, the blood volume was significantly greater even for infants delivered through cesarean section (DCC: 72.8 mL/kg; ECC: 63.6 mL/kg; P = .01; 95% CI for advantage: 2.0–16.4).

The blood volume of term infants delivered vaginally varies directly in relation to the time of cord clamping.³ Philip and Teng³³ reported that placental transfusion might be enhanced by lung expansion, in addition to DCC and gravity, at term cesarean section. For term infants delivered through cesarean section, blood volume is increased by DCC of up to 40 seconds; delaying beyond 40 seconds may reduce the infant's blood volume because of reversal of blood flow to the placenta.³⁴ We found that delaying cord clamping beyond 60 seconds after cesarean section deliveries achieved only small changes in neonatal blood volumes (Fig 1). This could reflect reversal of blood flow between the placenta and the infant because of uterine atonicity, despite the intravenous administration of oxytocin. All of our infants had their lungs expanded through natural crying or facemask or endotracheal ventilation, as required to facilitate reduction of pulmonary vascular resistance and increase of pulmonary blood flow.³³

Placental transfusion may increase term and preterm infants' hematocrit and hemoglobin concentrations measured at 2 to 4 hours of age,^7,11,17 but some studies did not confirm this.^19,27 There was no significant difference in hematocrit levels between the DCC and ECC groups in our study. The hematocrit levels were measured soon after admission to the neonatal unit (<1 hour of age). We think that our finding could be attributable to the proportionate transfer of red blood cells and plasma from placenta to infant. Nelle et al⁷ also found no difference in hematocrit levels of cord blood or those immediately after birth between DCC and ECC groups. In a randomized, controlled trial of infants at 24 to 28 weeks of gestation, Oh et al³⁵ noted no significant differences in mean hematocrit levels at 4 hours of age (DCC: 0.44; ECC, 0.40). However, the mean hematocrit values (DCC: 0.54; ECC: 0.50) at ∼1 hour of age in the present study were much higher than those found by Oh et al.³⁵

We and others^12,36–39 have shown that red blood cell volumes or blood volumes at birth are relevant to the outcomes for preterm infants. Deficiencies of red blood cell volumes and low blood volumes at birth are associated with severe RDS.^12,13,38,39 The potential clinical advantages of euvolemia after placental transfusion have been outlined previously.^11,40,41

CONCLUSIONS

Blood volume was, on average, increased by delaying cord clamping for at least 30 seconds in both vaginal and cesarean section deliveries. The placental transfusion was more marked after vaginal deliveries and seemed more apparent for preterm infants with lower gestational ages. The enhancement of blood volume we report here was small; euvolemia might not have been achieved for our infants with DCC. Blood volume is expressed in milliliters per kilogram; for preterm infants, whose body fat proportion is significantly less than that of more-mature infants, “optimal” blood volume is likely to exceed values found for term infants. Other tactics for management of the third stage of labor may need to be examined in attempts to achieve euvolemia