Oxygen administration to the mother aims to increase fetal oxygen diffusion across the placenta. This therapy is commonly performed during labor, especially in case of a non-reassuring fetal heart rate. However, benefits and potential risks are controversial, especially in case of a normoxemic pregnant patient. In fact, its impact on placental gas exchange and the fetal acid–base equilibrium is not fully understood; it probably affects the sensible placental oxygen equilibrium and causes a time-dependent vasoconstriction of umbilical and placental vessels. The subsequent hyperoxia might also cause the generation of radical oxygen species, raising concerns for the developing fetal cells. Moreover, this practice affects the maternal cardiovascular system: it can cause alterations of the cardiac index, heart rate and vascular resistance, and unclear effects on uterine blood flow. In conclusion, there is no evidence that maternal oxygen administration can provide any benefit in the case of a non-reassuring fetal heart rate pattern, while it bears possible collateral effects. Oxygen administration during labor should be reserved for cases of maternal hypoxia.
In clinical practice, oxygen therapy is often used as an intrauterine resuscitation measure during delivery, aiming to improve fetal oxygenation when there is a concern about fetal status. Clinicians often administer oxygen in the presence of a non-reassuring FHR pattern. Many of the previously discussed studies were limited by the fact that they did not specifically consider abnormal CTG tracings, and hypotheses exist of a possible therapeutic effect of oxygen in the case of alterations of fetoplacental gas exchanges.
During the period 2016–2018, a randomized trial on 117 singleton pregnancies in a single European center reported the effects of oxygen administration in the case of type II or type III FHR tracings during the second stage of labor [22]. The authors noted a positive effect on FHR tracings and the presence of fewer episiotomies in the oxygen group . The authors noted a positive effect on FHR tracings and the presence of fewer episiotomies in the oxygen group[22]. FHR tracings were accurately analyzed by three blinded clinicians, until a consensus was reached; however, the authors stated that FHR improvements did not necessarily correlate to a better fetal metabolic status [22]. In fact, there was no significant difference in UA gas components and the newborn and Apgar score in the two different groups, suggesting that exogenous oxygen did not improve fetal status . In fact, there was no significant difference in UA gas components and the newborn and Apgar score in the two different groups, suggesting that exogenous oxygen did not improve fetal status[22].
In 2016–2017, Raghuraman and colleagues conducted a randomized, unblinded non-inferiority clinical trial in a single tertiary health care center including 99 patients with singleton, term pregnancy developing type II FHR tracings during labor In 2016–2017, Raghuraman and colleagues conducted a randomized, unblinded non-inferiority clinical trial in a single tertiary health care center including 99 patients with singleton, term pregnancy developing type II FHR tracings during labor[23].
Patients were randomized in a ratio of 1:1 to breathing room air (51 women) or oxygen (48 women) [23]. The primary outcome was the measure of UA lactate, considered the most valuable index of metabolic acidosis (since it changes earlier than pH does) and neonatal hypoxia-associated morbidity. The results showed similar lactate values in both groups (30.6 mg/dl in oxygen vs. 31.5 mg/dl in room air) . The primary outcome was the measure of UA lactate, considered the most valuable index of metabolic acidosis (since it changes earlier than pH does) and neonatal hypoxia-associated morbidity. The results showed similar lactate values in both groups (30.6 mg/dl in oxygen vs. 31.5 mg/dl in room air)[23]. Other UA gas components were also similar in the two groups, as well as were the modes of delivery . Other UA gas components were also similar in the two groups, as well as were the modes of delivery[23]. This trial suggested that oxygen supplementation is not useful even in the setting of abnormal FHR tracings . This trial suggested that oxygen supplementation is not useful even in the setting of abnormal FHR tracings[23]. The authors hypothesized that the hemoglobin dissociation curve might explain the inefficacy of oxygen therapy . The authors hypothesized that the hemoglobin dissociation curve might explain the inefficacy of oxygen therapy[23]. If maternal oxygenation is normal, extra oxygen only causes a minimal increase in maternal arterial oxygen pressure, as well as in fetal oxygen pressure. The strengths of this study are the accurate selection of category II FHR tracings and the exclusion of pregnancies affected by maternal hypoxia.
To further complicate the issue of oxygen therapy, studies showed that its effect might vary in a time-dependent fashion. In as early as 1995, Thorp and colleagues showed a deterioration in cord blood values after oxygen administration for >10 min, which was not present for shorter periods; this led the authors to suggest that uteroplacental or fetoplacental vasoconstriction might take some time to occur To further complicate the issue of oxygen therapy, studies showed that its effect might vary in a time-dependent fashion. In as early as 1995, Thorp and colleagues showed a deterioration in cord blood values after oxygen administration for >10 min, which was not present for shorter periods; this led the authors to suggest that uteroplacental or fetoplacental vasoconstriction might take some time to occur[20].
A planned secondary analysis of the previously described trial by Raghuraman and colleagues was also conducted to investigate cord blood oxygenation and acid–base values after different durations of O2 exposure (cutoff: 75th percentile, 176 min) [24]. The authors concluded that newborns with longer durations of O2 exposure had a lower partial pressure of O2 in the UV (25.5 mmHg in the 12 patients receiving oxygen for >176 min vs. 32.5 mmHg in the 36 patients receiving oxygen for <176 min) . The authors concluded that newborns with longer durations of O2 exposure had a lower partial pressure of O2 in the UV (25.5 mmHg in the 12 patients receiving oxygen for >176 min vs. 32.5 mmHg in the 36 patients receiving oxygen for <176 min)[24]. This finding again suggested that impaired placental O2 transfer occurs after prolonged O2 exposure [24].
The potential risks of maternal oxygen administration also include the generation of reactive oxygen species (ROS). The administration of oxygen to the mother causes maternal hyperoxia, and this might increase free radical activity both in the mother and the fetus.
Khaw and colleagues conducted a double-blinded trial with the analysis of ROS activity in both neonatal and maternal blood samples of patients undergoing elective cesarean section, that were randomized to breathe room air or FiO2 at a concentration of 60% Khaw and colleagues conducted a double-blinded trial with the analysis of ROS activity in both neonatal and maternal blood samples of patients undergoing elective cesarean section, that were randomized to breathe room air or FiO2 at a concentration of 60%[25]. In the oxygen group, they detected an increase in lipid hydroperoxides (malondialdehyde, isoprostane, and organic hydroperoxides) that was more pronounced in umbilical blood than in maternal blood, suggesting that generation occurred in the fetoplacental unit. Given that the highest concentration was found in the UV, they suggested that ROS production and activity was greatest in the placenta, which represents the interface with highest hyperoxic distress. Since they did not detect any purine metabolite activity, the authors also excluded a concomitant pathogenic pathway involving hypoxia . In the oxygen group, they detected an increase in lipid hydroperoxides (malondialdehyde, isoprostane, and organic hydroperoxides) that was more pronounced in umbilical blood than in maternal blood, suggesting that generation occurred in the fetoplacental unit. Given that the highest concentration was found in the UV, they suggested that ROS production and activity was greatest in the placenta, which represents the interface with highest hyperoxic distress. Since they did not detect any purine metabolite activity, the authors also excluded a concomitant pathogenic pathway involving hypoxia[25].
This important study suggests that breathing high concentrations of FiO2 can damage both fetal and maternal cell structures via hyperoxic oxidative stress. On the other hand, it is expectable that when oxygen administration is provided for maternal hypoxia at the right dosage, it does not cause a rise in ROS activity, because it does not induce hyperoxia.
During normal pregnancy, major hemodynamic changes occur, such as an increase in blood volume, cardiac output and heart rate, as well as do reductions in systemic vascular resistance and blood pressure [26]. Furthermore, labor and delivery are associated with further significant modifications due to emotional distress and uterine activity, such as a greater rise in cardiac output and heart rate . Furthermore, labor and delivery are associated with further significant modifications due to emotional distress and uterine activity, such as a greater rise in cardiac output and heart rate[26]. Regarding the respiratory system, the rate of respiration is similar to that in the pre-pregnancy state, but a decrease in arterial carbon dioxide tension can be noted . Regarding the respiratory system, the rate of respiration is similar to that in the pre-pregnancy state, but a decrease in arterial carbon dioxide tension can be noted[26]. These physiological changes are crucial for the extensive metabolic demands of pregnancy.
The administration of maternal oxygen during the third trimester has been linked to several different changes of the cardiovascular system and to variations in respiration.
In 2005, Simchen and colleagues evaluated the respiratory results of brief hyperoxygenation on eight healthy near-term pregnant women and they reported resulting hypocapnia and hyperventilation In 2005, Simchen and colleagues evaluated the respiratory results of brief hyperoxygenation on eight healthy near-term pregnant women and they reported resulting hypocapnia and hyperventilation[27]. In 2019, Mchugh and colleagues showed that hyperoxygenation during the third trimester causes not only a decrease in the maternal heart rate and cardiac index, but also a rise in systemic vascular resistance, both without recovery after the cessation of oxygen administration . In 2019, Mchugh and colleagues showed that hyperoxygenation during the third trimester causes not only a decrease in the maternal heart rate and cardiac index, but also a rise in systemic vascular resistance, both without recovery after the cessation of oxygen administration[28]. They performed noninvasive hemodynamic monitoring during a brief period of hyperoxygenation in 46 women with singleton, non-anomalous, third-trimester pregnancies and compared them to 20 nonpregnant controls . They performed noninvasive hemodynamic monitoring during a brief period of hyperoxygenation in 46 women with singleton, non-anomalous, third-trimester pregnancies and compared them to 20 nonpregnant controls[28]. The authors hypothesized that lower heart rate is probably caused by increased vagal activity, while increased systemic vascular resistance depends either on the generation of ROS or on the long-lasting calcium channels that cause vasoconstriction . The authors hypothesized that lower heart rate is probably caused by increased vagal activity, while increased systemic vascular resistance depends either on the generation of ROS or on the long-lasting calcium channels that cause vasoconstriction[28].
These demonstrated cardiovascular effects warn against maternal oxygen administration because of the potential maternal complications, especially if it is given without proper hemodynamic monitoring. Furthermore, the effects on uterine blood flow still need further studies because they have not been assessed yet.
There is no evidence that maternal oxygen administration can have any benefit in case of a non-reassuring FHR pattern. In recent decades, many investigators studied the impact of oxygen administration to the mother on fetal status during labor. However, trials showed conflicting as well as worrying results. Furthermore, other possible collateral effects on the newborn and on the mother warn against its usage. Recent neonatal and maternal studies showed that hyperoxygenation might be detrimental to both types of patients, because it can cause ROS generation which eventually leads to structural cell damage, as well as potential consequences on maternal cardiovascular and respiratory systems.
To conclude, maternal oxygen administration should be reserved for cases of maternal hypoxia, as suggested by many authors and guidelines [1][2][28], with the aim to restore normal oxygen saturation, and therefore ensure oxygen delivery to the placenta and the fetus.
Given the potential harmful effects of hyperoxygenation, especially if oxygen is administrated for a long time, rwesearchers suggest its use in labor only in selected cases when the cause of the type II FHR tracings is due to fetal hypoxia secondary to maternal hypoxia.