What is Nitrous Oxide?
Commonly known as “laughing gas,” nitrous oxide (N2O) is an inhaled gas used for pain management and anxiety reduction in medical and dental settings [1.4.4]. When used for labor analgesia, it is not pure nitrous oxide but a blended mixture of 50% nitrous oxide and 50% oxygen [1.4.4, 1.7.1]. This mixture provides mild pain relief (analgesia) and significant anxiety relief (anxiolysis), helping laboring individuals cope with contractions [1.6.2]. Its primary pharmacological action is as a general anesthetic that functions as an N-methyl-D-aspartate (NMDA) receptor antagonist [1.2.4, 1.2.6].
Pharmacological Category of Nitrous Oxide in Pregnancy
The U.S. Food and Drug Administration (FDA) previously used a lettering system to categorize medication risk during pregnancy. Under this system, nitrous oxide is designated as Pregnancy Category C [1.3.2, 1.8.5]. A Category C classification indicates that while animal reproduction studies have shown a potential adverse effect on the fetus, there are no adequate and well-controlled studies in humans [1.3.2, 1.3.3]. However, the potential benefits of the drug may justify its use in pregnant women despite the potential risks [1.3.3]. It is also listed on California's Proposition 65 list because high levels of exposure can be associated with reproductive harm [1.3.4, 1.8.2]. Despite this classification, decades of clinical use for labor analgesia support its safety profile when administered correctly [1.3.5].
How Nitrous Oxide Works for Labor Pain
One of the key features of nitrous oxide in labor is its method of administration. It is always self-administered by the patient, who holds a face mask or mouthpiece and breathes in the gas mixture as needed [1.4.4, 1.7.1]. This gives the laboring person complete control over when and how much analgesia they receive [1.4.2].
Nitrous oxide works very quickly, with effects felt in under a minute [1.6.2]. It is most effective when inhalation begins about 30 seconds before a contraction starts, allowing the gas to reach its peak effect at the same time the contraction peaks [1.4.4]. The gas is also cleared from the body very rapidly through the lungs. As soon as the mask is removed, the effects dissipate within a few breaths [1.4.4, 1.6.6].
It's important to note that nitrous oxide does not eliminate pain in the way an epidural does. Most users report that it “takes the edge off” the contractions, making the pain more manageable by creating a sense of relaxation, dissociation, or euphoria [1.4.5, 1.6.6].
Safety Profile for Mother and Baby
For the laboring patient, nitrous oxide is considered safe. The most common side effects include nausea, dizziness, or drowsiness, but these effects are temporary and cease almost immediately upon removing the mask [1.4.3, 1.4.4].
For the baby, nitrous oxide is also considered safe. While it does cross the placenta, it is eliminated just as quickly from the baby's system once the baby begins breathing after birth [1.9.4]. Extensive research has shown no negative effects on fetal heart rate during labor, newborn Apgar scores, infant alertness, or the initiation of breastfeeding [1.4.2, 1.4.3, 1.9.4].
Risks and Contraindications
Despite its strong safety record, nitrous oxide is not suitable for everyone. There are specific contraindications and risks to consider.
Absolute Contraindications
The use of nitrous oxide is strictly contraindicated in patients with [1.5.1, 1.4.5]:
- A known severe vitamin B12 deficiency
- Pneumothorax (collapsed lung)
- Recent retinal, inner ear, or sinus surgery
- Pulmonary hypertension
- Bowel obstruction
Nitrous oxide can expand into air-filled spaces in the body, which can be dangerous in the conditions listed above [1.5.6].
Vitamin B12 Interaction
Nitrous oxide irreversibly inhibits an enzyme called methionine synthase, which is dependent on vitamin B12 [1.5.1, 1.5.6]. This enzyme is crucial for DNA synthesis and neurologic function. In individuals who already have a vitamin B12 deficiency (due to conditions like pernicious anemia, Crohn's disease, or a vegan diet), using nitrous oxide can lead to serious neurologic harm [1.5.1]. For this reason, screening for B12 deficiency risk is an important safety step [1.4.1].
Professional Guidelines
The American College of Obstetricians and Gynecologists (ACOG) acknowledges that nitrous oxide is a safe and effective pain relief option during labor [1.7.4]. However, ACOG issued a practice advisory recommending against the co-administration of inhaled nitrous oxide with systemic opioids or sedatives. This combination can lead to deeper sedation and increase the risk of respiratory depression and low oxygen levels in the mother [1.4.6, 1.7.3].
Comparison Table: Nitrous Oxide vs. Epidural
| Feature | Nitrous Oxide | Epidural Anesthesia |
|---|---|---|
| Pain Relief | Modest, anxiolytic; "takes the edge off" [1.4.5] | Significant to complete numbness from the waist down [1.6.1] |
| Administration | Self-administered by the patient via mask [1.4.4] | Administered by an anesthesiologist via a catheter in the spinal area [1.6.6] |
| Mobility | Patient can remain mobile, walk, and change positions [1.6.3, 1.6.6] | Patient is bed-bound with restricted movement [1.6.4] |
| Onset & Offset | Very rapid onset and offset (seconds to minutes) [1.4.4] | Slower onset (15-30 min) and effects last for hours [1.6.1] |
| Common Side Effects | Nausea, dizziness, drowsiness (all short-lived) [1.4.3] | Itching, low blood pressure, difficulty urinating, fever [1.6.1] |
| Fetal Effects | No known significant adverse effects on Apgar scores or breastfeeding [1.4.3, 1.9.4] | Generally safe, but may be associated with maternal fever or changes in fetal heart rate requiring monitoring [1.6.1] |
| User Control | High; patient decides when and how much to use [1.4.2] | None after initial placement and dosing |
Conclusion
Nitrous oxide, classified as FDA Pregnancy Category C, stands as a valuable and safe option for labor analgesia [1.3.2]. It functions not as a powerful painkiller but as an effective anxiolytic that provides a high degree of patient control, preserves mobility, and has a minimal impact on the baby [1.4.2, 1.6.3]. While 40-60% of women who start with nitrous oxide may later choose an epidural for more potent pain relief, it remains a popular choice for those seeking a less invasive option [1.4.1]. The primary contraindication relates to its interaction with vitamin B12, making patient screening a crucial safety measure before use [1.5.1].
For more information, consult resources from the American College of Obstetricians and Gynecologists (ACOG).
