A 26-year-old woman, Gravida 2, Para 1, was referred at 23-week gestation with acute abdominal emergency. Her past medical history was unremarkable. Her last obstetric visit was two weeks ago during her 20-week routine checkup. She had no previous history of any intra-abdominal procedure. The only medications are prenatal multivitamins, folate, and iron sulfate. Physical examination: vital signs were blood pressure 120/60 mmHg, heart rate 80/min, respiratory rate of 16/min and temperature of 97 °F. Her lungs, heart, and general appearance were all within normal limits for her gestation. Airway assessment showed Mallampati score of 2 with intact dentition, full range of neck motion and a thyromental distance of greater than 5 cm. White blood cell count was 18,600; other laboratory values were normal. Abdominal ultrasound showed cholelithiasis and gall bladder inflammation.

The incidence of nonobstetric surgery performed during pregnancy was estimated range from 0.3 to 2.2% [1, 2]. There are significant number of women who receive nonobstetric surgery during pregnancy. As many as 93,000 pregnant women in the United States may require surgery each year [3]. However, this numbers are probably underestimated because pregnancy is often unrecognized by both patient and physician during early pregnancy.

The incidence of positive pregnancy tests of menstruating women presenting for orthopedic surgery was 0.002% [4]. The incidence of previously unrecognized pregnancy in menstruating women presenting for ambulatory, nonobstetric surgery was 0.3% [5]. A significant number of women (2.6%) are already pregnant during elective sterilization procedures [6].

The UK National Patient Safety Agency documented that women should be offered a pregnancy test “if there is any possibility that a woman could be pregnant.” The American Society of Anesthesiologists Task Force on Preanesthesia Evaluation recommended that preanesthesia pregnancy testing, “may be considered for all female patients of childbearing age,” ASA advocates physicians and hospitals to implement their own policies and practices with regard to this. Many hospitals routinely carry out pregnancy tests on all women of childbearing age who are scheduled for elective surgery [4].

The most common first-trimester procedure was laparoscopy (34%), whereas appendectomy was the most common surgery in the second and third trimesters [1]. The common indications for nonobstetic surgery include acute abdominal disease, malignancies, and trauma [1]. The rate of major postoperative complications (such as infections, reoperation, wound problems, respiratory complications, venous thromboembolism, blood transfusion, maternal death) for nonobstetic surgery during pregnancy was about 6% [7].

Maternal alveolar ventilation is increased by 30% or more by mid-pregnancy and rises progressively to 70% at term [8]. There is a 20% decrease in functional residual capacity (FRC) at term as the uterus expands, which result in decreases oxygen reserve and potential for airway closure. Oxygen consumption increases significantly due to the development of placenta, fetus, and uterine muscle.

Early in pregnancy, significant cardiovascular changes are demonstrated. By 8 weeks’ gestation, a pregnant woman has a 57% of increase in cardiac output, 78% of the increase in stroke volume, and 90% of decrease in systemic vascular resistance [10]. Pregnant woman also has a 40–50% increase in blood volume and a 20% reduction in hematocrit due to dilution. Anemia begins during the first trimester of pregnancy and is most significant in the mid-second trimester. Inferior vena caval occlusion is also significant during second trimester, which can result in decrease cardiac output 30% [3]. Vena caval compression result in distention of the epidural venous plexus, therefore increase the possibility of local anesthetic toxicity during the administration of epidural anesthesia.

Reduction of gastrointestinal motility and lower esophageal sphincter pressure, distortion of gastric and pyloric anatomy during pregnancy increase the risk for aspiration of gastric content [11]. It is unclear exactly at which point in gestation a pregnant woman becomes more prone to regurgitation and aspiration under anesthesia [3]. Any pregnant woman with acid reflux presentation should be considered at risk for aspiration.

The potential effects of anesthetic agents as teratogens should be considered.

Teratogenicity is defined as any significant postnatal change in function or anatomy in an offspring after prenatal treatment [3].

When mice were injected pentobarbital or phenobarbital, many anomalies were detected [16]. Thiamylal can cause growth suppressing defects in the offspring of mice [17]. Exposure of the immature brain of rodents to anesthetic agents such as propofol, thiopental, ketamine are related with brain cell apoptosis and functional deficiency [18, 19].

Induction agents (barbiturates, ketamine, benzodiazepines) have not been shown to be teratogenic in human when they were used in clinical doses during anesthesia [27]. There is no change in the incidence of structural abnormality among offspring of pregnant women who use morphine or methadone [27].

Nitrous oxide is a weak teratogen in rodents. Rats continually exposed to 50–70% nitrous oxide for 2–6 days (starting on day 8 of gestation) had an increased incidence of fetal morphological abnormalities [33]. When rats exposed to 70% nitrous oxide or to a similar concentration of xenon for 24 h on day 9 of gestation, fetal resorption, skeletal anomalies, and macroscopic lesions occurred only in the nitrous oxide group [34]. Nitrous oxide resulted in growth retardation and an increased incidence of morphological abnormalities and altered body laterality in rats [35].

The possible mechanism of nitrous oxide teratogenicity is that nitrous oxide inhibits methionine synthetase. Nitrous oxide can affect DNA synthesis. Transmethylation from methyltetrahydrofolate to homocysteine to produce tetrahydrofolate (THF) and methionine is catalyzed by methionine synthase. Therefore, methionine synthase inhibition by nitrous oxide could decrease THF and reduce methionine level. Reduction of THF resulted in decrease in DNA synthesis. However, this description has been questioned. Folinic acid bypasses the effect of methionine synthase inhibition on THF synthesis. Administration of folnic acid partially (not completely) reduced the teratogenic effects of nitrous oxide in the rat [36]. Use of isoflurane or halothane with nitrous oxide prevents almost all of teratogenic effects but does not prevent inhibitory effects of nitrous oxide on methionine synthase activity [37]. Therefore, the etiology of nitrous oxide teratogenicity in rats remained to be determined.

Human studies are more challenging to conduct. Prospective clinical studies are impractical, unethical. Human studies methods included retrospective epidemiologic surveys of adverse reproductive outcomes in groups chronically exposed to low levels of anesthetic gases or in women who have undergone surgery during their pregnancy.

These epidemiologic surveys had imperfections because of lack of comparable control groups, lack of details on duration and amounts of actual exposure, exposure to multiple environmental factors. These studies were limited by the small sample sizes, lack of a control group, and low response rate. These studies indicated that the incidence of miscarriage among the exposed women is approximately 25–30% greater than nonexposed women. However this difference is almost insignificant because incidence of spontaneous abortions is increased 250% in pregnant women who take more than three alcoholic drinks daily [41], and 80% in pregnant women who are smokers [42]. A 10-year prospective survey of all female physicians in United Kingdom showed no difference in reproductive outcomes when anesthesiologists were compared with others working female physicians [43]. These epidemiologic studies do not support an increased risk for congenital anomalies with long-term exposure to low levels of anesthetic gases.

Studies were conducted in women who had surgery during pregnancy. Review medical records of 9073 obstetric patients showed there were 147 patients who had surgery during pregnancy. These 147 patients were compared to 8926 patients who delivered at the same time. The incidence of congenital anomalies was not significantly different between two groups [44]. Among the patients who had surgery during pregnancy, the incidence of preterm delivery followed surgery was 8.8%, and the incidences of perinatal mortality and low-birth-weight infants were increased [44]. Canada data showed that there was no significant difference in the incidence of congenital anomalies in 2565 women who had undergone surgery during pregnancy. There was an increased risk of spontaneous abortion in women undergoing surgery with general anesthesia in the first or second trimester [45]. Analysis of three Swedish health care registries data showed 5405 operations in the population of 720,000 pregnant women [1]. 2252 were performed in the first trimester, 65% received general anesthesia. The incidence of congenital malformations and stillbirths were not increased in the offspring of women having surgery. However, the incidences of very low and low-birth-weight infants were increased. No specific types of anesthesia were associated with increased incidence.

Diagnostic ultrasonography during pregnancy has no embryotoxic effects. Prenatal ultrasound in rats showed no consistent evidence of neurobehavioral effects at low exposure ultrasound intensities (up to 20 W/cm² ) [49]. However, higher intensities (>30 W/cm²) can cause postnatal neurobehavioral effects [50]. Ultrasound can increase the fetal temperature. Hyperthermia is a recognized teratogen in mammalian laboratory animals and is a suspected teratogen for humans. Human epidemiology does not indicate that diagnostic ultrasound presents a measurable risk to the developing embryo or fetus [51]. Because higher exposures of ultrasound can elevate the temperature of the embryo, the use of diagnostic procedures should take into consideration the hyperthermic potential of higher exposures of ultrasound [51]. To prevent hyperthermia, exposure time and acoustic output should be set to the lowest level possible.

Behavioral teratology was described as the adverse effects of a drug on the behavior or functional adaptation of the offspring to its environment [52]. In animal studies, brief intrauterine exposure to halothane resulted in postnatal learning deficit, CNS degeneration and decrease brain weight in rats [53]. Maternal administration of systemic drugs, including barbiturates, meperidine, resulted in behavioral changes in rat offspring [54, 55]. Maternal administration of lidocaine showed no effect on behavioral changes or clinical dysfunction in rat offspring [25]. The researchers administered to 7-day-old infant rats a combination of drugs commonly used in pediatric anesthesia (midazolam, nitrous oxide, and isoflurane) in doses sufficient to maintain a surgical level of anesthesia for 6 h, and have demonstrated that this causes widespread apoptotic neurodegeneration in the developing brain, deficits in hippocampal synaptic function, and persistent memory/learning impairments [56]. However, there is no evidence to prove that anesthesia administered to a pregnant woman has adverse effects on later intelligence, neuromuscular physiology, learning ability, and behavior of her infant [57].

Animal studies demonstrated that congenital abnormalities have been described after exposure to hypoxia during organogenesis [58]. In humans, brief experience of hypoxia and hypercarbia has not proven to be teratogenic [59, 60]. Common causes of maternal hypoxia in pregnant women during surgery include laryngospasm, airway obstruction, esophagus intubation, inadequate ventilation, low inspired oxygen in anesthetic gas mixture, severe toxic reactions, high spinal or epidural blocks with maternal hypoventilation.

Intrauterine asphyxia can cause serious damage to fetus. It is important to maintain normal maternal arterial oxygen tension, oxygen-carrying capacity, oxygen affinity, and uteroplacental perfusion in pregnant women during surgery [3].