Introduction

Although carbon monoxide (CO) intoxication is one of the most common causes of morbidity due to poisoning, it is relatively rare during pregnancy [1, 2]. It may have potentially serious adverse effects to the mother and fetus and a result of intrauterine hypoxia, it leads to fetal death or severe neurological sequelae [1, 3–5]. In this article, a severe clinical picture of a preterm infant who was acutely exposed to CO at the 33rd weeks of gestation before delivery was presented. Results and treatment modalities of CO poisoning during pregnancy were reviewed.

Case

A healthy 29-year-old G2P1 mother was admitted to the Maternal and Fetal unit of our hospital at the 34th weeks of gestation with complaint of decreased fetal movements. In the prenatal history, there was no problem during the antenatal period until the 33rd weeks of gestation. One week ago, she was found half-consciousness in bathroom because of exposure to CO and was admitted to a state hospital. Oxygen with mask was applied and carboxyhemoglobin (CO-Hb) level was 25%. She was discharged after 1 day of hospitalization. She had no additional problem for 1 week until she was brought to our hospital with complaint of decreased fetal movements. Emergent cesarean section was performed due to findings of fetal distress.

The birth weight of male infant was 2,340 g and the Apgar scores at 1 and 5 min were 1 and 3, respectively. Urgent cardiopulmonary resuscitation was initiated for the severely asphyxic infant for the establishment of satisfactory heart rate and respiration in the delivery room. After the transportation to the neonatal intensive care unit, depressed baby was placed on mechanical ventilation and given one dose of surfactant. Antibiotic treatment and parenteral fluids were started. Volume, electrolyte, blood pressure homeostasis were maintained. The patient had severe hypoxic ischemic encephalopathy (HIE). All the joints were in flexion posture; there was axial hypotonia of the body and increased clonuses in the lower extremities.

Laboratory analyses indicated normal complete blood counts and normal blood chemistry. Blood gas analyses revealed metabolic acidosis with a pH 7.12, pCO2 48 mmHg, HCO3 11 mmol/L, BE 14 mmol/L. Lactate level (8.0 mmol/L) was higher and ammonia level (150 micg/dl) was little higher than normal. Infection markers were normal. CO-Hb level was 5%. Tandem mass spectrophotometry of blood was negative for organic acid and acylcarnitine. Urine organic acid analysis was normal. Cranial ultrasonography revealed prominent increase of parenchymal echogenity especially in the basal ganglia. An electroencephalography result was abnormal with low amplitude background activity, irregular teta rhythm and diffuse organization disturbance. Magnetic resonance imaging was performed on day 24 and revealed high signal intensity in T1-weighted images and low signal intensity in T2-weighted images at bilateral thalamus and lentiformis nucleus, encephalomalacic changes in both temporal and frontoparietal cortex and transaxonal degeneration at corpus callosum (Fig. 1).

Fig. 1
figure 1

Magnetic resonance T1-weighted images at bilateral thalamus and lentiformis nucleus

Full size image

Our patient was followed by restricted parenteral fluid therapy. The clinical course was complicated by the convulsions in the second day of life and they were intractable to phenobarbital. Regimen was switched to a combination of midazolam and clonazepam due to the absence of any signs of the improvement in the hypertonisity and persistent convulsions. He remained comatose and there was no response to pain. During follow-up, reflex response and clonuses of the patient improved but he patient had no spontaneous respiration and had ongoing mechanical ventilation need. Unfortunately, because of poor response to supportive treatment, the infant died at the 56th day of admission due to ventilator-associated pneumonia, nosocomial sepsis, disseminated intravascular coagulation and multiorgan failure.

Discussion

Carbon monoxide exposure in pregnancy is a severe medical condition and resulted intrauterine hypoxia causes fetal death or severe neurological sequelae [1]. The frequency of acute CO poisoning during pregnancy is difficult to estimate. In a French study, 4.6% of hospitalized victims of CO poisoning were pregnant women [6] and this rate was as high as 8.5% in USA [7].

CO is a tasteless, odorless, colorless gas that cannot be realized by five senses and is formed as a result of partial burning of compounds that have carbon in structure like wood, coal, exhaust and fuel gases [2]. Affinity of CO to hemoglobin is 200 times higher than oxygen and it causes tissue hypoxia by sliding oxyhemoglobin dissociation curve to left, decreasing oxygen delivery to the tissues and resulting in tissue hypoxia [8, 9]. With the high levels of CO poisoning, CO is also bound to intracellular myoglobulin and to the cytochromes a3 and P450. This process creates a reservoir and accounts for the persistence of CO poisoning, even with oxygen therapy [10].

CO dissolved in maternal plasma crosses the placental barrier by passive diffusion and it combines with fetal hemoglobin, creating CO-Hb reaching maternal levels in 14–24 h [5, 11, 12]. A state of equilibrium is reached in 36–48 h. The CO-Hb levels can reach 10–15% higher levels in fetus than maternal levels. The elimination half-life is 2 h for the mother and 7 h for the fetus. Binding ability of CO to fetal hemoglobin is 2.5–3 times greater than the adult hemoglobin and CO-Hb in fetus has a longer half-life relative to adults [11, 12].

Acute maternal CO poisoning is associated with a maternal mortality between 19 and 24% and a fetal mortality between 36 and 67% [6]. Fetal outcome is proportional to the severity of maternal involvement and the gestation at which the poisoning occurred [2]. Clinically, the risk to the fetus is very high, once signs of altered maternal consciousness appear [2]. Anatomical malformations were higher if intoxication occurs during the first stage of gestation and skeletal abnormalities especially limb malformations were common [13]. During the late gestational stage, the fetal brain seems to be more sensitive to CO leading to anoxic encephalopathy [2, 14]. However, involvement at any stage of pregnancy, functional changes in psychomotor and mental development can appear [3, 15].

The level of CO-Hb in the blood of newborn infant of a nonsmoking mother is about 2%, which increases to 6–9% if the mother is a smoker [2]. Adult level increases to 30–50% in acute poisoning and levels greater than 50% are accepted as life-threatening levels [2]. The relatively short half-life of CO in a patient breathing oxygen (which is supplied by rescue squad for many indications) frequently causes a rapid decrease of CO-Hb value to an indiscriminate level at the moment of hospital admission [1, 16].

Treatment of CO intoxication involves removing the patient from the source of CO and administering 100% oxygen via a tight-fitting face mask. Based on a mathematical model, Hill et al. [11] have recommended that a pregnant women should receive 100% oxygen for up to five times as long as necessary to reduce her own CO-Hb level close to normal (less than 5%) due to the longer elimination of CO for the fetus. Silverman et al. [17] recommended the following criteria for pregnant women presenting with acute CO poisoning: treatment with hyperbaric oxygen (HBO) if maternal CO-Hb levels are >20%; if the patient reveals neurological signs of symptoms of CO toxicity; if signs of fetal compromise are present (tachycardia, decreased variability or late decelerations) or continued treatment with HBO if persistent signs of maternal neurological impairment or fetal compromise are noted 12 h after initial hyperbaric treatment. Some published studies suggest that HBO administration entails a risk of abortion and fetal defects. However, Elkharrat et al. [6] showed that there is no evidence of fetal or obstetrical morbidity if the following protocol is observed: a two hour session of HBO administrated at two atmospheres absolute. Because the binding ability of CO to fetal hemoglobin is 2.5–3 times greater than the adult hemoglobin and CO-Hb in fetus has a longer half-life relative to adults, the duration of HBO therapy needs to be longer for pregnant women [11, 12].

In our patient, mother lost her consciousness and the maternal CO-Hb level was 25% suggesting higher CO-Hb levels in the fetus. As explained earlier, duration and the degree of CO-Hb levels affect the involvement of neonate particularly fetal brain. We found all the signs of acute encephalopathy signs including clinical, electroencephalographical and laboratory findings. In our patient’s blood gas studies, respiratory acidosis was detected and lactate level (8.0 mmol/L) was considerably higher than normal. Although CO-Hb level of neonate was seemingly normal (5%), it was measured 1 week after the intoxication and some amount of oxygen was given to the mother.

Loss of consciousness with a CO-Hb level >25%, CO-Hb level >15% with a history of cardiac disease or CO-Hb level >10% in a pregnant patient are the criteria for intensive care admission and prolonged observation [18]. CO poisoning is an indication for emergent cesarean section in pregnancy in some literature especially before the era of HBO [5, 19]. If a HBO facility has not been available locally as in our case, the mother with the signs of acute CO poisoning should be internalized to intensive care unit, administered 100% oxygen through a tight-fitting face mask and monitored for the fetus wellbeing closely [20]. In our case, we could not obtain any information about the fetal signs of compromise during maternal acute CO poisoning and the duration of oxygen treatment. At the time of acute CO poisoning, our case was at the 33th weeks of gestation which had a very high chance of survival with a less risk of morbidity. After the stabilization of the mother, delivery option should be thought as soon as possible.

In conclusion, CO poisoning in pregnancy is an unusual cause in the context of HIE, but it is a public health problem that is not rare. The important point of this topic is the problematic management owing to the lack of knowledge of correct treatment despite complete medical history. Emphasis on the correct treatment can prevent its most tragic consequences for both mother and her neonate. In cases with unavailability of HBO facility the choice can be elective cesarean section for near term babies after the condition of mother is suitable.