A multicenter, prospective study of fetal outcome following accidental carbon monoxide poisoning in...

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Reproductive Toxicology, Vol. 5. pp. 397-403, 1991 0890-6238/91$3.00 + .00 Printed in the U.S.A. Copyright© 1991Pergamon Pressplc • Original Contributions A MULTICENTER, PROSPECTIVE STUDY OF FETAL OUTCOME FOLLOWING ACCIDENTAL CARBON MONOXIDE POISONING IN PREGNANCY GIDEON KOREN,* TERESA SHARAV, ANNE PASTUSZAK,* LORNE K. GARRETTSON, -t KELLY HILL, IVANSAMSON,MARK ROREM, ARLENE KINC and JILL E. DOLGIN *Motherisk Program, Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, and Department of Pediatrics and Pharmacology, The University of Toronto; *Georgia Poison Control Center and Emory University; *Department of Hyperbaric Medicine, Our Lady of The Lake Regional Hospital, Baton Rouge, Louisiana; ~HyperbaricMedicine, Geisinger Medical Center, Danville, Pennsylvania; IIFairview Hospital, Fairview, Alberta, Canada; ~Western New York Regional Poison Center, Buffalo, New York; **Department of Medical Genetics, University of Wisconsin, Madison, Wisconsin Abstract -- We report the results of the first prospective, multicenter study of acute carbon monoxide (CO) poisoning in pregnancy. We collected and followed eases of CO poisoning occurring during pregnancy be- tween December 1985 and March 1989. The sources of CO were malfunctioning furnaces (n = 16), hot water heaters (n = 7), ear fumes (n = 6), and methylene chloride inhalation (n = 3). Pregnancy outcome was ad- versely affected in 3 of 5 pregnancies with severe toxicity; two stillbirths, and one cerebral palsy with tomo- graphic findings consistent with iscbemic damage. All adverse outcome occurred in cases treated with high flow oxygen, whereas the 2 cases of severe toxicity with normal outcomes followed hyperbaric oxygen therapy. All 31 babies exposed in utero to mild or moderate CO poisoning exhibited normal physical and neurobehav- ioral development. Severe maternal CO toxicity was associated with significantly more adverse fetal cases when compared to mild maternal toxicity (P < 0.001). It is concluded that while severe CO poisoning poses serious short- and long-term fetal risk, mild accidental exposure is likely to result in normal fetal outcome. Because fetal accumulation of CO is higher and its elimination slower than in the maternal circulation, hyperbaric ox- ygen may decrease fetal hypoxia and improve outcome. Key Words: carbon monoxide; poisoning; pregnancy; fetus. INTRODUCTION Carbon monoxide (CO) poisoning accounts for many fatalities in North America and Europe. This odorless, colorless gas binds to hemoglobin 250 times more av- idly than oxygen and reduces the capacity of the blood to transport oxygen. In addition, CO poisons a variety of intracellular cytochrome oxidase and P45o enzymes, further impairing cellular respiration. Carbon monoxide readily crosses the placenta and, although it takes several hours for fetal carboxyhemo- globin to equilibrate with maternal levels, final fetal Ram Kumar, Shyam Radhakrishnan, Monica Bologa, and Michael McGuigan were additional participants. Address correspondence to Gideon Koren, MD, Division of Clinical Pharmacology, The Hospital for Sick Children, 555 Univer- sity Avenue, Toronto Ontario, M5G 1XS, Canada. Received 25 October 1990; Revision received 7 December 1990; Accepted 16 December 1990. concentrations are higher due to greater affinity of fetal hemoglobin for the gas (1). Equally important, the elim- ination half-life of CO from the fetal circulation is longer than from the maternal circulation (1). While the hypoxic change of CO to the fetus is bi- ologically predictable, available experience is sketchy, retrospective, and uncontrolled. Most reported cases in the literature involved se- vere poisoning, often with loss of maternal conscious- ness; in many of these, stillbirths and anoxic fetal brain damage were noted (2-32). However, as documented by the American Association of Poison Control Centers National Data Collection System, most cases of CO poi- soning are not severe (33). While the adult or pediatric patient can be expected to recover completely from less severe poisoning, no study has addressed fetal safety following exposure at lower grades of CO poisoning, especially when the pregnant woman does not exhibit changes in state of consciousness. 397

Transcript of A multicenter, prospective study of fetal outcome following accidental carbon monoxide poisoning in...

Page 1: A multicenter, prospective study of fetal outcome following accidental carbon monoxide poisoning in pregnancy

Reproductive Toxicology, Vol. 5. pp. 397-403, 1991 0890-6238/91 $3.00 + .00 Printed in the U.S.A. Copyright © 1991 Pergamon Press plc

• Original Contributions

A MULTICENTER, PROSPECTIVE STUDY OF FETAL OUTCOME FOLLOWING ACCIDENTAL CARBON MONOXIDE POISONING IN

PREGNANCY

GIDEON KOREN,* TERESA SHARAV, ANNE PASTUSZAK,* LORNE K. GARRETTSON, -t KELLY

HILL, IVAN SAMSON, MARK ROREM, ARLENE KINC and JILL E. DOLGIN ¶

*Motherisk Program, Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, and Department of Pediatrics and Pharmacology, The University of Toronto; *Georgia Poison Control Center and Emory University; *Department of Hyperbaric Medicine, Our Lady of The Lake Regional Hospital, Baton Rouge,

Louisiana; ~Hyperbaric Medicine, Geisinger Medical Center, Danville, Pennsylvania; IIFairview Hospital, Fairview, Alberta, Canada; ~Western New York Regional Poison Center, Buffalo, New York; **Department of

Medical Genetics, University of Wisconsin, Madison, Wisconsin

Abstract -- We report the results of the first prospective, multicenter study of acute carbon monoxide (CO) poisoning in pregnancy. We collected and followed eases of CO poisoning occurring during pregnancy be- tween December 1985 and March 1989. The sources of CO were malfunctioning furnaces (n = 16), hot water heaters (n = 7), ear fumes (n = 6), and methylene chloride inhalation (n = 3). Pregnancy outcome was ad- versely affected in 3 of 5 pregnancies with severe toxicity; two stillbirths, and one cerebral palsy with tomo- graphic findings consistent with iscbemic damage. All adverse outcome occurred in cases treated with high flow oxygen, whereas the 2 cases of severe toxicity with normal outcomes followed hyperbaric oxygen therapy. All 31 babies exposed in utero to mild or moderate CO poisoning exhibited normal physical and neurobehav- ioral development. Severe maternal CO toxicity was associated with significantly more adverse fetal cases when compared to mild maternal toxicity (P < 0.001). It is concluded that while severe CO poisoning poses serious short- and long-term fetal risk, mild accidental exposure is likely to result in normal fetal outcome. Because fetal accumulation of CO is higher and its elimination slower than in the maternal circulation, hyperbaric ox- ygen may decrease fetal hypoxia and improve outcome.

Key Words: carbon monoxide; poisoning; pregnancy; fetus.

I N T R O D U C T I O N

Carbon monoxide (CO) poisoning accounts for many fatalities in North America and Europe. This odorless, colorless gas binds to hemoglobin 250 times more av- idly than oxygen and reduces the capacity of the blood to transport oxygen. In addition, CO poisons a variety of intracellular cytochrome oxidase and P45o enzymes, further impairing cellular respiration.

Carbon monoxide readily crosses the placenta and, although it takes several hours for fetal carboxyhemo- globin to equilibrate with maternal levels, final fetal

Ram Kumar, Shyam Radhakrishnan, Monica Bologa, and Michael McGuigan were additional participants.

Address correspondence to Gideon Koren, MD, Division of Clinical Pharmacology, The Hospital for Sick Children, 555 Univer- sity Avenue, Toronto Ontario, M5G 1XS, Canada.

Received 25 October 1990; Revision received 7 December 1990; Accepted 16 December 1990.

concentrations are higher due to greater affinity of fetal hemoglobin for the gas (1). Equally important, the elim- ination half-life of CO from the fetal circulation is longer than from the maternal circulation (1).

While the hypoxic change of CO to the fetus is bi- ologically predictable, available experience is sketchy, retrospective, and uncontrolled.

Most reported cases in the literature involved se- vere poisoning, often with loss of maternal conscious- ness; in many of these, stillbirths and anoxic fetal brain damage were noted (2-32). However, as documented by the American Association of Poison Control Centers National Data Collection System, most cases of CO poi- soning are not severe (33). While the adult or pediatric patient can be expected to recover completely from less severe poisoning, no study has addressed fetal safety following exposure at lower grades of CO poisoning, especially when the pregnant woman does not exhibit changes in state of consciousness.

397

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398 Reproductive Toxicology

In the past, there have been no data to construct a dose-response relationship of CO toxicity on the human fetus; consequently, it has been impossible to counsel the pregnant woman and her family on the likelihood of the unborn baby suffering permanent anoxic damage. While available case reports partially address the risk of severe cases (2-32), the lack of a denominator (ie, total number of exposed cases in pregnancy) precludes an accurate risk assessment. More importantly, previous reports have never dealt with the more commonly oc- curring mild or moderate maternal poisoning.

The Motherisk Program in Toronto is an antenatal counseling clinic for women exposed to drugs, chemi- cals, radiation, and infections in pregnancy and lacta- tion (34). Lack of data to help counsel women with mild-to-moderate carbon monoxide poisoning in preg- nancy led us to conduct this prospective, multicenter study.

PATIENTS AND METHODS

In October 1985, letters explaining the purpose of the study were sent to all the listed Poison Control Cen- ters in North America, to various hyperbaric treatment units, and to teratogen information programs. In addi- tion, the study was advertised at the annual meeting of the American Academy of Clinical Toxicology, Ameri- can Board of Medical Toxicology, American Associa- tion of Poison Control Centers, and the Canadian Association of Poison Control Centres, and in the offi- cial journals of these organizations (35). Referrals were, in most instances, by telephone to the Motherisk pro- gram or, less frequently, by mail. If the referral was made by a physician, the study questionnaire was sent to him or her to complete in addition to the infor- mation obtained by the telephone. If the contact was made by the pregnant woman, she was interviewed ac- cording to the same protocol and referred to her physi- cian. Women living within a reasonable distance of Toronto were offered the opportunity of counseling at the Motherisk Clinic.

The questionnaire explored the type and duration of CO exposure, nature and severity of symptoms, time elapsed before treatment (if any), carboxyhemoglobin (COHb) levels, and measurements of the CO in the am- bient air. In 6 cases we estimated COHb levels from the known ambient CO concentrations (38). The type, tim- ing, and duration of treatment (eg, hyperbaric or high- flow oxygen) were recorded. A general medical and obstetric history was obtained including cigarette smok- ing, alcohol consumption, and nonmedical drug/chemi- cal use in pregnancy. The clinical severity of the CO exposure was graded according to the system used by the New York Hyperbaric group (Table 1) (36).

A second telephone contact was made a few weeks after the expected day of confinement to record the

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Table 1. Severity of CO exposure

Grade 1

Grade 1 + Grade 2

Grade 3

Grade 4

Grade 5

Alert, oriented Symptoms headache, dizziness, nausea

As above, but a relative was unconscious Alert, alterations of mental state

Symptoms more pronounced than above Not alert, disorientation, loss of recent memory,

muscle weakness, or incoordination Disoriented, depressed sensorium,

Response to simple commands limited and inappropriate

Comatose, responding only to pain or not responding to any stimulus

course of pregnancy and birth. Infant follow-up was re- peated annually by telephone and included items con- cerning health and physical growth. A developmental questionnaire derived from the Denver Developmental Screening Test (37) was used. Detailed, structured questions were asked of the mother by a developmental pediatrician to determine milestones in the areas of gross motor, adaptive, language, and personal social develop- ment. In addition, an attempt was made to obtain qual- itative information of the child's development includ- ing not only milestones but whether the child was floppy, hypertonic, or showed inappropriate lateraliza- tion. Structured questions were asked about the child's temperament and behavior, the mother's own assess- ment of the child, and any anxieties she might have concerning his or her health or development.

Data analysis We recorded fetal outcome and correlated it with

the severity of maternal exposure by stratifying the ex- posure to mild stages (Grades 1-2) compared with se- vere stages (Grades 3-5).

Statistical analysis Means of values among subgroups (birth weight by

trimester of CO exposure) were compared by analysis of variance. Differences in proportions of adverse preg- nancy outcome in relation to grade of clinical severity (Grades 1-2 compared with 3-5) were compared using Fisher's exact test.

Results Between December 1985 and March 1989, a total

of 40 cases of CO poisoning during pregnancy were collected. Their geographic locations are presented in Table 2. All pregnant women were in good health prior to the CO poisoning and had not suffered from a known chronic illness. The 40 pregnancies included 3 twin births, 1 termination of pregnancy at 16 weeks gesta- tion, and 4 births that are pending. Analyses are based

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Fetal outcome following CO poisoning • G. KO~F~ EV AL. 399

Table 2. Geographic distr ibution o f CO poisoning in p regnancy

Ontario (Canada) 18 (Toronto) (8) Wisconsin 5 Pennsylvania 3 Alberta (Canada) 2 Georgia 2 Louisiana 2 Minnesota 2 Connecticut 2 Illinois 1 Nebraska 1 New York 1 Ohio 1

Total 40

on a total of 38 babies. The CO poisoning was second- ary to malfunctioning furnaces (n = 23), malfunction- ing hot water heaters (n = 7), car fumes (n = 6) methylene chloride (n = 3), and yacht engine fumes (n = 1). The exposure occurred during the first trimester in 12 pregnancies, second trimester in 14, and third tri- mester in 14. The clinical grade of poisoning was based on clinical symptoms and signs in all cases: cases where COHb levels were available or could be estimated from the known ambient CO concentrations are presented in Table 3.

The trimester at the time of CO exposure did not affect mean birth weight. Mean birth weight of the in- fants was 3.4 ___ .5 kg, after excluding 3 twin pregnan- cies whose mean birth weight was 2.1 _ .9 kg, 2 infants of mothers who smoked more than 20 cigarettes a day during pregnancy (birth weights 3.4 and 3.9 kg), and an infant exposed at term.

Table 4 presents stratification of clinical severity of CO outcome (Grades 1-2 compared with 3-5) by pro- portion of adverse pregnancy outcome. Adverse fetal outcome occurred only after Grade 4 or 5 poisoning. There were 2 cases with Grade 5 symptoms. The first case, a stillbirth at 29 weeks of gestation with COHb level of 26%, was treated with high-flow oxygen. The second case for which COHb levels were available re- suited in fetal death at term followed by maternal de- mise. In both cases fetal death was temporally related to the poisoning.

Of the 3 cases with Grade 4 severity, two pregnan- cies resulted in normal fetal outcome, and one infant was diagnosed as having cerebral palsy at the age of 8 months. The two women who had Grade 4 poisoning and had normal outcome were exposed to CO at 27 and 28 weeks gestation, had COHb levels of 39% and 21%, respectively, an hour after the end of exposure, and were treated with hyperbaric oxygen. Both infants were developing well at one year of age. The woman with Grade 4 symptoms and adverse outcome was poisoned

Table 3. Rela t ionship be tween measu red or calculated C O H b , clinical scor ing, and fetal ou tcome

Time of exam (h) Length

COHb% after expos. Grade Rx of Rx (h) Outcome

40-50 2 5 HfO 2 2 Elective termination 39 2 4 HybO z 2 Normal 26 1 4 HfO 2 3 Stillborn 25 2 4 HfO2 2 Cerebral palsy 21 2 4 HybO 2 2 Normal 18 nk 1 HfO2 12 Normal 14 nk I nil Normal 13.8 1 2 HfO2 7

+HybO 2 2 Normal 6.2 1.5 1 nil Normal 2.4 nk 1 nil Normal 0.8 2 1 nil Normal 2 nk 1 nil Normal

Indirect measures of exposure (calculated from ambient ppm)

32 a 2 1 + HfO 2 12 32 1 + nil 32 1 nil 14 1 nil 14 1 nil

5 1 nil

Normal developmental quotient Fetal bradycardia Normal Normal 36-week gestation Normal

~COI-Ib measurement of affected son. nk = not known. HybO 2 = hyperbaric 0 2. HfO 2 = high-flow 0 2.

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Table 4. Outcome of pregnancy as related to severity of CO poisoning and treatment

Grade of severity of exposure

1-2 4-5

Outcome Hyperbaric 0 2 High-flow 0 2

Normal 31 2 0 Adverse 0 0 3 Total 31 2 3

Grades 4-5 were associated with significantly worse outcome when compared to Grades 1-2, (P < 0.001, Fisher's exact test).

by CO at 23 weeks of gestation and had a COHb of 25% two hours after the exposure. She was treated with high-flow 100% 02 for 2 hours. The remainder of the pregnancy was uneventful, and a baby girl was born at term after an uneventful delivery, with birth weight of 4 kg. Immediately after birth, the infant had an apneic spell, but there was no recurrence. At 8 months she was examined by a neurologist due to poor head control and developmental delay. A computerized tomography scan showed enlargement of the ventricles, bilateral calcifi- cation in the basal ganglia, and altered white matter density. The changes were judged to be compatible with postanoxic encephalopathy.

There were two cases with Grade 2 severity. One woman was exposed at 20 weeks gestation, and the baby, born at 25 weeks, had respiratory distress syn- drome and jaundice. Follow-up at 3 months of age showed the infant to be developing appropriately. The second Grade 2 poisoning occurred at 30 weeks gesta- tion; maternal COHb was 13.8% at the time of expo- sure, and she was treated initially with high-flow oxygen for 7 hours followed by 2 hours of hyperbaric oxygen. The rest of her pregnancy was uneventful and resulted in delivery of a 3.2-kg infant who was devel- oping normally at three weeks.

All infants born to mothers with Grade 1 symptoms had normal outcomes. Some of these women were treated with high-flow oxygen (n = 10), but most of them were untreated after cessation of CO exposure (n = 19).

To date, follow-up has been completed at 3 years in 6 children, 2 years in 6 children, 1 year in 12 chil- dren, up to 6 months in 6 infants, and up to 1 month in 5 infants. Apart from the single infant described above with cerebral palsy, the development of the children has been normal (Table 5). Al l physical growth parameters were within age-appropriate growth percentiles. The mean age of sitting without support was 6.5 +_ 1.4 months, mean age of walking independently was 12 --- 1.4 months, and kicking a ball 22 ___ 1.5 months. Ob- ject constancy was observed at 8 +- 5 months, a pincer

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Table 5. Developmental milestones of babies exposed in utero to CO poisoning a

Mean age Normal range ( -+ SD) (months)

First smile 1.4 +- 0.5 0-2 Sitting without support 6.5 -- 1.4 4.8-7.8 Object constancy 8 -+ 0.5 Pincer grasp 8.6 - 1.5 9.4-14.7 Waving good-bye 10.8 +- 2.4 9 Walking independently 12 _+ t.4 11.3-14.3 Building a tower of 2 cubes 16.2 ~ 1.8 12.5-20 Independent use of spoon 16.3 -.+- 2.9 First word 11.4 -+ 2.1 8.5-13.5 Combination of 2 words 15.6 - 1.2 14-26

aExcluding 1 child with cerebral palsy (see text).

grasp at 8.6 _+ 1.5 months, building a tower of two cubes 16.2 ___ 1.8 months, and independent use of a spoon at 16.3 _ 2.9 months. The first smile was noted at 1.4 ___ .5 months and waving good-bye at 10.8 +__ 2.4 months. The first word was at 11.4 ___ 2.1 months and Combining two words was reported at 15.6 ___ 1.2 months. All the children above 3 years of age were re- ported to have normal developmental milestones and were integrating socially. All the mothers reported sat- isfaction with the development of their children.

D I S C U S S I O N

Acute CO poisoning became a common part of life after the introduction of coal heating. Incomplete com- bustion of carbonaceous compounds may be associated with faulty furnaces and stoves, gas and kerosene space heaters, improperly vented charcoal or sterno fires, and car fumes. Inhaled methylene chloride is metabolized in the body to CO and may cause various degrees of CO poisoning and even death (39). Smoking is by far the most common source of chronic exposure to CO, and smokers of 20 cigarettes per day may maintain COHb levels up to 10% (normal value for nonsmokers is 0.85%) (1,38,40).

After crossing the placenta and binding to fetal Hb, CO decreases the amount of oxygen reaching the devel- oping organism, thus creating a state of hypoxia. Initial animal studies documented that at CO levels causing severe maternal toxicity, fetuses are invariably affected, with permanent damage to the developing brain being the most consistent finding (41). Recent studies have documented that chronic exposure of pregnant animals to CO levels not associated with measurable maternal toxicity may be associated with developmental delay and permanent CNS damage (1,41).

Recent human studies suggest that offspring of heavy smokers may have lower scores in developmen- tal tests (42) or may achieve less scholastically in high

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Fetal outcome fol lowing C O poisoning • G. KOI~N ET At.. 401

Table 6. Maternal CO toxicity grade in relation to fetal outcome--literature cases

Fetal outcome

Maternal grade o f CNS Reference toxicity # of cases Normal damage Stillbirth numbers

1 3 3 - - - - 26 1 + 1 1 - - - - 25 2 . . . . .

3 1 1 - - - - 29 a 4 . . . . .

5 22 - - 5 17 2 - 5 , 7 , 1 6 - 2 2 , 24 ,26 ,28 ,46

Unknown 24 9 12 3 6 , 8 - 1 4 , 2 3 , 2 7 , 3 1

Total 51 14 17 20

aPatient received 100% 0 2 at 2 .4 a tmospheres for 90 minutes.

school (43). These studies have attempted to correct for a variety of maternal socioeconomic and environ- mental variables before identifying heavy smoking as the culprit.

The available 51 case reports of accidental CO poi- soning in pregnancy (Tables 6 and 7) are consistent with controlled animal studies, showing stillbirth and perma- nent fetal brain damage consistent with hypoxia. How- ever, very few of these cases dealt with mild to moderate CO exposures (Grades 1-3), which are much more common than the more severe ones (33). The lit- erature suggests that of the 22 cases of Grade 5 expo- sures, 17 resulted in stillbirth and 5 in fetal brain damage. None of the Grade 5 cases were judged to be healthy, although most reports do not specify their di- agnostic criteria or length of follow-up. Because of poor documentation, the clinical grade of severity could not be determined in half of these cases, of which 9 babies were normal, 12 were reported to have CNS damage, and 3 were stillborn (Table 6).

Methodologically, any assessment of fetal outcome following maternal CO poisoning is hampered by seri- ous problems. The accidental exposure is never a "con- trolled" event, and the exposure may have been much longer than initially assumed. Secondly, upon suspect- ing CO poisoning, the pregnant woman is often evacu- ated from the contaminated area and treated before COHb levels can be established. Similarly, the source of CO (eg, furnace, engine) is usually stopped and proper ventilation of the area is restored, thus making the interpretation of ambient CO levels impossible or inaccurate. In addition, there is a poor correlation be- tween COHb levels and clinical toxicity (36,44); clini- cal symptoms and signs may better correlate with the degree of CO toxicity (36,38,43).

Like any other adverse event in pregnancy, it is crucial to rule out other risk factors that may cause ad- verse fetal outcome before CO can be incriminated as a

potential fetotoxin. These factors include drug and alco- hol consumption, genetic background, maternal general health, and obstetric history.

Assessment of fetal outcome imposes additional methodologic problems. Because our series was col- lected prospectively from all over North America, the evaluation of pregnancy outcome had to be based on maternal reports. Without an appropriate control group, these reports may not identify subtle CNS damage that would be unmasked by elaborate developmental tests.

Beating in mind these limitations, this prospective study was designed to record data available a few hours after the initial contact. The grading of clinical toxicity was based on a widely accepted system (36); and fol- low-up of fetal outcome was performed by a develop- mental pediatrician. In Toronto, several children had a more complete assessment with the Bayley scales. The child with cerebral palsy had additional tests.

The data represent the first multicenter prospective collection and evaluation of CO poisoning in pregnancy. The proportion of numbers between mild-to-moderate and severe poisoning closely reflects that of CO poison- ing in the general population (33), thus ruling out a re- porting bias towards milder cases.

Pregnancy outcome following Grade 4-5 in our pa- tients closely resembles that described in case reports (Tables 6 and 7). Two of our patients were treated with hyperbaric oxygen and had normal outcome, whereas the 3 treated with high-flow oxygen masks had adverse fetal outcome. Although these numbers are too small to draw definite conclusions, they agree with recent case reports (29) documenting good outcome after hyperbaric oxygen treatment. Equally important, in none of these cases could we detect adverse maternal or fetal effects caused by this mode of treatment.

The elimination half-life of COHb in the body is 5 hours in room air, 1 hour in high-flow oxygen, and 23 minutes with hyperbaric oxygen (45). While hyperbaric

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Table 7. Reported cases of fetal/infant neurologic disorders resulting from maternal carbon monoxide poisoning

Reference (number) Neurologic disorders

1. Maresch, 1929 (2) 2. Neubuerger, 1935 (3) 3. Brander, 1940 (4) 4. Zourbas, 1947 (5) 5. Hallervorden, 1949 (6)

6. Desclaux et al., 1951 (7) 7. Beau et al., 1956 (8)

8. Beau et al., 1956 (8)

9. Beau et al., 1956 (8) 10. Beau et al., 1956 (8) 11. Solcher, 1957 (9)

12. Schwedenberg, 1959 (10)

13. Csermely, 1962 ( l l )

14. Colmant & Wever, 1963 (12)

15. Bankl & Jellinger, 1967 (13)

16. Lombard, cited by Longo, 1977 (15) 17. Lombard, cited by Longo, 1977 (15)

softening in the basal ganglia hydrocephalus intemus microcephaly and tetraplegia retardation of psychomotor development extensive damage to the globus pallidus, striatum, red zone of substantia nigra, and lateral nucleus of the thalamus areas of the cortex, manifested a diffuse loss of neurons, and polymicrogyria affected the frontal and anterior central regions mental retardation injury to putamen and globus pallidus, injury to cerebral cortex convulsions and behavior indicative of brain toxicity slight retardation in development; strabismus cyanotic, no reflexes bilateral status marmoratus of the putamen, medial globus pallidus and subthalamic nucleus suffered neural loss injury to putamen and globus pallidus, injury to cerebral cortex, extensive damage to centrum semiovale multicystic cavitary degeneration of the white matter, cortex and basal ganglia showed a total loss of nerve cells injury to putamen and globus pallidus, injury to cerebral cortex, extensive damage to centrum semiovale symmetrical temporal micogyria was present, along with massive hemispheric destruction mental retardation, strabismus mental retardation, athetosis, spasticity

oxygen is efficacious in treating adults and children with severe CO poisoning, it may be even more impor- tant for fetal therapy. After equilibration, fetal COHb levels are higher and have a longer half-life than the matemal COHb levels (1). Because the potential for de- veloping irreversible CNS damage depends upon the se- verity of hypoxia, it makes biologic sense to try to remove fetal CO as quickly as possible. It is generally recommended that maternal oxygen therapy should con- tinue 5 times longer than the period it took for matemal COHb to return to normal (1).

The mother with Grade 4 severity who gave birth to a child with cerebral palsy was treated with high- flow oxygen for 2 hours only. Based on a COHb elim- ination half-life of 1 hour, this therapy would not have reduced her COHb level (25%) to normal; the fetal COHb levels would be pathologic for a longer period.

Pregnancy outcome following Grade 1 and 2 acci- dental exposures to CO was normal in all cases. Ex- cluding the 3 sets of twins, which tend to be small for their gestational age, the other babies, including two preterm infants, did not appear to suffer from intrauter- ine growth retardation. It is conceivable that short, al- beit substantial, hypoxia does not impair the growth potential once pregnancy continues normally.

Of special concern to the pregnant woman, her family, and health professionals who have to counsel her about fetal risk, is the potential long-term fetal CNS damage that may be caused by mild CO poisoning. Within the limitations of the follow-up that could be performed in the present study, we could not document adverse developmental effects in these babies (Table 5). Because of the rarity of CO poisoning in pregnancy, it is very unlikely that more sensitive, controlled tests can be performed. It is, therefore, theoretically possible that our analysis missed more subtle CNS damage.

In summary, this prospective study confirmed the substantial fetal risks following Grades 4-5 CO poison- ing in pregnancy. It is possible that hyperbaric oxygen therapy improves fetal outcome.

In the case of mild poisoning (Grades 1 and 2), the present study did not detect increased fetal risk as the outcome measurements were compatible with normal infant neurobehavioral development.

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Fetal outcome following CO poisoning • G. KOREN ET AL. 403

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