Poisonings and toxins

Arsenic

Reports of arsenic poisoning in pregnancy all involve exposure after the first trimester with variable outcomes. The first describes maternal ingestion of 340 mg of sodium arsenate at 20 weeks, resulting in a healthy live-born at 36 weeks gestation after maternal treatment with 150 mg dimercaprol (4 hourly) 2 hours post ingestion. At birth, 24 hour urinary arsenic levels were <50 μg/L in the infant and <100 μg/L in the mother ( ). The second reports ingestion at 28 weeks of an unknown amount of arsenic with subsequent intrauterine fetal demise, and high arsenic concentrations documented in the fetus ( ). The last case involved a third-trimester ingestion of arsenic-based rat poison. The baby was born live 4 days post-ingestion but then died from hyaline membrane disease. An autopsy showed a high concentration of arsenic accumulation in the liver, brain and kidneys ( ).

Chronic environmental exposure to arsenic may also occur, with populations in West Bengal, Bangladesh, China, Taiwan, Argentina and Chile exposed to drinking water from ground water wells with naturally occurring arsenic levels up to 3,000 mcg/L. A study of Mexican–American women who were exposed to arsenic >10 mcg/L in drinking water, and who lived within 2 miles of a facility with air emissions of heavy metals at the time of conception, showed no increased risk of NTD-affected pregnancies compared to women living near the Mexican border in Texas ( ). Data from other populations suggest an association between chronic exposure to arsenic in drinking water and an increased incidence of maternal anemia, spontaneous abortion, preterm birth and low birth weight ( ). See also Chapter 2.13.19 .

Carbon monoxide

Carbon monoxide (CO) crosses the placenta with maximum fetal blood concentrations likely to reach, and in some cases exceed, those of the mother. However, empirical observations, data from animal studies and theoretical models, show that there is a delay of up to 24 hours between maternal exposure and CO accumulating in the fetus. Maternal COHb (carboxyhemoglobin)-concentration may therefore not reflect fetal COHb-concentration at that time. Similarly, the elimination half-life in the fetus may be up to four to five times longer than in the mother.

Maternal COHb-concentrations and symptoms are proposed to predict risk of adverse fetal outcome, and risk of neurological damage in the fetus is thought to be increased if the mother was somnolent or lost consciousness. Fetal death occurred in 10 out of 15 cases where maternal toxicity was reported to be moderate to severe, and associated with loss of consciousness or coma ( ).

However, whilst severe maternal toxicity increases the risk of adverse fetal outcome, low maternal COHb-concentrations do not necessarily correlate with a good fetal outcome, and a threshold for fetal toxicity has not been established. In a case series by , in utero death occurred in two women who were exposed to CO at 38 weeks gestation. Whilst COHb was high, 32% in one woman, it was only 5% in the other. It should, however, be noted that maternal loss of consciousness was reported in both cases.

Reports of acute first trimester CO poisoning are scarce. Pregnancy loss and congenital malformation have been described following early pregnancy exposure associated with moderate to severe maternal poisoning (loss of consciousness or coma) ( ). However, there are no large epidemiological studies on which to accurately assess these risks. Acute CO poisoning in the later stages of pregnancy has been associated with fetal or neonatal death, prematurity and low birth weight ( ).

Chronic exposure to CO in pregnancy (via ambient air pollution or cigarette smoking), has been associated with an increased risk of congenital heart defects ( ), sudden infant death syndrome ( ), and prematurity ( ).

Third trimester in utero exposure to CO via environmental sources (e.g. wood smoke) has been associated with poorer performance in various neuropsychological tests, including long- and short-term memory recall, and fine motor performance amongst school age children ( ).

The use of hyperbaric oxygen therapy (HBO) is controversial in the nonpregnant patient, with use during pregnancy raising further concerns regarding toxic effects such as retinopathy, and premature closure of the ductus arterious in the fetus as a result of high oxygen concentrations. However, the limited published data do not indicate that treatment of pregnant women with HBO poses an increased risk to the fetus, and HBO is advised by some units in cases where maternal COHb-concentration is >20%, or associated with an altered level of consciousness.

Methanol

Maternal and fetal effects of methanol poisoning are not immediately evident, owing to the relatively slow metabolism of methanol to toxic metabolites like formaldehyde. Maternal acidosis may therefore be delayed for several hours following ingestion, particularly if alcohol has been consumed simultaneously.

Early treatment of maternal methanol poisoning is therefore key to preventing both maternal and fetal toxicity, and should be as for the nonpregnant patient. Where use of an antidote is clinically indicated, treatment with ethanol or fomepizole to reduce metabolism of methanol to its toxic metabolites should be initiated as soon as possible. Although adverse fetal effects are well described with both regular and “binge” consumption of alcohol during pregnancy, intravenous ethanol should not be withheld if fomepizole is not available and use of an antidote is clinically indicated in the treatment of methanol poisoning at any stage of pregnancy.

The published literature includes only three cases of methanol poisoning in pregnancy. described a pregnant woman with HIV infection and asthma who presented at around 30 weeks of gestation with respiratory distress following methanol exposure due to assumed ingestion. She was acidotic (pH 7.17) with an anion gap of 26, and the fetus was reported to be bradycardic. An emergency caesarean section was performed. The male infant weighed 950 g and required aggressive resuscitation, but died 4 days later following a grade 4 intraventricular bleed. Maternal metabolic acidosis persisted despite treatment with fluids, bicarbonate, and dopamine. Laboratory tests included undetectable ethanol and salicylates and showed an osmolar gap of 41. Intravenous ethanol was only commenced at this stage (3 days post ingestion), when a methanol concentration of 54 mg/dL was detected. The regional poisons service recommended maternal hemodialysis and fomepizole. It is unclear from the report whether this treatment was implemented and maternal death occurred on day 10.

A further report describes mild acidosis in a woman who ingested 250–500 mL methanol during the 38th week of pregnancy. She was treated with ethanol, hemodialysis and alkalinization, and delivered a normal healthy infant 6 days after the exposure ( ). The child was followed up for more than 10 years, during which time clinical course was uneventful and no visual disturbances were reported. The remaining report describes fomepizole treatment at 11 and again at 16 weeks gestation for chronic maternal abuse of methanol ( ). An ultrasound at week 16 did not show any gross congenital abnormalities; however, the case was lost to follow-up and the outcome of the pregnancy is unknown.

Organophosphorus pesticides

The published data detail approximately 30 pregnancies in which accidental or deliberate exposure to organophosphates (OPs) occurred ( ). Maternal antidote treatment with either atropine ( n = 23) or atropine and pralidoxime ( n = 4) was reported in 27 of these cases.

A case series of 21 women who ingested OPs in pregnancy and were treated with atropine, reported two maternal and fetal deaths, one spontaneous abortion, and 15 healthy live-born infants. Three women were lost to follow-up. In five cases, ventilatory support was needed. In two cases, where exposure occurred at 10 and 20 weeks gestation, the mothers died. Although no congenital malformations were reported, only three exposures occurred in the first trimester ( ). Dilated unresponsive pupils were reported in an infant following maternal ingestion of 15 to 20 mL of diazinon at 40 weeks of pregnancy, and treatment with 83 mg of atropine for 28 hours ( ). A further case report describes maternal ingestion of chlorpyrifos in a suicide attempt at 29 weeks of pregnancy. Atropine was administered over a period of 3 hours and the maternal symptoms resolved. However, premature labor ensued 2 days after the exposure, and the infant died 2 days later due to prematurity and hyaline membrane disease ( ).

There are two published case reports of three normal healthy term infants following use of atropine and pralidoxime in the treatment of maternal ingestion of fenthion at 16 weeks gestation ( ), methamidophos at 36 weeks ( ), and maternal inhalation of undiluted diazinon fumes at 26 weeks ( ). Fetal death has been reported in one case in which the mother was admitted to hospital 12 hours after the ingestion of chlorpyrifos at 19 weeks gestation, as she was unable to feel any fetal activity 2 hours post ingestion. Fetal blood chloropyrifos was 264 ppb ( ).

Paraquat

Paraquat has been withdrawn from the EU market. The literature regarding acute exposure to paraquat during pregnancy is limited. Eight published reports document paraquat exposure in the third trimester, associated with maternal toxicity which required hospitalization for treatment. Six cases resulted in maternal and fetal death ( ), and survival of both the mother and the fetus was reported in only two ( ).

One case series documents four instances of first or second trimester exposure to paraquat. Maternal and fetal mortality occurred in two cases, maternal survival but fetal death in one, and maternal survival with an elective termination for social reasons in the last ( ).

A case report described delivery of a normal term infant following a reported suicide attempt involving a few sips of Weedol, containing paraquat, at 20 weeks gestation ( ). The placenta showed signs of infarction in the absence of a maternal history of toxaemia or stroke. The child was reported to be healthy at 3 years of age. Maternal toxicity requiring hospital treatment occurred in all the above cases of acute exposure.

Paraquat was found in cord blood at about four times the maternal blood concentration ( ), and ulceration of lips and oral mucosa, pulmonary toxicity and hepatic necrosis has been observed at fetal autopsy ( ) following severe maternal poisoning. In another case, paraquat concentrations in a conceptus were five times those present in the amniotic fluid, and greater than that in maternal blood. Even though maternal ingestion was considerable and accompanied by toxicity, the fetus was viable at three weeks after ingestion, at which stage the pregnancy was electively terminated ( ).

Thallium

Experience of thallium poisoning in the first 13 weeks of pregnancy is limited to a few published case reports. Most describe associated maternal toxicity. In three cases, healthy infants were delivered at term. Two pregnancies resulted in preterm delivery with respiratory insufficiency, cryptorchidism, imperforate anus, jaundice, alopecia and psychomotor impairment at 3 years of age reported in one infant ( ). No maternal symptoms were reported after thallium poisoning around the time of conception in a woman who was treated with gastric lavage, catharsis and Prussian blue , but subsequently miscarried at 9 weeks ( ).

Around 13 cases of thallium poisoning in the second or third trimester of pregnancy have been published. All report associated maternal symptoms, and although the outcome for each was a live born infant. Features consistent with thallium toxicity were reported in some (alopecia in five, dermal effects in two and failure to thrive in three), with some infants having more than one of these features. In one case, maternal ingestion of thallium occurred at term and the neonate subsequently died ( ).

Use of the antidote Prussian blue has only been reported in two separate cases of thallium poisoning in pregnancy. The first resulted in the premature delivery of an infant at 6 months gestation after maternal thallium poisoning, and treatment with Prussian blue at an unknown stage of pregnancy ( ). The second case involved chronic intoxication from thallium-containing rodenticide in the workplace at 13 weeks gestation. The patient was treated with Prussian blue and nutritional support, but fetal loss was reported three weeks later and maternal symptoms of nausea, vomiting, and lumbar and epigastric pain persisted for 6 weeks after the exposure ( ).