Three studies involving more than 10,000 newborns exposed to acetaminophen during the first trimester did not find an association between acetaminophen and major malformations [1,3,4].

In a prospective study of 300 women who had self-administered an overdose of (acetaminophen) paracetamol, either alone, or as part of a combined preparation there were 219 liveborn infants with no malformations, 61 of whom had been exposed in the first trimester. None of the mothers died. Eleven liveborn infants had malformations; none was exposed in the first trimester.  There were seven full-term infants with neonatal problems that seem unrelated to paracetamol exposure. Six premature infants also had neonatal problems, which were more likely to be related to their degree of prematurity rather than paracetamol exposure [5].

Char et al reported a case of severe maternal anemia and fatal kidney disease in the newborn following a continuous high daily dosage of acetaminophen [6].

Although the above studies are, overall,  reassuring the findings of a retrospective study evaluating the relation between maternal use of cough/cold/analgesic medications and risks of gastroschisis and small intestinal atresia (SIA) raise questions about  interactions between acetaminophen and  pseudoephedrine.  Werler MM,  et al. , found that among mothers of 206 infants with gastroschisis and 126 mothers of infants with small intestinal atresia infants with gastroschisis had an increased risk (odds ratio = 1.5) of having been exposed to acetaminophen during gestation. The risk for gastroschisis was increased further (odds ratio = 4.2) among infants who had been exposed to pseudoephedrine combined with acetaminophen. The risk of small intestinal atresia was increased for use of pseudoephedrine in combination with acetaminophen (odds ratio = 3.0)  [7].

Gastroschisis is a congenital defect of the anterior abdominal wall characterized by an opening beside the umbilical cord that allows bowel to protrude. Gastroschisis is thought to arise from disruption of blood flow  to the affected abdominal wall [8]. The defect is uncommon and occurs in the general population with an incidence of  2.4 to 3.2 per 10,000 births in the general population with the highest incidence in women 15-19 years of age ( 26.5 per 10,000 births) [9,10]. The uncommon occurrence of gastroschisis should  be considered when counseling patients or interpreting the literature as to the increased risk for gastroschisis after any particular drug ingestion.

BREAST FEEDING: The mean milk/plasma ratio was 0.76 in 3 lactating women after ingestion of a single 500 mg dose of paracetamol [11]. Another study found  peak milk levels were achieved by one to two hours after a single oral dose of 650 mg. Assuming an infant ingested 90 ml milk at 3, 6, and 9 hours after maternal ingestion of paracetamol, the amount of paracetamol available for ingestion would have been less than 0.23% of the maternal dose [12].
The American Academy of Pediatrics has classified acetaminophen (paracetamol ) as a drug "Usually Compatible With Breastfeeding" [13].

NEONATAL SIDE EFFECTS: One case of rash after breast feeding [13].

SEARCH LITERATURE

1. Briggs GG,Freeman RK, Yaffe SJ, Drugs in Pregnancy and Lactation 6th edition,Baltimore, MD: Williams & Wilkins,2002 p 6-9
2. Levy G, et al. Letter: Evidence of placental transfer of acetaminophen.Pediatrics. 1975 ;55:895.  MEDLINE
3.Heinonen OP et al: Birth Defects and Drugs in Pregnancy Littleton, Publishing Sciences Group, 1977, pp 286-295
4. Aselton P, et al First-trimester drug use and congenital disorders.Obstet Gynecol. 1985;65:451-5. MEDLINE
5. McElhatton PR, Sullivan FM, Paracetamol overdose in pregnancy analysis of the outcomes of 300 cases referred to the Teratology Information Service. Reprod Toxicol. 1997;11:85-94. MEDLINE
6.Char VC, et al Letter: Polyhydramnios and neonatal renal failure--a possible association with maternal acetaminophen ingestion.J Pediatr. 197586:638-9.MEDLINE
7.Werler MM, et al Maternal medication use and risks of gastroschisis and small intestinal atresia. Am J Epidemiol. 2002;155:26-31 MEDLINE
8. Hoyme HE, et al. ;The vascular pathogenesis of gastroschisis: intrauterine interruption of the omphalomesenteric artery.J Pediatr. 1981;98:228-31. MEDLINE
9. Reid KP, et al., The epidemiologic incidence of congenital gastroschisis in Western Australia. Am J Obstet Gynecol. 2003;189:764-8. MEDLINE
10. Nichols CR, et al., Rising incidence of gastroschisis in teenage pregnancies. J Matern Fetal Med. 1997;6:225-9.MEDLINE
11. Bitzen PO,et al Excretion of paracetamol in human breast milk.Eur J Clin Pharmacol. 1981;20:123-5. MEDLINE
12. Berlin Jr CM, et al. Disposition of acetaminophen in milk, saliva, and plasma of lactating women.Pediatr Pharmacol (New York).1980;1:135-41. MEDLINE
13.Transfer of drugs and other chemicals into human milk. Pediatrics. 2001;108:776-89.

 

Created: 1/7/2004
Update: 1/7/2004 Mark Curran, M.D, FACOG
Update: 6/26/2007 Mark Curran, M.D, FACOG