Short‐term paracetamol therapy during pregnancy and a lower rate of preterm birth

Abstract

The relationships between short-term oral paracetamol treatment during pregnancy and mean gestational age and birthweight, in addition to the prevalence of preterm birth and low birthweight were estimated using newborn infants in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996. Gestational age and birthweight were medically recorded. Of 38 151 newborn infants, 173 were born to mothers who had paracetamol treatment during pregnancy. A 0.4-week increase in the mean gestational age was found among exposed relative to unexposed, and with the use of paracetamol during pregnancy there was a significant reduction in the proportion of preterm birth (3.5% vs. 9.2%) (adjusted P = 0.01). The possible preterm birth protective effect of paracetamol may be associated with paracetamol-induced reduction of prostacyclin production in pregnant women. The clinical relevance of these findings needs further studies.

Use of acetaminophen during pregnancy and risk of adverse pregnancy outcomes

“…Acetaminophen use during pregnancy was not associated with a change in the risk of miscarriage, LBW or SGA. In contrast to previous reports, 5,6 we found no reduced risk of stillbirth or of preterm birth among pregnancies with acetaminophen exposure. However, our results are based on a large population-based study and included both over-the-counter and prescribed medication.…”

“…8 Inhibition of Prostacyclin (PGI 2 ) synthesis and an imbalance between PGI 2 (a vasodilator) and Thromboxane A2 (TXA 2 , a vasoconstrictor) have been suggested as an explanation for these associations. 6,8 In contrast, a reduction in PGI 2 synthesis could also be associated with an increased risk of pre-eclampsia, 9 leading to an increased risk of induced preterm birth which would not be detected in a study using only spontaneous preterm births as endpoints. Induced preterm delivery occurs in 15-25% of all preterm births, with hypertensive disorders as the major proximal cause.…”

“…[1][2][3] There are few studies on potential teratogenic effects, 4 other pregnancy effects and birth outcomes following acetaminophen use and most of these studies are based on very small numbers of exposed women. A reduced risk of stillbirth 5 and preterm birth 6 has been reported, although not consistently, [5][6][7] and no association with miscarriage has been reported in the literature. 8 Inhibition of Prostacyclin (PGI 2 ) synthesis and an imbalance between PGI 2 (a vasodilator) and Thromboxane A2 (TXA 2 , a vasoconstrictor) have been suggested as an explanation for these associations.…”

Prenatal paracetamol exposure is associated with shorter anogenital distance in male infants

“…Remarkably, a retrospective Hungarian study reported an identical increase in mean gestational age of infants exposed to paracetamol during pregnancy (2.8 days), with a significant reduction in preterm deliveries (3.5% versus 9.2%), although they did not distinguish between male and female offspring (Czeizel et al ., 2005). The authors speculated that paracetamol may prolong pregnancy via a reduction in prostacyclin synthesis, consistent with findings from a randomised controlled trial showing that low-dose aspirin (another COX inhibitor) also reduced preterm delivery (CLASP (Collaborative Low-dose Aspirin Study in Pregnancy) Collaborative Group, 1994).…”

Monster Phase of Acetaminophen Use in Pregnancy: Current Vision of an Old Drug

“…One of the suggested explanation for this association is inhibition of Prostacyclin (PGI2) synthesis and inequality between PGI2 (a vasodilator) and Thromboxane A2 (TXA2, a vasoconstrictor) [8,9]. Similarly, a reduction in PGI2 synthesis could also be coupled with an augmented risk of pre-eclampsia leading to an amplified risk induced preterm birth that could not be detected in a study using only spontaneous preterm births as endpoints [10].…”