Fever in pregnancy and the risk of congenital malformations: a cohort study

Abstract

BackgroundIn a variety of animal species, hyperthermia in pregnancy has been recognized as teratogenic. Hyperthermia interferes with protein synthesis via heat-shock proteins, which can entail membrane disruption, cell death, vascular disruption, and placental infarction. This can induce severe fetal malformations or death. Fever during pregnancy, especially during embryogenesis, has also been associated with congenital malformations in human offspring.The purpose of this large cohort study of clinically recognized pregnancies was to investigate whether fever during first trimester was associated with an increased risk of congenital malformations in the offspring.MethodsThe Danish National Birth Cohort is a population-based cohort of 100,418 pregnant women and their offspring recruited in 1996 to 2002. Information on fever during pregnancy was collected prospectively by means of two telephone interviews.The study population comprised the 77,344 pregnancies enrolled in the Danish National Birth Cohort where self-reported information on fever during first trimester of pregnancy was available. Pregnancy outcomes were identified through linkage with the National Patient Registry. Congenital malformations within the first three and a half years of life were categorized according to EUROCAT’s classification criteria. Logistic regression models were used to estimate the associations between fever in first trimester and overall congenital malformations and congenital malformations by subgroups.ResultsEight thousand three hundred twenty-one women reported fever during first trimester (10.8%) and 2876 infants were diagnosed with a congenital malformation (3.7%). Fever during first trimester did not affect the risk of overall fetal congenital malformation (OR 0.99, 95% CI 0.88–1.12). The subgroup analyses indicated slightly higher risk of congenital anomalies in the eye, ear, face and neck (OR 1.29, 95% CI 0.78–2.12) and in the genitals (OR 1.17, 95% CI 0.79–1.12), whereas lower risk of malformations in the nervous system (OR 0.47, 95% CI 0.21–1.08), the respiratory system (OR 0.56, 95% CI 0.23–1.29) and in the urinary subgroup (OR 0.58, 95% CI 0.35–0.99) was suggested, the latter constituting the only statistically significant finding.ConclusionsOverall, this study did not show any association between maternal fever in pregnancy and risk of congenital anomalies.

Global interim guidance on coronavirus disease 2019 (COVID‐19) during pregnancy and puerperium from FIGO and allied partners: Information for healthcare professionals

“…28 Among the 77 344 viable pregnancies with data collected at 16-29 weeks of pregnancy, in the 8321 pregnant women with a reported temperature above 38°C lasting 1-4 days in early pregnancy, compared with those without a fever in early pregnancy, the overall risk of fetal malformation was not increased (odds ratio [OR]=0.99 (95% CI, 0.88-1.12). 28 It has been reported that viral pneumonia in pregnant women is associated with an increased risk of preterm birth, fetal growth restriction (FGR), and perinatal mortality. 29 Based on nationwide populationbased data it was demonstrated that pregnant women with other viral pneumonias (n=1462) had an increased risk of preterm birth, FGR, and having a newborn with low birth weight and an Apgar score of less than 7 at 5 minutes, compared with those without pneumonia (n=7310).…”

Thermal Effects Associated with RF Exposures in Diagnostic MRI: Overview of Existing and Emerging Concepts of Protection

“…A retrospective review supported concerns for potential negative health impact associated with first trimester fever in humans [76]. To the contrary, a subsequent large-scale prospective study by the same authors concludes that there is no evidence that maternal fever during pregnancy induces congenital defects [77]. The latter finding corroborates reports that Concepts in Magnetic Resonance Part B 9 (noncontrast enhanced) MRI during pregnancy does not negatively impact childhood outcomes [78,79].…”

ISUOG Interim Guidance on 2019 novel coronavirus infection during pregnancy and puerperium: information for healthcare professionals

“…However, a recent study, including 80 321 pregnant women, reported that the rate of fever in early pregnancy was 10%, while the incidence of fetal malformation in this group was 3.7%. Among the 77 344 viable pregnancies with data collected at 16–29 weeks of gestation, in the 8321 pregnant women with a reported temperature > 38°C lasting 1–4 days in early pregnancy, compared to those without a fever in early pregnancy, the overall risk of fetal malformation was not increased (odds ratio = 0.99 (95% CI, 0.88–1.12)). Previous studies have reported no evidence of congenital infection with SARS‐CoV 61 , and currently there are no data on the risk of congenital malformation when COVID‐19 infection is acquired during the first or early second trimester of pregnancy.…”

“…Previous data have demonstrated that maternal fever in early pregnancy can cause congenital structural abnormalities involving the neural tube, heart, kidney and other organs. However, a recent study, including 80 321 pregnant women, reported that the rate of fever in early pregnancy was 10%, while the incidence of fetal malformation in this group was 3.7%. Among the 77 344 viable pregnancies with data collected at 16–29 weeks of gestation, in the 8321 pregnant women with a reported temperature > 38°C lasting 1–4 days in early pregnancy, compared to those without a fever in early pregnancy, the overall risk of fetal malformation was not increased (odds ratio = 0.99 (95% CI, 0.88–1.12)).…”