Fever in pregnancy and the risk of congenital malformations: a cohort study
Open accessAbstract
BACKGROUND: In 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. METHODS: The 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. RESULTS: Eight 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. CONCLUSIONS: Overall, this study did not show any association between maternal fever in pregnancy and risk of congenital anomalies.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Febrile morbidity in pregnancy has been associated with congenital malformations when it occurs in the first trimester, and with adverse neurodevelopmental outcomes in offspring, although the level of risk remains controversial.
“Febrile morbidity in pregnancy has been associated with congenital malformations 24 when it occurs in the first trimester, and adverse neurodevelopmental outcomes in offspring 25 , although the level of risk remains controversial 26 .”
From Coronavirus disease 2019 vaccine response in pregnant and lactating women: a cohort study (2021) · cites this paper as [26]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Murray, C. J. L., Vos, T., Lozano, R., Naghavi, M., Flaxman, A. D., Michaud, C., Ezzati, M., Shibuya, K., Salomon, J. A., Abdalla, S., et al. (2012) · The Lancet · doi:10.1016/s0140-6736(12)61689-4 · Cited by 8,888 · see citing works
The Danish National Patient Registry: a review of content, data quality, and research potential
Schmidt, M., Schmidt, S. A. J., Sandegaard, J. L., Ehrenstein, V., Pedersen, L. H., & Sørensen, H. T. (2015) · Clinical Epidemiology · doi:10.2147/clep.s91125 · Cited by 4,788 · see citing works
The Danish National Patient Register
Lynge, E., Sandegaard, J. L., & Rebolj, M. (2011) · Scandinavian Journal of Public Health · doi:10.1177/1403494811401482 · Cited by 3,968 · see citing works
The Effects of Climate Change on Cardiac Health
De Blois, J., Kjellstrom, T., Agewall, S., Ezekowitz, J. A., Armstrong, P. W., & Atar, D. (2015) · Cardiology · doi:10.1159/000398787 · Cited by 1,697 · see citing works
The Danish National Birth Cohort - its background, structure and aim
Olsen, J., Melbye, M., Olsen, S. F., Sørensen, T. I. A., Aaby, P., Andersen, A. N., Taxbøl, D., Hansen, K. D., Juhl, M., Schow, T. B., et al. (2001) · Scandinavian Journal of Public Health · doi:10.1177/14034948010290040201 · Cited by 1,071 · see citing works
Self‐selection and bias in a large prospective pregnancy cohort in Norway
Nilsen, R. M., Vollset, S. E., Gjessing, H. K., Skjærven, R., Klungsøyr, K., Schreuder, P., Alsaker, E. R., Haug, K., Daltveit, A. K., & Magnus, P. M. (2009) · Paediatric and Perinatal Epidemiology · doi:10.1111/j.1365-3016.2009.01062.x · Cited by 836 · see citing works
Does Low Participation in Cohort Studies Induce Bias?
Nohr, E. A., Frydenberg, M., Henriksen, T. B., & Olsen, J. (2006) · Epidemiology · doi:10.1097/01.ede.0000220549.14177.60 · Cited by 570 · see citing works
Systematic review and meta-analyses: fever in pregnancy and health impacts in the offspring
Dreier, J. W., Andersen, A.-M. N., & Berg-Beckhoff, G. (2014) · PEDIATRICS · doi:10.1542/peds.2013-3205 · Cited by 204 · see citing works
Self-citationMATERNAL HYPERTHERMIA AS A POSSIBLE CAUSE OF ANENCEPHALY
MILLER, P. (1978) · The Lancet · doi:10.1016/s0140-6736(78)90549-4 · Cited by 195 · see citing works
Hyperthermia and birth defects
Edwards, M. J., Shiota, K., Smith, M. S. R., & Walsh, D. A. (1995) · Reproductive Toxicology · doi:10.1016/0890-6238(95)00043-a · Cited by 194 · see citing works
Maternal illness, including fever, and medication use as risk factors for neural tube defects
Shaw, G. M., Todoroff, K., Velie, E. M., et al. (1998) · Teratology · doi:10.1002/(sici)1096-9926(199801)57:1 · Cited by 162 · see citing works
Maternal fever and birth outcome: A prospective study
Chambers, C., Johnson, K. A., Dick, L. M., Felix, R. J., & Jones, K. L. (1998) · Teratology · doi:10.1002/(sici)1096-9926(199812)58:6 · Cited by 135 · see citing works
Maternal fever and neural tube defects
Layde, P. M., Edmonds, L. D., & Erickson, J. D. (1980) · Teratology · doi:10.1002/tera.1420210114 · Cited by 128 · see citing works
Larsen, H., Nielsen, G. L., Bendsen, J., Flint, C., Olsen, J., & Sørensen, H. T. (2003) · Scandinavian Journal of Public Health · doi:10.1080/14034940210134194 · Cited by 126 · see citing works
Congenital Heart Defects, Maternal Febrile Illness, and Multivitamin Use: A Population-Based Study
Botto, L. D., Lynberg, M. C., & Erickson, J. D. (2001) · Epidemiology · doi:10.1097/00001648-200109000-00004 · Cited by 126 · see citing works
Li, Z., Ren, A., Zhang, L., Guo, Z., & Li, Z. (2006) · Paediatric and Perinatal Epidemiology · doi:10.1111/j.1365-3016.2006.00694.x · Cited by 123 · see citing works
Congenital malformations in the rat following induced hyperthermia during gestation
Edwards, M. J. (1968) · Teratology · doi:10.1002/tera.1420010206 · Cited by 119 · see citing works
Maternal hyperthermia during pregnancy and cardiovascular malformations in the offspring
Tikkanen, J., & Heinonen, O. P. (1991) · European Journal of Epidemiology · doi:10.1007/bf00218673 · Cited by 115 · see citing works
Li, Z., Ren, A., Liu, J., Pei, L., Zhang, L., Guo, Z., & Li, Z. (2007) · Birth Defects Research Part A Clinical and Molecular Teratology · doi:10.1002/bdra.20342 · Cited by 86 · see citing works
Risk factors for oral clefts: a population‐based case‐control study in Shenyang, China
Wang, Z., Guan, P., Xu, W., et al. (2009) · Paediatric and Perinatal Epidemiology · doi:10.1111/j.1365-3016.2009.01025.x · Cited by 83 · see citing works
Suarez, L., Felkner, M. M., & Hendricks, K. (2004) · Birth Defects Research Part A Clinical and Molecular Teratology · doi:10.1002/bdra.20077 · Cited by 82 · see citing works
Associations Between Maternal Fever and Influenza and Congenital Heart Defects
Oster, M. E., Riehle‐Colarusso, T. J., Alverson, C. J., & Correa, A. (2011) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2010.11.058 · Cited by 74 · see citing works
Fever in pregnancy and risk of fetal death: a cohort study
Andersen, A. N., Vastrup, P., Wohlfahrt, J., Andersen, P. K., Olsen, J., & Melbye, M. (2002) · The Lancet · doi:10.1016/s0140-6736(02)11518-2 · Cited by 70 · see citing works
Socio-occupational status and congenital anomalies
Varela, M. M. M.-S., Nohr, E. A., González, A. L., et al. (2009) · European Journal of Public Health · doi:10.1093/eurpub/ckp003 · Cited by 68 · see citing works
Maternal fever during early pregnancy and the risk of oral clefts
Hashmi, S. S., Gallaway, M. S., Waller, D. K., Langlois, P. H., & Hecht, J. T. (2010) · Birth Defects Research Part A Clinical and Molecular Teratology · doi:10.1002/bdra.20646 · Cited by 64 · see citing works
Hyperthermia, teratogenesis and the heat shock response in mammalian embryos in culture
Edwards, M. J., Walsh, D. A., & Li, Z. (1997) · The International Journal of Developmental Biology · doi:10.1387/ijdb.9184344 · Cited by 63 · see citing works
Pizzi, C., Stavola, B. L. D., Pearce, N. E., Lazzarato, F., Ghiotti, P., Merletti, F., & Richiardi, L. (2011) · Journal of Epidemiology & Community Health · doi:10.1136/jech-2011-200065 · Cited by 55 · see citing works
Maternal febrile illnesses, medication use, and the risk of congenital renal anomalies
Abe, K., Honein, M. A., & Moore, C. A. (2003) · Birth Defects Research Part A Clinical and Molecular Teratology · doi:10.1002/bdra.10130 · Cited by 53 · see citing works
A population-based case-control study of risk factors for neural tube defects in Shenyang, China
Yin, Z., Xu, W., Xu, C., Zhang, S., Zheng, Y., Wang, W., & Zhou, B. (2010) · Child s Nervous System · doi:10.1007/s00381-010-1198-7 · Cited by 50 · see citing works
MATERNAL HYPERTHERMIA AND NEURAL-TUBE DEFECTS
Halperin, L. R., & Wilroy, R. S. (1978) · The Lancet · doi:10.1016/s0140-6736(78)91957-8 · Cited by 46 · see citing works
Congenital heart defects after maternal fever
Botto, L. D., Panichello, J. D., Browne, M. L., Krikov, S. V., Feldkamp, M. L., Lammer, E. J., & Shaw, G. M. (2013) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2013.10.880 · Cited by 42 · see citing works
The impact of congenital malformations on public health
Sever, L. E., Lynberg, M. C., & Edmonds, L. D. (1993) · Teratology · doi:10.1002/tera.1420480603 · Cited by 42 · see citing works
Teratogenic and lethal effects of 2–24 h hyperthermia episodes on chick embryos
Krausova, T., & PETERKA, M. (2007) · Journal of Thermal Biology · doi:10.1016/j.jtherbio.2006.12.003 · Cited by 24 · see citing works
Graham (1998) · doi:10.1002/(sici)1096-9926(199811)58:5
Flagged first, then by citations
Cited by
Sorted by citations
Coronavirus disease 2019 vaccine response in pregnant and lactating women: a cohort study
Gray, K. J., Bordt, E. A., Atyeo, C., Deriso, E., Akinwunmi, B., Young, N., Baez, A. M., Shook, L. L., Cvrk, D., James, K., et al. (2021) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2021.03.023 · Cited by 699 · see citing works
Paracetamol use during pregnancy — a call for precautionary action
Bauer, A. Z., Swan, S. H., Kriebel, D., Liew, Z., Taylor, H. S., Bornehag, C.-G., Andrade, A. M., Olsen, J., Jensen, R. H., Mitchell, R. T., et al. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00553-7 · Cited by 228 · see citing works
The coronavirus disease 2019 vaccine in pregnancy: risks, benefits, and recommendations
Stafford, I. A., Parchem, J. G., & Sibai, B. M. (2021) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2021.01.022 · Cited by 89 · see citing works
- Authors
- Sass, L., Urhoj, S. K., Kjærgaard, J., Dreier, J. W., Strandberg-Larsen, K., & Nybo Andersen, A.-M.
- Affiliations
- University of Copenhagen (DK)
- Rigshospitalet (DK)
- Aarhus University (DK)
- Corresponding author
- Sass, L.
- Venue
- BMC Pregnancy and Childbirth
- Published
- 2017-12
- Volume
- 17
- Issue
- 1
- Pages
- 413-413
- ISSN
- 1471-2393 (ISSN-L)
- PMC
- PMC5723098
- OpenAlex
- W2773603825
- Cited by
- 66
- References
- 34
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 10 · 2021: 16 · 2020: 17 · 2019: 5
- FWCI
- 5.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Pregnancy and Childbirth (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- March of Dimes Foundation
- National Research Foundation
- Danmarks Grundforskningsfond
- Augustinus Fonden
- Egmont Fonden
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
- Keywords
- fever in pregnancy, first trimester, congenital malformations, hyperthermia, teratogenicity, fetal development, genital malformations, nervous system malformations, urinary tract anomalies, Danish National Birth Cohort, pregnancy outcomes, heat shock proteins
- MeSH terms
- Congenital Abnormalities, Adult, Denmark, Female, Fever, Humans, Infant, Newborn, Pregnancy, Pregnancy Complications, Infectious, Pregnancy Outcome, Pregnancy Trimester, First, Prospective Studies, Risk Factors, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
