Fever in Pregnancy
Saturday, October 13, 2007
Kenneth F. Trofatter, Jr., MD, PhD
Professor Marshall J. Edwards at the University of Sydney, Australia, is generally considered to be the individual who pioneered the discovery that maternal hyperthermia during pregnancy can be teratogenic (Birth Defects Res A Clin Mol Teratol. 2005;73:857-64). In animal studies over the course of 40 years, Edwards demonstrated that mechanisms for hyperthermia-induced fetal damage included “cell death, membrane disruption, vascular disruption, and placental infarction…” Modest elevations in temperature prior to implantation and more sustained elevations during early embryogenesis may cause fetal death and abortion. Embryos surviving maternal hyperthermia during early development are at risk for a host of congenital anomalies, including neural tube and central nervous system (CNS), micrencephaly, microphthalmia, cataracts, craniofacial, heart, renal, dental, and abdominal wall defects among others.
The most common cause of hyperthermia during pregnancy is fever related to viral illnesses (and other common causes include bacterial infections associated with pyelonephritis, tonsillitis, and appendicitis). Since we are heading into the cold and flu season, women who are either anticipating or already are in the early stages of pregnancy, should be especially cautious (start taking your folic acid now!). Over the years, several studies have confirmed that temperature elevations in pregnant women accompanying influenza and common cold virus infections are associated with greater risk for congenital anomalies, multiple and isolated, especially, neural tube defects.
A meta-analysis of 15 separate studies by Moretti and colleagues (Epidemiology. 2005;16:216-9) included 1,719 cases and 37,898 controls and found an overall odds ratio for neural tube defects associated with maternal hyperthermia of 1.92 (95% CI = 1.61-2.29). Acs and colleagues (Birth Defects Res A Clin Mol Teratol. 2005;73:989-96) evaluated 22,843 newborns or fetuses with congenital anomalies and 38,151 matched controls and found “there was a higher prevalence of maternal influenza during the second and/or third month of pregnancy for the group of newborns with cleft lip +/- palate (adjusted prevalence odds ratio (POR), 3.2; 95% CI, 2.0-5.3), neural tube defects (adjusted POR, 1.9; 95% CI, 1.1-3.3) and cardiovascular malformations (adjusted POR, 1.7; 95% CI, 1.3-2.3).” They also concluded that “a direct teratogenic effect from influenza viruses appears unlikely” and the higher prevalence of congenital anomalies “can be explained mainly by fever, because this risk was reduced by the use of antifever drugs.” These same congenital defects have been found at a higher prevalence in women with folic acid deficiencies and aberrations of folate metabolism, such as those associated with polymorphisms of methylene tetrahydrofolatereductase (MTHFR), so it was most interesting to see that the authors found that “periconceptional folic acid supplementation also showed some preventive effect…”
One other study worth mentioning, conducted by Suarez and colleagues (Birth Defects Res A Clin Mol Teratol. 2004;70:815-9), is interesting because it looked not only at febrile illnesses, but other causes of maternal hyperthermia as well. They studied a population of high-risk Mexican-American women who lived in 14 Texas counties bordering Mexico. To quote their results, the odds ratio (OR) “associated with maternal fever in the first trimester, compared to no fever, was 2.9 (95% CI, 1.5-5.7). Women taking fever-reducing medications showed a lower risk effect (OR, 2.4; 95% CI, 1.0-5.6) than those who did not (OR, 3.8; 95% CI, 1.4-10.9). First-trimester maternal exposures to heat devices such as hot tubs, saunas, or electric blankets were associated with an OR of 3.6 (95% CI, 1.1-15.9). Small insignificant effects were observed for activities such as cooking in a hot kitchen (OR, 1.6; 95% CI, 1.0-2.6) and working or exercising in the sun (OR, 1.4; 95% CI, 0.9-2.2).”
In closing, I would also like to point out that although the period of early fetal development carries the greatest risk from maternal hyperthermia, severe temperature elevations during the second and third trimesters may still put the baby at jeopardy, particularly for CNS damage, and might be responsible for some cases of behavioral and developmental compromise and even more severe neurological conditions, such as schizophrenia, autism, and cerebral palsy. In my experience as well, high fever associated with both viral and bacterial illnesses in late second and third trimester also dramatically increases the risk for subsequent premature labor and delivery and may precipitate preeclampsia!
Labels: birth defects, fever, folic acid, hyperthermia, neural tube defects, teratogenesis, viral infections
8 Comments:
At Wed Mar 12, 08:34:00 AM 2008,
Bree said…
Thank you for all of your knowledge. We recently lost our baby at 20 weeks to severe neural tube defects. All of our tests showed that we were in good shape. But our 20 weeks ultrasound showed otherwise. I am learning that I may have contributed to the problems. I had a very hard first 4 months... I was very sick. I did take hot baths, as I was told that if it made me comfortable, it was ok. I was unable to take my prenatal every day, and was told that everything should be fine, that if I could not stomach the prenatal, make sure that I was taking a folic supplement (OTC). This is my second miscarriage in two years and I have had three terminated pregnanacies. We are not yet ready to try again, but Iwant to make sure that I am doing everything in my power to ensure a happy, healthy and complete prgnancy. Other than upping my intake of folic acid to the prescribed dosage, should I have any tests done? Should I start taking any other supplements? Will my failure to carry my preganacies to term effect our future efforts? My mother has MS. Is there any connection? Thank you again.
At Wed Mar 12, 06:36:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
Hi Bree: Sorry for your loss. Please don't kick yourself too hard over this. Neural tube defects usually are 'multifactorial' in etiology. Did the baby only have neural tube defects or were other abnormalities found. The reason I ask is that if other abnormalities were present, the baby may have had a 'syndromic (genetic)' problem and depending on what that might be, your risk for recurrence may be greater than if this was just a neural tube defect alone. You might want to discuss that possibility with a genetic counselor before you try to get pregnant again, if you haven't already. Prior to your next pregnancy, you might get screened for polymorphisms (mutations) of the MTHFR genes. These can affect folic acid metabolic pathways and increase your risk for neural tube and congenital heart defects. Might also want to have a fasting homocysteine level done as well. I would recommend taking folic acid at a dose of 4-5 mg/day for several months with a B-vitamin supplement before conceiving the next time around as well. The neural tube is closed by about 28 days after conception (6 weeks from the first day of your last normal menstrual period, so that is the critical time of development with which you need to be concerned and have the extra folic acid on-board. Anything you do after that isn't going to have much effect on the neural tube! The heart takes a few weeks longer to form completely. Hope that answers some of your questions. Thanks for reading! Dr T
At Thu Jan 29, 10:29:00 AM 2009,
Anonymous said…
Hi, dear doctor!!!
I had a miscarriage 2 month ago. I am pregnant again, that was very unexpected, we were planning to take our time. I had a cold, probably on the first week, and high fever, about 38.8 degrees, for 2 days I had fever, going up and down.But I did not take any strong medicine, i dont like medicine. Yesterday i saw some brown spots. I am so stressed out. I am terrified to lose a baby again to the point that I am scared to see a doctor.
At Sun Feb 01, 08:58:00 PM 2009,
Mooka said…
Oh wow thanks for not making me feel better. The other night my temperature spiked up to 102, I have been sick the past week or so and I figured there was nothing to really worry about. The fever lasted for about 10-12 hours and through the night I nursed it only by drinking a lot of fluids. By the time I got up the next morning the fever was gone and I felt fine but now I'm scared that I should have taken something or gone to the ER. I am about 7 weeks pregnant. So now I will worry that something will be wrong with the baby.
At Wed Jun 24, 10:33:00 PM 2009,
Anonymous said…
Hi! I am 9 weeks pregnant and I've had fever of 37C for 3 weeks. My doctor could not tell me the reason I have it. How dangerous it can be for the baby? What should I do about it?
Thanks.
At Thu Jul 02, 08:17:00 AM 2009,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous June 24: 37C is a NORMAL temperature?!?
Dr T
At Tue Oct 13, 08:41:00 AM 2009,
wombat767 said…
Hi, My wife got what we think might be H1N1 this last week (starting about Thursday, getting serious on Friday). We didn't have a thermometer and didn't know that she was pregnant yet (her period should have started on Sunday). Friday night when I got in bed she felt pretty warm, but she wasn't warm when we woke up. She also felt warm a couple of other times, but not for very long and not as warm as Friday night. She hasn't had a fever since Sunday. She has been taking prenatal pills faithfully for probably 3 weeks, and Sunday was the start of her fourth week. We are planning on going to a doctor, but since we just found out that she is pregnant, we don't have one yet. Do you think that there is a serous chance of miscarriage or birth defects?
At Thu Oct 15, 06:27:00 PM 2009,
Kenneth F. Trofatter, Jr., MD, PhD said…
To wombat Oct 13: That early in pregnancy, if the virus caused a serious problem for the baby, it would be more likely to miscarry than go on to have birth defects. I wish you both the best.
Dr T
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