Hyperthermia can be caused by fevers and by environmental exposure to heat sources. Maternal temperature increases are transmitted to the fetus. For several decades it has been demonstrated that elevated body temperature can cause malformations in animal studies. There is growing evidence that the same also applies to humans; mild exposure during the pre-implantation period and more severe exposure during embryonic and fetal development often resulL in prenatal death and abortion. Hyperthermia also causes a wide range of structural and functional defects. The central nervous system (CNS) is most at risk, probably because it cannot compensate for the loss of prospective neurons by additional divisions by the surviving neuroblasts, and it remains at risk at stages throughout pre- and postnatal life, although its possible effects at these stages have not been studied in detail (Edwards 2006). There are indications that some malformations, such as neural tube defects (Shaw 1998), but also heart defects, renal anomalies, and gastroschisis, were more frequently observed after prolonged periods of high fever in early pregnancy (e.g. Abe 2003, Chambers 1998). in this prospective study, 115 pregnant women with high fever (38.9° C for 24 hours or more) were compared with 147 women with moderate fever (<38.9° C, or <24 hours) and with women without fever. About 80% of these febrile periods occurred in the first trimester. The relative risk for congenital malformations calculated in this study, however, was not of statistical significance. In a cohort study of 24 040 pregnant women, where 1145 pregnancies resulted in a miscarriage or stillbirth, there was no evidence that fever in the first 16 weeks of pregnancy is associated with fetal death was found (Andersen 2002). In a commentary it was pointed out that the main limitation of this study was that the risk of fetal death before week 6 could not be assessed, and therefore no definite conclusions could be made (Chambers 2006). The question of whether elevated body temperature may be responsible for the so-called "vascular disruption disorders", where developing organs are deprived of sufficient blood supply, is still under discussion (Martínez-Frías 2001, Graham 1998). A rise in body temperature of = 2" C for more than 24 hours is acknowledged nowadays to be associated with an increased risk of developmental defects.

An increased risk from sauna or hot-tub bathing has been discussed (Li 2003, Milunsky 1992), but data are not sufficient for definite conclusions (Chambers 2006, Herz-Picciotto 2003). However, in view of the relatively large volume of animal data and the association between high maternal fever and NTDs, a risk cannot be excluded. In a hot-tub (39-40° C), body temperature (studied in nonpregnant women) may reach 38.9° C after only 10-20 minutes (Harvey 1981). Women of reproductive age and who may be pregnant should limit exposure to hot-tubs to less than 15 minutes in 39° C water and less than 10 minutes in 40° C water (Chambers 2006). Time limits for hot-tubs are shorter than for saunas; the latter permit greater heat loss by evaporation and perspiration. In Finland, where sauna bathing is very common, even during pregnancy, no association with adverse pregnancy outcomes has been detected.

Use of electric blankets or heated waterbeds has not demonstrated any additional risk of congenital malformations to date. The use of birthing pools has raised some concern in a case report (Rosevaer 1993), where, after staying in water of 39° C for several hours, two mothers delivered infants in poor condition; both newborns died shortly afterwards.

Recommendation. When high fever does arise in early pregnancy, paracetamol (acetaminophen) should be taken to lower the body temperature, together if necessary with other measurements such as cool wrappings and sufficient fluid intake. Saunas or hot-tubs should not exceed 10 minutes. In general, sources of possible overheating should be avoided. In cases of high fever episodes in early pregnancy, diagnostic measurements such as detailed fetal ultrasound should be considered.

2.6.57 Traveling

When pregnant patients are traveling long distances, or going abroad, several possible risks should be discussed:

■ Prophylactic measurements to prevent infections (for malaria prophylaxis, see section 2.6.24; for vaccinations, see Chapter 2.7)

■ The risk of other infections (fever, fluid loss), and required therapy

■ In long-distance air travel, cosmic radiation, the increased risk of thrombotic events due to prolonged immobilization, decreased air (oxygen) pressure comparable with an altitude of approximately 2500 m, and physical and psychic stress.

No specific malformations have been associated with established vaccinations or with malaria prophylaxis. However, with some of them there is insufficient experience with use in pregnancy (see Chapter 2.7). It should be pointed out that the increased physical stress associated with long-distance travel in predisposed women might increase their risk for spontaneous abortion. Another risk is of "common" infections, due to altered hygienic standards in the destination country. The accompanying fever, dehydration or other complications may also endanger the fetus.

The quantity of ionizing radiation in air travel will vary according to several conditions, but as far as we know doses will not be high enough to incorporate an additional risk of malformations.

Staying at high altitudes carries the problem of decreased air pressure and the risk of high altitude sickness. Although a decreased birth weight in infants bom to mothers who live at (moderate) high altitudes has been observed, a short-term stay in conditions with moderate decreased air pressure does not seem to carry a risk of fetal hypoxia. Fetal oxygen supply at very high altitudes (>3300 m or 11 000 ft) cannot be guaranteed, and the risk of maternal high altitude sickness may endanger the mother and child. Healthy pregnant women can probably stay at a moderately high altitude for a short period, but avoiding exercise, or maintaining hydration and waiting several days for acclimatization before starting moderate exercise, is recommended (Jean 2005, Rodway 2004, Niermeyer 1999). Heavy exercise with increasing body temperature must be avoided (Samuel 1998). During long-distance flights, air pressure and the oxygen partial pressure are kept to the same level as at an altitude of 2500 m, which carries no risk for healthy (pregnant) individuals.

Recommendation. The need for long journeys, especially to tropical destinations, by pregnant women should be critically evaluated. Women with a history of spontaneous abortion should preferably postpone their journey, Women with risk factors for spontaneous abortion, pre-eclampsia or placental abruption, or whose babies are at risk of intrauterine growth restriction (IUGR), should not go to (very) high altitudes. When a journey has been made during pregnancy without any complications, further diagnostic procedures are not warranted.


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