1. Hackett P: High altitude and common medical conditions, T. Hornbein and R. Schoene: High Altitude: An Exploration of Human Adaptation, NY, NY: Dekker, 2001, 839. (Used by permission) Pregnancy and reproduction of high altitude dwellers are discussed in Chapter 3. Here I will deal with the effects of ascent to altitude on the pregnant lowlander, and whether altitude poses any risk to the well being
   of mother and fetus. The discussion draws from what has been learned from research on altitude residents, and what is known of the effects of acute hypoxia or ascent to high altitude in pregnant animals and humans.
   
   First, consideration of the fetal milieu is in order. A normal mother breathing room air at sea level has an arterial PO2 of 85 to
   100 mm Hg, and a uterine venous PO2 of approximately 40 mm Hg. The PO2 in the umbilical vein (analogous to the pulmonary vein or systemic artery in the adult) will be 30 to 35 mm Hg, and in the umbilical artery (similar to the pulmonary artery) 10 to 15 mm Hg. Breathnach has argued that this situation should be considered fetal normoxia, and applying the term fetal hypoxia to it is inappropriate.181 This low oxygen fetal environment is remarkably stable. Due to the shape of the oxygen dissociation curve and
   the high affinity of fetal hemoglobin for oxygen, changes in maternal arterial oxygenation are minimized in the fetus.182 The placenta acts as a buffer in multiple ways: it maintains a constant PCO2 gradient (10 mm Hg), is relatively impermeable to bicarbonate ions (to protect the fetus from maternal changes in hydrogen ion concentration), and maintains the fetal oxygen environment.181 Additional strategies to maintain fetal stability include increased maternal ventilation during pregnancy (even in high altitude residents who may normally be insensitive to the chronic hypoxia, see below), and increased oxygen extraction by the fetus. As a result, oxygen consumption remains stable even when stressed with a 50% reduction in either placental blood flow or blood oxygen content.183 In a mother with cyanotic congenital heart disease, e.g., a SaO2 of only 82%, the fetal umbilical oxygen saturations are 40% venous and 7% arterial, and oxygen consumption is maintained. Further, the fetus must avoid a high PO2 as well
   as a severely low PO2, for raised PO2 is the trigger for the drop in pulmonary vascular resistance and closure of the ductus arteriosus.181, 182 Given a stable fetal environment, what degree of maternal hypoxia can be detrimental, and what evidence is there for compromise of the lowland fetus or mother upon ascent to high altitude?
   
   Studies of high altitude residents: implications for pregnant lowlanders
   
   In native residents at an altitude of 6,000 ft (1830 m) umbilical cord arterial and venous oxygen tensions are the same as at sea-level, while a slightly lower PCO2 reflects the mild maternal hyperventilation. At altitudes over 3000 m, fetal response to hypoxia is evidenced by increased hematocrit (2 to 3% higher), increased fraction that is fetal hemoglobin and increased eryhropoietin in the cord blood.184, 185
   
   Research from Colorado, South America, Africa and Asia has suggested various effects of high altitude residence on pregnancy. The effect best documented is intrauterine growth retardation, which leads to healthy, full term infants that are small for gestational age. (See chapter 3) In high altitude areas of the world with accessible medical care intrauterine growth retardation is not associated with increased morbidity or mortality unless the infants are also premature. Lower birth weight has even been suggested as a possible survival advantage at high altitude,186 a concept refuted by data from Unger et al in Colorado.187 Intrauterine growth
   retardation, however, does indicate an apparent regulatory effect of oxygen on the developing fetus.182 Similar reductions in birth weight are seen with mothers who smoke, but unlike the altitude infants, the infants of mothers who smoke have higher perinatal mortality at every birth weight. This important difference indicates that effects on fetal growth can occur independently of effects on mortality,188 and also that smoking may involve other mechanisms than oxygen transport affecting fetal growth and well
   being. Small size for gestational age at sea-level is also associated with preeclampsia, maternal hypoxic lung disease,189 maternal cyanotic congenital heart disease,190 and various anemia's; all have diminished fetal oxygen/nutrient delivery as a common pathway. Unlike some of these other conditions, particularly preeclampsia, low birth weight due to high altitude (in full term infants) may not be associated with increased morbidity and mortality.
   
   In a study of women in Colorado, Moore et al observed a positive relationship between birth weight at high altitude and maternal oxygen transport.191 In contrast, at low altitude the reverse is true: the physiological anemia of pregnancy, with a reduced arterial oxygen content, is correlated with higher birth weight than those who do not develop this anemia. To help clarify the role of maternal arterial oxygen content, Moore and colleagues compared infant birth weights in women from low and high altitude who had the same maternal arterial O2 content values (Hgb X SaO2% X 1.34). For the same oxygen content, the high altitude women still had smaller infants.191 Further investigations by Zamudio et al suggested that the mechanism of intrauterine growth retardation at high altitude was perhaps in larger part due to lower uteroplacental blood flow and relative ischemia of the placenta.192 Three factors seemed to explain the decreased blood flow at high altitude: a lesser maternal blood volume increase, less uterine artery dilatation, and lack of appropriate redistribution of blood flow to the uteroplacental circulation. How hypoxia might produce these changes in unknown. The authors speculated that a common explanation for these findings could be impaired placentation, the process by which the
   placenta invades the uterus to establish its blood supply. Indeed, recent in vitro work has suggested a role for oxygen tension in the differentiation and invasion of cytotrophoblasts in the human placenta; the result of hypoxia was shallower placentation and higher vascular resistance, like that seen in preeclampsia.193 Although this finding needs to be confirmed anatomically in normal high altitude placentas, this work makes one wonder whether during placentation (9 to 12 weeks) a hypoxic exposure could be detrimental. A corollary question to consider is whether altitude exposure is advisable for lowland women with any suggestion of impaired placentation and/or fetal compromise, such as hypertension or preeclampsia, at any time during pregnancy.
   
   A second lesson to be learned from high altitude residents is that intrauterine growth retardation is not linear throughout pregnancy. Only after 32 weeks gestation does fetal growth at altitude become appreciably slowed compared to sea level.187 Does this observation mean that the otherwise healthy pregnant lowlander need not worry about the possibility of impaired fetal growth at altitude until after 32 weeks gestation? Or is the stage set for intrauterine growth retardation earlier in the pregnancy, such as during placentation, so that altitude exposure afterwards has no effect on growth? Is the intrauterine growth retardation of altitude residents even relevant to lowlanders? Without answers to these questions, it seems premature to admonish all women to avoid altitude exposure
   throughout pregnancy, as some have done because of concerns about intrauterine growth retardation.194 At the present time, we have no evidence that exposure, at least to moderate altitudes, increases risk to the healthy pregnant lowlander or her fetus.
   
   Acute ascent - the altitude sojourner
   
   Clinical and physiological investigations of pregnant lowlanders ascending to altitude are conspicuously lacking, especially to altitudes over 2500 meters. Thousands of pregnant women travel to the moderate altitude of ski resorts for recreation, and the lack of any reported adverse effects could be reassuring. On the other hand, the safety of altitude exposure during pregnancy has not been systematically evaluated. Is adding the stress of exercise (e.g., skiing) to that of hypoxia a cause for concern? The few studies available are reassuring. Artal et al. studied 7 sedentary women at 34 weeks gestation. Maximal and submaximal exercise tests were completed at sea level and 6000 ft. (1830 m) after 2 to 4 days of acclimatization.195 They reported the expected decrease in maximal aerobic work, but found no difference from sea level in submaximal endurance. Fetal heart rate responses, and maternal lactate, epinephrine, and norepinephrine levels were not changed from sea level. The reduction in peak VO2 was 13%, which is large for that altitude, and possibly related to poor conditioning. Acknowledging the small number of subjects, the authors concluded that it was safe for 3rd trimester women to engage in brief bouts of submaximal exercise at moderate altitude. Drawing similar conclusions was a study of
   twelve pregnant subjects who exercised after ascent to 2225 m. Finding no abnormal fetal heart rate responses, the authors considered the exercise at altitude benign for mother and fetus.196 The experience of the airline industry may have some bearing on altitude exposure during pregnancy. Although the exposures are brief, cumulative time at cabin altitudes up to 2500 m is high. Pregnant cabin crew are generally permitted to fly until 7 months gestation with some variance among airline companies. Untoward effects have not yet been demonstrated in this large population, though studies are continuing. In summary, the only available data, though rather
   inadequate, suggest that short-term exposure to altitudes up to 2500 m, with exercise, is safe for a lowland woman with a normal pregnancy. To ascertain whether and to what extent fetal morbidity or mortality might be affected by increasing altitude would require investigation of outcomes in a large number of pregnant women.
   
   Acute hypoxia
   
   Acute hypoxic challenge may provide information on the response of mother and fetus to altitude exposure. Human investigations have generally used hypoxic gas mixtures of known concentration of oxygen, but without control of SaO2%, PaO2, or PaCO2, and the effect on the fetus has been limited to heart rate response. Hypoxic effects have been variable, with only slight tachycardia as the usual response to moderate maternal hypoxia (12% or 15% inhaled oxygen), and a bradycardic response to more severe hypoxia (10%
   oxygen). In sheep, acute, severe hypoxia (10% oxygen), with an average maternal PaO2 of 40 mm Hg resulted in no change in uterine or umbilical blood flow, but substantial increases in fetal heart rate.197, 198 Researchers have suggested acute hypoxic gas breathing as a tool for detecting placental insufficiency and potential labor and delivery problems; fetuses with abnormal responses, such as prolonged recovery from tachycardia, were much more likely to have fetal distress in labor.199, 200 Another way to assess relative hypoxia/ischemia of the uteroplacental unit is to determine fetal response to oxygen breathing; improved physiological function with oxygen implies correction of a deficit. While no reports of this intervention could be found at high altitude, maternal hyperoxia at
   sea-level had no effect in normal pregnancy or mild preeclampsia, but caused observable physiological changes (increased heart rate, increased variability, and fetal breathing movements) in severe preeclampsia, in fetal growth retardation and in small for gestational age infants.200-202 The importance of these studies for lowland women is that they suggest that a compromised placental-fetal circulation could be unmasked at high altitude. On the other hand, in the absence of such complications, the fetus seems to tolerate a level of acute hypoxia far exceeding a moderate altitude exposure.
   
   Given the available data, it seems prudent to recommend that women with any complication of pregnancy avoid unnecessary altitude
   exposure. An ultrasound or other assessment may help to reassure the clinician and mother about the absence of the more common complications. For women with no known abnormalities, there appears to be little risk to the fetus or the mother undertaking a sojourn to an altitude at which SaO2 will remain above 85% most of the time (up to 3000 m altitude), but the data are very limited. It is not the altitude per se that determines whether the fetus becomes stressed, of course, but the maternal (and fetal) PaO2 and SaO2. A woman with high altitude pulmonary edema at 2500 m, for example, is much more hypoxemic than a healthy woman at 5,000 meters. Altitude illness, especially pulmonary edema, must be carefully avoided. Similarly, carboxyhemoglobin from smoking, lung disease and other
   problems of oxygen transport will render the pregnant patient at altitude more hypoxemic, and physiologically at a higher altitude. Whether breathing a hypoxic gas mixture could be a useful challenge test has not been evaluated. The question of the safety of modest hypoxia to the fetus and mother at different stages of pregnancy and at different altitudes (levels of hypoxia), the issue of whether persons at risk for any possible untoward effects can be identified prior to exposure, and the interaction of hypoxia with other stresses such as exercise, clearly require much more investigation. Basic science and clinical and physiological research are all necessary. Outcome studies comparing large populations of women with and without high altitude exposure during pregnancy would be especially
   useful to help the pregnant lowlander make informed decisions about potential risks of high altitude.
   
   
   181. Breathnach C. The stability of the fetal oxygen environment. Irish J of Med Science 1991; 160:189-191.
   182. Meschia G. Supply of oxygen to the fetus. The Journal of Reproductive Medicine 1979; 23:160-165.
   183. Carter A. Factors affecting gas transfer across the placenta and the oxygen supplt to the fetus. J Develop Physiol 1989; 12:305-322.
   184. Leibson C, Brown M, Thibodeau S, et al. Neonatal hyperbilirubinemia at high altitude. Am J Dis Child 1989; 143:983-987.
   185. Ballew C, Haas JD. Hematologic evidence of fetal hypoxia among newborn infants at high altitude in Bolivia. Am J Obstet Gynecol 1986;155:166-169.
   186. Beall C. Optimal birth weights in Peruvian populations at high and low altitudes. Am J Phys Anthropol 1981; 56:209-216.
   187. Unger C, Weiser JK, McCullough RE. Altitude, low birth weight, and infant mortality in Colorado. J Am Med Assoc 1988; 259:3427-3432.
   188. Wilcox AJ. Birth weight and perinatal mortality: The effect of maternal smoking. Am J Epidemiol 1993; 137:1098-1104.
   189. Templeton A. Intauterine growth retardation associated with hypoxia due to bronchiectasis. Br J Obstet Gynaecol 1977; 84:389-390.
   190. Novy M, Petersen E, Metcalf J. Respiratory characteristics of maternal and fetal blood in cyanotic congenital heart disease. Am J Obstet Gynecol 1968; 100:821-828.
   191. Moore LG, Brodeur P, Chumbe O, D'Brot J, Hofmeister SE, Monge CC. Maternal hypoxic ventilatory response, ventilation, and infant birth weight at 4,300m. J Appl Physiol 1986; 60:1401-1406.
   192. Zamudio S, Palmer SK, Droma T, Stamm E, Coffin C, Moore LG. Effect of altitude on uterine artery blood flow during normal pregnancy. J Appl Physiol 1995; 79:7-14.
   193. Genbacez O, Joslin R, Damsky C, Polliotti B, Fisher S. Hypoxia alters early gestational human cytotrophoblast
   deifferentiation/invasion in vitro and models the placental defects that occur in preeclampsia. J Clin Invest 1996; 97:540-550.
   194. Barry M, Bia F. Pregnancy and travel. J Am Med Assoc 1989; 261:728-731.
   195. Artal R, Fortunato V, Welton A, et al. A comparison of cardiopulmonary adaptations to exercise in pregnancy at sea level and
   altitude. Am J Obstet Gynecol 1995; 172:1170-1178.
   196. Baumann H, Bung P, Fallenstein F, Huch A, Huch R. Reaktion von mutter und fetus auf die Koperliche belastung in oler hohe.
   Geburtshilfe Frauenheilkd 1985; 45:869-876.
   197. Parer JT. Effects of hypoxia on the mother and fetus with emphasis on maternal air transport. Am J Obstet Gynecol 1982; 142:957-961.
   198. Greiss F. Concepts of uterine blood flow. In: Wynn R, ed. Obstetrics and Gynecology Annual. New York: Appleton-Century-Crofts,
   1973:55-83.
   199. Baillie P. Nonhormonal methods of antenatal monitoring. Clin Obstet Gynecol 1974; 1:103-122.
   200. Copher DE, Huber CP. Heart rate response of the human fetus to induced maternal hypoxia. Am J Obstet Gynecol 1967; 98:320-335.
   201. Ritchie J, Lakhani K. Fetal breathing movements and maternal hyperoxia. Br J Obstet Gynaecol.
   202. Bartnicki J, saling E. Influence of maternal oxygen administration on the computer-analysed fetal heart rate patterns in
   small-for-geastational-age fetuses. Gynecologic and Obstetric Investigation 1994; 37:172-175.

2. Niermeyer S.  The pregnant altitude visitor.  Adv Exp Med Biol 1999;474:65-77. The human fetus develops normally under low-oxygen conditions. Exposure of a pregnant woman to the hypoxia of high altitude results in acclimatization responses which act to preserve the fetal oxygen supply. The fetus also utilizes several compensatory mechanisms to survive brief periods of hypoxia. While fetal heart rate monitoring  data during air travel suggest no compromise of fetal oxygenation, exercise at high altitude may place further stress on oxygen delivery to the fetus. The limited data on maternal exercise at high altitude suggest  good tolerance in most pregnancies; however, short-term abnormalities in fetal heart rate and subsequent pregnancy complications have been observed, as well. A survey of Colorado obstetrical care providers yielded consensus that preterm labor and bleeding complications of pregnancy are the most commonly encountered pregnancy complications among high-altitude pregnant visitors. Dehydration, engaging in strenuous exercise before acclimatization, and participation in activities with high risk of trauma are  behaviors that may increase the risk of pregnancy complications. Medical and obstetrical conditions which  impair oxygen transfer at any step between the environment and fetal tissue may compromise fetal oxygenation.  Knowledge of the medical, obstetrical, and behavioral risk factors during pregnancy at high altitude can help  the pregnant visitor to high altitude avoid such complications.

3. Jensen GM, Moore LG.  The effect of high altitude and other risk factors on birthweight: independent or interactive

   effects?  Am J Public Health 1997 Jun;87(6):1003-7. OBJECTIVES: This study examined whether the decline in

        birth-weight with increasing altitude is due to an independent effect of altitude or an exacerbation of other risk

        factors. METHODS: Maternal, paternal, and infant characteristics were obtained from 3836 Colorado birth

        certificates from 1989 through 1991. Average altitude of residence for each county was determined.

        RESULTS: None of the characteristics related to birthweight (gestational age, maternal weight gain, parity,

        smoking, prenatal care visits, hypertension, previous small-for-gestational-age infant, female newborn)

         interacted with the effect of altitude. Birthweight declined an average of 102 g per 3300 ft (1000 m) elevation

        when the other characteristics were taken into account, increasing the percentage of low birthweight by 54%

        from the lowest to the highest elevations in Colorado. CONCLUSIONS: High altitude acts independently from

        other factors to reduce birthweight and accounts for Colorado's high rate of low birthweight.

4. Weigel MM, Caiza ME, Lascano Y, Barreno G, Mosquera L. Early pregnancy nausea and vomiting in a high-altitude

   Andean population. Int J Gynaecol Obstet 2000 Apr;69(1):9-21

5. Palmer SK, Moore LG, Young D, Cregger B, Berman JC, Zamudio S. Altered blood pressure course during normal pregnancy and increased preeclampsia at high altitude (3100 meters) in Colorado. Am J Obstet Gynecol 1999 May;180(5):1161-8. OBJECTIVE: Our purpose was to determine the case incidences of preeclampsia at low and high altitudes and whether maternal blood pressure course during pregnancy differs between low and high altitudes. STUDY DESIGN: This was a retrospective cohort study of pregnancies in sociodemographically matched communities  at low and high altitudes in Colorado; each community had a small hospital served by family practitioners and was  located >100 miles from major urban areas. Included were consecutive singleton pregnancies of women without chronic disease that resulted in live-born infants at >28 weeks' gestation during an 18-month period (n = 116 at 1260 m, n = 93  at 3100 m). Clinic and hospital medical records were searched and data pertaining to hypertensive complications of  pregnancy and serial blood pressure measurements were abstracted. RESULTS: Despite similar maternal risk factors, the case incidences of preeclampsia were 16% at 3100 m and 3% at 1260 m. As in sea-level pregnancies, mean blood  pressure fell until week 20 in normotensive pregnancy at 1260 m. Mean pressure rose linearly, however, in normotensive women at 3100 m and in women with preeclampsia at both 1260 m and 3100 m. High altitude acted independently of known risk factors and yielded an odds ratio for preeclampsia of 3.6 (95% confidence interval 1. 1-11.9). Birth weight was 285 g lower at 3100 m despite similar gestational ages. CONCLUSION: The normal pregnancy-associated fall in blood pressure was absent at 3100 m, even in women who remained normotensive. The incidence of preeclampsia was  increased at high altitude. Residence at high altitude interferes with the normal vascular adjustments to pregnancy, increasing the incidence of preeclampsia, and is perhaps analogous to other conditions that decrease uteroplacental oxygen delivery.

6. Ali KZ, Ali ME, Khalid ME. High altitude and spontaneous preterm birth. Int J Gynaecol Obstet 1996 Jul;54(1):11-5

7.  Huch R. Physical activity at altitude in pregnancy. Semin Perinatol 1996 Aug;20(4):303-14

8.  Hankins GD, Clark SL, Harvey CJ, Uckan EM, Cotton D, Van Hook JW. Third-trimester arterial blood gas and acid base

       values in normal pregnancy at moderate altitude. Obstet Gynecol 1996 Sep;88(3):347-50

9.  Jensen GM, Moore LG. The effect of high altitude and other risk factors on birthweight: independent or interactive effects?

   Am J Public Health 1997 Jun;87(6):1003-7

10.  Klocke DL, Decker WW, Stepanek J. Altitude-related illnesses. Mayo Clin Proc 1998 Oct;73(10):988-92; quiz 992-3

11. Kametas NA; Savvidou MD; Donald AE; McAuliffe F; Nicolaides KH.  Flow-mediated dilatation of the brachial artery in

    pregnancy at high altitude.  BJOG 2002 Aug;109(8):930-7 OBJECTIVE: Pregnancy at high altitude has been associated with

         increased prevalence of pre-eclampsia and reduced maternal oestrogen levels, factors that have been associated with

         endothelial dysfunction. The aim of this study was to examine the effect of high altitude (4370 m above sea level) on

         endothelial function during pregnancy as assessed by a non-invasive method. DESIGN: Cross-sectional study.

         SETTING: Two maternity units providing routine antenatal care: one at high altitude (District General Hospital--IPSS in

         Cerro de Pasco, Peru) and one at sea level (Instituto Materno-Perinatal in Lima, Peru). POPULATION: Sixty pregnant

         women at 6-42 weeks of gestation resident at high altitude (Cerro de Pasco, Peru, 4370 m above sea level) and 54 at

         sea level (Lima, Peru). Comparisons were performed also in 11 and 14 non-pregnant women at each altitude, respectively.

         METHODS: Endothelial function was assessed by flow-mediated dilatation of the brachial artery using high-resolution

         ultrasound. MAIN OUTCOME MEASURES: Differences in flow mediated dilatation of the brachial artery in two groups

         of pregnant women, one at high altitude and one at sea level. RESULTS: Both at high altitude and sea level flow-mediated

         dilatation of the brachial artery increased in the first two trimesters to levels 32% higher than non-pregnant controls.

         However, in the third trimester, flow-mediated dilatation of the brachial artery was lower than non-pregnant levels. Resting

         vessel size increased during pregnancy by 15% compared with non-pregnant controls at term, with no difference between

         the two populations at high and low altitude. Pregnancy at high altitude, compared with sea level, was associated with 59%

         lower baseline blood flow and 76% higher reactive hyperaemia. Similarly, non-pregnant controls at high altitude compared

         with sea level demonstrated similar flow-mediated dilatation of the brachial artery and 40% lower resting blood flow of the

         brachial artery. However, the difference in reactive hyperaemia did not reach statistical significance. CONCLUSION: These

         data suggest that, during pregnancy at high altitude, endothelial function, as assessed by flow-mediated dilatation of the

         brachial artery, is not impaired.

Heat stress

1.      Rao DL, Mittal S, Modi G. Heat stroke--a probable cause of multiple fetal anomalies. Indian J Pediatr 1995 Jul-Aug;62(4):493-5

2.      Porter KR, Thomas SD, Whitman S. The relation of gestation length to short-term heat stress. Am J Public Health 1999 Jul;89(7):1090-2. OBJECTIVES: This study examined the association between gestation length and heat exposure during the summer months of

     the Chicago heat wave of 1995. METHODS: Birth data from Illinois vital records containing 11,792 singleton vaginal births

     were analyzed to calculate mean gestational ages. RESULTS: No evidence was found to suggest an association between

     shortened gestation and increased maximum apparent temperature. CONCLUSIONS: The data propose no special precautions

     for pregnant women exposed to short-term heat stress of the intensity evaluated in this study. However, the possible effects of

     chronic heat exposure on gestation cannot be ruled out.

3.      Pirhonen JP, Vaha-Eskeli KK, Seppanen A, Vuorinen J, Erkkola RU. Does thermal stress decrease uterine blood flow in hypertensive

     pregnancies? Am J Perinatol 1994 Sep;11(5):313-6

4.     Vaha-Eskeli K, Erkkola R. The effect of short-term heat stress on uterine contractility, fetal heart rate and fetal movements at late

     pregnancy. Eur J Obstet Gynecol Reprod Biol 1991 Jan 4;38(1):9-14. The aim of the study was to determine the acute effects of

     thermal stress on maternal and fetal circulatory responses in normal and hypertensive patients. Therefore we studied 14 healthy

     pregnant women and 12 women with compromised pregnancies during short-term heat stress using color Doppler ultrasound in

    addition to conventional follow-up methods. The uterine vascular resistance increased significantly during the exposure in the

     high-risk pregnancy group without change in the control group. The results of the present study give strong support to our earlier

     studies that short-term heat stress seems to be safe in uncomplicated pregnancies but may be detrimental in high-risk pregnancies.

5.     Vaha-Eskeli KK, Erkkola RU, Seppanen A, Poranen AK, Sateri U. Haemodynamic response to moderate thermal stress in pregnancy.

     Ann Med 1991 Apr;23(2):121-6

6.      Vaha-Eskeli K, Erkkola R, Seppanen A. Is the heat dissipating ability enhanced during pregnancy? Eur J Obstet Gynecol Reprod

     Biol 1991 May 10;39(3):169-74

7.      Vaha-Eskeli K, Pirhonen J, Seppanen A, Erkkola R. Doppler flow measurement of uterine and umbilical arteries in heat stress during

     late pregnancy. Am J Perinatol 1991 Nov;8(6):385-9

1.      ACOG Committee Opinion #158—Guidelines for Diagnostic Imaging During Pregnancy

2.      Brent RL.  The effect of embryonic and fetal exposure to x-ray, microwaves, and ultrasound: counseling the pregnant and nonpregnant

     patient about these risks.  Semin Oncol 1989:16:347-368

3.      Committee on Biological Effects of Ionizing Radiation, Board on Radiation Effects Research Commission on Life Sciences,

     National Research Council.  Health effects of exposure to low levels of ionizing radiation:  BEIR V.  Washington, DC:  National Academy Press, 1990:352-370

4.      Nicholas JS, Copeland KA, Duke FE, Friedberg W, O’Brien K 3rd.  Galactic cosmic radiation exposure of pregnant flight crewmembers. 

     Aviat Space Environ Med 2000 Jun;71(6):647-8. BACKGROUND: In recommending the occupational dose limit of ionizing radiation for pregnant women, the International Commission on Radiological Protection apparently assumes that the dose to the conceptus

     from ionizing radiation exposure is about half the dose at the surface of the mother's abdomen. METHODS: To test this assumption

     with respect to galactic cosmic radiation, calculations were made using FAA computer program CARI-LF2, which calculates

     equivalent doses from galactic cosmic rays at selected depths in soft tissue at any specified location in the atmosphere or on

     user-entered flight profiles. RESULTS: The calculations showed that the equivalent dose of galactic radiation was almost the

     same at all depths. CONCLUSIONS: Thus the assumption of considerable shielding of the conceptus being provided by the

     woman's body is not correct with respect to galactic cosmic radiation, the principal type of radiation to which aircrews are exposed.

     The effective dose as calculated with FAA computer program CARI-5E, which calculates effective dose in an anthropomorphic

     phantom at any specified location in the atmosphere or on user-entered flight profiles, was found to be a good estimate of the

     equivalent dose at the depth of the conceptus.

5. Grajewski B, Waters MA, Whelan EA, Bloom TF. Radiation dose estimation for epidemiologic studies of flight attendants. Am J Ind Med 2002; 41(1):27-37. (Cosmic Radiation of Flight Attendants) CONCLUSION: Female flight attendants, working a mix of short- and long-haul flights from airports in the USA, do not receive a dangerous dose of cosmic ionizing radiation: it is less that one-tenth the recommended occupational maximum. Pregnant attendants should take advice on what flights they should work on, but any risk that there might be to the fetus is extremely small.  ABSTRACT: Over 97,000 flight attendants work in conventional aircraft cabins and may be exposed to doses of cosmic ionizing radiation that are higher than those received by the ground crew. The National Institute for Occupational Safety and Health (NIOSH) is carrying out 2 studies on the reproductive health of female flight attendants, one of which is prospective on the ovulatory function of 44 flight attendants. This paper reports a retrospective calculation of the duration and altitude of flights of these 44 attendants out of Miami and Seattle during 1992-1996.
 

1.        Backer H.  Water disinfection for international and wilderness travelers.  Clin Infect Dis 2002 Feb 1;34(3):355-64.

     Acquisition of waterborne disease is a substantial risk for international travelers to countries with inadequate sanitation

     facilities. It also poses smaller but still significant risks for wilderness travelers who rely on surface water in developed countries

     with low rates of diarrheal illness, such as the United States. This article reviews the etiology and risks associated with waterborne

     disease that might be encountered by both types of travelers. It also summarizes--and makes recommendations for--the various

     water-treatment methods available to travelers for reducing their risk of contracting waterborne disease.

2.      Khan LK, Li R, Gootnick D. Thyroid abnormalities related to iodine excess from water purification units. Peace Corps Thyroid

     Investigation Group. Lancet 1998 Nov 7;352(9139):1519.

3. Goodyer L , Behrens RH. Safety of iodine based water sterilization for travelers. J Travel Med 2000 Jan;7(1):38.

Abstract: The recent report by Khan et al. of an unexpectedly high concentration of free iodine in water filters, which may have led to the high proportion of abnormal thyroid function tests in Peace Corps workers, is of concern for travel advisors when asked to recommend suitable means of water sterilization. Many travelers use iodine based filters and/or chemicals for purification of water when traveling in areas with contaminated water supplies and may therefore be at risk of excess iodine intake. Aside from iodine impregnated resin filtration systems, tetraglycine hydroperiodide tablets, tincture of iodine 2% and more commonly, chlorine-based proprietary products are widely used to sterilize water for drinking, and usually purchased by travelers without advice on how they should be used. A single tetraglycine hydroperiodide tablet in a liter of water releases 8 mg of iodine in comparison to the 10 mg/liter released from the iodinated resin pumps described by Khan et al. Although the instructions for using iodine tincture are imprecise, the normal recommendation is 5 drops per liter of water, increasing this to 12 drops where Giardia cysts may be present. The lower of the two doses would yield about 2 mg/liter of free iodine per liter depending on the pipette used, although, because of the potassium iodide present in the formulation, a total of 4 mg iodine would be available for absorption.