Lucijan Mohorovic Private Gynecological Practice, Labin (Albona), Croatia

1. METHEMOGLOBINEMIA AND SULFHEMOGLOBINEMIA AS INDICATORS OF MOTHER HEALTH AND FETAL DEVELOPMENT IN ECO – RISK PREGNANCY Lucijan Mohorovic Private Gynecological Practice, Labin (Albona), Croatia

3. Abstract • Pregnancy anemia is well known, however aquired methemoglo-binemia and sulfhemoglobinemia, as added factors of hypoxemia are still not sufficiently investigated in human reproduction.External toxins or other factors have influence on the level of methemogobinemia and sulfhemoglobinemia.

4. Objective • The purpose of this report is to point out the behaviour of practical opstetricians and also authors of textbooks who undervalue environmental harmful factors. Epidemiologic, laboratory and other clinical researches show a significant improvement of knowledge of complicated and uncomplicated pregnancies and the role of exogen toxic compounds and the effects of exposure on mother and fetus health. • This report has also the intention to get the oportunity to follow the health condition of mother and fetus during pregnancy and to find in time the harmful effects of environmental factors. Proper epidemiologic and laboratory investigations show that continuous and lower concentrations of inhaled products of coal burning, result in higher concentration of methemoglobin and sulfhemoglobin which have additional adverse effects on pregnancy anemia and consecutive hypoxia of mother and fetus, despite unexisting iron deficiency.

5. Discussion • The power plant TE Plomin ( Labin, Croatia) which every hour emits about 8.5 tons (18080 mg/m3) of SO2, is so geographically located that within a radius of 40 km there are no other large sources of air pollution .The burned domestic coal is caracterised by very high level of sulfur ( 9-11 % ), and high level of radioactivity, where activity of U238 is a factor 10 – 15 times greater than average for world coals. • Around the coal-fired power plant TE Plomin 1 are unprotected, average 700.000 t of crude radioactive waste, and other coal combustion products.

6. Methods • The power plant was not operational from February 19, 1989 to September 6, 1989 and this enabled research planned in two separate periods : “clean “(April 1989 to July 1989), and “dirty” (December 1989 to March 1990), when it was operational. • In the "dirty period"the daily ground level of SO2 and meteorological situations were monitored in three areas of the commune of Labin where the coal combustion power plant is located. • Blood samples were taken from every pregnant woman, three times by distance of one month between. In both periods,“clean period” (n = 138), and in the “dirty period” (n = 122), were included clinically uncomplicated and complicated pregnacies. The following parameters were analysed : hemoglobin, methemoglobin and sulfhemoglobin, urin sulfates and pH.Monitored SO2 ground level value in the “dirty” period was from 34.1 mg/m3 to maximum of 252.9 mg/m3, associated with weather conditions.

7. I. Prospective study It was also shown that there exists a significant rise of average amount of methemoglobin (r=0,73, p<=0,001) and the growth trend of sulfhemoglobin in the “dirty period”, where the linear correlation also shows statistical significance (r=0,80, p<=0,01). ( Graph 1)

8. Distribution of methemoglobin concentration in pregnant women blood samples, the level more than 1.5 g/l (10%) falls from 22.7 to 13.4 % in the “clean period” but in the dirty period” the level grows from 10.8 to 32.8 %. (Graph 4) The average weekly exposure to immissions-ground level of SO2 in the”clean period” was 17.9 weeks, but in the “dirty period “ this exposure was 32.2 weeks.

9. There exists a significant positive correlation between the growing level of methemoglobin (p< 0,01) and sulfhemoglobin (p< 0,05) and the daily ground level of SO2 in the “dirty” period. ( Graph 2)

10. It is interesting that the level of sulfate in urine significantly falls in the “clean period” (r = - 0,48 , p < 0,05), while in the“dirty period” there is a rise, but it is not statistically significant ( r = 0,41, p > 0,05).(Graph 3)

11. There also exists a significant incidence of miscarriage and stilborn babies, between the “clean” and “dirty” period (p< 0,05) which can be linked to the microregional conditions, the exposure effect of coal combustion products.(Table 1)

12. II. Retrospective study • In the period from January 01, 1987 to December 31, 1989, there were 704 pregnant women covered by research. Coal daily consumption and combustion and SO2 discharge were calculated for each individual pregnant woman in that period from the beginning to the end of pregnancy. In that period the power plant did not work many times and periodically because of break down or technical remonts. • From the results reached, a conclusion was drawn which shows that greater and longer exposure to SO2 emissions through the initial two months of pregnancy resulted in a shorter gestation (- .0914, p = .008 )and a smaller body mass of the newborn (- .080, p = .016, Pearson correlation).

13. The positive correlation coeficient between the exposition to SO2 and the diagnoses of complicated pregnancies, diagnoses in delivery and of newborn status is also statistically significant. That practically means that pregnant women who were longer and more exposed to SO2 emissions have had more health problems during the pregnancy, during the delivery and have had more health problems of newborns. (Table 2)

14. Conclusion • Systemic, today undervalued control of the mother and fetal methemoglobin level during pregnancy as result of xenobiotics, could present a new high grade indicator that in pregnant women, blood samples examination can presume and predestine effects and consequences of oxidative stress in complicated and uncomplicated pregnancies.The mother blood sample examination makes it possible to find the objective sign of eco- risk pregnancy.According to current knowledge available, the maximum permissible ground level concentration of SO2 is calculated only as a risk factor on the healthy persons. However, from the results of these investigations, it would seem imperative that in calculating the risk factor-SO2 concentration on m3 as indicator of air pollution, its effect on pregnant women, children and chronically ill persons need be taken into consideration with accentuation on long-lower and long-lasting discontinued ground level exposure. (1) • From the discontinued presence of free radicals causing oxidative stress on placental level and pregnancy complications including numerous disease states, it can be assumed that the course of pregnancy and birth can be affected by discontinued long-lasting exposure to low ground level concentration of SO2 and other coal combustion products.These facts can also inform us of the pattern of change of lipid peroxides produced in placenta). (2) These facts give an explanation that maternal exposure to environmental oxidants can increase the risk of pregnancy complications through stimulation of the formation of cell damaging lipid peroxides where increased lipid peroxidation is associated with poor birth outcome, anaemia, signs of preeclampsia and significantly elevated concentration of methemoglobin. (3)

15. Literature • 1. Mohorović L : “Impact of coal combustion products on Human reproduction in microregional conditions” Sveučilište u Rijeci, Medicinski fakultet,1991. • 2. Little RE, Gladen BC :Levels of lipid peroxides in uncomplicated pregnancy: a review of the literature, Reprod.Toxicol.1999 Sept.Oct;13(5):347-52 • 3.Tabacova S, Balabaeva L,Little RE : Maternal exposure to exogenous nitrogen compounds and complications of pregnancy. Arch EnvirronHealth, 1997, Sep-Oct ; 52(5):341-7

16. Washington, September 8-11, 2001