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Motherisk Newsletters: Summer 1997, No. 7Summer 1997, No. 7
MISOPROSTOL - A NEW HUMAN TERATOGEN
Misoprostol (Cytotec) « is a prostaglandin-E1 (PGE1) analogue and is approved for use in preventing NSAID-induced gastrointestinal lesions and in treating duodenal and gastric ulcers. In rats, mice or rabbits, there was no evidence of adverse developmental effects independent of maternal toxicity. In Brazil where abortion is not a legal procedure, there is a widespread popular misuse of this drug in abortion attempts. Case reports of congenital anomalies after maternal use of misoprostol have been published.
Recently, the Motherisk Program in collaboration with the University of Porto Alegre and other Brazilian teratogen information services, conducted a case-control and a prospective cohort study to quantify the fetal risk of this drug, if any (1-2).
We designed a multicentre, hospital-based, analytical case-control study and hypothesized that in contrast with infants who are not diagnosed with M?bius sequence, infants with M?bius are more likely to have been born to mothers who used misoprostol in the first 9 weeks of gestation for the purpose of aborting the pregnancy. The primary objective was to compare the frequency of and report the odds ratio (OR) and 95% confidence intervals (CI95) for misoprostol use between mothers of children born and diagnosed by hospital-based clinical geneticists with M?bius sequence (cases), and mothers of Brazilian children born and diagnosed with a neural tube defect (NTD) (controls). In order to detect a relative risk of 5.0 in this population where the prevalence of misoprostol use by pregnant women is estimated to be 10%, a sample of 54 cases of M?bius sequence will be needed (2-sided a of 0.05, 90% power, 1:1 ratio of cases to controls). Ninety-four cases of M?bius sequence and 121 NTD controls were received from the Brazilian centres and analyzed in Toronto. As hypothesized, 46.7% (44/94) of infants with M?bius were exposed during the first trimester to misoprostol, whereas only 3.3% (4/121) of infants with NTD were exposed. All women who used misoprostol intended to abort their pregnancy; half using their dose orally and the remainder combining oral and vaginal routes. Preliminary unpaired analysis revealed a statistically significant OR of 25.7, CI95, 8.3 to 89.4. More than 60% of the cases involved bilateral paralysis of cranial nerve 7 (the remainder being unilateral), and paralysis of the 6th cranial nerve. In conclusion, our data suggest that gestational misoprostol use is associated with an increased risk for M?bius sequence.
The purpose of this cohort study was to compare the outcomes of pregnancies following misoprostol exposure with a matched control group. We conducted a prospective, observational cohort study with 86 exposed and 86 pair-matched, non-exposed controls. There was no significant difference in the rates of major or minor birth defects when the cases were compared with the control live births (2.9% vs 2.5% for major anomalies; relative risk [RR], 1.19; 95% confidence interval [CI] , 0, 17 to 8.23). There were significantly more miscarriages and fetal death in the exposed group (18.3% vs 5.8%; RR, 3.15, 95% CI, 1.20 to 8.27). There was no statistical difference in gestational age at delivery, birth weight or sex ratio between groups. Taken together, our studies indicate that misoprostol induces the rare M?bius sequence. However, overall, it does not increase in a major way the rates of major malformations.
AL, et al: Misoprostol use during pregnancy is associated with an
increased risk for M?bius sequence. Teratology 1997;55:36.
- Schuller L, et al: Pregnancy outcome after abortion attempt with misoprostol. Teratology 1997;55:36.
There is scarce information on fetal outcome after an accidental electric shock in pregnancy. Twenty case reports of women who had electric shock with alternating current (110, 220, and 5000 V) (1-5) and one from a taser gun (6) have been published. In 13 cases the electric current moved from hand to foot, thus crossing the uterus and potentially the fetus. Also, 6 women were wet when they had the electric shock, whereas one exhibited tetany and one had an electric burn. Fetal death occurred in 16 cases and there were only five healthy newborns. Moreover, of these 21 cases, there were 15 women who had an electric shock after 18 weeks of gestation; in seven instances an immediate cessation of fetal movement was noticed. One maternal death has also been reported. (2)
As demonstrated repeatedly in clinical teratologic studies, case reports may lead to unrealistically high perceptions of fetal risks because such reports almost always highlight adverse outcome. (7) Thus case reports cannot be used to assess true rates of fetal risk.
To date, no prospective cohort study of pregnant women who were accidentally exposed to electric shock has been reported. The possible risk factors associated with it, such as decreased skin resistance by water, the pathway of the current, or tetany has also not been addressed. (8) We have recently quantified the fetal risk after electric shock in pregnancy in women counselled by two Teratology Information Centers, the Motherisk Program and our colleagues in Vermont.
Twenty-eight women were exposed to electric shock from home appliances, with 110 (n=26) or 220 (n=2) V, between 4 and 36 weeks of gestation. Two were exposed to an electrified fence with high voltage (2000 and 8000 V) and 1 touched a telephone line with very low voltage, 12 V. In 28 cases the current did not cross the uterus, whereas in 3 cases a hand-to-foot transmission occurred, which suggests that the current could have crossed the uterus. In 14 cases women had wet hands when the electric shock occurred. Only 2 women had tetany and 1 had electric burns. There were no maternal deaths.
Twenty-eight of the pregnant women who were exposed to an electric shock were delivered of healthy newborns. One baby had a muscular-type ventricular septal defect that closed spontaneously during early childhood. There were two spontaneous abortions. The first one occurred at 6 weeks of gestation, 2 weeks after the electric shock; this woman was wet when she had the electric shock but did not have tetany, burn, or a current pathway that crossed the uterus. The second case occurred at 10 weeks of gestation, 1 week after the electric shock; this woman was not wet and did not have tetany, burn, or a current pathway that crossed the uterus. In this case the fetal death was most probably not caused by the electric shock because the postmortem examination showed a fetus of only 6 weeks' gestation. Among the controls there were 30 healthy infants; one woman had a spontaneous abortion.
There were no differences in mean birth weight or gestational age at delivery between the cohort and control groups: 3630 ▒ 413 versus 3475 ▒ 516 gm (p = 0.17) and 39.7 ▒ 1.0 and 39.5 ▒ 1.5 weeks (p = 0.45), respectively. There were also no differences between the study and control groups in rates of cesarean sections or neonatal distress: 17% versus 23% (p = 0.80) and 14% versus 10% (p = 0.96), respectively. However, the gestational age at the time of contact with Motherisk in the electric shock group was different from the time of first contact in the control group: 18.8 ▒ 10.1 versus 11.8 ▒ 4.3 weeks, respectively (p = 0.001).
When our cohort was compared with the published case reports, there were no differences in the rates of tetany, burn, decreased skin resistance by water, or maternal outcome. However, our cohort had higher rates of women with current that did not cross the uterus, had more women exposed to 110 volt electrical shock, and had more live births than the case reports. Gestational age at the time of the accident was not statistically different, but our cohort had a trend toward earlier gestational age. By trimester, we had 86% (12/14), 100% (9/9), and 100% (8/8) healthy newborns in our cohort compared with 0% (0/6), 33% (1/3), and 33% (4/12) in the reported cases in the first, second, and third trimesters, respectively (p=0.0007, 0.05, 0.01).
Our study suggests that in the typical home scenario in North America a hand-to-hand electric shock does not pose a major fetal risk. It is possible that one spontaneous abortion in our series resulted from fetal death as a result of the shock and the other one from a different cause; however, a rate of 2 cases out of 31 pregnancies is well within the expected rate of spontaneous abortions.
A distinctive difference between the published case reports and the current cohort is the pathway of electric current. In most published cases the electric current was reported to move from hand to foot, thus suggesting that the current crossed the uterus and potentially affected the fetus. In our cohort only 3 of 31 women reported a currrent pathway of hand to foot; the 28 others reported hand to hand or thigh to foot electric shock exposure. Even if not shown conclusively before, current pathway may be an important determinant of the outcome of the electric injury, thus potentially explaining the discrepancy between our cohort and the published cases. (8, 10) The profound difference between current pathways (i.e., 62% hand to foot in the published case report vs only 10% in our cohort) suggests that from a population-based perspective most cases involve exposure that is less harmful to the fetus because it does not pass through the uterus.
In addition, the women in our cohort usually had an electric shock of 110 volts, the lowest household electric currrent in North America, whereas the cases reported were mostly from Europe, involving 220 volts, which is the lowest household current available there. The impact of a twofold increase in voltage is probably not important: higher voltage does not always mean higher current (which is also dependent on the resistance of the skin), as shown by Ohm's law (V = RI, where V is the voltage, R the resistance of the skin, and I the current). (8) Furthermore, the two highest voltage injuries in our cohort, 2000 and 8000 volts, had a favourable outcome.
It would appear that the gestational age at the time of the electric injury is not important in predicting fetal risk, as shown by similar outcome in all trimesters in our cohort and in the cases published. The impact of tetany and decreased skin resistance by water on the outcome of the pregnancy are not clear but are potentially important because they are critical factors in determining the intensity of the current. (8) The only adverse outcome possibly linked to the electric shock in our cohort was in a woman who was wet.
Management of the pregnant woman after an accidental electric shock should address the well-being of both mother and fetus. Management of electric injury in the adult is controversial.(8) A potential concern for the pregnant woman in what looks like a trivial electric shock is the remote possibility of late cardiac arrhythmia. An electrocardiogram should be done in any woman who has had an electric shock of >220 volts or probably any time if she was wet, had tetany, or a current pathway that crossed the heart. (8,9) Cardiac monitoring for 24 hours should be done in any woman with abnormal initial electrocardiogram or with a history of loss of consciousness or cardiovascular disease. To detect whether the fetus is still alive, fetal heart Doppler monitoring should be done after the electric shock. Also, ultrasonography should be done if the woman had not had any performed before the accident. A Doppler assessment is suggested 2 weeks later to assess for the possibility of late fetal death. Some case reports show that fetal death may occur immediately after the electric shock; this is illustrated by the fact that in 7 of 15 cases reported after 18 weeks of gestation immediate cessation of fetal movement was noticed. However, the possibility of late death, as seen in adults, should be considered and thus a second Doppler assessment done.
- Fatovich DM. Electrical shock in pregnancy. J Emerg Med 1993;11:175-7.
- Toongsuwan S. Post mortem caesarean section following death by electrocution. Aust N Z J Obstet Gynaecol 1972;12:265-6.
- Hrozek OJ. Intrauterine death of the fetus in a mother shocked by electric current. Zentralbl Gynakol 1963;85:203-4.
- Esteve H. Avortement et ╚lectrocution: un accident de travail exceptionel. Arch Mal Prof Med Trav Sec Soc 1971;32:559-62
- Steer RG. Delayed fetal death following electrical injury in the first trimester. Aust N Z J Obstet Gynaecol 1992;32:377-8.
- Mehl LE. Electrical injury from tasering and miscarriage. Acta Obstet Gynecol Scand 1992;71:118-23.
- Koren G. Retinoid embryopathy. N Engl J Med 1986;315:262.
B, Gaudreault P, Thivierge RL, Turgeon JP. Cardiac monitoring of
children with household electrical injuries. Ann Emerg Med
- Bailey B, Gaudreault P. Low-voltage electrical injury. Ann Emerg Med 1996;28:103.
- Bruner JMR, Leonard PF. Electricity, safety, and the patient. St. Louis: Mosby-Year Book, 1989.
As the therapy for HIV infection improves and more agents become available, it is vital that medical professionals monitor the effects of these new agents in populations not studied in initial clinical trials. One such population is that of pregnant women. There is also an urgent need to provide the best information to help pregnant women make crucial decisions regarding antiretroviral therapy.
Motherisk and the Pediatric HIV Program at the Hospital for Sick Children are therefore establishing a national HIV healthline and registry for women and their families. This Canadian counselling and research program will serve pregnant women,while collecting and assessing information on fetal toxicity.
The objectives of this national effort are:
inform and counsel Canadian women, their families and health
professionals on the issues involved in HIV infections during pregnancy
and lactation, with special focus on the risks of antiretroviral therapy
- to follow-up pregnancy and pregnancy outcomes in women with HIV infections
- to establish the fetal safety/risk of antiretroviral agents and their combinations, both in terms of short term (e.g., morphology) and long-term (e.g., neurobehavioural) fetal outcome.
Canadian health professionals and programs dealing with women of reproductive age or with HIV infections are invited to contact Motherisk for more information about the HIV Healthline and Network. For more information please contact Dr. Gideon Koren, Director of the Motherisk Program. Fax: (416) 813-7562. E-mail: email@example.com
LETTERS TO MOTHERISK
January 23, 1997
To the Editor:
The article "Therapeutic Abortions due to Severe Morning Sickness; an Unacceptable Combination" (Motherisk 1996, No. 6) discusses severe hyperemesis gravidarum (HG) requiring hospitalizations, with a number of the women considering or undergoing therapeutic abortions despite wanting the pregnancies. The article mentions maternal weight loss, fetal risk, and small-for-dates infants. The article does not mention current nutritional support, which fosters weight gain and a feeling of well-being in the mother and successful outcome in the fetus. Severely malnourished pregnant women have an increased risk for spontaneous abortion. (1,2)
The response to antiemetics in women who are losing weight rapidly due to HG is generally poor. Weight loss of greater than 5% of prepregnant weight has been associated with retarded fetal growth.3 Many workers have administered total parenteral nutrition (TPN) for persisting HG, with weight gain and excellent results. (4-7)
Barclay (8) reported continuous nasoenteral bleeding in 8 women with HG, delivered down a narrow tube which had been placed distal to pylorus (after discussion with the radiologist, using minimal fluoroscopy and extra pelvic shielding) for a mean of 21 days between the 7th and 17th week. Hsu and associates (9) reported nasogastric feeding in 7 women with HG, via a fine tube passed into the stomach without x-ray. In these reports, (8,9) a commercial liquid diet was initiated in the hospital and continued at home via a portable infusion pump until an oral diet was tolerated, and resulted in weight gain and healthy babies in all women. There were occasional dislodgements and plugging of the feeding-tubes; however, although TPN has been very effective, enteral feeding is less expensive and generally safer. It appears that improvement occurred in these women because the smell and taste of food and the act of swallowing were removed, although the cause of HG is actually unknown.
With the starvation of HG, the mother metabolizes her fat reserves for energy. There is a postulated neurologic effect of ketones on the fetus in the first trimester; this may result in low intelligence in the offspring which may not be detected until age 4. (10-14) If patients are vomiting extensively, I.V. isotonic (5%) dextrose will maintain hydration and prevent oxidation of fatty acids to ketones.
Of the vitamins, folate deficiency is the most common15 and may result in neural-tube defects.
Mervyn Deitel, MD,
Artin M. Ternamian, MD,
St. Joseph's Health Centre,
University of Toronto
KH, Leader A, Deitel M. Maternal nutrition in pregnancy, Part II: The
implications of previous gastrointestinal operations and bowel
disorders. Can Med Assoc J 1981; 125:550-2.
- Leader A. Maternal Nutrition in Pregnancy, Vol. 6. Curr Prob Obstet Gynecol. Chicago: YearBook Medical Publ Inc. 1983.
S, Librach C, Cecutti A. Maternal weight loss associated with
hyperemesis gravidarum: a predictor of fetal outcome. Obstet Gynecol
- Hew RL, Deitel M. Total parenteral nutrition in obstetrics and gynecology. Obstet Gynecol 1980; 55:464-70.
MG, Esser D. Total parenteral nutrition for the treatment of severe
hyperemesis gravidarum: maternal nutritional effects and fetal outcome.
Obstet Gynecol 1988; 72:102-7.
R, Blackburn GL. Principles of hyperalimentation during pregnancy. In:
Berkowitz RL, ed. Critical Care of the Obstetric Patient. New York:
Churchill Livingston 1983: 149-63.
- Charlin V, Borghesi L, Hasbun J, et al. Parenteral nutrition in hyperemesis gravidarum. Nutrition 1993; 9:29-33.
- Barclay BA. Experience with enteral nutrition in the treatment of hyperemesis gravidarum. Nutr Clin Pract. 1990; 5:153-5.
JJ, Clark-Glena R, Nelson DK, et al. Nasogastric enteral feeding in
the management of hyperemesis gravidarum. Obstet Gynecol 1996;
JA, Brendes HW. Intelligence of children whose mothers had acetonuria
during pregnancy. In: Perinatal Factors Affecting Human Development.
Washington, D.C.: Scientific Publication No. 185, Pan-American Health
JA, Brendes HW, Nemore J. Neuropsychological deficits in children of
diabetic mothers: a report from the collaborative study of cerebral
palsy. Am. J Obstet Gynecol 1969; 105:257-68.
- Felig P. Body fuel metabolism and diabetes mellitus in pregnancy. Med Clin North Am 1977; 61:43-56.
- Paterson P, Sheath J, Taft P, et al. Maternal and fetal ketome concentrations in plasma and urine. Lancet 1967; 1:82-5.
- Galler JR. Malnutrition - a neglected cause of learning failure. Postgrad Med 1986; 80:225-9.
- Fraser JL, Watt HJ. Megaloblastic anemia in pregnancy and puerperium. Am J Obstet Gynecol 1964; 89:532-6.
Dear Dr. Koren,
Your fax of 8th July was forwarded to me by my previous employers and, at a risk of "teaching granny to suck eggs" would offer the following comments based on 30 plus years of experience in reproductive toxicology.
I would suggest that what you have observed may be equivalent to seeing the tip of an iceberg. If you contact people, such as Frank Sullivan, who have worked in or been associated with the work of Poisons Centres, you will find, at least, apocryphal evidence of the adverse consequences of the failure to administer medication. The failure to administer medication is based on fear either of causing harm to the patient (mother and conceptus) or being sued for malpractice. The latter would appear to be of great concern in North America. I wonder what would happen if someone was sued for failure to attempt medication?
I suppose the problem is the lack of information on relative risk, i.e. a numerical assessment to enable judgement of the merits of non-action against action. In many cases there is no information on risk, only an indication of hazard in which situation an appreciation of true risk is distorted by fear. The involvement of psychologists (such as Paul Slovic) in risk assessments could help attenuate the wide variations. It might also help in alleviating the fears of women (and fathers). It is surprising what they can do if given some odds to think about.
For your specific focus you may be able to attenuate this problem of accentuated perception of risk by comparing rates of adverse outcome for non medication as opposed to medication for morning sickness. You should include terminations as an adverse outcome. In this area Robert Brent must have masses of data on the outcome of pregnancy for mothers treated with Bendectin (Diebendox). To put these data in perspective for the general public you could continue the exercise by making comparisons with the outcome from uncomplicated pregnancies (= the base line) and, at the other end of the scale, following treatment with Accutane or Dioxin or even Thalidomide. For these latter three you might have difficulty finding accurate data on the number that did not have an adverse outcome or where the outcome was early death of the conceptus but, despite this, the magnitude of difference should still show.
To you this might sound trivial but, in trying to explain my work, I have found that many people can understand and compare numbers when they cannot understand words, especially medical and scientific "jargon" and the creations of the latest fashion topic in toxicology (currently, endocrine disruption).
Cambs PEl8 7XJ
January 30, 1997
Hello Dr. Koren:
I received a copy of your Motherisk newsletter. I am concerned that a conclusion was made that neither of the two terminations which you described "was due to life threatening complications of NVP". It appears that both women may have had serious cases of malnutrition... although the percent weight loss is not noted in either situation. (1-3)
I would speculate that both were close to Wernicke's enchalopathy which has been described in the world's literature, although very rarely in North America. Having done a reader survey with SHAPE Magazine on NVP in 1994 with a follow up report in 1995, TAB is certainly on many women's minds as they try to cope.
- Erick, M.A: No more morning sickness: a survival guide for pregnant women. 1993, Plume.
M.A: Take two crackers and call me in the morning! A real life guide
for surviving morning sickness. 1995 Grinnen-Barrett Publ. Co.
- Erick, M.A: Morning Sickness: Myths, miseries and management. (Video)
January 14, 1997
Dear Dr. Koren:
Just a note to thank you for your efforts producing the Motherisk Newsletter. I find the articles and the work you are doing extremely useful. I hope you will manage to find time to keep up the good work.
Alasdair Hunter, M.D.
Children's Hospital of Eastern Ontario
January 28, 1997.
I believe that the information which you impart is useful for pediatricians, family physicians and obstetricians principally, to the extent that the information is not otherwise available to them.
Regarding your lead article, "Therapeutic abortions due to severe morning sickness: an unacceptable combination", it appears to me that case finding was not in accord with ideal approaches in that it was retrospective and inherently selective of respondents. The denominator is therefore indeterminate. You ascertained four instances of therapeutic abortion for hyperemesis. The title of the article suggests that therapeutic abortion for hyperemesis is unacceptable. The text of the article suggests that hyperemesis is sometimes not treated in a timely and adequate fashion. I am sure that the latter contention is true but one cannot ascertain how often, i.e., in what proportion of instances.
I do not agree that therapeutic abortion may not in rare instances be a correct option, certainly if perceived as necessary to preserve maternal life and in some instances less urgently if the health threat to the pregnant woman is perceived as less serious but still a threat to her physical or emotional health. The mother has to be given the opportunity for an informed choice but the decision ultimately is hers alone. Thus, I believe that the comment, "an unacceptable combination" risks being construed as prejudicial, moralistic and/or of questionable scientific merit.
W.D. MacDiarmid, MD, FRCPC, FCCMG, FACP
January 7, 1997
Dear Dr. Koren:
I am writing to you with regards to your article on nausea and vomiting in pregnancy in the Motherisk Newsletter, Fall 1996; No. 6. I found the entire scenario totally distasteful and offensive. The implication that patients don't get treated with anti-emetics in pregnancy, I am sure is the exception rather than the rule, and the entire issue is singularly unhelpful. The major problem for the majority of us who look after pregnant women with severe hyperemesis is what to do when the Diclectin fails. To suggest, as your article does, that all the patient needs is Diclectin, is condescending and totally incorrect. I have had many patients over the years who have not responded to Diclectin, despite maximum use. The quandry then left is to what to use, even when gut rest and the intravenous fluids are insufficient.
Petr Landau, M.D., F.R.C.S.C.
Fredericton Medical Clinic
Reply to Letters to the Editor
Dr. Landau believes that what we describe is "distasteful and offensive". We apologize for not depicting TA and severe NVP in a nicer way, but unfortunately this is not fiction and our task is not to satisfy Dr. Landau's taste buds. This is what our patients describe. Despite Dr. Landau's submission that his patients are treated pharmacologically for NVP, many Canadian women are not, nor are most American women.
Both Ms. Erick and Dr. Deitel make excellent points regarding the importance of the woman's nutritional status. Dr. Deitel also offers a very valuable review of the adverse effects of starvation in NVP.
Dr. MacDiarmid is correct that our study, retrospective and self-selective in nature, does not allow population based estimate of the size of the issue of therapeutic abortion due to severe forms of NVP. This was not the objective of that report; rather, we wished to highlight a widely ignored complication of hyperemesis. Other research approaches are being employed by us currently to estimate the magnitude of the issue. We strongly agree that the mother has to be given an opportunity to make an informed choice, however the information provided to make such a choice must include all available pharmacological interventions. Our survey clearly shows that such information is often not given.
TESTING WOMEN FOR HIV INFECTION
Q: I am practicing in an area with many young people with high risk lifestyles. I am hesitant to talk about HIV with them because some are quite offended by it. Should all pregnant women be offered HIV screening?
Today perinatal transmission of Human Immunodeficiency Virus has become the major cause of HIV infection and death in North America. Currently, in the United States approximately 7000 HIV-positive women become pregnant each year and approximately 1000-2000 of their newborns will be HIV positive. (1) In Canada an estimated 120 infants are born to HIV-positive women annually. This estimate is based on several seroprevalence studies in women of child-bearing age. (2-12) These studies were conducted by unlinked anonymous testing of samples such as cord blood or blood spots from newborn heel pricks.
The provinces with the largest number of AIDS cases, (Ontario, Quebec and British Columbia) had seroprevalence rates of approximately 2.5, 5.6 and 3.5 per 10,000 respectively. The rates have remained almost the same in 1989-1994. The rates are higher in urban areas than rural areas. For example in Montreal the rates were 13.0- 18.4/ 10,000 compared to 0-2.4/10,000 in other regions in Quebec. In Vancouver the rate was 5.1, whereas in the rest of British Columbia it was 1.94 (9,10).
In Canada women have made up an increasing proportion of newly diagnosed HIV infections over the last few years and now account for about 20% of newly diagnosed HIV positive cases. ( 13 ) Most of these women are in the child-bearing age group. The rate of maternal-infant human immunodeficiency virus (HIV) type 1 transmission in the absence of a therapeutic intervention is between 15% and 40% (14). Between 25%-50% of all children with perinatally acquired HIV infection develop clinical acquired immunodeficiency syndrome (AIDS) within their first year, and 80% go on to develop clinical AIDS within 3-5 years. ( 15 )
The ideal way to reduce perinatal transmission of HIV is through prevention of HIV infection in women. However, inspite of educational efforts towards prevention, the rate of infection among women of child-bearing age continues to increase. Other interventions to prevent perinatal infection should be given serious thought. The AIDS Clinical Trial Group (ACTG) Protocol 076, a multicenter, phase3, randomized, placebo - controlled trial, demonstrated that peripartum zidovudine treatment reduced the rate of transmission from 25.5% to 8.3% ( 16 )
This effect was achieved with 3 phase zidovudine therapy. In the first phase, HIV positive pregnant women initiate oral zidovudine (100mg, 5 times per day) on an out patient basis at between 14 to 34 weeks of gestation and continue until the onset of labour. In the second phase, intravenous zidovudine is given during labour as a loading dose of 2mg/kg of body weight, followed by a continuous infusion of 1mg/kg of body weight per hour until delivery. In the final phase, the newborns are treated orally with zidovudine syrup at 2 mg/kg of body weight every 6 hours beginning 8 to 12 hours after birth and continuing for 6 weeks. ( 16 )
This dramatic prevention breakthrough offers both the hope of significant control of HIV infection in children and a challenge to the medical profession to implement it. The first step in this intervention strategy would be to identify HIV positive pregnant women. The controversy appears to be whether to test all pregnant women or only those women in high risk populations.
A recent study done in the United States to determine physician attitudes regarding voluntary versus mandatory status of HIV testing in pregnant women showed that, only 2/3 of the responders favoured mandatory HIV testing in all pregnant women. A persistent percentage do not offer HIV counselling or testing. ( 17 )
A standard screening regimen is assumed to consist of pretest counselling, an initial enzyme-linked immunosorbent assay (ELIZA) test for HIV, followed by duplicate repeat ELIZA tests for those testing positive. The fourth step is a confirmatory Western blot test for those with 2 of 3 positive ELIZA tests. ( 18 ) Those in the high risk population who test negative may benefit from multiple testing during pregnancy as a single screen early in pregnancy is assumed to identify only 98.1% of all HIV positive pregnant women. ( 19 )
False-positive/ False-negative Rates
The false- positive rates for both the ELIZA and the Western blot tests are extremely low, ( 20 ) and are assumed to be .15% for ELIZA and 0 for the combination testing regimen in the base case. ( 21,22 ) The false negative rates may be higher because of the time between infection and seroconversion. Overall false negative rates of 1.9% are assumed for the base case, based on an average seroconversion of 3 months and life expectancy with HIV infection of 13 years. (19)
Assuming a 17.1 per 10,000 seroprevalence of HIV positive women of the child-bearing age group (US population), voluntary screening programs including counselling for all pregnant women receiving prenatal care, and treatment for those found to be HIV positive would be equal to savings of between $154,461 and $184,423 per averted case of perinatally acquired HIV. ( 18 )
Reducing the number of HIV infected infants has more far reaching effects than the potential reduction of health care costs; there are also the humanitarian costs to be considered, the avoided grief and burden on the family or caregivers, as well as a normal life expectancy for the infant.
Several studies have looked at the willingness of pregnant women in high risk populations to participate in voluntary screening programs. Some targeted those women who reported high risk behaviours ( 23-25 ), and others offered HIV screening routinely to all pregnant women. ( 26,27 ) These studies show that screening only women who report risk factors for HIV infection is not the best approach because acceptance of screening is lower among those women and almost 50% of the HIV-positive cases found were in women who did not report risk factors for HIV infection. ( 23 ) When all pregnant women were routinely offered HIV screening after either individual or group counselling sessions, the acceptance rates for voluntary screening programs ranged between 75% and 100%. ( 26,27 )
A study conducted in Ontario showed that many mothers of infants followed in perinatal HIV programs were not aware of having been at risk of HIV infection. Therefore, even by taking a thorough history many of these mothers would not have been considered high risk. ( 28 )
Voluntary screening programs offered to all pregnant women avoid problems of discrimination and as shown in the studies mentioned, would be generally more widely accepted since less stigma may be attached when all are offered screening. The existence of a treatment strategy that significantly reduces the risk of perinatal HIV transmission should increase the likelihood of acceptance of the test and consent to treatment in both low-risk and high risk populations.
A: You should discuss the benefit of HIV testing with every patient. This discussion should mention risk factors, including illicit drug use, multiple partners and a husband/ male partner with multiple partners, encouraging women falling within these groups to be tested. Do remember that studies in Ontario show that during such discussions many women do not mention factors which put them at high risk.
Savithiri Ratnapalan, MBBS MRCP(UK)
Susan King M.D, Msc, FRCPC
Gideon Koren MD, ABMT, FRCPC
Center for Disease Control and Prevention. National HIV
serosurveillance summary ; results through 1992. US Department of
Health and Human services, Public Health Service 1994.
Coates RA, Frank JW, Arshinoff R et al. The Ontario HIV seroprevalence
study of childbearing women: results from the first year of testing.
Clinical and Investigative Medicine 1992; 1591: 1-7
Coates RA, Frank JW, Jackson L et al. The Ontario HIV seroprevalence
study of childbearing women. Can JID 1992; 3(suppl A): 16A-17A
Hankins C, Laberge C, Lapointe N, et al. HIV infection among Quebec
women giving birth to live infants. CMAJ 1990; 143:885-93 and 1991;
Hankins C, Laberge C, Lapointe N, et al. Quebec : Seroprevalence in
childbearing women, 1989-1990. Can JID 1992; 3(suppl A): 15A-16A
JohnstonL, HaaseDA, ArmsonBA, et al. HIV seroprevalence in Halifax
County, Nova Scotia. CAHR 1994, Program and Abstracts of 4th Ann Can
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