Motherisk Newsletters: Spring 2002, No. 14

• Biochemical tests show relationship between environmental tobacco smoke and the risk of SIDS
• Motherisk Lab conducts meconium testing for prenatal exposure to alcohol
• Use of atypical antipsychotics during pregnancy linked to risk of neural tube defects in infants
• Decreased infections in nursing infants may be related to natural antibacterial molecule recently found in human milk
• Koren, Rovet and Ungar awarded New Emerging Team (NET) Grant
• Motherisk studies rate of immunity to toxoplasmosis among veterinary workers
• Motherisk to host CFP Accredited Workshop - November 13, 2002

Biochemical tests show relationship between environmental tobacco smoke and the risk of SIDS

Researchers at The Hospital for Sick Children, the University of Toronto and the University of Maryland have shown the relationship between environmental tobacco smoke and the risk of sudden infant death syndrome (SIDS) using biochemical tests. Higher concentrations of nicotine were found in the lungs of SIDS victims compared with infants whose deaths were not attributed to SIDS, regardless of whether smoking was reported by the parents or not. This research is reported in the February issue of The Journal of Pediatrics.

Studies have documented that smoking during pregnancy and after birth are two major and independent risk factors for SIDS. However, past studies on SIDS and smoking have relied on parental reports. There is evidence that families may not volunteer accurate information about cigarette smoking probably because of guilt, perception of fetal risk, or litigious fear. This research was the first to use objective, biochemical tests (concentrations of nicotine in lung tissue) to look at the correlation between smoking and SIDS deaths.

"This research shows that a baby's exposure to second-hand smoke during the postnatal period (up to six months) is a risk factor for SIDS," said Dr. Gideon Koren, the study's principal investigator, a senior scientist in The Hospital for Sick Children Research Institute and a professor of Paediatrics, Pharmacology, Pharmacy and Medicine and Medical Genetics at the University of Toronto.

Environmental tobacco smoke (ETS), also known as second-hand smoke, has greater amounts of ammonia, benzene, carbon monoxide, nicotine, and carcinogens such as nitrosamines in contrast with mainstream smoke. Since the lung is the port of entry for environmental tobacco smoke, the measurement of nicotine levels in lung tissue indicates the baby's exposure to smoke after birth. "We now need to improve the use of biological markers of exposure to toxic substances when we try to determine the risk of SIDS and other paediatric conditions. Such techniques will help define why some babies are affected while others are not," added Dr. Koren, who is also a holder of a Canadian Institutes of Health Research Senior Investigator Award. This research was supported by the Canadian Institutes of Health Research, the Brain and Tissue Bank for Developmental Disorders (funded by the National Institute of Child Health and Human Development in the United States), the Canadian Foundation for the Study of Infant Deaths, and The Hospital for Sick Children Foundation.

Motherisk Lab conducts meconium testing for prenatal exposure to alcohol

Prenatal exposure to alcohol can lead to Fetal Alcohol Syndrome (FAS) and Alcohol Related Neurodevelopmental Disorder (ARND) -- leading causes of preventable brain damage in children. Children with FAS and ARND suffer physical and neurological damage, severe learning disabilities, and life-long behavioural problems.

Together, FAS and ARND affect nearly 1% of all children in Canada, yet only a fraction of these children is properly assessed. Some are misdiagnosed with conduct disorders, but most go undiagnosed. Those who eventually find their way to FAS/ARND specialists are often not seen until major problems have occurred -- problems that will lead many to failure in school, trouble with the law, inappropriate sexual behaviour, depression, homelessness and a renewed cycle of alcohol and drug dependence.

Only early diagnosis and treatment can save these kids from the burden of FAS and ARND before it takes hold of their lives. That's why the Motherisk Laboratory for Drug Exposure has developed a screening test using meconium - baby's first stool after birth.

How does it work?

Meconium samples (collected directly from diapers) are analyzed for the presence of alcohol by-products called fatty acid ethyl esters (FAEE). Minimal amounts of FAEE are found in the meconium of neonates who were not exposed to alcohol before birth. Significantly greater amounts of FAEE are found in the meconium of neonates who were exposed to alcohol before birth.

How long does it take to get the test results?

It takes two days to complete the analysis of a single meconium sample. However, samples are tested in batches. Depending on the number of samples received, a new batch may be tested every one or two weeks.

What are the advantages of meconium testing?

Since meconium starts forming during the second trimester of pregnancy, it provides information about alcohol exposure during the second and third trimesters.

What are its limitations?

Meconium testing cannot pinpoint the specific time (day, week or month) during the pregnancy when the drinking occurred. Also, we do not currently know the correlation between the number of drinks the mother had during pregnancy and the concentration of FAEE found in the meconium.

What does it cost?

The fee for meconium analysis may vary if you submit several samples at the same time. For information please contact 1-877-FAS-INFO (1-877-327-4636).

The Motherisk Lab offers other neonatal screening for prenatal exposure to a wide variety of drugs. The Lab's Specialized Hair Testing for newborns can detect prenatal exposure to amphetamines, barbiturates, cannabis, cocaine, nicotine, opiates, phencyclidine and more. Call the Motherisk Alcohol and Substance Use Helpline for details.

Use of atypical antipsychotics during pregnancy linked to risk of neural tube defects in infants.

A common adverse effect of the new antipsychotic drugs is various degrees of weight gain. Maternal adiposity during pregnancy is associated with an increased risk of neural tube defects (NTD). After encountering a case of NTD in a woman with schizophrenia receiving olanzepine who gained weight excessively, we wished to assess the folate status of patients with schizophrenia receiving atypical antipsychotic drugs.

Study Participants

Seventy randomly selected in-patients and outpatients (25 women) with schizophrenia and schizoaffective disorder on a single antipsychotic medication for more than three months. They received olanzapine (18), clozapine (17) risperidone (14), and other antipsychotics.

Methods

Body weight, body mass index (BMI), daily folate intake and folate serum concentrations were determined. Serum folate was compared between men and women, and between the study group and 540 general hospital patients. Correlations between serum folate among psychiatric patients and folate intake, body weight, age and other factors were determined.

Results

The psychiatric patients had a mean body weight of 84.2 ± 21 kg (range 52-167, median 79.2). Their mean daily folate intake was 278 ± 194 mcg (range 39-1174, median 249) (n=37). Only 8/37 (22%) had intake above 400 mcg/d, shown to be protective against NTD. Mean serum folate was 23.2 ± 12 nmol/L (range 5.7-58.4; median 20.7), significantly lower than general hospital patients (35.8 ± 30 nmol/L) (P=0.0005). There were no differences between women and men. Folate intake correlated with serum folate levels. (r=.51 p=.001).

Conclusion

The vast majority of psychiatric patients were overweight and had folate intake and serum concentrations associated with increased risk for NTD.

References

1. Mossman D, Lehrer DS: Conventional and atypical antipsychotics and the evolving standard of care. Psychiatr Serv 2000; 51(12): 1528-35.
2. Kapur S, Remington G: Atypical antipsychotics. Patients value the lower incidence of extrapyramidial side effects. Bmj 2000l 321 (7273): 1360-1.
3. Blackburn GL: Weight gain and antipsychotic medicaton. J Clin Psychiatry 2000; 61 (Suppl 8): 36-41; discussion 42.
4. Green AI, Patel JK, Goisman RM, Allison DB, Blackburn G: Weight gain from novel antipsychotic drugs: need for action. Gen Hosp Psychiatry 2000; 22(4): 224-35.
5. Taylor DM, McAskill R: Atypical antipsychotics and weight gainÑa systematic review. Acta Psychiatr Scand 2000; 101 (6): 416-32.
6. Werler MM, Louik C, Shapiro S, Mitchell AA: Pre-pregnancy weight in relation to risk of neural tube defects. JAMA 1996; 275: 1089-92.
7. Shaw GM, Velie EM, Schaffer D: Risk of neural tube defect-affected pregnancies among obese women. JAMA 1996; 275: 1093-6.
8. Shaw GM, Todoroff K, Finnell RH, Lammer EJ: Spina bifida phenotypes in infants or fetuses of obese mothers. Teratology 2000; 61: 376-81.
9. Statistics-Canada: National Population Health Survey Overview 1994-95, Statistics Canada, 1995, pp. 1-17.
10. Goldstein DJ, Carbin LA, Fung MC: Olanzapine-exposed pregnancies and lactation; early experience. J Clin Psychopharm 2000; 20: 399-403.
11. Stones SC, Sommi RW, Rasken PA, Anya I, Vaughn J: Clozapine use in two full term pregnancies. J Clin Psychiatr 1997; 58: 364-5.
12. Mukherjee S, Decina P, Bocola V, Saraceni F, Scapicchio PL: Diabetes mellitus in schizophrenic patients. Compr Psychiatry 1996; 37(1): 68-73.
13. Dixon L, Weiden P, Delahanty J, Goldberg R, Postrado L, Lucksted A, Lehman A: Prevalence and correlates of diabetes in national schizophrenia samples. Schizophr Bull 2000; 26(4): 903-12.
14. Henderson DC, Cagliero E, Gray C, Nasrallah RA, Hayden DL, Schoenfeld DA, Goff DC: Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: A five-year naturalistic study. Am J Psychiatry 2000; 157(6): 975-81.

PMID: 11772703 [PubMed - indexed for MEDLINE]

Decreased infections in nursing infants may be related to natural antibacterial molecule recently found in human milk

Feeding with mother's milk is a biological standard in mammalian newborns. In humans, exclusive breastfeeding of 4-6 months (or longer) is the present norm [1]. It has been long known that breastfeeding is associated with decreased chance of infection in the nurslings [1,2,3].

The protecting effects of breast milk against infection are best illustrated in necrotizing enterocolitis (NEC) of premature newborns, which occurs even in state-of-the-art neonatal intensive care units [4]. Lucas and Cole [4] examined the relation between feeding practice and the incidence of NEC in a randomized, multicenter study, involving more than 900 infants. Supporting the previous anecdotal reports on preventive effects of breast milk, these authors found that NEC was 10 times less common in babies fed breast milk only, when compared to those who were formula fed [4].

There are multiple factors in human milk, which incapacitate bacteria. In searching for a novel, heat-stable, antimicrobial factor present in human milk [5], we have recently found that the human mammary gland expresses an antimicrobial peptide, known as human BETA-defensin-1 [6]. This small protein is seen on tissue surfaces such as the airway and intestinal mucosa, contributing to the innate immunity of the body. Our prediction that human milk contains significant amounts of the protein was confirmed by other researchers.

References

1. Work group on breastfeeding [American Academy of Pediatrics]. Breastfeeding and the use of human milk. Pediatrics 1997;100:1035-1039.
2. Cunningham AS, Jelliffe DB, Jelliffe EFP. Breast-feeding and health in the 1980s: a global epidemiologic review. J Pediatr 1991;118:659-66.
3. Ruiz-Palacios GM, Calva JJ, Pickering LK, Lopez-Vidal Y, Volkow P, Pezzarossi H, West MS. Protection of breast-fed infants against Campylobacter diarrhea by antibodies in human milk. J Pediatr 1990;116:707-13.
4. Lucas A, Cole TJ. Breast milk and neonatal necrotising enterocolitis. Lancet 1990;336:1519-1523.
5. Ruth A. Lawrence. Host-resistance factors an dimmunologic significance of human milk. In: Breastfeeding. R.A. Lawrence. Mosby (St. Loius. MO, USA). 1994. p149-180.
6. Tunzi C, Harper PA, Bar-Oz B, Valore E, Semple JL, Watson-MacDonell J, Ganz T, and Ito S. b-defensin expression in human mammary gland epithelia. Ped Res 2000;48:30-35.

PMID: 10879797 [PubMed - indexed for MEDLINE]

Koren, Rovet and Ungar awarded New Emerging Team (NET) Grant

The CIHR Institute of Neurosciences, Mental Health and Addiction (INMHA) has announced its support for two new research groups under the New Emerging Team (NET) grant program.

HSC scientists Dr. Gideon Koren (Population Health and Motherisk), Dr. Joanne Rovet (Brain and Behavior) and Dr. Wendy Ungar (Population Health), together with scientists at Queens University and the University of Western Ontario are among the NET grant recipients. This multidisciplinary team will study oxidative damage to the brain caused by Fetal Alcohol Syndrome (FAS), as well as identify and validate reliable biomarkers for prenatal ethanol exposure. The term of the NET grant is 5 years, at $250,000 per year.

"This is very exciting for us, as it is the first time that a group grant is totally dedicated to the study of Fetal Alcohol Syndrome," said Dr. Koren. "Every year, FAS and related disorders are causing thousands of Canadian children to be developmentally delayed. The cost to society is staggering, while the impact on the quality of life of nearly 1% of CanadaÕs paediatric population is devastating."

Motherisk is focusing much of its research and counseling efforts on FAS. In late April the Motherisk Program will launch a national training program for physicians in the diagnosis of FAS.

Motherisk studies rate of immunity to toxoplasmosis among veterinary workers The poster advertising toxoplasmosis testing at the OVMA Annual conference and Tradeshow raised a few eyebrows.

Motherisk researchers collected more than 160 blood samples and questionnaires during a recent three-day conference of the Ontario Veterinary Medical Association.

How will these blood samples save a cat? Although most of the medical literature shows that humans are more likely to contract toxoplasmosis through ingestion of raw infected meat than through cats, women often ask whether it is safe to keep a cat during pregnancy.

The risk to pregnant women depends on whether they have previously acquired immunity. Since veterinary employees are continuously exposed to cats, Motherisk and the OVMA are conducting a study to determine the rate of immunity to toxoplasmosis among veterinary workers.

Participants will receive their results directly from Motherisk within four to six weeks.

Click here for more information about toxoplasmosis.

MOTHERISK UPDATE 2002 ACCREDITED BY COLLEGE OF FAMILY PHYSICIANS

On November 13, 2002 the Motherisk Program will host Motherisk Update 2002.
This one-day workshop will be held at The Hospital for Sick Children, Main Auditorium, 1st Floor, 555 University Ave., Toronto.

Motherisk Update 2002 was developed to share Motherisk's latest research and clinical insights into the risk and/or safety of drugs, chemicals, diseases and other exposures during pregnancy and lactation. The program will offer physicians, nurse practitioners, pharmacists and other health care providers, a unique opportunity for professional update and development in this sensitive and rapidly growing field.

This program meets the accreditation criteria of the College of Family Physicians of Canada and has been accredited for 7.0 MAINPRO^®-M1 credits.

The program includes findings in maternal-fetal toxicology concerning:

• Treatment of chronic diseases in pregnancy
• Alcohol and substance use in pregnancy
• Maternal medication while breastfeeding
• Nausea and vomiting of pregnancy

MOTHERISK UPDATE 2002 PROGRAM