Washing our hands of the congenital cytomegalovirus disease epidemic
© Cannon and Davis; licensee BioMed Central Ltd. 2005
Received: 09 December 2004
Accepted: 20 June 2005
Published: 20 June 2005
Each year in the United States, an estimated 40,000 children are born with congenital cytomegalovirus (CMV) infection, causing an estimated 400 deaths and leaving approximately 8000 children with permanent disabilities such as hearing or vision loss, or mental retardation. More children are affected by serious CMV-related disabilities than by several better-known childhood maladies, including Down syndrome, fetal alcohol syndrome, and spina bifida.
Congenital CMV is a prime target for prevention not only because of its substantial disease burden but also because the biology and epidemiology of CMV suggest that there are ways to reduce viral transmission. Because exposure to the saliva or urine of young children is a major cause of CMV infection among pregnant women, it is likely that good personal hygiene, especially hand-washing, can reduce the risk of CMV acquisition. Experts agree that such measures are likely to be efficacious (i.e., they will work if consistently followed) and the American College of Obstetricians and Gynecologists recommends that physicians counsel pregnant women about preventing CMV acquisition through careful attention to hygiene. However, because of concerns about effectiveness (i.e., Will women consistently follow hygienic practices as the result of interventions?), the medical and public health communities appear reluctant to embrace primary CMV prevention via improved hygienic practices, and educational interventions are rare. Current data on the effectiveness of such measures in preventing CMV infection are promising, but limited. There is strong evidence, however, that educational interventions can prevent other infectious diseases with similar transmission modes, suggesting that effective interventions can also be found for CMV. Until a CMV vaccine becomes available, effective educational interventions are needed to inform women about congenital CMV prevention.
Perhaps no single cause of birth defects and developmental disabilities in the United States currently provides greater opportunity for improved outcomes in more children than congenital CMV. Given the present state of knowledge, women deserve to be informed about how they can reduce their risk of CMV infection during pregnancy, and trials are needed to identify effective educational interventions.
The history of public health in twentieth century America is replete with successes in the prevention of birth defects and childhood disabilities. Vaccines have virtually eliminated polio, congenital rubella syndrome, and Haemophilus influenzae meningitis [1–3]. Educational efforts aimed at preventing fetal alcohol syndrome have reduced maternal alcohol consumption during pregnancy . Prenatal vitamins and folic acid fortification of cereals have lowered rates of neural tube defects , while antiretroviral treatments have caused the occurrence of mother-to-child human immunodeficiency virus (HIV) transmission to plummet . Notably absent from the list of successes, however, is the prevention of congenital cytomegalovirus (CMV) disease .
CMV and congenital CMV disease
As with other human herpesviruses, initial infection by CMV (also known as primary infection) is followed by the establishment of lifelong latent infection, from which periodic reactivation is common [10, 11]. Symptoms are usually absent during primary infection and reactivation, but CMV is shed in various bodily secretions, particularly urine and saliva . CMV excretion can be continuous or intermittent, generally lasting several weeks in adults but often continuing for months or years in young children [13–15]. CMV infection is widespread, with estimates of CMV seroprevalence in the United States ranging from 40% to 80% [16–18].
CMV is transmitted person-to-person via close non-sexual contact, sexual activity, breastfeeding, blood transfusions, and organ transplantation . CMV has not been shown to be transmitted via respiratory secretions or aerosolized virus. For the pregnant woman, the most likely source of infection may be contact with the urine or saliva of young children, especially her own children [19, 20].
Reducing the burden of congenital CMV disease
Of all the ways to fight congenital CMV disease, the development of a vaccine is viewed as the most promising. Considerable progress has been made over the last 30 years, but insufficient interest by vaccine manufacturers (Stanley Plotkin, personal communication) and technical challenges make it is uncertain when a vaccine will become available . Avenues for improving outcomes in congenitally infected children have also been explored, including anti-CMV therapies (e.g., ganciclovir) for seriously infected infants [25, 26] and supportive care, such as hearing screening, language therapy, and special education [27, 28]. In contrast, insufficient emphasis has been given to preventing CMV infection in pregnant women. While women may be infected via several routes, the remainder of this article focuses on preventing transmission via the important child-to-mother route, by encouraging hygienic practices such as frequent hand washing.
Preventing CMV infection through hygienic practices
Why the ambivalence toward hygienic practices? Studies have shown that transmission of CMV via the urine and saliva of children is a major cause of infection among pregnant women [19, 20]. In addition, more than 100 years of evidence conclusively demonstrates that hand washing reduces risk of infection for a wide range of pathogens . Thus, nearly everyone would agree that, in theory, hand washing can prevent CMV infection because hands are an important vehicle for transmission. The concern, then, is not the efficacy of hygienic practices (i.e., Will they work if consistently followed?) but, instead, the effectiveness of interventions to promote them (i.e., Will women consistently follow hygienic practices as the result of interventions?).
It is important to recognize the implications of the consensus that hygienic practices are efficacious for preventing CMV transmission. Individual women have the right to know that, under ideal conditions, risk of child-to-mother CMV transmission can be reduced by proper hygienic practices. This is equivalent to the ethical obligation to inform individuals that, under ideal conditions, safer sexual practices will reduce the risk of acquiring HIV. This obligation is independent of whether any particular educational program or intervention is effective. All women of childbearing age, whether they are CMV seropositive or seronegative, carry some risk of new CMV infection during pregnancy and thus should be informed of hygienic practices that reduce that risk. As Revello and Gerna aptly remind us, "...withholding information on possible medical interventions is unethical (and legally risky)" . The terrible burden of congenital CMV disease (Figure 1) should make the provision of such information a priority.
As there is consensus on the efficacy of hygienic practices in preventing CMV transmission, the next step is to evaluate the effectiveness of educational interventions in preventing CMV transmission. Current evidence of effectiveness is promising, but limited. In one study, after non-pregnant women were educated about CMV prevention, hygienic practices improved . In a small study of Houston families, Demmler and colleagues found that behavioral changes prevented transmission of CMV (unpublished report described in Yow and Demmler ). Adler and colleagues studied the effectiveness of hygienic practices in a randomized, controlled trial of 39 seronegative, non-pregnant women with young children who were shedding CMV . Although the study was underpowered to detect significant differences in infection rates between the intervention and control groups (and thus the intervention was deemed unsuccessful by some), seroconversion rates decreased as CMV education and support increased. Furthermore, in the same study, 14 pregnant women were educated regarding hygienic practices and then followed for comparison with the randomized groups; none of the women seroconverted – a significant difference compared with the randomized groups. A more recent study also reported that pregnant women who received an intervention involving hygienic practices were significantly less likely to acquire CMV infection than were non-pregnant women .
More conclusive evidence of effectiveness can be found in the literature on community-based interventions for the prevention of other infectious diseases with similar transmission modes. For example, a meta-analysis found that community intervention trials that encouraged washing hands with soap reduced the risk of diarrheal diseases by 47% . Hand-washing programs reduced respiratory illness among military recruits  and children in daycare , and interventions involving hand sanitizers reduced absenteeism among elementary school teachers and children . An in-depth review of the literature would be useful for determining the key factors associated with the success of these and other community interventions.
Although all women of childbearing age deserve to be informed about CMV, interventions for preventing CMV transmission are most likely to be effective for pregnant women, who tend to be highly motivated, often changing behavior to protect the health of their developing fetuses. As a case in point, 25% of low-income smokers spontaneously quit smoking during pregnancy ; this percentage is higher than that achieved by most smoking cessation programs . Studies by Adler and colleagues suggest that motivation for avoiding CMV infection is considerably higher among pregnant than non-pregnant women [31, 41].
In sum, the evidence to date gives every indication that effective interventions can be found for preventing CMV infection among pregnant women. Thus, the paradigm must shift from wondering whether such interventions will be effective to developing and evaluating interventions until effective ones are identified.
Given the consequences of allowing the congenital CMV disease epidemic to continue unabated, it is imperative that women receive the educational message about congenital CMV disease prevention (see http://www.cdc.gov/cmv) . Promotion of this message could translate years of careful CMV research into an immediate public health benefit. Encouraging hygienic practices would be relatively inexpensive (requires no laboratory testing or additional doctor visits), ethically responsible (allows women to make informed decisions), and likely to prevent disabilities and save lives. Based on studies of the economic impact of future CMV vaccines, which estimate savings of $50,000 per quality adjusted life-year saved , it is likely that CMV education efforts would provide a highly favorable cost-benefit ratio as well. CMV educational messages should emphasize hygienic practices as a precaution for all women who are pregnant or planning to become pregnant, and reasonable but not extreme measures for minimizing risk during interactions with young children (Figure 3). In many instances, a CMV education message could build upon and strengthen other public health messages about infection prevention through improved hand hygiene. Once effective hand-hygiene messages are identified, more ambitious goals might also be considered, such as prevention of sexual transmission or transmission between children in daycare.
Enlisting the support of healthcare providers to convey the gravity of CMV infection and the importance of good hygienic practices is crucial. Healthcare providers have many opportunities to provide women with such information, such as during annual gynecological exams or well-baby visits as women accompany their children to the pediatrician's office. Other steps, such as community education by healthcare providers (including information sessions with daycare directors, daycare providers, and parents) and provision of information by the Public Health Service and other professional organizations, can supplement the healthcare provider's information . Success in delivering the message will depend on the active involvement of all relevant healthcare professionals.
In addition, trials are needed to identify effective community-based interventions for preventing CMV transmission to pregnant women. These trials will be important for quantifying the effectiveness of the proposed hygienic practices and for assessing the proportion of CMV infections that result from child-to-mother transmission as opposed to other routes, such as sexual transmission. However, such trials should not delay nor hinder the educational effort, just as we would not wait to inform skydivers about the prudence of parachute use because the results of controlled trials are not yet in. "As with many interventions intended to prevent ill health, the effectiveness of parachutes has not been subjected to rigorous evaluation by using randomised controlled trials...[One option] is that we accept that, under exceptional circumstances, common sense might be applied when considering the potential risks and benefits of interventions [our emphasis]." Common sense tells us that avoiding CMV-laden secretions will prevent transmission and that the potential benefits of educational interventions far outweigh the potential risks.
Although an effective CMV vaccine would be ideal and vaccine development deserves increased support, hope for a vaccine tomorrow should not stand in the way of a vigorous educational message today. Prevention through improved hygienic practices will not be easy, but washing our hands of the problem by staying the present course guarantees that each year in the United States, hundreds of children will die and thousands of others will swell the ranks of CMV-affected children growing up with serious disabilities. Just as the medical and public health communities are successfully meeting the challenges posed by polio, rubella, HIV, and neural tube defects, now is the time to meet the congenital CMV challenge head on by making awareness and prevention high priorities.
Each year in the United States, congenital CMV
causes an estimated 400 deaths
leaves more than 8000 children with permanent disabilities such as hearing or vision loss, or mental retardation
Exposure to the saliva or urine of young children is a major cause of CMV infection among pregnant women.
Risk of CMV infection is likely to be reduced by careful attention to good personal hygiene, especially hand-washing.
Women should be informed about how to reduce their risk of CMV infection during pregnancy.
Trials are needed to identify educational interventions that are effective in preventing CMV infection.
We thank Larry Anderson, Pamela Buchalter, Gail Demmler, Sheila Dollard, Philip Pellett, Stanley Plotkin, Scott Schmid, Stephanie Staras, and Laura Wagner for helpful discussions and comments.
This research was supported in part by an appointment (KFD) to the Research Participation Program at the Centers for Disease Control and Prevention, National Center for Infectious Diseases, Division of Viral and Rickettsial Diseases administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the CDC.
- Centers for Disease Control and Prevention: Progress toward global eradication of poliomyelitis, 2002. MMWR Morb Mortal Wkly Rep. 2003, 52: 366-369.Google Scholar
- Watson JC, Hadler SC, Dykewicz CA, Reef S, Phillips L: Measles, mumps, and rubella--vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 1998, 47: 1-57.PubMedGoogle Scholar
- Centers for Disease Control and Prevention: Progress toward elimination of Haemophilus influenzae type b invasive disease among infants and children--United States, 1998-2000. MMWR Morb Mortal Wkly Rep. 2002, 51: 234-237.Google Scholar
- Hankin JR: Fetal alcohol syndrome prevention research. Alcohol Res Health. 2002, 26: 58-65.PubMedGoogle Scholar
- Centers for Disease Control and Prevention: Spina bifida and anencephaly before and after folic acid mandate--United States, 1995-1996 and 1999-2000. MMWR Morb Mortal Wkly Rep. 2004, 53: 362-365.Google Scholar
- Sullivan JL, Luzuriaga K: The changing face of pediatric HIV-1 infection. N Engl J Med. 2001, 345: 1568-1569. 10.1056/NEJM200111223452111.View ArticlePubMedGoogle Scholar
- Yow MD, Demmler GJ: Congenital cytomegalovirus disease--20 years is long enough. N Engl J Med. 1992, 326: 702-703.View ArticlePubMedGoogle Scholar
- Institute of Medicine(U.S.) Committee to Study Priorities for Vaccine Development: Vaccines for the 21st Century: A Tool for Decision making. 2000, Washington D.C., National Academy Press, 460-Google Scholar
- Dobbins JG, Stewart JA, Demmler GJ: Surveillance of congenital cytomegalovirus disease, 1990-1991. Collaborating Registry Group. Mor Mortal Wkly Rep CDC Surveill Summ. 1992, 41: 35-39.Google Scholar
- Alford CA, Stagno S, Pass RF, Britt WJ: Congenital and perinatal cytomegalovirus infections. Rev Infect Dis. 1990, 12 Suppl 7: S745-S753.View ArticlePubMedGoogle Scholar
- Brown HL, Abernathy MP: Cytomegalovirus infection. Semin Perinatol. 1998, 22: 260-266.View ArticlePubMedGoogle Scholar
- Stagno S: Cytomegalovirus. Infectious diseases of the fetus and newborn infant. Edited by: Remington JS and Klein JO. 2001, Philadelphia, W.B. Saunders Company, 389-424.Google Scholar
- Zanghellini F, Boppana SB, Emery VC, Griffiths PD, Pass RF: Asymptomatic primary cytomegalovirus infection: virologic and immunologic features. J Infect Dis. 1999, 180: 702-707. 10.1086/314939.View ArticlePubMedGoogle Scholar
- Pass RF, Stagno S, Dworsky ME, Smith RJ, Alford CA: Excretion of cytomegalovirus in mothers: observations after delivery of congenitally infected and normal infants. J Infect Dis. 1982, 146: 1-6.View ArticlePubMedGoogle Scholar
- Noyola DE, Demmler GJ, Williamson WD, Griesser C, Sellers S, Llorente A, Littman T, Williams S, Jarrett L, Yow MD: Cytomegalovirus urinary excretion and long term outcome in children with congenital cytomegalovirus infection. Congenital CMV Longitudinal Study Group. Pediatr Infect Dis J. 2000, 19: 505-510. 10.1097/00006454-200006000-00003.View ArticlePubMedGoogle Scholar
- Montgomery JR, Mason EOJ, Williamson AP, Desmond MM, South MA: Prospective study of congenital cytomegalovirus infection. South Med J. 1980, 73: 590-3, 595.View ArticlePubMedGoogle Scholar
- Murph JR, Souza IE, Dawson JD, Benson P, Petheram SJ, Pfab D, Gregg A, O'Neill ME, Zimmerman B, Bale JFJ: Epidemiology of congenital cytomegalovirus infection: maternal risk factors and molecular analysis of cytomegalovirus strains. Am J Epidemiol. 1998, 147: 940-947.View ArticlePubMedGoogle Scholar
- Stagno S, Dworsky ME, Torres J, Mesa T, Hirsh T: Prevalence and importance of congenital cytomegalovirus infection in three different populations. J Pediatr. 1982, 101: 897-900.View ArticlePubMedGoogle Scholar
- Pass RF, Hutto C, Ricks R, Cloud GA: Increased rate of cytomegalovirus infection among parents of children attending day-care centers. N Engl J Med. 1986, 314: 1414-1418.View ArticlePubMedGoogle Scholar
- Adler SP: Cytomegalovirus and child day care: risk factors for maternal infection. Pediatr Infect Dis J. 1991, 10: 590-594.View ArticlePubMedGoogle Scholar
- Stagno S, Whitley RJ: Herpesvirus infection of pregnancy. N Engl J Med. 1985, 313: 1270-1274.View ArticlePubMedGoogle Scholar
- Preece PM, Blount JM, Glover J, Fletcher GM, Peckham CS, Griffiths PD: The consequences of primary cytomegalovirus infection in pregnancy. Arch Dis Child. 1983, 58: 970-975.View ArticlePubMedPubMed CentralGoogle Scholar
- Stagno S, Pass RF, Cloud G, Britt WJ, Henderson RE, Walton PD, Veren DA, Page F, Alford CA: Primary cytomegalovirus infection in pregnancy. Incidence, transmission to fetus, and clinical outcome. JAMA. 1986, 256: 1904-1908. 10.1001/jama.256.14.1904.View ArticlePubMedGoogle Scholar
- Plotkin SA: Is there a formula for an effective CMV vaccine?. J Clin Virol. 2002, 25: S13 - S21-10.1016/S1386-6532(02)00093-8.View ArticlePubMedGoogle Scholar
- Kimberlin DW, Lin CY, Sanchez PJ, Demmler GJ, Dankner W, Shelton M, Jacobs RF, Vaudry W, Pass RF, Kiell JM, Soong SJ, Whitley RJ: Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial. J Pediatr. 2003, 143: 16-25. 10.1016/S0022-3476(03)00192-6.View ArticlePubMedGoogle Scholar
- Michaels MG, Greenberg DP, Sabo DL, Wald ER: Treatment of children with congenital cytomegalovirus infection with ganciclovir. Pediatr Infect Dis J. 2003, 22: 504-509. 10.1097/00006454-200306000-00005.PubMedGoogle Scholar
- Fowler KB, McCollister FP, Dahle AJ, Boppana S, Britt WJ, Pass RF: Progressive and fluctuating sensorineural hearing loss in children with asymptomatic congenital cytomegalovirus infection. J Pediatr. 1997, 130: 624-630.View ArticlePubMedGoogle Scholar
- Guralnick MJ: Effectiveness of early intervention for vulnerable children: a developmental perspective. Am J Ment Retard. 1998, 102: 319-345. 10.1352/0895-8017(1998)102<0319:EOEIFV>2.0.CO;2.View ArticlePubMedGoogle Scholar
- Kinney JS, Onorato IM, Stewart JA, Pass RF, Stagno S, Cheeseman SH, Chin J, Kumar ML, Yaeger AS, Herrmann KL, .: Cytomegaloviral infection and disease. J Infect Dis. 1985, 151: 772-774.View ArticlePubMedGoogle Scholar
- Onorato IM, Morens DM, Martone WJ, Stansfield SK: Epidemiology of cytomegaloviral infections: recommendations for prevention and control. Rev Infect Dis. 1985, 7: 479-497.View ArticlePubMedGoogle Scholar
- Adler SP, Finney JW, Manganello AM, Best AM: Prevention of child-to-mother transmission of cytomegalovirus by changing behaviors: a randomized controlled trial. Pediatr Infect Dis J. 1996, 15: 240-246. 10.1097/00006454-199603000-00013.View ArticlePubMedGoogle Scholar
- Demmler GJ: Cytomegalovirus. Textbook of pediatric infectious disease. Edited by: Feigin RG and Cherry JD. 1998, Philadelphia, W.B. Saunders Company, 1732-1751. 4thGoogle Scholar
- American College of Obstetricians and Gynecologists: Perinatal viral and parasitic infections. ACOG Practice Bulletin 20. 2000, Washington, DC, ACOG, 20Google Scholar
- Vielfaure MKM, Milhalchuk D: Cytomegalovirus: no prevention, no cure. Can Nurse. 1995, 91: 25-28.Google Scholar
- Pass RF: Cytomegalovirus infection. Pediatr Rev. 2002, 23: 163-170.View ArticlePubMedGoogle Scholar
- Gaytant MA, Steegers EA, Semmekrot BA, Merkus HM, Galama JM: Congenital cytomegalovirus infection: review of the epidemiology and outcome. Obstet Gynecol Surv. 2002, 57: 245-256. 10.1097/00006254-200204000-00024.View ArticlePubMedGoogle Scholar
- Nigro G, Anceschi MM, Cosmi EV: Clinical manifestations and abnormal laboratory findings in pregnant women with primary cytomegalovirus infection. BJOG. 2003, 110: 572-577.View ArticlePubMedGoogle Scholar
- Larson E: A causal link between handwashing and risk of infection? Examination of the evidence. Infect Control. 1988, 9: 28-36.PubMedGoogle Scholar
- Revello MG, Gerna G: Diagnosis and management of human cytomegalovirus infection in the mother, fetus, and newborn infant. Clin Microbiol Rev. 2002, 15: 680-715. 10.1128/CMR.15.4.680-715.2002.View ArticlePubMedPubMed CentralGoogle Scholar
- Finney JW, Miller KM, Adler SP: Changing protective and risky behaviors to prevent child-to-parent transmission of cytomegalovirus. J Appl Behav Anal. 1993, 26: 471-472.View ArticlePubMedPubMed CentralGoogle Scholar
- Adler SP, Finney JW, Manganello AM, Best AM: Prevention of child-to-mother transmission of cytomegalovirus among pregnant women. J Pediatr. 2004, 145: 485-491. 10.1016/j.jpeds.2004.05.041.View ArticlePubMedGoogle Scholar
- Curtis V, Cairncross S: Effect of washing hands with soap on diarrhoea risk in the community: a systematic review. Lancet Infect Dis. 2003, 3: 275-281. 10.1016/S1473-3099(03)00606-6.View ArticlePubMedGoogle Scholar
- Ryan MA, Christian RS, Wohlrabe J: Handwashing and respiratory illness among young adults in military training. Am J Prev Med. 2001, 21: 79-83. 10.1016/S0749-3797(01)00323-3.View ArticlePubMedGoogle Scholar
- Roberts L, Smith W, Jorm L, Patel M, Douglas RM, McGilchrist C: Effect of infection control measures on the frequency of upper respiratory infection in child care: a randomized, controlled trial. Pediatrics. 2000, 105: 738-742. 10.1542/peds.105.4.738.View ArticlePubMedGoogle Scholar
- Hammond B, Ali Y, Fendler E, Dolan M, Donovan S: Effect of hand sanitizer use on elementary school absenteeism. Am J Infect Control. 2000, 28: 340-346. 10.1067/mic.2000.107276.View ArticlePubMedGoogle Scholar
- Ockene J, Ma Y, Zapka J, Pbert L, Valentine GK, Stoddard A: Spontaneous cessation of smoking and alcohol use among low-income pregnant women. Am J Prev Med. 2002, 23: 150-159. 10.1016/S0749-3797(02)00492-0.View ArticlePubMedGoogle Scholar
- Lawrence D, Graber JE, Mills SL, Meissner HI, Warnecke R: Smoking cessation interventions in U.S. racial/ethnic minority populations: an assessment of the literature. Prev Med. 2003, 36: 204-216. 10.1016/S0091-7435(02)00023-3.View ArticlePubMedGoogle Scholar
- Centers for Disease Control and Prevention: CMV. 2004, [http://www.cdc.gov/cmv]Google Scholar
- Osterholm MT, Reves RR, Murph JR, Pickering LK: Infectious diseases and child day care. Pediatr Infect Dis J. 1992, 11: S31 - S41-View ArticlePubMedGoogle Scholar
- Smith GC, Pell JP: Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials. BMJ. 2003, 327: 1459-1461. 10.1136/bmj.327.7429.1459.View ArticlePubMedPubMed CentralGoogle Scholar
- Centers for Disease Control and Prevention: HIV/AIDS Surveillance Report. 2001, 13(No.2): 39-Google Scholar
- Groseclose SL, Brathwaite WS, Hall PA, Connor FJ, Sharp P, Anderson WJ, Fagan RF, Aponte JJ, Jones GF, Nitschke DA, Chang MH, Doyle T, Dhara R, Jajosky RA, Hatmaker JD: Summary of notifiable diseases--United States, 2002. MMWR Morb Mortal Wkly Rep. 2004, 51: 1-84.PubMedGoogle Scholar
- May PA, Gossage JP: Estimating the prevalence of fetal alcohol syndrome. A summary. Alcohol Res Health. 2001, 25: 159-167.PubMedGoogle Scholar
- Habbick BF, Nanson JL, Snyder RE, Casey RE: Mortality in foetal alcohol syndrome. Can J Public Health. 1997, 88: 181-183.PubMedGoogle Scholar
- Nembhard WN, Waller DK, Sever LE, Canfield MA: Patterns of first-year survival among infants with selected congenital anomalies in Texas, 1995-1997. Teratology. 2001, 64: 267-275. 10.1002/tera.1073.View ArticlePubMedGoogle Scholar
- Vintzileos AM, Ananth CV, Smulian JC, Day-Salvatore DL, Beazoglou T, Knuppel RA: Cost-benefit analysis of prenatal diagnosis for Down syndrome using the British or the American approach. Obstet Gynecol. 2000, 95: 577-583. 10.1016/S0029-7844(99)00613-4.PubMedGoogle Scholar
- Davidoff MJ, Petrini J, Damus K, Russell RB, Mattison D: Neural tube defect-specific infant mortality in the United States. Teratology. 2002, 66 Suppl 1: S17-S22. 10.1002/tera.90005.View ArticlePubMedGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/5/70/prepub
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