neonatal prenatal screening

Prenatal & Neonatal Screening

Dr. Maria Knöbel, MBBS BSc (hons) ARCS

Screening Practices Raise Big Questions

Screening is to evaluate asymptomatic people in a population group to detect an unsuspected disease or risk thereof in order to prove outcome. Neonate screening serves to identify those who would benefit from early treatment while prenatal diagnosis serves to assist reproductive decision making. Both practises began in efforts to diagnose specific conditions, and the conditions that played a key role in the development of genetic screening are discussed in table 1. This paper aims to tell the story behind the development of prenatal and neonatal screening that is now common practise, and to briefly discuss in the confines of a few pages the ethical, legal, as well as individual questions that are raised.

A Short History of Prenatal and Neonatal Screening

Neonatal screening first began in the 1960s to detect phenylketonuria, which caused severe cognitive impairment if left untreated. This new concept of screening neonates was preceded by a 30-years of research into its biochemical basis, therapy, and to develop a reliable testing mechanism. Gradual expansion of screening involved other conditions with similar time urgency to phenylketonuria such as congenital hypothyroidism, as well as conditions with less time urgency such as sickle cell disease.  This evolution towards less urgent screening that also offered less dramatic benefit was described by an expert as a move from ‘public health emergency’ to ‘public health service’.1 In contrast to neonate screening, reproductive genetic screening involves tests during pregnancy (notably for trisomy 21 and neural tube defects) as well as carrier tests to identify couples at risk of having children with specific autosomal recessive conditions.2 The purpose is not to implement treatment after birth but to give the parents the opportunity to terminate a pregnancy. This practice continues to be a delicate matter influenced not just by parents’ reproductive autonomy, but also physician’s interests in avoiding litigation and other social and ethical concerns.

As decision to terminate a pregnancy is both personal and socially controversial, prenatal and carrier testing are characterised as an optional practise, and not mandated as neonatal screening.  For this reason, medical professionals often develop a counselling approach that avoids recommendations but instead assists couples in determining their own course of action.3  Currently, prenatal testing is limited to seeking early-onset diseases that cause untreatable impairment, such as Down’s syndrome and autism, amongst others.4, 5 However, there are cases where prenatal testing is used for  purposes such as sex selection or to assure sibling match for organ donation 4, and this suggests a growing acceptance of genetic testing beyond the regular boundaries. Nonetheless, these uses of prenatal testing are not yet wide-spread or part of any routine screening.

Even limited to severe early-onset conditions, prenatal testing raises questions both because abortion is surrounded by controversy and because judgements differ on severity of conditions that are screened for. Parents’ knowledge of conditions, whether from personal experience or from public awareness campaigns impacts heavily on their reaction to having a foetus diagnosed with any such condition, as well as their decision making process.  Simply allowing for prenatal screening is itself a point of contention. Disability advocates argue that allowing for selective abortion of foetuses with disorders such as trisomy 21 (which arguably already carry a certain level of stigma) brings about social harms.6 They argue that it implies a diminished social value for such individuals and also averts attention from the special needs of individuals living with disabilities.6 Yet others will argue that any use of selective termination is morally or religiously objectionable. However, currently the right of individuals to make autonomous decisions about pregnancy termination is supported with the argument that prospective parents receive complete and unbiased information surrounding such disabilities including their potential for a good quality of life, and ensure that decisions are not based on uninformed negative assumptions of disorders.2

Conditions and their Role in the Development of Genetic Screening.

Screening in the Primary /Community Care Setting

Currently there are no DNA-based tests routinely performed in primary care setting, but screening for genetic risk is widely recommended within family history assessments.2 Much of screening in community practice depends on the families individual urges and willingness to discuss family history with their health care providers. Anything from language, cultural, or socioeconomic barriers could hinder a build-up of such relationships between patient and care provider. However, having made that statement, there is little scientific basis that supports using family history as a risk assessment tool, and the National Institutes of Health State of the Science evaluation has found limited evidence to promote its use in clinical practise.15

Trisomy 21 and Prenatal screening

Legal Considerations

In 1970 the first prenatal identification of trisomy 21 was reported using analysis of amniotic fluid derived foetal cells.5 With the recognition that risk of trisomy 21 increases with maternal age16 and the legalisation of abortion, prenatal screening of trisomy 21 became accepted for women of advanced age.17 However, once again this proved to be a double-edged sword. Malpractice lawsuits began to emerge claiming “wrongful birth” based on failure to offer prenatal testing to pregnant women who subsequently gave birth to a child with a genetic disorder.18  These lawsuits claim physicians failed to disclose information pertinent to prenatal care, and are often successful in the United states.18  Interestingly, a comparable type of claim that may result from a similar situations is that of “wrongful life”, in which the child suffering from one such condition detectable by prenatal screening claims he or she should not have been born.18

Effect of screening on disease Incidence

In some cases, reduction of disease incidence is the explicit goal of screening programs, such as for β-thalassaemia and Tay-Sachs disease.13 In other situations such as with trisomy 21 and cystic fibrosis, there has been an effect on incidence whether or not it was an explicit goal of testing (Table 2).

Effect of screening on disease Incidence

Many studies reveal that while there is a trend towards increasing maternal age, pregnancy termination has reduced trisomy 21 births in several parts of the world. 13, 19-25  However because trisomy 21 incidence increases with maternal age, the net effect has often been found to be variable. 

Screening, The Family, and The Doctor

A recent encounter with a patient’s mother became a very memorable impact on me, and largely kindled my interest in this topic. She was the mother of three healthy children who subsequently gave birth to a daughter with Down’s Syndrome. Although she spoke communicable English on our encounter, it was clear that there were likely to be great cultural differences between her family and any healthcare workers she encountered during her pregnancy. She alleges to have never been offered any specific screening during her pregnancy, was not warned of any risk that her child might develop Down ’s syndrome, and that the first information she was given on the matter was immediately following her daughter’s birth. She knew nothing about Down’s Syndrome and nothing the doctors said to her that day remained with her. This short story highlights numerous flaws in the system. We will never be sure whether she was indeed not offered any prenatal screening, or whether it was a matter of failed communication and that she had refused it without realising. Another key moment in this is when she was told about her daughter’s Down’s Syndrome. How was she told? If the doctor became aware there was a language or cultural barrier, should she have called for an interpreter to discuss such an important matter? In addition to this, a good delivery method would have taken into consideration that she may require time to absorb the information and not deliver it all at once. Despite all the training and guidelines doctors are given, how much is it all implemented? How many more cases are there like this one?

To conclude, this is a topic riddled with minefields that could be endlessly discussed.  Various bodies will have their particular agendas ranging from legal to practical to personal, and even emotional. Questions may arise as to whether mothers may feel morally compelled to test now that it is widely offered.  Will the risks of prenatal testing, for example amniocentesis, prove worth their potential benefit?  Who ensures that information about testing and the resulting options is given in a non-biased and supportive way? As mentioned in earlier discussion, does this question the value or disabled people in society? Practice guidelines and legislations have changed continuously over the last 50 years and will continue to do so as more light is shed, court cases are battled, and advocate groups have campaigned. Nonetheless, it is a discussion for which spending even just a day in the community with affected families will provide much food for thought for.


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2.         Burke W, Tarini B, Press NA, Evans JP. Genetic Screening. Epidemiologic Reviews. July 1, 2011;33(1):148-164.

3.         Michie S, Smith JA, Heaversedge J, Read S. Genetic Counseling: Clinical Geneticists’ Views. Journal of Genetic Counseling. 1999;8(5):275-287.

4.         Clark RD, Fletcher J, Petersen G. Conceiving a fetus for bone marrow donation: an ethical problem in prenatal diagnosis. Prenat Diagn. May 1989;9(5):329-334.

5.         Nadler HL, Gerbie AB. Role of amniocentesis in the intrauterine detection of genetic disorders. N Engl J Med. Mar 12 1970;282(11):596-599.

6.         Parens E, Asch A. Disability rights critique of prenatal genetic testing: Reflections and recommendations. Mental Retardation and Developmental Disabilities Research Reviews. 2003;9(1):40-47.

7.         Antonio Cao, Renzo Galanello. Beta-Thalassemia. Seattle: GeneReviews; 1993-.

8.         Samuel M Moskowitz, James F Chmiel, Darci L Sternen, Edith Cheng, Cutting GR. CFTR-Related Disorders. Seattle: GeneReviews; 1993-.

9.         Hobbs MBW. Sickle Cell Disease. Seattle: GeneReviews; 1993-.

10.       Bredaki FE, Poon LC, Birdir C, Escalante D, Nicolaides KH. First-trimester screening for neural tube defects using alpha-fetoprotein. Fetal Diagn Ther.31(2):109-114.

11.       Petros M. Revisiting the Wilson-Jungner criteria: how can supplemental criteria guide public health in the era of genetic screening? Genet Med. Jan;14(1):129-134.

12.       Metcalfe SA. Carrier screening in preconception consultation in primary care. J Community Genet. Dec 20.

13.       Kaback MM, Nathan TJ, Greenwald S. Tay-Sachs disease: heterozygote screening and prenatal diagnosis–U.S. experience and world perspective. Prog Clin Biol Res. 1977;18:13-36.

14.       Megarbane A, Ravel A, Mircher C, et al. The 50th anniversary of the discovery of trisomy 21: the past, present, and future of research and treatment of Down syndrome. Genet Med. Sep 2009;11(9):611-616.

15.       Services UDoHaH. NIH state of the science; family history., 2012.

16.       Coleman M. Down’s syndrome. Pediatr Ann. Feb 1978;7(2):90-103.

17.       Golbus MS, Loughman WD, Epstein CJ, Halbasch G, Stephens JD, Hall BD. Prenatal genetic diagnosis in 3000 amniocenteses. N Engl J Med. Jan 25 1979;300(4):157-163.

18.       Klein RD, Mahoney MJ. Medical Legal Issues in Prenatal Diagnosis. Clinics in Perinatology. 2007;34(2):287-297.

19.       Cheffins T, Chan A, Haan EA, et al. The impact of maternal serum screening on the birth prevalence of Down’s syndrome and the use of amniocentesis and chorionic villus sampling in South Australia. BJOG. Dec 2000;107(12):1453-1459.

20.       Ekelund CK, Jørgensen FS, Petersen OBr, Sundberg K, Tabor A. Impact of a new national screening policy for Down’s syndrome in Denmark: population based cohort study. BMJ. 2008-11-27 00:00:00 2008;337.

21.       Siffel C, Correa A, Cragan J, Alverson CJ. Prenatal diagnosis, pregnancy terminations and prevalence of Down syndrome in Atlanta. Birth Defects Res A Clin Mol Teratol. Sep 2004;70(9):565-571.

22.       Binkert F, Mutter M, Schinzel A. Impact of prenatal diagnosis on the prevalence of live births with Down syndrome in the eastern half of Switzerland 1980-1996. Swiss Med Wkly. Aug 24 2002;132(33-34):478-484.

23.       Lai FM, Woo BH, Tan KH, et al. Birth prevalence of Down syndrome in Singapore from 1993 to 1998. Singapore Med J. Feb 2002;43(2):070-076.

24.       Verloes A, Gillerot Y, Van Maldergem L, et al. Major decrease in the incidence of trisomy 21 at birth in south Belgium: mass impact of triple test? Eur J Hum Genet. Jan 2001;9(1):1-4.

25.       Calda P, Sipek A, Gregor V. Gradual implementation of first trimester screening in a population with a prior screening strategy: population based cohort study. Acta Obstet Gynecol Scand. Aug;89(8):1029-1033.


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