Major congenital abnormalities are detected in 2 to 3 births per 100, and 1 per 100 is affected by several major anomalies or a syndrome (5;6; Finnish Registry of Congenital Malformations). The most severe anomalies can lead to perinatal death or permanent disability. Some disorders can be treated during the fetal period or require immediate treatment after birth to reduce permanent disability or prevent the death of the newborn.

The methods to screen for chromosomal abnormalities, especially trisomy 21 (Down syndrome) have been in use since the 1980s (7) and are still developing (12). Ultrasound techniques are increasingly used to screen for structural abnormalities of the fetus. The chances of detecting structural abnormalities vary depending on the type and severity of the anomaly, the scanning equipment, the experience of the sonographer and the timing of screening (5;9;10). The existing variations and difficulties in determining when a malformation is severe, moderate, or mild raises major ethical questions every time a malformation is identified during the fetal period.

Between and within countries there is considerable variation in the use of various existing screening methods. In Finland, each of the over 400 municipalities can independently decide which screening method to provide, resulting in a wide variety in practices, inequity, and major problems in counseling and organizing the investigations. According to a survey in 2002, forty of the forty-four hospitals with a maternity clinic offered a nuchal translucency measurement for chromosomal screening but only four of them combined it with serum markers (11). Forty hospitals offered age-based direct invasive diagnostic procedures (chorionic villi sample or amniocentesis) to detect chromosomal anomalies. Of these, four had set the age limit at 35, one at 36, seventeen at 37, three at 38, three at 39, and twelve at 40 years. In Finland, ultrasound examination has only been offered as part of screening (measurement of nuchal translucency or screening for structural malformations) or due to clinical symptoms.

The Finnish organization for gynecologists and the local health decision makers requested a health technology assessment (HTA) on the topic, while the Ministry of Health and Social Affairs also needed this information to be used as a basis for policy decisions. In this article, we describe the process from initial request to a national statute on screening. The questions identified by the HTA assessment, the process of answering these questions and the selection of screening methods to be offered for pregnant women in Finland are presented.

ASSESSMENT OF OPTIONS FOR SCREENING FOR STRUCTURAL AND CHROMOSOMAL ABNORMALITIES

The HTA assessment was conducted together with methodological experts on HTA (IAR, MM) and health economics, the head of the national registry for anomalies, and a panel of clinical experts in obstetrics, neonatology, general practice, and clinical genetics. In addition to being methodological experts, the authors of this article are also clinical experts in pediatric neurology (I.A.R.) and general practice (M.M.).

The possible screening models for Finland were constructed using evidence from the literature and the clinical experts (1). Optimal methods and time frames to be used when screening for chromosomal abnormalities were identified in a recent HTA report (12). For the chromosomal abnormalities, the following options were considered to be applicable in Finland. (i) The combination of serum markers (PAPP-A and β-HCG at gestation week 8 to 10) and measurement of nuchal translucency (ultrasound at gestation week 10 to 12), (ii) triple serum markers (estriol, β-HCG, AFP at gestation week 14 to 15), or (iii) a combination of i and ii. For structural abnormalities, the options were based on recent literature on the detection rate during different gestation weeks (5;8–10), on Finnish legislation on the termination of pregnancy, and on equity in care. The options were (i) ultrasound screening during gestation week 18 to 21 and (ii) ultrasound screening after gestation week 24 for parents to whom termination of pregnancy would not be an option. In Finland, induced abortion due to fetal abnormalities is legal until the end of the 24th gestation week.

The costs of the various screening methods were calculated in euros at the 2004 price level. The effects and costs of various screening options were compared against a no-screening situation with the assumption that 90 percent of the pregnant women would participate. Sensitivity analyses were done for screening costs based on different participation rates. An example of the comparison of both chromosomal and structural screening against no screening situation is presented in Table 1.

Table 1. Cost-Effectiveness Comparison between Participation in Both Chromosomal and Structural Screening before 24th Gestation Week and a No-Screening Situation

Note. Primary assumptions were 90% participation rate and annual birth rate of 56,000.

^a The number of natural miscarriages excluded.

^b Estimated number of chromosomal abnormalities that would lead to miscarriage or prenatal death.

^c Estimated from the national registry for anomalies, includes diagnosed miscarriages, perinatal death.

The expert group also identified the ethical consequences of each screening model. The HTA draft was sent to external experts for peer review before publishing and their comments were included in the ethical evaluation. A summary of the ethical evaluation has been previously published (2).

Although the expert group could identify the best possible screening methods, several critical questions needed answering before a national decision could be taken on a uniform screening system. Questions regarding the aims of the screening programs are presented in Table 2. The expert group further required that the decision has to provide equity within the country. In addition, the quality of the screening program needs to be ensured (e.g., improved counseling at all levels of the screening program, criteria for training the sonographs, the need for centralization, requirements for the ultrasound equipment, setting the sensitivity and specificity levels, follow-up of induced harm).

Table 2. Critical Questions on the Aim of Prenatal Screening

THE DECISION PROCESS IN THE NATIONAL SCREENING COMMITTEE

The Screening committee at the Finnish Ministry of Social Welfare and Health was ready in October 2003 to evaluate the existing and proposed screening programs in Finland. Both authors of this article are members of the Screening Committee and had, thus, the opportunity to inform the Screening Committee during the HTA project, present the report, and answer content-specific questions. The Screening Committee recognized that the goal of the prenatal screening programs is to allow parents to take informed decision about the pregnancy. These decisions range from termination of pregnancy to optimal care during pregnancy and delivery. It was considered important to discuss the list of questions (examples in Table 2) in the HTA report with all stakeholders and an open seminar was organized.

Four hundred persons, from laypersons to health decision makers, participated in the seminar in October 2005. The seminar started with a computerized survey of the participant's opinions. The participants answered each question through remote control, and the results were shown immediately. The seminar included lectures and a panel discussion also involving patient organizations and layperson. The survey questions were repeated at the end of the seminar. The information received during the seminar had a clear impact on the opinions of the participants (Table 3). The seminar revealed new issues for the Screening Committee to tackle before issuing a final statement.

Table 3. Survey of Opinions on Various Ethically Relevant Issues within the Context of Various Screening Options

Note. Only “yes” and “no” answers are presented in the table, percentage of “don't know” answers can be counted when adding up to 100%.

^aAnswers are given in parentheses.

The Screening Committee invited the principal investigator at the national registry for fetal abnormalities to discuss the various scenarios following the options of each screening program. Finally, after six meetings and close to 1 year of hard work, the Screening Committee unanimously recommended a national screening program (the content explained later) that would ensure equity in care by providing the best currently available screening options for the citizens. Furthermore, the Screening Committee recommended that the effects and quality of the screening programs must be continuously monitored and quality ensured by a national group of experts. This group will determine the requirements for equipment and personnel in the program. The personnel in primary care (maternal health clinics) and secondary and tertiary hospitals needs training to give adequate and objective information and counseling.

THE PROCESS AT THE MINISTRY OF HEALTH AND SOCIAL AFFAIRS

The Ministry of Health and Social Affairs accepted the statement of the Screening committee and sent it for a wide round of commenting, including health decision makers, content experts, ethicists, and patient organizations. A total of forty-seven comments were given. The statement was well received, with only minor clarifications required. The ministry had further asked whether the uniform screening program should be implemented through a recommendation, a code of practice or a statute. Twenty of the respondents favored compulsory implementation by means of a statute so as to reach equity in care, whereas seven favored a recommendation and the rest were undecided.

After weighing the different options, the Ministry decided to regulate the screening programs for fetal abnormalities through a statute. As this strategy would increase the cost burden for communities, the ministry requested an estimate on the cost-impact of the various screening options on the municipalities. This estimate was not possible within the given time frames, as the Finohta report on fetal abnormalities had not looked at the costs of all program options recommended by the Screening Committee. Furthermore, the change in cost-impact would have to be calculated for each municipality separately, as they were offering various screening methods and the participation rates varied markedly between the municipalities. Only crude estimates could be given but they were regarded as sufficient to proceed with the statute.

The Ministry of Health and Social Affairs decided to give a new umbrella statute on all screening programs. The official screening programs—mammography screening for women 50 to 69 years of age, screening for cervical cancer, and prenatal screening for structural and chromosomal abnormalities—are now included in one statute, approved by the Council of State on 21 December 21 2006. The uniform screening for structural and chromosomal abnormalities must be adopted in all municipalities by the end of 2010 at the latest.

The explanatory memorandum of the statute sets the criteria for the evaluation of all screening programs that have to be fulfilled before any program can be offered by public health care. These criteria were originally formed by the national Screening Committee (3). Furthermore, the quality and possible harms of any screening program have to be continuously monitored.

THE CONTENT OF THE NATIONAL PRENATAL SCREENING PROGRAM FOR STRUCTURAL AND CHROMOSOMAL ABNORMALITIES

The content of the statute for the prenatal screening program is explained in depth in the explanatory memorandum. The main content of the statute is as follows: (i) General ultrasound during gestation week 10–14 to provide information on length of gestation, plurality, site of fetus. (ii) Screening for chromosomal abnormalities primarily by a combination test: serum markers PAPP-A and β-HCG at 8–11 gestation weeks and nuchal translucency measurement in gestation weeks 10 to 12 in connection with a general ultrasound scan. Alternatively, the triple test (serum markers AFP, β-HCG, estriol) on gestation weeks 14 to 15. Women 40 years of age or older can be offered direct fetal chromosomal analysis (placental biopsy or amniocentesis) as an option. Nuchal translucency measurements have to be centralized so that the sonographer performs at least 200 measurements per year. (iii) Screening for structural abnormalities is offered during gestation weeks 18 to 21 if the parents consider termination of pregnancy due to identified severe fetal malformation as an option for their family. If the parents would not consider termination of pregnancy as their informed choice under any circumstances, the scan can be made first after the 24th gestation week. The ultrasound screening for structural abnormalities have to be centralized so that the unit performs at least 2000 screening scans per year and has the possibility to consult an obstetrician specialized in ultrasound investigations. The time frames and various options are summarized in Figure 1.

Figure 1. The various pathways when deciding on participation.

CONTACT INFORMATION

Ilona Autti-Rämö, MD, PhD (ilona.autti-ramo@stakes.fi), Senior Medical Officer, Finnish Office for Health Care Technology Assessment (Finohta), STAKES, Lintulahdenkuja 4, 00530 Helsinki, Finland; Adjunct Professor, Pediatric Neurology, University of Helsinki, Lastenlinnantie 2, 00250 Helsinki, Finland

Marjukka Mäkelä, MD, PhD, MSc (marjukka.makela@stakes.fi), Director, Finnish Office for Health Care Technology Assessment (Finohta), STAKES (National R&D Centre for Welfare and Health), P.O. Box 220, 00531 Helsinki, Finland; Professor, Department of General Practice, University of Copenhagen, P.O. Box 2099, 1014 Copenhagen K, Denmark