Prevalence, prenatal screening and neonatal features in children with Down syndrome: a registry- based national study

Congenital anomalies, including DS, present an important public health issue since the surviving children have special medical, social and educational needs. National prenatal screening programs for DS and clinical guidelines for the further care of DS newborns should exist. To create an efficient strategy, population-based data are necessary. The Croatian registry of congenital anomalies was established in 1983 and is limited to the northwest of Croatia, part of central Croatia and part of the Croatian coast (Primorje). This registry covers only 20.8 % of all births and provides data about DC prevalence for EUROCAT. In order to get more reliable data for our study, the prevalence and neonatal characteristics of children with DS were based on total births at health institutions, covering 99 % of all births in Croatia. In this study, for example, 51.7 % of all newborns with DS were born in three large counties that are not included in the Croatian registry of congenital anomalies [8]. The total prevalence of DS in Croatia in the period of 2009–2012 (7.01 per 10,000 births) was lower than the previously estimated prevalence based on EUROCAT data [4]. In the period of 2008–2012, the total prevalence, including terminated pregnancy for fetal anomaly (TOPFA), live births and fetal deaths obtained from EUROCAT were12.96, 8.93 and 8.90 per 10,000, respectively. According to EUROCAT, the total prevalence in Europe was also much higher (22 per 10,000 births) [3]. There are large differences in DS prevalence rates (5.99–43.03), which depend on sociocultural variables and abortion-legislation practices among EU countries. In the period of 2008–2012, TOPFA was performed in 52.3 % of cases of prenatal DS detection (7,335 of a total of 14,036 DS cases). In countries in which abortion is illegal, such as Ireland and Malta, the DS prevalence is higher, varying from 20 to 34 per 10,000 births [4]. In contrast, the DS prevalence in France is quite low (7.5 per 10,000), which is probably due to the high percentage (77 %) of DS pregnancy terminations [9]. In Croatia, TOPFA is legal until 22 weeks of gestation. However, we do not have information on prenatally detected DS, which could result in pregnancy termination and reduced overall prevalence of DS. After 22 weeks of gestation, it is possible to perform TOPFA outside of Croatia in countries with less-restrictive abortion legislation. Also, TOPFA data are not part of routine health statistics; only data about legally induced abortions, spontaneous abortions and pregnancy termination for all fetal anomalies are collected, which does not allow us to make conclusions about pregnancy terminations due to DS. Furthermore, it is important to emphasize that birth records from routine health statistics could be missing data about newborns’ pathologic conditions, which does not allow complete insight into DS prevalence.

EUROCAT has recently analyzed trends in DS prevalence for the period from 1990 to 2009, during which an increasing DS prevalence was noticed. The proportion of births in Europe in the population of mothers aged ≥35 years increased from 13 % in 1990 to 19 % in 2009, which is probably the reason for the increased total prevalence of DS over time [3]. In our study, we found a proportion of 33.3 % of mothers aged ≥35 years who delivered newborns with DS in Croatia. This is very similar to other European countries [3, 9, 10].

Since 1990, widening of and improvements in antenatal screening techniques have resulted in a relatively stable live-birth prevalence in Europe over time [11, 12]. One of the other probable reasons for the stable live-birth prevalence is the availability of prenatal care and routine prenatal ultrasounds. In Croatia, in accordance with national compulsory health insurance, a program of health care measures is recommended. The program includes one general and gynaecologic health examination, with two pregnancy controls in the first trimester, three pregnancy controls in the second trimester, and four pregnancy controls in the third trimester of pregnancy. In pregnancies with complications, the number of visits and diagnostic procedures depends on specialist assessments. In the framework of the program, the national recommendation is to perform three ultrasound scans during a normal pregnancy. The first scan is at 10–14 gestational weeks, followed by routine structural-anomaly scanning at 18–23 weeks, with the last scan at 34–37 weeks. Since 2006, first-trimester screening with biochemical markers and nuchal translucency measurements have been also introduced as optional. In the available records, 92.94 % of DS pregnancies had the first antenatal visit in the first 14 weeks of gestation, which meets the recommendations of the program. In addition, the first ultrasound examination was usually done at the same time as the first antenatal visit. According to a recent report by the Croatian Institute of Public Health, more than 70 % of pregnant women had first-trimester ultrasound screening after 12 weeks of gestation [8]. In most European countries, country-wide policies exist for routine anomaly-scanning ultrasounds. Prenatal screening for DS in many countries has led to large proportions of terminated pregnancies after prenatal diagnosis, which also influences the stable live-birth prevalence over time [13]. For example, according to the United Kingdom’s National Institute for Health and Clinical Excellence (NICE) guidelines, pregnant women in England and Wales should be offered screening for DS that should be performed by the end of the first trimester, no later than at 20 weeks of gestation. The combined test (biochemical markers and nuchal translucency measurement) should be offered between 11 and 14 weeks of gestation, and no later than 20 weeks [14]. According to EUROCAT, in 14 European countries, 66 % of DS cases are detected prenatally and 88 % of those resulted in termination of pregnancy [15]. Detection of fetal anomalies on antenatal ultrasound offers women and their partners information that may help them to better prepare for the birth of their child, including the option of delivery in a setting that permits rapid access to specialists and to surgical or medical care. In our study, we had no information about whether the DS was prenatally or postnatally diagnosed, but in 38 % (46 cases of a total of 120 DS pregnancies), structural anomalies were reported on scanning. The absence of a national screening policy is one of the reasons for the lack of prenatal DS detection data in Croatia. In previous studies, it was observed that in countries with national screening policies, there are measurable impacts on prenatal DS detection rates [13]. The detection rate was higher in countries with primarily first-trimester screening than in those with a mixed first- or second-trimester screening policy. Also, countries with no national screening policies had significantly lower prenatal detection rates for DS [13, 16].

In general, a higher level of education and having previous information on available screening tests, such as a nuchal translucency scan, biochemical tests and invasive diagnostic testing by chorionic villus sampling or amniocentesis, influence a woman’s decisions about which tests to perform [17]. Additionally, the knowledge level about first-trimester DS screening has been positively associated with length of education [18]. In our study, such conclusions could not be made. In the available data, most of the mothers had a secondary-school education followed by a college/university degree, and only three had a primary-school education. However, providing information about available screening options to all pregnant women at the local and national levels is a technique for early and frequent prenatal diagnosis of DS.

In our study, growth retardation in children with DS was found, similar to other results [19, 20]. Previously published charts for DS are based on American, Sicilian, Swedish and Dutch populations, though the American growth charts are most frequently used all over the world [21–24]. Due to significant differences among populations, it is important to have specific DS growth charts for our population, which could be incorporated into our future National Health Care Program for DS children. Also, DS newborns have more frequent cases of birth asphyxia (Apgar score of ≤6 after 5 min) which corresponds to recent literature (2–8 %) [19, 25, 26]. Consequently, newborns with DS have more complications at birth.

Furthermore, 7 of the DS newborns in this study had one or more additional structural anomalies, including 6 with CHD, corresponding to only 6 % of the children. In recent studies, the prevalence of CHD in DS children was much higher, ranging from 43 % to 57 % [25–28]. This low percentage of CHD could be partially explained by the lower number of diagnosed CHDs in our maternity wards. Several authors of studies of DS children with major cardiac malformations found no clinical signs in the first week of life, and therefore a normal neonatal examination does not exclude CHD [29]. If possible, due to these findings, newborns with DS should have echocardiography performed during the first month of life. Additionally, we had records from maternity wards, without further follow-up during the newborn and infant period, and those who were later diagnosed remain unrecorded. A follow-up system should be incorporated into national health policy to provide more accurate data on structural anomalies. Because of the high incidence of a significant CHD, early recognition can lead to the successful early surgical treatment of CHD in children with DS [30].

DS newborns are less frequently breastfed compared with healthy children. The ability to breastfeed may be influenced by a range of difficulties in the first few days of life, often as a consequence of facial and other anatomical structural abnormalities associated with DS. Also, severe neonatal illness is common among DS newborns, leading to hospital admissions that are usually associated with medical interventions and mother-infant separations that can interfere with breastfeeding. In our study, we found similar results, with 68.3 % of children with DS being breastfed from birth, compared with 94.72 % in the reference population. Our percentage of breastfed DS children was higher than that reported in some studies (43 %–48 %), suggesting that possible improvements, through the training of maternity-ward health professionals and home-based support of breastfeeding, could be made [19, 31].