Congenital limb reduction defects in 1.6 million births in Argentina

The objectives of this study were to describe the birth prevalence of limb reduction defects (LRD) in Argentina, their clinical features, and to review the literature on this topic. The data source was the National Network of Congenital Anomalies of Argentina, a surveillance system that has been operative since 2009. Data were collected from November 1, 2009 to December 31, 2016. 1,663,610 births and 702 affected patients were registered during this period. The prevalence of LRD was 4.22/10,000 births (CI 95%: 3.93–4.54). In 15,094 stillbirths, prevalence was 30.80/10,000 (CI 95%: 22.31–40.65). Perinatal mortality (stillbirths plus early neonatal deaths) was 24.6%, mostly explained by postnatal deaths. LRD were classified according to different variables, including Gold's anatomic classification. Then, 41.0% of patients had transverse terminal defects and 50.2% had longitudinal defects. We found multiple and syndromic clinical presentation to be associated with both preaxial LRD and lethality. The prevalence of LRD was lower and perinatal mortality was higher in our study compared to that of previously published studies. Because there is heterogeneity in the inclusion and exclusion criteria among publications, a greater effort should be made in order to include similar populations and to use a unified anatomic classification and nomenclature.     

Clinical epidemiology of skeletal dysplasias in South America

Currently accepted birth prevalence for osteochondrodysplasias (OCD) of about 2/10,000 is based on few studies from small series of cases. We conducted a study based on more than 1.5 million births. OCD cases were detected from 1,544,496 births occurring and examined in 132 hospitals of ECLAMC (Latin American Collaborative Study of Congenital Malformations) between 2000 and 2007. Cases were detected and registered according to a pre-established protocol, and then ranked in four diagnostic evidence levels (DEL), according to available documentation. For the analysis of risk factors, a healthy control sample born in the same period was used. OCD was diagnosed in 492 newborns, resulting in a prevalence per 10,000 of 3.2 (95% CI: 2.9-3.5). Perinatal lethality (stillbirths plus early neonatal deaths) occurred in 50% of cases. Prenatal ultrasound diagnosis was made in 73% of cases (n = 359). Among 211 cases from the best documented group (DEL-1) and according to international classification, 33% of cases fit into the G-25 (osteogenesis imperfecta), 29% in Group-1 (FGFR3), and 8% in Group-18 (Bent bones). The prevalence of the main OCD types were: OI-0.74 (0.61-0.89); thanatophoric dysplasia-0.47 (0.36-0.59); and achondroplasia-0.44 (0.33-0.55). Paternal age (31.2 ± 8.5), parity (2.6), and parental consanguinity rate (5.4%) were higher in cases than in controls (P < 0.001). In conclusion, the OCD overall prevalence of 3.2 per 10,000 found seems to be more realistic than previous estimates. This study also confirmed the high perinatal mortality, and the association with high paternal age, parity, and parental consanguinity rate.     

Prevalence and descriptive epidemiology of Turner syndrome in the United States, 2000–2017: A report from the National Birth Defects Prevention Network

The lack of United States population-based data on Turner syndrome limits assessments of prevalence and associated characteristics for this sex chromosome abnormality. Therefore, we collated 2000–2017 data from seven birth defects surveillance programs within the National Birth Defects Prevention Network. We estimated the prevalence of karyotype-confirmed Turner syndrome diagnosed within the first year of life. We also calculated the proportion of cases with commonly ascertained birth defects, assessed associations with maternal and infant characteristics using prevalence ratios (PR) with 95% confidence intervals (CI), and estimated survival probability. The prevalence of Turner syndrome of any pregnancy outcome was 3.2 per 10,000 female live births (95% CI = 3.0–3.3, program range: 1.0–10.4), and 1.9 for live birth and stillbirth (≥20 weeks gestation) cases (95% CI = 1.8–2.1, program range: 0.2–3.9). Prevalence was lowest among cases born to non-Hispanic Black women compared to non-Hispanic White women (PR = 0.5, 95% CI = 0.4–0.6). Coarctation of the aorta was the most common defect (11.6% of cases), and across the cohort, individuals without hypoplastic left heart had a five-year survival probability of 94.6%. The findings from this population-based study may inform surveillance practices, prenatal counseling, and diagnosis. We also identified racial and ethnic disparities in prevalence, an observation that warrants further investigation.     

Characteristics and associated anomalies in radial ray deficiencies in Finland—A population‐based study

Upper‐limb defects with deficiencies of the radial ray have varying etiologies, with a low proportion of true Mendelian disorders. We carried out a population‐based study to elucidate the birth prevalence and clinical spectrum of radial ray deficiencies in Finland. We identified all births with radial ray deficiency reported to the Finnish Register of Congenital Malformations in 1993–2005. Altogether 138 cases were identified (123 live births), with a birth prevalence of 1.83 per 10,000 births and a live birth prevalence of 1.64 per 10,000 live births. The proportion of infant deaths was as high as 35%. The majority of the cases were associated with known syndromes or multiple anomalies; only 13% were true isolated radial ray deficiencies. The most common syndrome was trisomy 18, and the most common in multiple anomalies was VACTERL association. In 8.7% of cases an association between radial ray deficiency and heart anomaly was observed. The high proportion of cases with associated major anomalies indicates that radial ray deficiency can be regarded isolated only after thorough assessment of the various organ systems in an affected infant. © 2013 Wiley Periodicals, Inc.     

Trisomy 13 and 18—Prevalence and mortality—A multi‐registry population based analysis

The aim of the study is to determine the prevalence, outcomes, and survival (among live births [LB]), in pregnancies diagnosed with trisomy 13 (T13) and 18 (T18), by congenital anomaly register and region. Twenty‐four population‐ and hospital‐based birth defects surveillance registers from 18 countries, contributed data on T13 and T18 between 1974 and 2014 using a common data‐reporting protocol. The mean total birth prevalence (i.e., LB, stillbirths, and elective termination of pregnancy for fetal anomalies [ETOPFA]) in the registers with ETOPFA (n = 15) for T13 was 1.68 (95% CI 1.3–2.06), and for T18 was 4.08 (95% CI 3.01–5.15), per 10,000 births. The prevalence varied among the various registers. The mean prevalence among LB in all registers for T13 was 0.55 (95%CI 0.38–0.72), and for T18 was 1.07 (95% CI 0.77–1.38), per 10,000 births. The median mortality in the first week of life was 48% for T13 and 42% for T18, across all registers, half of which occurred on the first day of life. Across 16 registers with complete 1‐year follow‐up, mortality in first year of life was 87% for T13 and 88% for T18. This study provides an international perspective on prevalence and mortality of T13 and T18. Overall outcomes and survival among LB were poor with about half of live born infants not surviving first week of life; nevertheless about 10% survived the first year of life. Prevalence and outcomes varied by country and termination policies. The study highlights the variation in screening, data collection, and reporting practices for these conditions.     

Prevalence and associated factors for agenesis of corpus callosum in Emilia Romagna (1981–2015)

Agenesis and hypoplasia of the corpus callosum (ACC and HCC) are heterogeneous group with a large variation in published prevalence based on few population based studies. The aim of this work is to describe prevalence, associated factors and other malformations present in cases with either agenesis or hypoplasia of the corpus callosum, using a population-based database of all malformations diagnosed in Emilia-Romagna, Italy, (the Emilia-Romagna Registry on Congenital Malformations, IMER).This registry links and integrates hospital discharge records, birth certificates with cases reported by referral clinicians to identify all structural malformations diagnosed within one year of life regarding live birth, fetal death or termination of pregnancy due to fetal malformations (TOPFA). During the study period (1981–2015) the number of cases with ACC or HCC was 255, in a reference population of 1,023,784 live births, giving an overall prevalence of 2.49 per 10,000 (1.47 per 10,000 only live birth). After 1996, with the inclusion of TOPFA in IMER registry, the overall prevalence rate increase significantly from 1.42 to 3.03 cases per 10,000 birth (p-value<0.001). Prenatal diagnosis was made in 192 cases (75.3%), at a median gestational age of 20.7 [IQR: 19.71–22.71]. Termination of pregnancy occurred in 105 of the 255 cases (41,2%). Where a prenatal diagnosis was available, 55% of cases ended in TOPFA (105/192), with higher prevalence of cases associated to central nervous system malformations and multiple birth defects, and median gestational age at diagnosis significantly less than in live birth cases (20.3 vs 29 weeks). Agenesis/hypoplasia ratio was 5.7 (217/38). The most frequently associated malformations were musculoskeletal. Trisomies were the most frequent chromosomal anomalies, in particularly trisomy18 and 13 (respectively 9/32 and 4/32 cases). Our study showed an increased risk for male infants (RR of 1.68, RR 95% CI 1.19–2.37). No differences were detected analyzing maternal age and ethnicity, and the increased risk associated to preterm birth disappeared when compared with other malformed infants.This is one of the few population based studies dealing with prevalence of agenesis and hypoplasia of corpus callosum. Prevalence is still debated, but this study adds comprehensive data, in particular inclusion of TOPFA cases. Early prenatal diagnosis, not always possible, could be crucial for decision making regarding continuation of pregnancy.     

Prevalence and risk factors for Down syndrome: A hospital‐based single‐center study in Western Mexico

Although Hispanics of Mexican origin in the United States have been identified as a population with a particularly higher rate of Down syndrome (DS), there is a paucity of studies concerning this topic in Mexico. The aim of this study was to determine the prevalence and risk factors for DS in a population from Western Mexico. For prevalence, 230 liveborn infants with DS were included from a total of 89,332 births occurring during the period 2009–2017 at the Dr. Juan I. Menchaca Civil Hospital of Guadalajara (Mexico). In order to evaluate potential DS risks, a case‐control study was conducted among 633 newborns, including those 211 DS patients with full trisomy 21 (cases) and 422 infants without birth defects (controls). Data were analyzed using multivariable logistic regression analysis. The overall prevalence for DS was 25.7 per 10,000 (95% confidence interval [95% CI]: 22.4–29.1). Patients with DS had a significantly higher risk for family history of DS in distant relatives (adjusted odds ratio [aOR] = 4.4, 95% CI: 2.5–7.7), relatives with thyroid disease (aOR = 2.3, 95% CI: 1.2–4.0), maternal age ≤ 19 years (aOR = 5.1, 95% CI: 2.7–9.6) or ≥ 35 years (aOR = 3.3, 95% CI: 1.5–6.9), paternal age ≤ 19 years (aOR = 3.5, 95% CI: 1.7–7.4), pre‐pregnancy BMI ≥ 25 kg/m² (aOR = 1.6, 95% CI: 1.0–2.4), and pre‐pregnancy alcohol consumption (aOR = 1.8, 95% CI: 1.1–2.9). The identified risks in family history, and previously mentioned nutritional disadvantages were associated with DS in our sample and probably also to its increased prevalence in our population.     

The population-based prevalence of achondroplasia and thanatophoric dysplasia in selected regions of the US

There have been no large population-based studies of the prevalence of achondroplasia and thanatophroic dysplasia in the United States. This study compared data from seven population-based birth defects monitoring programs in the United States. We also present data on the association between older paternal age and these birth defects, which has been described in earlier studies. The prevalence of achondroplasia ranged from 0.36 to 0.60 per 10,000 livebirths (1/27,780-1/16,670 livebirths). The prevalence of thanatophoric dysplasia ranged from 0.21 to 0.30 per 10,000 livebirths (1/33,330-1/47,620 livebirths). In Texas, fathers that were 25-29, 30-34, 35-39, and > or =40 years of age had significantly increased rates of de novo achondroplasia among their offspring compared with younger fathers. The adjusted prevalence odds ratios were 2.8 (95% CI; 1.2, 6.7), 2.8 (95% CI; 1.0, 7.6), 4.9 (95% CI; 1.7, 14.3), and 5.0 (95% CI; 1.5, 16.1), respectively. Using the same age categories, the crude prevalence odds ratios for de novo cases of thanatophoric dysplasia in Texas were 5.8 (95% CI; 1.7, 9.8), 3.9 (95% CI; 1.1, 6.7), 6.1 (95% CI; 1.6, 10.6), and 10.2 (95% CI; 2.6, 17.8), respectively. These data suggest that thanatophoric dysplasia is one-third to one-half as frequent as achondroplasia. The differences in the prevalence of these conditions across monitoring programs were consistent with random fluctuation. Birth defects monitoring programs may be a good source of ascertainment for population-based studies of achondroplasia and thanatophoric dysplasia, provided that diagnoses are confirmed by review of medical records.     

Analysis of skeletal dysplasias in the Utah population

The Utah Birth Defect Network (UBDN) collects population-based data for Utah on births from all resident women. The prevalence of skeletal dysplasias and epidemiologic characteristics/outcomes were evaluated. Cases categorized as a skeletal dysplasia from all live births, stillbirths, and pregnancy terminations (TAB) between 1999 and 2008 were reviewed by three clinical geneticists. After case review, 153 were included for analysis (88% live births, 3% stillborn, 9% TAB), and categorized by groupings defined by molecular, biochemical, and/or radiographic criteria as outlined in the 2010 Nosology and Classification of Genetic Skeletal Disorders. The overall prevalence for skeletal dysplasias was 3.0 per 10,000 births, and 20.0 per 10,000 stillbirths. The most common diagnostic groups were osteogenesis imperfecta (OI; n = 40; 0.79 per 10,000), thanatophoric dysplasia (n = 22; 0.43 per 10,000), achondroplasia (n = 18; 0.35 per 10,000), and cleidocranial dysplasia (n = 6; 0.12 per 10,000). The most common groups based on the 2010 Nosology and Classification of Genetic Skeletal Disorders were the FGFR3 chondrodysplasia group (n = 41; 0.81 per 10,000), the OI/decreased bone density group (n = 40; 0.79 per 10,000), and the type 2 collagen group (n = 10; 0.2 per 10,000). Median age of postnatal diagnosis was 30 days (range 1-2,162). Of those deceased, 88% were prenatally suspected; of those alive 29% prenatally suspected. Median age of death for live born individuals was 1 day (range 1-1,450 days). Previously reported prevalence rates vary, but our data provide a population-based approach not limited to the perinatal/neonatal period. Understanding the range for survival within each group/diagnosis is beneficial for health care providers when counseling families.     

山西省出生缺陷高发区重大体表出生缺陷的流行状况研究

目的了解山西省出生缺陷高发地区目前各种体表出生缺陷患病水平及流行特征.方法以人群为基础对山西省的4个县24种体表重大出生缺陷进行监测.结果 2003年四个县共监测到孕满20周以上的出生11534名,总出生缺陷患病率分别为232.4/万.神经管畸形患病率为138.7/万,占全部出生缺陷病例的59.7%.患病率高于10/万的出生缺陷有7种,依次为:无脑儿(65.9/万)、脊柱裂(58.1/万)、脑积水(47.7/万)、多指(26.0/万)、腭裂(21.7/万)、脑膨出(14.7/万)、唇裂(10.4/万).产妇文化程度低和女性胎婴神经管畸形的患病率显著增高.此外,居住在农村,妇女年龄不足20岁或30岁以上神经管畸形患病率有升高的趋势.结论神经管畸形仍然为山西省出生缺陷高发区最常见的先天畸形,目前其患病率仍然处于我国乃至世界最高的水平.居住在农村、文化程度低、怀孕年龄太小或较大的妇女生育出生缺陷儿的危险性较大.     

Recent trends in the prevalence of Down syndrome in Japan, 1980–1997

The aims of the present study were to determine recent trends in the prevalence of Down syndrome (DS) in Japan, and to determine whether recent changes in demographic and social habits and access to prenatal diagnosis have influenced the livebirth rates of DS. Livebirth statistics indicate that the birth rate in Japan has decreased for women in their 20s and has increased for those in their 30s and 40s. During an 18-year period between 1980 and 1997, 1,299 consecutive DS infants were born among a total of 2,232,694 births, a rate corresponding to approximately 10% of all births in Japan over the same period. The increasing risk of DS with advancing maternal age was confirmed. The overall prevalence was 5.82 DS births per 10,000 livebirths (8.3–9.7 per 10,000 after correction according to the estimated ascertainment ratio: 60–70%). The prevalence rate by year of child birth represents a statistically significant increase (P = 0.001). In conclusion, recent trends in the prevalence of DS in Japan from 1980 to 1997 failed to show a consistent tendency to decrease, probably because of the concomitant increase in pregnancy in advanced maternal age. Am. J. Med. Genet. 84:340–345, 1999. © 1999 Wiley-Liss, Inc.     

Congenital clubfoot in Europe: A population‐based study

We aimed to assess prevalence, birth outcome, associated anomalies and prenatal diagnosis of congenital clubfoot in Europe using data from the EUROCAT network, and to validate the recording of congenital clubfoot as a major congenital anomaly by EUROCAT registries. Cases of congenital clubfoot were included from 18 EUROCAT registries covering more than 4.8 million births in 1995–2011. Cases without chromosomal anomalies born during 2005–2009, were randomly selected for validation using a questionnaire on diagnostic details and treatment. There was 5,458 congenital clubfoot cases of which 5,056 (93%) were liveborn infants. Total prevalence of congenital clubfoot was 1.13 per 1,000 births (95% CI 1.10–1.16). Prevalence of congenital clubfoot without chromosomal anomaly was 1.08 per 1,000 births (95% CI 1.05–1.11) and prevalence of isolated congenital clubfoot was 0.92 per 1,000 births (95% CI 0.90–0.95), both with decreasing trends over time and large variations in prevalence by registry. The majority of cases were isolated congenital clubfoot (82%) and 11% had associated major congenital anomalies. Prenatal detection rate of isolated congenital clubfoot was 22% and increased over time. Among 301 validated congenital clubfoot cases, diagnosis was confirmed for 286 (95%). In conclusion, this large population‐based study found a decreasing trend of congenital clubfoot in Europe after 1999–2002, an increasing prenatal detection rate, and a high standard of coding of congenital clubfoot in EUROCAT.     

Altitude as a risk factor for congenital anomalies

The birth prevalence of specific types of congenital anomalies at low and high altitudes in South America were compared after adjustment for prenatal growth, ethnicity, and socioeconomic status. The material includes all 1,668,722 consecutive births occurring in 53 hospitals participating in the Latin-American Collaborative Study of Congenital Malformations (ECLAMC), having registered at least 100 malformed/control pairs between 1967 and 1995. The lowland subsample (below 2,000 m above the sea level) included 46,729 case-control pairs, ascertained in 1,539,432 births from 49 hospitals in 38 cities. The highlands (above 2,000 m) comprised 3,498 case-control pairs from 129,301 births, occurring in four hospitals from three cities. Unconditional logistic regression was used to estimate the relative risks for the exposure at high altitudes, adjusted by ethnicity (Amerindian yes/no), type of health service (public/private), and birth weight (below/equal and greater than 2,500 g). The adjusted relative risks showed significantly (P < 0.01) higher values in the high than in the lowlands for four types of defects: cleft lip [relative risks (RR): 1.57; 95% confidence interval (CI): 1.27–1.94], microtia (RR: 3.21; 95% CI: 2.35–4.79), preauricular tag (RR: 2.09; 95% CI: 1.86–2.36), branchial arch anomaly complex (RR: 1.79; 95% CI: 1.23–2.61), constriction band complex (RR: 1.92; 95% CI: 1.11–3.31), and anal atresia (RR: 1.61; 95% CI: 1.01–2.57). Conversely, lower risks in the highlands were registered for two neural tube defects: anencephaly (RR: 0.33; 95% CI: 0.20–0.54), spina bifida (RR: 0.57; 95% CI: 0.37–0.78), as well as for hydrocephaly (RR: 0.41; 95% CI: 0.22–0.77) and pes equinovarus (RR: 0.70; 95% CI: 0.51–0.96). Even though some of these differences may be caused by undetected confounders, the coincidental finding of four types of craniofacial defects with higher, and two types of neural tube defect with lower frequencies in the highlands, suggest a real biological foundation. Am. J. Med. Genet. 86:9–14, 1999. © 1999 Wiley-Liss, Inc.     

Neonatal outcome and congenital malformations in children born after in-vitro fertilization

BACKGROUND: To evaluate the neonatal outcome and the prevalence of congenital malformations in children born after IVF in northern Finland we carried out a population-based study with matched controls. METHODS: Firstly, 304 IVF children born in 1990-1995 were compared with 569 controls, representing the general population in proportion of multiple births, randomly chosen from the Finnish Medical Birth Register (FMBR) and matched for sex, year of birth, area of residence, parity, maternal age and social class. Secondly, plurality matched controls (n = 103) for IVF twins (n =103) were randomly chosen from the FMBR and analysed separately. Additionally, IVF singletons (n = 153) were compared with singleton controls (n = 287). Mortality rates were compared with national figures from FMBR. RESULTS: Most mortality rates were twice as high as national figures in the general population. When compared with the control group representing the general population, the incidences of preterm birth [odds ratio (OR) 5.6, 95% confidence interval (CI) 3.7-8.6], very low birth weight (OR 6.2, 95% CI 2.0-19.0), low birth weight (OR 9.8, 95% CI 5.6-17.3), neonatal morbidity (OR 2.4, 95% CI 1.7-3.4) and hospitalization (OR 3.2, 95% CI 2.2-4.6) were significantly higher in the IVF group. The prevalence of heart malformations was four-fold in the IVF population than in the controls representing the general population (OR 4.0, 95% CI 1.4-11.7). CONCLUSIONS: Neonatal outcome after IVF is worse than in the general population with similar maternal age, parity and social standing, mainly due to the large proportion of multifetal births after IVF. The higher prevalence of heart malformations does not solely arise from multiplicity but from other causes. In order to improve neonatal outcome after IVF, the number of embryos transferred should be limited to a minimum.     

Sex differences for major congenital heart defects in Down Syndrome: A population based study

Background

Down syndrome (DS) is the most common autosomal chromosomal anomaly in liveborn infants. About 40% of infants with DS have a major congenital heart defect (CHD). Among them, atrioventricular septal defects (AVSD), atrial septal defects (ASD), ventricular septal defect (VSD) and Tetralogy of Fallot (ToF) are the most common. The aim of this study was to estimate the sex difference in the occurrence of CHD in infants with DS comparing it with non-DS infants.

Hereditary tyrosinemia in the province of Quebec: Prevalence at birth and geographic distribution

Hereditary tyrosinemia is a severe metabolic disorder of the newborn for which a very low prevalence at birth has been reported throughout the world. During a 2-year period, the Quebec Network of Genetic Medicine has tested blood tyrosine in 81.6 % of newborns. Twelve babies with hereditary tyrosinemia were detected by biochemical screening and two more cases were identified by pediatricians. Prevalence at birth way 0.8 case per 10,000 live births in the province of Quebec as a whole; the Chicoutimi-Lac St. Jean region was found to have an exceptional concentration of 14.6 caqes per 10,000 live births and a frequency of carriers of 1 in 14 persons. such an experimental screening program helps define health problems in a population.     

Birth prevalence,mutation rate,sex ratio,parents' age,and ethnicity in Apert syndrome

Apert syndrome was studied to determine birth prevalence, mutation rate, sex ratio, parents' age, and ethnicity among 2,493,331 live births registered in the California Birth Defects Monitoring Program (CBDMP) from 1983 through 1993; 31 affected infants were identified. The sample was completed with an additional 22 cases from the Center for Craniofacial Anomalies (CCA), University of California, San Francisco, for a total of 53 affected children. Birth prevalence, calculated from the CBDMP subsample, was 12.4 cases per million live births (confidence interval [CI] 8.6,17.9). The calculated mutation rate was 6.2 × 10⁻⁶ per gene per generation. Asians had the highest prevalence (22.3 per million live births; CI 7.1,61.3) and Hispanics the lowest (7.6 per million, CI 3.3-16.4). In the large population-based CBDMP subsample, there was an almost equal number of affected males and females, (sex ratio 0.94) but in the clinical CCA subsample, there were more affected females (sex ratio 0.79). For all cases, the mean age of mothers was 28.9±6.0 years, and of fathers was 34.1±6.2 years. Almost half of fathers were older than 35 years when the child was born; for more than 20% of cases, both parents were older than 35 years. These findings may support the view that point mutations appear to be more commonly associated with paternal than with maternal alleles. Representing the largest systematically ascertained population-based study of Apert syndrome to date, they provide a reliable basis for genetic counseling and decision-making, and for focused research to define the cause of this syndrome. Am. J. Med. Genet. 72:394–398, 1997. © 1997 Wiley-Liss, Inc.