Birth Prevalence Rates Research Articles

Malformaciones congénitas asociadas alSíndrome Down en recién nacidos de un hospitalde referencia nacional: Experiencia de un registrode defectos congénitos

Objective: Down syndrome is the most common chromosomal abnormality in newborns and the first genetic cause of intellectual disability. The objective of this study was to describe associated birth defects with Down syndrome in newborns at the Edgardo Rebagliati MartinsHospital (HNERM). Materials and methods: A descriptive, retrospective and cross-sectionalstudy was conducted. The study population consisted of 191 births diagnosed with Downsyndrome, during the period 2013-2017 of the registry of the Latin American Collaborative Study of Congenital Malformations (ECLAMC) of the HNERM. Results: In the study period, a total of 191 newborns with suspected Down syndrome were reported, of which 180 wereconfirmed with karyotyping, out of a total of 34,326 live births. Free trisomy accounted for98.9%, while mosaicism and translocation trisomy occurred in 0.6% of newborns. The median maternal age was 39 years (range 20-46 years). Congenital heart disease was observed in 61.7%, gastrointestinal malformation 10%, craniofacial malformation 5%, genitourinary 3.9%, musculoskeletal malformation 1.7% and central nervous system malformation 1.7%. Conclusions: The birth prevalence rate of Down syndrome in the study period was 52.4 per 10,000 births. The most frequent malformations associated with Down syndrome are congenital heart disease and secondly malformations of the gastrointestinal tract. Other lessfrequently associated malformations are craniofacial, genitourinary, musculoskeletal and central nervous system malformations.

Elevated congenital heart disease birth prevalence rates found in Central Vietnam and dioxin TCDD residuals from the use of 2, 4, 5-T herbicides (Agent Orange) in the Da Nang region.

Congenital heart disease (CHD) birth prevalence rate in Da Nang City and two adjacent provinces in Central Vietnam reported by Giang et al. in 2019 was 20.09/1000 births, much higher than any CHD birth rates previously reported. In this current study, three physicians trained in pediatric cardiology reanalyzed and reclassified the Giang et al 2019 cardiac anomalies data, eliminating singular small PDAs and separating cardiac defects into 27 contemporary CHD subgroups. These CHD subgroups were then statistically compared with Liu et al. 2019 Global CHD birth prevalence study of Asian Low-Middle Income Countries (LMIC) CHD subgroup rate of 9.34/1000 births (95% CI 8.07-10.70). Despite applying newer diagnostic criteria and refining the cardiac anomalies data, the Da Nang region continued to show significantly (p<0.0001) elevated total CHD birth prevalence rates at 14.71/1000 births (95% CI 12.74-16.69) compared to the Asian LMIC CHD birth prevalence rate 9.34/1000 births. This finding raises the question of whether environmental persistence of the contaminant dioxin TCDD from 2,4,5-T herbicides (Agent Orange) used during the Vietnam War (1961-1971) in the Da Nang region might be a factor associated with elevated CHD birth prevalence, as it is not present in other LMIC surrounding Vietnam. We recommend testing of soils and sediments in rural and agricultural areas in Central Vietnam that received high volume applications of contaminated herbicides to assess the relationship of the higher CHD birth prevalence rate and the presence of residual dioxin TCDD. Enhanced fetal cardiac echocardiograpy in the region to screen for CHD would enable early interventions and could improve outcomes for infants and children.

Analysis of early neonatal case fatality rate among newborns with congenital hydrocephalus, a 2000-2014 multi-country registry-based study.

Congenital hydrocephalus (CH) comprises a heterogeneous group of birth anomalies with a wide-ranging prevalence across geographic regions and registry type. The aim of the present study was to analyze the early neonatal case fatality rate (CFR) and total birth prevalence of newborns diagnosed with CH. Data were provided by 25 registries from four continents participating in the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) on births ascertained between 2000 and 2014. Two CH rates were calculated using a Poisson distribution: early neonatal CFR (death within 7 days) per 100 liveborn CH cases (CFR) and total birth prevalence rate (BPR) per 10,000 births (including live births and stillbirths) (BPR). Heterogeneity between registries was calculated using a meta-analysis approach with random effects. Temporal trends in CFR and BPR within registries were evaluated through Poisson regression modeling. A total of 13,112 CH cases among 19,293,280 total births were analyzed. The early neonatal CFR was 5.9 per 100 liveborn cases, 95% confidence interval (CI): 5.4-6.8. The CFR among syndromic cases was 2.7 times (95% CI: 2.2-3.3) higher than among non-syndromic cases (10.4% [95% CI: 9.3-11.7] and 4.4% [95% CI: 3.7-5.2], respectively). The total BPR was 6.8 per 10,000 births (95% CI: 6.7-6.9). Stratified by elective termination of pregnancy for fetal anomalies (ETOPFA), region and system, higher CFR were observed alongside higher BPR rates. The early neonatal CFR and total BPR did not show temporal variation, with the exception of a CFR decrease in one registry. Findings of early neonatal CFR and total BPR were highly heterogeneous among registries participating in ICBDSR. Most registries with higher CFR also had higher BPR. Differences were attributable to type of registry (hospital-based vs. population-based), ETOPFA (allowed yes or no) and geographical regions. These findings contribute to the understanding of regional differences of CH occurrence and early neonatal deaths.

Time trends, geographic variation and risk factors for gastroschisis in Canada: A population-based cohort study 2006-2017.

BackgroundPrevious studies showed increases in rates of gastroschisis in Canada in the first decade of the 21st century.ObjectiveWe sought to examine the epidemiologic characteristics of gastroschisis in Canada in recent years.MethodsWe conducted a retrospective population‐based cohort study of all livebirths and stillbirths delivered in Canada (excluding Quebec) from 2006 to 2017, with information obtained from the Canadian Institute for Health Information. Gastroschisis rates by maternal age, region of residence, and maternal and infant characteristics were quantified using prevalence rate ratios (RR) and 95% confidence intervals (CI). Log‐binomial regression was used to quantify the associations between risk factors and gastroschisis.ResultsThere were 1314 gastroschisis cases among 3 364 116 births. The prevalence rate was 3.7 per 10 000 total births in 2006 and 3.4 per 10 000 total births in 2017, with substantial annual variation in rates. The proportion of mothers aged 20–24 years decreased from 16.5% in 2006 to 11.3% in 2017, while the proportion of mothers aged <20 years halved from 4.8% to 2.3%. The prevalence of gastroschisis at birth remained unchanged among mothers aged <20, 20–24 and 30–49 years but increased among mothers aged 25–29 years. The age‐adjusted prevalence rate of gastroschisis increased across the period (for 2016–2017 versus 2006–2007 rate ratio [RR] 1.28, 95% CI 1.05, 1.56), and there was substantial regional variation. Risk factors included problematic use of substances (RR 2.61, 95% CI 2.01, 3.39) and hypothyroidism (RR 2.76, 95% CI 1.56, 4.88). There was a North‐to‐South difference in gastroschisis prevalence (adjusted RR Far North compared with South 1.54, 95% CI 1.11, 2.15).ConclusionGastroschisis birth prevalence rates in Canada have stabilised in recent years compared with the increase documented previously. The substantial geographic variation and North‐to‐South difference in gastroschisis prevalence may indicate variation in socio‐economic status, lifestyle and nutritional patterns.

Omphalocele: national current birth prevalence and survival

PurposeThe increase in prenatal diagnosis together with the high rates of associated anomalies in omphalocele has led to increased rates of termination of pregnancies. The aim of this study was to examine the national Swedish birth prevalence and survival rates among these patients.MethodsThis study is based on a nationwide population-based cohort of all children born in Sweden between 1/1/1997 and 31/12/2016. All omphalocele cases were identified though the Swedish National Patient Register and the Swedish Medical Birth Register. Outcome of malformations and deaths were retrieved from the Swedish Birth Defects Register and the Swedish Causes of Death Register.ResultsThe study included 207 cases of omphalocele (42% females). The birth prevalence for omphalocele was 1/10,000 live births. About 62% of the cases had associated malformations and/or genetic disorders; most common was ventricular septal defect. The mortality within the first year was 13%. The rate of termination of pregnancy was 59%.ConclusionThe national birth prevalence for omphalocele in Sweden is 1/10,000 newborn, with high termination rates. Over half of the pregnancies with prenatally diagnosed omphalocele will be terminated. Among those who continue the pregnancy, 1-year survival rates are high.Type of studyNational register studyLevel of evidenceIII.

Observed birth prevalence of congenital anomalies among live births at a regional facility in KwaZulu Natal Province, South Africa.

Congenital disorders (CDs), defined as abnormalities in structure or function present at birth, are an important contributor to the disease burden in developing countries. The size and extent of the problem in South Africa (SA) are unknown due to the lack of recent, reliable, observed data on CDs. To address this empirical data gap, this study aimed to measure the birth prevalence of congenital anomalies (a sub-set of CDs) and to describe the pattern of these anomalies at a regional hospital in KwaZulu Natal (KZN), SA. A retrospective, observational, descriptive review of congenital anomalies diagnosed within the neonatal service at Edendale Hospital (EDH), KZN was undertaken between January and December 2018. All EDH in-house live births diagnosed and notified with congenital anomalies by discharge were included. Stillbirths, other pregnancy losses and out-born neonates were excluded. Data were actively collected from the birth register, neonatal admission register, and the individual paper-based surveillance tool developed by the National Department of Health. The in-facility birth prevalence rate for congenital anomalies was 15.57 per 1 000 live births. The most observed system was musculoskeletal (32%) followed by circulatory system anomalies (19%). When the observed birth prevalence rates of key congenital anomalies were compared with previously published, modelled South African data, no significant difference was found. This study responds to the paucity of birth prevalence data on CDs overall and offers evidence that obvious, structural CDs (congenital anomalies) need to be addressed in the SA public health system.

Childhood prevalence of achondroplasia in New South Wales and the Australian Capital Territory, Australia.

The aim of this study was to estimate the childhood prevalence of achondroplasia, trends over time in birth prevalence, and age at diagnosis in Australia. Children born between 1990 and 2019 with a clinical and radiological and/or molecular diagnosis of achondroplasia were identified from a tertiary hospital servicing New South Wales (NSW) and the Australian Capital Territory (ACT) and compared with population data from the Australian Bureau of Statistics. Childhood prevalence of achondroplasia, based on children ≤19 years of age and resident in NSW/ACT on June 30, 2019 (n = 109), was 5.2 per 100,000. A total of 127 individuals with achondroplasia were born in 1990-2019 in NSW/ACT. Birth prevalence rates increased across birth decades, from 3.3 per 100,000 live births in 1990-1999 to 5.3 per 100,000 in 2010-2019 (p < 0.0001). Median age at diagnosis decreased to 17 days in 2010-2019 compared with 30 days in 1990-1999 (p = 0.035), although the overall decreasing trend across consecutive decades did not reach statistical significance. This is the first study to show a rising birth prevalence rate for achondroplasia in Australia with a concurrent decreasing age at diagnosis, both of which were statistically significant after 2 decades.

Maternal age in the epidemiology of common autosomal trisomies.

The birth prevalence rate of each common autosomal trisomy generally increases with advancing maternal age and there is a substantial fetal loss rate between late first trimester and term. The literature is reviewed in order to provide the best estimates of these rates, taking account where possible of biases due to prenatal diagnosis and selective termination of pregnancy. There is an almost exponential increase in Down syndrome birth prevalence between ages 15 and 45 but at older ages the curve flattens. There is no evidence of the claimed relatively high birth prevalence at extremely low ages. Gestation-specific intra-uterine fetal loss rates are estimated by follow-up of women declining termination of pregnancy after prenatal diagnosis, comparison of observed rates with those expected from birth prevalence and comparison of age-specific curves developed for prenatal diagnosis and birth. Down syndrome fetal loss rates reduce with gestation and increase with maternal age. Edwards and Patau syndrome birth prevalence is approximately 1/8 and 1/13 that of Down syndrome overall, although the ratio differs according to maternal age, particularly for Patau syndrome where it reduces steadily from 1/9 to 1/19. Fetal loss rates are higher for Edwards and Patau syndromes than for Down syndrome.

Nationwide epidemiological survey of holoprosencephaly in Japan.

Holoprosencephaly (HPE) is a congenital malformation with an estimated prevalence of 0.10-6.06 per 10000 births but with no nationwide data specific to Japan. This nationwide retrospective questionnaire survey was conducted from 2011 to 2013. All 467 training hospitals for perinatal and neonatal care certified by the Japan Society of Perinatal and Neonatal Medicine were contacted. The birth prevalence rate (BPR) was assessed from the primary survey and clinical characteristics from the secondary survey. We received valid responses from 253 hospitals in the primary survey (54.6%). Of 390342 live births, 60 were diagnosed with HPE (23 males and 37 females), resulting in an actual BPR of 1.54 per 10000 live births. The point estimate for HPE cases was 100 (95% confidence interval [CI]: 80.7-120), and the estimated BPR of HPE was calculated to be 0.32 per 10000 live births (95% CI: 0.26-0.38) based on 3117853 live births according to Japanese national statistics during the study period. In the secondary survey, we obtained data for 49 cases (19 males and 30 females). Of these, 20 were alobar (40.8%), 20 were semilobar (40.8%), five were lobar (10.4%), and four were of unknown type. Genetic examination was performed in 37 of the 49 HPE patients and revealed that chromosomes 13, 18, and 7 were affected in eight, six, and four patients, respectively. This is the most extensive survey on holoprosencephaly to date in Japan. The estimated BPR was consistent with that reported in previous research.

Gastroschisis in Finland 1993 to 2014-Increasing Prevalence, High Rates of Abortion, and Survival: A Population-Based Study.

The study aims to assess the changes in prevalence and mortality of gastroschisis, and to identify associated anomalies. It is a population-based nationwide study. All gastroschisis cases were identified in the Finnish Register of Congenital Malformations and the Care Register for Health Care from 1993 to 2014 including live births, stillbirths, and terminations of pregnancy due to fetal anomalies. Associated anomalies were recorded, and analyzed, and prevalence and infant mortality were calculated. There were 320 cases of gastroschisis; 235 (73%) live births, 16 (5%) stillbirths, and 69 (22%) terminations of pregnancy. Live birth prevalence of gastroschisis in Finland was lower than generally reported (1.73 in 10,000). However, due to relatively high rates of abortion, our total prevalence of 2.57/10,000 was similar with other reports. The most common risk factor was young maternal age. Babies with gastroschisis were born prematurely, on average on the 36th week and most are delivered by caesarean section. There was a significant increasing trend in live birth prevalence (p = 0.0018). Overall infant mortality was 7.7% (18/235), 7.2% (16/222) in simple gastroschisis and 15% (2/13) in complex gastroschisis. Associated anomalies were rare both in aborted fetuses and neonates, and there was only one case with a chromosomal abnormality. Gastroschisis is usually an isolated anomaly with increasing birth prevalence and excellent survival rates. Regardless of the good prognosis, the abortion rates in Finland are higher than previously reported, and we hypothesize this to be due to lack of appropriate antenatal counselling.

Impact of Maternal Immunity on Congenital Cytomegalovirus Birth Prevalence and Infant Outcomes: A Systematic Review.

Congenital cytomegalovirus (cCMV) is the leading non-genetic cause of sensorineural hearing loss (SNHL), and efforts are geared towards prevention through vaccine development. Transmission rates following primary maternal infection occur at rates of 30–40%, however reported placental rates upon non-primary maternal infection is reported to be less than <4%. There is significant debate about whether this reduction in transmission rate is due to pre-existing maternal immunity, which could identify possible immunologic targets for vaccines. To address this question, we performed a systemic review of the literature using Preferred Reporting Items for Systematic Review and Analysis (PRISMA) guidelines. We identified cohort studies in high CMV seroprevalent (>80%) areas or in developing regions that examined a cohort of at least 50 infants for congenital CMV acquisition. We identified 19 articles that met criteria and were further categorized based on pre-conception serology, maternal seroprevalence, or previously known seroprevalence. Birth prevalence rates ranged from 0.4% to 6% (median 1.1%), with the studies reporting on clinical outcome (16/19 studies) noting the majority of infected infants as asymptomatic. We also utilized a recent study that differentiated primary maternal infections from chronic infections in a highly seropositive population to calculate a placental transmission rate in women with pre-existing immunity compared to that of no pre-existing immunity. This work confirms a low cCMV birth prevalence in highly seropositive populations, indicates via a calculated placental transmission rate that the CMV placental transmission rate is lower in non-primary infection than that of primary infection, and reveals gaps in data for further research aiming to identify targets for vaccine development.

The global burden of sickle cell disease in children under five years of age: a systematic review and meta-analysis.

BackgroundSickle cell disease (SCD) is a common haematological disorder, affecting millions of people worldwide. It is most prevalent in malarial endemic areas in the tropics where outcomes are often poor due to resource constraints, resulting in most children dying before reaching adulthood. As increasing progress is made towards reducing under 5 mortality from infectious causes, non-communicable diseases (NCDs) including SCD have risen to the forefront of the global health agenda. Despite this, the global mortality burden of SCD remains poorly understood. This study aimed to estimate the incidence and mortality of SCD in children under 5 years of age in order to inform policy and develop sustainable strategies to improve outcomes.MethodologyWe performed a systematic literature search of Medline, EMBASE, Journals@Ovid, and Web of Science for studies on the incidence and mortality of SCD in children under 5, with search dates set from January 1980 and July 2017. We conducted random effects meta-analysis to obtain pooled meta-estimates of birth prevalence and mortality rates globally, and for each World Health Organization (WHO) region.Results67 papers were found with relevant data. 52 contained data on incidence and prevalence and 15 contained data on mortality. The overall pooled estimate of mortality from the limited data available was 0.64 per 100 years of child observation (95% CI = 0.28-1.00) with the highest rate seen in Africa 7.3 (95% CI = 4.03-10.57). The global meta-estimate for the birth prevalence of homozygous sickle cell disease was 112 per 100 000 live births (95% CI = 101-123) with a birth prevalence in Africa of 1125 per 100 000 (95% CI = 680.43-1570.54) compared with 43.12 per 100 000 (95% CI = 30.31-55.92) in Europe.ConclusionThere were a number of limitations in the depth and breadth of available data however it is clear that both the highest prevalence and highest mortality of SCD is in Africa. In order to address this burden, there is a need for national comprehensive newborn screening to identify patients, and the development of holistic SCD care programmes to provide therapeutics and education for families and children with SCD. This targeted funding should form part of a broader increased global focus on NCDs in childhood.

Global birth prevalence and mortality from inborn errors of metabolism: a systematic analysis of the evidence.

BackgroundInborn errors of metabolism (IEM) are a group of over 500 heterogeneous disorders resulting from a defect in functioning of an intermediate metabolic pathway. Individually rare, their cumulative incidence is thought to be high, but it has not yet been estimated globally. Although outcomes can often be good if recognised early, IEM carry a high fatality rate if not diagnosed. As a result, IEM may contribute significantly to the burden of non-communicable childhood morbidity.MethodsWe conducted a systematic literature review of birth prevalence and case fatality of IEM globally, with search dates set from 1980 to 2017. Using random-effects meta-analysis, we estimated birth prevalence of separate classes of IEM and all-cause IEM, split by geographical region. We also estimated levels of parental consanguinity in IEM cases and global case fatality rates and resultant child deaths from all-cause IEM.Findings49 studies met our selection criteria. We estimate the global birth prevalence of all-cause IEM to be 50.9 per 100 000 live births (95% confidence intervals (CI) = 43.4-58.4). Regional pooled birth prevalence rates showed the highest rates of IEM to be in the Eastern Mediterranean region (75.7 per 100 000 live births, 95% CI = 50.0-101.4), correlating with a higher observed rate of parental consanguinity in studies from this area. We estimate case fatality rates to be 33% or higher in low- and middle-income countries (LMICs), resulting in a minimum of 23 529 deaths from IEM per year globally (95% CI = 20 382-27 427), accounting for 0.4% of all child deaths worldwide.ConclusionsIEM represent a significant cause of global child morbidity and mortality, comprising a notable proportion of child deaths currently not delineated in global modelling efforts. Our data highlight the need for policy focus on enhanced laboratory capacity for screening and diagnosis, community interventions to tackle parental consanguinity, and increased awareness and knowledge regarding management of IEM, particularly in LMICs.

PSY37 - SYSTEMATIC LITERATURE REVIEW ON THE WORLDWIDE EPIDEMIOLOGY OF PROPIONIC ACIDEMIA

Propionic acidemia or aciduria (PA) is a serious, life-threatening inherited metabolic disorder characterized by the accumulation of propionic acid and other toxic metabolites due to deficiency in propionyl-CoA carboxylase, a mitochondrial enzyme complex comprised of two subunits that participates in the breakdown of certain proteins and fats. PA is associated with significant morbidity and mortality, with the majority of patients presenting within the first few days or weeks of life. The objective of this systematic literature review was to assess and compile published epidemiological data on PA (OMIM #606054). The SLR was conducted and reported in compliance with the PRISMA statement and covered Medline, Embase, Cochrane Database of Systematic Reviews, CRD, Academic Search Complete, CINAHL and PROSPERO databases. Websites of rare disease organizations were also searched for eligible studies. Out of the 3312 identified records, 188 papers were assessed for eligibility in full text and finally, 79 articles were included into the qualitative synthesis. Newborn screening programs provided relatively precise estimates on the birth prevalence of PA. The overall detection rates of PA remained under 8.14 cases per 100,000 newborns in all geographic regions. A tendency towards increased birth prevalence rates was observed in the Middle East and North Africa. Studies conducted in North America and Europe reported birth prevalence rates lower than 2.2 cases per 100,000 newborns. Point prevalence was not reported in any article with the exception of one study from Oman that estimated 0.40 cases per 100,000 inhabitants. The majority of the relevant publications reported on newborn screening programs that provided valuable data on the birth prevalence of the disease. Only one study reported point prevalence for the disorder. The conducted literature review clearly indicates that PA is a rare disease.

Correlation between tobacco control policies and preterm births and low birth weight in Europe

ObjectiveTo assess the correlation between tobacco control policies— particularly smoking bans in work and public places—and the prevalence of preterm births and low birth weight in the European countries. MethodsThis is an ecological study and the unit of analysis set at the country level. Tobacco control data in Europe were obtained for the years 2010 and 2013 as measured by the Tobacco Control Scale (TCS), which reflects the level of implementation of tobacco control policies. Prevalence data for preterm births and low birth weight were obtained from two sources: the European Perinatal Health Report (EPHR), which provides data for 2010, and the Eurostat data, which includes the years 2013 and 2014. We analyzed the correlation between the TCS score and the prevalence of preterm birth and low birth weight in the European countries by means of Spearman (rsp) rank-correlation coefficients and their 95% confidence intervals (95%CI). ResultsThe 2010 TCS was negatively correlated with the prevalence of preterm births before week 37 (rsp = −0.51; 95% CI: −0.77, −0.15; p = 0.006) and week 32 (rsp = −0.42; 95%CI: −0.73, −0.01; p = 0.030) and with the prevalence of the low birth weight (< 2500g, (rsp = −0.42; 95% CI: −0.66, −0.09; p = 0.028) in European countries in 2010. We found a statistically significant inverse correlation between the level of restrictions on smoking in public places and the prevalence of low birth weight (< 2500g rsp: −0.54; 95%CI: −0.72, −0.10; p = 0.017). ConclusionThe level of smoke-free legislation in European countries correlates with lower preterm birth prevalence rates at the ecological level. Given the important negative effects of premature births for the public health system, these data support greater implementation of smoke-free policies and tend to support the implementation of tobacco control policies, but more research is needed.

Birth Prevalence of Anorectal Malformations for the Western Cape Province, South Africa, 2005 to 2012.

Introduction Anorectal malformations (ARMs) are a major birth anomaly worldwide. South Africa has ethnically and geologically diverse populations. A recent publication indicated an increased birth prevalence of ARMs in the Witwatersrand referral area between 2005 and 2010. The purpose of this study was to determine the birth prevalence of ARM and its various subtypes in the Western Cape referral district over an 8-year period. Methods For an 8-year period from January 1, 2005, to December 31, 2012; retrospective data were collected from the Pediatric Surgical Departments of Red Cross War Memorial Children's Hospital, Tygerberg Children's Hospital, as well as the private sector health registries. The number of live births per year for a specific municipal district was obtained from the National Department of Health. The chi-square for trend test was used to determine statistical significance. Results The birth prevalence for ARM in the Western Cape Province (WCP) in 2012 was shown to be 1:5,572 live births (1.79/10,000 live births). The West Coast municipality district had the highest average birth prevalence rate of 1:3,063 (3.26/10,000) live births for years studied. There was a male predominance (1.6:1), the most common ARM was the vestibular fistula (19.2%) and in 26% of the patients, there was an initial delay in the diagnosis. Conclusion This study has provided some recent data for ARMs for the WCP. There was no statistical significant change in the prevalence of ARMs over the 8-year period for the WCP as well as in any of the individual six municipal health districts (χ2 for trend, p = 0.52). The number of delayed diagnosis of ARM is of concern.

Clinical Characteristics, Mutation Spectrum, and Prevalence of Åland Eye Disease/Incomplete Congenital Stationary Night Blindness in Denmark.

PurposeTo assess clinical characteristics, foveal structure, mutation spectrum, and prevalence rate of Åland eye disease (AED)/incomplete congenital stationary night blindness (iCSNB).MethodsA retrospective survey included individuals diagnosed with AED at a national low-vision center from 1980 to 2014. A subset of affected males underwent ophthalmologic examinations including psychophysical tests, full-field electroretinography, and spectral-domain optical coherence tomography.ResultsOver the 34-year period, 74 individuals from 35 families were diagnosed with AED. Sixty individuals from 29 families participated in a follow-up study of whom 59 harbored a CACNA1F mutation and 1 harbored a CABP4 mutation. Among the subjects with a CACNA1F mutation, subnormal visual acuity was present in all, nystagmus was present in 63%, and foveal hypoplasia was observed in 25/43 subjects. Foveal pit volume was significantly reduced as compared to normal (P < 0.0001). Additionally, outer segment length at the fovea was measured in 46 subjects and found to be significantly reduced as compared to normal (P < 0.001). Twenty-nine CACNA1F variations were detected among 34 families in the total cohort, and a novel CABP4 variation was identified in one family. The estimated mean birth prevalence rate was 1 per 22,000 live-born males.ConclusionsOur data support the viewpoint that AED, iCSNB, and X-linked cone–rod dystrophy 3 are designations that refer to a broad, continuous spectrum of clinical appearances caused in the majority by a variety of mutations in CACNA1F. We argue that the original designation AED should be used for this entity.

Effect of Folic Acid Food Fortification in Canada on Congenital Heart Disease Subtypes.

Previous studies have yielded inconsistent results for the effects of periconceptional multivitamins containing folic acid and of folic acid food fortification on congenital heart defects (CHDs). We carried out a population-based cohort study (N=5 901 701) of all live births and stillbirths (including late-pregnancy terminations) delivered at ≥20 weeks' gestation in Canada (except Québec and Manitoba) from 1990 to 2011. CHD cases were diagnosed at birth and in infancy (n=72 591). We compared prevalence rates and temporal trends in CHD subtypes before and after 1998 (the year that fortification was mandated). An ecological study based on 22 calendar years, 14 geographic areas, and Poisson regression analysis was used to quantify the effect of folic acid food fortification on nonchromosomal CHD subtypes (n=66 980) after controlling for changes in maternal age, prepregnancy diabetes mellitus, preterm preeclampsia, multiple birth, and termination of pregnancy. The overall birth prevalence rate of CHDs was 12.3 per 1000 total births. Rates of most CHD subtypes decreased between 1990 and 2011 except for atrial septal defects, which increased significantly. Folic acid food fortification was associated with lower rates of conotruncal defects (adjusted rate ratio [aRR], 0.73, 95% confidence interval [CI], 0.62-0.85), coarctation of the aorta (aRR, 0.77; 95% CI, 0.61-0.96), ventricular septal defects (aRR, 0.85; 95% CI, 0.75-0.96), and atrial septal defects (aRR, 0.82; 95% CI, 0.69-0.95) but not severe nonconotruncal heart defects (aRR, 0.81; 95% CI, 0.65-1.03) and other heart or circulatory system abnormalities (aRR, 0.98; 95% CI, 0.89-1.11). The association between food fortification with folic acid and a reduction in the birth prevalence of specific CHDs provides modest evidence for additional benefit from this intervention.

Inborn errors of metabolism detectable by tandem mass spectrometry in Egypt: The first newborn screening pilot study.

To estimate the burden of metabolic disorders detectable by tandem mass spectrometry in Egypt, through a pilot expanded newborn screening programme at Cairo University Children's Hospital in 2008, and examining the results of 3,900 clinically at-risk children, investigated at Cairo University Children's Hospital for the same disorders over the past 7 years using the same technology. Dried blood spots of 25,276 healthy newborns from three governorates in Upper, Middle, and Lower Egypt were screened, to give a representative sample of the Egyptian newborn population. Based on the pilot study outcomes and the results of clinically suspected children, we estimated the total birth prevalence of tandem mass spectrometry detectable metabolic disorders, and the relative frequency of several individual disorders. Among the healthy newborns, 13 metabolic disorder cases (five phenylketonuria [1:5,000], two methylmalonic acidemia, and isovaleric acidemia [1:12,500], one each of maple syrup urine disease, propionic acidemia, β-ketothiolase deficiency, and primary carnitine deficiency [1:25,000]) were confirmed, giving a total birth prevalence of 1:1944 live births. Among the clinically suspected children, 235 cases were diagnosed, representing a much wider disease spectrum. Egypt has one of the highest reported birth prevalence rates for metabolic disorders detectable by tandem mass spectrometry. Early diagnosis and management are crucial for the survival and well-being of affected children. A nationwide NBS programme by tandem mass spectrometry is recommended.

Descriptive analysis of high birth prevalence rate geographical clusters of congenital anomalies in South America.

The birth prevalence rate (BPR) of congenital anomalies (CAs) is heterogeneous and exhibits geographical and sociocultural variations throughout the world. In South America (SA), high birth prevalence regions of congenital anomalies have been observed. The aim of this study was to identify, describe, and characterize geographical clusters of congenital anomalies in SA. This observational descriptive study is based on clinical epidemiological data registered by the Latin-American Collaborative Study of Congenital Malformations network. Between 1995 and 2012, a total of 25,082 malformed newborns were ascertained from 2,557,424 births at 129 hospitals in SA. The spatial scan statistic was used to determine geographical regions with high BPR of CAs. The BPR was obtained with a Poisson regression model. Odds ratios were estimated for several risk factors inside the geographical clusters. We confirmed the existence of high BPR regions of CAs in SA. Indicators of low socioeconomic conditions, such as a low maternal education, extreme age childbearing, infectious diseases, and medicine use during pregnancy were detected as risk factors inside these regions. Native and African ancestries with high frequency of consanguineous marriages could explain partially these high BPR clusters. The recognition of clusters could be a starting point in the identification of susceptibility genes associated with the occurrence of CA in high BPR regions.