Descriptive and risk factor analysis of infantile cataracts: National Birth Defects Prevention Study, 2000-2011.

Using National Birth Defects Prevention Study (NBDPS) data, we sought to estimate birth prevalence, describe clinical characteristics, and examine risk factors for infantile cataracts. We calculated birth prevalence using the numbers of NBDPS-eligible cataract cases and live births in the study area. We described case infants by the presence of associated ipsilateral eye defects (IEDs) and non-eye-related major birth defects. Using maternal exposure information collected via telephone interview, we conducted logistic regression analyses among the interviewed cases and controls. Birth prevalence of infantile cataracts was 1.07/10,000 live births. Unilateral cataracts were more often associated with IEDs, while infants with bilateral cataracts were more often preterm, full-term with low birth weight, or had non-eye-related major birth defects. Unilateral cataracts were positively associated with maternal nulliparity (adjusted odds ratio [aOR] = 1.61, 95% confidence interval [CI] = 1.18, 2.20; reference: multiparity), whereas bilateral cataracts were positively associated with maternal education <12 years (aOR = 2.08, 95% CI = 1.13, 3.82; reference: education >12 years), and foreign-born nativity (aOR = 1.92, 95% CI = 1.04, 3.52; reference: U.S.-born nativity). The current analysis can inform future epidemiological studies aimed at identifying mechanisms underlying the associations between infantile cataracts and complex maternal exposures, such as lower levels of education and foreign-born nativity.

100 years of inherited metabolic disorders in Austria-A national registry of minimal birth prevalence, diagnosis, and clinical outcome of inborn errors of metabolism in Austria between 1921 and 2021.

Inherited metabolic disorders (IMDs) are a heterogeneous group of rare disorders characterized by disruption of metabolic pathways. To date, data on incidence and prevalence of IMDs are limited. Taking advantage of a functioning network within the Austrian metabolic group, our registry research aimed to update the data of the "Registry for Inherited Metabolic Disorders" started between 1985 and 1995 with retrospectively retrieved data on patients with IMDs according to the Society for the Study of Inborn Errors of Metabolism International Classification of Diseases 11 (SSIEM ICD11) catalogue. Included in this retrospective register were 2631 patients with an IMD according to the SSIEM ICD11 Classification, who were treated in Austria. Thus, a prevalence of 1.8/10 000 for 2020 and a median minimal birth prevalence of 16.9/100 000 (range 0.7/100 000-113/100 000) were calculated for the period 1921 to February 2021. We detected a male predominance (m:f = 1.2:1) and a mean age of currently alive patients of 17.6 years (range 5.16 months-100 years). Most common diagnoses were phenylketonuria (17.7%), classical galactosaemia (6.6%), and biotinidase deficiency (4.2%). The most common diagnosis categories were disorders of amino acid and peptide metabolism (819/2631; 31.1%), disorders of energy metabolism (396/2631; 15.1%), and lysosomal disorders (395/2631; 15.0%). In addition to its epidemiological relevance, the "Registry for Inherited Metabolic Disorders" is an important tool for enhancing an exchange between care providers. Moreover, by pooling expertise it prospectively improves patient treatment, similar to pediatric oncology protocols. A substantial requirement for ful filling this goal is to regularly update the registry and provide nationwide coverage with inclusion of all medical specialties.

Birth prevalence of neural tube defects in eastern Africa: a systematic review and meta-analysis.

BACKGROUND: Neural tube defects (NTDs) are associated with high rates of neonatal mortality and morbidity worldwide. The promotion of folic acid fortification and supplementation in pregnant women by the Food and Drug Administration significantly decreased the incidence of NTDs in the United States. This practice is not widely adopted in Eastern Africa countries. We hypothesized that these countries experience a higher burden of NTDs than countries that promote the use of folic acid. We aimed to estimate the birth prevalence of NTDs in the United Nations (UN) Eastern African region. METHODS: PubMed (Medline), Embase, and Cochrane Library databases were systematically searched from inception to December 17, 2021. We included randomized controlled trials or observational studies that reported the prevalence estimates of NTDs in Eastern Africa. Random effects model was used to pool the effect estimates. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to assess the certainty of the evidence. Outcome measures were overall and specific (spina bifida, anencephaly, encephalocele) rates of NTDs per 10,000 births, including live and stillborn cases. RESULTS: The meta-analysis included 20 studies consisting of 752,936 individuals. The pooled prevalence of all NTDs per 10,000 births in Eastern Africa was 33.30 (95% CI: 21.58 to 51.34). Between-study heterogeneity was high (I2 = 97%, p < 0.0001), The rate was highest in Ethiopia (60 per 10,000). Birth prevalence of spina bifida (20 per 10,000) was higher than anencephaly (9 per 10,000) and encephalocele (2.33 per 10,000). No studies on NTDs were identified in 70% of the UN Eastern Africa region. Birth prevalence increased by 4% per year from 1983 to 2018. The level of evidence as qualified with GRADE was moderate. CONCLUSION: The birth prevalence of NTDs in the United Nations region of Eastern Africa is 5 times as high as observed in Western countries with mandatory folic acid supplementation in place. Therefore, mandatory folic acid supplementation of stable foods may decrease the risk of NTDs in Eastern Africa.

National birth prevalence, associated anomalies and mortality for gastroschisis in Sweden.

AIM: An increased incidence has been reported for the congenital abdominal wall defect gastroschisis. The reason for this increasing trend is not known, nor the aetiology. The aim of this study was to examine the national birth prevalence in Sweden, the termination rate, associated anomalies and the mortality of gastroschisis within the cohort. METHODS: A nationwide, population-based descriptive study of children born with gastroschisis in Sweden between 1/1 1997 and 31/12 2016 was conducted. The cohort was collected from the Swedish Medical Birth Register and the Swedish National Patient Register. Several other national registers were then interlinked to identify outcome data. RESULTS: The study included 361 cases of gastroschisis, 54% female. The birth prevalence was 1.52 in 10,000 live births. The termination rate was 21%. The mortality within the cohort was 4.4% with a 1-year mortality of 3.9%. Most frequent associated anomalies were gastrointestinal (11.4%), musculoskeletal (9.8%) and cardiovascular anomalies (7.9%). CONCLUSION: During the 20-year study period, a stable birth prevalence of 1.52 per 10 000 live births was seen in Sweden. The mortality was low, 4.4%, but the termination of pregnancies was high, 21%. Almost one-third had associated congenital anomalies where gastrointestinal anomalies were the most common.

Birth Prevalence and Risk Factors Associated With CL/P in Thailand.

INTRODUCTION: The objectives of this study were to obtain the birth prevalence of cleft lips and/or cleft palates (CL±P) and to identify potential associated risk factors in the population of the Northeast (NE) region of Thailand. METHODS: The data were collected from October 1, 2012, to September 30, 2013, for infant deliveries with nonsyndromic CL±P in all hospitals of 4 provinces in the region. Workshops were conducted to establish diagnostic criteria, treatment guidelines, referral systems, data collection, and data reporting. All patients included in this study, including a case (the child born with cleft lip and palate [CLP]) and 2 control cases (2 following children born without CLP in the same hospital), completed a questionnaire regarding demographics, cleft characteristics, and factors of interest such as alcohol intake, smoking, vitamin use, and medication. Unadjusted and adjusted odds ratio were presented for the magnitude of associations between proposed risk factors and CL±P along with 95% CIs. RESULTS: The overall birth prevalence of CL±P was 1.93 per 1000 live births. There was a significant difference in percentages of infants with low birth weights (P = .03), family history of CL±P (P = .01) in cases than controls. Mothers who took self-medication or a menstrual regulation supplement were more likely to have the child with CL±P (P = .01 adjusted). CONCLUSIONS: The prevalence of CL±P in the NE Thailand was high. Low infant birth weight, family history of CL±P, and the use of self-medication or menstrual regulation herbal supplement was significant factors.

Estimated birth prevalence of mucopolysaccharidoses in Brazil.

Several studies have been published on the frequency of the mucopolysaccharidoses (MPS) in different countries. The objective of the present study was to estimate the birth prevalence (BP) of MPS in Brazil. MPS diagnosis registered at MPS-Brazil Network and in Instituto Vidas Raras were reviewed. BP was estimated by (a) the number of registered patients born between 1994 and 2015 was divided by the number of live births (LBs), and (b) a sample of 1,000 healthy individuals was tested for the most frequent variant in IDUA gene in MPS I (p.Trp402Ter) to estimate the frequency of heterozygosity and homozygosity. (a) The BP based on total number of LBs was (cases per 100,000 LBs): MPS overall: 1.25; MPS I: 0.24; MPS II: 0.37; MPS III: 0.21; MPS IV: 0.14; MPS VI: 0.28; MPS VII: 0.02. (b) The overall frequency of p.Trp402Ter was 0.002. Considering the frequency of heterozygotes for the p.Trp402Ter IDUA variant in the RS state, the frequency of this variant among MPS I patients and the relative frequency of the different MPSs, we estimated the birth prevalence of MPS in total and of each MPS type, as follows: MPS overall: 4.62; MPS I: 0.95; MPS II: 1.32; MPS III: 0.56; MPS IV: 0.57; MPS VI: 1.02; MPS VII: 0.05. This study provided original data about BP and relative frequency of the MPS types, in Brazil, based on the frequency of the commonest IDUA pathogenic variant and in the records of two large patient databases.

Birth prevalence of achondroplasia: A systematic literature review and meta-analysis.

Achondroplasia is a genetic disorder that results in disproportionate short stature. The true prevalence of achondroplasia is unknown as estimates vary widely. This systematic literature review and meta-analysis was conducted to better estimate worldwide achondroplasia birth prevalence. PubMed, Embase, Scielo, and Google Scholar were searched, complemented by manual searching, for peer-reviewed articles published between 1950 and 2019. Eligible articles were identified by two independent researchers using predefined selection criteria. Birth prevalence estimates were extracted for analysis, and the quality of evidence was assessed. A meta-analysis using a quality effects approach based on the inverse variance fixed effect model was conducted. The search identified 955 unique articles, of which 52 were eligible and included. Based on the meta-analysis, the worldwide birth prevalence of achondroplasia was estimated to be 4.6 per 100,000. Substantial regional variation was observed with a considerably higher birth prevalence reported in North Africa and the Middle East compared to other regions, particularly Europe and the Americas. Higher birth prevalence was also reported in specialized care settings. Significant heterogeneity (Higgins I2 of 84.3) was present and some indication of publication bias was detected, based on visual asymmetry of the Doi plot with a Furuya-Kanamori index of 2.73. Analysis of pooled data from the current literature yields a worldwide achondroplasia birth prevalence of approximately 4.6 per 100,000, with considerable regional variation. Careful interpretation of these findings is advised as included studies are of broadly varying methodological quality.

Nationwide epidemiological survey of holoprosencephaly in Japan.

BACKGROUND: Holoprosencephaly (HPE) is a congenital malformation with an estimated prevalence of 0.10-6.06 per 10 000 births but with no nationwide data specific to Japan. METHODS: 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. RESULTS: We received valid responses from 253 hospitals in the primary survey (54.6%). Of 390 342 live births, 60 were diagnosed with HPE (23 males and 37 females), resulting in an actual BPR of 1.54 per 10 000 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 10 000 live births (95% CI: 0.26-0.38) based on 3 117 853 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. CONCLUSIONS: This is the most extensive survey on holoprosencephaly to date in Japan. The estimated BPR was consistent with that reported in previous research.

Data Linkage: Cleft Live-Birth Prevalence and Hospitalizations in Western Australia: 1980 to 2016.

OBJECTIVE: To provide information on live-birth prevalence and hospitalizations, including anxiety and depression, for cleft lip and/or palate (CL/P) in Western Australia (WA), using live-birth data 1980 to 2015. DESIGN: Retrospective data linkage. SETTING: Tertiary hospital. PATIENTS: Cleft cohort consisted of people live-born with CL/P in WA between 1980 and 2015, and a gender and age-matched control group. MEASURES: Live-birth prevalence for CL/P by year. Hospital event counts, event ages, and length of stay (LOS) days by 18 diagnosis groups and 4 birth year categories between the cleft cohort and control group, and between cleft types. Count of events per alive persons per calendar year, and relative risk for proportions of persons in the cleft cohort and control group by diagnosis group. RESULTS: Live-birth prevalence for CL/P was 19.7 per 10 000 (1 in 522). The cleft cohort had significantly higher event counts, lower event ages, and higher LOS days than the control group. Cleft lip and palate had significantly higher event counts, lower event ages, and higher LOS days than cleft lip or cleft palate only. There were 2 significant differences for anxiety or depression between the cleft cohort and control group, lower event ages, and higher LOS days in 1990s birth year category. CONCLUSIONS: This study provides a cleft data reference for WA. Live-birth prevalence for all clefts and by cleft type offers an appropriate method for estimating service utilization and provision. Patients with cleft accessed hospital services more frequently, at an earlier age, with higher LOS days than the control group.

Analysis of the Prevalence and Incidence of Cleft Lip and Palate in Colombia.

OBJECTIVE: To analyze the population prevalence and birth prevalence of oral clefts in Colombia from 2009 to 2017. METHODS: A cross-sectional study using information from the National Administrative Records of Colombia. The data came from 2 types of administrative records (Surveillance System and the Individual Registry of Service Provision) and the oral health national survey. Population prevalence and birth prevalence by type of cleft lip and/or cleft (CL/P) ratios were calculated using Poisson distribution for count data and to assess stationary tests on time series (Dickey-Fuller) and (Phillips-Perron) was used. RESULTS: Population prevalence in Colombia was 3.27 per 10 000 inhabitants (95% confidence interval [CI], 3.21-3.32) and birth prevalence was 6.0 per 10 000 live births (95% CI, 5.67-6.35). Bogotá have the highest population prevalence with CL/P. In the analysis of trends for the prevalence proportion by type of clefts in newborn babies with cleft, it was observed that the highest proportion was for babies with CLP. Cleft lip (CL) has increased from 17.4% in 2014 to 34.2% in 2017, cleft palate (CP) has decreased from 32.9% to 20.2%; and CLP changed from 49.6% to 45.5% in the same period. CONCLUSIONS: The population prevalence was 3.27 per 10 000 inhabitants. Births prevalence was 6.0 per 10 000 live births, and Orinoquia and Amazonia have higher rates than the national average. The administrative registers are adequate systems to know the behavior of oral clefts. The CL/P had a nonstationary trend during the period 2014 to 2017.

Descriptive and risk factor analysis of nonsyndromic sacral agenesis: National Birth Defects Prevention Study, 1997-2011.

Sacral agenesis is a rare birth defect characterized by partial or complete absence of the sacrum. We sought to (a) describe case characteristics, (b) estimate birth prevalence, and (c) identify risk factors for nonsyndromic sacral agenesis using data from the National Birth Defects Prevention Study (NBDPS). The NBDPS was a population-based, case-control study involving pregnancies with estimated dates of delivery from October 1997 through December 2011. We estimated birth prevalence using all NBDPS eligible cases. Using self-reported maternal exposure information, we conducted multivariable logistic regression analysis to identify potential risk factors overall and among women without diabetes. The birth prevalence of sacral agenesis was 2.6/100,000 live births. In the multivariable analysis, multifetal pregnancy, pre-existing Type 1 diabetes, and pre-existing Type 2 diabetes were positively and significantly associated with sacral agenesis, albeit estimates were imprecise. Preexisting Type 1 diabetes was the strongest risk factor (adjusted odds ratio = 96.6, 95% confidence interval = 43.5-214.7). Among women without diabetes, periconceptional smoking was positively and significantly associated with sacral agenesis. Our findings underscore the importance of smoking cessation programs among women planning pregnancy and the importance of better understanding the role of glycemic control before and during pregnancy when designing interventions for primary prevention of sacral agenesis.

A hospital-based birth defects surveillance system in Kampala, Uganda.

BACKGROUND: In 2010, the World Health Assembly passed a resolution calling upon countries to prevent birth defects where possible. Though birth defects surveillance programs are an important source of information to guide implementation and evaluation of preventive interventions, many countries that shoulder the largest burden of birth defects do not have surveillance programs. This paper shares the results of a hospital-based birth defects surveillance program in Uganda which, can be adopted by similar resource-limited countries. METHODS: All informative births, including live births, stillbirths and spontaneous abortions; regardless of gestational age, delivered at four selected hospitals in Kampala from August 2015 to December 2017 were examined for birth defects. Demographic data were obtained by midwives through maternal interviews and review of hospital patient notes and entered in an electronic data collection tool. Identified birth defects were confirmed through bedside examination by a physician and review of photographs and a narrative description by a birth defects expert. Informative births (live, still and spontaneous abortions) with a confirmed birth defect were included in the numerator, while the total informative births (live, still and spontaneous abortions) were included in the denominator to estimate the prevalence of birth defects per 10,000 births. RESULTS: The overall prevalence of birth defects was 66.2/10,000 births (95% CI 60.5-72.5). The most prevalent birth defects (per 10,000 births) were: Hypospadias, 23.4/10,000 (95% CI 18.9-28.9); Talipes equinovarus, 14.0/10,000 (95% CI 11.5-17.1) and Neural tube defects, 10.3/10,000 (95% CI 8.2-13.0). The least prevalent were: Microcephaly, 1.6/10,000 (95% CI 0.9-2.8); Microtia and Anotia, 1.6/10,000 (95% CI 0.9-2.8) and Imperforate anus, 2.0/10,000 (95% CI 1.2-3.4). CONCLUSION: A hospital-based surveillance project with active case ascertainment can generate reliable epidemiologic data about birth defects prevalence and can inform prevention policies and service provision needs in low and middle-income countries.

The Birth Prevalence of Cleft Lip and/or Cleft Palate After the 2011 Tohoku Earthquake and Tsunami.

OBJECTIVE: This study examined whether the 2011 Tohoku earthquake and tsunami affected the birth prevalence of cleft lip and/or cleft palate (CL/P) in Miyagi Prefecture, where the earthquake and tsunami caused severe damage. DESIGN: This was a retrospective cohort study. SETTING: The study was conducted at university and children's hospitals in Miyagi Prefecture. PARTICIPANTS: The annual and monthly numbers of infants born with CL/P were obtained from medical records. The affected period of birth was defined as 1 year from December 1, 2011, to November 30, 2012. The control period was 5 years from January 1, 2006, to December 31, 2010. The annual and monthly numbers of births in Miyagi Prefecture were obtained using e-Stat, which is a portal for Japanese government statistics. MAIN OUTCOME MEASURES: Main outcome measures were birth prevalence of CL/P during the control and affected periods. RESULTS: There were no significant differences between the control and affected periods in the prevalence (per 10 000 live births) of cleft lip with or without palate (13.8 vs 16.7; P = .342), isolated cleft palate (5.2 vs 3.2; P = .267), or overall CL/P (19.0 vs 19.9; P = .799). CONCLUSIONS: We did not observe that the 2011 Tohoku earthquake and tsunami affected the birth prevalence of CL/P in Miyagi Prefecture, even though it severely impacted human health in the area.

A national estimate of the birth prevalence of congenital anomalies in India: systematic review and meta-analysis.

BACKGROUND: A quarter of all global neonatal deaths occur in India. Congenital anomalies constitute the fifth largest cause of neonatal mortality in the country, but national estimates of the prevalence of these conditions are lacking. The objective of the study was to derive an estimate of the birth prevalence of congenital anomalies in India. METHODS: The search was carried out in PubMed and pooled prevalence was estimated using the inverse variance method. A random effects model was used due to high heterogeneity between the studies. Forest plots were generated using the Review Manager software. RESULTS: The PubMed search identified 878 articles from which 52 hospital based and three community based studies were included in the meta-analysis. The pooled prevalence of congenital anomaly affected births was 184.48 per 10,000 births (95% CI 164.74-204.21) among 802,658 births. Anomalies of the musculoskeletal system were highest among live births while the prevalence of central nervous system defects was highest when stillbirths were included in the analysis. Anencephaly and talipes were the most commonly reported anomalies. CONCLUSIONS: Data from this meta-analysis suggests that there may be as many as 472,177 (421,652 to 522,676) congenital anomaly affected births in India each year. Population based studies using standard definitions are needed to validate these estimates. The two most frequently reported anomalies were anencephaly that is potentially preventable through preconception folate supplementation, and talipes which can be corrected using relatively low cost interventions. Studies are needed to determine the impact of congenital anomalies on neonatal mortality in India.

Congenital limb deficiency in Japan: a cross-sectional nationwide survey on its epidemiology.

BACKGROUND: Congenital limb deficiency is a rare and intractable disease, which impairs both function and appearance of the limbs. To establish adequate medical care, it is necessary to reveal the actual conditions and problems associated with this disease. However, there have been no extensive epidemiological surveys in Japan addressing this disease. This is the first nationwide epidemiological survey of congenital limb deficiency in this country. METHODS: With the cooperation of epidemiology experts, we performed a two-stage nationwide survey to estimate the number of patients with congenital limb deficiency and reveal basic patient features. We targeted orthopaedic surgery, paediatric, and plastic surgery departments. Hospitals were categorized according to the institution type and the number of hospital beds; hospitals were randomly selected from these categories. We selected 2283 departments from a total 7825 departments throughout Japan. In this study, we defined congenital limb deficiency as partial or total absence of the limbs, proximal to the proximal interphalangeal joint of the fingers/lesser toes or interphalangeal joint of the thumb/great toe. We distributed the first survey querying the number of initial patient visits from January 2014 to December 2015. Targets of the second survey were departments that reported one or more initial patient visits in the first survey. RESULTS: In the first survey, 1767 departments responded (response rate: 77.4%). Among them, 161 departments reported one or more initial patient visits. We conducted the second survey among these 161 departments, of which 96 departments responded (response rate: 59.6%). The estimated number of initial visits by patients with congenital limb deficiency was 417 (95% confidence interval: 339-495) per year in 2014 and 2015. The estimated prevalence of congenital limb deficiency in Japan was 4.15 (95% confidence interval: 3.37-4.93) per 10,000 live births. The sex ratio was 1.40. Upper limbs were more affected than lower limbs. CONCLUSIONS: We revealed the estimated number of initial patient visits per year and birth prevalence of congenital limb deficiency in Japan. Our results will contribute to establishing the disease concept and grades of severity of congenital limb deficiency.

Birth prevalence of congenital malformations in singleton pregnancies resulting from in vitro fertilization/intracytoplasmic sperm injection worldwide: a systematic review and meta-analysis.

PURPOSE: We conducted a systematic review and meta-analysis to estimate the worldwide birth prevalence of total congenital malformations (CMs), major CMs, and specific CMs according to organs and systems classification associated with IVF/ICSI singleton pregnancies. METHODS: Unrestricted searches were conducted, with an end-date parameter of 1 June 2017, of PubMed, Embase, Google Scholar, Cochrane Libraries, and Chinese databases, to identify cohort studies assessing CMs associated with IVF/ICSI singleton pregnancies. The prevalence estimates were summarized and analyzed by meta-analysis. RESULTS: Thirty-four cohort studies comprising 159,021 IVF/ICSI and 6704,405 spontaneously conceived singleton pregnancies met the inclusion criteria. Among IVF/ICSI singleton pregnancies, pooled estimates of total CMs and major CMs (per 10,000) were 484.3 (95% CI 363.8-641.9) and 475.8 (95% CI 304.9-735.2), respectively; for specific CMs, pooled estimates 13.04 (95% CI 9.90-17.18) for cleft lip and/or palate, 17.01 (95% CI 8.01-36.06) for eye, ear, face, and neck malformations, 16.51(95% CI 11.56-23.57) for nervous system malformations, 36.21 (95% CI 26.20-50.02) for chromosomal defects, 8.31 (95% CI 4.21-16.40) for respiratory system malformations, 38.01 (95% CI 24.06-60.00) for digestive system malformations, 110.25 (95% CI 66.92-181.12) for musculoskeletal system malformations, 108.92 (95% CI 68.73-172.21) for urogenital system malformations, and 77.20 (95% CI 53.25-111.80) for circulatory system malformations. The IVF/ICSI singleton pregnancies compared with those conceived naturally experienced higher prevalence of total CMs, major CMs, and most specific CMs. Significant differences across continents, countries, types of assisted conception, and diagnose time of CMs were observed for total CMs birth prevalence among IVF/ICSI singleton pregnancies. CONCLUSIONS: The IVF/ICSI singleton pregnancies were significantly associated with high birth prevalence of CMs, representing a major global health burden. Significant differences across continents, countries, types of ART, and diagnose time of CMs were found. However, it remains uncertain whether detected differences represent true or methodological differences. In the future, population wide prospective CMs' registries covering the entire world population are needed to determine the exact birth prevalence.

Birth prevalence of congenital talipes equinovarus in low- and middle-income countries: a systematic review and meta-analysis.

OBJECTIVE: Congenital talipes equinovarus (CTEV), or clubfoot, is a structural malformation that develops early in gestation. Birth prevalence of clubfoot is reported to vary both between and within low- and middle-income countries (LMICs), and this information is needed to plan treatment services. This systematic review aimed to understand the birth prevalence of clubfoot in LMIC settings. METHODS: Six databases were searched for studies that reported birth prevalence of clubfoot in LMICs. Results were screened and assessed for eligibility using pre-defined criteria. Data on birth prevalence were extracted and weighted pooled estimates were calculated for different regions. Wilcoxon rank-sum test was used to examine changes in birth prevalence over time. Included studies were appraised for their methodological quality, and a narrative synthesis of findings was conducted. RESULTS: Forty-eight studies provided data from 13 962 989 children in 20 countries over 55 years (1960-2015). The pooled estimate for clubfoot birth prevalence in LMICs within the Africa region is 1.11 (0.96, 1.26); in the Americas 1.74 (1.69, 1.80); in South-East Asia (excluding India) 1.21 (0.73, 1.68); in India 1.19 (0.96, 1.42); in Turkey (Europe region) 2.03 (1.54, 2.53); in Eastern Mediterranean region 1.19 (0.98, 1.40); in West Pacific (excluding China) 0.94 (0.64, 1.24); and in China 0.51 (0.50, 0.53). CONCLUSION: Birth prevalence of clubfoot varies between 0.51 and 2.03/1000 live births in LMICs. A standardised approach to the study of the epidemiology of clubfoot is required to better understand the variations of clubfoot birth prevalence and identify possible risk factors.

Estimates of live birth prevalence of children with Down syndrome in the period 1991-2015 in the Netherlands.

BACKGROUND: In Western countries, increasing maternal age has led to more pregnancies with a child with Down syndrome (DS). However, prenatal screening programs, diagnostic testing and termination of pregnancy influence the actual DS live birth (LB) prevalence as well. The aim of this study is to examine these factors in the Netherlands for the period 1991-2015. In our study, we establish a baseline for DS LB prevalence before non-invasive prenatal testing will be made available to all pregnant women in the Netherlands in 2017. METHODS: Full nationwide data from the Dutch cytogenetic laboratories were used to evaluate the actual DS LB prevalence. In addition, nonselective DS prevalence, which is the DS LB prevalence that would be expected in absence of termination of pregnancies, was estimated on the basis of maternal age distribution in the general population. RESULTS: Because of an increase in maternal age, nonselective DS prevalence increased from around 15.6 [95% confidence interval (CI) 13.9-17.4] per 10 000 LBs in 1991 (311 children in total) to around 22.6 (95% CI 20.3-24.9) per 10 000 in 2015 (385), the increase levelling off in recent years. Actual LB prevalence rose from around 11.6 (95% CI 10.9-12.2) per 10 000 in 1991 (230 children) to an estimated peak of 15.9 (95% CI 15.6-16.2) per 10 000 in 2002 (322), gradually decreasing since to 11.1 (95% CI 10.8-11.5) per 10 000 in 2015 (190). Reduction of DS LBs resulting from elective terminations had been fairly constant between 1995 and 2002 at around 28% and rose afterwards from 35% in 2003 to around 50% in 2015. CONCLUSIONS: In spite of expansion of antenatal screening in the Netherlands in the 1990s and early 2000s, actual DS LB prevalence increased during this period. However, after 2002, this trend reversed, probably because of informing all pregnant women about prenatal testing since 2004 and the implementation of a national screening program in 2007.

Systematic Review and Meta-Analysis of the Birth Prevalence of Orofacial Clefts in Low- and Middle-Income Countries.

BACKGROUND: In the last comprehensive review of the literature published in 2002, little information on the prevalence of orofacial clefts was available from low- and middle-income countries (LMICs). OBJECTIVE: To analyze published data on the birth prevalence of cleft lip and/or palate (CL/P) from LMIC. DESIGN: Systematic review of the literature and meta-analysis of data from original papers on the birth prevalence of cleft lip and/or cleft palate (CL/P) in LMICs between 1990 and 2014. Secondary inclusion criteria were developed to analyze lower-quality studies from countries with scarce data. MAIN OUTCOME MEASURE: Birth prevalence of undifferentiated CL/P (with or without associated syndrome or other anomaly). RESULTS: Twenty-eight studies met strict inclusion criteria. Among 31,475,278 total births, the pooled birth prevalence of undifferentiated CL/P was 1.38 per 1000 births (95% confidence interval [CI]: 1.20 to 1.56). Four studies met criteria for secondary analysis, providing data on 75,627 births, with a pooled prevalence of 0.75 CL/P cases per 1000 births (95% CI: 0.56 to 0.95). Comparison of studies was limited by variable definitions of cases and of the reference population and by inconsistent reporting of outcomes. There is significant heterogeneity in the findings. CONCLUSIONS: In LMICs, approximately 1 in every 730 children is born with CL/P. To optimize comparability across settings, future research should use a standard classification system and standard criteria for data collection and presentation. As clefting is associated with deprivation, understanding the true scale, risks, and preventive measures for orofacial clefts in LMIC is a matter of both scientific and humanitarian importance.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.