Background
Even small amounts of alcohol consumed during pregnancy can have adverse effects on the embryo and the fetus. We estimated how alcohol intake among pregnant women in Spain changed between ...1980 and 2014, and identified factors associated with alcohol use.
Methods
Data came from the Spanish Collaborative Study of Congenital Malformations (ECEMC). The sample includes ECEMC′s control mothers, 40,268 pregnant women from all regions of Spain. We classified alcohol consumption during pregnancy into 3 categories: no consumption; sporadic consumption of small amounts of alcohol; and regular consumption, or sporadic but in large quantities including drunkenness. Independent variables included sociodemographic factors, planned/unplanned pregnancy, maternal chronic diseases, gestational diabetes, and tobacco and illegal drug use during pregnancy. Trend analyses were performed using data from 1980 to 2014. The multinomial logistic regression models designed to identify associated factors differentiated between 2 periods: 1994 to 2004 and 2005 to 2014.
Results
Prevalence of alcohol consumption declined from 29.6% (95% CI: 27.1 to 32.2) in 1980 to 5.4% (95% CI: 3.7 to 7.6) in 2014, mostly due to the reduction in regular intake. This decline was especially acute between 1980 and 1994. Sporadic and regular consumption increased among women working outside the home, born outside Spain, those whose pregnancy was unplanned, and those reporting using tobacco or other drugs. Comparing 1994 to 2004 versus 2005 to 2014, a stronger association was observed between regular alcohol consumption and tobacco consumption in the latter period (interaction p = 0.003).
Conclusions
Alcohol consumption among expectant mothers has declined substantially in the last 35 years. However, it is worth highlighting the significant and substantial associations between alcohol use and consumption of tobacco, which have become stronger in the most recent years.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Serine biosynthesis disorders comprise a spectrum of very rare autosomal recessive inborn errors of metabolism with wide phenotypic variability. Neu–Laxova syndrome represents the most severe ...expression and is characterized by multiple congenital anomalies and pre‐ or perinatal lethality. Here, we present the mutation spectrum and a detailed phenotypic analysis in 15 unrelated families with severe types of serine biosynthesis disorders. We identified likely disease‐causing variants in the PHGDH and PSAT1 genes, several of which have not been reported previously. Phenotype analysis and a comprehensive review of the literature corroborates the evidence that serine biosynthesis disorders represent a continuum with varying degrees of phenotypic expression and suggest that even gradual differences at the severe end of the spectrum may be correlated with particular genotypes. We postulate that the individual residual enzyme activity of mutant proteins is the major determinant of the phenotypic variability, but further functional studies are needed to explore effects at the enzyme protein level.
Dimeric PSAT1 structure with the bound pyridoxal 5′‐phosphate shown in stick presentation. In one subunit, variants associated with lethal and nonlethal phenotypes are highlighted by red and orange balls, respectively
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This paper presents the annual time series and the average annual growth rate of the European Gender Equality Index, which was proposed by Bericat (Soc Indic Res 108:1–28, 2012), for the EU and its ...27 member countries for the period 2000–2011. The paper also reports the time series and average annual growth rate for each of the three subdimensions of gender equality—education, work, and power—and the underlying indicators for each subdimension for EU as a whole. The calculated index shows that in the period 2000–2011, overall gender equality, equality in education, work, and power in the EU has been improving at a rate of 1.7, 0.92, 0.65, and 3.48 % per year, respectively. By 2011, overall gender equality, and equality in education, work, and power has reached 58.3, 77.4, 60.9, and 42.7, respectively. In short, this paper offers the scientific community, as well as those that design and implement public policies, a robust, valid and precise synthetic description of the current situation and evolution, from 2000 to 2011, of structural gender equality in European countries.
In recent years, safety concerns about modafinil exposure during pregnancy have emerged. In particular, increased risks for major congenital anomalies (MCA) and impaired fetal growth were reported, ...although study results were conflicting. Our investigation aims to examine previously reported safety signals.
Multicenter case series based on data from 18 Teratology Information Services from 12 countries. Modafinil exposed pregnancies with an estimated date of birth before August 2019 were included in this study. For prospectively ascertained pregnancies, cumulative incidences of pregnancy outcomes, rate of nonchromosomal MCA in first trimester exposed pregnancies and percentiles of neonatal/infant weight and head circumference (HC) were calculated. Potential dose-dependent effects on fetal growth were explored by linear regression models. Retrospectively ascertained cases were screened for pattern of MCA and other adverse events.
One hundred and seventy-five prospectively ascertained cases were included, of which 173 were exposed at least during the first trimester. Cumulative incidences for live birth, spontaneous abortion and elective termination of pregnancy were 76.9% (95% CI, 68.0%-84.8%), 9.3% (95% CI, 5.0%-16.9%), and 13.9% (95% CI, 8.1%-23.1%), respectively. Nonchromosomal MCA was present in 3/150 live births, corresponding to an MCA rate of 2.0% (95%CI, 0.6%-6.1%), none were reported in pregnancy losses. Compared to reference standards, birth weight (BW) tended to be lower and neonatal HC to be smaller in exposed newborns (data available for 144 and 73 of 153 live births, respectively). In nonadjusted linear regression models, each 100 mg increase of average dosage per pregnancy day was associated with a decrease in standard deviation score (SDS) of -0.28 SDS (95% CI, -0.45 to -0.10) for BW and of -0.28 SDS (95% CI, -0.56 to 0.01) for HC. Screening of 22 retrospectively reported cases did not reveal any specific pattern of MCA or other adverse outcomes.
The results do not indicate an increased risk of MCA after in utero exposure to modafinil, but a tendency toward lower BW and reduced neonatal HC. However, these findings should be regarded as preliminary. Until further studies allow for a definite conclusion, modafinil should not be used during pregnancy.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Disruption of the autism susceptibility candidate 2 (AUTS2) gene through genomic rearrangements, copy number variations (CNVs), and intragenic deletions and mutations, has been recurrently involved ...in syndromic forms of developmental delay and intellectual disability, known as AUTS2 syndrome. The AUTS2 gene plays an important role in regulation of neuronal migration, and when altered, associates with a variable phenotype from severely to mildly affected patients. The more severe phenotypes significantly correlate with the presence of defects affecting the C‐terminus part of the gene. This article reports a new patient with a syndromic neurodevelopmental disorder, who presents a deletion of 30 nucleotides in the exon 9 of the AUTS2 gene. Importantly, this deletion includes the transcription start site for the AUTS2 short transcript isoform, which has an important role in brain development. Gene expression analysis of AUTS2 full‐length and short isoforms revealed that the deletion found in this patient causes a remarkable reduction in the expression level, not only of the short isoform, but also of the full AUTS2 transcripts. This report adds more evidence for the role of mutated AUTS2 short transcripts in the development of a severe phenotype in the AUTS2 syndrome.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
World Birth Defects Day (WorldBDDay), observed annually on March 3, was launched in 2015 to advocate for public health surveillance, research, and prevention of birth defects, along with improved ...care and treatment for affected individuals. Following its fifth observance in 2019, we assessed WorldBDDay by analyzing: (a) engagement and content of over 2000 WorldBDDay posts on Facebook, Twitter, and Instagram; (b) interview responses from 9 WorldBDDay charter (founding) organizations on their perceptions of strengths and areas for improvement for WorldBDDay; (c) survey responses from 61 WorldBDDay 2019 partner (participating) organizations on their WorldBDDay 2019 activities; and (d) post‐2019 social media engagement. Most social media posts (60%) occurred from organizations using Twitter (80% vs. 14% for Instagram and 6% for Facebook), although posts from individuals had higher levels of engagement (e.g., likes and comments). The highest engagement occurred for posts focused on general awareness, prevention, or events. Charter organizations reported the need for existing and new partner engagement, including a designated WorldBDDay contact for regular communication and coordination of activities and prepared prevention‐focused messaging. Partner organizations reported using the WorldBDDay toolkit, especially key messages and social media tips, and suggested expanding the toolkit with relevant resources. Post‐2019 Twitter engagement was lower than 2019 WorldBDDay (peak event) but showed similar reach to WorldBDDay events prior to 2019. Our assessment identified WorldBDDay health observance events as an important tool to support knowledge dissemination and global community engagement around birth defects. Moving forward, engagement with more individuals and organizations may improve the reach of WorldBDDay.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Pathogenic hemizygous or heterozygous mutations in the IQSEC2 gene cause X-linked intellectual developmental disorder-1 (XLID1), characterized by a variable phenotype including developmental delay, ...intellectual disability, epilepsy, hypotonia, autism, microcephaly and stereotypies. It affects both males and females typically through loss of function in males and haploinsufficiency in heterozygous females. Females are generally less affected than males. Two novel unrelated cases, one male and one female, with de novo IQSEC2 variants were detected by trio-based whole exome sequencing. The female case had a previously undescribed frameshift mutation (NM_001111125:c.3300dup; p.Met1101Tyrfs*5), and the male showed an intronic variant in intron 6, with a previously unknown effect (NM_001111125:c.2459+21C>T). IQSEC2 gene expression study revealed that this intronic variant created an alternative donor splicing site and an aberrant product, with the inclusion of 19bp, confirming the pathogenic effect of the intron variant. Moreover, a strong reduction in the expression of the long, but also the short IQSEC2 isoforms, was detected in the male correlating with a more severe phenotype, while the female case showed no decreased expression of the short isoform, and milder effects of the disease. This suggests that the abnormal expression levels of the different IQSEC2 transcripts could be implicated in the severity of disease manifestations.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose
We examined the total prevalence, trends in prevalence, and age‐specific mortality among individuals with anorectal malformation (ARM)
Methods
We conducted a retrospective cohort study using ...data from 24 population‐ and hospital‐based birth defects surveillance programs affiliated with the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) from 18 countries and for births from 1974 to 2014. We estimated pooled and program‐specific total prevalence per 10,000 total births. Poisson regression was used to assess time trends in prevalence from 2001 to 2012 when most programs contributed data. We calculated selected age‐specific proportions of deaths, stratified by case status
Results
The pooled total prevalence of ARM was 3.26 per 10,000 total births (95% Confidence Interval = 3.19, 3.32) for birth years 1974–2014. About 60% of cases were multiple or syndromic. Prevalence of multiple, syndromic, and stillborn cases decreased from 2001 to 2012. The first week mortality proportion was 12.5%, 3.2%, 28.3%, and 18.2% among all, isolated, multiple, and syndromic cases, respectively
Conclusions
ARM is relatively rare, with multiple and syndromic cases showing decreasing prevalence during the study period. Mortality is a concern during the first week of life, and especially among multiple and syndromic cases. Our descriptive epidemiological findings increase our understanding of geographic variation in the prevalence of ARM and can be used to plan needed clinical services. Exploring factors influencing prevalence and mortality among individuals with ARM could inform future studies.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Tetralogy of Fallot (TOF) is the most frequent cyanotic congenital heart defect. TOF mortality has fallen remarkably in recent years due to therapeutic advances. Accordingly, the aim of this study ...was to assess temporal and spatial variability in TOF-related mortality in Spain across the period 1981-2016, using data drawn from the nationwide population-based registry.
Annual deaths due to TOF were sourced from the Spanish National Institute of Statistics database by reference to International Classification of Diseases (ICD), 9th and 10th Revision codes, namely, ICD-9 code 745.2 (period 1981-1998) and ICD-10 code Q21.3 (period 1999-2016). Age-specific and age-adjusted mortality rates were calculated, as were standardised mortality ratios (SMRs) by province, district and municipality for the period 1999-2016.
A total of 1035 deaths were attributed to TOF (57.78% of them were men and 42.22% were women). The age-adjusted mortality rate ranged from 0.75 per 1,000,000 inhabitants (95% confidence interval CI: 0-1.36) in 1981 to 0.03 per 1,000,000 (95% CI: 0.01-0.06) in 2016 for both sexes. In 2011, there was a change in the mortality trend, with a significant decrease of 49.22% per year (p < 0.001). In terms of geographical analysis, some areas with a significantly higher risk of TOF mortality were identified in the south of Spain, though no specific spatial pattern was in evidence.
The decrease in TOF mortality may be related to improvements in diagnostic and treatment techniques. More studies are needed to analyse regions with a higher mortality risk, in order to improve medical planning and resource allocation, and identify risk factors and preventive measures.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
Gastroschisis is a serious birth defect with midgut prolapse into the amniotic cavity. The objectives of this study were to evaluate the prevalence and time trends of gastroschisis among ...programs in the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR), focusing on regional variations and maternal age changes in the population.
Methods
We analyzed data on births from 1980 to 2017 from 27 ICBDSR member programs, representing 24 countries and three regions (Europe+ (includes Iran), Latin America, North America). Cases were identified using diagnostic codes (i.e., 756.7, 756.71, or Q79.3). We excluded cases of amniotic band syndrome, limb–body wall defect, and ruptured omphalocele. Programs provided annual counts for gastroschisis cases (live births, stillbirths, and legally permitted pregnancy terminations for fetal anomalies) and source population (live births, stillbirths), by maternal age.
Results
Overall, gastroschisis occurred in 1 of every 3268 births (3.06 per 10,000 births; 95% confidence intervals CI: 3.01, 3.11), with marked regional variation. European+ prevalence was 1.49 (95%CI: 1.44, 1.55), Latin American 3.80 (95%CI: 3.69, 3.92) and North American 4.32 (95%CI: 4.22, 4.42). A statistically significant increasing time trend was observed among six European+, four Latin American, and four North American programs. Women <20 years of age had the highest prevalence in all programs except the Slovak Republic.
Conclusions
Gastroschisis prevalence increased over time in 61% of participating programs, and the highest increase in prevalence was observed among the youngest women. Additional inquiry will help to assess the impact of the changing maternal age proportions in the birth population on gastroschisis prevalence.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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