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Birth Defects Research Nov 2019Neural tube defects (NTDs) are the second most common congenital malformations in humans affecting the development of the central nervous system. Although NTD... (Review)
Review
Neural tube defects (NTDs) are the second most common congenital malformations in humans affecting the development of the central nervous system. Although NTD pathogenesis has not yet been fully elucidated, many risk factors, both genetic and environmental, have been extensively reported. Classically divided in two main sub-groups (open and closed defects) NTDs present extremely variable prognosis mainly depending on the site of the lesion. Herein, we review the literature on the histological and pathological features, epidemiology, prenatal diagnosis, and prognosis, based on the type of defect, with the aim of providing important information based on NTDs classification for clinicians and scientists.
Topics: Anencephaly; Female; Humans; Neural Tube Defects; Pregnancy; Prenatal Diagnosis; Risk Factors
PubMed: 30421543
DOI: 10.1002/bdr2.1380 -
Birth Defects Research Nov 2019Using the National Birth Defects Prevention Network (NBDPN) annual data report, U.S. national prevalence estimates for major birth defects are developed based on birth...
BACKGROUND
Using the National Birth Defects Prevention Network (NBDPN) annual data report, U.S. national prevalence estimates for major birth defects are developed based on birth cohort 2010-2014.
METHODS
Data from 39 U.S. population-based birth defects surveillance programs (16 active case-finding, 10 passive case-finding with case confirmation, and 13 passive without case confirmation) were used to calculate pooled prevalence estimates for major defects by case-finding approach. Fourteen active case-finding programs including at least live birth and stillbirth pregnancy outcomes monitoring approximately one million births annually were used to develop national prevalence estimates, adjusted for maternal race/ethnicity (for all conditions examined) and maternal age (trisomies and gastroschisis). These calculations used a similar methodology to the previous estimates to examine changes over time.
RESULTS
The adjusted national birth prevalence estimates per 10,000 live births ranged from 0.62 for interrupted aortic arch to 16.87 for clubfoot, and 19.93 for the 12 critical congenital heart defects combined. While the birth prevalence of most birth defects studied remained relatively stable over 15 years, an increasing prevalence was observed for gastroschisis and Down syndrome. Additionally, the prevalence for atrioventricular septal defect, tetralogy of Fallot, omphalocele, and trisomy 18 increased in this period compared to the previous periods. Active case-finding programs generally had higher prevalence rates for most defects examined, most notably for anencephaly, anophthalmia/microphthalmia, trisomy 13, and trisomy 18.
CONCLUSION
National estimates of birth defects prevalence provide data for monitoring trends and understanding the impact of these conditions. Increasing prevalence rates observed for selected conditions warrant further examination.
Topics: Adult; Cardiovascular Abnormalities; Central Nervous System Diseases; Congenital Abnormalities; Eye Diseases; Female; Genetic Diseases, Inborn; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Middle Aged; Musculoskeletal Diseases; Population Surveillance; Pregnancy; Prevalence; Registries; United States; Young Adult
PubMed: 31580536
DOI: 10.1002/bdr2.1589 -
Trends in Neurosciences Jul 2020Neural tube defects (NTDs) represent a failure of the neural plate to complete the developmental transition to a neural tube. NTDs are the most common birth anomaly of... (Review)
Review
Neural tube defects (NTDs) represent a failure of the neural plate to complete the developmental transition to a neural tube. NTDs are the most common birth anomaly of the CNS. Following mandatory folic acid fortification of dietary grains, a dramatic reduction in the incidence of NTDs was observed in areas where the policy was implemented, yet the genetic drivers of NTDs in humans, and the mechanisms by which folic acid prevents disease, remain disputed. Here, we discuss current understanding of human NTD genetics, recent advances regarding potential mechanisms by which folic acid might modify risk through effects on the epigenome and transcriptome, and new approaches to study refined phenotypes for a greater appreciation of the developmental and genetic causes of NTDs.
Topics: Folic Acid; Humans; Neural Tube Defects
PubMed: 32423763
DOI: 10.1016/j.tins.2020.04.009 -
Journal of Clinical Pharmacology Feb 2016During the last decade critical new information has been published pertaining to folic acid supplementation in the prevention of neural tube defects (NTDs) and other... (Review)
Review
During the last decade critical new information has been published pertaining to folic acid supplementation in the prevention of neural tube defects (NTDs) and other folic acid-sensitive congenital malformations. These new data have important implications for women, their families, and health care professionals. We performed a review looking for the optimal dosage of folic acid that should be given to women of reproductive age who are planning or not avoiding conception to propose updated guidelines and thus help health care providers and patients. In addition to fortification of dietary staples with folic acid, women of reproductive age should supplement before conception with 0.4-1.0 mg of folic acid daily as part of their multivitamins. In the United States all enriched rice is also fortified with folic acid at 0.7 mg per pound of raw rice. However, this is not the case in many countries, and it has been estimated that only 1% of industrially milled rice is fortified with folic acid. In countries where rice is the main staple (eg, China), this does not allow effective folate fortification. Whereas the incidence of NTDs is around 1/1000 in the United States, it is 3- to 5-fold higher in Northern China and 3-fold higher in India. A recent population-based US study estimated that the reduction in NTD rates by folic acid is more modest than previously predicted. The potential of NTD prevention by folic acid is underutilized due to low adherence with folic acid supplementation, and calls for revising the policy of supplementation have been raised. We identified groups of women of reproductive age who may benefit from higher daily doses of folic acid, and this should be considered in current practice. These include women who have had previous pregnancies with NTDs, those who did not plan their pregnancy and hence did not supplement, and women with low intake or impaired adherence to daily folic acid supplementation. In addition, women with known genetic variations in the folate metabolic cycle, those exposed to medications with antifolate effects, smokers, diabetics, and the obese may benefit from higher doses of folic acid daily during the first trimester.
Topics: Anencephaly; Dietary Supplements; Dose-Response Relationship, Drug; Female; Folic Acid; Humans; Pregnancy; Vitamins
PubMed: 26272218
DOI: 10.1002/jcph.616 -
JAMA Psychiatry Dec 2020Antidepressants are commonly used during pregnancy, but limited information is available about individual antidepressants and specific birth defect risks.
IMPORTANCE
Antidepressants are commonly used during pregnancy, but limited information is available about individual antidepressants and specific birth defect risks.
OBJECTIVE
To examine associations between individual antidepressants and specific birth defects with and without attempts to partially account for potential confounding by underlying conditions.
DESIGN, SETTING, AND PARTICIPANTS
The population-based, multicenter case-control National Birth Defects Prevention Study (October 1997-December 2011) included cases with selected birth defects who were identified from surveillance systems; controls were randomly sampled live-born infants without major birth defects. Mothers of cases and controls participated in an interview after the expected delivery date. The data were analyzed after the completion of the National Birth Defects Prevent Study's data collection.
EXPOSURES
Self-reported antidepressant exposure was coded to indicate monotherapy exposure to antidepressants.
MAIN OUTCOMES AND MEASURES
We used multivariable logistic regression to calculate adjusted odds ratios (aORs) and 95% confidence intervals for associations between maternal antidepressant use and birth defects. We compared early pregnancy antidepressant-exposed women with those without antidepressant exposure and, to partially account for confounding by underlying maternal conditions, those exposed to antidepressants outside of the birth defect development critical period.
RESULTS
This study included 30 630 case mothers of infants with birth defects and 11 478 control mothers (aged 12-53 years). Early pregnancy antidepressant use was reported by 1562 case mothers (5.1%) and 467 control mothers (4.1%), for whom elevated aORs were observed for individual selective serotonin reuptake inhibitors (SSRIs) and selected congenital heart defects (CHD) (eg, fluoxetine and anomalous pulmonary venous return: aOR, 2.56; 95% CI, 1.10-5.93; this association was attenuated after partially accounting for underlying conditions: aOR, 1.89; 95% CI, 0.56-6.42). This pattern was observed for many SSRI-CHD combinations. Associations between SSRIs and non-CHD birth defects often persisted or strengthened after partially accounting for underlying conditions (eg, citalopram and diaphragmatic hernia: aOR, 5.11; 95% CI, 1.29-20.24). Venlafaxine had elevated associations with multiple defects that persisted after partially accounting for underlying conditions (eg, anencephaly and craniorachischisis: aOR, 9.14; 95% CI, 1.91-43.83).
CONCLUSIONS AND RELEVANCE
We found some associations between maternal antidepressant use and specific birth defects. Venlafaxine was associated with the highest number of defects, which needs confirmation given the limited literature on venlafaxine use during pregnancy and risk for birth defects. Our results suggest confounding by underlying conditions should be considered when assessing risk. Fully informed treatment decision-making requires balancing the risks and benefits of proposed interventions against those of untreated depression or anxiety.
Topics: Abnormalities, Drug-Induced; Adolescent; Adult; Bupropion; Case-Control Studies; Child; Female; Humans; Middle Aged; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Venlafaxine Hydrochloride; Young Adult
PubMed: 32777011
DOI: 10.1001/jamapsychiatry.2020.2453 -
Epidemiologia E Prevenzione 2018Congenital anomalies (CAs) represent one of the main cause of foetal death, infant mortality and morbidity, and long-term disability. CAs have been object of systematic... (Review)
Review
INTRODUCTION
Congenital anomalies (CAs) represent one of the main cause of foetal death, infant mortality and morbidity, and long-term disability. CAs have been object of systematic registration activity for a long-time in many geographical areas in Europe and worldwide. CAs are often associated with disabilities of different types and severity, including the developed Countries worldwide. According to the World Health Organization (WHO), each year approximately 3,2 million of children worldwide are born with a CA and approximately 300,000 newborns with a diagnosis of birth defect die within the first 28 days of life. In Europe, CAs are the leading cause of perinatal mortality: the European Surveillance of Congenital Anomalies (EUROC AT) network estimated a perinatal mortality associated with CAs of 9.2 per 10,000 births in 2008-2012. In Italy, the Ministry of Health estimates that, on the average of 500,000 births each year, about 25,000 present at least one CA. Moreover, approximately 25% of infant mortality is due to CAs and about 50% of infant mortality is attributable to perinatal morbidity, almost always of prenatal origin. Regarding long-term survival, a recent population study conducted between 1985 and 2003 in the UK estimated a 20.5-year survival of 85.5% of children born with at least one CA. According to the Centre for Disease Control and Prevention, approximately 3.3% of live births in the United States have a severe birth defect. Since CAs represent a significant public health issue, an effective primary prevention strategy should be a priority for public policies and healthcare system. Regarding aetiology, although in many cases the cause is still unknown, it has been hypothesized that CAs may be developed during the first trimester of pregnancy as a result of hereditary polygenic defects or of a gene-environment interaction. The aetiology is predominantly multifactorial, caused by complex interactions between genes and environment, which modify the normal embryo-foetal development, especially during the organogenesis phase. In particular, environmental factors (e.g., chemical toxicants, infection agents, maternal disease, and exogenous factors) can have preconceptional mutagenic action, postconceptional teratogenic effects, periconceptional endocrine disruption or epigenetic action. Regarding genetic causes, there are genetic chromosomal aberrations or dysgeneses. Furthermore, socioeconomic factors affect reproductive health by differentiating the exposure to the other risk factors as well as the access to prevention measures. In recent years, the importance of the environment as a major factor of reproductive risk has been highlighted. An individual may be exposed to pollutants present in the workplace and the population may be exposed to multiple sources of environmental contamination of water, soil, and air matrices. Pregnant women and the developing foetus are particularly sensitive to the effects of environmental exposure.
OBJECTIVE
The aim of the present working paper is to produce an updated review of the epidemiological evidence on the risk of CAs associated with environmental exposures, socioeconomic, and main individual risk factors, such as cigarette smoking and alcohol consumption, according to the approach proposed by Pirastu et al. 2010 in the framework of the SENTIERI Project (the Italian Epidemiological Study of Residents in National Priority Contaminated Sites).
DESIGN AND METHODS
Literature search was carried out in PubMed, following the SENTIERI project criteria to evaluate evidence, by selecting articles in English or Italian language published from 2011 to 2016 regarding human studies. For this review, descriptive and analytical epidemiological studies (cohort, case-control, cross-sectional, and ecological), systematic reviews, and metanalyses reporting association estimates between the outcome and at least one of the risk factors were selected. As in Pirastu et al., the sources of environmental exposure have been classified into four macrocategories: industries, mines, landfills, and incinerators. The sources of individual exposure considered were: active and passive cigarette smoking, alcohol consumption, socioeconomic status (SES), occupational and environmental exposures related to air pollutants from vehicular traffic only. The obtained results were assessed according to the evaluation criteria on the epidemiological evidence related to the association between the outcome and exposures predefined and published by the SENTIERI working group (WG). For the evidence assessment, the SENTIERI WG criteria favoured firstly primary sources and quantitative metanalyses, secondly, consistency among sources. The evaluation of the epidemiological evidence for the association between outcome and the exposure has been classified into three categories: sufficient (S), limited (L), inadequate (I).
RESULTS
Industries: during the period under review, six single studies evaluating the association between industrial sites exposure and the risk of CAs were found. The epidemiological evidence of association between outcome and exposure has been considered limited. Mines: from the bibliographic research, three single studies investigating possible cause-effect relationship between maternal residential proximity to mines and the risk of CAs have been collected providing inadequate epidemiological evidence. Landfills: during the period under review, one systematic review and one literature review evaluating the causal associations between maternal residential proximity to landfills and CAs were identified. The epidemiological evidence is limited and concerns almost exclusively sites containing industrial or hazardous waste. Incinerators: a systematic review has been selected; it concludes that the evidence for the association between maternal residential proximity to incinerators and CAs are inadequate. Cigarette smoking: the literature search identified eight systematic reviews with metanalysis, five multicentre studies, and ten single studies assessing the causal association between maternal and/or paternal exposure to smoking and the risk of CAs in the offspring providing sufficient evidence for a causal association between maternal exposure to cigarette smoke and the risk of congenital heart defects, oro-facial clefts, neural tube defects, and gastrointestinal malformations. Alcohol: three systematic reviews with metanalysis, two metanalyses, one multicentre study, and four single studies were collected for the period under review. The acquired literature has provided limited epidemiological evidence for associations between alcohol consumption and CAs in the nervous system, particularly for anencephaly and spina bifida. Socioeconomic status: the evidence of an association with socioeconomic factors was inadequate due to an insufficient number of studies selected during the period under consideration. Occupational exposure: the literature search collected one metanalysis, eight multicentre studies, and five single studies. The epidemiological evidence for associations between paternal occupational exposure to solvents and neural tube defects and between maternal pesticide exposure and gold-facial clefts were judged limited. Air pollution: two systematic reviews with metanalyses, two multicentre studies, and nine single studies were selected by literature search; the epidemiological evidence for a causal association between air pollutants exposure and the risk of CAs is still to be considered limited.
CONCLUSIONS
For future epidemiological studies, a better exposure assessment, using in particular more accurate spatial measurements or models, a standardized case definition, a larger sample and more accurate control of the recognized or presumed confounding variables are needed.
Topics: Congenital Abnormalities; Environmental Exposure; Humans; Italy; Risk Factors; Socioeconomic Factors
PubMed: 30066535
DOI: 10.19191/EP18.3-4.S1.P001.057 -
The Pan African Medical Journal 2023
Topics: Humans; Neural Tube Defects
PubMed: 37013212
DOI: 10.11604/pamj.2023.44.24.35962