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Nutrients Jun 2022In preconception and pregnancy, women are encouraged to take folic acid-based supplements over and above food intake. The upper tolerable limit of folic acid is 1000 mcg... (Review)
Review
Women Taking a Folic Acid Supplement in Countries with Mandatory Food Fortification Programs May Be Exceeding the Upper Tolerable Limit of Folic Acid: A Systematic Review.
BACKGROUND
In preconception and pregnancy, women are encouraged to take folic acid-based supplements over and above food intake. The upper tolerable limit of folic acid is 1000 mcg per day; however, this level was determined to avoid masking a vitamin B12 deficiency and not based on folic acid bioavailability and metabolism. This review's aim is to assess the total all-source intake of folate in women of childbearing age and in pregnancy in high-income countries with folate food fortification programs.
METHODS
A systematic search was conducted in five databases to find studies published since 1998 that reported folate and folic acid intake in countries with a mandatory fortification policy.
RESULTS
Women of childbearing age do not receive sufficient folate intake from food sources alone even when consuming fortified food products; however, almost all women taking a folic acid-based supplement exceed the upper tolerable limit of folic acid intake.
CONCLUSIONS
Folic acid supplement recommendations and the upper tolerable limit of 1000 mcg set by policy makers warrant careful review in light of potential adverse effects of exceeding the upper tolerable limit on folic acid absorption and metabolism, and subsequent impacts on women's health during their childbearing years.
Topics: Dietary Supplements; Female; Folic Acid; Folic Acid Deficiency; Food, Fortified; Humans; Neural Tube Defects; Pregnancy; Women's Health
PubMed: 35807899
DOI: 10.3390/nu14132715 -
BMC Neurology Jun 2022Neural tube defects (NTDs) are associated with high rates of neonatal mortality and morbidity worldwide. The promotion of folic acid fortification and supplementation... (Meta-Analysis)
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 (I = 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.
Topics: Anencephaly; Encephalocele; Female; Folic Acid; Humans; Infant, Newborn; Neural Tube Defects; Pregnancy; Prevalence; Spinal Dysraphism; United States
PubMed: 35650541
DOI: 10.1186/s12883-022-02697-z -
Seminars in Reproductive Medicine Jul 2022Preconception care (PCC) involves a wide-ranging set of interventions to optimize health prior to pregnancy. These interventions seek to enhance conception rates,...
Preconception care (PCC) involves a wide-ranging set of interventions to optimize health prior to pregnancy. These interventions seek to enhance conception rates, pregnancy outcomes, childhood health, and the health of future generations. To assist health care providers to exercise high-quality clinical care in this domain, clinical practice guidelines from a range of settings have been published. This systematic review sought to identify existing freely accessible international guidelines, assess these in terms of their quality using the AGREE II tool, and assess the summary recommendations and the evidence level on which they are based. We identified 11 guidelines that focused on PCC. Ten of these were classified as moderate quality (scores ranging from 3.5 to 4.5 out of 7) and only one was classified as very high quality, scoring 6.5. The levels of evidence for recommendations ranged from the lowest possible level of evidence (III) to the highest (I-a): the highest quality evidence available is for folic acid supplementation to reduce risk of neural tube defects and the role of antiviral medication to prevent HIV transmission. This systematic review identified that high-quality guidelines on PCC are lacking and that few domains of PCC recommendations are supported by high-quality evidence.
Topics: Child; Exercise; Female; Fertilization; Health Personnel; Humans; Preconception Care; Pregnancy; Quality of Health Care
PubMed: 35576970
DOI: 10.1055/s-0042-1748190 -
European Journal of Physical and... Aug 2022Spinal dysraphism (SD) or spina bifida (SB) is a congenital deformity that results from embryonic neural tube closure failure during fetal development. This...
Evidence-based position paper of the UEMS PRM on the role of Physical and Rehabilitation Medicine (PRM) physician in the management of children and adults with spinal dysraphism.
Spinal dysraphism (SD) or spina bifida (SB) is a congenital deformity that results from embryonic neural tube closure failure during fetal development. This evidence-based position paper represents the official position of the European Union through the UEMS PRM Section. This paper aims to evaluate the role of the physical and rehabilitation medicine (PRM) physician and PRM practice for children and adults with spinal dysraphism. A systematic literature review and a consensus procedure involved all European countries delegates represented in the UEMS PRM section through a Delphi process. The systematic literature review is reported together with thirty-two recommendations resulting from the Delphi procedure. The professional role of the PRM physician requires specific expertise in the treatment of patients with SD to plan, lead and monitor the rehabilitation process in an interdisciplinary setting and to participate in the assessment of the needs of these patients in the transitional phase from childhood to adulthood, with particular attention to the activity limitation and participation restriction.
Topics: Adolescent; Child; Europe; European Union; Humans; Physical and Rehabilitation Medicine; Physicians; Spinal Dysraphism; Young Adult
PubMed: 35575455
DOI: 10.23736/S1973-9087.22.07536-0 -
Nutrition Journal Mar 2022Folic acid (FA), as a synthetic form of folate, has been widely used for dietary supplementation in pregnant women. The preventive effect of FA supplementation on the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Folic acid (FA), as a synthetic form of folate, has been widely used for dietary supplementation in pregnant women. The preventive effect of FA supplementation on the occurrence and recurrence of fetal neural tube defects (NTD) has been confirmed. Incidence of congenital heart diseases (CHD), however, has been parallelly increasing worldwide. The present study aimed to evaluate whether FA supplementation is associated with a decreased risk of CHD.
METHODS
We searched the literature using PubMed, Web of Science and Google Scholar, for the peer-reviewed studies which reported CHD and FA and followed with a meta-analysis. The study-specific relative risks were used as summary statistics for the association between maternal FA supplementation and CHD risk. Cochran's Q and I statistics were used to test for the heterogeneity.
RESULTS
Maternal FA supplementation was found to be associated with a decreased risk of CHD (OR = 0.82, 95% CI: 0.72-0.94). However, the heterogeneity of the association was high (P < 0.001, I = 92.7%). FA supplementation within 1 month before and after pregnancy correlated positively with CHD (OR 1.10, 95%CI 0.99-1.23), and high-dose FA intake is positively associated with atrial septal defect (OR 1.23, 95%CI 0.64-2.34). Pregnant women with irrational FA use may be at increased risk for CHD.
CONCLUSIONS
Data from the present study indicate that the heterogeneity of the association between maternal FA supplementation and CHD is high and suggest that the real relationship between maternal FA supplementation and CHD may need to be further investigated with well-designed clinical studies and biological experiments.
Topics: Dietary Supplements; Female; Folic Acid; Heart Defects, Congenital; Humans; Neural Tube Defects; Pregnancy; Prenatal Care
PubMed: 35346212
DOI: 10.1186/s12937-022-00772-2 -
SAGE Open Medicine 2022Various trial and epidemiological studies consistently documented the association between maternal folic acid supplementations and neural tube defects. However, existing...
INTRODUCTION
Various trial and epidemiological studies consistently documented the association between maternal folic acid supplementations and neural tube defects. However, existing literatures revealed inconclusive findings about maternal periconceptional folic acid supplementations and the risk of congenital heart defects. Thus, the current systematic review and meta-analysis was aimed to estimate the pooled association between maternal periconceptional folic acid supplementations and congenital heart defects.
METHODS
Electronic searches of PubMed, Web of Science/Scopus, Cochrane library and Google Scholar databases were conducted to access the required studies published up to March 2021. Predetermined eligibility criteria were used for study selections. Data extraction were independently done on excel. STATA version 14 software was used to calculate the pooled effect size with 95% confidence intervals (95% CI) of maternal periconceptional folic acid supplementations on congenital heart defects using the DerSimonian and Laird random effects meta-analysis (random effects model). Statistical heterogeneity was checked using the Cochran Q test (chi-squared statistic), I statistic, and by visual inspection of the funnel plot.
RESULTS
A total of 37 studies of case-control, cohort and randomized controlled trial in nature were included in the review. The finding of the present systematic review and meta-analysis indicated that periconceptional folic acid supplementation significantly decreases the risk of congenital heart defects (risk ratio (RR), 0.79; CI, 0.71, 0.89). Both Cochrane Q test statistic (χ = 19.33, p = 0.962) and I test statistic (I = 0.0%, p = 0.962) did not reveal statistically significant heterogeneity among included studies. In this meta-analysis, traditional funnel plot, Begg's funnel plot, Egger's weighted regression (p = 0.13) as well as Begg's rank correlation statistic (p = 0.676) revealed no evidence of publication bias.
CONCLUSION
The present systematic review and meta-analysis found that maternal periconception folic acid supplementation was significantly associated with the risk of congenital heart defects. The risk of congenital heart defects was significantly reduced by 21% among those children of mothers who use periconceptional folic acid supplementations in high-income countries. We recommend that a large prospective study be conducted to investigate the association between maternal periconceptional folic acid supplementation and occurrence of congenital heart defect of various types, especially in the developing countries.
PubMed: 35284077
DOI: 10.1177/20503121221081069 -
The Journal of Urology Jun 2022We systematically reviewed the variability in definitions of kidney abnormality (KA) outcomes in individuals with spina bifida (SB). (Review)
Review
PURPOSE
We systematically reviewed the variability in definitions of kidney abnormality (KA) outcomes in individuals with spina bifida (SB).
MATERIALS AND METHODS
A systematic scoping review was conducted using MEDLINE, Embase™, Cochrane Library, CINAHL, PsycInfo®, Web of Science™ and ClinicalTrials.gov for articles from time of database inception to September 2020. No language or patient age restrictions were applied. Primary research articles involving individuals with SB where KA was assessed as an outcome were included. Means of assessing KA and defining KA severity were abstracted.
RESULTS
Of 2,034 articles found, 274 were included in the review. Most articles were published after 1990 (63.5%) and included pediatric-only populations (0-18 years; 60.5%). KA outcomes were identified by imaging-based anatomical outcomes (84.7%), serum-based outcomes (44.9%), imaging-based functional outcomes (5.5%), urine-based outcomes (3.3%) and diagnoses of end-stage kidney disease (2.6%) or chronic kidney disease otherwise unspecified (1.8%). Hydronephrosis was the most commonly used specific outcome (64.6%, 177/274) with 19.8% (35/177) of articles defining hydronephrosis severity. Hydronephrosis was used more frequently in articles with pediatric-only populations. Creatinine and cystatin-C were used in 82.1% (101/123) and 17.9% (22/123) of articles reporting serum-based outcomes, respectively, with 32.7% and 50.0% of articles defining estimated glomerular filtration rate (GFR) severity. Serum-based outcomes were more common in articles including adults >18 years. Measured GFR was assessed in 9.9% (27/274) of articles, with 44.4% (12/27) of articles defining GFR severity.
CONCLUSIONS
Significant variability exists in how authors define KA with few specifically defining KA severity. Consensus and consistency in defining KA outcomes are needed.
Topics: Adult; Child; Female; Glomerular Filtration Rate; Humans; Hydronephrosis; Kidney; Male; Renal Insufficiency, Chronic; Spinal Dysraphism
PubMed: 35050700
DOI: 10.1097/JU.0000000000002432 -
Clinical Orthopaedics and Related... Apr 2022Life expectancy of individuals with spina bifida has continued to improve over the past several decades. However, little is known about the longitudinal course of...
BACKGROUND
Life expectancy of individuals with spina bifida has continued to improve over the past several decades. However, little is known about the longitudinal course of scoliosis in individuals with myelomeningocele (MMC), a spina bifida subtype, across their lifespan. Specifically, it is not known whether management during or after the transition years from adolescence to adulthood is associated with comorbidities in adulthood nor if these individuals benefit from scoliosis treatment later in life.
QUESTIONS/PURPOSES
In this systematic review, we asked: (1) Is the risk of secondary impairments (such as bladder or bowel incontinence, decreased ambulation, and skin pressure injuries) higher among adolescents and adults with MMC and scoliosis than among those with MMC without scoliosis? (2) Is there evidence that surgical management of scoliosis is associated with improved functional outcomes in adolescents and adults with MMC? (3) Is surgical management of scoliosis associated with improved quality of life in adolescents and adults with MMC?
METHODS
We performed a systematic review of articles in Medline and Embase from 2000 until February 5, 2021. Search terms such as "spinal dysraphism," "spina bifida," "meningomyelocele," and "scoliosis" were applied in diverse combinations. A total of 1429 publications were identified, and 13 were eligible for inclusion. We included original studies reporting on scoliosis among individuals older than 15 years with MMC. When available, we extracted the prevalence of MMC and scoliosis, studied population age, percentage of patients experiencing complications, functional outcomes, and overall physical function. We excluded non-English articles and those with fewer than 10 individuals with scoliosis and MMC. We used the Preferred Reporting Items for Systematic Reviews and Meta-analyses, and registered the review before data collection (PROSPERO: CRD42021236357). We conducted a quality assessment using the Methodologic Index for Nonrandomized Studies (MINORS) tool. In 13 included studies, there were 556 individuals with MMC and scoliosis. Most were retrospective case series, although a minority were retrospective/comparative studies. The mean MINORS score was 12.3 ± 1.65 (a MINORS score over 12 generally is considered good reporting quality, scores below 12 are considered at high risk of bias).
RESULTS
In general, studies found that individuals with MMC and scoliosis were more likely to have secondary impairments such as bladder/bowel incontinence, decreased ambulation, and pressure injuries than were patients with MMC without scoliosis. These secondary impairments were associated with hydrocephalus and high-level MMC lesions. However, when one study evaluated mortality, the results showed that although most deceased individuals who had spina bifida had scoliosis, no association was found between the age of death and scoliosis. Among the studies evaluating functional outcomes, none supported strong functional improvement in individuals with MMC after surgery for scoliosis. No correlation between the Cobb angle and sitting balance was noted; however, the degree of pelvic obliquity and the level of motor dysfunction showed a strong correlation with scoliosis severity. There was no change in sitting pressure distributions after spinal surgery. The lesion level and scoliosis degree independently contributed to the degree of lung function impairment. Although studies reported success in correcting coronal deformity and stopping curve progression, they found no clear benefit of surgery on health-related quality of life and long-term outcomes. These studies demonstrated that the level of neurologic function, severity of hydrocephalus, and brainstem dysfunction are greater determinants of quality of life than spinal deformity.
CONCLUSION
This systematic review found that adolescents and adults with MMC and scoliosis are more likely to have secondary impairments than their peers with MMC only. The best-available evidence does not support strong functional improvement or health-related quality of life enhancement after scoliosis surgery in adolescents and adults with MMC. The level of neurologic dysfunction, hydrocephalus, and brainstem dysfunction are greater determinants of quality of life. Future prospective studies should be designed to answer which individuals with MMC and scoliosis would benefit from spinal surgery. Our findings suggest that the very modest apparent benefits of surgery should cause surgeons to approach surgical recommendations in this patient population with great caution, and surgeons should counsel patients and their families that the risk of complications is high and the benefits may be small.
LEVEL OF EVIDENCE
Level IV, therapeutic study.
Topics: Adolescent; Adult; Fecal Incontinence; Humans; Hydrocephalus; Meningomyelocele; Prospective Studies; Quality of Life; Retrospective Studies; Scoliosis; Spinal Dysraphism
PubMed: 34939968
DOI: 10.1097/CORR.0000000000002087 -
Scientific Reports Dec 2021Anencephaly is a severe anomaly of the brain that results from the failure of the cephalic part of the neural tube to close during the fourth week. It occurs at least in... (Meta-Analysis)
Meta-Analysis
Anencephaly is a severe anomaly of the brain that results from the failure of the cephalic part of the neural tube to close during the fourth week. It occurs at least in one per thousand births and is the major cause of fetal loss and disabilities in newborns. The objective of this review is to determine the birth prevalence of anencephaly in Africa. We identified relevant studies via a search of databases like PubMed Central, PubMed/Medline, Science Direct, Joanna Briggs Institute, African Journals Online, Embase, Google Scholar, Web of Science, and Cochrane Library. After examining the heterogeneity of studies via the Cochran Q test and I test (and Forest plot for visual inspection), the prevalence of anencephaly was estimated using the random-effect meta-analysis model. Consequently, we carried out subgroup, sensitivity, meta-regression, trim and fill, time-trend, and meta-cumulative analyses. In this systematic review and meta-analysis, the twenty-four studies reported a total of 4,963,266 births. The pooled birth prevalence of anencephaly in Africa was 0.14% (95% CI: 0.12, 0.15%). Higher burden of anencephaly was detected in Ethiopia (0.37%, CI: 0.15, 0.58%), Algeria (0.24%, CI: 0.24, 0.25%), and Eritrea (0.19%, CI: 0.19, 0.19%). The higher pooled prevalence of anencephaly was observed in the studies that included both live births and stillbirths (0.16%) and in studies done after the year 2010 (0.25%) whereas, the lower burden was detected among countries that had a mandatory folic acid fortification (0.05%). High birth prevalence of anencephaly was detected in Africa. Strong prevention and control measures should be the priority because of an increment in the magnitude of anencephaly. Helping in prevention programs, which should be the ultimate contribution of this study to the field.
Topics: Africa; Anencephaly; Disease Susceptibility; Female; Humans; Male; Population Surveillance; Prevalence
PubMed: 34887455
DOI: 10.1038/s41598-021-02966-w -
Neuroradiology Feb 2022Open spina bifida (OSB) encompasses a wide spectrum of intracranial abnormalities. With foetal surgery as a new treatment option, robust intracranial imaging is... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Open spina bifida (OSB) encompasses a wide spectrum of intracranial abnormalities. With foetal surgery as a new treatment option, robust intracranial imaging is important for comprehensive preoperative evaluation and prognostication. We aimed to determine the incidence of infratentorial and supratentorial findings detected by magnetic resonance imaging (MRI) alone and MRI compared to ultrasound.
METHODS
Two systematic reviews comparing MRI to ultrasound and MRI alone were conducted on MEDLINE, EMBASE, and Cochrane databases identifying studies of foetal OSB from 2000 to 2020. Intracranial imaging findings were analysed at ≤ 26 or > 26 weeks gestation and neonates (≤ 28 days). Data was independently extracted by two reviewers and meta-analysis was performed where possible.
RESULTS
Thirty-six studies reported brain abnormalities detected by MRI alone in patients who previously had an ultrasound. Callosal dysgenesis was identified in 4/29 cases (2 foetuses ≤ 26 weeks, 1 foetus under any gestation, and 1 neonate ≤ 28 days) (15.1%, CI:5.7-34.3%). Heterotopia was identified in 7/40 foetuses ≤ 26 weeks (19.8%, CI:7.7-42.2%), 9/36 foetuses > 26 weeks (25.3%, CI:13.7-41.9%), and 64/250 neonates ≤ 28 days (26.9%, CI:15.3-42.8%). Additional abnormalities included aberrant cortical folding and other Chiari II malformation findings such as lower cervicomedullary kink level, tectal beaking, and hypoplastic tentorium. Eight studies compared MRI directly to ultrasound, but due to reporting inconsistencies, it was not possible to meta-analyse.
CONCLUSION
MRI is able to detect anomalies hitherto underestimated in foetal OSB which may be important for case selection. In view of increasing prenatal OSB surgery, further studies are required to assess developmental consequences of these findings.
Topics: Brain; Female; Fetus; Humans; Infant, Newborn; Magnetic Resonance Imaging; Pregnancy; Spinal Dysraphism; Ultrasonography, Prenatal
PubMed: 34792623
DOI: 10.1007/s00234-021-02853-1