Maternal Folic Acid Supplementation During Pregnancy Promotes Neurogenesis and Synaptogenesis in Neonatal Rat Offspring

Abstract Maternal folic acid supplementation during pregnancy is associated with improved cognitive performances in offspring. However, the effect of supplementation on offspring’s neurogenesis and synaptogenesis is unknown, and whether supplementation should be continued throughout pregnancy is controversial. In present study, 3 groups of female rats were fed a folate-normal diet, folate-deficient diet, or folate-supplemented diet from 1 week before mating until the end of pregnancy. A fourth group fed folate-normal diet from 1 week before mating until mating, then fed folate-supplemented diet for 10 consecutive days, then fed folate-normal diet until the end of pregnancy. Offspring were sacrificed on postnatal day 0 for measurement of neurogenesis and synaptogenesis by immunofluorescence and western blot. Additionally neural stem cells (NSCs) were cultured from offspring’s hippocampus for immunocytochemical measurement of their rates of proliferation and neuronal differentiation. The results demonstrated that maternal folic acid supplementation stimulated hippocampal neurogenesis by increasing proliferation and neuronal differentiation of NSCs, and also enhanced synaptogenesis in cerebral cortex of neonatal offspring. Hippocampal neurogenesis was stimulated more when supplementation was continued throughout pregnancy instead of being limited to the periconceptional period. In conclusion, maternal folic acid supplementation, especially if continued throughout pregnancy, improves neurogenesis and synaptogenesis in neonatal offspring.

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Maternal Folic Acid Intake and Risk of Nonsyndromic Orofacial Clefts: A Hospital-Based Case–Control Study in Bangalore, India

The Cleft Palate-Craniofacial Journal ◽

10.1177/1055665619893214 ◽

2019 ◽

Vol 57 (6) ◽

pp. 678-686

Author(s):

Vivienne J. Mendonca

Keyword(s):

Folic Acid ◽

Case Control Study ◽

Folic Acid Supplementation ◽

Folic Acid Intake ◽

Orofacial Clefts ◽

Dietary Folate ◽

Acid Supplementation ◽

Folic Acid Supplements ◽

Periconceptional Period ◽

Control Study

Background: Orofacial clefts are the most common congenital anomaly worldwide. Cleft etiology appears to be multifactorial, with genetic and environmental components. Although periconceptional folic acid supplementation has been shown to be protective for neural tube defects, current evidence for its role in cleft prevention is mixed with few studies from low- and middle-income countries. Aim: To investigate the association between periconceptional folic acid intake and incidence of nonsyndromic orofacial clefts among infants in Bangalore, India. Methods: A hospital-based case–control study (106 cases, 212 controls) utilizing a questionnaire to collect data on prenatal supplements, dietary folate, and potentially confounding factors. Multivariate logistic regression analysis was used to assess relationships between folic acid supplementation and all nonsyndromic clefts, and in separate analyses for cleft lip and/or palate (CL/P) and cleft palate (CP), adjusting for statistically significant variables. Results: A statistically significant protective association was found for separate folic acid supplements (not combined with iron or multivitamins) taken in the periconceptional period and all clefts combined (adjusted odds ratio [OR]: 0.62, 95% confidence interval [CI], 0.45-0.86) and CL/P (adjusted OR: 0.57; 95% CI, 0.38-0.86). Higher levels of dietary folate were found to be associated with a reduced risk for all clefts (adjusted OR: 0.98, 95% CI, 0.96-0.99), CL/P (adjusted OR: 0.98, 95% CI, 0.96-0.99), and CP (adjusted OR: 0.96, 95% CI, 0.93-0.99). Conclusion: This study provides limited evidence for a protective association of periconceptional folic acid supplementation with nonsyndromic orofacial clefts. The low proportion of mothers taking folic acid supplements in the periconceptional period highlights the need for increased education and awareness regarding prenatal nutrition.

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Social Inequalities in Prenatal Folic Acid Supplementation: Results from the ELFE Cohort

Nutrients ◽

10.3390/nu11051108 ◽

2019 ◽

Vol 11 (5) ◽

pp. 1108 ◽

Cited By ~ 4

Author(s):

Aurore Camier ◽

Manik Kadawathagedara ◽

Sandrine Lioret ◽

Corinne Bois ◽

Marie Cheminat ◽

...

Keyword(s):

Folic Acid ◽

Family Income ◽

Social Inequalities ◽

Multinomial Logistic Regression ◽

Unplanned Pregnancy ◽

Folic Acid Supplementation ◽

Sociodemographic Characteristics ◽

Acid Supplementation ◽

Periconceptional Period ◽

Maternal Overweight

Most professional and international organizations recommend folic acid supplementation for women planning pregnancy. Various studies have shown high levels of non-compliance with this recommendation. This study aimed to identify sociodemographic characteristics related to this compliance. The analyses were based on 16,809 women from the French nationwide ELFE cohort (Etude Longitudinale Française depuis l’Enfance). Folic acid supplementation was assessed at delivery, and sociodemographic characteristics were collected at two months postpartum. The association between sociodemographic characteristics and compliance with recommendations on folic acid supplementation (no supplementation, periconceptional supplementation, and supplementation only after the periconceptional period) was examined using multivariate multinomial logistic regression. Only 26% of French women received folic acid supplementation during the periconceptional period, 10% of women received supplementation after the periconceptional period, and 64% received no supplementation. Young maternal age, low education level, low family income, multiparity, single parenthood, maternal unemployment, maternal overweight, and smoking during pregnancy were related to lower likelihood of folic acid supplementation during the periconceptional period compared to no supplementation. These associations were not explained by unplanned pregnancy. Immigrant and underweight women were more likely to receive folic acid supplementation after the periconceptional period. Our study confirms great social disparities in France regarding the compliance with the recommendations on folic acid supplementation.

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Folic Acid Supplementation in the Gestational Phase of Female Rats Improves Age-Related Memory Impairment and Neuroinflammation in Their Adult and Aged Offspring

The Journals of Gerontology Series A ◽

10.1093/gerona/glaa298 ◽

2020 ◽

Author(s):

Michelle Lima Garcez ◽

Francielle Mina ◽

Tatiani Bellettini-Santos ◽

Fernanda Melo Ribeiro ◽

Alessandra Zanette Ghisi Frassetto ◽

...

Keyword(s):

Prefrontal Cortex ◽

Folic Acid ◽

Memory Impairment ◽

Natural Aging ◽

Female Offspring ◽

Folic Acid Supplementation ◽

Female Rats ◽

Deficient Diet ◽

Age Related ◽

Maternal Supplementation

Abstract Folic acid (FA) supplementation is important during pregnancy to avoid malformations in the offspring. However, it is unknown if it can affect the offspring throughout their lives. To evaluate the offspring, female mother rats (dams) were separated into 5 groups: Four groups received the AIN-93 diet, divided into control and FA (5, 10, and 50 mg/kg), and an additional group received a FA-deficient diet, and the diet was performed during pregnancy and lactation. We evaluated the female offspring of these dams (at 2 and 18 months old). The aged offspring fed with FA-deficient diet presented habituation, spatial and aversive memory impairment and the FA maternal supplementation prevented this. The natural aging caused an increase in the TNF-α and IL-1β levels in the hippocampus from 18-month-old offspring. FA maternal supplementation was able to prevent the increase of these cytokines. IL-4 levels decreased in the prefrontal cortex from aged control rats and FA prevented it. FA deficiency decreased the levels of IL-4 in the hippocampus of the young offspring. In addition, natural aging and FA deficiency decreased brain-derived neurotrophic factor levels in the hippocampus and nerve growth factor levels in the prefrontal cortex and FA supplementation prevented it. Thus, the present study shows for the first time the effect of FA maternal supplementation on memory, cytokines, and neurotrophins in the aged offspring.

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Incidence of neural tube defects and their risk factors within a cohort of Moroccan newborn infants

BMC Pediatrics ◽

10.1186/s12887-021-02584-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Khenata Forci ◽

El Arbi Bouaiti ◽

Mohamed Hassan Alami ◽

Asmaa Mdaghri Alaoui ◽

Amal Thimou Izgua

Keyword(s):

Risk Factors ◽

Folic Acid ◽

Neural Tube ◽

Neural Tube Defects ◽

Newborn Infants ◽

First Trimester ◽

Folic Acid Supplementation ◽

Medical Monitoring ◽

Acid Supplementation ◽

Periconceptional Period

Abstract Background Neural tube defects (NTDs) are a group of birth defects that result from a partial or complete failure of the neural tube to close during embryogenesis. Their prevalence varies between 0.5 to 2 per 1000 births in countries without folic acid supplementation. The aim of our study is to assess the NTDs incidence and describe the risk factors within Moroccan newborn infants. Method This is a descriptive study over a period of 5 and a half years including all births at “Les Orangers” Maternity and Reproductive Health Hospital of Rabat with notification of NTD cases, whether isolated or combined with other anomalies. Data were reported on pre-established sheets and on the teratovigilance registry. Statistical analysis was performed with SPSS version 18 statistical software. Results During the study period, 43,923 births were recorded including 44 cases of neural tube defects, an incidence rate of 1 per 1000 births, with a female predominance; sex ratio = 0.8. These defects included anencephaly (50%), spina bifida (38.6%) and encephalocele (11.4%). The risk factors detected during this study include consanguinity (34%), consumption of fenugreek or other plants (36%), diabetes (4.5%) and medication (2.2%). A family history of malformation was reported in 6.8% of cases and among siblings in 4.5% of cases. The average maternal age was 30.38 ± 6.88 and the average gestational age was 36.80 ± 5.11. A quarter of mothers did not benefit from any medical monitoring during pregnancy while 59% did not take folic acid supplementation during the first trimester of pregnancy and none of them took B9 vitamin during the periconceptional period. The antenatal diagnosis was performed in 63% of cases. The mortality rate was 3.8 per 10,000 and 16% of cases evolved positively. Conclusion NTDs require high intensity and multidisciplinary care which stresses the importance, in our context, of strengthening and optimizing acid folic supplementation strategies during the periconceptional period.

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Folate and folic acid in the periconceptional period: recommendations from official health organizations in thirty-six countries worldwide and WHO

Public Health Nutrition ◽

10.1017/s1368980015000555 ◽

2015 ◽

Vol 19 (1) ◽

pp. 176-189 ◽

Cited By ~ 54

Author(s):

Sandra Gomes ◽

Carla Lopes ◽

Elisabete Pinto

Keyword(s):

Folic Acid ◽

First Trimester ◽

Developed Countries ◽

Folic Acid Supplementation ◽

Healthy Diet ◽

Folate Intake ◽

Childbearing Age ◽

Health Organizations ◽

Acid Supplementation ◽

Periconceptional Period

AbstractObjectiveTo summarize the recommendations on folate intake and folic acid supplementation and fortification in the periconceptional period, aimed at prevention of neural tube defects (NTD), provided by official health organizations in different countries worldwide and WHO.DesignInformation on recommendations for folate and folic acid intake in the periconceptional period was gathered from the websites of official national health organizations of several countries worldwide and from the WHO website.SettingWHO, selected developed countries and emerging economies, totalling thirty-six countries worldwide (some European, BRICS, G8, Asian Tiger/Asian Dragon and Australia).ResultsRecommendations differ between countries, although the majority (69·4 %) recommend a healthy diet plus a folic acid supplement of 400 µg/d from preconception (4–12 weeks) until the end of the first trimester of pregnancy (8–12 weeks). The same recommendation is issued by the WHO. Dosages for women at high risk of NTD are up to 4–5 mg/d (for 41·7 % of studied countries). The recommended intake for folate is in the range of 300–400 µg/d for women of childbearing age and 500–600 µg/d for pregnant women in different countries and WHO. Five countries emphasize the importance of a healthy diet rendering supplementation needless. By contrast, five others advise a healthy diet and supplementation plus mandatory fortification. Only one mentions the importance of ensuring an adequate folate status and refers to checking with a health-care provider on the need for supplements.ConclusionsDifferent recommendations regarding folate and folic acid, seeking NTD prevention, are available worldwide; however, most countries and WHO focus on a healthy diet and folic acid supplementation of 400 µg/d periconceptionally.

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Myoinositol: The Bridge (PONTI) to Reach a Healthy Pregnancy

International Journal of Endocrinology ◽

10.1155/2017/5846286 ◽

2017 ◽

Vol 2017 ◽

pp. 1-5 ◽

Cited By ~ 5

Author(s):

Pietro Cavalli ◽

Elena Ronda

Keyword(s):

Folic Acid ◽

Neural Tube ◽

Neural Tube Defects ◽

Case Series ◽

Recurrence Risk ◽

Folic Acid Supplementation ◽

Rodent Models ◽

Acid Supplementation ◽

Healthy Pregnancy ◽

Periconceptional Period

The use of folic acid in the periconceptional period can prevent about 70% of neural tube defects (NTDs). In the remaining cases, no medical prevention is available, and those conditions should be defined as folate-resistant NTDs. Rodent models suggest that some folate-resistant NTDs can be prevented by inositol (myoinositol and chiroinositol) supplementation prior to pregnancy. Should folic acid be combined with myoinositol periconceptional supplementation to reduce the overall risk of NTDs even in humans? Hereafter, we discuss the results from the PONTI study that strongly support both the effectiveness and safety of myoinositol periconceptional supplementation in preventing human NTDs. We further report on the largest case series of pregnancies treated with myoinositol and folic acid. At our institution, a sequential study during 12 years involved mothers at risk of fetal NTDs, and 29 babies from 27 pregnancies were born after periconceptional combined myoinositol and folic acid supplementation. No case of NTDs was observed, despite the high recurrence risk in the mothers. Taken together, those data suggest that periconceptional folic acid plus myoinositol can reduce both the occurrence and recurrence risks of NTDs in a greater number of cases than folic acid alone.

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Periconceptional folic acid supplementation and risk of parent-reported asthma in children at 4–6 years of age

ERJ Open Research ◽

10.1183/23120541.00250-2019 ◽

2020 ◽

Vol 6 (1) ◽

pp. 00250-2019

Author(s):

Jufen Liu ◽

Zhiwen Li ◽

Rongwei Ye ◽

Jianmeng Liu ◽

Aiguo Ren

Keyword(s):

Folic Acid ◽

Low Dose ◽

Allergic Diseases ◽

Folic Acid Supplementation ◽

Acid Supplementation ◽

Child Bearing ◽

Increased Risk ◽

Increase Risk ◽

Periconceptional Period ◽

Asthma In Children

BackgroundFolic acid supplementation is universally recommended for women of child-bearing age to prevent fetal neural tube defects (NTDs). Concerns have arisen over the potential risk for childhood allergy and asthma due to folic acid supplementation. We examined whether periconceptional supplementation with low-dose folic acid only was associated with an increased risk for allergy symptoms or asthma in offspring at 4–6 years of age.MethodsOut of 247 831 participating women enrolled in 1993–1996, 9090 were randomly selected and their children were followed up in 2000–2001. Information on mothers' demographic characteristics, folic acid supplementation and allergic diseases among children was collected. We used logistic regression to evaluate the association between folic acid intake and risk for allergic disease while adjusting for potential confounding factors.ResultsThe rate of allergy symptoms was 1.54% among children whose mothers had taken folic acid compared with 2.04% among those whose mothers had not taken folic acid, and the rate of asthma was 0.92% and 0.88%, respectively. Maternal folic acid supplementation was not associated with risk for allergy symptoms or asthma, with odds ratios (95% CI) of 0.80 (0.58–1.11) and 1.04 (0.67–1.61), respectively. No differences in the occurrence of allergy symptoms or asthma were observed when data were analysed by timing of supplementation or compliance with folic acid supplementation.ConclusionsSupplementation with low-dose folic acid only during the periconceptional period did not increase risk for allergy symptoms or asthma in children at 4–6 years of age in a population without staple fortification with folic acid.

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