Folic acid fortification and prevalences of neural tube defects, orofacial clefts, and gastroschisis in California, 1989 to 2010

Yang, Wei; Carmichael, Suzan L.; Shaw, Gary M.

doi:10.1002/bdra.23514

Cited by 28 publications

(27 citation statements)

References 27 publications

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“…They attributed this declining trend to the folic acid fortification of US enriched grain products (Saad et al, ). We have previously observed a temporal decline in orofacial clefts associated with dietary fortification with folic acid (Yang et al, ). This is consistent with other studies in the United States (Canfield et al, ; Yazdy, Honein, & Xing, ) and elsewhere (Golalipour, Vakili, & Kaviani, ).…”

Section: Discussionmentioning

confidence: 87%

“…That is, increased awareness and prenatal control of certain risk factors for oral clefts may also explain this declining trend. For example, decreased periconceptional cigarette smoking or increased intake of folic acid might contribute to such a decline (Lie et al, ; Yang, Carmichael, & Shaw, ). A similar declining trend was reported by the California Office of Statewide Health Planning and Development from 1995 to 2010 (Saad et al, ).…”

Section: Discussionmentioning

confidence: 99%

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Change in Prevalence of Orofacial Clefts in California between 1987 and 2010

Andrew

Yang

Bernstein

et al. 2018

American J of Med Genetics Pt A

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Change in Prevalence of Orofacial Clefts in California between 1987 and 2010

Andrew

Yang

Bernstein

et al. 2018

American J of Med Genetics Pt A

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“…Folate supplementation during the periconceptional period reduces the risk of OFC 8. Women who used multivitamins containing folic acid during the periconceptional period have a 25–50% reduction in risk of OFC occurrence compared with non-user women 9 10. In a prospective study, the OFC recurrence decreased from 7.4% to 4.1% in women who received folate-containing multivitamins supplements compared with non-supplemented women 11.…”

Section: Introductionmentioning

confidence: 98%

Cystathionine β-synthase genetic variant rs2124459 is associated with a reduced risk of cleft palate in French and Belgian populations

et al. 2016

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“…Unfortunately, FA supplementation started after the first trimester of pregnancy, does not prevent NTDs. In response to this concern, FA fortification of grains and cereal products has been mandatory in the United States since 1999, and post-fortification monitoring indicates that this has been effective in decreasing the occurrence of NTDs [17][18][19] . Initially isolated from human placenta, the folate receptor isoforms have been shown to have tissuespecific and cell-specific expression patterns [20][21][22][23] .…”

mentioning

confidence: 99%

The Antagonism of Folate Receptor by the Integrase Inhibitor Dolutegravir: Developmental Toxicity Reduction by Supplemental Folic Acid

Cabrera

Souder²,

Steele³

et al. 2019

Preprint

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Human immunodeficiency virus (HIV) integrase inhibitors are increasingly being used for antiretroviral therapy (ART), and dolutegravir (DTG/Tivicay) has emerged as a leading core agent. In 2018, the Tsepamo study reported a 6-to 9-fold increase for neural tube defect (NTD) risk among the offspring of mothers receiving DTG during early gestation. Maternal folate (vitamin B9) status is the largest known modifier of NTD risk, so we evaluated folate-related mechanisms of action and the critical period for DTG developmental toxicity. Folate receptor (FOLR1) binding studies indicate DTG is a non-competitive FOLR1 antagonist at therapeutic concentrations. In vitro testing indicates calcium (2mM) increases FOLR1-folate interactions and alters DTG-FOLR1-folate interactions and cytotoxicity. DTG does not inhibit downstream folate metabolism by dihydrofolate reductase (DHFR). Early embryonic exposure toDTG is developmentally toxic in zebrafish, and supplemental folic acid can mitigate DTG developmental toxicity. The results from these studies are expected to inform and guide future animal models and clinical studies of DTG-based ART in women of childbearing age. The human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) epidemic remains a prominent public health challenge. Globally, there are approximately 36.7 million people living with HIV, with 2.1 million new infections occurring annually, resulting in 1.1 million AIDS-related deaths per year 1 . Current HIV antiretroviral therapy (ART) includes C-C chemokine receptor type 5 (CCR5) antagonists, fusion inhibitors, integrase inhibitors, nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs), and protease inhibitors. Dolutegravir (DTG) is the clinically preferred integrase inhibitor used alone (Tivicay, ViiV Healthcare), or in combination (e.g. Triumeq, ViiV Healthcare) as ART for HIV infection in adults and children. A teratogenic risk for DTG was recently reported after neural tube defects (NTDs) were observed in four infants from mothers who had been taking DTG at the time of conception in Botswana 2 . The World Health Organization (WHO) subsequentlyprovided guidelines that DTG use be avoided by women of childbearing potential unless they used adequate contraception methods 3 . Based on this cohort study, the current guidelines are warranted and prudent, but more evidence is needed before scientific and medical communities can support a causal relationship between DTG and developmental toxicity, including NTDs. Developmental Toxicity of DTG:There is increasing usage of the HIV integrase inhibitors are for ART, and DTG has emerged as the leading compound in this class of medications. The DTG/Tivicay manufacturer reports (US FDA approved Tivicay Prescribing Information, 09/2018) animal reproduction studies showed no evidence of adverse developmental outcomes. Specifically, DTG was administered orally at up to 1,000 mg per kg daily, in rats and rabbits, during the period of organogenesis, days 6-17 and 6-18, respectively...

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Folic acid fortification and prevalences of neural tube defects, orofacial clefts, and gastroschisis in California, 1989 to 2010

Cited by 28 publications

References 27 publications

Change in Prevalence of Orofacial Clefts in California between 1987 and 2010

Change in Prevalence of Orofacial Clefts in California between 1987 and 2010

Cystathionine β-synthase genetic variant rs2124459 is associated with a reduced risk of cleft palate in French and Belgian populations

The Antagonism of Folate Receptor by the Integrase Inhibitor Dolutegravir: Developmental Toxicity Reduction by Supplemental Folic Acid

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