What are the pregnancy complications of folate deficiency?

Answer

Possible pregnancy complications secondary to maternal folate status may include spontaneous abortion, abruption placentae, congenital malformations (eg, neural tube defect), and severe language delay in the offspring. In a literature review, Ray et al examined 8 studies that demonstrated association between hyperhomocystinemia and placental abruption/infarction.^[35]Folate deficiency also was a risk factor for placental abruption/infarction, although less statistically significant.^[36]

Several observational and controlled trials have shown that neural tube defects can be reduced by 80% or more when folic acid supplementation is started before conception. In countries like the United States and Canada, the policy of widespread fortification of flour with folic acid has proved effective in reducing the number of neural tube defects.^[37]

Although the exact mechanism is not understood, a relative folate shortage may exacerbate an underlying genetic predisposition to neural tube defects.

In a prospective observational study in Norway, where food is not fortified with folic acid, lack of supplementation with folic acid from 4 weeks before to 8 weeks after conception was associated with increased risk of severe language delay in the child at age 3 years.^[38]No association between folic acid supplementation and gross motor skills was reported.

A more recent Norwegian prospective cohort study reexamined the maternal use of supplemental folic acid prior to and during pregnancy and demonstrated an association between child autism and lack of supplementation. There was no association between maternal folic acid supplementation and child Asperger syndrome or pervasive developmental disorder-not otherwise specified.^[11]

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Media Gallery

The chemical structure of folic acid and amethopterin (methotrexate), a folic acid antagonist, shows the similarity of structure.
The transformation of formiminoglutamic acid to glutamic acid is dependent upon both vitamin B-12 and tetrahydrofolate. In contrast, the transformation of homocysteine to methionine is a vitamin B-12–dependent reaction.
Both folic acid and vitamin B-12 participate in the synthesis of DNA and RNA.
Histologically, the megaloblastosis caused by folic acid deficiency cannot be differentiated from that observed with vitamin B-12 deficiency.
Peripheral smear of blood in a patient with pernicious anemia. Macrocytes are observed and some of the red blood cells show ovalocytosis. A 6-lobed polymorphonuclear leucocyte is present.
Bone marrow aspirate from a patient with untreated pernicious anemia. Megaloblastic maturation of erythroid precursors is shown. Two megaloblasts occupy the center of the slide with a megaloblastic normoblast above.

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Author

Katherine Coffey-Vega, MD Fellow, Department of Internal Medicine, Division of Geriatrics, Virginia Commonwealth University School of Medicine

Katherine Coffey-Vega, MD is a member of the following medical societies: Alpha Omega Alpha

Disclosure: Nothing to disclose.

Coauthor(s)

Angela Gentili, MD Director of Geriatric Medicine Fellowship Program, Professor of Internal Medicine, Division of Geriatric Medicine, Virginia Commonwealth University Health System and McGuire Veterans Affairs Medical Center, Richmond, VA

Angela Gentili, MD is a member of the following medical societies: Virginia Geriatrics Society, American Geriatrics Society

Disclosure: Nothing to disclose.

Muhammad I Vohra, MD Geriatrician, Lucy Corr Life Care

Muhammad I Vohra, MD is a member of the following medical societies: American College of Physicians, American Geriatrics Society, Medical Society of Virginia, Virginia Geriatrics Society

Disclosure: Nothing to disclose.

David Kuan-Hua Chen, MD Consulting Staff, Department of Neurology, Michael E DeBakey Veterans Affairs Medical Center

David Kuan-Hua Chen, MD is a member of the following medical societies: Alpha Omega Alpha, Phi Beta Kappa

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Marcel E Conrad, MD Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, The Society of Federal Health Professionals (AMSUS), International Society of Hematology, Society for Experimental Biology and Medicine, SWOG

Disclosure: Partner received none from No financial interests for none.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Pradyumna D Phatak, MBBS, MD Chair, Division of Hematology and Medical Oncology, Rochester General Hospital; Clinical Professor of Oncology, Roswell Park Cancer Institute

Pradyumna D Phatak, MBBS, MD is a member of the following medical societies: American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous coauthor Ahmed Mosalem, MD, to the development and writing of this article.

The authors and editors of Medscape Reference also gratefully acknowledge the contributions of previous coauthors Subir Vij, MD, MPH and Waleed Siddiqi, MD to the development and writing of this article.

What are the pregnancy complications of folate deficiency?

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