Maternal Health and the Dental, Oral, and Craniofacial Health and Development of their Children

Oral and Comprehensive Health Research Program
Center for Clinical Research
Division of Extramural Research

Goal

The purpose of this initiative is to support research on prenatal environmental and physical stressors experienced by women during pregnancy that affect their child’s dental, oral, and craniofacial (DOC) tissues through altered maternal physiology.

Background

In the United States, the childbirth-associated maternal morbidity and mortality rate is one of the highest worldwide.1 Maternal mortality has been associated with diabetes, poor prenatal care, hemorrhaging and limited access to hospitals. It is recognized that highest rates of maternal morbidity and mortality disproportionately impact underrepresented minorities, lower socioeconomic and rural populations.2 There is a nationwide public health awareness of the need to improve maternal health, and the NIH Office of the Director, Office of Research on Women’s Health (ORWH), and National Institute of Child Health and Human Development (NICHD) are co-leading the Task Force on Maternal Mortality to reduce life threatening complications and identify biomarkers for the risk of morbidity and mortality during and after pregnancy.3 The recently released White House Maternal Health Blueprint outlines inter agency actions that will be undertaken to improve maternal care.

Maternal health not only impacts the mother but also their children. Poor maternal health is associated with premature deliveries and lower birth weights. Placental epigenetic changes have been associated with antenatal depression and stress.4 Maternal gestational diabetes and oligohydramnios have been associated with non-syndromic craniosynostosis.5 Maternal viral infections have been shown to result in altered tooth formation and enamel hypoplasia in their children.6 Children whose mothers were infected with Zika virus during pregnancy often suffer from microcephaly, micrognathia and hypodontia.7 Because the teeth and craniofacial structures of fetuses are developing in utero, deciduous teeth defects may be linked to maternal deleterious environmental exposures or other stressors. For example, enamel hypoplasia in the primary dentition has been associated with differences in maternal and neonatal calcium homeostasis.8 Maternal stressors have been identified with microscopic changes of their children’s deciduous teeth.9 Exfoliated deciduous teeth (such as those available in biorepositories) have served as a proxy for maternal environmental exposures and their intensity, thus providing a window into fetal exposures.10,11

The impact of maternal environmental, nutritional, pharmaceutical, and infectious exposures upon the developing and formed oral and craniofacial complex is unclear.12,13 Understanding the relationship between maternal health and the developing craniofacial complex of their children may enhance the management of pregnancy and improve the DOC health of children.

Gaps and Opportunities

The link between maternal prenatal health (e.g., diabetes, hypertension, autoimmune, infectious agents) and exposures (e.g., diet, pharmaceuticals, substances) and a child’s DOC development, is still being investigated. Identification and characterization of these mechanisms may elucidate modifiable prenatal maternal risk factors and the development of potential diagnostic and therapeutic modalities for DOC anomalies in their children.

This concept has shared interest with other NIH institutes and offices, and we are seeking their collaboration. Further, this concept is in alignment with priority #1 in the NIDCR Strategic Plan 2021-2026: “Elucidate the genetic, epigenetic, molecular, cellular and environmentally-driven mechanisms that drive the normal development of DOC tissues and characterize how disturbances in these mechanisms cause disorders and diseases of the DOC complex.”

This concept builds upon research initiatives as listed below.

  • (R01) PA-18-776 Maternal Nutrition and Pre-pregnancy Obesity: Effects on Mothers, Infants and Children.
  • (R01) PAR-21-115 Natural History of Disorders Screenable in Newborn Period.
  • HEAL Initiative: HEALthy Brain and Child Development Data Coordinating Center (U24).
  • RFA-DA-21-023 supports understanding of in utero substance exposure on the outcome of brain and behavioral development from birth to childhood.
  • ECHO supports multiple studies to investigate environmental exposures on child health and development with a focus on 5 noncraniofacial pediatric outcomes.

Specific Areas of Interest

Potential areas of research that address gaps in knowledge include:

  • Studies elucidating the interplay of prenatal maternal health including biologic, immunologic, infectious, and/or signaling pathways that disrupt the DOC tissues in human and nonhuman offspring.
  • Existing cohort studies using exfoliated deciduous teeth as biomarkers that measure intensity and timing of maternal environmental exposures to correlate with DOC phenotypes in their children.
  • Observational and mechanistic studies of pregnant mothers who have undergone emotional stress during pregnancy and its impact on the developing teeth and craniofacial structures of their offspring.
  • Epidemiologic studies comparing maternal prenatal health and disease and their children’s dental and craniofacial development to gain a better understanding of underlying disease mechanisms.
  • Observational and mechanistic studies monitoring the maternal prenatal exposome and the DOC development of their children. (e.g., dietary habits, tobacco, opioids, trauma).

References

  1. CDC, National Center for Health Statistics. Maternal Mortality Rates in the United States, 2019. April 2021.
  2. Howell EA, Egorova NN, Janevic T, Brodman M, Balbierz A, Zeitlin J, Hebert, PL. Race and Ethnicity, medical insurance, and within-hospital severe maternal morbidity disparities. Obstetrics and Gynecology.
  3. NIH Office of Research on Women's Health. Maternal Morbidity & Mortality Web Portal. Accessed: October 4, 2022.
  4. Tesfaye M, Chatterjee S, Zeng X. Impact of Depression and Stress on Placental DNA Methylation in Ethnically Diverse Pregnant Women. Epigenomics. 2021 Sept;13(18):1485-1496.
  5. Sergesketter AR, Elsamadicy AA, Lubkin DT, Krucoff KB, Krucoff MO, Muh CR. Characterization of Perinatal Risk Factors and Complications Associated With Nonsyndromic Craniosynostosis. J Craniofac Surg. 2019 Mar/Apr;30(2):334-338. doi: 10.1097/SCS.0000000000004997. PMID: 30358747.
  6. Kraus BS, Ames MD, Clark GR. Effects of Maternal Rubella and Crown Development. Clin Pediatrics. 1969 8(4):204-215.
  7. Zika and Microcephaly Center for Disease Control. Microcephaly and Other Birth Defects. Page last reviewed: May 14, 2019.
  8. Reed SG, Miller CS, Wagner CL, Hollis BW, Lawson AB. Toward Preventing Enamel Hypoplasia: Modeling Maternal and Neonatal Biomarkers of Human Calcium Homeostasis. Caries Res. 2020;54(1):55-67. doi:10.1159/000502793.
  9. Dunn EC, Mountain RV, et al. Association Between Measures Derived From Children's Primary Exfoliated Teeth and Psychopathology Symptoms: Results From a Community-Based Study. Front Dent Med. 29 Mar 2022 (not yet available in PubMed).
  10. Petrick LM, Arora M, Niedzwiecki MM. Minimally Invasive Biospecimen Collection for Exposome Research in Children's Health. Curr Environ Health Rep. 2020 Sep;7(3):198-210. doi: 10.1007/s40572-020-00277-2. PMID: 32535858; PMCID: PMC7895307.
  11. Austinc C, Niedzwiecki MM, Arora M. Multielemental Bioimaging of Tissues in Children's Environmental Health Research. Curr Opin Pediatr. 2016 Apr;28(2):216-220. doi: 10.1097/MOP.0000000000000328. PMID: 26845145; PMCID: PMC4949600.
  12. Bell JC, Raynes-Greenow C, Turner RM, Bower C, Nassar N, O'Leary CM. Maternal alcohol consumption during pregnancy and the risk of orofacial clefts in infants: a systematic review and meta-analysis. Paediatr Perinat Epidemiol. 2014 Jul;28(4):322-32. doi: 10.1111/ppe.
  13. Bhagirath AY, Medapati MR, de Jesus VC, Yadav S, Hinton M, Dakshinamurti S, Atukorallaya D. Role of Maternal Infections and Inflammatory Responses on Craniofacial Development. Front Oral Health. 2021 Sep 6;2:735634. doi: 10.3389/froh.2021.735634. PMID: 35048051; PMCID: PMC8757860.
Last Reviewed
September 2022