October 7, 2020

Coronavirus, Pregnancy, and Infant Brain Development

Making a case for choline
The link between maternal choline intake during pregnancy and infant outcomes is a hot topic in prenatal nutrition. This article shows that higher levels of the essential nutrient during pregnancy may protect infants from the neurological effects of maternal viral infections. It contributes to a growing body of work suggesting that all providers working with pregnant women should assess choline intake.

Reference

Freedman R, Hunter SK, Law AJ, et al Maternal choline and respiratory coronavirus effects on fetal brain development. J Psychiatr Res. 2020;128:1-4.

Study Objective

To examine the impact of maternal choline levels on the inflammatory immune response triggered by viral respiratory infections during pregnancy and subsequent impact on infant neurological development.

Design

Researchers analyzed a data subset acquired from a 2019 study that surveyed pregnant women about viral infections during pregnancy, tested C-reactive protein (CRP) and choline levels in the blood, and analyzed trends related to infant development at 3 months.1

Participants

Ninety-six pregnant women, including 43 who had experienced viral respiratory infections prior to 16 weeks gestation and 53 who had not.

Study Parameters Assessed

The researchers asked the participants at 16 weeks gestation if they had experienced viral respiratory infections causing illness in the preceding 6 weeks. If the answer was yes, the women were asked to rate their symptom severity; researchers confirmed this self-reporting with retrospective chart review. Maternal choline and CRP levels were drawn at 16 weeks. When the infants were 3 months of age, the mothers completed the Infant Behavior Questionnaire–Revised Short Form (IBQ-R).

Primary Outcome Measures

History of viral respiratory infection, maternal CRP and choline levels, and infant IBQ-R scores at 3 months, specifically the ratings of Regulation and Attention.

Key Findings

Viral respiratory infections were correlated with elevated CRP levels in women at 16 weeks gestation. For women with serum choline levels equal to or above 7.5 µmol/L, there were no differences in infant scores of Regulation and Attention compared to the uninfected women. Infants born to mothers who reported viral respiratory infections and had serum choline levels less than 7.5 µmol/L had significantly lower ratings of Attention (2.64) compared to infants born to mothers with no infection (5.00).

Practice Implications

The link between maternal choline intake during pregnancy and infant outcomes is a hot topic in prenatal nutrition. This article contributes to a growing body of work suggesting that all providers working with pregnant women should assess maternal choline intake.

The study currently under review used a data subset that suggests that a viral infection during the early second trimester may have a negative neurologic impact later seen in the neurological development of the infant, at least in those women who have lower choline levels at 16 weeks of pregnancy.

Research in animals has shown that inflammation during pregnancy may affect later brain function in the offspring. For example, a rodent study suggested that there is a vulnerable window early in the second trimester when inhibitory interneurons in the hippocampus are vulnerable to maternal inflammation.2

While the cohort used for the current study did not have overt SARS-Cov-2 infection, the authors propose that the same protective benefit maternal choline appeared to have against general upper respiratory tract infections in their study may be relevant to inflammation caused by coronavirus. Supporting their hypothesis, they cite a small case series of 9 women in Wuhan, China, that found elevated CRP levels in pregnant women with coronavirus infection.3

This article contributes to a growing body of work suggesting that all providers working with pregnant women should assess maternal choline intake.

We are still in the early days of understanding the SARS-Cov-2 virus. There is no information on how it may impact vulnerable populations like pregnant people and the development of infants. While this study does not present new data on COVID specifically, it does examine past data and offer an interesting hypothesis that may be relevant to coronavirus infections.

Average choline intake in American women is 278 mg per day.4 This is well below the 450 milligrams recommended by the U.S. Food and Drug Administration for pregnant women. Many prenatal vitamins contain little to no choline, leaving most women choline-deficient and likely under the 7.5 µmol/L level that appears to offer neuroprotection from maternal inflammation for the infant.

This fact, plus the growing body of research supporting the safety and potential benefit of sufficient choline in pregnancy,5,6 makes a strong case for monitoring maternal choline intake during pregnancy and suggesting dietary change or supplementation to reach the desired intake. The possibility of adding a layer of protection for infant brain development during a viral pandemic makes adopting this idea more appealing, even as we wait for more conclusive data in the future.

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References

  1. Freedman R, Hunter SK, Law AJ, et al. Higher gestational choline levels in maternal infection are protective for infant brain development [published correction appears in J Pediatr. 2019;213:254]. J Pediatr. 2019;208:198-206.e2.
  2. Vasistha NA, Pardo-Navarro M, Gasthaus J, et al. Maternal inflammation has a profound effect on cortical interneuron development in a stage and subtype-specific manner. Mol Psychiatry. 2019. doi: 10.1038/s41380-019-0539-5. Online ahead of print. Accessed August 10, 2020.
  3. Chen H, Guo J, Wang C, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records [published correction appears in Lancet. 2020;395(10229):1038]. Lancet. 2020;395(10226):809-815.
  4. Moore CJ, Perreault M, Mottola MF, Atkinson SA. Diet in early pregnancy: focus on folate, Vitamin B12, Vitamin D, and choline. Can J Diet Pract Res. 2020;81(2):58-65.
  5. Wiedeman AM, Barr SI, Green TJ, Xu Z, Innis SM, Kitts DD. Dietary choline intake: current state of knowledge across the life cycle. Nutrients. 2018;10(10):1513.
  6. Korsmo HW, Jiang X, Caudill MA. Choline: Exploring the growing science on its benefits for moms and babies. Nutrients. 2019;11(8):1823.