Biomarkers of nutrition and stress in pregnant women with a history of eating disorders in relation to head circumference and neurocognitive function of the offspring

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Abstract

Background

Eating disorders during pregnancy can affect fetal growth and the child’s early development, but the underlying mechanisms have not been elucidated. The aim of the present study was to investigate serum biomarkers of nutrition and stress in pregnant women with previous eating disorders compared to controls and in relation to head circumference and early neurocognitive development of the offspring.

Methods

In a longitudinal cohort study, pregnant nulliparous non-smoking women with a history of anorexia nervosa ( n = 20), bulimia nervosa ( n = 17) and controls ( n = 59) were followed during pregnancy and their children’s growth and neurocognitive development were followed up to five years of age. We investigated maternal serum biomarkers of nutrition and stress (ferritin, cortisol, thyroid-stimulating hormone, free thyroxine, insulin, insulin-like growth factor I (IGF-I) and IGF binding protein 1) in blood samples collected during early pregnancy and compared between groups (ANOVA, LSD post-hoc test). The results were related to previous data on head circumference at birth and neurocognitive development at five years of age of the offspring (Spearman rank correlation or Pearson correlation test).

Results

Serum levels of ferritin in the women with previous anorexia nervosa, but not in those with a history of bulimia nervosa, were significantly lower than in the controls ( p < 0.01), and correlated strongly to impaired memory function in their children (rs = −0.70, p < 0.001). Maternal serum levels of free thyroxine were similar between groups but correlated positively to reduced head circumference at birth of the children in the bulimia nervosa group (r = 0.48, p < 0.05), and with the same tendency in the anorexia nervosa group (r = 0.42, p = 0.07), but not in the controls (r = 0.006). There were no significant differences in cortisol or the other biomarkers between groups.

Conclusions

Low maternal serum ferritin in women with previous anorexia nervosa may be of importance for impaired memory capacity in the offspring at five years of age. Our results also indicate that thyroxin levels in pregnant women with previous eating disorders are positively associated with fetal head growth.

Electronic supplementary material

The online version of this article (doi:10.1186/s12884-015-0741-7) contains supplementary material, which is available to authorized users.

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Most cited references 26

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Abnormalities of maternal thyroid function during pregnancy affect neuropsychological development of their children at 25-30 months.

Yushu Li, Yuanbin Li, Yanyan Chen … (2010)

To examine the relationship between specific thyroid abnormalities (subclinical hypothyroidism, hypothyroxinaemia or elevated thyroid peroxidase antibody titres) in women during pregnancy and the subsequent neuropsychological development of their offspring. Serum was collected from 1268 women at 16-20 weeks of gestation and thyroid stimulating hormone (TSH), total thyroxine (tT(4)), free thyroxine (fT(4)), and Thyroid peroxidase antibodies (TPOAb) levels were measured. Thyroid function reference ranges specific for pregnancy were used to screen for thyroid abnormalities. Patients with isolated subclinical hypothyroidism (18 cases), hypothyroxinaemia (19 cases), and those who were euthyroid patients with elevated titres of TPOAb (34 cases) were identified. One hundred and forty-two euthyroid and TPOAb-negative women matched for gestational age from the same cohort were selected as controls. Intellectual and motor development score evaluations were performed on the children from the pregnancies at 25-30 months of age. Children of women with subclinical hypothyroidism, hypothyroxinemia and elevated TPOAb titres had mean intelligence scores 8.88, 9.30 and 10.56 points lower than those of the control group (P = 0.008, P = 0.004 and P = 0.001, respectively); mean motor scores were 9.98, 7.57 and 9.03 points lower than those of the controls [P < 0.001, P = 0.007 and P < 0.001, respectively (t-test)]. Unconditional multivariate logistic regression analysis showed that increased maternal serum TSH, decreased maternal serum tT(4), and elevated maternal TPOAb titres were separately associated with lower intelligence scores (ORs 15.63, 12.98, and 6.69, respectively) and poorer motor scores (ORs 9.23, 5.52, and 8.25, respectively). Intellectual and motor development of children at 25-30 months of age is separately associated with abnormalities of maternal thyroid at 16-20 weeks gestation. Maternal subclinical hypothyroidism, hypothyroxinaemia or euthyroidism with elevated TPOAb titres were all statistically significant predictors of lower motor and intellectual development at 25-30 months.

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Perinatal iron deficiency and neurocognitive development

Emily Radlowski, Rodney Johnson (2013)

Iron deficiency is the most common form of nutrient deficiency worldwide. It is highly prevalent due to the limited availability of high quality food in developing countries and poor dietary habits in industrialized countries. According to the World Health Organization, it affects nearly 2 billion people and up to 50% of women who are pregnant. Maternal anemia during pregnancy is especially burdensome to healthy neurodevelopment in the fetus because iron is needed for proper neurogenesis, development, and myelination. Maternal anemia also increases the risk of low birth weight, either due to premature birth or fetal growth restriction, which is associated with delayed neurocognitive development and even psychiatric illness. As rapid neurodevelopment continues after birth infants that received sufficient iron in utero, but that receive a low iron diet after 6 months of age, also show deficits in neurocognitive development, including impairments in learning and memory. Unfortunately, the neurocognitive complications of iron deficiency during critical pre- and postnatal periods of brain development are difficult to remedy, persisting into adulthood. Thus, preventing iron deficiency in the pre- and postnatal periods is critical as is devising new means to recapture cognitive function in individuals who experienced early iron deficiency. This review will discuss the prevalence of pre- and postnatal iron deficiency, the mechanism, and effects of iron deficiency on brain and cognitive development.

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Biological mechanisms that might underlie iron's effects on fetal growth and preterm birth.

Brett Allen (2001)

A negative association between anemia and duration of gestation and low birth weight has been reported in the majority of studies, although a causal link remains to be proven. This paper explores potential biological mechanisms that might explain how anemia, iron deficiency or both could cause low birth weight and preterm delivery. The risk factors for preterm delivery and intrauterine growth retardation are quite similar, although relatively little is understood about the influence of maternal nutritional status on risk of preterm delivery. Several potential biological mechanisms were identified through which anemia or iron deficiency could affect pregnancy outcome. Anemia (by causing hypoxia) and iron deficiency (by increasing serum norepinephrine concentrations) can induce maternal and fetal stress, which stimulates the synthesis of corticotropin-releasing hormone (CRH). Elevated CRH concentrations are a major risk factor for preterm labor, pregnancy-induced hypertension and eclampsia, and premature rupture of the membranes. CRH also increases fetal cortisol production, and cortisol may inhibit longitudinal growth of the fetus. An alternative mechanism could be that iron deficiency increases oxidative damage to erythrocytes and the fetoplacental unit. Iron deficiency may also increase the risk of maternal infections, which can stimulate the production of CRH and are a major risk factor for preterm delivery. It would be useful to explore these potential biological mechanisms in randomized, controlled iron supplementation trials in anemic and iron-deficient pregnant women.

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Author and article information

Contributors

Saloua Koubaa: saloua.koubaa@ki.se

Tore Hällström: tore.hallstrom@ki.se

Kerstin Brismar: kerstin.brismar@ki.se

Per M Hellström: per.hellstrom@medsci.uu.se

Angelica Lindén Hirschberg: +46 8 517 733 26 , angelica.linden-hirschberg@karolinska.se

Journal

Journal ID (nlm-ta): BMC Pregnancy Childbirth

Journal ID (iso-abbrev): BMC Pregnancy Childbirth

Title: BMC Pregnancy and Childbirth

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2393

Publication date (Electronic): 27 November 2015

Publication date PMC-release: 27 November 2015

Publication date Collection: 2015

Volume: 15

Electronic Location Identifier: 318

Affiliations

[ ]Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden

[ ]Department of Clinical Neuroscience, Division for Psychiatry, Huddinge, Karolinska Institutet, Stockholm, Sweden

[ ]Department of Neuroscience and Physiology, Division for Psychiatry and Neurochemistry, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

[ ]Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

[ ]Department of Medical Sciences, Uppsala University, Uppsala, Sweden

[ ]Department of Obstetrics and Gynecology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden

Article

Publisher ID: 741

DOI: 10.1186/s12884-015-0741-7

PMC ID: 4662826

SO-VID: ab230000-51a8-4879-a634-9ddb0f0bc8d1

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 3 May 2015

Date accepted : 17 November 2015

Custom metadata

ScienceOpen disciplines: Obstetrics & Gynecology

Keywords: anorexia nervosa,bulimia nervosa,pregnancy,ferritin,thyroxine,head circumference,neurocognitive development,offspring

Data availability:

ScienceOpen disciplines: Obstetrics & Gynecology

Keywords: anorexia nervosa, bulimia nervosa, pregnancy, ferritin, thyroxine, head circumference, neurocognitive development, offspring

Biomarkers of nutrition and stress in pregnant women with a history of eating disorders in relation to head circumference and neurocognitive function of the offspring

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Animal models of intrauterine growth restriction (IUGR)

Most cited references 26

Abnormalities of maternal thyroid function during pregnancy affect neuropsychological development of their children at 25-30 months.

Perinatal iron deficiency and neurocognitive development

Biological mechanisms that might underlie iron's effects on fetal growth and preterm birth.

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