Elsevier

Early Human Development

Volume 88, Issue 11, November 2012, Pages 879-884
Early Human Development

Slower postnatal motor development in infants of mothers with latent toxoplasmosis during the first 18 months of life

https://doi.org/10.1016/j.earlhumdev.2012.07.001Get rights and content

Abstract

Toxoplasmosis, a zoonosis caused by a protozoan, Toxoplasma gondii, is probably the most widespread human parasitosis in developed countries. Pregnant women with latent toxoplasmosis have seemingly younger fetuses especially in the 16th week of gestation, which suggests that fetuses of Toxoplasma-infected mothers have slower rates of development in the first trimester of pregnancy. In the present retrospective cohort study, we analyzed data on postnatal motor development of infants from 331 questionnaire respondents including 53 Toxoplasma-infected mothers to search for signs of early postnatal development disorders. During the first year of life, a slower postnatal motor development was observed in infants of mothers with latent toxoplasmosis. These infants significantly later developed the ability to control the head position (p = 0.039), to roll from supine to prone position (p = 0.022) and were slightly later to begin crawling (p = 0.059). Our results are compatible with the hypothesis that the difference in the rates of prenatal and early postnatal development between children of Toxoplasma-negative and Toxoplasma-positive mothers might be caused by a decreased stringency of embryo quality control in partly immunosuppressed Toxoplasma-positive mothers resulting in a higher proportion of infants with genetic or developmental disorders in offspring. However, because of relatively low return rate of questionnaires and an associated risk of a sieve effect, our results should be considered as preliminary and performing a large scale prospective study in the future is critically needed.

Introduction

Probably the most widespread human parasitosis in developed countries is caused by the protozoan Toxoplasma gondii. Life-long latent toxoplasmosis is usually considered to pose no health threat to immunocompetent persons; however, it is accompanied by specific changes in the psychomotor performance, behavior and personality profile [1], [2], [3]. The most serious is congenital toxoplasmosis; in pregnant women in the acute phase of the infection, the parasite can infect the placenta and, after a lag period, also the fetus. About 20% of infants with congenital infection have severe disease. Approximately 70% of them are asymptomatic at birth but can develop clinical symptoms later. For example, they have slower neurological and mental development and can also later develop hearing and vision impairments, the latter being typically associated with chorioretinitis [4].

Neither pathological changes nor health damage was reported in neonates born to mothers with latent toxoplasmosis. Kimball et al. [5] speculated on possible effects of latent toxoplasmosis on the risk of abortion; however, this speculation was not confirmed in later studies [6], [7]. Pregnant women with latent toxoplasmosis were reported to have seemingly younger (less developed) fetuses, especially at the 16th week of pregnancy [8], [9]. Two different immunological hypotheses were suggested to explain this effect of toxoplasmosis on pregnancy. One assumes that the changes in the immune system could delay the implantation of the blastocyst in multiparous women with toxoplasmosis. The other posits that Toxoplasma could weaken or switch off the mechanism of spontaneous abortions, which is under normal conditions responsible for the elimination of embryos with developmental defects and therefore with a (statistically) slower fetal growth rate. The latter hypothesis was recently supported by the observed increase in the secondary sex ratio in children of women with latent toxoplasmosis [10]. The probability of the birth of a boy increased up to 0.71, which means that about 250 boys were born for every 100 girls to women with moderate concentrations of anti-Toxoplasma antibodies (and therefore probably with recent but already latent infection). This effect of latent toxoplasmosis was later confirmed in experimentally infected mice [11]. Mice with toxoplasmosis produced a higher sex ratio (expressed as the proportion of males in the offspring) than controls, in the early phase of latent infection. A recent study [12] showed significant modifications of cytokine production and modulation of some parameters of the immune response during latent toxoplasmosis. These results for the infected mice are in accordance with the hypothesis that the increased probability of the birth of male offspring in Toxoplasma-infected mice and humans might be just a nonadaptive side effect of Toxoplasma-induced immunosuppression. Similarly, the immunosuppression could also be responsible for the observed longer pregnancy in mothers with latent toxoplasmosis [9], either due to reduced implantation potential of the fertilized ovum in immunosuppressed females [13] or to higher probability of survival of fetuses with genetic or developmental disorders [8], [9] including those with chromosomal aberrations. This can explain the extremely high prevalence of latent toxoplasmosis in mothers of children with Down syndrome (about 84% vs. 32% in controls) [14].

If Toxoplasma actually allows the development of embryos that would be miscarried when born by Toxoplasma-negative mothers, then differences in the rates of postnatal development should be probably observed between infants of infected and non-infected mothers. If the children with genetic or developmental disorders are overrepresented in the offspring of infected mothers, then we should expect slower rates of early postnatal development in children of mothers with latent toxoplasmosis in comparison with those of Toxoplasma-negative mothers. The aim of the present study is to search for signs of delayed postnatal motor development in children of mothers with latent toxoplasmosis within the first 18 months after delivery using a questionnaire survey among 351 mothers tested for latent toxoplasmosis during pregnancy.

Section snippets

Subjects

The experimental set consisted of women from two private clinics (Centres of Reproductive Medicine in Prague 5 and Prague 8). The experimental design was a retrospective cohort study. All study subjects were sent a questionnaire form to be filled out at home. Clinical records contained data on maternal age, newborn's sex and results of the serological test for toxoplasmosis at about the 16th week of pregnancy. The concentration of anamnestic titres of IgG antibodies against Toxoplasma was

Questionnaire response rates in Toxoplasma-positive and Toxoplasma-negative mothers

The results showed that Toxoplasma-positive mothers returned the questionnaire marginally less frequently than Toxoplasma-negative mothers (χ2 = 3.663, df = 1, p = 0.056). The questionnaire was sent to 197 Toxoplasma-positive and 817 Toxoplasma-negative mothers and was returned by 53 Toxoplasma-positive (26.9%) and 278 Toxoplasma-negative mothers (34%). The separate tests for mothers who gave birth to a boy or a girl showed that the effect of toxoplasmosis was significant for 517 women who gave birth

Discussion

Our results showed that children of mothers with latent toxoplasmosis expressed lower rates of postnatal development in the first 18 months of life. The infants of Toxoplasma-positive mothers later developed the ability to control the head and to turn from supine to prone position and were slightly later to begin crawling. They also had a higher weight than infants of Toxoplasma-negative mothers. Mothers with latent toxoplasmosis failed to adhere to the home physiotherapy program significantly

Conflict of interest

Neither of the authors have any conflicts of interest to disclose.

Acknowledgments

The research was supported by the Charles University, project UNCE 204004.

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