Slower postnatal motor development in infants of mothers with latent toxoplasmosis during the first 18 months of life
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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2020, Medical HypothesesCitation Excerpt :The strongest effect of latent toxoplasmosis is probably its effect on human reproductive function [9]. In particular, women with latent toxoplasmosis have more sons [10–12] and their children exhibit slower prenatal [13,14] as well as postnatal development [15]. The most harmful form of toxoplasmosis is congenital toxoplasmosis.
The effects of toxoplasmosis on sex ratio at birth
2020, Early Human DevelopmentHuman Toxoplasma infection
2020, Toxoplasma Gondii: The Model Apicomplexan - Perspectives and MethodsAn updated literature review on maternal-fetal and reproductive disorders of Toxoplasma gondii infection
2018, Journal of Gynecology Obstetrics and Human ReproductionCitation Excerpt :When maternal infection occurs during the third trimester the most of neonates (more than 80%) are asymptomatic, however retinochoroiditis and neurologic deficits in childhood or early adulthood might be developed, if these newborns not treated appropriately in early age [40–59,60,61]. Moreover, some retrospective or prospective cohort studies have reported that the risk of schizophrenia and related psychoses and also intellectual disability, hearing loss, slower postnatal motor development during the first year of life, chorioretinitis during the ages of 20–30, cryptogenic epilepsy, autism spectrum disorders, Down syndrome, Alzheimer's disease are increased in infants of mothers with latent toxoplasmosis [62–70]. Acute infection in immunecomponent pregnant women is asymptomatic, although 10% of women have some symptoms include lymphadenopathy, flu-like illness, fever, fatigue, headache, polymyositis, dermatomyositis, and chorioretinitis [57,71].
Human Toxoplasma Infection
2013, Toxoplasma Gondii: The Model Apicomplexan - Perspectives and Methods: Second EditionHow and why Toxoplasma makes us crazy
2013, Trends in ParasitologyCitation Excerpt :Infected women also have a higher probability to deliver children with a developmental defect, for example Down syndrome [72]. It was also observed that Toxoplasma-free children of infected mothers have slower prenatal and postnatal development [73,74]. A possible explanation for all of these phenomena is that Toxoplasma lowers the stringency of embryo quality control [75], probably through immunosuppression [76,77], and in this way increases the probability that more immunogenic male embryos and embryos with various developmental defects are not aborted, and instead survive until delivery.