Document Detail

Effects of maternal worm infections and anthelminthic treatment during pregnancy on infant motor and neurocognitive functioning.
Jump to Full Text
MedLine Citation:
PMID:  23158229     Owner:  NLM     Status:  MEDLINE    
We tested the hypothesis that maternal worm infections in pregnancy affect infant motor and neurocognitive development, and that anthelminthic treatment during pregnancy can reverse these effects. We used measures which examine infant motor, cognitive and executive function, including inhibition. We assessed 983 Ugandan infants aged 15 months, using locally appropriate measures within the Entebbe Mother and Baby Study, a trial of anthelminthic treatment during pregnancy. Key exposures were maternal worm infections and anthelminthic treatment during pregnancy. Effects of other health and social factors were controlled for statistically. Of the five major worm species found in the pregnant women, two had influences on the developmental measures: Maternal Mansonella perstans and Strongyloides stercoralis infections showed negative associations with the A-not B-task, and Language, respectively. Performance on other psychomotor and cognitive measures was associated with illnesses during infancy and infants' behavior during assessment, but not with maternal worm infections. There were no positive effects of maternal anthelminthic treatment on infant abilities. Mansonella perstans and Strongyloides stercoralis infection during pregnancy seem associated with impaired early executive function and language, respectively, but single-dose anthelminthic treatment during pregnancy was not beneficial. The biological mechanisms that could underlie these neurocognitive effects are discussed.
Margaret Nampijja; Barbara Apule; Swaib Lule; Hellen Akurut; Lawrence Muhangi; Emily L Webb; Charlie Lewis; Alison M Elliott; Katie J Alcock
Related Documents :
19517699 - Uterine torsion in delayed diagnosis of abnormal anterior placentation: a report of 2 c...
23147969 - Autism after infection, febrile episodes, and antibiotic use during pregnancy: an explo...
20364099 - The placenta: transcriptional, epigenetic, and physiological integration during develop...
10486489 - Maternal arterial connections to the placental intervillous space during the first trim...
11023169 - Maternal complications with placenta previa.
17230289 - Avoiding manual removal of placenta: evaluation of intra-umbilical injection of uteroto...
25330709 - Multiple sclerosis and pregnancy prescriptions.
23747129 - Trophoblast invasion and oxygenation of the placenta: measurements versus presumptions.
1503649 - Early prenatal diagnosis and therapy of fetal hypothyroid goiter.
Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the International Neuropsychological Society : JINS     Volume:  18     ISSN:  1469-7661     ISO Abbreviation:  J Int Neuropsychol Soc     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-19     Completed Date:  2013-11-15     Revised Date:  2014-03-11    
Medline Journal Info:
Nlm Unique ID:  9503760     Medline TA:  J Int Neuropsychol Soc     Country:  England    
Other Details:
Languages:  eng     Pagination:  1019-30     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Anthelmintics / adverse effects*
Antiparasitic Agents / adverse effects*
Child Development / drug effects
Cognition Disorders / chemically induced*
Double-Blind Method
Movement Disorders / etiology*
Parasitic Diseases / drug therapy,  epidemiology
Pregnancy Complications / chemically induced*
Prenatal Exposure Delayed Effects / chemically induced*
Psychomotor Performance / drug effects
Reproducibility of Results
Retrospective Studies
Statistics as Topic
Young Adult
Grant Support
064693//Wellcome Trust; 079110//Wellcome Trust; 095778//Wellcome Trust
Reg. No./Substance:
0/Anthelmintics; 0/Antiparasitic Agents

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): J Int Neuropsychol Soc
Journal ID (iso-abbrev): J Int Neuropsychol Soc
Journal ID (publisher-id): INS
ISSN: 1355-6177
ISSN: 1469-7661
Publisher: Cambridge University Press, New York, USA
Article Information
Download PDF
© The International Neuropsychological Society 2012
Received Day: 25 Month: 2 Year: 2011
Revision Received Day: 05 Month: 5 Year: 2012
Accepted Day: 07 Month: 5 Year: 2012
Print publication date: Month: 11 Year: 2012
Volume: 18 Issue: 6
First Page: 1019 Last Page: 1030
PubMed Id: 23158229
ID: 3948080
DOI: 10.1017/S1355617712000768
Publisher Item Identifier: S1355617712000768
Publisher Id: 00076

Effects of Maternal Worm Infections and Anthelminthic Treatment during Pregnancy on Infant Motor and Neurocognitive Functioning Alternate Title:M. Nampijja et al. Alternate Title:Developmental effects of maternal worms
Margaret Nampijja12
Barbara Apule3
Swaib Lule1
Hellen Akurut1
Lawrence Muhangi1
Emily L. Webb4
Charlie Lewis2
Alison M. Elliott14
Katie J. Alcock2
1Co-infections Studies Programme, MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda
2Department of Psychology, Lancaster University, Lancaster, United Kingdom
3Department of Obstetrics & Gynecology, Entebbe General Hospital, Entebbe, Uganda
4Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, United Kingdom
Correspondence: Correspondence and reprint requests to: Margaret Nampijja, Department of Psychology, Lancaster University, Fylde College, Lancaster LA1 4YF, UK. E-mail:


Early cognitive development underlies individual differences in children's behavior and academic performance (Cooper & Farran, 1988; Rohde & Thompson, 2007; see Tramontana, Hooper, & Selzer, 1988, for a review). In the developing world, poverty, disease and malnutrition inhibit children from attaining their developmental potential. Several studies suggest that worms, affecting approximately 90 million school-age children (Brooker, Clements, & Bundy, 2006), impair cognitive functions (e.g., Boivin et al., 1993; Ezeamama et al., 2005; Jukes et al., 2002; Nokes et al.,1992, 1999; Sakti et al., 1999).

Worms also infect approximately a third of pregnant women in Sub-Saharan Africa (Bundy, Chan, & Savioli, 1987). We hypothesized that maternal worm infections might influence the development of cognitive function in infants. Animal studies suggest that by depleting nutrients available to the fetus, maternal worm infections may interfere with processes such as myelination and the development of neurotransmitter systems vital for neurological and cognitive functioning (Beard et al., 2007). Beard et al. (2005) found that offspring of iron-deficient rats had lower iron content, lowered activity in the dopamine transporter system in the caudate nucleus and substantia nigra, reduced motor activity, and higher anxiety levels than controls. In humans, dopamine influences the limbic system and frontal cortex: disruptions in the dopamine system interfere with psychomotor and executive function (Goto & Grace, 2005; Smith & Kieval, 2000). Hence, we postulated that early human executive function might be particularly vulnerable to effects of maternal worm infections. Executive function comprises processes involved in goal-directed behavior or planning and consists of complementary sub-skills including working memory, inhibitory control and attentional flexibility (Hughes, 1998; Miyake et al., 2000).

Maternal worm infections co-exist with several important potential confounders, such as maternal under-nutrition (Goldenberg, Hoffman, & Cliver, 1998; Hack, 1998), maternal infections, including HIV and malaria (Gay et al., 1995; Gentile, Boll, Stagno, & Pass, 1989) and exposures in infancy including malaria (Dugbartey & Spellacy, 1997), recurrent diarrhea (Berkman, Lescano, Gilman, Lopez, & Black, 2002), anemia (Clarke, Grantham-McGregor, & Powell, 1991; Lozoff, Brittenham, & Wolf, 1987), malnutrition (Galler, Ramsey, Solimano, Kucharski, & Harrison, 1984; Grantham-McGregor, Powell, Walker, Chang, & Fletcher, 1994), and inadequate social stimulation (Bradley et al., 1989; Grantham-McGregor, Powell, Walker, & Himes, 1991; Ramey & Ramey, 1998).

Measuring executive function in young children in resource-limited settings is difficult. Measures that take into account immature verbal and motor skills and low attentional spans, and adapted to local conditions, are required (Espy, 2004). One task designed to test motor inhibition that has been translated and adapted for various cultures is the A-not-B task. In this test, an object is hidden repeatedly at location A and then at location B. Infants who persistently search at A show poor motor inhibition. Devised by Piaget (1954) to study object permanence in infants, initial cognitive explanations regarding this task focused on short term memory (Schacter, Moscovitch, Tulving, McLachlan, & Freedman, 1986). Subsequently, it was suggested that executive functions were important (Diamond, 1988; Diamond & Goldman-Rakic, 1989): two meta-analyses of over 100 studies (Marcovitch & Zelazo, 1999; Wellman, Cross, & Bartsch, 1986) both proposed that the infant's response is driven by interaction between representation of the location and inhibition of the motoric tendency to search at the previous location. Initial findings suggested that younger infants perseverate more than older infants. Subsequent longitudinal studies (e.g., Clearfield et al., 2006) showed that at first infants do not perseverate, that this is followed by a stage of perseveration and then at around 12 months competence on the task. Thus Clearfield and colleagues argue that performance on A-not-B may be determined by competition between active (faster) and latent (slower) memory processes, and perseveration may be a consequence of immaturity in processes that guide application of past experience. Initially, Thelen and Smith (1994) attributed perseveration to motoric rather than cognitive schemes, but more recently Smith, Thelen, Titzer, and McLin (1999) proposed that infants’ reaching is guided by a dynamic interplay between cognitive, motor, and visuospatial systems. While processes that underlie the A-not-B task are yet to be ascertained, the task covers a wide age-group, is sensitive for even very young infants (e.g., Clearfield et al., 2006; Diamond & Doar, 1989) and, hence, seems suitable for measuring early executive function.

A second important aspect of executive function is delay inhibition. Conflict inhibition tasks such as A-not-B require inhibiting an inappropriate prepotent response while activating a conflicting novel response. Delay inhibition tasks (e.g., the Self Control task) require the child simply to refrain from responding until a given signal, and may be purer measures of inhibition (Carlson, Davis, & Leach, 2005).

Executive function emerges in infancy (Diamond, 1985; Thompson & Nelson, 2001), and is thought to integrate input from several developing systems including attention (Rothbart & Ahadi, 1994), memory and language (Kopp, 1982), and psychosocial functioning (Londerville & Main, 1981; Stayton, Hogan, & Ainsworth, 1971). Psychomotor skills, language and socioemotional skills develop concurrently, but draw less upon executive mechanisms and may therefore be less affected by maternal worm infections.

We aimed to examine effects of maternal worm infections and anthelminthic treatment in pregnancy on motor and cognitive outcomes in infants at age 15 months. Our hypothesis was that two measures known to have high executive loads (the A-not-B and Delay Inhibition tasks) would be particularly sensitive to effects of maternal worm infections. In a large sample, we therefore examined different subtests of a locally appropriate assessment battery, the Kilifi Developmental Inventory-KDI (Abubakar, Holding, Van Baar, Newton, & Van de Vijver, 2008), to establish effects of maternal worm infections and their treatment on infants’ developing executive functions, and other developing cognitive and psychomotor skills.

Design and Participants

This research was part of the Entebbe Mother and Baby Study (EMaBS), a double-blind randomized placebo-controlled trial of anthelminthic treatment during pregnancy (Elliott et al., 2007). Between 2003 and 2005, a total of 2507 pregnant women were enrolled, investigated for parasitic infections and hemoglobin level, and randomized to receive albendazole (400 mg) or its matching placebo and praziquantel (40 mg/kg) or its matching placebo in a 2 × 2 factorial design. Albendazole treats roundworms (nematodes), and has some antiprotozoal effects. Praziquantel targets flatworms (trematodes), including schistosomiasis. Neither drug has known effects on bacterial infections. All mothers including those who had received placebos during pregnancy were treated effectively soon after delivery.

Infants underwent psychomotor assessments at 15 months using a modification of the KDI. Cognitive and social abilities were assessed using additional measures. Of 2507 women enrolled, there were 2345 live births of whom 1022 children were assessed but 39 were excluded from analysis because they were not tested within 2 months of age 15 months. Of those not tested, 94 had died (complications of labor or neonatal sepsis) before reaching age 15 months (infant mortality was not related to maternal worm infections [unpublished data] or their treatment [Webb et al., 2011]), 174 were lost to follow-up, 427 were seen at 15 months before the developmental assessments were introduced, 628 missed the 15 month visit. Of the 983 children (500 boys) tested, mean age was 15.59 months (SD 0.49; min 14.23 months; max 17 months). Of their mothers, 249 received praziquantel and albendazole; 241 praziquantel and albendazole-matching placebo; 251 albendazole and praziquantel-matching placebo; and 242 received both placebos.


This research was approved by the Science and Ethics Committee of the Uganda Virus Research Institute and the Uganda National Council of Science and Technology. Written informed consent was obtained from all eligible participants. In 1996, WHO recommended mass treatment of pregnant women in the second and third trimester with albendazole (400 mg) (WHO, 1996) in settings with high prevalence of hookworm and anemia. In 2002, WHO recommended treatment of schistosomiasis with praziquantel (40 mg/kg) during pregnancy and breast-feeding (WHO, 2002) but there was limited evidence on the risk-benefit ratio of this intervention. There was concern that anthelminthic drugs might lead to adverse birth outcomes (Bradley & Horton, 2001) and that among HIV positive women anthelminthic treatment might lead to an increase in HIV load and increased vertical HIV transmission (Elliott et al., 2003). Thus a condition of equipoise was considered to exist (Elliott et al., 2007). Indeed, WHO subsequently called for placebo-controlled trials of praziquantel during pregnancy (WHO, 2006). Our population had a moderate prevalence of hookworm (45%) and schistosomiasis (18%) but rates of anemia were relatively low and women with severe anemia (hemoglobin level less than 8.0 g/dL) were excluded from the study and treated. Hence a placebo-controlled study design was considered justified.

Motor and Cognitive Assessments

We used two executive function measures, the A-not-B task and a Self Control (delay inhibition) task, previously translated and used in rural Kenya (Abubakar, Holding, Van de Vijver, Bomu, & Van Baar, 2010). Infants’ skills on Language, Self Care and Recognition of Self and Others were determined using parental reports (Abubakar et al., 2010). Fine-motor and gross-motor function, and non-task behavior (mood, interaction, and activity) were assessed using ratings originally developed for the KDI (Abubakar et al., 2008). Details of measures are described below.

Fine Motor

Control of small hand-movements was assessed using items such as building a tower with blocks and scribbling with a pen. Twenty-seven items were scored as pass/fail and summed to give a score.

Gross Motor

Control of the limbs was assessed using 35 items such as kicking a ball or climbing onto a platform; a total was calculated.

Child's mood, activity, and interaction

The assessor observed the child's activity, mood, and level of interaction and rated them on a six-point scale. High scores indicated good mood, activity, or interaction.

Self Control (delay inhibition)

In two trials, a biscuit (trial 1) or wrapped gift (trial 2) was presented to the child who was instructed not to take it until the assessor had completed what he/she was doing. Waiting time (in seconds) was recorded to a maximum of 150 s. Average waiting time for the two trials was computed.

The A-not-B task

A biscuit was placed in one of two wells as the child watched and both wells were then covered with opaque cups. The board was taken out of sight for 10 s during which the child was distracted with a song. The board was then brought back and the child asked to point to the well with the biscuit. The child was given the biscuit if she or he successfully located it. The location of the biscuit was switched to the other well after two consecutive correct responses. Ten trials were given; the number of correct responses was scored.


This was assessed by interviewing the mother or guardian, asking whether the infant produced common pre-speech items such as vowels (e.g., aa, aa), babble (e.g., ma, ma) or gestures (e.g., waving for “bye’), spoke definite words, or named and identified common household objects (11 items overall).

Recognition of Self and Others

The caregiver was asked whether the infant reacted to his/her name, or distinguished his mother and other familiar people from strangers (altogether 12 items).

Self Care

The interview collected information about behaviors such as how much the infant helped during dressing and feeding (15 items).

Piloting, training, and scale reliability

The measures were translated into Luganda and piloted on 50 children. Seven nurses and two doctors were trained. To assess reliability, every 10th infant was rated by two assessors on all measures. Comparisons of 80 paired records showed inter-rater reliability coefficients ranging from 0.75 to 1.00 (Table 1). Scores showed normal distributions on all measures except Self Control. Overall psychomotor performance (mean 29.58; SD 3.79) was found to be similar to that of an age-matched sample of Kenyan infants (Abubakar et al., 2008). Internal consistency was examined using Cronbach's alpha and poorly correlated items were deleted. The edited measures had internal consistency coefficients ranging from 0.62 to 0.78 (Table 1). Principal component analysis confirmed that motor measures loaded on one component, cognitive measures on another. There was a negative correlation (r = −0.04; p = .26) between the two measures of executive function (A-not-B and Self Control) which was not statistically significant. Psychomotor items in the KDI had exhibited high test–retest reliability in the Kenyan sample suggesting that the tool was stable over time (Abubakar et al., 2008). These psychometric features are summarized in Table 1.

Testing Procedure

Testing at age 15 months was postponed if mother or clinician judged the child to be unwell. Sessions lasted 45 to 65 min. Short breaks were allowed as judged by the assessor and mother. After the session, a small age-appropriate gift was given to the child and transport money reimbursed to the parent.

Additional Data

Stool samples of the pregnant women and infants were examined for helminth ova using Kato Katz technique (Katz, Chaves, & Pellegrino, 1972), and cultured for Strongyloides stercoralis. Blood was examined for Mansonella perstans using the modified Knott's method (Melrose, Turner, Pisters, & Turner, 2000) and for malaria parasites using thick smears.

Antenatal history and delivery data

We recorded information on maternal illnesses, medications and vaccines during pregnancy, mode of delivery, Apgar score at 10 min, birth weight, congenital abnormalities, and immunization received at birth.

HIV status of the child

Overall, 97 mothers tested HIV positive during pregnancy. At 6 weeks of age, their infants were tested for HIV using DNA and RNA polymerase chain reaction. Specific management of HIV positive women and exposed children is elaborated elsewhere (Elliott et al., 2007; Mpairwe et al., 2005).

Growth monitoring

Infants’ weight, height, head circumference, and mid upper arm circumference were recorded at week 6, 10, and 14, and at 6, 9, and 12 months. At 1 year, hemoglobin levels were measured.

Illnesses in infancy

Numbers of episodes of malaria, diarrhea, lower respiratory tract infections, and upper respiratory tract infections were recorded at the study clinic.

Sociodemographic data

Sociodemographic data including marital status, gravidity, age, education, occupation, income, and number of people in the home, were collected at enrolment, by interview. Household socioeconomic status was derived from items owned, building material of the house and number of rooms.

Participants’ Characteristics

Characteristics of the 983 participating mothers and children are summarized in Table 2. Characteristics of mothers of participating and non-participating children were similar with respect to education, household socioeconomic status, and prevalence of Schistosoma mansoni infection. However, mothers of participants were older and less likely to be primigravida, and had a lower prevalence of HIV and hookworm (p < .01). Children who participated had mean birth weight, height and weight for age, and hemoglobin level within WHO normal ranges.

Descriptive Statistics for Psychomotor and Cognitive Measures

Descriptive statistics for the various measures are summarized in Table 3. The numbers of infants who completed the tasks varied. Fewer completed the A-not-B task because they cried for the treat on the first trial and refused to continue. Scores on five of the seven measures were normally distributed. Performance on Self Control was slightly positively skewed and Recognition of Self and Others was negatively skewed. Appropriate transformations were conducted before analysis.

Prevalence of Worms in Mothers

Prevalence of worm species identified in the mothers is shown in Table 4. Hookworm had the highest prevalence followed by Mansonella perstans. Thirty percent of mothers had mixed infections with some women having up to five species of worms. A total of 352 (34.9%) women did not have any worm. Only effects of maternal worms with at least 2% prevalence were subsequently analyzed.

Effects of Albendazole and Praziquantel

T tests were used to compare performance between children born to treated versus untreated mothers first across the whole sample to assess the benefit of mass treatment, and then just those where the mothers had worms susceptible to the drugs. We found no interactions between albendazole and praziquantel (p > .05). Therefore, the effect of each drug was examined separately (albendazole vs. placebo; praziquantel vs. placebo). Overall neither albendazole nor praziquantel had significant effects on developmental outcomes (all values of p > .05). Of note, after delivery stool analysis showed a significant decline of the prevalence of hookworm and schistosomiasis among albendazole or praziquantel-treated women, respectively, but no reductions in Mansonella perstans, Trichuris trichiura, and Strongyloides stercoralis (Ndibazza et al., 2010).

We found, however, a significant effect of praziquantel on the A-not-B task and Self Control in children whose mothers were infected with schistosomiasis during pregnancy. Children whose mothers were treated for schistosomiasis during pregnancy performed better on Self Control than those who were not treated [t(140) = 2.58; mean difference = 5.96; p = .01; Cohen's d = 0.47]. However for the A-not-B task, children whose mothers were treated performed more poorly than those whose mothers were not treated [t(145) = −2.23; mean difference = −0.93; p = .03; Cohen's d = .37]. We found no effect of albendazole among infants of mothers with the principal susceptible species, hookworm.

Associations Between Maternal Worm Infections And Other Exposures, And Infant Outcomes
Raw Correlations

First, raw correlations between child test scores and exposure variables were explored to identify factors that might mediate or mask effects of maternal worm infections. Maternal worms included were Schistosoma mansoni, hookworm, Mansonella perstans, Ascaris lumbricoides, Trichuris trichiura, and Strongyloides stercoralis.

Background factors included were mother's age, education, occupation, income, gravidity, HIV status, and hemoglobin at enrolment; household socioeconomic status, family size and father's occupation; and the child's sex, gestational age at birth, birth weight, Apgar score at 10 min, malaria, diarrhea, and respiratory infections in the first year, activity, mood and interaction level during assessment, hemoglobin, weight, and height. These correlations and regressions were examined across the entire sample irrespective of treatment status since neither treatment showed any overall effect.

Three maternal worms showed correlations with the infant test scores: Strongyloides stercoralis correlated positively (in the opposite to expected direction) with scores on Self Control and negatively with Language. Trichuris trichiura and Mansonella perstans correlated negatively with scores on the A-not-B task. Other factors variably correlated with performance on the motor and cognitive measures. Of 112 correlations calculated, 34 were significant at the 0.05 cutoff, even after adjusting for multiple comparisons with false discovery rate. Only exposures with at least one significant correlation with the outcomes are shown in Table 5.

Multivariate Regression Analysis

To test the hypothesis that maternal worm infections would independently affect performance of children on measures of executive function, we performed a series of hierarchical linear regression analyses in which associations with maternal worms were examined taking into account associations with potential confounding factors. Using this technique we explored the unique contribution of maternal worm infections over and above effects of additional exposures. The independent variables were entered in a single model which comprised three blocks: maternal-related factors (SES and family factors, health factors), child-related factors (gender, health, and behavioral factors), and maternal worms (entered in that order). Each subtest of the motor and cognitive assessment was examined separately. Categorical measures (worm exposure and drug treatment) were loaded as dummy variables. Non-significant explanatory variables were dropped from the model one at a time leaving only the significant factors and therefore the best model that accounts for performance on each of the measures. Associations between maternal worm infections, and other factors, and each of the outcomes are summarized in Table 6 and described below; the order of entering variables into the analysis is also listed in this table.

Fine motor

Child's mood and maternal HIV status were positively associated with fine motor function, whereas activity, interaction and height were negatively associated with this outcome (R2 = 0.08; F(5,956) = 15.89; p < .001). Maternal worm infections had no association.

Gross Motor

Performance on Gross Motor was positively associated with the child's hemoglobin level at 1 year, height and weight at 15 months, mood and interaction during assessment and child's age (R2 = 0.13; F(6,884) = 21.76; p < .001). Maternal worms had no association.


Maternal Strongyloides stercoralis showed a negative association with infants’ Language. Household socioeconomic status, child's activity and height at the time of assessment showed positive associations with Language; and child's interaction during assessment showed a negative association (R2 = 0.06; F(6,860) = 9.42; p < .001). This model accounted for more variance than the model without maternal worms (ΔR2 = 0.005).

Self Care

This measure was positively associated with child's sex, activity, and weight at the time of assessment (R2 = 0.05; F(3,974) = 16.90; p < .001). Maternal worms had no association.

Recognition of Self and of Others was negatively associated with maternal gravidity and activity of child during assessment (R2 = 0.03; F(2,975) = 16.29; p < .001). Maternal worm infections had no association.

Self Control

Performance on Self Control was negatively associated with infant's height, activity, and interaction during assessment and positively related with malaria episodes in infancy. The raw association with maternal Strongyloides stercoralis infection was no longer significantly associated with the function when we controlled for the other exposures (R2 = 0.11; F(5,810) = 19.94; p < .001).

A-not-B task

Child's activity, interaction, and height were positively associated, while malaria episodes in infancy and maternal Mansonella perstans were negatively associated on this outcome. The raw association with maternal Trichuris trichiura was no longer significant when we controlled for other factors (R2 = 0.16; F(5,774) = 28.71; p < .001). The model with Mansonella perstans infection accounted for more variance than the model without the worm (ΔR2 = 0.004).

In summary, significant maternal worm effects were observed between Mansonella perstans and performance on the A-not-B task, and between Strongyloides stercoralis and performance on Language. Hookworm and schistosomiasis did not show significant associations with the outcomes although these were the most prevalent worms in the sample.

The Impact of Anthelminthic Treatment During Pregnancy

Treating pregnant women with albendazole or praziquantel had no significant effects on infant developmental measures. The absence of treatment effects in a setting with high prevalence of worm infection suggests that there is not much benefit of single-dose mass anthelminthic treatment during pregnancy for cognitive and psychomotor outcomes in the child.

Subgroup analysis suggested that praziquantel treatment in mothers who had Schistosoma mansoni infection had significant effects on both the A-not-B and Self Control tasks even though the worm did not have significant effects on these outcomes. We observed a positive effect on Self Control. However, the negative effect of the drug on the A-not-B task is difficult to explain since Schistosoma mansoni infection has been associated with cognitive deficits and treatment was therefore expected to be beneficial. This result could have occurred by chance, or the negative effect of praziquantel might be linked to changes in the host immune responses following treatment. Treatment of schistosomiasis is associated with an increase in circulating proinflammatory as well as anti-inflammatory cytokines (Azim, Sedky, el-Tahawy, Fikry, & Mostafa, 1995; Mwatha et al., 1998); the killing of schistosomes following praziquantel treatment results in release of worm antigens and a boost in anti-worm responses (Tweyongyere et al., 2008; Walter et al., 2006). The infection may be effectively cleared but the high concentration of cytokines induced might perhaps interfere with neurotransmitter systems, particularly the dopaminergic systems, thereby affecting cognitive functioning (Reichenberg et al., 2001).

Effects of Maternal Worm Infections

The results provide some support for the main hypothesis that maternal worm infections in pregnancy might have negative effects, particularly on infant executive function, but this is restricted to only two species. In line with our prediction, certain maternal worm infections were associated with performance on both the A-not-B and Self Control tasks. We observed a negative association between maternal Mansonella perstans and infants’ later performance on the A-not-B task and a positive correlation between Strongyloides stercoralis and Self Control. The latter was contrary to our predictions and might be an incidental finding, as it suggests that infection improves infant's skills on this function. It could be that children born to mothers with this infection are not more self-controlled but rather less active and less interested in their environment, and hence less interested in the treat. Indeed infant malaria and respiratory infections likewise showed positive associations with performance on this measure. Thus apathy may mediate the effect of ill-health on Self Control. However, delay tasks may not be reliable measures of inhibitory control since performance on these measures varies greatly with the task, including the type of treat used (Carlson et al., 2005).

The results suggest that executive functions might be particularly susceptible to influences of maternal worms; the effect observed on language has been reported in earlier childhood studies of worms (e.g., Ezeamama et al., 2005), and this might be secondary to effects on executive function given that the two domains emerge within the same period and are reported to be interdependent throughout life. Moreover, the two domains often show comorbidity (Ribeiro et al., 2011; Tannock & Schachar, 1996; Willinger et al., 2003 for a review). Rebiero et al. explored the comorbidity between language and executive functions and found that early executive function (attention) impairment predicted later language problems but not vice-versa. Therefore, the disruption of executive function by worms may explain the effect observed on language. Given these specific influences, the results suggest that maternal worm infections during pregnancy do not cause generalized cognitive deficits in infancy. Plausible explanations for the selective nature of maternal worm effects in infancy have been proposed. Maternal worms are believed to compete with the fetus for nutrients that are vital for formation of neurological systems (Beard et al., 2007).

Naismith (1969) suggests that, in cases of moderate deprivation (e.g., due to mild worm infections), the fetus takes priority over the nutrients that remain and thrives with minimal effects. Executive functions may however be more vulnerable due to more specific metabolic effects. It has been proposed, for example, that the availability of certain neurotransmitters is dependent on the dietary supply of their amino acid precursors (Wainwright & Colombo, 2006); for example, tryptophan is the dietary precursor of serotonin, and tyrosine is the precursor for dopamine and norepinephrine (Fernstrom, 1990). Reduced levels of tyrosine may lead to impaired executive function in children with phenylketonuria (Sharman, Sullivan, Young, & McGill, 2009). Therefore, changes in the availability of different amino acids may result in disturbances of specific brain functions and behavior. Dopamine, in particular, acts in the prefrontal cortex in which executive functions including planning, inhibition, and attention are represented, both in animals (Gaarlen, Brueggeman, Bronius, Schoffelmeer, & Vanderschuren, 2006) and humans (Goto & Grace, 2005; Smith & Kieval, 2000).

However, in worms as in other organisms, tyrosine is an essential nutrient (Moran, 2005). Impaired tyrosine catabolism in worms is associated with dramatic effects including a short life span, destruction of the intestine, and decreased fertility. Given that intestinal worms depend on the host's digestive contents for this amino acid, prolonged infestation of worms may deprive the body of this nutrient and this may in turn impact on dopamine synthesis resulting in impairment of the executive function.

The associations observed in this study were based on only two measures of executive function. It is possible that worms affect other executive skills not measured by the Delay inhibition task, and by the A not B task. Moreover, because assessments were done later in infancy, we may not completely rule out the possibility that earlier in life worms could show more generalized cognitive deficits. These are important issues that need to be resolved by longitudinal studies measuring various cognitive abilities.

Effects of maternal worm infections on infant cognitive functioning could also be mediated by iron deficiency. However, in this study we found very weak associations between maternal worm infections and maternal anemia (Muhangi et al., 2007), or benefit of anthelminthic treatment for anemia (Ndibazza et al., 2010). Moreover, all women were routinely treated with iron and folic acid during pregnancy, perhaps compensating for any iron loss due to worm infections. Worms were not causing major iron deficiency anemia in these mothers, so cognitive effects of worms mediated by maternal anemia would not have been detectable in this study.

In addition to worm infections, infant abilities were examined in relation to other factors. Common infections in infancy, particularly repeated malaria, were found to influence infants’ performance. As expected, child nutritional factors (hemoglobin, height, and weight) showed significant positive correlations with developmental outcomes. Infant mood, activity, and interaction level also consistently influenced scores on the various developmental measures highlighting the role non-task behavior plays in performance. Given that numerous factors were affecting infants’ development before and after birth, a relatively small amount of variance explained by worms alone might be expected. However, worms affect millions of mothers and children, and hence, the global impact of even a small effect on child development may be important enough to raise concern. Regardless of the effect size, these findings are in keeping with our prediction and deserve further exploration.

Our study had an experimental design, and this was a strength of our analysis of the effects of anthelminthic intervention. However, it is of note that the majority of pregnant women who participated had a low intensity of worm infections; mothers with hemoglobin below 8 g/dL were excluded from the study, and iron and folic acid were given during antenatal care. These characteristics limit the extrapolation of our findings to other populations. It could be that, where infections are heavy and nutritional and micronutrient status is marginal, maternal worms have stronger and more diverse effects on the development of the executive system. Future studies should aim specifically to investigate effects in populations with high intensities of worms.

Furthermore, in early infancy, cognitive processes are not yet fully developed, which undermines the validity of developmental effects measured. Moreover, future studies should assess effects of worms on other aspects of executive functions, other than those measured in this study. We continue to follow-up these infants and reassess the worm effects at older ages and to include aspects of executive functions not examined in this study to re-evaluate the selectivity of these effects.

In conclusion, the results of this study suggest that certain maternal worm infections during pregnancy may have negative influences on early executive function in the offspring but anthelminthic treatment is unlikely to reverse these effects. Further research should aim to replicate these findings in the light of the limitations mentioned above.


This research was funded by Wellcome Trust grant numbers 064693 and 079110 as part of the overall Entebbe Mother and Baby Study. We thank the EMaBS team for their hard work and commitment. We also thank the team in Kenya Medical Research Institute for permission to use their measures and support in training the assessors. We thank the mothers and children from Entebbe and Katabi for their participation in the study. There were no conflicts of interest in this study.

Abubakar A.,, Holding P.,, Van Baar A.,, Newton C.R.,, Van de Vijver F.J., (Year: 2008). Monitoring psychomotor development in a resource limited setting: An evaluation of the Kilifi developmental inventory. Annals of Tropical Paediatrics, 28, 217–22618727851
Abubakar A.,, Holding P.,, Van de Vijver F.,, Bomu G.,, Van Baar A., (Year: 2010). Developmental monitoring using caregiver reports in a resource-limited setting: the case of Kilifi, Kenya. Acta Paediatrica, 99, 291–29720353499
Azim A.A.,, Sedky H.A.,, el-Tahawy M.A.,, Fikry A.A.,, Mostafa H., (Year: 1995). Serum levels of tumour necrosis factor in different stages of Schistosoma infection. Journal of Egyptian Society of Parasitology, 25, 279–287
Beard J.L.,, Hendricks M.K.,, Perez E.M.,, Murray-Kolb L.E.,, Berg A.,, Vernon-Feagans L.,, Tomlinson L., (Year: 2005). Maternal iron deficiency anemia affects postpartum emotions and cognition. Journal of Nutrition, 135, 267–27215671224
Beard J.L.,, Unger E.L.,, Bianco L.E.,, Paul T.,, Rundle S.E.,, Jones B.C., (Year: 2007). Early post-natal iron repletion overcomes lasting effects of gestational iron deficiency in rats. Journal of Nutrition, 137, 1176–118217449578
Berkman D.S.,, Lescano A.G.,, Gilman R.H.,, Lopez S.L.,, Black M.M., (Year: 2002). Effects of stunting, diarrhoeal disease, and parasitic infection during infancy on cognition in late childhood: a follow-up study. Lancet, 359, 564–57111867110
Boivin M.J.,, Giordan B.,, Ndanga K.,, Makakala M.M.,, Manzeki K.M.,, Ngunu N.,, Kibungu M., (Year: 1993). Effects of treatment for intestinal parasites and malaria on the cognitive abilities of school children in Zaire, Africa. Health Psychology, 12, 220–2268500452
Bradley M.,, Horton J., (Year: 2001). Assessing the risk of benzimidazoles therapy during pregnancy. Transactions of the Royal Society of Hygiene and Tropical Medicine, 95, 72–73
Bradley R.H.,, Cladwell B.M.,, Rock S.L.,, Ramey C.T.,, Barnard K.E.,, Gray C.,, Johnson D.L.. (Year: 1989). Home environment and cognitive development in the first three years of life: A collaborative study involving six sites and three ethnic groups in North America. Developmental Psychology, 25, 217–235
Brooker S.,, Clements A.C.A.,, Bundy D.A.P., (Year: 2006). Global epidemiology, ecology and control of soil-transmitted helminth infections. Advances in Parasitology, 62, 221–26116647972
Bundy D.A.P.,, Chan M.S.,, Savioli L., (Year: 1987). Hookworm infection in pregnancy. Transactions of the Royal Society of Tropical Medicine and Hygiene, 89, 521–5228560530
Carlson S.M.,, Davis A.C.,, Leach J.G., (Year: 2005). Less is more: Executive function and symbolic representation in preschool children. Psychological Science, 16(8), 609–61616102063
Clarke N.,, Grantham-McGregor S.M.,, Powell C., (Year: 1991). Nutrition and health predictors of school failure in Jamaican children. Ecology of Food and Nutrition, 26, 1–11
Clearfield M.W.,, Diedrich F.J.,, Smith L.B.,, Thelen E., (Year: 2006). Young infants reach correctly in A not B tasks: On the development of stability and perseveration. Infant Behaviour and Development, 29, 435–444
Cooper D.H.,, Farran D.C., (Year: 1988). Behavioural risk factors in kindergarten. Early Childhood Research Quarterly, 3, 1–19
Diamond A., (Year: 1985). Development of the ability to use recall to guide action, as indicated by infants’ performance on AB. Child Development, 56, 868–8834042750
Diamond A., (Year: 1988). Abilities and neural mechanisms underlying AB performance. Child Development, 59, 523–5273359870
Diamond A.,, Doar B., (Year: 1989). The performance of human infants on a measure of frontal cortex function, the delayed response task. Developmental Psychobiology, 22(3), 271–2942707496
Diamond A.,, Goldman-Rakic P.S., (Year: 1989). Comparison of human infants and rhesus monkeys in Piaget's AB task: Evidence for dependence on dorsolateral prefrontal cortex. Experimental Brain Research, 74, 24–402924839
Dugbartey A.T.,, Spellacy F.J., (Year: 1997). Simple reaction time and cognitive processing ability after cerebral malaria in Ghanaian children. Neurological Infections and Epidemiology, 2, 141–144
Elliott A.M.,, Kizza M.,, Quingley M.A.,, Ndibazza J.,, Nampijja M.,, Muhangi L.,, Whitworth J.A.G., (Year: 2007). The impact of helminths on the response to immunization and the incidence of infection and disease in childhood in Uganda: design of a randomized, double-blind, placebo-controlled, factorial trial of de-worming interventions delivered in pregnancy and early childhood. Clinical Trials, 4, 42–5717327245
Elliott A.M.,, Mawa P.A.,, Joseph S.,, Namujju P.B.,, Kizza M.,, Nakiyingi J.S.,, Whitworth J.A.G.. (Year: 2003). Associations between helminths and CD4+ Tcell count, viral load and cytokine responses in HIV-1-infected Ugandan adults. Transactions of the Royal Society of Hygiene and Tropical Medicine, 97, 103–108
Espy K.A., (Year: 2004). Using developmental, cognitive, and neuroscience approaches to understand executive control in young children. Developmental Neuropsychology, 26(1), 379–38415276900
Ezeamama A.E.,, Friedman J.F.,, Acosta L.P.,, Bellinger D.C.,, Langdon G.C.,, Manalo D.L.,, McGavey S.T., (Year: 2005). Helminth infection and cognitive impairment among Filipino children. American Journal of Tropical Medicine & Hygiene, 72(5), 540–54815891127
Fernstrom J.D., (Year: 1990). Aromatic amino acids and monoamine synthesis in the CNS: influence of the diet. Journal of Nutritional Biochemistry, 1, 508–51715539167
Gaarlen M.M.,, Brueggeman R.J.,, Bronius P.F.C.,, Schoffelmeer A.N.M.,, Vanderschuren L.J.M.J., (Year: 2006). Behavioural disinhibition requires dopamine receptor activation. Psychopharmacology, 187, 73–8516767417
Galler J.R.,, Ramsey F.,, Solimano G.,, Kucharski L.T.,, Harrison R., (Year: 1984). The Influence of early malnutrition on subsequent behavioral development. IV. Soft neurologic signs. Pediatric Research, 18, 826–8326207479
Gay C.L.,, Armstrong F.D.,, Cohen D.,, Lai S.,, Hardy M.D.,, Swales T.P.,, Scott G.B., (Year: 1995). Effects of HIV on cognitive and motor development in children born to HIV sero- positive women with no reported drug use: birth to 24 months. Pediatrics, 96, 1078–10827491224
Gentile M.A.,, Boll T.J.,, Stagno S.,, Pass R.F., (Year: 1989). Intellectual ability of children after peri-natal cytomegalovirus infection. Developmental Medicine and Child Neurology, 31, 782–7862557252
Goldenberg R.L.,, Hoffman H.J.,, Cliver S.P., (Year: 1998). Neuro-developmental outcomes of small for gestational-age infants. European Journal of Clinical Nutrition, 52, S54–S589511020
Goto Y.,, Grace A.A., (Year: 2005). Dopaminergic modulation of limbic and cortical drive of nucleus accumbens in goal directed behaviour. Nature Neuroscience, 8, 805–812
Grantham-McGregor S.M.,, Powell C.A.,, Walker S.,, Chang S.,, Fletcher P., (Year: 1994). The long-term follow up of severely malnourished children who participated in an intervention program. Child Development, 65, 428–4398013232
Grantham-McGregor S.M.,, Powell C.A.,, Walker S.P.,, Himes J.H., (Year: 1991). Nutritional supplementation, psychosocial stimulation, and mental development of stunted children: The Jamaican study. Lancet, 338(8758), 1–51676083
Hack M., (Year: 1998). Effects of intra-uterine growth retardation on mental performance and behavior: outcomes during adolescence and adulthood. European Journal of Clinical Nutrition, 52, S65–S719511022
Hughes C., (Year: 1998). Executive function in preschoolers: Links with theory of mind and verbal ability. British Journal of Developmental Psychology, 16, 233–253
Jukes M.C.H.,, Nokes C.A.,, Alcock K.J.,, Lambo K.J.,, Kihamia C.,, Ngorosho N.,, Bundy A.P., (Year: 2002). Heavy schistosomiasis associated with poor short term memory and slower reaction times in Tanzanian school children. Tropical Medicine and International Health, 7(2), 104–11711841700
Katz N.,, Chaves A.,, Pellegrino N., (Year: 1972). A simple device for quantitative stool thick-smear technique in Schistosomiasis mansoni. Revista do Instituto de Medicina Tropical de Sao Paulo, 14, 397–4004675644
Kopp C.B., (Year: 1982). Antecedents of self-regulation: A developmental perspective. Developmental Psychology, 18, 199–214
Londerville S.,, Main M., (Year: 1981). Security of attachment, compliance and maternal training methods in the second year of life. Developmental Psychology, 17, 289–299
Lozoff B.,, Brittenham G.M.,, Wolf A.W., (Year: 1987). Iron deficiency anemia and iron therapy: Effects on infant developmental test performance. Pediatrics, 79, 981–9952438638
Marcovitch S.,, Zelazo P.D., (Year: 1999). The A not B error: Results from a logistic meta-analysis. Child Development, 70(6), 1297–1313
Melrose W.D.,, Turner P.F.,, Pisters P.,, Turner B., (Year: 2000). An improved Knott's concentration test for the detection of microfilariae. Transactions of the Royal Society of Tropical Medicine and Hygiene, 94, 17610897361
Miyake A.,, Friedman N.P.,, Emerson M.J.,, Witzki A.H.,, Howerter A.,, Wager T.D., (Year: 2000). The unity and diversity of executive functions and their contributions to complex ‘frontal lobe’ tasks: A latent variable analysis. Cognitive Psychology, 41, 49–10010945922
Moran G.R., (Year: 2005). 4-Hydroxyphenylpyruvate dehydrogenase. Archives of Biochemistry and Biophysics, 433, 117–12815581571
Mpairwe H.,, Muhangi L.,, Namujju P.B.,, Kisitu A.,, Tumusiime A.,, Muwanga M.,, Elliott A.M., (Year: 2005). HIV risk perception and prevalence in a program for prevention of mother-to-child HIV transmission—Comparison of women who accept voluntary counseling and testing and those tested anonymously. Journal of Acquired Immune deficiency Syndromes, 39(3), 354–35815980698
Muhangi L.,, Woodburn P.,, Omara M.,, Omoding N.,, Kizito D.,, Mpairwe H.,, Elliot A.M., (Year: 2007). Associations between mild-moderate anaemia in pregnancy and helminth, malaria and HIV infection in Entebbe, Uganda. Transactions of the Royal Society of Tropical Medicine and Hygiene, 101, 899–90717555783
Mwatha J.K.,, Kimani G.,, Kamau T.,, Mbugua G.G.,, Ouma J.H.,, Mumo J.,, Dunne D.W.. (Year: 1998). High levels of TNF, soluble TNF receptors, soluble ICAM-1, and INF-gamma, but low levels of IL-5, are associated with hepatosplenic disease in human Schistosomiasis mansoni. Journal of Immunology, 160, 1992–1999
Naismith D.J., (Year: 1969). Nutrition of the foetus and the newly born. Proceedings of the Nutrition Society, 28, 25–315786604
Ndibazza J.,, Muhangi L.,, Akishule D.,, Kiggundu M.,, Ameke C.,, Oweka J.,, Elliott A.M., (Year: 2010). Effects of deworming in pregnancy on maternal and perinatal outcomes in Entebbe Uganda: A randomised controlled trial. Clinical Infectious Diseases, 50, 531–54020067426
Nokes C.,, Grantham-McGregor S.M.,, Sawyer A.W.,, Cooper E.S.,, Robinson B.A.,, Bundy D.A.P., (Year: 1992). Moderate to heavy infections of Trichuris trichiura affect cognitive function in Jamaican school children. Parasitology, 104, 539–5471641252
Nokes C.,, McGarvey S.T.,, Shiue L.,, Guanling W.,, Hawai W.,, Bundy A.P.,, Olds G.R., (Year: 1999). Evidence for an improvement in cognitive function following treatment of Schistosoma japonicum infection in Chinese primary school children. American Journal of Tropical Medicine and Hygiene, 60(4), 556–56510348228
Piaget J., (Year: 1954). The construction of reality in the child. New York: Basic Books
Ramey C.T.,, Ramey S.L., (Year: 1998). Prevention of intellectual disabilities: early interventions to improve cognitive development. Preventive Medicine, 27, 224–2329579000
Reichenberg A.,, Yirmiya R.,, Schuld A.,, Kraus T.,, Haack M.,, Morag A.,, Pollmacher T., (Year: 2001). Cytokine associated emotional and cognitive disturbances in humans. Archives of General Psychiatry, 58, 445–45211343523
Ribeiro L.A.,, Zachrisson H.D.,, Schjoberg S.,, Aase H.,, Rohrer-Baumgartner N.,, Magnus P., (Year: 2011). Attention problems and language development in preterm low birth weight children: Cross-lagged relations from 18-36 months. BioMed Central, Pediatrics, 11, 5921714885
Rohde T.E.,, Thompson L.A., (Year: 2007). Predicting academic achievement with cognitive ability. Intelligence, 35, 83–92
Rothbart M.A.,, Ahadi S.K., (Year: 1994). Temperament and the development of personality. Journal of Abnormal Psychology, 103, 55–668040481
Sakti, H., Nokes, C., Subagio, W.H., Hendratino, S., Hall, A., Bundy, D.A., & Satoto. (Year: 1999). Evidence of an association between hookworm infection and cognitive function in Indonesian school-children. Tropical Medicine and International Health, 4(5), 322–33410402967
Schacter D.L.,, Moscovitch M.,, Tulving E.,, McLachlan D.R.,, Freedman M., (Year: 1986). Mnemonic precedence in amnesic patients: An analogue of the AB error in infants. Child Development, 57, 816–8233720406
Sharman R.,, Sullivan K.,, Young R.,, McGill J., (Year: 2009). Biochemical markers associated with executive function in adolescents with early and continuously treated phenylketonuria. Clinical Genetics, 75(2), 169–17419215250
Smith Y.,, Kieval J.Z., (Year: 2000). Anatomy of the dopamine system in the basal ganglia. Trends in Neuroscience, 23, 23–33
Smith L.B.,, Thelen E.,, Titzer R.,, McLin D., (Year: 1999). Knowing in the context of acting: the task dynamics of the A not B error. Psychological Review, 106(2), 235–25010378013
Stayton D.J.,, Hogan R.,, Ainsworth M.D.S., (Year: 1971). Infant obedience and maternal behavior: The origins of socialization reconsidered. Child Development, 42, 1057–10695157102
Tannock R.,, Schachar R., (Year: 1996). Executive dysfunction as an underlying mechanism of behavior and language problems in attention deficit hyperactivity disorder In J.H. Beitchman, N. Cohen, M.M. Konstantareas, & R. Tannock (Eds.), Language learning and behavior disorders: Developmental, biological, and clinical perspectives (pp. 128–155). Cambridge, England: Cambridge University Press
Thelen E.,, Smith L.B., (Year: 1994). A dynamic systems approach to the development of cognition and action. Cambridge, MA: MIT Press
Thompson R.A.,, Nelson C.A., (Year: 2001). Developmental science and the media: Early brain development. American Psychologist, 56(1), 5–1511242988
Tramontana M.G.,, Hooper S.R.,, Selzer S.C., (Year: 1988). Research on the preschool prediction of later academic achievement: A review. Developmental Review, 8, 89–146
Tweyongyere R.,, Mawa P.A.,, Ngom-Wegi S.,, Ndibazza J.,, Duong T.,, Vennervald B.J.,, Elliott A.M., (Year: 2008). Effect of praziquantel treatment during pregnancy on cytokine responses to schistosome antigens: results of a randomized, placebo-controlled trial. Journal of Infectious Diseases, 198, 1870–187918983246
Wainwright P.E.,, Colombo J., (Year: 2006). Nutrition and the development of cognitive functions: interpretation of behavioural studies in animals and human infants. American Journal of Nutrition, 84, 961–970
Walter K.,, Fulford A.J.,, McBeath R.,, Joseph S.,, Jones F.M.,, Kariuki H.C.,, Dunne D.W., (Year: 2006). Increased human IgE induced by killing Schistosoma mansoni in vivo is associated with pretreatment Th2 cytokine responsiveness to worm antigens. Journal of Immunology, 177(8), 5490–5498
Webb E.L.,, Mawa P.A.,, Ndibazza J.,, Kizito D.,, Namatovu A.,, Kyosimire J.,, Ameke C., (Year: 2011). Effect of single-dose anthelmintic treatment during pregnancy on an infant's response to immunisation and on susceptibility to infectious diseases in infancy: A randomised, double-blind, placebo-controlled trial. Lancet, 377(9759), 52–6221176950
Wellman H.M.,, Cross D.,, Bartsch K., (Year: 1986). Infant search and object permanence: A meta- analysis of the A not B error. Monographs of Society for Research in Child Development, 51, 1–51
WHO. (Year: 1996). Report of the WHO informal consultation on hookworm infection and anaemia in girls and women World Health Organization, Geneva. WHO/CTD/SIP/ 96.1.
WHO. (Year: 2002). Report of the who informal consultation on the use of praziquantel during pregnancy/lactation and albendazole/mebendazole in children under 24 months Geneva 8–9 April 2002. World Health Organization, Geneva, WHO/CDS/CPE/PVC/2002.4.
WHO. (Year: 2006). Report of the Scientific Working Group meeting on Schistosomiasis Geneva, 14–16 November, 2006. TDR/SWG/07.
Willinger U.,, Brunner E.,, Diendorfer-Radner G.,, Sams J.,, Sirsch U.,, Eisenwort B., (Year: 2003). Behaviour in children with language development disorder. Canadian Journal of Psychiatry, 48, 607–614

[TableWrap ID: tab1] Table 1 

Inter-rater reliability and internal consistency of the measures and factor loadings

Measure Inter-rater reliability coefficient N = 80 Cronbach's alpha N = 983 Component 1 Component 2
Fine Motor .71 .72 .62 −.32
Gross Motor .77 .78 .63 −.19
Language 1.00 .76 .42 .70
Self Control 1.00 N/A −.31 .60
Self Care 1.00 .64 .70 .18
Self Recognition 1.00 .62 .41 .16
A not B 1.00 N/A .27 .13

[TableWrap ID: tab2] Table 2 

Characteristics of participating women and infants

Alb+praz Praziquantel Albendazole Placebos Overall
Demographic and clinical characteristics Treatment arms N = 249 N = 241 N = 251 N = 242 N = 983 p value
Mothers’ age (years) Mean 23.9 23.9 24.4 23.2 24.1 .789
Mothers’ education None/primary 141 (56.9)a 118 (49.2) 141 (56.2) 129 (53.5) 529 (54.0) .325
Secondary/tertiary 107 (43.1) 122 (50.8) 110 (43.8) 112 (46.5) 451 (46.0)
Household SES Lower 105 (43.0) 113 (47.5) 107 (43.3) 105 (44.5) 430 (44.6) .509
Upper 139 (57.0) 125 (52.5) 140 (56.7) 131 (55.5) 535 (55.4)
Mothers’ occupation Fishing/farming 10 (3.9) 9 (3.5) 13 (5.1) 11 (4.4) 43 (4.2) .278
Unskilled manual 20 (7.8) 22 (8.7) 9 (3.5) 11 (4.4) 44 (6.1)
Bar/hotel 10 (3.9) 7 (2.8) 16 (6.2) 11 (4.4) 44 (4.3)
housewife 169 (61.9) 174 (68.5) 166 (64.6) 167 (67.1) 666 (65.5)
business 32 (12.5) 25 (9.8) 33 (12.5) 35 (14.1) 125 (12.3)
student 6 (2.3) 5 (2.0) 5 (1.9) 1 (.4) 17 (1.7)
professional 20 (7.8) 12 (4.7) 15 (5.8) 13 (5.2) 60 (5.9)
Fathers’ occupation None 2 (.8) 2 (.8) 3 (1.2) 3 (2.1) 5 (1.2) .859
Farmer/fishing 29 (12.2) 37 (15.4) 30 (12.1) 29 (12.2) 125 (13.0)
Unskilled manual 81 (34.2) 84 (35.0) 74 (30.0) 81 (34.0) 320 (33.3)
Bar/hotel 6 (2.5) 2 (.8) 3 (1.2) 3 (1.3) 14 (1.5)
Business 37 (15.6) 33 (13.8) 40 (16.2) 41 (17.2) 151 (15.7)
Student 4 (1.7) 6 (2.5) 3 (1.2) 3 (1.3) 16 (1.7)
Professional 78 (32.9) 76 (31.7) 94 (38.1) 76 (31.9) 324 (33.7)
Mothers’ income <30,000 (£10) 208 (82.5) 208 (83.9) 212 (85.1) 216 (88.2) 844 (84.9) .096
(Uganda Shillings) 30,000–60,000 31 (12.3) 28 (11.3) 15 (6.0) 20 (8.2) 94 (9.5)
60,001–100,000 7 (2.8) 4 (1.6) 11 (4.4) 4 (1.6) 26 (2.6)
>100,000 6 (2.4) 8 (3.2) 11 (4.4) 5 (2.0) 30 (3.0)
Family size mean 3.8 4.0 3.79 3.77 3.84 .602
Mothers’ HIV status Positive 22 (8.8) 19 (7.9) 26 (10.4) 25 (10.3) 92 (9.4) .973
Mothers’ gravidity Primigravida 72 (28.9) 61 (25.3) 59 (23.5) 54 (22.3) 246 (25.0) .310
Mothers’ hookworm status Positive 108 (43.7) 111 (46.0) 89 (35.7) 97 (40.1) 405 (41.4) .150
Mother's S. mansoni status Positive 44 (17.8) 50 (20.8) 47 (18.9) 46 (19.0) 187 (19.1) .857
Sex of the child Female 110 (44.2) 127 (52.7) 122 (48.6) 124 (51.2) 483 (49.1) .122
Age of the child (months) Mean (SD) 15.6 (.50) 15.6 (.50) 15.6 (.50) 15.6 (.50) 15.6 (.50) .561
Min. 14.2 14.3 15.1 15.0 14.2
Max. 17.0 17.0 17.0 16.9 17.00
Gestation age at birth full term (≥38 wks) 240 234 245 233 952 .212
preterm 8 6 6 6 26
Gestation age in weeks Mean (SD) 39.30 (3.41) 39.29 (3.64) 39.68 (3.23) 39.46 (3.48) 39.42 (3.44) .558
Birth weight (kg) Mean (SD) 3.11 (.47) 3.15 (.48) 3.21 (.48) 3.21 (.50) 3.17 (.48) .172
Apgar Score at 10 minutes Mean (SD) 9.82 (.54) 9.68 (.53) 9.83 (.59) 9.77 (.65) 9.77 (.71) .172
Weight at 15 months (kg) Mean (SD) 9.56 (1.18) 9.55 (1.19) 9.63 (1.38) 9.64 (1.27) 9.59 (1.26) .740
Height at 15 months (cm) Mean (SD) 75.51 (3.26) 75.54 (3.61) 75.73 (3.31) 75.66 (3.11) 75.61 (3.33) .813
Infant hemoglobin (g/dL) Mean (SD) 10.06 (1.37) 10.05 (1.34) 10.10 (1.48) 10.28 (1.45) 10.12 (1.41) .334

aFigures are proportions (percent) unless otherwise indicated.

[TableWrap ID: tab3] Table 3 

Descriptive statistics of infants’ scores on the various measures

Domain N Min Max. (max. possible) Mean SD
Fine Motor 978 1 22 (32) 13.16 1.74
Gross Motor 982 12 25 (35) 17.62 2.32
Language 983 1 22 (22) 15.39 4.29
Self Control 832 1 150 (150) 6.60 17.55
Self Care 982 0 29 (30) 17.14 4.22
Self Recognition 982 0 18 (24) 10.25 .99
A not B task 792 0 10 (10) 4.01 2.36

Note. The numbers under each domain are discrete scores therefore no units are available.

[TableWrap ID: tab4] Table 4 

Prevalence of the various worms in the pregnant women whose infants were assessed on the motor and cognitive measures at 15 months

Worm species Infected N (%)
Hookworm 405 (41)
Mansonella perstans 192 (20)
Schistosoma mansoni 187 (19)
Strongyloides stercoralis 123 (13)
Trichuris trichiura 84 (9)
Ascaris lumbricoides 21 (2)
Trichostrongylus 6 (.60)
Hymenolepsis nana 2 (.20)
Fasciola hepaticus 1 (.10)
Dicrocoelium dendriticum 1 (.10)
Enterobius vermicularis 1 (.10)

[TableWrap ID: tab5] Table 5 

Pearson correlations between maternal worms and other health and sociodemographic exposures, and the outcomes

Fine Motor Gross Motor Language Sociocognition Self Care A not B Self Control
Maternal worms in pregnancy
Trichuris trichiura .08 −.07 −.07 −.04 −.05 −.14* .01
Strongyloides stercoralis .09 −.03 −.14* −.03 −.04 .03 .18**
Mansonella perstans .07 −.01 −.04 .07 −.04 −.20** .00
Maternal & birth related factors
Maternal income .10 .13* .12 .04 .08 .06 −.03
Maternal education −.14* −.13* .10 −.03 −.03 .10 −.05
Maternal occupation −.01 −.004 .03 .08 −.03 −.09 −.01
Father's occupation −.07 .12 −.03 −.11 .02 .07 −.10
Household SES −.03 −.03 .16* −.10 .02 .08 .01
HIV exposure .18** −.12 .05 −.02 −.01 .07 −.05
Mother's hemoglobin −.15* .10 −.01 −.05 .09 −.01 −.05
Gestation age −.06 .09** .06 −.05 −.02 .04 −.07
Gender .01 −.12 −.14* .12 .03 −.06 .01
Nutritional factors
Weight at 15 months −.02 .23** .07 −.07 .08 .00 −.05
Height at 15 months −.13 .17** .06 −.10 .01 −.02 −.10
MUAC .05 .13* .14* −.04 .05 −.02 −.06
Malaria episodes .03 −.17** .05 .10 .00 −.02 .20**
Diarrhea episodes .01 −.04 .08 −.08 .11 −.11 .18*
Respiratory infections −.02 −.04 −.07 −.05 .06 .04 .22*
Child's behavior during the testing session
Mood −.04 .24** .13* −.20** .12 .15** −.21**
Activity −.23** .19** .25** −.31*** .22** .29** −.20**
Interaction −.17** .25** .06 −.25** .20** .18* −.18**

Note. MUAC = mid upper-arm circumference.

*p < .05.

**p < .01.

***p < .001.

[TableWrap ID: tab6] Table 6 

Effects of maternal worm infections and of other health and sociodemographic exposures on the various functions

Measure Worm/other exposure Unstandardized coefficients (B) Standardized coefficients (B) Std. Error of B
Fine motor
Maternal HIV .41* .07* .19
Mood .11* −.10* .05
Activity −.39*** −.20*** .08
Interaction −.12* −.11* .05
Height −.07*** −.13*** .02
Gross Motor
Mood .21** .14** .06
Interaction .24*** .16*** .06
Hb at 1 yr .10* .06* .05
Height .07* .09* .03
Weight .20** .11** .08
Child's age .45** .09** .16
Household SES .33** 09** .12
Activity 1.10*** .23*** .21
Interaction −.30* −.11* .12
Height .11* .08* .04
Strongyloides stercoralis −.90* −.07* .44
Self Control Activity −.10*** −.16*** .03
Interaction −.06*** −.17*** .01
Height −.02*** −.10*** .01
Malaria episodes .06*** .11*** .02
Self Care
Activity .71*** .16*** .15
weight .26* .08* .11
Sex 1.32*** .16*** .27
Recognition of self and others
Activity −.18*** −.17*** .03
Gravidity −.11* −.07* .05
A not B task
Activity −.75*** −.26*** .12
Interaction .22*** .14*** .07
Height .08*** .11*** .02
Malaria −.18* −.08* .08
Mansonella perstans −.40* −.07* .20

Note. Maternal-related factors were entered into the model in this order: mother's age, education level, occupation, income, gravidity, HIV status, and hemoglobin level at enrollment; household socioeconomic status, family size, and father's occupation. Child factors were entered into the model in this order: child's sex, gestation age at birth, birth weight, Apgar score, malaria, diarrhea, and respiratory infections in the first year, activity, mood, and interaction level during assessment, hemoglobin level, weight, and height. Hb = hemoglobin; SES = socioeconomic status.

*p < .05.

**p < .01.

***p < .001.

Article Categories:
  • Research Articles

Keywords: Keywords Pregnancy, Helminths, De-worming, Infancy, Psychomotor, Executive function.

Previous Document:  Social Cognition and Emotional Assessment (SEA) is a Marker of Medial and Orbital Frontal Functions:...
Next Document:  Expert versus proxy rating of verbal communicative ability of people with aphasia after stroke.