Prenatal anxiety during the pandemic context is related to neurodevelopment of 6-month-old babies

Prenatal anxiety and depression in pandemic context could introduce changes in the fetal developmental trajectories that, ultimately, could alter the adaptive behaviors of the offspring, potentially affecting, for example, general neurodevelopment. The sample consisted of 105 mother–child dyads, recruited between March and May 2020. The dyads were evaluated longitudinally, prenatally and postnatally (6 months). The Pandemic Impact Questionnaire, the State-Trait Anxiety Inventory, and the Beck-II Depression Inventory were used to assess indicators of maternal anxiety and depression, respectively. Regarding the babies, their mothers responded to Age and Stages: 3, which assesses different dimensions of early neurodevelopment, in addition to a closed questionnaire to identify sociodemographic and maternal and child health variables. A series of mediation models were tested to examine the association between prenatal psychopathology/negative experiences of the pandemic and neurodevelopment. The results indicated that the negative experiences of the pandemic were indirectly associated with the socio-individual and fine motor neurodevelopment of the offspring, through maternal anxiety symptoms, during the third trimester, which functioned as a mediator. Conclusions: This study provides evidence on the mediating effects of maternal anxiety on infant neurodevelopment in contexts of early adversity. It is important to point out the need to implement public health policies that allow a timely evaluation of neurodevelopmental variables during early childhood, which can implement early interventions to reduce the risks associated with these deficits. What is Known: • Effects of maternal mental health have been reported, effects on child neurodevelopment, in motor, cognitive, linguistic and socio-emotional dimensions. • Contexts of early adversity have been associated with maternal mental health and offspring development. What is New: • The context of pandemic adversity caused by COVID-19 is associated with motor and socio-individual neurodevelopment, mediated by maternal prenatal anxiety. What is Known: • Effects of maternal mental health have been reported, effects on child neurodevelopment, in motor, cognitive, linguistic and socio-emotional dimensions. • Contexts of early adversity have been associated with maternal mental health and offspring development. What is New: • The context of pandemic adversity caused by COVID-19 is associated with motor and socio-individual neurodevelopment, mediated by maternal prenatal anxiety.


Introduction
The most recent guideline on prenatal care by the World Health Organization (WHO) has underscored the significance of recognizing and intervening in psychosocial factors in pregnant women and newborns to optimize the physical and psychosocial well-being of the mother, infant, and family, both in the short and long term [1,2].Currently, there is no conclusive evidence to suggest that the transmission of the coronavirus could occur vertically from mother to fetus or through breastfeeding [3].Although studies reporting increased risks of severe COVID-19 infections in pregnant women continue to emerge [4], it is important to note that there is insufficient evidence to suggest that pregnant women are more susceptible to catching COVID-19, and further research is needed to draw accurate conclusions [5].
Given the uncertainties surrounding the transmission modes and impact of the virus on pregnant women, it is imperative to investigate the potential side effects of the pandemic, such as mental health problems in mothers and children.Pregnancy could serve as an additional risk factor for the onset of psychological distress or the development or exacerbation of psychopathological disorders during the COVID-19 pandemic, which may affect both mothers and their offspring [6][7][8].
Approximately, 116 million infants were born globally during the first 9 months of the COVID-19 pandemic [9].Despite the growing interest in studying the mental health of pregnant women during the pandemic, few studies have explored the medium and long-term effects of this adversity on newborns and infants due to increased prenatal maternal stress and early childhood adversity [10].
In low and middle-income countries, it is estimated that the prevalence of perinatal mental disorders in women is 15.6% during pregnancy and 19.8% postnatally [11].However, these indicators may have increased in the context of the pandemic, as suggested by some studies [12][13][14], as contexts characterized by inequity and disparity predispose individuals to perceive the pandemic as a chronic and extreme stressor [15].
Several studies have been published that provide evidence of the relationship between maternal mental health and the context of the COVID-19 pandemic.These studies have reported an increase in symptoms of depression [12,[16][17][18] and anxiety [3,13,19], lower mental quality of life [20], increased perceived levels of distress [21], and a moderate psychological impact due to the pandemic context [22].
Moreover, high levels of prenatal depression and anxiety in mothers may have negative effects on the early development of offspring at physiological, cognitive, motor, and emotional levels [23,24], and increase the predisposition to mental disorders in the future, even extending into childhood, adolescence, or adulthood [25,26].
Limited research has been conducted thus far on the associations between prenatal stress during the pandemic and early developmental outcomes.Existing studies have reported reduced motor and socio-personal development in 6-month-old infants [27], as well as decreased verbal, motor, and overall cognitive performance [28].Furthermore, negative links have been identified between communication, gross motor skills, and socio-personal development in the domains of mother-baby separation days [29].Previous investigations examining the impact of public health emergencies, catastrophes, or natural disasters have also indicated that prenatal stress may have detrimental effects on the mental health of pregnant women and the well-being of their offspring [30].Specifically, prenatal and early childhood stress have been associated with long-term consequences on cognitive and emotional development, including lower cognitive, emotional, and linguistic performance, reduced play skills, and an increased risk of developing psychopathological conditions such as post-traumatic stress disorder, depression, anxiety, and schizophrenia [8,31].These findings suggest that significant increases in prenatal depression and anxiety may potentially alter fetal developmental trajectories, which in turn could impact the adaptive behaviors of the offspring.Therefore, the investigation of early neurodevelopment, a critical maturational process encompassing the acquisition of motor (gross and fine), cognitive, language, behavioral, and social skills during the first 2 postnatal years [32,33], is of particular interest in this context.
Biological, environmental, and contextual risk factors can have detrimental effects on fetal and infant development.In particular, prenatal stress has been linked to various negative consequences in children, including lower overall cognitive performance [34], poorer general verbal skills [35], deficits in productive and receptive language skills [36], variations in mental and motor development [25], lower overall neurodevelopmental scores, and an increased likelihood of exhibiting at least mild developmental delays in communication, gross motor, fine motor, problem-solving, and personal/social skills [37,38].
However, despite the considerable literature associating maternal mental health and/or early adverse experiences, there are few studies that have differentiated objective stress from subjective perception of stress [39,40].Regarding objective stress, it is necessary to consider the type of threat one is exposed to, the losses and impacts generated by the context of adversity, and the resulting changes.On the other hand, subjective perception of stress refers to experiencing the situation in a negative, neutral, or positive manner, and above all, the subjective distress it caused, such as symptoms of anxiety, depression, or post-traumatic stress.For these reasons, it is relevant to explore both dimensions of stress-objective and subjective-to determine their differential effects on child variables.In this line of research, it is necessary to investigate the objective negative aspects of the pandemic context (e.g., illness from the coronavirus, death of loved ones, loss of employment or income, difficulty obtaining food, medication, and medical assistance) and the subjective indicators of anxiety and depression.In line with the aforementioned, stress proliferation models suggest that the effects observed in infants due to the pandemic may be primarily mediated by maternal mental health [41].Mothers experiencing new pandemic-related stressors could lead to the emergence or exacerbation of indicators of anxiety and depression, ultimately affecting certain dimensions of child development, as suggested by some studies [42,43].
Initially, based on previous research, the hypothesis is proposed that objective maternal stress due to the pandemic will be positively associated with maternal subjective stress, as measured by indicators of maternal anxiety and depression [12,13,16,18].Secondly, it is expected that objective maternal stress due to the pandemic (negative pandemic experiences) will be negatively associated with various dimensions of neurodevelopment, as previously reported [27][28][29].Finally, supported by the literature of previous studies linking objective maternal stress to different dimensions of child development and maternal subjective stress to alterations in neurodevelopment, it is expected to find that maternal psychopathological indicators act as mediators between negative objective experiences due to the pandemic and child neurodevelopment.In other words, the context of prenatal adversity could set up a negative stimulus that predisposes to an increase in psychopathological symptoms in pregnant women, affecting the trajectory of early development of children gestated during the pandemic, especially in times of isolation and/or confinement.

Participants
The study utilized a sample of 105 mother-child dyads, consisting of singleton and term pregnancies, recruited between March and May 2020.Longitudinal assessments were conducted during the second trimester (mean gestational age = 21.68;SD = 2.58) and third trimester (mean gestational age = 30.8;SD = 1.37), as well as a postnatal assessment at 6 months (n = 103) for both the mothers and their children (see Fig. 1).The study's participant pool was limited to a specific subset of mothers who had completed all three surveys (n = 105), while excluding those who had not done so for various reasons such as a decline in participation (n = 31) or pregnancy loss (n = 1).No imputation methods were employed to address missing data in the excluded participants since they did not meet the minimum 80% data threshold required for such techniques to be viable [44].The socioeconomic, demographic, and health history characteristics of the sample are summarized in Table 1.Inclusion criteria for mothers were as follows: aged 18-45, residing in Argentina, not suffering from serious physical/psychological diseases, and absence of additional COVID-19 risk factors apart from pregnancy.Pregnant women who reported use of psychotropic drugs or steroids during pregnancy, as well as consumption of alcohol and/or illicit drugs, were excluded.Regarding offspring, only newborns from singleton and term pregnancies (≥ 37 y < 42 weeks gestational age) were included, while those with increased risk of neurodevelopmental disorders, such as birth weight < 2.5 kg, congenital anomalies, neurological damage, and diagnosis of intrauterine growth restriction, were excluded from the sample [45].
The group of women who did not participate in the follow-up assessment did not exhibit any significant differences when compared to the group of participating women in terms of prenatal anxiety (Z = − 0.049, p = 0.085), prenatal depressive symptoms (Z = − 0.350, p = 0.200), negative pandemic impact (Z = − 0.708, p = 0.059), as well as the sociodemographic variables.

Procedure
The surveys were administered via Google Forms and disseminated through social networks utilizing a snowball sampling approach.The data collection procedure was entirely online, considering that at the time of data collection, various measures of control and social distancing were still in place due to COVID-19.No paid platforms were used, and participants did not receive any financial compensation for their responses.Individuals responded entirely intentionally and voluntarily.There were no missing data as the system did not allow participants to proceed unless they answered all the questions.Participants were asked to complete four surveys at different time points during the pandemic, including two prenatal assessments during the second and third trimesters, and two postnatal assessments at 6 months after birth for both the mother and the child (see Fig. 1).

Negative experiences of the pandemic
The CAIR Pandemic Impact Questionnaire (C-PIQ) exposure scale, developed by Lang [46], was utilized.This 28-item questionnaire evaluates the psychological impact, growth, and exposure to stressful factors related to the COVID-19 pandemic, either directly or indirectly through close contacts.For this study, only the exposure subscale, consisting of eight dichotomous response items (yes-no), assessing whether the respondent was exposed to various stressors generated by the pandemic, was employed (e.g., illness from the coronavirus, death of loved ones, loss of employment or income, difficulty obtaining food, medication, medical assistance, and negative impact on relationships with family and friends).Scores are calculated by adding the "yes" responses from both columns ("it happened to me" and "it happened to someone close to me"), resulting in a final score for negative pandemic experiences.Scores range from 0 to 16 points (item 3, which refers to the death of a close person, can only be answered in the "happened to someone close to me" column, but contributes 2 points).
The internal consistency of this scale in our study was high, with a Cronbach's α of 0.88.

Depression symptoms
The Spanish adaptation of the Beck Depression Inventory-II (BDI-II; [47] by Sanz et al. [48] and [49] was used.The BDI-II is a widely employed measure for assessing the presence and severity of depression symptoms, comprising 21 items that inquire about symptoms such as sadness, crying, loss of pleasure, guilt, and pessimism.Previous research has reported good reliability (α = 0.89, [50] and validity of the BDI-II in pregnant women [51], and it is widely used internationally for assessing depression during pregnancy [52].
In our study, the BDI-II exhibited excellent internal consistency, with a Cronbach's α of 0.93.

Anxiety symptoms
The state anxiety scale of the Spanish version [53] of the State-Trait Anxiety Inventory (STAI [54], was employed.
The STAI is a self-report measure that comprises 40 items designed to assess state and trait anxiety separately.For this study, only the 20 items of the state anxiety subscale were administered.The STAI has previously demonstrated good reliability (α = 0.84 to 0.93, [55] and validity in pregnant women [56], and is widely used in studies involving pregnant populations due to its favorable indicators of validity and reliability [52].In our study, the STAI exhibited good internal consistency, with a Cronbach's α of 0.86.

Overall neurodevelopment
The Ages and Stages: 3 scale (ASQ:3) was administered, a questionnaire for screening children's maturational neurodevelopment through the observation of patterns to be followed at ages between 0 months and 5 years and 6 months [57].The instrument has 30 items to assess five areas: (1) communication (vocalication, hearing and comprehension),(2) gross motor (movement of arms, body and legs); (3) fine motor (movement of hands and fingers); (4) problem-solving (learning and playing with toys); and (5) personal-social area (solitary social play and interactions with others).Each of these five domains correspond to the baby's emerging language skills, gross and fine motor development, cognitive functioning, and the development of social behavior, respectively.ASQ-3 is the most validated surveillance scale of development worldwide.The questions are multiple choice and were completed by the mother.Items are scored using a three-point Likert scale (i.e., 10 = yes, 5 = sometimes, 0 = not yet).The scores obtained are summed and the total is compared with a cutoff point established according to age [58].This cut-off points outlines qualitative categories: above the cut-off point, neurodevelopment is within expected,close to the cut-off point, the child requires additional monitoring and follow-up actions; below the cut-off point, the child is at risk, requires further evaluation and eventually, an intervention.It has a sensitivity of 88% and specificity of 94% for the Argentine version [58].For this project, the 5 months 0 days to 6 months 30 days questionnaire was selected.

Covariates
In this study, participants were asked a series of close-ended questions to collect relevant information.These questions covered various aspects, including age, gestational age, education level, history of previous pregnancies, economic impact due to the pandemic, and presence of prenatal illnesses or medical complications.In addition, for infants, close-ended questions were administered to gather data on sex, birth weight, and age.The use of close-ended questions allowed for structured and standardized data collection, facilitating analysis and interpretation of the findings in a rigorous and systematic manner.

Data analysis
Data analysis was conducted using IBM SPSS 26 software for Windows, with a significance level set at p < 0.05.Descriptive statistics were computed for socio-economic and demographic characteristics, as well as for all variables reported in the evaluation instruments section.Continuous variables were summarized using measures of central tendency and dispersion, while categorical variables were expressed as percentages.To ensure the normality of the dependent variables, skewness, and kurtosis were examined, with acceptable limits set at ± 2 points according to George and Mallery [59].All variables showed acceptable values within these limits, indicating that the assumptions of normality were met for the statistical analyses.
Pearson's correlations were used to assess associations between continuous variables.Hierarchical regression analysis models were employed to investigate the predictive relationship between prenatal anxiety/depression/negative experiences due to the pandemic and early neurodevelopment at 6 months.Variables that exhibited significant correlations (p < 0.05) with ASQ:3 subscale scores were included as covariates in the models, including economic impact due to the pandemic context, maternal education level, postnatal anxiety, infant sex, and birth weight.The predictors were sequentially introduced into the regression analysis in the following steps: (1) covariates were included to control for background factors; (2) postnatal anxiety/depression was added to control for the effects of maternal psychological context; and (3) variables related to prenatal anxiety/depression (during the second and third trimester) or negative experiences due to the pandemic were added to the model.Furthermore, serial mediation models (Model 4) were estimated using the PROCESS tool [60].In these models, negative experiences due to the pandemic were considered as the independent variable, anxiety/depression levels as the mediators, and overall neurodevelopment dimensions as the dependent variables, as appropriate.The same covariates utilized in the linear regression analyses were included in the serial mediation models.A bootstrapping procedure with 10,000 resamples was employed to assess the indirect effect, generating 95% accelerated and bias-corrected confidence intervals (CI of 95%) of the indirect effects.Indirect effects were considered significant when the upper and lower CI did not include zero.

Sample characteristics and descriptive and inferential statistics of psychopathological and neurodevelopmental measures
Table 1 displays the socio-economic and demographic variables of the sample, while Table 2 presents the descriptive statistics of the administered tests.Furthermore, Table 3 provides an overview of the percentages of the qualitative scales for each of the ASQ:3 subscales.It is noteworthy that only a small percentage of the sample demonstrated performance below expectations based on age.However, for the fine motor and socio-individual subscales, these percentages were 16.2% and 12.4%, respectively.

Correlations between negative pandemic experiences, maternal psychopathology, infant neurodevelopment, and covariables
Correlations among study variables are presented in Table 4.As can be seen, most of the significant correlations are low (> 0.2-0.4) and moderate (> 0.4-0.6),except for the correlation between anxiety during the 2nd trimester and negative pandemic experiences, which show a high correlation (r = 0.646, p < 0.001).

Associations among prenatal psychopathology, negative experiences due to the pandemic, and infant neurodevelopment
Hierarchical regression analyses (adjusted by covariates) revealed that higher levels of anxiety during the third trimester (R 2 ajus = 0.184, p < 0.01, β = − 0.440, p < 0.01) and a greater number of negative experiences due to the pandemic (R 2 ajus = 0.077, p < 0.05, β = − 0.249, p < 0.05) predicted slower fine motor development.In turn, higher levels of anxiety during the third trimester (β = − 0.268, p < 0.05) were also associated with slower socio-individual development in the infant (R 2 ajus = 0.074, p < 0.05).Testing the rest of the regression models did not show significant results (p > 0.05).

Mediation models
Based on the results yielded by the hierarchical linear regressions, two serial mediation models were tested:

Model A
In this model, negative experiences due to the pandemic were the independent variable, anxiety level during the third trimester was the mediator and fine motor development of infants was the dependent variable.As can be seen in Fig. 2A, maternal anxiety levels during the third trimester were significantly and negatively associated with fine motor development in 6-month-old infants (β = −0.39,p < .01)and, together with covariates, explained 15% of the variance (R 2 = .15,p < .01).While negative experiences due to the pandemic and fine motor development (β = 0.01, p > .05)were not significantly associated, there was a significant indirect mediation effect among negative pandemic experiences, maternal anxiety, and fine motor development (β = −.25,IC = −.39/−.11).

Model B
In this model, negative experiences due to the pandemic were the independent variable, anxiety level during the third trimester was the mediator, and infants' socio-individual development was the dependent variable.As can be seen in Fig. 2B, maternal anxiety levels during the third trimester Although the direct effect (β = −0.04,p > .05) of negative pandemic experiences on socio-individual development was not significant, a significant the total effect (β = −0.17,p > .05)and indirect effect was found.Specifically, negative pandemic experiences were found to be indirectly associated with the socio-individual development of the offspring through the mediator (β = −0.13,IC = −.29/−0.07).

Discussion
The present study aimed to investigate the effects of negative pandemic experiences, prenatal anxiety, and depression among women exposed to COVID-19 confinement on the early neurodevelopment of their infants at 6 months postnatal.The hypothesis posited that the current adversity context due to the pandemic, along with other associated variables, may contribute to increased maternal psychopathological symptoms, which in turn could impact the developmental trajectory of infants born during confinement.Pregnancy is a complex period involving physiological, psychological, and social dimensions, and exposure to adverse situations affecting any of these dimensions can increase the likelihood of women experiencing depression, anxiety, or stress, consequently exposing their children to potential negative physiological, emotional, or cognitive consequences [40].
Initially, the present study revealed significant associations between objective measures, specifically negative pandemic experiences, and subjective stress, specifically levels of anxiety, in relation to the neurodevelopment of fine motor skills and socio-individual functioning.Subsequently, noteworthy effects were observed indicating that negative pandemic experiences and anxiety levels significantly impact the neurodevelopment of fine motor skills and socio-individual functioning.Furthermore, significant effects were identified between negative pandemic experiences and maternal anxiety levels.Finally, a mediation model was employed, providing empirical support for the indirect association between negative pandemic experiences as objective stressors and the socio-individual and fine motor neurodevelopment of offspring, mediated by anxiety symptoms as subjective stress experienced during the third trimester.
In terms of offspring neurodevelopment, our study found that a small proportion of the sample demonstrated performance below age expectations.Specifically, less than 4% of the participants exhibited atypical or clinically atrisk performance on the communication, gross motor, and problem-solving subscales.However, more than 12% of the participants showed such performance on the fine motor and socio-individual subscales.These findings indicate that, for the majority of infants, differences in neurodevelopment fall within the typical range, irrespective of the varying levels of prenatal anxiety experienced by their mothers.
To date, only a few studies have reported on the effects of objective measures of stress on the early neurodevelopment of infants born during the COVID-19 pandemic.Similar to our research findings, these studies have shown that compared to pre-pandemic samples, infants exhibited reduced motor and socio-personal development at 6 months of age [27], or reduced verbal, motor, and overall cognitive performance [28].Other studies conducted during previous public health emergencies or critical events such as catastrophes or natural disasters have also demonstrated that prenatal and early childhood stress can have long-term consequences on cognitive and emotional development [8,31,[61][62][63][64][65].
Consistent with these assumptions, our study revealed that negative pandemic experiences were indirectly and positively associated with slower fine motor neurodevelopment.However, when examining the existing literature on similar research designs, we conclude that the relationship between maternal psychopathology and motor development is one of the least studied aspects of early neurodevelopment (van den [66].The few studies that have addressed this issue have reported mixed results, with some showing negative associations between maternal stress and motor development at 8 months [25,67], 2 years [68,69], and even long-term effects persisting until late childhood and adolescence [70].On the other hand, some studies have reported no significant associations [71,72], and even positive relationships between moderate levels of stress and motor development at the age of two [73].Further research is needed to better understand the complex relationship between maternal psychopathology, pandemic context, and motor development in early infancy.
More precisely, regarding the effects of maternal adversity due to natural catastrophes or similar events, findings from Project Ice Storm have shown that severe levels of subjective prenatal stress predict poorer motor development in 5 and half-year-old children [74].More recently, Fig. 2 Model A Statistical diagram of the serial mediation model for the influence of anxiety during the third trimester on the association between negative experiences of the pandemic and fine motor neurodevelopment of 6-month-old infants.Model B Statistical diagram of the serial mediation model for the influence of anxiety during the third trimester in the association between negative experiences of the pandemic and the socio-individual development of 6-month-old babies.Note: path values represent non-standardized regression coefficients.The c value represents the total effect of the model.The c value represents the direct effect of the initial analysis of the negative experiences of the pandemic on the socio-emotional development after the inclusion of the mediator.The economic impact due to the pandemic context, the mother's educational level, postnatal anxiety, the sex of the baby, and the birth weight were entered as covariates in the regression model.For simplicity, these covariates are not shown in the figure.*p < 0.05/**p < 0.01 ◂ Simcock et al. [75] reported that high levels of maternal stress showed positive associations with motor development at 2 months, but such effects became negative in infants aged 6 and 16 months, particularly when the stressful events occurred in late gestation and the mother had a negative perception of the context of adversity experienced.
The findings of this study align with previous research regarding the effects of maternal anxiety during pregnancy on behavioral and emotional development in children.While the hypothesis that maternal anxiety during pregnancy predicts maladjustment in children is not new [76], the available studies in human populations have had limitations such as lack of statistical control for confounding factors or covariates, retrospective data collection, cross-sectional designs, and lack of distinction between prenatal and postnatal stress [77].However, this current study has attempted to address some of these limitations.
The relationship between prenatal anxiety and behavioral neurodevelopment in young infants is still a growing field of study, and few studies have explored this association.Some studies have reported that prenatal anxiety is associated with higher levels of colicky behavior, infant activity, distress, sadness, negative infant effort, crying, and fussiness in infants as young as 3 months old [78][79][80][81].
The mechanisms mediating the influence of prenatal health on fetal and early childhood development have not been sufficiently elucidated yet [82].Maternal mental health, as a mediator between maternal adversity experiences and infant neurodevelopment, can be explained by two complementary analytical perspectives: a psychological perspective and a neurobiological perspective.From a psychological perspective, stress proliferation models propose that the psychological impact on infants resulting from the pandemic is primarily influenced by the mental health of mothers [41,83].Mothers are currently facing new stressors related to the pandemic, such as economic difficulties, disruptions to routines, medical check-ups, and the loss of loved ones.The transmission of stress effects can vary depending on individual differences in coping skills and underlying factors, including mental health conditions like depression and anxiety [43].Specifically, maternal mental health can undermine mothers' ability to engage in sensitive and supportive parenting behaviors, potentially hindering their capacity to provide effective care for their children.Ultimately, these maternal challenges may explain the observed alterations in infant development.
On the other hand, from a neurobiological perspective the fetal programming hypothesis [84] would suggest that physical, behavioral, and emotional characteristics in the offspring of mothers with prenatal stress result from sufficiently stable alterations in the structure and function of the brain and other organs of the offspring [85].There is now some consensus that maternal influence on the fetus is mediated by the impact of maternal cortisol on the development of the fetal hypothalamic-pituitary-adrenal (HPA) axis.Stress-associated glucocorticoids could dramatically affect fetal growth [86], the function of neurotransmitters [87] and oligodendrocyte development [88], which could alter neurodevelopmental trajectories.
It is important to acknowledge the limitations of any research study to appropriately interpret and generalize the findings.Some limitations of the study you mentioned include (1) small sample size and purposive sampling: the study used a relatively small sample size and purposive sampling method, which may limit the generalizability of the findings to the broader population.Purposive sampling involves selecting participants based on certain characteristics or criteria, which may introduce selection bias and limit the representativeness of the sample; (2) reliance on mother's reports: the study relied exclusively on the mother's reports of indicators of their infants' neurodevelopment and their own symptoms.This reliance on self-report measures may introduce biases, such as recall bias or social desirability bias, which could affect the accuracy and reliability of the findings; (3) uncontrolled variables: the study did not control for other variables that may influence infant neurodevelopment, such as postnatal factors like mother-infant bonding or social maturation.These uncontrolled variables could confound the results and limit the ability to establish causality between prenatal health and neurodevelopmental outcomes; and (4) potential confounding factors: the study did not account for other potential confounding factors, such as genetic factors or other environmental influences that may contribute to neurodevelopmental outcomes in infants.These factors could impact the results and interpretations of the findings.It is important to consider these limitations when interpreting the results of the study and drawing conclusions.Future research with larger sample sizes, randomized controlled designs, and comprehensive control of confounding factors could provide more robust and generalizable evidence on the influence of prenatal health on neurodevelopment in infants.Additionally, incorporating objective measures of neurodevelopmental outcomes and accounting for relevant postnatal variables could further enhance the validity and reliability of the findings.
In conclusion, the present investigation represents a pioneering effort in examining the early effects of prenatal exposure to psycho-social adversity, specifically the context of the COVID-19 pandemic, on neurodevelopment in infants.The findings of this study reveal that negative experiences related to the pandemic are indirectly associated with socio-individual and fine motor neurodevelopmental outcomes in offspring, mediated by maternal anxious symptomatology during the third trimester of pregnancy.These results suggest that the gestational and early childhood period may be characterized by adversity due to the pandemic, which should be acknowledged as a potential risk factor in future infant development.The indicators elucidated in this study could potentially contribute to emotional, cognitive, and behavioral deficits during childhood and adolescence, as well as increase the likelihood of developing various psychopathological and neurodevelopmental disorders, as demonstrated in previous studies [82,[89][90][91][92][93][94][95][96][97][98][99]

Table 1
Socio-economic and demographic variables and health covariates

Table 3
Qualitative assessment of the results of the ASQ:3 scales