Risk of Developmental Delay in Infants Born to Perinatal COVID-19-Positive Mothers at a Tertiary Care Hospital: A Cross-Sectional Study
Article information
Abstract
Purpose
Prenatal and perinatal experiences of the mother are known to influence infant development. Maternal exposure to coronavirus disease 2019 (COVID-19) during pregnancy has been associated with increased morbidity and mother-baby separation. However, the developmental outcomes of infants born to COVID-19-positive mothers remain unclear. This study represents an initial exploratory effort to assess the developmental risks faced by infants born to mothers who tested positive for COVID-19.
Methods
This cross-sectional study involved telephonic interviews and developmental screenings of 45 infants, aged 9 to 15 months, who were born to perinatal COVID-19-positive mothers between July 2020 and May 2021. The Ages & Stages Questionnaire was used for the developmental assessment. The impacts of maternal, infant and separation-related factors on development were analyzed.
Results
Within the study population, 28.8% (13 of 45 infants) presented with a risk of developmental delay. The gross motor and problem-solving domains were the most frequently impacted. Among the factors studied, prolonged separation period (exceeding 7 days), advanced maternal age, and gestational age (preterm birth) were associated with higher proportions of infants at risk of developmental delay; however, these associations were not statistically significant.
Conclusion
This study suggests that infants born to mothers who tested positive for COVID-19 during the perinatal period face a risk of developmental delay. Factors such as maternal age, gestational age at birth, metabolic disease during pregnancy, and infant-mother separation could exacerbate this risk. Future research should prioritize objective assessments of development and long-term follow-up to monitor developmental outcomes in this population.
Introduction
The understanding of coronavirus disease 2019 (COVID-19), its evolution, and its long-term effects on human health has advanced rapidly as the pandemic has progressed. Research and analysis continue to examine various aspects of this unique virus, including its transmission dynamics and potential long-term impacts on humans [1]. In India, the pandemic affected more than half of the population, with vulnerable groups comprising up to 20% [2]. The most severely impacted individuals included people with compromised or suppressed immune systems, older adults, healthcare workers, and pregnant women [3].
Maternal well-being is crucial for the optimal growth and development of an infant. Mother-infant bonding in the first 2 years is key to the child’s long-term social and emotional health [4,5]. Stress and social isolation during the prenatal and postnatal periods can influence immunological pathways; accordingly, infection during pregnancy can trigger higher cytokine levels in response to maternal stress. These interrelated factors may contribute to compromised maternal health and well-being, as well as adverse developmental outcomes for the infant [6]. The pandemic has significantly impacted maternal mental health, with mothers facing heightened concerns about transmitting the virus to their infants. Social distancing, isolation, and quarantine measures have increased the risk of psychological issues among pregnant women [7]. Mental health challenges faced by mothers before and during pregnancy, as well as post-pregnancy difficulties (in short, the perinatal health of the mother), have been reported to meaningfully impact infant development [8].
According to the World Health Organization, the prevalence of global developmental delay (DD) ranges from 1% to 3% across various regions of the world. In India, this rate is reported to be approximately 1.5% to 2.0% in children under 2 years old [9,10]. Timely detection of DD is possible through early intervention. As such, developmental surveillance and screening are critical actions that healthcare professionals should undertake. Multiple studies have demonstrated that soliciting parent’s concerns about their child’s development in areas such as communication, learning, social, and motor skills yields valuable information for assessing a child’s developmental progress [11,12]. Maintaining records of a child’s developmental history at each visit can aid in identifying any delays, deviations, or regressions in health status.
While maternal and fetal outcomes associated with COVID-19 exposure have been documented, insufficient research is available on the developmental outcomes of infants. Consequently, it is essential to screen infants born to COVID-19-positive mothers to understand their risk of DD. To our knowledge, the developmental outcomes of infants born to COVID-19-positive mothers in India have not yet been reported. This study aimed to explore the risk of DD in infants born to mothers who tested positive for COVID-19 during the perinatal period.
Materials and Methods
1. Study design
This descriptive cross-sectional study was conducted between 2020 and 2021, following the receipt of ethical clearance from the Institutional Ethics Committee of Ramaiah Medical College (reference number: MSRMC/EC/SP-17/07-2021; dated: July 30, 2021). Information was obtained from hospital records regarding pregnant mothers who tested positive for COVID-19 at the time of delivery between July 2020 and May 2021.
2. Sample size
The reported prevalence of DD in India is approximately 2% among children up to 2 years old [10]. We hypothesized that the risk of DD in infants born to COVID-19-positive mothers may be slightly higher. Consequently, with an anticipated prevalence of 3% and a desired precision of 5%, a sample size of 44 was determined. Convenience sampling was employed for data collection.
3. Procedure
The purpose of this study was to identify infants at risk of DD. The study included infants born to mothers who tested positive for COVID-19 during the perinatal period between July 2020 and May 2021. Records of previous episodes or COVID-19 infections during earlier trimesters were unavailable. Thus, only mothers who tested positive at the time of delivery were included. The exclusion criteria were infants with perinatal asphyxia, neonatal seizures, congenital malformations, and genetic disorders. A total of 77 participants, aged 9 to 15 months, were screened (Fig. 1).
Flowchart representing the process of data collection. COVID-19, coronavirus disease 2019; ASQ, Ages & Stages Questionnaire.
The parents were contacted by phone and informed about the purpose and procedures of the study. Those who agreed to participate received a Google Form to provide informed consent. Telephone interviews were then conducted using the Ages & Stages Questionnaire-3 (ASQ-3), a validated parent-completed screening tool for detecting DD in infants aged 2 to 66 months. The ASQ-3 comprises 21 intervals, each containing 30 items across five developmental areas: communication, gross motor, fine motor, personal-social, and problem-solving. Each item offers three response options: “yes,” “sometimes,” or “not yet,” scored as 10, 5, or 0 points, respectively. The total score for each domain is calculated by summing the item scores, with a maximum of 60 points per domain. These scores are used to determine developmental status, categorizing children as “development on schedule” if their scores are above the cutoff in all domains or “at risk” if their scores fall below the cutoff in any domain, indicating a need for further evaluation [13]. Additional data collected included maternal age, previous abortion, metabolic disease, mode of delivery, birth weight, gestational age (GA), and separation period duration.
Results
Of the 77 infants screened, 45 met the inclusion criteria and were enrolled in the study. The ages of the participants ranged from 9 to 15 months, with the largest subgroup (31% of the total) between 13 and 14 months old (Table 1). The gender distribution was 44% male and 55% female. Within the study population, eight infants (18%) had been born preterm, and 25 infants (56%) had been delivered by cesarean section. DD was more commonly observed in male than in female infants, with nine of the 20 male infants and four of the 25 female infants exhibiting delays.
Demographic distribution of infants in the study
In accordance with the guidelines of the ASQ, the overall risk of DD was calculated as follows.
In this study population, the risk of DD was found to be 28.8%. Delay risk was most prevalent in the gross motor and problem-solving domains (Table 2). Among the 45 infants included in the study, two tested positive for COVID-19.
Distribution of domain-specific risk of developmental delay among infant study participants
The variables potentially influencing DD in any domain—including the duration of separation between mother and infant, maternal metabolic disease, GA at birth, maternal history of abortion, and maternal age at delivery—were analyzed using the chi-square test for association. Factors associated with a higher prevalence of risk of DD included maternal metabolic disease, maternal age, GA, and a separation period exceeding 7 days (Table 3).
Association of maternal, infant and separation factors with development
Discussion
This study aimed to estimate the risk of DD in infants aged 9 to 15 months who were born to COVID-19-positive mothers at a tertiary care hospital. Infants born to mothers who were infected with COVID-19 during the perinatal period were screened for DD risk. The prevalence of this risk was found to be 28.8%, which substantially exceeded the anticipated level for the study population. This figure may be compared with a recent Brazilian study, which reported a prevalence of motor DD of 27.8% [14]. In the present study, we systematically collected and analyzed data on factors associated with DD. These included the duration of separation between mother and infant, maternal metabolic disease, previous abortion, infant birth weight, GA at birth, and maternal age at delivery (Table 3).
In the present study, among the maternal factors, maternal metabolic disease and maternal age above 30 years were associated with a higher proportion of infants at risk of DD, although these results were not statistically significant. A history of abortion was not linked to any significant difference in the risk of delay. Maternal factors have been documented to impact fetal, infant, and adult outcomes in low- and middle-income countries [15]. Due to the small sample size, the influence of these factors on the present study population remains inconclusive.
In this study, eight infants (18%) were born preterm, and among these, 50% were at risk of DD. Considerable brain development occurs during the last 4 to 6 weeks of gestation. Since preterm infants experience a shorter gestational period, their development is compromised [16]. Purnasari et al. [17] investigated the risk of preterm delivery in pregnant women with COVID-19 and found that the risk of preterm birth in women with COVID-19 was 2.18 times higher than in pregnant women without the infection. Therefore, despite the lack of a known direct influence, COVID-19 may be associated with other factors that could lead to DD. While birth weight is known to influence development, this study found no association between birth weight and the risk of DD. This lack of association may stem from the fact that some infants were preterm and potentially had birth weights appropriate for their GA, which could represent a confounding factor.
In this study, only two infants tested positive for COVID-19. However, those identified as at risk of DD were not infected with the virus. Consequently, no evidence suggests that direct transmission directly impacts development. Research indicates that the risk of direct transmission of COVID-19 during rooming-in and breastfeeding for infants born to COVID-19-positive mothers is low [18]. Nevertheless, mother-infant separation was practiced during the perinatal period for mothers with the infection. In the present study, the average duration of separation ranged from 2 to 15 days, which consequently delayed the initiation of direct breastfeeding. The rate of DD observed in infants who were separated for more than 7 days was 43.8%, compared to 20.7% for those separated for less than 7 days. This pattern suggests that the length of separation could be a contributing factor to DD, although the results did not reach statistical significance. Evidence suggests that early separation of the infant from the mother can interfere with breastfeeding, mother-infant bonding, and infant regulatory issues. A study conducted in Wuhan, China, by Wang et al. [19] assessed the impact of COVID-19 during pregnancy and found a negative association between mother-infant separation and infant development. The mean duration of separation in their study ranged from 7 to 52 days, which is considerably long. Due to concerns about transmission of the infection, mothers and infants continued to be separated even after the quarantine period.
The COVID-19 pandemic has heightened fears of viral infection, which in turn has been associated with increased levels of anxiety [20]. Research suggests that elevated maternal anxiety symptoms are associated with a broad spectrum of adverse outcomes for offspring, including cognitive, behavioral, and neurophysiological issues [21], as well as temperamental and developmental challenges [22]. Furthermore, evidence indicates that maternal stress and depression can lead to changes in the grey and white matter in the brains of infants [23].
In the present study, infants demonstrated diminished problem-solving abilities, which may be attributable to environmental constraints faced during the pandemic. Most of the families self-isolated, and the resulting dramatic reduction in their interactions and bonding with others could have contributed to developmental issues.
Edlow et al. [24] conducted a retrospective study to assess the association between in utero exposure to COVID-19 and the risk of neurodevelopmental disorders in the first year after birth. The findings indicated an association between COVID-19 infection and an increased rate of neurodevelopmental disorders. Potential risk factors identified included the stress of childbirth during the COVID-19 pandemic, characterized by limited social support due to visitor restrictions, prolonged hospital stays, and separation of the mother and infant. The authors concluded that larger follow-up studies are needed [24].
Evidence regarding maternal COVID-19 infection indicates that the inflammatory response triggered by the virus can lead to complications in the fetus. Additionally, the effects of related complications and environmental factors may contribute to developmental challenges in infants [25]. This study is among the first in India to report on the developmental screening of infants born to mothers who tested positive for COVID-19 during the perinatal period. Given the study findings and emerging evidence, we recommend that the development of infants born to COVID-19-positive mothers be regularly monitored.
1. Conclusion
Infants born to mothers who tested positive for COVID-19 were observed to be at risk of DD. Consequently, these infants should undergo regular developmental screenings and assessments. This will enable the early identification of delays and allow for timely interventions to support their overall well-being.
2. Limitations
This study has several limitations. Notably, only women who tested positive for COVID-19 at the time of delivery were recruited for the study, as data on previous infections were not accessible within the hospital records. Consequently, any trimester-specific influence of COVID-19 infection during pregnancy could not be studied. Additionally, this was a single-center study with a limited sample size, hindering the generalizability of the results. Furthermore, the study was exploratory in nature, confined to screening infants using a parent-reported questionnaire. Therefore, the findings can only suggest a potential risk of DD.
3. Future implications
Further research should focus on conducting longitudinal studies over various time intervals. In this study, developmental screening was performed to understand the risk of DD. Subsequent studies can aim to incorporate a comprehensive and objective developmental assessment. Notably, multiple environmental constraints, socioeconomic factors, and behavioral changes may contribute to delays in development and warrant detailed evaluation.
Notes
Conflicts of interest
No potential conflict of interest relevant to this article was reported.
Author contribution
Conceptualization: KTK. Data curation: KTK. Formal analysis: KTK and KJ. Methodology: KTK and KJ. Visualization: KTK. Writing - original draft: KTK. Writing - review & editing: KTK and KJ.
Acknowledgements
The authors extend their heartfelt thanks to the parents whose participation was essential to the advancement of this study. We are also grateful to Ms. Rajitha Alva (PT), Assistant Professor, and Aditi Bhandarkar, PhD Scholar, for their guidance in manuscript preparation. Our appreciation extends to Ms. Monika Vempadapu, Research Associate at M.S. Ramaiah Medical College, for her assistance and support in the preparation of this manuscript. The authors also acknowledge Dr. Shivaraj, Associate Professor of Community Medicine at M.S. Ramaiah Medical College, for his assistance with the data analysis. A special acknowledgment is due to Dr. Jane Squires for granting permission for use and access to the Ages & Stages Questionnaire in this research.