Description of Maternal Sample
Table 1 shows that the total population (N = 671) was categorized into three distinct groups based on maternal SARS-CoV-2 severity: non-infected mothers (N = 272), mothers with mild symptoms (N = 346), and mothers with severe symptoms (N = 53). The analysis of maternal characteristics revealed a statistically significant difference in age among the groups (Kruskal-Wallis H = 10.987, df = 2, p = 0.004). However, perceived stress scores during pregnancy did not differ significantly among the groups (Kruskal-Wallis H = 2.028, df = 2, p = 0.363). Regarding maternal education level, there was a marginally non-significant difference observed among the groups (χ2 = 11.045, df = 6, p = 0.087). The majority of participants in all groups had attained a university degree, with proportions ranging from 186 out of 345 mothers with mild infection (53.9%; one mother did not response) to 161 out of 272 non-infected mothers (59.2%). Occupational activity varied significantly among the groups (χ2 = 13.274, df = 6, p = 0.039), with the majority of participants being employed or working for themselves across all groups. Analysis of racial groups showed no significant difference among the groups (χ2 = 8.243, df = 4, p = 0.083), with the majority of participants identifying as Caucasian. Substance use during pregnancy did not significantly differ among the groups (χ2 = 3.608, df = 2, p = 0.165). Regarding offspring characteristics, there was no significant difference in the distribution of sexes among the groups (χ2 = 3.719, df = 2, p = 0.156), with approximately half of the offspring being female. These findings highlight the demographic characteristics of the study population and their association with maternal SARS-CoV-2 severity. The analysis of maternal SARS-CoV-2 infection during pregnancy revealed significant differences in the distribution of infection trimesters among severity groups (χ2 = 27.445, df = 2, p < 0.001). Notably, a higher proportion of severe SARS-CoV-2 cases occurred in the third trimester (34 out of 53 mothers with severe infection; 64.2%) compared to the first (4 out of 53 mothers with severe infection; 7.5%) and second (15 out of 53 mothers with severe infection; 28.3%) trimesters. These findings underscore the potential impact of the timing of maternal infection on SARS-CoV-2 severity during pregnancy.
Table 1
| Total | Non-infected mothers | Mild SARS-COV-2 | Severe SARS-COV-2 | | |
n (%) | 671 (100) | 272 (40.54) | 346 (51.56) | 53 (7.90) | | P value |
Maternal age (mean +/- SD) | 33.11 ± 5.36 | 33.53 ± 7.707 | 33.08 ± 5.081 | 31.21 ± 5.00 | Krukal-Wallis 10.987 | 0.004* |
Maternal perceived stress score (mean +/- SD) | 22.97 ± 7.76 | 22.68 ± 7.607 | 23.01 ± 7.612 | 24.25 ± 9.37 | Krukal-Wallis 2.028 | 0.363 |
Educational level | Reading and writing n (%) | 3 (0.4) | 0 (0.0) | 2 (0.6) | 1 (1.9) | χ2 = 11.045 | 0.087 |
Elementary school n (%) | 55 (8.2) | 20 (7.4) | 27 (7.8) | 8 (15.1) |
High school n (%) | 243 (36.3) | 91 (33.5) | 130 (37.7) | 22 (41.5) |
University n (%) | 369 (55.1) | 161 (59.2) | 186 (53.9) | 22 (41.5) |
Occupational status | Studying n (%) | 15 (2.2) | 7 (2.6) | 8 (2.3) | 0 (0.0) | χ2 = 13.274 | 0.039 |
Looking for a job n (%) | 78 (11.6) | 38 (14.0) | 29 (8.4) | 11 (20.8) |
Employee n (%) | 453 (67.6) | 170 (62.5) | 249 (72.2) | 34 (64.2) |
Retired n (%) | 124 (18.5) | 57 (21) | 59 (17.1) | 8 (15.1) |
Ethnicity | Caucasian n (%) | 599 (89.3) | 239 (87.9) | 317 (91.6) | 43 (81.1) | χ2 = 8.243 | 0.083 |
N Caucasian n (%) | 60 (8.9) | 29 (10.7) | 22 (6.4) | 9 (17.0) |
No response n (%) | 12 (1.8) | 4 (1.5) | 7 (2.0) | 1 (1.9) |
Drug consumption during pregnancy n (%) | 183 (32.0) | 79 (33.8) | 96 (32.5) | 8 (19.0) | χ2 = 3.608 | 0.165 |
Birth sex | Female n (%) | 350 (51.4) | 144 (52) | 185 (52.9) | 21 (38.9) | 3.719 | 0.156 |
Infected women n (%) | 399 (100) | | 346 (86.72) | 53 (13.28) | | |
Trimester of SARS-CoV-2 Infection | First trimester n (%) | 89 (22.3) | | 85 (24.6) | 4 (7.5) | χ2 = 27.445 | < 0.001* |
Second trimester n (%) | 178 (44.6) | | 163 (47.1) | 15 (28.3) |
Third trimester n (%) | 132 (33.1) | | 98 (28.3) | 34 (64.2) |
*Significance was considered at p value < 0.005 after applying Bonferroni correction |
Developmental Assessment Results at 6 and 12 Months in relation to SARS-CoV-2 Severity
The total sample of children assessed in at least one of the two assessment moments included 681 newborns (including 10 twin births). The distributions of scores across the different ASQ-3 domains in offspring born to non-infected mothers, mothers with mild SARS-CoV-2 infection, and mothers with severe SARS-CoV-2 infection can be seen in Fig. 1. The assessment of neurodevelopmental outcomes using the ASQ-3 at 6 and 12 months provided insights into the developmental delays present in infants in the three comparison groups (see Table 2). At 6 months, a total of 601 out of 681 children (88.25%) were assessed. No significant differences were observed in ASQ-3 scores for communication (χ2 = 1.138, df = 2, p = 0.566), gross motor (χ2 = 0.331, df = 2, p = 0.848), fine motor (χ2 = 0.126, df = 2, p = 0.939), problem-solving (χ2 = 0.135, df = 2, p = 0.935), or personal-social skills (χ2 = 2.434, df = 2, p = 0.296) among the comparison groups. A total of 537 children out of the 681 children (78.85%) were assessed at 12 months. A total of 457 children were assessed at both assessment moments (6 and 12 months). No significant differences were found in ASQ-3 scores for communication (χ2 = 3.211, df = 2, p = 0.201), gross motor (χ2 = 0.574, df = 2, p = 0.751), fine motor (χ2 = 1.022, df = 2, p = 0.600), or problem-solving (χ2 = 0.936, df = 2, p = 0.626) at 12 months among the comparison groups. However, at 12 months, significant differences were observed in personal-social skills (χ2 = 8.282, df = 2, p = 0.016). Specifically, a higher proportion of infants born to mothers with severe SARS-CoV-2 infection exhibited delayed personal-social skills compared to those born to mothers with mild SARS-CoV-2 infection or non-infected mothers. Given the found difference in the personal-social domain at 12 months, we performed a univariate logistic regression analysis, exploring the correlation between personal-social skills at 12 months, assessed using the ASQ-3, and the severity of SARS-CoV-2 symptoms in the group of infected mothers (mothers with mild SARS-CoV-2 infection and with severe SARS-CoV-2 infection). We found personal-social skills at 12 months to exhibit a significant association with SARS-CoV-2 symptom severity (Table 3; p = 0.005). Specifically, the odds ratio (OR) for SARS-CoV-2 severity was 2.967 (95% CI [1.384, 6.361]). Subsequently, in a multivariate logistic regression model adjusting for trimester of infection, offspring sex, mother's age at birth, perceived stress, and drug use during pregnancy, personal-social skills at 12 months remained significantly associated with SARS-CoV-2 symptom severity (Table 3; p = 0.028). The odds ratio (OR) for SARS-CoV-2 severity in this adjusted model was 3.000 (95% CI [1.129, 7.969]). However, trimester of infection, offspring sex, maternal age at birth, perceived stress during pregnancy, and drug consumption during pregnancy did not exhibit significant associations with personal-social skills at 12 months.
Table 2
Proportion of children with developmental delays in the ASQ-3 scale at 6 and 12 months across maternal SARS-COV-2 severity groups.
| Total | Non-infected mothers | Mild SARS-COV-2 | Severe SARS-COV-2 | χ2 | P value |
ASQ-3 6 months n (%) | 601 (88.25) | 244 (35.83) | 313 (45.96) | 44 (6.46) | | |
Communication n (%) | 14 (2.3) | 6 (2.5) | 8 (2.6) | 0 (0.0) | 1.138 | 0.566 |
Gross motor n (%) | 50 (8.3) | 22 (9.0) | 25 (8.0) | 3 (6.8) | 0.331 | 0.848 |
Fine motor n (%) | 19 (3.2) | 8 (3.3) | 10 (3.2) | 1 (2.3) | 0.126 | 0.939 |
Problem solving n (%) | 18 (3.0) | 7 (2.9) | 10 (3.2) | 1 (2.3) | 0135 | 0.935 |
Socio-individual n (%) | 16 (2.7) | 5 (2.0) | 11 (3.5) | 0 (0.0) | 2.434 | 0.296 |
ASQ-3 12 months n (%) | 537 (78.85) | 222 (32.60) | 275 (40.38) | 40 (5.87) | | |
Communication n (%) | 49 (9.1) | 23 (10.4) | 20 (7.3) | 6 (15.0) | 3.211 | 0.201 |
Gross motor n (%) | 66 (12.3) | 30 (13.5) | 31 (11.3) | 5 (12.5) | 0.574 | 0.751 |
Fine motor n (%) | 26 (4.9) | 9 (4.1) | 14 (5.1) | 3 (7.7) | 1.022 | 0.600 |
Problem solving n (%) | 82 (15.3) | 37 (16.7) | 38 (13.8) | 7 (17.5) | 0.936 | 0.626 |
Socio-individual n (%) | 91 (16.9) | 31 (14.0) | 47 (17.1) | 13 (32.5) | 8.282 | 0.016* |
ASQ-3, Ages & Stages Questionnaire, 3rd Edition; *Significance was considered at p value < 0.005 after applying Bonferroni correction. The total number of children assessed at any assessment point was 681. |
Table 3
Socio-individual skills and severe SARS-COV-2 infection.
Univariate analysis | Multivariate analysis OR adjusted by severity of maternal SARS-COV-2 infection, trimester of SARS-CoV-2 infection, maternal age, drugs consumption during pregnancy, maternal perceived stress and sex |
| P value | Crude OR | CI | P value | Adjusted OR | CI |
L | U | L | U |
Severe SARS-COV-2 (ref non infected) | 0.005 | 2.967 | 1.384 | 6.361 | 0.028 | 3.000 | 1.129 | 7.969 |
*Significance was considered at p value < 0.005 after applying Bonferroni correction |