Early‐life exposures in infants born during and after the COVID‐19 pandemic: A comparative prospective observational study of the CORAL and FLORAL birth cohorts

Abstract

Background

The CORAL 2020 birth cohort examined health outcomes and feeding practises in infants born during the COVID‐19 pandemic, a period of reduced social mixing and altered healthcare utilization during a critical period of immune development. The 2025 FLORAL (FoLlow‐on from CORAL) cohort was established to determine whether findings from the CORAL cohort were specific to the pandemic period or reflected broader evolving trends.

Methods

FLORAL is a prospective observational birth cohort study recruiting term infants born between March and May 2025 across three Dublin maternity hospitals using almost identical methodology to the CORAL cohort. Assessments included parent‐completed questionnaires and in‐patient study visits. Outcomes at 6 months were compared between FLORAL and CORAL cohorts to examine differences in early‐life exposures.

Results

Of 574 infants whose parents provided consent, 485 completed the enrolment questionnaire. At 6 months, 442 participants completed the six‐month follow‐up questionnaire and 440 attended the in‐person study visit. Demographic characteristics were broadly comparable between cohorts. FLORAL infants had numerically higher rates of reported infections (33.3% vs. 28%, p = .12), hospitalization (13.1% vs. 5.1%, p < .001), and antibiotic exposure (13.1% vs. 6.2%, p = .002) compared with CORAL infants. However, the introduction of allergenic foods occurred significantly more frequently in FLORAL, with peanut introduced in 44% of infants compared with 13.6% in CORAL (p < .0001).

Conclusion

Compared with pandemic‐born infants, post‐pandemic infants experienced increased infection‐related healthcare utilization and increased antibiotic exposure, alongside sustained high breastfeeding rates and substantially earlier allergen introduction. These may influence microbiome development and later atopic outcomes.

Early‐life exposure profiles differed between pandemic and post‐pandemic birth cohorts, with higher hospitalization and antibiotic exposure post‐pandemic, alongside sustained breastfeeding and substantially greater allergen introduction. These descriptive findings characterize how infant exposures differed following societal reopening and provide a framework for future longitudinal assessment of microbiome and atopic outcomes.

Key message.

Early‐life environmental and microbial exposures are known to influence atopic disease risk, yet infants born during COVID‐19 restrictions had unexpectedly lower atopic outcomes despite reduced social exposure. This may reflect pandemic‐related changes in feeding practices, reduced antibiotic use and infection rates. In this study, the infants had broadly similar demographics to the pandemic cohort but experienced higher rates of hospitalization and antibiotic exposure, sustained changes in feeding practices, and significantly greater introduction of allergenic foods. These findings help distinguish differences in early‐life exposure profiles observed between pandemic and post‐pandemic birth cohorts and provide a framework for understanding which changes may reflect pandemic‐related disruption versus broader secular trends, offering insight to future pandemic preparedness strategies for infant and child health.

1. INTRODUCTION

The development of atopic disease is influenced by a complex interplay of genetic predisposition and environmental exposures in early life. These may either promote immune tolerance or predispose to allergic disease. ¹ , ² The 2020 CORAL study (Impact of Coronavirus Pandemic on Allergic and Autoimmune Dysregulation in Infants Born During Lockdown) examined health outcomes in infants born between March and May 2020, during the most stringent phase of the COVID‐19 public health restrictions in Ireland, a period of marked social isolation, and reduced environmental and microbial exposure. ³ The reduced social interaction, daycare attendance, travel, and exposure to diverse environmental microbes, alongside heightened hygiene practices and prolonged indoor living during lockdown had the potential to limit microbial diversity during this critical period of immune development. We had hypothesized that rates of allergic conditions would increase due to lockdown‐related social isolation and reduced microbial diversity, but that was not the case. Breastfeeding rates at 6 months were higher than previously reported in Ireland, where rates have traditionally been among the lowest in the EEA. ¹ , ⁴ Additionally, this cohort had early dietary allergen introduction advice provided by the CORAL research group. Antibiotic use, infection rates, and hospital admissions were also reduced during this period. Collectively, these factors may have created a more protective microbiome profile for the CORAL cohort.

It remained unclear whether these observations reflected transient consequences of the COVID‐19 pandemic and associated public health restrictions, or broader and potentially sustained changes in infant feeding practices, healthcare utilization, antibiotic exposure, and patterns of social mixing. With removal of pandemic restrictions, infants born in the post‐pandemic period experienced a markedly different social and healthcare environment, characterized by restoration of routine healthcare access, increased social interaction, return to normal childcare attendance, greater circulation of viral and bacterial pathogens, and consequently greater exposure to antibiotics. Distinguishing between these possibilities is important when interpreting the potential influence of these exposures on immune development, microbiome development, and later atopic outcomes.

To determine whether these observations were pandemic‐specific or were persisting following societal reopening, we established the 2025 FLORAL (Follow‐on from CORAL) birth cohort using a study design aligned with that of the original CORAL cohort. To our knowledge, this is the first prospective study to directly compare closely aligned birth cohorts recruited during and after the COVID‐19 pandemic, enabling evaluation of how early‐life exposure profiles changed following societal reopening. In this study, we describe the FLORAL cohort at 6 months of age and present an interim comparison between the CORAL and FLORAL cohorts, examining multiple early‐life immune‐relevant exposures, including feeding practices, infections, hospitalization, antibiotic exposure, healthcare utilization, childcare attendance, and immunization uptake. This comparison was designed to determine whether the early‐life exposure patterns observed in the CORAL cohort were unique to the pandemic period or reflected broader changes in infant care practices and environmental exposures following societal reopening, providing a framework for interpreting future longitudinal microbiome and atopic outcomes.

2. METHODS

FLORAL is a prospective observational birth cohort study. It recruited infants born between March and May 2025 across three Dublin maternity hospitals. Eligible participants were term infants, while exclusion criteria included preterm birth, intravenous antibiotic exposure in the first week of life, or major congenital anomalies. The inclusion and exclusion criteria were largely consistent with those of the CORAL cohort. The CORAL cohort had additionally excluded multiple births, which were permitted in FLORAL, and infants from households with PCR‐confirmed SARS‐CoV‐2 infection before birth. This exclusion criterion was not applied in FLORAL because recruitment occurred after the pandemic.

A total of 574 infants were initially enrolled in the study following parental consent. Of these, 485 parents completed the baseline enrolment questionnaire. At 6 months old, 442 participants remained in the study and completed a follow‐up questionnaire. Attendance at the in‐person 6‐month study visit was high, with 440 participants completing the visit. Recruitment, retention, and participant completion rates at 6 months are summarized in Figure 1. The primary comparison in this study was between the CORAL (2020) ³ and FLORAL (2025) birth cohorts. Differences in early‐life exposures, including feeding practices, infections, healthcare utilization, antibiotic exposure, childcare attendance, and immunization uptake, were then compared between cohorts. The analyses were intended to describe and compare early‐life exposure profiles and healthcare experiences between the CORAL and FLORAL cohorts. They were not designed to estimate independent causal effects of cohort membership on individual outcomes. The hypothesized relationships between birth cohort, baseline characteristics, and early‐life exposures are illustrated in a directed acyclic graph (Figure 2).

FIGURE 1.

Floral study recruitment, retention and completion at 6 months.

FIGURE 2.

Directed acyclic graph illustrating hypothesized relationships between birth cohort and early‐life exposures at 6 months in the CORAL and FLORAL cohorts. Environmental and social exposure includes sibling presence, childcare attendance, and contact with individuals outside the household.

The present analysis examined six‐month infant feeding practices, healthcare utilization, parent‐reported infections and medication exposures. All questionnaires were parent‐completed, either online or in paper format. The enrolment questionnaire consisted of a detailed baseline assessment designed to characterize participant demographics and early‐life exposures. Data collected included infant and family demographic characteristics, environmental exposures, and family history of atopic disease. The six‐month questionnaire captured information relating to healthcare utilization, parent‐reported infections, hospital admissions, antibiotic exposure, and immunization uptake. Infant feeding practices were assessed, including exclusive breastfeeding, exclusive formula feeding, or combination feeding, as well as the timing of introduction of solid and allergenic foods. Stool and blood samples were collected for planned microbiome and metagenomic analyses. These analyses will be reported separately.

Ethical approval was granted by the CHI Research Ethics Committee (CHI REC‐513‐24). Parents provided informed consent for study procedures and online data storage. De‐identified data were analyzed using Stata/SE 17.0 (StataCorp, College Station, TX, USA). Categorical variables were compared using chi‐squared (χ ²) tests as appropriate; continuous variables were summarized descriptively, with comparisons undertaken where appropriate. Comparisons between cohorts were unadjusted and were interpreted as descriptive rather than causal. A two‐sided p‐value of less than 0.05 was considered statistically significant. For selected outcomes within the CORAL/FLORAL cohorts, denominators differed due to incomplete questionnaire responses or in‐person visit attendance.

3. RESULTS

Demographics were broadly comparable between the CORAL (2020) and FLORAL (2025) cohorts (Table 1). Compared with national data, both cohorts had similar distributions of infant sex and ethnicity. ⁵ , ⁶ Maternal smoking was reported in 4 cases (0.8%). Household smoking exposure, defined as smoking by another member of the household, was reported in 27 cases (5.6%). In addition, 16 infants (3.3%) were exposed to passive smoking outside the home environment. Most participants resided in urban areas, with 422 infants (87%) living in urban locations and 63 (13%) living in rural areas. Pet ownership within the household was reported in 208 families (42.9%). Just over half of infants, 260 (53.6%), were born via spontaneous vaginal delivery. Both the FLORAL and CORAL cohorts had higher proportions of first‐born infants than national estimates, with rates of 52% and 45%, respectively. ⁷ Maternal educational attainment was also higher than national averages, with 95% of mothers reporting third‐level education or higher compared with approximately 62%–66% nationally. ⁸ This may limit the generalisability of the findings to the wider population.

TABLE 1.

Baseline demographic characteristics of the CORAL and FLORAL cohorts at 6 months.

	CORAL at 6 months (2020)	FLORAL at 6 months (2025)	p‐value
Male sex	193 (54.5%)	227 (46.8%)	0.03
White Irish/Other White	322 (91%)	427 (88.8%)	0.29
Maternal education; third level or higher	335 (95%)	455 (95%)	0.99
Birthweight, mean (SD), kg	3.50 (0.47)	3.48 (0.46)	0.53
Birth order			0.03 a
First born	160 (45.2%)	251 (52%)
Second born	135 (38%)	153 (32%)
Third born	42 (12%)	80 (16.5%)
Maternal allergic rhinitis	129 (36%)	206 (42.5%)	0.09
Paternal allergic rhinitis	108 (30.5%)	165 (34%)	0.30

^a p‐value for overall comparison across birth order categories.

Parent‐reported allergic rhinitis was the most commonly reported atopic condition in both cohorts, followed by asthma, atopic dermatitis, and food allergy, with a similar distribution observed among mothers and fathers. Overall, rates of parent‐reported atopic conditions were comparable between cohorts. However, maternal‐reported asthma was reported more frequently in 2025 compared with 2020 (21.9% vs. 14.4%, p = .01). Of the 233 infants with siblings, atopic dermatitis was the most commonly reported atopic condition among siblings (15%), followed by asthma (14.6%), allergic rhinitis (8.6%), and food allergy (6%). A similar pattern was observed in the CORAL cohort, where atopic dermatitis (15.4%) was also the most commonly reported sibling atopic condition, followed by asthma (12.4%) and food allergy (11.4%).

Early‐life infection exposure and healthcare utilization differed between the FLORAL and CORAL cohorts at 6 months of age. FLORAL infants had numerically higher rates of reported infections, hospitalization, and antibiotic exposure compared with the CORAL cohort (Table 2) but the difference in infection rates was not statistically significant (p = .12). Respiratory infections accounted for the majority of reported infections (n = 111), including both upper and lower respiratory tract infections. Ear, nose, and throat infections were reported in 11 infants and included cases of conjunctivitis. Skin and soft tissue infections were reported in nine infants, while eight infants experienced genitourinary infections, all of which were urinary tract infections. Four infants experienced invasive or systemic infections, including bacteraemia, viral meningitis, and varicella (routine varicella vaccination had not yet been introduced into Ireland's primary immunization schedule). Gastrointestinal infections were reported in four infants. Infant hospitalization and antibiotic exposure were higher in the FLORAL group (13.1% vs. 5.1%, p < .001; and 13.1% vs. 6.2%, p = .002, respectively). Among the 58 infants admitted to hospital, infection‐related illnesses were the most common cause of admission (n = 35).

TABLE 2.

Early‐life exposures in the CORAL and FLORAL cohorts at 6 months.

	CORAL at 6 months (2020) N = 360	FLORAL at 6 months (2025) N = 442	p‐value
2‐month vaccines received	99%	98%	0.45
4‐month vaccines received	99%	96%	0.02
6‐month vaccines received	99%	83%	<0.001
Reported infections	99 (28%) a	147 (33.3%) b	0.12
Infant hospitalization	18 (5.1%) a	58 (13.1%) b	<0.001
Antibiotic exposure by 6 months	22 (6.2%) a	58 (13.1%) b	0.002

^a CORAL denominator N = 354.

^b FLORAL denominator N = 442.

Early vaccine coverage remained high at 2 months, with similar uptake in CORAL and FLORAL infants (99% vs. 98%, p = .45). However, uptake of the 4‐month and 6‐month vaccines was lower among FLORAL infants (96% vs. 99%, p = .02 and 83% vs. 99%, p < .001, respectively; Table 2). In FLORAL, 30/442 infants (6.8%) attended out‐of‐home childcare by 6 months, compared with 15/354 infants (4.2%) in CORAL (p = .12). The lower proportion in CORAL reflects COVID‐19‐related restrictions and childcare closures during 2020.

Feeding practices during the first 6 months of life were assessed and compared between cohorts. Rates of exclusive breastfeeding were identical in both cohorts (38%). However, combined breast and formula feeding was more common in the FLORAL cohort compared with CORAL (21% vs. 15%, p = .02). Solid feeding had been established in 85% of FLORAL infants by 6 months of age, compared with 92% in the CORAL cohort (median age 5.5 months vs. 5 months, p = .002). Introduction of allergenic foods occurred significantly more frequently in the FLORAL cohort. Peanut introduction by 6 months had occurred in nearly half of FLORAL infants, compared with 14% of infants in the CORAL cohort (Table 3).

TABLE 3.

Introduction of allergenic foods at 6 months.

Allergenic food at 6 months	CORAL at 6 months (2020) N = 360	FLORAL at 6 months (2025) N = 442	p‐value
Cow's milk	166 (46%)	282 (64%)	<0.0001
Egg	95 (26%)	248 (56%)	<0.0001
Wheat	151 (42%)	208 (47%)	0.15
Peanut	49 (13.6%)	195 (44%)	<0.0001
Tree nut	12 (3.3%)	39 (8.8%)	<0.002
Fish	59 (16.4%)	129 (29%)	<0.0001

4. DISCUSSION

This prospective study used closely aligned recruitment criteria, timing, and otherwise identical methodology to compare sequential birth cohorts recruited during the 2020 pandemic restrictions and following societal re‐normalization (2023–2025). The findings suggest that not all early‐life exposures reverted uniformly following societal reopening. While infection‐related healthcare utilization and antibiotic exposure increased as expected, favorable infant feeding practices, including sustained breastfeeding and substantially earlier allergen introduction, persisted despite otherwise comparable demographic profiles. These findings may provide new insights into which early‐life exposures were likely unique to the pandemic period and which appear to represent broader changes in infant care practices that have evolved over time.

The numerically higher infection rates, hospitalization, and antibiotic exposure are unlikely to reflect a true increase in disease burden, although objective measures of infection were not assessed prospectively. Instead, they may indicate rapid normalization of environmental and healthcare influences. During the COVID‐19 pandemic, reduced social mixing, lower childcare attendance, and decreased circulation of common respiratory viruses were associated with marked reductions in pediatric infectious disease presentations and healthcare utilization, as demonstrated in population‐based studies. ⁹ Respiratory infections represented the majority of infections reported in FLORAL infants, reflecting patterns commonly observed in infancy with social mixing and childcare exposure, both of which were evident in the FLORAL cohort. These findings are consistent with previous population‐based studies demonstrating high rates of infection and antibiotic exposure during the first year of life under typical pre‐pandemic conditions. ¹⁰ Although increased social mixing and childcare attendance are plausible contributors to the higher rates of infection‐related healthcare utilization observed in FLORAL, the lower reported uptake of routine immunisations at 6 months may also have contributed. Conversely, increased intercurrent illness may itself have delayed scheduled immunisations. Vaccine uptake remained high overall in both cohorts. The divergence at 6 months is unlikely to reflect widespread vaccine hesitancy, as only a small minority of parents (9/442) provided a stated reason for non‐vaccination. Delayed immunization among a minority of infants may therefore relate more closely to intercurrent illness and healthcare access than to parental vaccine hesitancy.

In parallel, sustained higher rates of breastfeeding and earlier introduction of allergenic foods, particularly peanut and egg, were also observed in FLORAL infants, likely reflecting evolving infant feeding guidance and increased awareness among caregivers and healthcare providers. Together, these findings demonstrate that infants in the FLORAL cohort experienced a distinct profile of early‐life immune‐relevant exposures during infancy. These findings may have important implications for microbiome development and later atopic outcomes.

This study has several limitations that should be considered. As this study compared sequential birth cohorts recruited 5 years apart, some of the observed differences may also reflect broader secular/temporal changes in infant care practices, healthcare delivery, and parental behaviors that occurred over time, independent of the COVID‐19 pandemic. The analyses were unadjusted comparisons between cohorts. Although the cohorts were broadly comparable, differences in infant sex and birth order were observed, and residual confounding cannot be excluded. These findings can only be interpreted as descriptive comparisons rather than as evidence of causality. In addition, as multiple pre‐specified outcomes were compared, statistically significant findings should be interpreted with appropriate caution because some observed differences may have occurred by chance. Consequently, the relative contribution of pandemic‐related restrictions and temporal changes cannot be fully disentangled. Data on feeding practices, infections, and healthcare utilization were parent‐reported and therefore subject to recall and reporting bias. In addition, participation may reflect a cohort of more health‐engaged families, and the overrepresentation of highly educated parents and first‐time mothers may limit generalisability. Despite these limitations, the study provides a unique opportunity to compare sequential pandemic and post‐pandemic birth cohorts using consistent methodology during a critical period of immune development. Planned longitudinal follow‐up of the FLORAL cohort will determine whether these early differences, including earlier allergen introduction, high breastfeeding rates and higher antibiotic exposure, translate into altered rates of atopic disease, given their potentially opposing effects on immune development and the infant microbiome. By distinguishing birth cohorts exposed to different social and healthcare contexts following societal reopening, these longitudinal analyses may help identify which early‐life exposures are most relevant to immune development and later allergic disease.

AUTHOR CONTRIBUTIONS

Anitha Sokay: Investigation; writing – original draft; formal analysis; data curation; writing – review and editing; visualization; methodology. Maria Iatan: Investigation. Sarah Byrne: Investigation; data curation; resources. Jordan Crupper: Investigation; project administration; data curation; resources. Jay Hanoudi: Investigation. Siobhan Verdon: Investigation; data curation; resources. Madeline Dimakos: Investigation. Martin White: Investigation; writing – review and editing; supervision. Nicole Bout: Investigation. Leah Halpenny: Investigation. Naomi McCallion: Investigation; writing – review and editing; supervision. Iria Manas Miramontes: Investigation. Anna Curley: Investigation. Susan Byrne: Investigation; conceptualization; writing – review and editing; supervision. Liam O'Mahony: Writing – review and editing; supervision. Sinead Burke: Investigation; writing – review and editing. Jonathan Hourihane: Conceptualization; investigation; funding acquisition; writing – review and editing; resources; supervision; methodology.

FUNDING INFORMATION

Research Ireland Frontiers for the Future Programme (23/FFP‐A/12076) provided funding.

CONFLICT OF INTEREST STATEMENT

None declared.

Sokay A, Burke S, Iatan M, et al. Early‐life exposures in infants born during and after the COVID‐19 pandemic: A comparative prospective observational study of the CORAL and FLORAL birth cohorts. Pediatr Allergy Immunol. 2026;37:e70471. doi: 10.1111/pai.70471

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.