Impact of Maternal COVID-19 Infection on Long-Term Neonatal Outcomes in Gestational Diabetes Mellitus Pregnancies: A Cohort Study Around the Lifting of COVID-19 Restrictions in China

Impact of Maternal COVID-19 Infection on Long-Term Neonatal Outcomes in Gestational Diabetes Mellitus Pregnancies: A Cohort Study Around the Lifting of COVID-19 Restrictions in China | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Impact of Maternal COVID-19 Infection on Long-Term Neonatal Outcomes in Gestational Diabetes Mellitus Pregnancies: A Cohort Study Around the Lifting of COVID-19 Restrictions in China Ling Sun, Lixia Zhang, Chee Shin Lee, Yingying Bao, Jiajun Zhu, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7328288/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective This study aimed to delineate the long-term outcomes for neonates born to mothers with GDM who contracted COVID-19 around the lifting of COVID-19 restrictions in china. Study Design: We enrolled 288 neonates born to GDM mothers who were admitted to the neonatal intensive care unit (NICU) between November 1, 2022, and January 31, 2023. The exposure was a positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in GDM mothers. Neonates were followed up for 12 months, with long-term outcomes including infant anthropometrics measures, hospital readmission, and subsequent SARS-CoV-2 infection. Associations between maternal COVID-19 status and infant outcomes were assessed using multivariable logistic regression. Results Neonates born to GDM mothers who had COVID-19 required increased respiratory support (1.6% vs. 6.3%; P = 0.031) and experienced higher rates of neonatal dysglycemia (14.1% vs. 24.0%; P = 0.037), while the incidence of neonatal infection decreased (11.5% vs. 24.0%; P = 0.012). There was a significant association between maternal SARS-CoV-2 positivity and two distinct outcomes in infants: an increased risk of hospital readmission (odds ratio [OR] 1.75; 95% confidence interval [CI] 1.01–3.04) and a reduced risk of subsequent SARS-CoV-2 infection during the follow-up period (OR 0.26; 95% CI 0.15–0.46). Conclusions Around the lifting of COVID-19 restrictions, maternal SARS-CoV-2 infection was associated with an increased risk of neonatal rehospitalization and a reduced risk of subsequent SARS-CoV-2 infection in infants during the 12-month follow-up. Intensive care for newborns of GDM mothers with COVID-19 is essential to minimize the risk of rehospitalization. COVID-19 Infant Outcomes Rehospitalization Gestational Diabetes Mellitus Figures Figure 1 Introduction The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019 has led to a global pandemic, resulting in coronavirus disease 2019 (COVID-19), a potentially fatal illness. This pandemic has affected individuals of all ages and has been shown to have a significant impact on the health of pregnant women and newborns with increased neonatal mortality rates 1 .Although severe SARS-CoV-2 infections are uncommon in children, maternal SARS-CoV-2 infection around the time of delivery has been associated with adverse neonatal outcomes, including preterm birth 2 , neonatal infection 3 – 5 , and an increased need for neonatal intensive care unit (NICU) admission 6 , 7 . Notably, Norman et al. 8 reported higher rates of respiratory distress syndrome and the need for continuous positive airway pressure among neonates born to mothers who tested positive for SARS-CoV-2 compared to those who were not. Gestational diabetes mellitus (GDM) is a common pregnancy complication that affects approximately 14% of pregnant women 9 , with significant implications for both maternal and fetal health in the short and long term 10 . GDM is associated with various adverse outcomes, such as preterm birth, birth trauma, increased birthweight, macrosomia, neonatal hypoglycemia, hyperbilirubinemia, shoulder dystocia, and neonatal respiratory distress syndrome 11 , 12 . As reported, the prevalence of GDM increased during the COVID-19 pandemic 13 , 14 . Perhaps there is a potential "bidirectional influence" between metabolic disorders (such as insulin resistance and hyperglycemia) in the GDM subgroup and the pathological mechanism of COVID-19. For this large and high-risk subgroup, there is currently a lack of individualized prevention and control strategies for them after infection, especially for their offspring. The management of such high-risk groups in the NICU is complex and lacks clear policies. To address this gap and provide a more robust evidence base for clinical practice, we conducted a longitudinal cohort study focusing on this high-risk population to investigate the hypothesis that SARS-CoV-2 infection in mothers with GDM may be associated with adverse neonatal outcomes. Specifically, we aimed to evaluate the impact of COVID-19 on neonatal outcomes in GDM population, with a particular emphasis on long-term outcomes. Methods Study design and participants This study was a prospective longitudinal cohort study conducted at the Women’s Hospital, School of Medicine, Zhejiang University. Neonates born to GDM mothers who were admitted to the NICU between November 1, 2022, and January 31, 2023 were included, this period coincided with the COVID-19 restriction-lifting phase. Neonates delivered to mothers who had a positive SARS-CoV-2 test during pregnancy were compared with two randomly selected NICU neonates whose mothers tested negative, matched on gestational age and birth weight. Neonates with major congenital anomalies were excluded from this study. The sample size was determined using the Power Analysis and Sample Size Software. The primary exposure of interest was a positive SARS-CoV-2 test in mothers from the third trimester of pregnancy to delivery. During the study period, SARS-CoV-2 testing was only performed on pregnant women who were admitted to the hospital with symptoms of COVID-19. Follow-up assessments were conducted by trained medical staff via telephone, and infants whose guardians declined to participate or who were lost to follow-up were excluded from the study. Data collection Baseline demographic and clinical characteristics were collected at recruitment. Maternal and neonatal data were all extracted from electronic medical records and systematically collected by trained researchers. Maternal factors documented included age, educational level, pregnancy comorbidities, and antimicrobial use. Neonatal data included gestational age, birth weight, sex, mode of delivery, birth asphyxia, low birth weight, respiratory disorders (respiratory distress syndrome, transient tachypnea of the newborn, and meconium aspiration syndrome), respiratory support requirements, resuscitation status, neonatal infection (sepsis), hyperbilirubinemia, hypoglycemia, electrolyte disorders (hypernatremia, hyponatremia, hypercalcemia, hypocalcemia, hyperkalemia, hypokalemia), and length of NICU stay. Outcomes The primary outcomes of interest were evaluated at 12 months of follow-up and included long-term outcomes such as offspring anthropometrics, readmission rates, and the incidence of COVID-19 infection. At 12 months of age, anthropometric measurements were meticulously performed by primary child healthcare physicians following standardized protocols. Weight-for-age, length-for-age, and weight-for-length z-scores (premature infants were calculated according to the corrected gestational age) at 12 months were calculated based on the World Health Organization Child Growth Standards 15 . Follow-up consultations with patient post-discharge including COVID-19 status, medical history, anthropometric measurements, readmission occurrences, and subsequent SARS-CoV-2 infection. COVID-19 testing is performed only when the infant develops symptoms of SARS-CoV-2 infection. A positive SARS-CoV-2 test result was defined by the presence of at least one positive finding from a nasopharyngeal swab specimen, identified through a polymerase chain reaction (PCR)-based assay or by detecting SARS-CoV-2 antigens or antibodies. Infant SARS-CoV-2 infection was identified by the detection of viral RNA through PCR testing or antigen testing of nasopharyngeal, oropharyngeal, or rectal swabs (The definitions of the relevant variables in the study are explained in the supplementary materials.). Statistical analysis Continuous variables are expressed as mean ± standard deviation or, when appropriate, as medians with interquartile ranges. Differences in normally distributed continuous variables between groups were evaluated using the independent samples t-test, while the Mann-Whitney U-test was applied for non-normally distributed variables. Categorical data are presented as frequencies and percentages, with comparisons using the chi-square test. Logistic regression analysis was conducted to determine the associations between maternal COVID-19 and infant outcomes, including readmission and COVID-19 infection. For each outcome, two logistic regression models were formulated and variable selection for the multivariable model was based on previous results and clinical plausibility to avoid overfitting in the model. Model 1 and Model 2 were constructed to sequentially assess the incremental contribution of key variables, with the goal of isolating the independent effect of maternal COVID-19. Statistical significance was defined as a two-sided p-value of less than 0.05. All statistical analyses were performed using IBM SPSS Statistics for Windows, version 26.0 (IBM Corp., Armonk, NY, USA). Results Baseline characteristics of participants During the study period, a total of 296 infants born to mothers with GDM were admitted to the NICU (because of neonatal diseases), among them, 193 mothers were not infected with COVID-19, and one infant was excluded due to a congenital malformation, 103 mothers were infected with COVID-19, but 7 infants were lost to follow-up. The final analysis included 288 patients who completed the 12-month follow-up (Figure). Of these 288 newborns, 96 (33.3%) had mothers with GDM who contracted COVID-19, while 192 (66.7%) were born to GDM mothers without COVID-19. The demographic and clinical characteristics of the 288 included patients were shown in Table 1 . Of these 288 newborns, 23 (8%) infants had a gestational age of less than 32 weeks and a birth weight of less than 1,500 g. The reasons for larger gestational age newborns to be admitted to the NICU include jaundice, hypoglycemia, sepsis, etc. There’s no significant difference in maternal age, educational level, pregnancy comorbidities, antimicrobial use, gestational age, birth weight, sex, or mode of delivery between mothers with and without COVID-19. Table 1 Demographic characteristics of the study population (n = 288). Characteristics All subjects (n = 288) Mothers with COVID-19(n = 96) Mothers without COVID-19(n = 192) P-value Maternal age, mean (SD), y 32.1(4.5) 32.0(4.1) 32.1(4.7) 0.889 Maternal educational, n (%) 0.436 ≥ some college or above 183(63.5) 64(66.7) 119(62.0) < some college or below 105(36.5) 32(33.3) 73(38.0) Pregnancy comorbidities, n (%) 162(56.3) 47(49.0) 115(59.9) 0.102 Antibiotic treatment before delivery, n (%) 238(82.6) 84(87.5) 154(80.2) 0.124 Gestational age, mean (SD), weeks 37.3(2.6) 37.1(2.9) 37.4(2.4) 0.368 Birth weight, mean (SD) , g 2933.1(681.5) 2915.8(731.1) 2941.7(657.1) 0.762 Preterm birth, n (%) 106(36.8) 30(31.3) 76(39.6) 0.167 Neonatal sex 0.671 Male, n (%) 173(60.1) 56(58.3) 117(60.9) Female, n (%) 115(39.9) 40(41.7) 75(39.1) Cesarean section, n (%) 181(62.8) 67(69.8) 114(59.4) 0.085 Low birth weight, n (%) 64(22.2) 21(21.9) 43(22.4) 0.920 Birth asphyxia, n (%) 9(3.1) 2(2.1) 7(3.6) 0.719 Receipt of any resuscitation, n (%) 74(25.7) 25(26.0) 49(25.5) 0.924 Respiratory disorders, n (%) 109(37.8) 40(41.7) 69(35.9) 0.345 Respiratory support, n (%) 9(3.1) 6(6.3) 3(1.6) 0.031 Oxygen use, mean (SD) , d 0.55(3.6) 1.0(4.7) 0.30(2.8) 0.163 Sepsis, n (%) 57(19.8) 11(11.5) 46(24.0) 0.012 Anaemia, n (%) 35(12.2) 13(13.5) 22(11.5) 0.610 Hyperbilirubinemia, n (%) 79(27.4) 24(25.0) 55(28.6) 0.513 Hypoglycemia, n (%) 50(17.4) 23(24.0) 27(14.1) 0.037 Neonatal Electrolyte disorders, n (%) 25(8.7) 9(9.4) 16(8.3) 0.767 Length of stay, mean (SD) , d 7.2(10.3) 8.8(12.8) 6.4(8.6) 0.105 During hospitalization, infants born to GDM mothers with COVID-19 were more likely to require respiratory support (1.6% vs. 6.3%; P = 0.031) and experience neonatal hypoglycemia (14.1% vs. 24.0%; P = 0.037) compared to those born to GDM mothers without COVID-19. Conversely, there was a reduced incidence of sepsis (24.0% vs. 11.5%; P = 0.012) among infants born to mothers with COVID-19. Other characteristics were similar between the two groups, as shown in Table 1 . Incidence of offspring outcomes during 12-month follow-up among women with and without COVID-19 Over the course of the 12-month follow-up, the clinical characteristics of the 288 infants were tracked, and the results are presented in Table 2 . Notably, nearly a third (29.5%) of the offspring experienced at least one re-hospitalization within the first year. Although not statistically significant, infants born to mothers with COVID-19 tended to have higher rates of re-hospitalization at the 6-month mark (27.2% vs 18.8%; P = 0.094). However, univariate analysis revealed a significant difference in hospital readmission rates between the two groups over the entire follow-up period (37.5% vs 25.5%; P = 0.036). During the first postnatal year, almost half (49.2%) of the infants tested positive for SARS-CoV-2 at some point. Interestingly, infants born to mothers with COVID-19 exhibited a significantly lower incidence of SARS-CoV-2 positivity during their first 12 months, with univariate analysis revealing a rate of 27.1% in these infants, compared to 62.0% in those not exposed to maternal COVID-19 (P < 0.001), as detailed in Table 2 . At the end of the follow-up period, there were no significant differences in offspring weight or corresponding z-scores for weight-for-age, length-for-age, and weight-for-length between the two groups. Table 2 Follow-up data of neonates in the first 12 months after hospital discharge. Outcomes All subjects (n = 288) Mothers with COVID-19(n = 96) Mothers without COVID-19(n = 192) P-value Rehospitalizations in 6 months, n (%) 64(21.7) 28 (27.2) 36(18.8) 0.094 SARS- CoV-2 positive in 6 months, n (%) 118(40.0) 26 (25.2) 92(47.9) < 0.001 Rehospitalizations in 12 months, n (%) 85(28.8) 36(37.5) 49(25.5) 0.036 SARS- CoV-2 positive in 12 months, n (%) 145(49.2) 26(27.1) 119(62.0) < 0.001 Height at 12 months, mean (SD), cm 75.8(3.4) 76.0(3.9) 75.7(3.1) 0.551 Weight at 12 months, mean(SD), kg 10.0(1.3) 10.2(1.7) 10.2(1.7) 0.119 Weight-for- age z score at 12 months, mean(SD) 0.51(1.0) 0.65(1.2) 0.44(0.93) 0.114 Length-for-age z score at 12 months, mean(SD) 0.28(1.4) 0.37(1.6) 0.24(1.3) 0.480 Weight-for-length z score at 12 months, mean(SD) 0.46(1.0) 0.50(1.0) 0.43 (1.1) 0.620 Association between COVID-19 and offspring outcomes during 12-month follow-up Among the 288 patients who completed the 12-month follow-up, a significant association was observed between GDM mothers with COVID-19 and certain offspring outcomes, specifically hospital readmission and SARS-CoV-2 positivity. Infants born to mothers with COVID-19 at higher risk of infant re-hospitalization during their first 12 months. After adjusting for potential confounders in the multivariate analysis, this association remained significant, with an odds ratio of 1 .75 (95% CI 1.01–3.04, P = 0.047), as detailed in Table 3 . Table 3 Associations between maternal COVID-19 and neonatal outcomes. Outcomes Crude Model Model 1 Model 2 OR(95%CI) P-values aORs(95%CI) P-values aORs(95%CI) P-values 6-month Rehospitalizations 1.62(0.92–2.85) 0.094 0.55(0.30–1.01) 0.055 1.77(0.96–3.26) 0.068 SARS-CoV-2 positive 0.37(0.22–0.62) 0.000 0.43(0.24–0.75) 0.003 0.43(0.24–0.76) 0.004 12-month Rehospitalizations 1.75(1.04–2.96) 0.036 1.84(1.06–3.19) 0.029 1.75(1.01–3.04) 0.047 SARS-CoV-2 positive 0.23(0.13–0.39) 0.000 0.26(0.15–0.45) < 0.001 0.26(0.15–0.46) < 0.001 Model 1 of infant rehospitalizations adjusted for maternal age, educational level, pregnancy comorbidity, cesarean section, preterm birth, low birth weight. Model 2 was further adjusted for respiratory disorders, and infectious diseases based on adjustment Model 1. Model 1 of infant SARS-CoV-2 positive adjusted for maternal age, educational level, pregnancy comorbidity, antimicrobials use, infant infectious diseases and length of stay. Model 2 was further adjusted for neonate gestational age and birth weight based on adjustment Model 1. GDM mothers with COVID-19 also had a reduced risk of their infants developing subsequent SARS-CoV-2 infection over the 12-month follow up period. Even after adjusting for potential confounders, multivariate analysis confirmed that having a mother with COVID-19 was associated with a significantly lower risk of subsequent SARS-CoV-2 infection in their infants (OR 0.26; 95% CI 0.15–0.46, P < 0.001), as further described in Table 3 . Discussion This study indicated that GDM mothers with COVID-19 was associated with an increased risk of hospital readmission for infants within the first 12 months of life. In addition, we found an unexpected correlation between GDM mothers with COVID-19 and a reduced risk for subsequent SARS-CoV-2 infection in their infants during the 12-month follow-up period. These findings raise substantial concerns about the potential effects of COVID-19 on the health of infants born to GDM mothers around the lifting of COVID-19 restrictions. The COVID-19 pandemic poses a serious threat to neonatal health. In our cohort, the need for respiratory support increased, which was consistent with the findings reported by Norman 8 . Similarly, Angelidou's study 16 noted an increase in adverse neonatal health outcomes, including the need for respiratory support, among newborns born to mothers with COVID-19. However, Shah et al. 17 found no statistically significant difference in respiratory support requirements between infants delivered by test-positive and non-test-positive women. Furthermore, we identified an increased risk of neonatal dysglycemia in neonates born to GDM mothers with COVID-19, suggesting that maternal COVID-19 infection may exacerbate glucose metabolism disorders. Interestingly, there was a reduced incidence of infectious diseases among infants born to SARS-CoV-2 positive mothers. Shah et al. 17 also reported no statistically significant difference in late-onset sepsis among neonates born to mothers with or without COVID-19 infection during pregnancy. We hypothesize that maternal COVID-19 infection during pregnancy may stimulate the maternal immune system, potentially conferring fetal protection against infection through maternal antibodies. This proposed protective mechanism, if validated, could inform targeted strategies to enhance neonatal immunity against COVID-19 and shed light on broader maternal-fetal immune crosstalk in infectious disease contexts. In contrast to Angelidou’s 16 finding that only 14.3% of neonates were re-hospitalized within the first 30 days post-discharge from mothers with confirmed SARS-CoV-2 infection, our study documented significantly higher re-hospitalization rates of 27.2% at 6 months and 37.5% at 12 months. This discrepancy may be attributed to differences in follow-up duration and the fact that our study focused on newborns of GDM mothers admitted to the NICU, suggesting that these infants might be more susceptible to illness. Most studies have tested SARS-CoV-2 in neonates during their hospital stay, reporting low positivity rates, with positive test results more likely to occur in infants born to mothers with symptomatic COVID-19 16 . The positivity rate among neonates born to mothers with positive SARS-CoV-2 tests varied significantly, ranging from 3.1–9.1% 16 . Even larger cohorts from New York City reported no positive newborn test results, despite high rates of rooming-in and direct breastfeeding practices 18 – 20 . Few previous studies have extended their assessment of neonatal outcomes beyond the initial birth hospitalization. In the US-based Pregnancy Coronavirus Outcomes Registry (PRIORITY) study 21 , no re-hospitalizations and only two positive SARS-CoV-2 test results were reported during the follow-up period of 6 to 8 weeks of age. In contrast, our study provided a longer follow-up period of 12 months, during which we found a significant lower incidence of infant SARS-CoV-2 infection in the group of GDM mothers with COVID-19 (27.1% vs. 62.0%; P < 0.001). We posit that maternal antibodies, capable of crossing the maternal-fetal interface to provide passive immunity, along with breastfeeding, may contribute to this reduced risk of infection 22 . Such observations not only illuminate the intricate interplay between maternal metabolic status, infectious exposure, and neonatal immune protection but also offer critical insights for designing maternal-infant health strategies that leverage natural immune transfer mechanisms to mitigate infectious risks in vulnerable populations. This cohort study adds knowledge on long-term outcomes of neonates admitted to NICU after exposure to GDM mothers with SARS-CoV-2 positive. Results from this study provide valuable insights into health management of GDM mothers during pregnancy with COVID-19 infection, both in research and clinical application. Our study included a broader range of outcomes, but it was not comprehensive, and the number of included infants was limited. Further prospective, longitudinal studies are needed to better understand the clinical outcomes of children exposed to SARS-CoV-2 in utero and in the early postnatal life. Our study possesses several noteworthy strengths. First and foremost, our cohort study focuses on a unique population of infants admitted to a tertiary NICU who were exposed to COVID-19 in utero through their mothers with GDM around the lifting of COVID-19 restrictions in China. This allowed us to assess the relationship between maternal COVID-19 infection in the late stages of pregnancy and the long-term outcomes of the infants. This distinct focus not only fills a critical gap in understanding how maternal comorbidities modulate in utero pathogen exposure during periods of public health transition but also carries implications for tailoring post-pandemic care strategies for high-risk mother-infant dyads. Second, our follow-up period was extended beyond the initial newborn discharge, spanning up to 12 months post-birth, enabling us to capture a more comprehensive picture of infant outcomes. Third, we also discussed a wide range of infant outcomes associated with SARS-CoV-2 and tracked the COVID-19 infection rate of infants during their first 12 months of life. A recent study 23 on GDM and COVID-19 was limited to perinatal neonatal outcomes, neglecting to address long-term consequences for infants. Carrasco Colom 24 noted that the majority of infants born to mothers with SARS-CoV-2 infection during pregnancy appear healthy, exhibiting normal cranial ultrasound findings, no hearing loss, and normal neurodevelopment through the first year of life. Similarly, Shuffrey et al. 25 observed no statistically significant differences in neurodevelopmental outcomes at 6 months of age, as measured by the Ages and Stages Questionnaire-3, between neonates born to mothers with SARS-CoV-2 infection and those born to uninfected mothers. While these findings are promising, further comprehensive studies are needed to fully understand the potential long-term effects of maternal COVID-19 infection on infant health and development. While our study provides valuable insights into the outcomes of neonates exposed to SARS-CoV-2 in utero, it is not without its limitations. First, some mothers may have had asymptomatic COVID-19 but were not tested for SARS-CoV-2, as our study commenced around the relaxation of COVID-19 lockdown policies. This could potentially dilute any differences in outcomes between groups, a concern also noted by Shah et al. 17 , who noted that including asymptomatic COVID-19 cases in their matched cohort could have influence the observed group differences in outcomes. Second, the single-center nature of our study limits the generalizability of our findings, given the smaller sample size and potentially variable outcome rates. Third, we regret that anthropometric data for the offspring at the 6-month mark were not available for inclusion in our analysis. Conclusions In conclusion, our study highlights the potential impact of COVID-19 on infants born to GDM mothers, demonstrating a statistically significant association between short- and long-term outcomes of neonates admitted to NICU and their in-utero exposure to SARS-CoV-2. These findings highlight the need for enhanced vigilance and tailored management strategies for neonates born to GDM mothers exposed to SARS-CoV-2. To fully elucidate the effects of COVID-19 on these infants and refine clinical guidance, further research with extended follow-up periods and larger, more diverse cohorts is imperative. Such studies will be instrumental in establishing evidence-based practices for the care of GDM mothers and their infants in the context of ongoing and future pandemics. Declarations Acknowledgements We thank the mothers, newborns and their families who participated in the study; staff and providers in labour and delivery, postpartum unit, NICU, pathology and laboratory services, at the Women’s Hospital, School of Medicine, Zhejiang University. Authors’contributions Ling Sun wrote the first draft of the article. Lixia Zhang carried out a critical revision of the manuscript for important intellectual content. Ling Sun and Lixia Zhang carried out the data curation and analyses. Zhaoxia Liang and Jiajun Zhu as guarantor accepts full responsibility for the conduct of the study, had access to the data, and controlled the decision to publish. Zhaoxia Liang, Jiajun Zhu and Yingying Bao have accessed and verified the data underlying the study. Chee Shin Lee performed language editing and proofreading of the manuscript. Yingying Bao reviewed and refined the language of the manuscript for clarity and accuracy. All authors edited and approved the final version of the article. Data availability statement The data that support the findings of this study are not publicly available due to privacy reasons but are available from the corresponding author upon request. Ethics approval and consent to participate: The research was conducted in accordance with the Declaration of Helsinki and was approved by the research ethics board of Women’s Hospital, School of Medicine, Zhejiang University (NO. IRB-20240166-R) and written informed consent was obtained from the parents of all the infants that participated in the study. Consent for publication: not applicable. Funding/support: This study was not specically founded by any source. Declaration of Interest statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. 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Infant Outcomes Following Maternal Infection With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): First Report From the Pregnancy Coronavirus Outcomes Registry (PRIORITY) Study. Clin Infect Dis. 2021;73(9):e2810–3. 10.1093/cid/ciaa1411 . Fich L, Christiansen AMH, Nilsson AC, et al. SARS-CoV-2 Antibodies in Breastmilk Three and Six Months Postpartum in Relation to the Trimester of Maternal SARS-CoV-2 Infection-An Exploratory Study. Int J Mol Sci. 2024;25(6):3269. 10.3390/ijms25063269 . Kleinwechter HJ, Weber KS, Mingers N, et al. Gestational diabetes mellitus and COVID-19: results from the COVID-19-Related Obstetric and Neonatal Outcome Study (CRONOS). Am J Obstet Gynecol. 2022;227(4):631. .e1-631.e19. Carrasco Colom J, Manzanares Á, Álvaro Gómez A, et al. Clinical outcomes and antibody transfer in a cohort of infants with in utero or perinatal exposure to SARS-CoV-2 (Coronascope Study). Eur J Pediatr. 2023;182(10):4647–54. 10.1007/s00431-023-05147-1 . Shuffrey LC, Firestein MR, Kyle MH, et al. Association of Birth During the COVID-19 Pandemic With Neurodevelopmental Status at 6 Months in Infants With and Without In Utero Exposure to Maternal SARS-CoV-2 Infection. JAMA Pediatr. 2022;176(6):e215563. 10.1001/jamapediatrics.2021.5563 . Additional Declarations No competing interests reported. Supplementary Files Supplementarymaterial.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7328288","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":526482477,"identity":"eca891a4-8f0c-4364-948c-2815268dfeb8","order_by":0,"name":"Ling Sun","email":"","orcid":"","institution":"Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Ling","middleName":"","lastName":"Sun","suffix":""},{"id":526482478,"identity":"bf04831b-3124-4645-ac75-0f9d8d1d833c","order_by":1,"name":"Lixia Zhang","email":"","orcid":"","institution":"Zhejiang University School of 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1","display":"","copyAsset":false,"role":"figure","size":170084,"visible":true,"origin":"","legend":"\u003cp\u003eFlow diagram of the study.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7328288/v1/49af541a7f14d95fa8c52133.jpeg"},{"id":94116450,"identity":"d5e83563-8a73-48d9-b927-47de4abf4d31","added_by":"auto","created_at":"2025-10-22 14:31:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1039180,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7328288/v1/532572a7-4963-4975-a1f1-7ee185233749.pdf"},{"id":93251735,"identity":"b67cf86d-1272-4aa5-b9bc-d355df6181b1","added_by":"auto","created_at":"2025-10-10 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This pandemic has affected individuals of all ages and has been shown to have a significant impact on the health of pregnant women and newborns with increased neonatal mortality rates \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e.Although severe SARS-CoV-2 infections are uncommon in children, maternal SARS-CoV-2 infection around the time of delivery has been associated with adverse neonatal outcomes, including preterm birth\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e, neonatal infection\u003csup\u003e\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e, and an increased need for neonatal intensive care unit (NICU) admission \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Notably, Norman et al. \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e reported higher rates of respiratory distress syndrome and the need for continuous positive airway pressure among neonates born to mothers who tested positive for SARS-CoV-2 compared to those who were not.\u003c/p\u003e\u003cp\u003eGestational diabetes mellitus (GDM) is a common pregnancy complication that affects approximately 14% of pregnant women \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e, with significant implications for both maternal and fetal health in the short and long term \u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. GDM is associated with various adverse outcomes, such as preterm birth, birth trauma, increased birthweight, macrosomia, neonatal hypoglycemia, hyperbilirubinemia, shoulder dystocia, and neonatal respiratory distress syndrome \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. As reported, the prevalence of GDM increased during the COVID-19 pandemic \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Perhaps there is a potential \"bidirectional influence\" between metabolic disorders (such as insulin resistance and hyperglycemia) in the GDM subgroup and the pathological mechanism of COVID-19. For this large and high-risk subgroup, there is currently a lack of individualized prevention and control strategies for them after infection, especially for their offspring. The management of such high-risk groups in the NICU is complex and lacks clear policies.\u003c/p\u003e\u003cp\u003eTo address this gap and provide a more robust evidence base for clinical practice, we conducted a longitudinal cohort study focusing on this high-risk population to investigate the hypothesis that SARS-CoV-2 infection in mothers with GDM may be associated with adverse neonatal outcomes. Specifically, we aimed to evaluate the impact of COVID-19 on neonatal outcomes in GDM population, with a particular emphasis on long-term outcomes.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eStudy design and participants\u003c/p\u003e\u003cp\u003eThis study was a prospective longitudinal cohort study conducted at the Women\u0026rsquo;s Hospital, School of Medicine, Zhejiang University. Neonates born to GDM mothers who were admitted to the NICU between November 1, 2022, and January 31, 2023 were included, this period coincided with the COVID-19 restriction-lifting phase. Neonates delivered to mothers who had a positive SARS-CoV-2 test during pregnancy were compared with two randomly selected NICU neonates whose mothers tested negative, matched on gestational age and birth weight. Neonates with major congenital anomalies were excluded from this study. The sample size was determined using the Power Analysis and Sample Size Software. The primary exposure of interest was a positive SARS-CoV-2 test in mothers from the third trimester of pregnancy to delivery. During the study period, SARS-CoV-2 testing was only performed on pregnant women who were admitted to the hospital with symptoms of COVID-19. Follow-up assessments were conducted by trained medical staff via telephone, and infants whose guardians declined to participate or who were lost to follow-up were excluded from the study.\u003c/p\u003e\u003cp\u003eData collection\u003c/p\u003e\u003cp\u003eBaseline demographic and clinical characteristics were collected at recruitment. Maternal and neonatal data were all extracted from electronic medical records and systematically collected by trained researchers. Maternal factors documented included age, educational level, pregnancy comorbidities, and antimicrobial use. Neonatal data included gestational age, birth weight, sex, mode of delivery, birth asphyxia, low birth weight, respiratory disorders (respiratory distress syndrome, transient tachypnea of the newborn, and meconium aspiration syndrome), respiratory support requirements, resuscitation status, neonatal infection (sepsis), hyperbilirubinemia, hypoglycemia, electrolyte disorders (hypernatremia, hyponatremia, hypercalcemia, hypocalcemia, hyperkalemia, hypokalemia), and length of NICU stay.\u003c/p\u003e\u003cp\u003eOutcomes\u003c/p\u003e\u003cp\u003eThe primary outcomes of interest were evaluated at 12 months of follow-up and included long-term outcomes such as offspring anthropometrics, readmission rates, and the incidence of COVID-19 infection. At 12 months of age, anthropometric measurements were meticulously performed by primary child healthcare physicians following standardized protocols. Weight-for-age, length-for-age, and weight-for-length z-scores (premature infants were calculated according to the corrected gestational age) at 12 months were calculated based on the World Health Organization Child Growth Standards \u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Follow-up consultations with patient post-discharge including COVID-19 status, medical history, anthropometric measurements, readmission occurrences, and subsequent SARS-CoV-2 infection. COVID-19 testing is performed only when the infant develops symptoms of SARS-CoV-2 infection. A positive SARS-CoV-2 test result was defined by the presence of at least one positive finding from a nasopharyngeal swab specimen, identified through a polymerase chain reaction (PCR)-based assay or by detecting SARS-CoV-2 antigens or antibodies. Infant SARS-CoV-2 infection was identified by the detection of viral RNA through PCR testing or antigen testing of nasopharyngeal, oropharyngeal, or rectal swabs (The definitions of the relevant variables in the study are explained in the supplementary materials.).\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eContinuous variables are expressed as mean \u0026plusmn; standard deviation or, when appropriate, as medians with interquartile ranges. Differences in normally distributed continuous variables between groups were evaluated using the independent samples t-test, while the Mann-Whitney U-test was applied for non-normally distributed variables. Categorical data are presented as frequencies and percentages, with comparisons using the chi-square test. Logistic regression analysis was conducted to determine the associations between maternal COVID-19 and infant outcomes, including readmission and COVID-19 infection. For each outcome, two logistic regression models were formulated and variable selection for the multivariable model was based on previous results and clinical plausibility to avoid overfitting in the model. Model 1 and Model 2 were constructed to sequentially assess the incremental contribution of key variables, with the goal of isolating the independent effect of maternal COVID-19. Statistical significance was defined as a two-sided p-value of less than 0.05. All statistical analyses were performed using IBM SPSS Statistics for Windows, version 26.0 (IBM Corp., Armonk, NY, USA).\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003eBaseline characteristics of participants\u003c/h2\u003e\u003cp\u003eDuring the study period, a total of 296 infants born to mothers with GDM were admitted to the NICU (because of neonatal diseases), among them, 193 mothers were not infected with COVID-19, and one infant was excluded due to a congenital malformation, 103 mothers were infected with COVID-19, but 7 infants were lost to follow-up. The final analysis included 288 patients who completed the 12-month follow-up (Figure). Of these 288 newborns, 96 (33.3%) had mothers with GDM who contracted COVID-19, while 192 (66.7%) were born to GDM mothers without COVID-19. The demographic and clinical characteristics of the 288 included patients were shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Of these 288 newborns, 23 (8%) infants had a gestational age of less than 32 weeks and a birth weight of less than 1,500 g. The reasons for larger gestational age newborns to be admitted to the NICU include jaundice, hypoglycemia, sepsis, etc. There\u0026rsquo;s no significant difference in maternal age, educational level, pregnancy comorbidities, antimicrobial use, gestational age, birth weight, sex, or mode of delivery between mothers with and without COVID-19.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic characteristics of the study population (n\u0026thinsp;=\u0026thinsp;288).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAll subjects (n\u0026thinsp;=\u0026thinsp;288)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMothers with COVID-19(n\u0026thinsp;=\u0026thinsp;96)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMothers without COVID-19(n\u0026thinsp;=\u0026thinsp;192)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMaternal age, mean (SD), y\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e32.1(4.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e32.0(4.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e32.1(4.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.889\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMaternal educational, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.436\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ge; some college or above\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e183(63.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e64(66.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e119(62.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt; some college or below\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e105(36.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e32(33.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e73(38.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePregnancy comorbidities, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e162(56.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e47(49.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e115(59.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.102\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAntibiotic treatment before delivery, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e238(82.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e84(87.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e154(80.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.124\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGestational age, mean (SD), weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e37.3(2.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e37.1(2.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e37.4(2.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.368\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBirth weight, mean (SD) , g\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2933.1(681.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2915.8(731.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2941.7(657.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.762\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePreterm birth, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e106(36.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e30(31.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e76(39.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.167\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeonatal sex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.671\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e173(60.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e56(58.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e117(60.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e115(39.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e40(41.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e75(39.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCesarean section, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e181(62.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e67(69.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e114(59.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.085\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLow birth weight, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e64(22.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e21(21.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e43(22.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.920\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBirth asphyxia, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e9(3.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2(2.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e7(3.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.719\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReceipt of any resuscitation, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e74(25.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e25(26.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e49(25.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.924\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRespiratory disorders, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e109(37.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e40(41.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e69(35.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.345\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRespiratory support, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e9(3.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6(6.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3(1.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.031\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOxygen use, mean (SD) , d\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.55(3.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.0(4.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.30(2.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.163\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSepsis, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e57(19.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e11(11.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e46(24.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.012\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnaemia, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e35(12.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e13(13.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e22(11.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.610\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHyperbilirubinemia, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e79(27.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e24(25.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e55(28.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.513\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypoglycemia, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e50(17.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e23(24.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e27(14.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.037\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeonatal Electrolyte disorders, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e25(8.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e9(9.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e16(8.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.767\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLength of stay, mean (SD) , d\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e7.2(10.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e8.8(12.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e6.4(8.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.105\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eDuring hospitalization, infants born to GDM mothers with COVID-19 were more likely to require respiratory support (1.6% vs. 6.3%; P\u0026thinsp;=\u0026thinsp;0.031) and experience neonatal hypoglycemia (14.1% vs. 24.0%; P\u0026thinsp;=\u0026thinsp;0.037) compared to those born to GDM mothers without COVID-19. Conversely, there was a reduced incidence of sepsis (24.0% vs. 11.5%; P\u0026thinsp;=\u0026thinsp;0.012) among infants born to mothers with COVID-19. Other characteristics were similar between the two groups, as shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eIncidence of offspring outcomes during 12-month follow-up among women with and without COVID-19\u003c/h3\u003e\n\u003cp\u003eOver the course of the 12-month follow-up, the clinical characteristics of the 288 infants were tracked, and the results are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Notably, nearly a third (29.5%) of the offspring experienced at least one re-hospitalization within the first year. Although not statistically significant, infants born to mothers with COVID-19 tended to have higher rates of re-hospitalization at the 6-month mark (27.2% vs 18.8%; P\u0026thinsp;=\u0026thinsp;0.094). However, univariate analysis revealed a significant difference in hospital readmission rates between the two groups over the entire follow-up period (37.5% vs 25.5%; P\u0026thinsp;=\u0026thinsp;0.036). During the first postnatal year, almost half (49.2%) of the infants tested positive for SARS-CoV-2 at some point. Interestingly, infants born to mothers with COVID-19 exhibited a significantly lower incidence of SARS-CoV-2 positivity during their first 12 months, with univariate analysis revealing a rate of 27.1% in these infants, compared to 62.0% in those not exposed to maternal COVID-19 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), as detailed in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. At the end of the follow-up period, there were no significant differences in offspring weight or corresponding z-scores for weight-for-age, length-for-age, and weight-for-length between the two groups.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eFollow-up data of neonates in the first 12 months after hospital discharge.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOutcomes\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAll subjects (n\u0026thinsp;=\u0026thinsp;288)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMothers with COVID-19(n\u0026thinsp;=\u0026thinsp;96)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMothers without COVID-19(n\u0026thinsp;=\u0026thinsp;192)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRehospitalizations in 6 months, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e64(21.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e28 (27.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e36(18.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.094\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSARS- CoV-2 positive in 6 months, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e118(40.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e26 (25.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e92(47.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRehospitalizations in 12 months, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e85(28.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e36(37.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e49(25.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.036\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSARS- CoV-2 positive in 12 months, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e145(49.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e26(27.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e119(62.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeight at 12 months, mean (SD), cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e75.8(3.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e76.0(3.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e75.7(3.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.551\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWeight at 12 months, mean(SD), kg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e10.0(1.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10.2(1.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e10.2(1.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.119\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWeight-for- age z score at 12 months, mean(SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.51(1.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.65(1.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.44(0.93)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.114\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLength-for-age z score at 12 months, mean(SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.28(1.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.37(1.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.24(1.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.480\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWeight-for-length z score at 12 months, mean(SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.46(1.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.50(1.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.43 (1.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.620\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\n\u003ch3\u003eAssociation between COVID-19 and offspring outcomes during 12-month follow-up\u003c/h3\u003e\n\u003cp\u003eAmong the 288 patients who completed the 12-month follow-up, a significant association was observed between GDM mothers with COVID-19 and certain offspring outcomes, specifically hospital readmission and SARS-CoV-2 positivity. Infants born to mothers with COVID-19 at higher risk of infant re-hospitalization during their first 12 months. After adjusting for potential confounders in the multivariate analysis, this association remained significant, with an odds ratio of 1 .75 (95% CI 1.01\u0026ndash;3.04, P\u0026thinsp;=\u0026thinsp;0.047), as detailed in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAssociations between maternal COVID-19 and neonatal outcomes.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eOutcomes\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCrude Model\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eModel 1\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eModel 2\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOR(95%CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eP-values\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eaORs(95%CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP-values\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eaORs(95%CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eP-values\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6-month\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRehospitalizations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.62(0.92\u0026ndash;2.85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.094\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.55(0.30\u0026ndash;1.01)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.055\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.77(0.96\u0026ndash;3.26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.068\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSARS-CoV-2 positive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.37(0.22\u0026ndash;0.62)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.43(0.24\u0026ndash;0.75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.43(0.24\u0026ndash;0.76)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e12-month\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRehospitalizations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.75(1.04\u0026ndash;2.96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.036\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.84(1.06\u0026ndash;3.19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.029\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.75(1.01\u0026ndash;3.04)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.047\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSARS-CoV-2 positive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.23(0.13\u0026ndash;0.39)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.26(0.15\u0026ndash;0.45)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.26(0.15\u0026ndash;0.46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003eModel 1 of infant rehospitalizations adjusted for maternal age, educational level, pregnancy comorbidity, cesarean section, preterm birth, low birth weight. Model 2 was further adjusted for respiratory disorders, and infectious diseases based on adjustment Model 1.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003eModel 1 of infant SARS-CoV-2 positive adjusted for maternal age, educational level, pregnancy comorbidity, antimicrobials use, infant infectious diseases and length of stay. Model 2 was further adjusted for neonate gestational age and birth weight based on adjustment Model 1.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eGDM mothers with COVID-19 also had a reduced risk of their infants developing subsequent SARS-CoV-2 infection over the 12-month follow up period. Even after adjusting for potential confounders, multivariate analysis confirmed that having a mother with COVID-19 was associated with a significantly lower risk of subsequent SARS-CoV-2 infection in their infants (OR 0.26; 95% CI 0.15\u0026ndash;0.46, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), as further described in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study indicated that GDM mothers with COVID-19 was associated with an increased risk of hospital readmission for infants within the first 12 months of life. In addition, we found an unexpected correlation between GDM mothers with COVID-19 and a reduced risk for subsequent SARS-CoV-2 infection in their infants during the 12-month follow-up period. These findings raise substantial concerns about the potential effects of COVID-19 on the health of infants born to GDM mothers around the lifting of COVID-19 restrictions.\u003c/p\u003e\u003cp\u003eThe COVID-19 pandemic poses a serious threat to neonatal health. In our cohort, the need for respiratory support increased, which was consistent with the findings reported by Norman \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Similarly, Angelidou's study\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e noted an increase in adverse neonatal health outcomes, including the need for respiratory support, among newborns born to mothers with COVID-19. However, Shah et al. \u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e found no statistically significant difference in respiratory support requirements between infants delivered by test-positive and non-test-positive women. Furthermore, we identified an increased risk of neonatal dysglycemia in neonates born to GDM mothers with COVID-19, suggesting that maternal COVID-19 infection may exacerbate glucose metabolism disorders. Interestingly, there was a reduced incidence of infectious diseases among infants born to SARS-CoV-2 positive mothers. Shah et al. \u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e also reported no statistically significant difference in late-onset sepsis among neonates born to mothers with or without COVID-19 infection during pregnancy. We hypothesize that maternal COVID-19 infection during pregnancy may stimulate the maternal immune system, potentially conferring fetal protection against infection through maternal antibodies. This proposed protective mechanism, if validated, could inform targeted strategies to enhance neonatal immunity against COVID-19 and shed light on broader maternal-fetal immune crosstalk in infectious disease contexts.\u003c/p\u003e\u003cp\u003eIn contrast to Angelidou\u0026rsquo;s\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e finding that only 14.3% of neonates were re-hospitalized within the first 30 days post-discharge from mothers with confirmed SARS-CoV-2 infection, our study documented significantly higher re-hospitalization rates of 27.2% at 6 months and 37.5% at 12 months. This discrepancy may be attributed to differences in follow-up duration and the fact that our study focused on newborns of GDM mothers admitted to the NICU, suggesting that these infants might be more susceptible to illness.\u003c/p\u003e\u003cp\u003eMost studies have tested SARS-CoV-2 in neonates during their hospital stay, reporting low positivity rates, with positive test results more likely to occur in infants born to mothers with symptomatic COVID-19\u003csup\u003e16\u003c/sup\u003e. The positivity rate among neonates born to mothers with positive SARS-CoV-2 tests varied significantly, ranging from 3.1\u0026ndash;9.1% \u003csup\u003e16\u003c/sup\u003e. Even larger cohorts from New York City reported no positive newborn test results, despite high rates of rooming-in and direct breastfeeding practices \u003csup\u003e\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Few previous studies have extended their assessment of neonatal outcomes beyond the initial birth hospitalization. In the US-based Pregnancy Coronavirus Outcomes Registry (PRIORITY) study \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e, no re-hospitalizations and only two positive SARS-CoV-2 test results were reported during the follow-up period of 6 to 8 weeks of age. In contrast, our study provided a longer follow-up period of 12 months, during which we found a significant lower incidence of infant SARS-CoV-2 infection in the group of GDM mothers with COVID-19 (27.1% vs. 62.0%; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). We posit that maternal antibodies, capable of crossing the maternal-fetal interface to provide passive immunity, along with breastfeeding, may contribute to this reduced risk of infection \u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Such observations not only illuminate the intricate interplay between maternal metabolic status, infectious exposure, and neonatal immune protection but also offer critical insights for designing maternal-infant health strategies that leverage natural immune transfer mechanisms to mitigate infectious risks in vulnerable populations.\u003c/p\u003e\u003cp\u003eThis cohort study adds knowledge on long-term outcomes of neonates admitted to NICU after exposure to GDM mothers with SARS-CoV-2 positive. Results from this study provide valuable insights into health management of GDM mothers during pregnancy with COVID-19 infection, both in research and clinical application. Our study included a broader range of outcomes, but it was not comprehensive, and the number of included infants was limited. Further prospective, longitudinal studies are needed to better understand the clinical outcomes of children exposed to SARS-CoV-2 in utero and in the early postnatal life.\u003c/p\u003e\u003cp\u003eOur study possesses several noteworthy strengths. First and foremost, our cohort study focuses on a unique population of infants admitted to a tertiary NICU who were exposed to COVID-19 in utero through their mothers with GDM around the lifting of COVID-19 restrictions in China. This allowed us to assess the relationship between maternal COVID-19 infection in the late stages of pregnancy and the long-term outcomes of the infants. This distinct focus not only fills a critical gap in understanding how maternal comorbidities modulate in utero pathogen exposure during periods of public health transition but also carries implications for tailoring post-pandemic care strategies for high-risk mother-infant dyads. Second, our follow-up period was extended beyond the initial newborn discharge, spanning up to 12 months post-birth, enabling us to capture a more comprehensive picture of infant outcomes.\u003c/p\u003e\u003cp\u003eThird, we also discussed a wide range of infant outcomes associated with SARS-CoV-2 and tracked the COVID-19 infection rate of infants during their first 12 months of life. A recent study\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e on GDM and COVID-19 was limited to perinatal neonatal outcomes, neglecting to address long-term consequences for infants. Carrasco Colom \u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e noted that the majority of infants born to mothers with SARS-CoV-2 infection during pregnancy appear healthy, exhibiting normal cranial ultrasound findings, no hearing loss, and normal neurodevelopment through the first year of life. Similarly, Shuffrey et al. \u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e observed no statistically significant differences in neurodevelopmental outcomes at 6 months of age, as measured by the Ages and Stages Questionnaire-3, between neonates born to mothers with SARS-CoV-2 infection and those born to uninfected mothers. While these findings are promising, further comprehensive studies are needed to fully understand the potential long-term effects of maternal COVID-19 infection on infant health and development.\u003c/p\u003e\u003cp\u003eWhile our study provides valuable insights into the outcomes of neonates exposed to SARS-CoV-2 in utero, it is not without its limitations. First, some mothers may have had asymptomatic COVID-19 but were not tested for SARS-CoV-2, as our study commenced around the relaxation of COVID-19 lockdown policies. This could potentially dilute any differences in outcomes between groups, a concern also noted by Shah et al. \u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e, who noted that including asymptomatic COVID-19 cases in their matched cohort could have influence the observed group differences in outcomes. Second, the single-center nature of our study limits the generalizability of our findings, given the smaller sample size and potentially variable outcome rates. Third, we regret that anthropometric data for the offspring at the 6-month mark were not available for inclusion in our analysis.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, our study highlights the potential impact of COVID-19 on infants born to GDM mothers, demonstrating a statistically significant association between short- and long-term outcomes of neonates admitted to NICU and their in-utero exposure to SARS-CoV-2. These findings highlight the need for enhanced vigilance and tailored management strategies for neonates born to GDM mothers exposed to SARS-CoV-2. To fully elucidate the effects of COVID-19 on these infants and refine clinical guidance, further research with extended follow-up periods and larger, more diverse cohorts is imperative. Such studies will be instrumental in establishing evidence-based practices for the care of GDM mothers and their infants in the context of ongoing and future pandemics.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the mothers, newborns and their families who participated in the study; staff and providers in labour and delivery, postpartum unit, NICU, pathology and laboratory services, at the Women\u0026rsquo;s Hospital, School of Medicine, Zhejiang University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo;contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLing Sun wrote the first draft of the article. Lixia Zhang carried out a critical revision of the manuscript for important intellectual content. Ling Sun and Lixia Zhang carried out the data curation and analyses. Zhaoxia Liang and Jiajun Zhu as guarantor accepts full responsibility for the conduct of the study, had access to the data, and controlled the decision to publish. Zhaoxia Liang, Jiajun Zhu and Yingying Bao have accessed and verified the data underlying the study. Chee Shin Lee performed language editing and proofreading of the manuscript. Yingying Bao reviewed and refined the language of the manuscript for clarity and accuracy. All authors edited and approved the final version of the article.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are not publicly available due to privacy reasons but are available from the corresponding author upon request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e The research was conducted in accordance with the Declaration of Helsinki and was approved by the research ethics board of Women\u0026rsquo;s Hospital, School of Medicine, Zhejiang University (NO. IRB-20240166-R) and written informed consent was obtained from the parents of all the infants that participated in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding/support:\u003c/strong\u003e This study was not specically founded by any source.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of Interest statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCondensation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study found that maternal COVID-19 in GDM pregnancies increases neonatal rehospitalization risk but reduces subsequent infant SARS-CoV-2 infection risk within the first 12 months around the lifting of COVID-19 restrictions in china.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMorens DM, Taubenberger JK, Harvey HA, Memoli MJ. 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JAMA Pediatr. 2022;176(6):e215563. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jamapediatrics.2021.5563\u003c/span\u003e\u003cspan address=\"10.1001/jamapediatrics.2021.5563\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"COVID-19, Infant Outcomes, Rehospitalization, Gestational Diabetes Mellitus","lastPublishedDoi":"10.21203/rs.3.rs-7328288/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7328288/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eThis study aimed to delineate the long-term outcomes for neonates born to mothers with GDM who contracted COVID-19 around the lifting of COVID-19 restrictions in china.\u003c/p\u003e\u003ch2\u003eStudy Design:\u003c/h2\u003e\u003cp\u003eWe enrolled 288 neonates born to GDM mothers who were admitted to the neonatal intensive care unit (NICU) between November 1, 2022, and January 31, 2023. The exposure was a positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in GDM mothers. Neonates were followed up for 12 months, with long-term outcomes including infant anthropometrics measures, hospital readmission, and subsequent SARS-CoV-2 infection. Associations between maternal COVID-19 status and infant outcomes were assessed using multivariable logistic regression.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eNeonates born to GDM mothers who had COVID-19 required increased respiratory support (1.6% vs. 6.3%; P\u0026thinsp;=\u0026thinsp;0.031) and experienced higher rates of neonatal dysglycemia (14.1% vs. 24.0%; P\u0026thinsp;=\u0026thinsp;0.037), while the incidence of neonatal infection decreased (11.5% vs. 24.0%; P\u0026thinsp;=\u0026thinsp;0.012). There was a significant association between maternal SARS-CoV-2 positivity and two distinct outcomes in infants: an increased risk of hospital readmission (odds ratio [OR] 1.75; 95% confidence interval [CI] 1.01\u0026ndash;3.04) and a reduced risk of subsequent SARS-CoV-2 infection during the follow-up period (OR 0.26; 95% CI 0.15\u0026ndash;0.46).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eAround the lifting of COVID-19 restrictions, maternal SARS-CoV-2 infection was associated with an increased risk of neonatal rehospitalization and a reduced risk of subsequent SARS-CoV-2 infection in infants during the 12-month follow-up. Intensive care for newborns of GDM mothers with COVID-19 is essential to minimize the risk of rehospitalization.\u003c/p\u003e","manuscriptTitle":"Impact of Maternal COVID-19 Infection on Long-Term Neonatal Outcomes in Gestational Diabetes Mellitus Pregnancies: A Cohort Study Around the Lifting of COVID-19 Restrictions in China","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-10 15:43:56","doi":"10.21203/rs.3.rs-7328288/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1a180863-5d21-4c59-9086-76e93faa540d","owner":[],"postedDate":"October 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-22T14:23:37+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-10 15:43:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7328288","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7328288","identity":"rs-7328288","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}