Long-term Infectious Morbidity Research Articles

The Association between Term Chorioamnionitis during Labor and Long-Term Infectious Morbidity of the Offspring

Background: Chorioamnionitis during labor exposes the fetus to an intrauterine state that may alter the future immune response and may expose the offspring to future susceptibility to infectious disease. We evaluated the long-term pediatric infectious morbidity of children born at term to mothers who have chorioamnionitis during labor. Methods: This was a population-based cohort analysis including only term singleton deliveries at a regional tertiary hospital between the years 1991 and 2021. Offspring to mothers with and without a diagnosis of chorioamnionitis during labor were compared. Offspring hospitalizations up to the age of 18 years involving infectious morbidity were evaluated using the Kaplan–Meier survival curve and a Cox regression model to control possible confounders. Results: A total of 331,598 deliveries were included, 988 (0.3%) of which were of mothers diagnosed with chorioamnionitis during labor. All infectious morbidity rates included in the analysis were comparable between groups. The Kaplan–Meier survival curves were similar for both groups (log-rank = 0.881) and the multivariable analysis ascertained that chorioamnionitis during labor was not a risk factor for offspring’s long-term infectious morbidity (HR 0.929, 95%CI 0.818–1.054, p = 0.254). Conclusions: In our cohort, term chorioamnionitis during labor was not associated with a higher risk of pediatric hospitalization due to infections. The infectious/inflammatory state during labor did not expose nor increase the susceptibility of the term offspring to future infectious morbidity.

660 Offspring long-term infectious morbidity following pregnancies with cervical cerclage

660 Offspring long-term infectious morbidity following pregnancies with cervical cerclage

711 Maternal endometriosis: an independent risk factor for long-term infectious morbidity of the offspring

711 Maternal endometriosis: an independent risk factor for long-term infectious morbidity of the offspring

Perinatal outcomes and long-term infectious morbidity of offspring born to mothers with familial Mediterranean fever.

To investigate perinatal outcomes and long-term infectious morbidity in children of mothers with familial Mediterranean fever (FMF). A population-based cohort study comparing perinatal outcomes and long-term infectious morbidity of offspring of mothers with and without FMF was conducted. All singleton deliveries between the years 1991-2021 in a tertiary medical center were included. The study groups were followed until 18years of age for long-term infectious morbidity. A Kaplan-Meier survival curve was used to compare the cumulative incidence of long-term infectious morbidity, and generalized estimation equation (GEE) models as well as Cox proportional hazards models were constructed to control for confounders. During the study period, 356,356 deliveries met the inclusion criteria. 411 of them were women with FMF. The mean follow-up period interval was 9.7years (SD = 6.2) in both study groups. Using GEE models, preterm delivery, cesarean delivery, and low birth weight were independently associated with maternal FMF. The total infectious-related hospitalization rate was significantly higher in offspring born to mothers with FMF compared to the comparison group (Kaplan-Meier survival curve, log-rank p < 0.001). Using a Cox proportional hazards model, controlling for gestational age, maternal age, diabetes mellitus, cesarean delivery, and hypertensive disorders, being born to a mother with FMF was found to be an independent risk factor for long-term infection-related hospitalization of the offspring. Maternal FMF was found to be independently associated with long-term infection-related hospitalization of the offspring. This positive correlation may reflect an intra-uterine pro-inflammatory environment which may result in the offspring's long-term susceptibility to infection.

Intrapartum Maternal Fever and Long-Term Infectious Morbidity of the Offspring.

Maternal intrapartum fever can lead to various maternal and neonatal complications and is attributed to various etiologies including infectious and non-infectious processes. In this study, we evaluated whether intrapartum fever affects the offspring's tendency to long-term infectious morbidity. A population-based cohort analysis including deliveries between 1991 and 2021 was conducted. The incidence of hospitalizations of the offspring up to the age of 18 years, due to various infectious conditions, was compared between pregnancies complicated by intrapartum fever and those that were not. A Kaplan-Meier survival curve was used to assess cumulative hospitalization incidence. A Cox proportional hazards model was used to control for confounders. Overall, 538 of the 356,356 included pregnancies were complicated with fever. A higher rate of pediatric hospitalizations due to various infectious conditions was found among the exposed group, which was significant for viral, fungal and ENT infections (p < 0.05 for all). The total number of infectious-related hospitalizations was significantly higher (30.1% vs. 24.1%; OR = 1.36; p = 0.001), as was the cumulative incidence of hospitalizations. This association remained significant after controlling for confounders using a Cox proportional hazards model (adjusted HR = 1.21; 95% CI 1.04-1.41, p = 0.016). To conclude, fever diagnosed close to delivery may influence offspring susceptibility to pediatric infections.

Exposure to maternal vaginal flora during labor and long-term infectious morbidity of the offspring

Cesarean deliveries (CD) have been associated with an increased risk for offspring long-term infectious morbidity, as suboptimal exposure to maternal vaginal microbiome alters offspring immunologic milieu. We hypothesized that children who had varying exposure level to vaginal microbiome during labor, would differ in their long-term infectious morbidity.

Maternal Anemia and Long-Term Offspring Infectious Morbidity.

Anemia of pregnancy is a common condition associated with adverse obstetric outcomes. However, little is known about its long-term effect on the offspring. This study aimed to evaluate a possible association between anemia during pregnancy and the long-term incidence of infectious morbidity in the offspring. A large population-based retrospective study was conducted at the Soroka University Medical Center, the sole tertiary medical center in the south of Israel. The study included deliveries between the years 1991 and 2014 and compared long-term infectious morbidity of offspring of women with and without anemia during pregnancy (defined as hemoglobin level below 11 g/dL). The long-term incremental incidence of hospitalizations of offspring up to 18 years of age due to infectious morbidity was evaluated using Kaplan-Meier survival curves, while Cox's regression model was used to control for confounders. During the study period, 214,244 deliveries met the inclusion criteria, of which 110,775 (51.7%) newborns were born to mothers with anemia during pregnancy. The overall infectious-related hospitalization rate was significantly higher in children from the exposed group (odds ratio [OR] = 1.07, 95% confidence interval [CI]: 1.04-1.10, p < 0.01). Kaplan-Meier survival curves showed a significantly higher cumulative incidence of hospitalizations due to infectious diseases as compared with children in the unexposed group (log-rank test, p < 0.01). The Cox model demonstrated a significant and independent association between maternal anemia and the long-term risk for hospitalization due to infectious diseases of the offspring (adjusted hazard ratio [aHR]: 1.09, 95% CI: 1.06-1.12, p < 0.01). Offspring of anemic mothers are at a greater risk for infectious-related hospitalizations in their first 18 years of life. · Anemia is highly common in pregnancy.. · Maternal anemia has multiple short-term implications.. · Our study shows anemia of pregnancy is independently associated with long-term offspring infectious morbidity..

The association between fetal gender in twin pregnancies and the risk of pediatric infectious diseases of the offspring: A population-based cohort study with long-term follow up.

We aimed to study the association between fetal gender in twin pregnancies and the risk for childhood infectious morbidity of the offspring. A population-based cohort analysis was performed comparing total and subtypes of infectious related pediatric hospitalizations among males versus females offspring of twin pregnancies. The analysis included all dichorionic twins born between the years 1991-2021. A Kaplan-Meier survival curve was used to compare the cumulative infectious morbidity incidence, and a Cox proportional hazards model was constructed to adjust for confounders. The study population included 4222 newborns (2111 males and 2111 females). Males had higher rates of infectious-related hospitalizations using a Cox proportional hazards model, an independent association was shown between male gender and infectious related hospitalizations of the offspring (Adjusted HR = 1.2, 95% CI: 1.1-1.4; p < 0.001). Male gender in twin pregnancies is associated with an increased risk for long-term pediatric infectious morbidity.

Long- term infectious morbidity of offspring born to women with latent syphilis

Maternal-foetal successful coexistence is possible due to reciprocal important immunological adaptations. Such an environment may seriously affect the offspring's immune system in the short and long term. As other maternal infections such as Tuberculosis and Hepatitis which were shown to be associated with offspring infectious morbidity, a continuous infectious state such as latent syphilis may have a major effect on the offspring's immunity. In this study, we opted to investigate long-term infectious morbidity of offspring to mothers with latent syphilis.

Maternal fever during labor and long-term infectious morbidity of the offspring

Maternal intrapartum fever (i.e., fever of over 38.0°C encountered just before or during delivery) can lead to a variety of maternal and neonatal complications and is attributed to various etiologies including benign infectious and non-infectious processes. In this study we sought to evaluate whether intrapartum fever carries an impact on the long-term infectious morbidity of the offspring. A population-based cohort analysis including deliveries between the years 1991 to 2014 in a tertiary referral hospital was conducted. Incidence of hospitalizations of the offspring up to the age of 18 years due to various infectious conditions was compared between pregnancies complicated by intrapartum fever, and those who were not. A Kaplan-Meier survival curve was used to assess cumulative hospitalization incidence. A Cox proportional hazards model was used to control for baseline selected confounders. During the study period, 249,840 pregnancies met the inclusion criteria. Of those, 407 (0.2%) were accompanied by intrapartum fever. Hospitalization rate of the offspring due to bacterial infections (0.7% vs. 0.1%; OR=5.35, 95% CI 1.7-16.73; p=0.02), ear, nose and throat infections (2.9% vs. 1.5%; OR=2.03, 95% CI 1.14-3.61; p=0.014) and total infectious morbidity (14.7% vs. 11.0%; OR=1.4, 95% CI 1.06-1.84; p=0.017) was higher among the exposed group (Table), as was the cumulative incidence of hospitalizations presented in the Kaplan-Meier survival curve (log rank p=0.005; Figure). This association remained significant after controlling for potential confounders (including gestational age, maternal age, hypertensive disorders of pregnancy and diabetes mellitus) using a Cox proportional hazards model (adjusted HR = 1.36; 95% CI 1.05–1.76, p=0.018). Maternal fever diagnosed close to delivery may influence offspring susceptibility to pediatric infections, as it is linked to higher rates of long-term infectious morbidity of the offspring.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Gestational Diabetes Mellitus and Offspring Infectious Morbidities- A Sibling Analysis

The aim of our study was to investigate the association between GDM and offspring long-term infectious morbidity while employing sibling matched analysis, which can assist in revealing whether maternal intrinsic or environmental factors are involved in the studied association.

The significance of maternal asymptomatic bacteriuria during pregnancy on long-term offspring infectious hospitalizations.

Asymptomatic bacteriuria (ASB) is a well-acknowledged infectious entity during pregnancy; yet its long-term implications are not well investigated. The present study aimed to test the association between maternal ASB during pregnancy and long-term offspring infectious hospitalizations. A population-based cohort analysis was conducted, comparing the incidence of long-term infectious-related hospitalizations of offspring born to mothers who were diagnosed with ASB during pregnancy, and those who did not have ASB. The study was conducted at a tertiary medical center and included all singleton deliveries between the years 1991 and 2014. Infectious morbidities were based on a predefined set of International Classification of Disease-9 codes. A Kaplan-Meier survival curve compared cumulative infectious hospitalization incidence between the groups, and a Cox regression model was used to adjust for confounding variables. During the study period, 212,984 deliveries met inclusion criteria. Of them, 5378 (2.5%) were diagnosed with ASB. As compared to offspring of non-ASB mothers, total long-term infectious hospitalizations were significantly higher among children to mothers who were diagnosed with ASB (13.1% vs. 11.1%, OR = 1.2, 95% CI 1.11-1.30, P ≤ 0.001). Likewise, a Kaplan-Meier curve demonstrated higher cumulative incidence of infectious hospitalizations among children born to mothers with ASB (log rank, P = 0.006). In the Cox regression model, while controlling for maternal age, diabetes mellitus, ethnicity, hypertensive disorders, and gestational age, maternal ASB was noted as an independent risk factor for long-term infectious morbidity in the offspring (adjusted HR = 1.1, 95% CI 1.01-1.17, P = 0.042). ASB during pregnancy increases offspring susceptibility to long-term infectious hospitalizations.

Maternal celiac disease and the risk for long-term infectious morbidity of the offspring.

Celiac disease is an autoimmune disease, patients with celiac have increased risk for infections, and offspring of celiac mothers have increased morbidity. The aim of the study was to assess long-term infectious morbidity among offspring of pregnant women with celiac disease. A population-based cohort study was conducted, including all singleton deliveries between the years 1991-2014 at a tertiary medical center. The offsprings were subdivided into two groups: offsprings of mothers with and without celiac disease. Data on demographics, maternal, perinatal, and long-term hospitalizations for infectious morbidity were compared between the two groups. During the study period there were 210 (0.09%) deliveries of mothers with celiac, and they were compared to 242170 (99.91%) deliveries of non-celiac mothers. Cumulative infectious morbidity was significantly higher in offspring of mothers with celiac compared to offspring of mothers without celiac (Kaplan-Meier, log-rank p=.004). Specifically, among the offspring of mothers with celiac significantly higher rates of bacteremia was noted (1.0% vs. 0.1%; p=.001), and infections of the central nervous system (1% vs. 0.2%; p=.028). In the Cox multivariable model which accounted for confounding variables, being born to mothers with celiac disease was associated with significantly increased risk for long-term infectious morbidity of the offspring (adjusted HR=1.6, 95% CI 1.165-2.357, p=.005). Maternal celiac disease is an independent risk factor for long-term infectious morbidity for the offspring.

Long-Term Infectious Morbidity of Premature Infants: Is There a Critical Threshold?

In this study, we sought to ascertain a relationship between gestational age at birth and infectious morbidity of the offspring via population-based cohort analysis comparing the long-term incidence of infectious morbidity in infants born preterm and stratified by extremity of prematurity (extreme preterm birth: 24 + 0–27 + 6, very preterm birth: 28 + 0–31 + 6, moderate to late preterm birth: 32 + 0−36 + 6 weeks of gestation, and term deliveries). Infectious morbidity included hospitalizations involving a predefined set of International Classification of Diseases 9 (ICD9) codes, as recorded in hospital records. A Kaplan–Meier survival curve compared cumulative incidence of infectious-related morbidity. A Cox proportional hazards model controlled for confounders and time to event. The study included 220,594 patients: 125 (0.1%) extreme preterm births, 784 (0.4%) very preterm births, 13,323 (6.0%) moderate to late preterm births, and 206,362 term deliveries. Offspring born preterm had significantly more infection-related hospitalizations (18.4%, 19.8%, 14.9%, and 11.0% for the aforementioned stratification, respectively, p < 0.001). Multivariate analysis found being born very or late to moderate preterm was independently associated with long-term infectious morbidity (adjusted hazard ratio (aHR) 1.5, 95% confidence interval (CI) 1.27–1.77 and aHR 1.23, 95% CI 1.17–1.3, respectively, p < 0.001). A comparable risk of long-term infectious morbidity was found in the two groups of premature births prior to 32 weeks gestation. In our population, a cutoff from 32 weeks and below demarks a significant increase in the risk of long-term infectious morbidity of the offspring.

Perinatal Outcome and Long-Term Infectious Morbidity of Offspring Born to Women with Known Tuberculosis.

Objective: To evaluate the perinatal outcome of women with tuberculosis and to assess a possible association between maternal tuberculosis and long-term infectious morbidity of the offspring. Study design: Perinatal outcome and long-term infectious morbidity of offspring of mothers with and without tuberculosis were assessed. The study groups were followed until 18 years of age tracking infectious-related morbidity and infectious-related hospitalizations and then compared. For perinatal outcome, generalized estimation equation models were used. A Kaplan-Meier survival curve was used to compare cumulative incidence of long-term infectious morbidity. A Cox proportional hazards model was conducted to control for confounders. Results: During the study period, 243,682 deliveries were included, of which 46 (0.018%) occurred in women with tuberculosis. Maternal tuberculosis was found to be independently associated with placental abruption, cesarean deliveries, and very low birth weight. However, offspring born to mothers with tuberculosis did not demonstrate higher rates of infectious-related morbidity. Maternal tuberculosis was not noted as an independent risk factor for long-term infectious morbidity of the offspring. Conclusion: In our study, maternal tuberculosis was found to be independently associated with adverse perinatal outcomes. However, higher risk for long-term infectious morbidity of the offspring was not demonstrated. Careful surveillance of these women is required.

Delivery mode and future infectious morbidity of the offspring: a sibling analysis.

Cesarean delivery (CD) has been recently suggested to be associated with offspring's long-term health implications. We aimed to investigate the association between delivery mode and long-term infectious morbidity of the offspring while employing sibling matched analysis to maximize confounder control. A retrospective population-based cohort study was performed, which included all sibling deliveries occurring between 1991 and 2014 at a regional tertiary medical center. Offsprings were followed up until the age of 18years. The study included 13,516 individuals (6758 sibling pairs): the first born was via vaginal delivery and the second via CD. Each siblings pair was considered a matched set, with the aim to perform a within-family analysis. A Kaplan-Meier survival curve was used to compare the cumulative infectious morbidity incidence and a multivariable Cox survival hazards regression model to control for confounders. Crude rates of total infectious hospitalizations were found to be significantly higher in the CD group (OR 1.25; 95% CI 1.12-1.40). Specifically, bronchiolitis (OR 2.02, 95% CI 1.56-2.63), otitis (OR 1.52, 95% CI 1.21-1.9), and gastroenteritis (OR 1.41, 95% CI 1.05-1.9) were all found to be significantly more common in the CD group. The survival curve demonstrated significantly higher cumulative infection-related hospitalization rates in the CD group (log-rank p < 0.001). The Cox model, adjusted for several confounders, confirmed the significant association between CD and offspring's infection-related morbidity (adjusted HR 1.25; 95% CI 1.02-1.53). CD appears to be independently associated with later offspring infection-related morbidity, even while rigorously adjusting for confounders.

Maternal hepatitis B or hepatitis C virus carrier status and long-term infectious morbidity of the offspring: A population-based cohort study.

The objective of the study was to investigate the long-term effects of maternal hepatitis B virus (HBV) or hepatitis C virus (HCV) carrier status on the long-term infectious morbidity of their offspring. A population-based cohort study was conducted, including all singleton deliveries between the years 1991 and 2014 at a tertiary medical centre. The mothers were subdivided into three groups: HBV carriers, HCV carriers and non-carriers. Data on demographics, maternal, perinatal and long-term hospitalization for infectious morbidity were compared between the groups. During the study period, 242905 (99.7%) non-carrier mothers, 591 (0.2%) HBV carriers and 186 (0.1%) HCV carriers were observed. Hospitalizations related to infectious morbidity was significantly higher in the offspring of HBV carriers compared with HCV and non-carriers (15.6% vs 11.3% vs 11.0%; P=.002, respectively; Kaplan-Meier, log-rank P<.001). Specifically, a significantly higher rate of hospitalizations gastrointestinal infectious morbidity was noted among the offspring of HBV carrier mothers (3.6% in the HBV carrier group, 1.6% in the HCV carrier group and 1.6% in the non-carrier group [P=.001]). There was a respiratory infectious morbidity of 8.1% among the offspring of HBV carriers, 8.6% among HCV carriers and 5.5% in non-carriers (P=.005). Using a Cox multivariable model, controlling for confounding variables, maternal HBV carrier status was associated with a significantly increased long-term infectious morbidity of the offspring, with an adjusted HR of 1.7 (95% CI, 1.388-2.077, P<.001). Maternal HBV carrier status is an independent risk factor for long-term infectious morbidity of the offspring, particularly for gastrointestinal and respiratory infections.

Maternal preeclampsia and long-term infectious morbidity in the offspring - A population based cohort analysis.

We evaluated the association between maternal preeclampsia and long-term infectious morbidity of the offspring. A retrospective cohort analysis was performed, evaluating risk of long-term infectious morbidity in children born to women with and without preeclampsia between the years 1991-2014. Infectious morbidity included hospitalizations of offspring during childhood. Infants were followed until age 18years or until hospitalization. Multiple gestations, newborns with congenital malformations and perinatal deaths were excluded. Cumulative incidence rates of infectious morbidity were compared. A Cox proportional hazards model was employed to control for various confounders including gestational age and cesarean delivery (CD). During the study period 239,725 newborns were included: 96% (n=230,217) without preeclampsia, 3% (n=7280) with mild preeclampsia and 0.9% (n=2228) with severe preeclampsia, defined mostly by evidence of maternal organ dysfunction. Hospitalization rate due to infectious morbidity was significantly higher for offspring to mothers with severe preeclampsia in comparison to those with no preeclampsia (13.1% vs 11%, P=0.008), specifically respiratory and bacterial infections. The Kaplan-Meier survival curve demonstrated that offspring born to mothers with severe preeclampsia had a significantly higher cumulative incidence of hospitalization (Log-rank test P value=0.026). However, while controlling for confounders in the Cox regression model, severe preeclampsia was not found as an independent risk factor (adjusted hazard ratio 0.95, 95% confidence interval 0.8-1.1, P=0.36). While severe preeclampsia is associated with higher risk for long-term infectious morbidity of the offspring, it seems that the association is due to prematurity and CD, but not the preeclampsia per-se.

Low Apgar score in term newborns and long-term infectious morbidity: a population-based cohort study with up to 18years of follow-up.

Since introduced, the Apgar score has remained the most widespread predictor for neonatal morbidity and mortality. We aimed to investigate the association between low 5-min Apgar score and long-term infectious pediatric morbidity. A population-based cohort analysis was performed comparing total and specific subtypes of infectious morbidity leading to hospitalization among term newborns with normal (≥ 7) and low (< 7) 5-min Apgar scores, born between 1999 and 2014 at a single tertiary regional hospital. Infectious morbidity included hospitalizations involving a pre-defined set of infection-related ICD-9 codes. A Kaplan-Meier survival curve was constructed to compare cumulative infectious morbidity incidence and a Cox proportional hazards model to adjust for confounders. The long-term analysis of 223,335 children (excluding perinatal death cases) yielded 585 (0.3%) infants with low 5-min Apgar scores. The rate of infection-related hospitalizations was 9.8% and 12.4% among newborns with normal and low 5-min Apgar scores, respectively (p = 0.06). Adjusting for maternal age, gestational age, hypertension, diabetes, cesarean delivery, and fertility treatments, the association proved to be statistically significant (adjusted HR = 1.28; 95% CI 1.01-1.61).Conclusion: Term infants with low 5-min Apgar scores may be at an increased risk for long-term pediatric infectious morbidity.What is Known:• Though not meant to be a prognostic tool for long-term morbidity, studies assessing the correlation between low Apgar score and long-term outcomes were and are being performed, reporting significant associations with many outcomes-such as cerebral palsy (CP), ophthalmic disorders, GI disorders, and several types of malignancies.• Yet, an association between low Apgar scores and future health remains a matter of controversy.What is New:• Our work shows that a low 5-min Apgar score is independently associated with long-term pediatric infection-related hospitalizations among term singleton newborns.

672: Is there a critical threshold? Preterm delivery and long term infectious morbidity of the offspring

Infectious disease is a well-established cause of preterm birth (PTB), but the significance of PTB as a risk factor for subsequent long-term infectious morbidity of the offspring is more elusive. We sought to ascertain a relationhip between the gestational age at delivery and long-term pediatric infectious morbidity. A population-based cohort analysis comparing the long-term incidence of infectious morbidity in infants born preterm according to gestational age at birth. Cases were divided into groups according to the extremity of prematurity (extreme PTB 24+0-27+6, very PTB 28+0-31+6, moderate to late PTB 32+0-36+6 weeks of gestation and term deliveries). infectious morbidity included hospitalizations involving a predefined set of ICD9 codes, as recorded in hospital records. Deliveries occured between 1991-2014 in a tertiary medical center. A Kaplan Meier survival curve was constructed to compare cumulative incidence of infectious-related morbidity. A Cox proportional hazards model controlled for confounders. 220,594 patients met the inclusion criteria of which 125 (0.1%) were extreme PTB, 784 (0.4%) were very PTB, 13,323 (6.0%) were moderate to late PTB and 206,362 were term deliveries. Offspring born preterm had significantly more hospitalizations due to infectious morbidity compared to term offspring (18.4%, 19.8%, 14.9% and 11.0% for offspring born in extreme PTB, very PTB, moderate to late PTB and term respectively p< 0.001, Table). Using a Cox proportional hazards model, controlling for confounders including maternal age, birth weight, diabetes, hypertensive disease and mode of delivery, delivery at very, and late to moderate PTB was independently associated with long-term infectious morbidity (aHR 1.5 95% CI 1.27-1.77 and aHR 1.23 95% CI 1.17-1.3 respectively, p< 0.001, Figure). An increased risk was also found with extreme PTB (aHR 1.24 95% CI 0.83-1.89 p=0.34) but this association did not achieve statistical significance. Preterm delivery is an independent risk factor for long-term infectious morbidity of the offspting, starting from 28 weeks.View Large Image Figure ViewerDownload Hi-res image Download (PPT)