Prenatal Exposure to Preeclampsia and Long-Term Ophthalmic Morbidity of the Offspring

The aim of this population-based study was to evaluate whether prenatal exposure to preeclampsia poses a risk for long-term ophthalmic morbidity. A population-based cohort analysis compared the risk of long-term ophthalmic morbidity among children who were prenatally exposed to preeclampsia and those who were not. The study population was composed of children who were born between the years 1991 and 2014 at a single tertiary medical center. Total ophthalmic hospitalization and time-to-event were both evaluated. A Kaplan–Meier survival curve was conducted to compare cumulative ophthalmic hospitalization incidence based on the severity of preeclampsia. Confounders were controlled using a Cox regression model. A total of 242,342 deliveries met the inclusion criteria, of which 7279 (3%) were diagnosed with mild preeclampsia and 2222 (0.92%) with severe preeclampsia or eclampsia. A significant association was found between severe preeclampsia or eclampsia and the risk of long-term vascular-associated ophthalmic morbidity in the offspring (no preeclampsia 0.3%, mild preeclampsia 0.2% and severe preeclampsia or eclampsia 0.5%, p = 0.008). This association persisted after controlling for maternal age and ethnicity (adjusted hazard ratio (HR) 1.861, 95% CI 1.051–3.295). In conclusion, within our population, prenatal exposure to severe preeclampsia or eclampsia was found to be a risk factor for long-term vascular-associated ophthalmic morbidity in the offspring.

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

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174421000593 ◽

2021 ◽

pp. 1-6

Author(s):

Bluma Nae ◽

Tamar Wainstock ◽

Eyal Sheiner

Keyword(s):

Regression Model ◽

Cox Regression ◽

Medical Center ◽

Survival Curve ◽

Cohort Analysis ◽

Asymptomatic Bacteriuria ◽

Population Based ◽

Cox Regression Model ◽

Kaplan Meier

Abstract 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.

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Isolated oligohydramnios and long-term neurological morbidity of the offspring

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174419000795 ◽

2019 ◽

Vol 11 (6) ◽

pp. 648-652

Author(s):

Avital Dorot ◽

Tamar Wainstock ◽

Eyal Sheiner ◽

Asnat Walfisch ◽

Daniella Landau ◽

...

Keyword(s):

Developmental Disorders ◽

Medical Center ◽

Survival Curve ◽

Neurological Complications ◽

Population Based ◽

Exposed Group ◽

Kaplan Meier ◽

Neurological Morbidity ◽

Independent Association

AbstractThis study aimed to assess the association between maternal-isolated oligohydramnios (IO) and offspring long-term neurological complications. A population-based retrospective cohort study was conducted, including all births at a single tertiary medical center in Israel between the years 1991 and 2014. Multiple pregnancies and potential pregnancy complications associated with oligohydramnios were excluded. The computerized obstetrical database was linked with the computerized dataset of all pediatric hospitalizations of the same medical center. Evaluation of cumulative neurological-associated hospitalizations rate over time was compared using a Kaplan–Meier survival curve. The Weibull survival parametric model was conducted to assess the neurological-associated hospitalization risk in the presence of IO, while accounting for potential confounders. A total of 190,259 pregnancies were included in the study, of which 4063 (2.13%) pregnancies were complicated with IO. Total neurological-related hospitalizations were significantly more common in the IO group (3.7% in the IO group and 3.0% in the comparison group, p = 0.005). Pervasive developmental disorder, movement disorders, developmental disorders, and degenerative and demyelization disorders were all specific neurological diagnoses significantly more common in the exposed group. The survival curve demonstrated a significantly higher cumulative hospitalization rate in the exposed group (log-rank p = 0.001). Using a multivariate model adjusting for gestational age, maternal age, and labor induction, an independent association between IO and long-term neurological morbidity of the offspring was observed (adjusted hazard ratio 1.203; 95% CI 1.02–1.42). In summary, a significant association was found between pregnancies complicated by IO and long-term neurological morbidity of the offspring.

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The Significance of True Knot of the Umbilical Cord in Long-Term Offspring Neurological Health

Journal of Clinical Medicine ◽

10.3390/jcm10010123 ◽

2020 ◽

Vol 10 (1) ◽

pp. 123

Author(s):

Yael Lichtman ◽

Tamar Wainstock ◽

Asnat Walfisch ◽

Eyal Sheiner

Keyword(s):

Umbilical Cord ◽

Cox Regression ◽

Survival Curve ◽

Study Groups ◽

Population Based ◽

Kaplan Meier ◽

Group A ◽

Independent Association ◽

Multivariable Regression Models

We aimed to study both the short- and long-term neurological implications in offspring born with confirmed knotting of the umbilical cord—“true knot of cord”. In this population based cohort study, a comparison of perinatal outcome and long-term neurological hospitalizations was performed on the basis of presence or absence of true knot of cord. A Kaplan–Meier survival curve was constructed to compare the cumulative incidence of neurological hospitalizations between the study groups. Multivariable regression models were used to assess the independent association between true knot of cord, perinatal mortality and long term neurological related hospitalizations, while controlling for potential confounders. The study included 243,639 newborns, of them 1.1% (n = 2606) were diagnosed with true knot of the umbilical cord. Higher rates of intrauterine fetal demise (IUFD) were noted in the exposed group, a finding which remained significant in the multivariable generalized estimation equation, while controlling for confounders. The cumulative incidences of neurological hospitalizations over time were comparable between the groups. The Cox regression confirmed a lack of association between true knot of cord and total long term neurological related hospitalizations. While presence of true knot of the umbilical cord is associated with higher IUFD rates, in our population, however, its presence does not appear to impact the long term neurological health of exposed offspring.

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Maternal Obesity and Offspring Long-Term Infectious Morbidity

Journal of Clinical Medicine ◽

10.3390/jcm8091466 ◽

2019 ◽

Vol 8 (9) ◽

pp. 1466 ◽

Cited By ~ 4

Author(s):

Gil Gutvirtz ◽

Tamar Wainstock ◽

Daniella Landau ◽

Eyal Sheiner

Keyword(s):

Maternal Obesity ◽

Cox Regression ◽

Survival Curve ◽

Cohort Analysis ◽

Cox Proportional Hazards Model ◽

Obese Patients ◽

Infectious Morbidity ◽

Kaplan Meier ◽

Meier Survival Curve

Obesity is a leading cause of morbidity world-wide. Maternal obesity is associated with adverse perinatal outcomes. Furthermore, Obesity has been associated with increased susceptibility to infections. The purpose of this study was to evaluate long-term pediatric infectious morbidity of children born to obese mothers. This population-based cohort analysis compared deliveries of obese (maternal pre-pregnancy BMI ≥ 30 kg/m2) and non-obese patients at a single tertiary medical center. Hospitalizations of the offspring up to the age of 18 years involving infectious morbidities were evaluated according to a predefined set of ICD-9 codes. A Kaplan–Meier survival curve was used to compare cumulative hospitalization incidence between the groups and Cox proportional hazards model was used to control for possible confounders. 249,840 deliveries were included. Of them, 3399 were children of obese mothers. Hospitalizations involving infectious morbidity were significantly more common in children born to obese mothers compared with non-obese patients (12.5% vs. 11.0%, p < 0.01). The Kaplan–Meier survival curve demonstrated a significantly higher cumulative incidence of infectious-related hospitalizations in the obese group (log rank p = 0.03). Using the Cox regression model, maternal obesity was found to be an independent risk factor for long-term infectious morbidity of the offspring (adjusted HR = 1.125, 95% CI 1.021–1.238, p = 0.017).

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Infertility Treatments and Long-Term Neurologic Morbidity of the Offspring

American Journal of Perinatology ◽

10.1055/s-0038-1675159 ◽

2018 ◽

Vol 36 (09) ◽

pp. 949-954 ◽

Cited By ~ 5

Author(s):

Shai Levin ◽

Eyal Sheiner ◽

Tamar Wainstock ◽

Asnat Walfisch ◽

Idit Segal ◽

...

Keyword(s):

Medical Center ◽

Cohort Analysis ◽

Multivariable Analysis ◽

Maternal Diabetes ◽

Population Based ◽

Vitro Fertilization ◽

Increased Risk ◽

Attention Deficit Hyperactivity Disorders

Objective To determine the risk of long-term neurologic morbidity among children (up to 18 years) born following in vitro fertilization (IVF) or ovulation induction (OI) treatments as compared with spontaneously conceived. Study Design A population-based cohort analysis was performed, including data from the perinatal computerized database on all singleton infants born at the Soroka University Medical Center (SUMC) between the years 1991 and 2014. This perinatal database was linked and cross-matched with the SUMC computerized dataset of all pediatric hospitalizations. Results Neurologic morbidity was significantly more common in IVF (3.7%) and OI (4.1%) offspring as compared with those following spontaneous pregnancies (3.1%; p = 0.017). In particular, attention deficit/hyperactivity disorders and headaches were more common in the OI group and sleep disorders in the IVF group, whereas autism and cerebral palsy were comparable between the groups. In the Weibull multivariable analysis, while controlling for maternal age, preterm delivery, birthweight centile, maternal diabetes, and hypertensive disorders, IVF (adjusted hazard ratio [HR]: 1.40; 95% confidence interval [CI]: 1.14–1.71; p = 0.001), but not OI (adjusted HR: 1.17' 95% CI: 0.92–1.48; p = 0.196), was noted as an independent risk factor for long-term pediatric neurologic morbidity. Conclusion IVF offspring appear to be at an increased risk of long-term neurologic morbidity up to 18 years of age.

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Maternal Hypothyroidism during Pregnancy and the Risk of Pediatric Endocrine Morbidity in the Offspring

American Journal of Perinatology ◽

10.1055/s-0038-1675834 ◽

2018 ◽

Vol 36 (09) ◽

pp. 975-980 ◽

Cited By ~ 2

Author(s):

Tamar Eshkoli ◽

Tamar Wainstock ◽

Eyal Sheiner ◽

Ofer Beharier ◽

Merav Fraenkel ◽

...

Keyword(s):

Cox Regression ◽

Survival Curve ◽

Mode Of Delivery ◽

Cumulative Risk ◽

Maternal Diabetes ◽

Population Based ◽

Rank Test ◽

Increased Risk

Objective Previous studies suggested maternal hypothyroidism during pregnancy to be associated with cognitive impairment of the offspring. Scarce data exist regarding long-term endocrine health of the offspring. This study was aimed to assess whether children born to mothers with hypothyroidism during pregnancy are at an increased risk for long-term endocrine morbidity. Study Design A retrospective population-based cohort study compared long-term endocrine morbidity of children born between the years 1991 and 2014 to mothers with and without hypothyroidism. Multiple gestations, fetuses with congenital malformations, and women lacking prenatal care were excluded. Hospitalizations of the offspring up to the age of 18 years involving endocrine morbidity were evaluated according to a predefined set of ICD-9 codes. Kaplan–Meier's survival curves were used to compare the cumulative risk and a Cox multivariable model was used to adjust for confounders. Results During the study period, 217,910 deliveries met the inclusion criteria; 1.1% of which were with maternal hypothyroidism (n = 2,403). During the follow-up period, the cumulative incidence of endocrine morbidity among children born to mothers with hypothyroidism was 27 per 1,000 person-years and 0.47 per 1,000 person-years in the comparison group (relative risk: 2.14; 95% confidence interval [CI]: 1.21–3.79). The Kaplan–Meier's survival curve demonstrated a significantly higher cumulative endocrine morbidity in children born to mothers with hypothyroidism (log-rank test, p = 0.007). In the Cox regression model controlled for maternal age, birth weight, preterm birth, maternal diabetes, hypertensive disorders of pregnancy, induction of labor, and mode of delivery, maternal hypothyroidism was found to be independently associated with pediatric endocrine morbidity in the offspring (adjusted hazard ratio = 1.92, 95% CI: 1.08–3.4, p = 0.025). Conclusion Maternal hypothyroidism appears to be independently associated with long-term pediatric endocrine morbidity of the offspring.

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Maternal hepatitis B or C carrier status and long-term risk for offspring neurological morbidity: a population-based cohort study

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174420001397 ◽

2021 ◽

pp. 1-5

Author(s):

Israel Yoles ◽

Eyal Sheiner ◽

Naim Abu-Freha ◽

Tamar Wainstock

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Survival Curve ◽

Population Based ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Carrier Status ◽

Hazards Model ◽

Kaplan Meier

Abstract Hepatitis B and hepatitis C (HBV/HCV) are important global public health concerns. We aimed to evaluate the association between maternal HBV/HCV carrier status and long-term offspring neurological hospitalisations. A population-based cohort analysis compared the risk for long-term childhood neurological hospitalisations in offspring born to HBV/HCV carrier vs. non-carrier mothers in a large tertiary medical centre between 1991 and 2014. Childhood neurological diseases, such as cerebral palsy, movement disorders or developmental disorders, were pre-defined based on ICD-9 codes as recorded in hospital medical files. Offspring with congenital malformations and multiple gestations were excluded from the study. A Kaplan–Meier survival curve was constructed to compare cumulative neurological hospitalisations over time, and a Cox proportional hazards model was used to control for confounders. During the study period (1991–2014), 243,682 newborns met the inclusion criteria, and 777 (0.3%) newborns were born to HBV/HCV mothers. The median follow-up was 10.51 years (0–18 years). The offspring from HBV/HCV mothers had higher incidence of neurological hospitalisations (4.5 vs. 3.1%, hazard ratio (HR) = 1.91, 95% CI 1.37–2.67). Similarly, the cumulative incidence of neurological hospitalisations was higher in children born to HBV/HCV carrier mothers (Kaplan–Meier survival curve log-rank test p < 0.001). The increased risk remained significant in a Cox proportional hazards model, which adjusted for gestational age, mode of delivery and pregnancy complications (adjusted HR = 1.40, 1.01–1.95, p = 0.049). We conclude that maternal HBV or HCV carrier status is an independent risk factor for the long-term neurological hospitalisation of offspring regardless of gestational age and other adverse perinatal outcomes.

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Identifying the Critical Threshold for Long-Term Pediatric Neurological Hospitalizations of the Offspring in Preterm Delivery

Journal of Clinical Medicine ◽

10.3390/jcm10132919 ◽

2021 ◽

Vol 10 (13) ◽

pp. 2919

Author(s):

Shiran Zer ◽

Tamar Wainstock ◽

Eyal Sheiner ◽

Shayna Miodownik ◽

Gali Pariente

Keyword(s):

Preterm Delivery ◽

Gestational Age ◽

Cox Model ◽

Survival Curve ◽

Cohort Analysis ◽

Critical Threshold ◽

Kaplan Meier ◽

Neurological Morbidity ◽

Meier Survival Curve

We opted to investigate whether a critical threshold exists for long-term pediatric neurological morbidity, and cerebral palsy (CP), in preterm delivery, via a population-based cohort analysis. Four study groups were classified according to their gestational age at birth: 24–27.6, 28–31.6, 32–36.6 weeks and term deliveries, evaluating the incidence of long-term hospitalizations of the offspring due to neurological morbidity. Cox proportional hazard models were performed to control for confounders. A Kaplan–Meier survival curve was used to compare the cumulative neurological morbidity incidence for each group. A total of 220,563 deliveries were included: 0.1% (118) occurred at 24–27.6 weeks of gestation, 0.4% (776) occurred at 28–31.6 weeks of gestation, 6% (13,308) occurred at 32–36.6 weeks of gestation and 93% (206,361) at term. In a Cox model, while adjusting for confounders, delivery before 25 weeks had a 3.9-fold risk for long-term neurological morbidity (adjusted HR (hazard ratio) = 3.9, 95% CI (confidence interval) 2.3–6.6; p < 0.001). The Kaplan–Meier survival curve demonstrated a linear association between long-term neurological morbidity and decreasing gestational age. In a second Cox model, adjusted for confounders, infants born before 25 weeks of gestation had increased rates of CP (adjusted HR = 62.495% CI 25.6–152.4; p < 0.001). In our population, the critical cut-off for long-term neurological complications is delivery before 25 weeks gestation.

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P-Cresyl Sulfate Is a Valuable Predictor of Clinical Outcomes in Pre-ESRD Patients

BioMed Research International ◽

10.1155/2014/526932 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 7

Author(s):

Cheng-Jui Lin ◽

Chi-Feng Pan ◽

Chih-Kuang Chuang ◽

Fang-Ju Sun ◽

Duen-Jen Wang ◽

...

Keyword(s):

Clinical Outcomes ◽

Cardiovascular Event ◽

Cox Regression ◽

Medical Center ◽

Serum Biochemistry ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Valuable Marker ◽

Valuable Predictor

Background/Aims. Previous studies have reported p-cresyl sulfate (PCS) was related to endothelial dysfunction and adverse clinical effect. We investigate the adverse effects of PCS on clinical outcomes in a chronic kidney disease (CKD) cohort study.Methods. 72 predialysis patients were enrolled from a single medical center. Serum biochemistry data and PCS were measured. The clinical outcomes including cardiovascular event, all-cause mortality, and dialysis event were recorded during a 3-year follow-up.Results. After adjusting other independent variables, multivariate Cox regression analysis showed age (HR: 1.12,P=0.01), cardiovascular disease history (HR: 6.28,P=0.02), and PCS (HR: 1.12,P=0.02) were independently associated with cardiovascular event; age (HR: 0.91,P<0.01), serum albumin (HR: 0.03,P<0.01), and PCS level (HR: 1.17,P<0.01) reached significant correlation with dialysis event. Kaplan-Meier analysis revealed that patients with higher serum p-cresyl sulfate (>6 mg/L) were significantly associated with cardiovascular and dialysis event (log rankP=0.03, log rankP<0.01, resp.).Conclusion. Our study shows serum PCS could be a valuable marker in predicting cardiovascular event and renal function progression in CKD patients without dialysis.

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Coronary artery aneurysms: outcomes following medical, percutaneous interventional and surgical management

Open Heart ◽

10.1136/openhrt-2020-001440 ◽

2021 ◽

Vol 8 (1) ◽

pp. e001440

Author(s):

Shameer Khubber ◽

Rajdeep Chana ◽

Chandramohan Meenakshisundaram ◽

Kamal Dhaliwal ◽

Mohomed Gad ◽

...

Keyword(s):

Coronary Artery ◽

Surgical Management ◽

Medical Management ◽

Cox Regression ◽

Artery Bypass ◽

Management Strategies ◽

Coronary Artery Aneurysms ◽

Kaplan Meier

BackgroundCoronary artery aneurysms (CAAs) are increasingly diagnosed on coronary angiography; however, controversies persist regarding their optimal management. In the present study, we analysed the long-term outcomes of patients with CAAs following three different management strategies.MethodsWe performed a retrospective review of patient records with documented CAA diagnosis between 2000 and 2005. Patients were divided into three groups: medical management versus percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG). We analysed the rate of major cardiovascular and cerebrovascular events (MACCEs) over a period of 10 years.ResultsWe identified 458 patients with CAAs (mean age 78±10.5 years, 74.5% men) who received medical therapy (N=230) or underwent PCI (N=52) or CABG (N=176). The incidence of CAAs was 0.7% of the total catheterisation reports. The left anterior descending was the most common coronary artery involved (38%). The median follow-up time was 62 months. The total number of MACCE during follow-up was 155 (33.8%); 91 (39.6%) in the medical management group vs 46 (26.1%) in the CABG group vs 18 (34.6%) in the PCI group (p=0.02). Kaplan-Meier survival analysis showed that CABG was associated with better MACCE-free survival (p log-rank=0.03) than medical management. These results were confirmed on univariate Cox regression, but not multivariate regression (OR 0.773 (0.526 to 1.136); p=0.19). Both Kaplan-Meier survival and regression analyses showed that dual antiplatelet therapy (DAPT) and anticoagulation were not associated with significant improvement in MACCE rates.ConclusionOur analysis showed similar long-term MACCE risks in patients with CAA undergoing medical, percutaneous and surgical management. Further, DAPT and anticoagulation were not associated with significant benefits in terms of MACCE rates. These results should be interpreted with caution considering the small size and potential for selection bias and should be confirmed in large, randomised trials.

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