Sex-Specific Developmental Scales for Surveillance.

BACKGROUND: Developmental surveillance, conducted routinely worldwide, is fundamental for early detection of children at risk for developmental delay. We aimed to explore sex-related difference in attainment rates of developmental milestones and to evaluate the clinical need for separate sex-specific scales. METHODS: This is a cross-sectional, natiowide retrospective study, utilizing data from a national child surveillance program of ∼1000 maternal child health clinics. The main cohort, used for constructing sex-specific developmental scales, included all children born between January 2014 to September 2020, who visited maternal child health clinics from birth to 6 years of age (n = 839 574). Children with abnormal developmental potential were excluded (n = 195 616). A validation cohort included all visits between 2020 and 2021 (n = 309 181). The sex-differences in normative attainment age of 59 developmental milestones from 4 domains were evaluated. The milestones with a significant gap between males and females were identified, and the projected error rates when conducting unified versus sex-specific surveillance were calculated. RESULTS: A new sex-specific developmental scale was constructed. In total, females preceded males in most milestones of all developmental domains, mainly at older ages. Conducting routine developmental surveillance using a unified scale, compared with sex-specific scales, resulted in potential missing of females at risk for developmental delay (19.3% of failed assessments) and over-diagnosis of males not requiring further evaluation (5.9% of failed assessments). CONCLUSIONS: There are sex-related differences in the normative attainment rates of developmental milestones, indicating possible distortion of the currently used unified scales. These findings suggest that using sex-specific scales may improve the accuracy of early childhood developmental surveillance.

Estimated glomerular filtration rate and the risk of stroke in individuals with diabetes mellitus and atrial fibrillation insight from a large contemporary population study.

BACKGROUND: Diabetes mellitus (DM) is associated with increased risk of embolic complications in non-valvular atrial fibrillation (NVAF). Impaired renal function (IRF) increases the risk of stroke as well, but this finding is not consistent among all studies. Our aim was to assess the incidence rates and risk of ischemic stroke and mortality by baseline Estimated Glomerular Filtration Rate (eGFR) levels Among individuals with AF and DM. METHODS: A prospective, historical cohort study using the Clalit Health Services electronic medical records database. Among patients with AF and DM, we compared three groups according to eGFR levels: eGFR ≥ 60, between 30 and 60, and ≤ 30 (mL/min/1.73m2). RESULTS: A total of 17,567 cases were included in the final analysis; of them, 11,013 (62.7%) had eGFR ≥ 60, 4930 (28%) had eGFR between 30 and 60, and 1624 (9.24%) with eGFR ≤ 30. The incidence of stroke per 100 person-years in the three study groups was: 1.88, 2.69, and 3.34, respectively (p < 0.001). IRF was associated with increased risk of stroke in univariate analysis, but not after multivariate adjustment (Adjusted Hazard Ratio (AHR) 0.96 {95%CI; 0.74-1.25} for eGFR 30-60 and 0.96 {95%CI; 0.60-1.55} for eGFR ≤ 30). Mortality per 100 person-years was 10.78, 21.49, and 41.55, respectively (p < 0.001). IRF was associated with increased mortality risk in univariate analysis, as well as in multivariate analysis (AHR 1.08 {95%CI; 0.98-1.18} for eGFR 30-60, and 1.59 {95%CI; 1.37-1.85} for eGFR ≤ 30. CONCLUSION: In patients with NVAF and DM, IRF was not associated with an increased risk of stroke, but severe IRF (eGFR ≤ 30) was associated with increased mortality risk.

Utilizing machine learning to predict unplanned cesarean delivery.

OBJECTIVE: To develop a comprehensive machine learning (ML) model predicting unplanned cesarean delivery (uCD) among singleton pregnancies based on features available at admission to labor. METHODS: A retrospective cohort study from a tertiary medical center. Women with singleton vertex pregnancy of 34 weeks or more admitted for vaginal delivery between March 2011 and May 2019 were included. The cohort was divided into training (80%) and validation (20%) data sets. A separate cohort between June 2019 and April 2021 served as a test data set. Features selection was performed using a Random Forest ML algorithm. RESULTS: The study population included 73 667 women, of which 4125 (6.33%) underwent uCD. The final model consisted of 13 features, based on prediction importance. The XGBoost model performed best with areas under the curve for the training, validation, and test data sets of 0.874, 0.839, and 0.840, respectively. The model showed a 65% positive predictive value for uCD among women in the 100th centile group, and a 99% or more negative predictive value in the less than 50th centile group. Positive and negative predictive values remained high among subgroups with high pretest probability of uCD. CONCLUSION: An ML model for the prediction of uCD provides clinically useful risk stratification that remains accurate across gestational weeks 34-42 and among clinical risk groups. The model may be clinically useful for physicians and women admitted for labor. SYNOPSIS: A machine learning model predicts unplanned cesarean delivery and can inform women's individualized decision making.

Relation of Hemoglobin A1C Levels to Risk of Ischemic Stroke and Mortality in Patients With Diabetes Mellitus and Atrial Fibrillation.

Diabetes mellitus (DM) is associated with an increased risk of complications in atrial fibrillation (AF). This study aimed to assess the incidence and risks of ischemic stroke and mortality according to baseline HbA1c levels in patients with DM and AF. We conducted a cohort study using Clalit Health Services electronic medical records. The study population included all Clalit Health Services members aged ≥25 years, with the first diagnosis of AF between January 1, 2010, and December 31, 2016, who had a diagnosis of DM. The risk of stroke and all-cause death were compared according to HbA1c levels at the time of AF diagnosis: <7.0%, between 7% and 9%, and ≥9%. A total of 44,451 patients with DM and AF were identified. The median age was 75 years (interquartile 65 to 83), and 52.5% were women. During a mean follow-up of 38 months, higher levels of HbA1c were associated with an increased risk of stroke with a dose-dependent response when compared with patients with HbA1c <7% (Adjusted hazard ratio [aHR] =1.30 [95% confidence interval 1.10 to 2.05] for levels between 7% and 9% and 1.60 (95% confidence interval 1.25 to 2.03) for HbA1c >9%, even after adjusting for CHA2DS2-Vasc risk factors and use of oral anticoagulants. The risk for overall mortality was significantly higher in the HBA1C >9% group (aHR = 1.17 [1.07 to 1.28]). In conclusion, in this cohort of patients with AF and DM, HbA1c levels were associated with the risk of stroke in a dose-dependent manner even after accounting for other recognized risk factors for stroke.

Standardization of a Developmental Milestone Scale Using Data From Children in Israel.

Importance: Routine developmental screening tests for children are used worldwide for early detection of developmental delays. However, assessment of developmental milestone norms lacks strong normative data, and there are inconsistencies among different screening tools. Objective: To establish milestone norms and build an updated developmental scale. Design, Setting, and Participants: This is a cross-sectional, population-based study conducted between 2014 and 2020. Developmental assessments were conducted by trained public health nurses, documented in national maternal child health clinics, known as Tipat Halav, which serve all children in Israel. Participants included all children born between January 2014 and September 2020, who were followed at the maternal child health clinics from birth to age 6 years. Exclusion criteria were preterm birth, missing gestational age, low birth weight (<2.5 kg), abnormal weight measurement (<3% according to standardized child growth charts), abnormal head circumference measurement (<3% or >97% according to standardized child growth charts), and visits without developmental data or without the child's age. Data analysis was performed from September 2020 to June 2021. Exposures: In total, 59 milestones in 4 developmental domains were evaluated, and the achievement rate per child's age was calculated for each milestone. Main Outcomes and Measures: A contemporary developmental scale, the Tipat Halav Israel Screening (THIS) Developmental Scale, was built, presenting the 75%, 90%, and 95% achievement rates for each milestone. The THIS scale was compared with other commonly used screening tests, including the Denver Developmental Screening Test II (Denver II), the Alberta Infant Motor Scale (AIMS), and the Centers for Disease Control and Prevention (CDC) Developmental Assessment. Results: A total of 839 574 children were followed in the maternal child health clinics between January 2014 and September 2020 in Israel, and 195 616 children were excluded. A total of 3 774 517 developmental assessments were performed for the remaining 643 958 children aged 0 to 6 years (319 562 female children [49.6%]), resulting in the establishment of new developmental norms. In terms of the comparable milestones, THIS milestones had a match of 18 of 27 (67%) with the Denver II, 7 of 7 (100%) with AIMS, and 10 of 19 (53%) with the CDC Developmental Assessment. The remaining unmatched milestones were achieved earlier in the THIS scale compared with other screening tools. Conclusions and Relevance: The THIS developmental scale is based on the largest population evaluated to date for developmental performance, representing the heterogeneous, multicultural population comprising this cohort. It is recommended for further evaluation worldwide.

Identifying patients with atrial fibrillation with a single CHA2DS2-VASC risk factor who are at higher risk of stroke.

AIMS: Management of patients with a single CHA2DS2-VASc score risk factor is controversial. We attempt to identify the "truly low risk" AF patients who will not benefit from oral anticoagulation (OAC) treatment. METHODS: Retrospective cohort analysis, all incident non-valvular AF (NVAF) cases between 2004 and 2015, and age 21 and older, with up to one thromboembolic risk factor besides sex (CHA2DS2-VASc score of up to 1 for men and up to 2 for women). A "low risk" score was created for these patients using a logistic regression model on the incidence of stroke within 30-2500 days following the NVAF diagnosis. RESULTS: We identified 15,621 patients. Average age was 53.7 ± 12.3 years, 56.6% male. Mean follow-up was 5.5 years. Significant predictors of ischemic stroke were age 65-74 and diabetes (2 points each), hypertension, vascular disease, and chronic kidney disease stage 2-3 (1 point each). Stroke incidence ranged from 0.8% for score 0 and up to 3.4% for scores ≤ 2. Odds ratio for stroke among patient group with a score ≤ 2 was 4.3 (2.9-6.6) compared with score 0. Our risk score's area-under-the-curve (AUC) for prediction of stroke was 0.68 (0.65-0.71), compared with 0.60 (0.57-0.62) for the CHAD2S2-VASc score, within this low-risk group. CONCLUSION: Patients considered at low or intermediate risk using traditional risk stratification schemes, with ≥ 2 points using this proposed low-risk index (65-74 years old, diabetics or a combination of chronic renal failure and an additional risk factor), had an overall stroke risk that may justify anticoagulation therapy.

Machine learning based study of longitudinal HbA1c trends and their association with all-cause mortality: Analyses from a National Diabetes Registry.

OBJECTIVE: The association of long-term HbA1c variability with mortality has been previously suggested. However, the significance of HbA1c variability and trends in different age and HbA1c categories is unclear. RESEARCH DESIGN AND METHODS: Data on patients with diabetes listed in the Israeli National Diabetes Registry during years 2012-2016 (observation period) were collected. Patients with >4 HbA1c measurements, type 1 diabetes, eGFR < 30mg/ml/min, persistent HbA1c < 6% or malignancy were excluded. Utilizing machine learning methods, patients were classified into clusters according to their HbA1c trend (increasing, stable, decreasing). Mortality risk during 2017-2019 was calculated in subgroups defined by age (35-54, 55-69, 70-89 years) and last HbA1c (≤7% and >7%) at end of observation period. Models were adjusted for demographic, clinical and laboratory measurements including HbA1c, standard deviation (SD) of HbA1c and HbA1c trend. RESULTS: This historical cohort study included 293,314 patients. Increased HbA1c variability (high SD) during the observation period was an independent predictor of mortality in patients aged more than 55 years (p < 0.01). The HbA1c trend was another independent predictor of mortality. Patients with a decreasing versus stable HbA1c trend had a greater mortality risk; this association persisted in all age groups in patients with HbA1c > 7% at the end of the observation period (p = 0.02 in age 35-54; p < 0.01 in aged >55). Patients with an increasing versus stable HbA1c trend had a greater mortality risk only in the elderly group (>70), yet in both HbA1c categories (p < 0.01). CONCLUSIONS: HbA1c variability and trend are important determinants of mortality risk and should be considered when adjusting glycaemic targets.

Pre-Diabetes Increases Stroke Risk in Patients With Nonvalvular Atrial Fibrillation.

BACKGROUND: Diabetes mellitus (DM) increases the risk of embolism in nonvalvular atrial fibrillation (NVAF). The association between pre-diabetes and risk of ischemic stroke has not been studied separately in this population. OBJECTIVES: The purpose of this study was to evaluate whether pre-diabetes is associated with increased risk of stroke and death in patients with NVAF. METHODS: We conducted a historical cohort study using the Clalit Health Services electronic medical records. The study population included all members aged ≥25 years, with a first diagnosis of NVAF between January 1, 2010, and December 31, 2016. We compared 3 groups of individuals: those with pre-diabetes, those with diabetes, and normoglycemic patients. RESULTS: A total of 44,451 cases were identified. The median age was 75 years, and 52.5% were women. During a mean follow-up of 38 months, the incidence rates of stroke (per 100 person-years) were: 1.14 in normoglycemic individuals, 1.40 in those with pre-diabetes, and 2.15 in those with diabetes. In both univariate and multivariate analyses, pre-diabetes was associated with an increased risk of stroke compared with normoglycemic persons (adjusted hazard ratio [adjHR]: 1.19; 95% confidence interval [CI]: 1.01 to 1.4) even after adjustment for CHA2DS2-Vasc risk factors and use of anticoagulants, while diabetes conferred an even higher risk (vs. normoglycemia (adjHR: 1.56; 95% CI: 1.37 to 1.79). The risk for mortality was higher for individuals with diabetes (adjHR: 1.47; 95% CI: 1.41 to 1.54) but not for those with pre-diabetes (adjHR: 0.98; 95% CI: 0.92 to 1.03). CONCLUSIONS: In this cohort of patients with incident NVAF, pre-diabetes was associated with an increased risk of stroke even after accounting for other recognized risk factors.

Long-term risk of stroke and bleeding post-atrial fibrillation ablation.

BACKGROUND: Catheter ablation (CA) is an established therapy for atrial fibrillation (AF). Studies regarding long-term real-world outcomes post-CA have inconsistently accounted for oral anticoagulation (OAC). OBJECTIVES: To describe patterns of OAC use post-CA and to compare the OAC-adjusted long-term risk of stroke and major bleeding in AF patients with and without CA. METHODS: A population-based cohort of AF patients was constructed in Quebec and Ontario, Canada (1999-2014). Propensity score matching was performed to determine the incidence rates of stroke and major bleeding among those undergoing CA, adjusted for time-dependent OAC use. RESULTS: From the entire cohort, 6391 patients were identified as having undergone CA as compared to 482 977 patients who did not. Of these, 1240 patients with government medical insurance undergoing CA were matched with 2427 patients without CA. Post-CA, 78%, 65%, and 61% remained on an OAC at 1, 2, and 5 years, while 75%, 71%, and 68% of patients not undergoing CA were on OACs at 1, 2, and 5 years. At follow-up, there was no statistically significant difference for stroke (adjusted hazard ratio [HR], 0.88; 95% CI, 0.63 to 1.21) or major bleeding (adjusted HR, 0.88; 95% CI, 0.73 to 1.06). CONCLUSION: No evidence was found that CA significantly decreases the risk of stroke or major bleeding when adjusting for OAC use over time. It may be prudent to continue anticoagulation post-CA based on patient-risk profile until randomized trials demonstrate both reduced stroke rates with CA, and improved safety (balancing stroke and bleeding risk) with OAC discontinuation post-CA.

Population-Based Evaluation of Major Adverse Events After Catheter Ablation for Atrial Fibrillation.

OBJECTIVES: The purpose of this study was to evaluate the safety and incidence of periprocedural adverse events (AEs) among patients who underwent catheter ablation (CA) for atrial fibrillation (AF) in Quebec and Ontario, Canada. BACKGROUND: CA is evolving into the mainstay therapy for patients with symptomatic AF refractory to antiarrhythmic medication. However, the safety of CA at the population level over time requires further evaluation. METHODS: A population-based cohort was constructed using administrative databases of all patients who underwent CA between 1999 and 2014 in Quebec and Ontario, Canada. Incidence and predictors of AEs were assessed within 30 days of CA. Major AEs included all-cause mortality, cerebrovascular accident (CVA) including transient ischemic attack, pericardial effusion requiring drainage (PERD), vascular AEs, hemorrhage/hematoma, and pulmonary embolism. RESULTS: Of 6,388 patients who had a CA (mean age 57.3 years; mean CHA2DS2-VASc 1.1 ± 1.4; 27.6% female), 221 (3.5%) patients developed major AEs within 30 days of index CA. Hemorrhage/hematoma was the most frequent (1.4%), followed by PERD (1.0%) and CVA (0.6%). PERD was more likely to occur post-discharge than during the index CA (p < 0.05). CVA decreased by more than 50% in patients with recent compared with remote CA (p < 0.05). Compared with index CA, the incidence of PERD and hemorrhage/hematoma was greater at first repeat CA (p < 0.05 for both). CONCLUSIONS: CA is a relatively safe procedure with low incidence of major AEs. The incidence of procedure-related CVA appeared to decline significantly over time. Incidence of PERD remained relatively stable and was more likely to be diagnosed after discharge and following repeat CA.

Sex differences in prodromal symptoms in acute coronary syndrome in patients aged 55†years or younger.

BACKGROUND: Studies suggest that young women are at highest risk for failing to recognise early symptoms of acute coronary syndrome (ACS). OBJECTIVES: To examine sex differences in prodromal symptoms occurring days and weeks prior to the acute presentation of ACS. We also examined health-seeking behaviours and prehospital management in young patients. METHODS: Prospective cross-sectional analysis of 1145 patients (368 women) hospitalised for ACS, aged ≤55 years, from the GENdEr and Sex DetermInantS of Cardiovascular Disease: From Bench to Beyond Premature Acute Coronary SYndrome cohort study (January 2009-April 2013). Prodromal symptoms were determined using the McSweeney Acute and Prodromal Myocardial Infarction Symptom questionnaire. Health-seeking behaviour and prehospital care were determined by questionnaires. RESULTS: The median age was 49 years. The prevalence of prodromal symptoms was high and more women reported symptoms than men (85% vs 72%, p<0.0001). Symptoms were similar between sexes and included unusual fatigue, sleep disturbances, anxiety and arm weakness/discomfort. Chest pain was less common in both sexes (24%). Women were more likely to seek care (49% vs 42%, p=0.04). Among those who sought care, women were more likely to use an ambulance for their ACS compared with men (52% vs 39%). Cardiovascular risk-reduction therapy use was low (≤40%) in all patients and less than half perceived their care provider suspected a cardiac source. CONCLUSIONS: Prior to ACS, women were more likely to experience prodromal symptoms and seek medical attention than men. Prehospital care was generally similar between sexes but demonstrated underutilisation of risk-reduction therapies in at-risk young adults.

Sex-related differences in access to care among patients with premature acute coronary syndrome.

BACKGROUND: Access to care may be implicated in disparities between men and women in death after acute coronary syndrome, especially among younger adults. We aimed to assess sex-related differences in access to care among patients with premature acute coronary syndrome and to identify clinical and gender-related determinants of access to care. METHODS: We studied 1123 patients (18-55 yr) admitted to hospital for acute coronary syndrome and enrolled in the GENESIS-PRAXY cohort study. Outcome measures were door-to-electrocardiography, door-to-needle and door-to-balloon times, as well as proportions of patients undergoing cardiac catheterization, reperfusion or nonprimary percutaneous coronary intervention. We performed univariable and multivariable logistic regression analyses to identify clinical and gender-related determinants of timely procedures and use of invasive procedures. RESULTS: Women were less likely than men to receive care within benchmark times for electrocardiography (≤ 10 min: 29% v. 38%, p = 0.02) or fibrinolysis (≤ 30 min: 32% v. 57%, p = 0.01). Women with ST-segment elevation myocardial infarction (MI) were less likely than men to undergo reperfusion therapy (primary percutaneous coronary intervention or fibrinolysis) (83% v. 91%, p = 0.01), and women with non-ST-segment elevation MI or unstable angina were less likely to undergo nonprimary percutaneous coronary intervention (48% v. 66%, p < 0.001). Clinical determinants of poorer access to care included anxiety, increased number of risk factors and absence of chest pain. Gender-related determinants included feminine traits of personality and responsibility for housework. INTERPRETATION: Among younger adults with acute coronary syndrome, women and men had different access to care. Moreover, fewer than half of men and women with ST-segment elevation MI received timely primary coronary intervention. Our results also highlight that men and women with no chest pain and those with anxiety, several traditional risk factors and feminine personality traits were at particularly increased risk of poorer access to care.

Sex differences in acute coronary syndrome symptom presentation in young patients.

IMPORTANCE: Little is known about whether sex differences in acute coronary syndrome (ACS) presentation exist in young patients and what factors determine absence of chest pain in ACS presentation. OBJECTIVES: To evaluate sex differences in ACS presentation and to estimate associations between sex, sociodemographic, gender identity, psychosocial and clinical factors, markers of coronary disease severity, and absence of chest pain in young patients with ACS. DESIGN, SETTING, PARTICIPANTS: We conducted a prospective cohort study of 1015 patients (30% women) 55 years or younger, hospitalized for ACS and enrolled in the GENESIS PRAXY (Gender and Sex Determinants of Cardiovascular Disease: From Bench to Beyond Premature Acute Coronary Syndrome) study (January 2009-September 2012). MAIN OUTCOMES AND MEASURES: The McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey was administered during hospitalization. RESULTS: The median age for both sexes was 49 years. Women were more likely to have non-ST-segment elevation myocardial infarction (37.5 vs 30.7; P = .03) and present without chest pain compared with men (19.0% vs 13.7%; P = .03). Patients without chest pain reported fewer symptoms overall and no discernable pattern of non-chest pain symptoms was found. In the multivariate model, being a woman (odds ratio [OR], 1.95 [95% CI, 1.23-3.11]; P = .005) and tachycardia (OR, 2.07 [95% CI, 1.20-3.56]; P = .009) were independently associated with ACS presentation without chest pain. Patients without chest pain did not differ significantly from those with chest pain in terms of ACS type, troponin level elevation, or coronary stenosis. CONCLUSIONS AND RELEVANCE: Chest pain was the most common ACS symptom in both sexes. Although women were more likely to present without chest pain than men, absence of chest pain was not associated with markers of coronary disease severity. Strategies that explicitly incorporate assessment of common non-chest pain symptoms need to be evaluated.

Rhythm versus rate control therapy and subsequent stroke or transient ischemic attack in patients with atrial fibrillation.

BACKGROUND: Stroke is a debilitating condition with an increased risk in patients with atrial fibrillation. Although data from clinical trials suggest that both rate and rhythm control are acceptable approaches with comparable rates of mortality in the short term, it is unclear whether stroke rates differ between patients who filled prescriptions for rhythm or rate control therapy. METHODS AND RESULTS: We conducted a population-based observational study of Quebec patients ≥65 years with a diagnosis of atrial fibrillation during the period 1999 to 2007 with the use of linked administrative data from hospital discharge and prescription drug claims databases. We compared rates of stroke or transient ischemic attack (TIA) among patients using rhythm (class Ia, Ic, and III antiarrhythmics), versus rate control (ß-blockers, calcium channel blockers, and digoxin) treatment strategies (either current or new users). The cohort consisted of 16 325 patients who filled a prescription for rhythm control therapy (with or without rate control therapy) and 41 193 patients who filled a prescription for rate control therapy, with a mean follow-up of 2.8 years (maximum 8.2 years). A lower proportion of patients on rhythm control therapy than on rate control therapy had a CHADS(2) (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and previous stroke or TIA) score of ≥2 (58.1% versus 67.0%, P<0.001). Treatment with any antithrombotic drug was comparable in the 2 groups (76.8% in rhythm control versus 77.8% in rate control group). Crude stroke/TIA incidence rate was lower in patients treated with rhythm control in comparison with rate control therapy (1.74 versus 2.49, per 100 person-years, P<0.001). This association was more marked in patients in the moderate- and high-risk groups for stroke according to the CHADS(2) risk score. In multivariable Cox regression analysis, rhythm control therapy was associated with a lower risk of stroke/TIA in comparison with rate control therapy (adjusted hazard ratio, 0.80; 95% confidence interval, 0.74, 0.87). The lower stroke/TIA rate was confirmed in a propensity score-matched cohort. CONCLUSIONS: In comparison with rate control therapy, the use of rhythm control therapy was associated with lower rates of stroke/TIA among patients with atrial fibrillation, in particular, among those with moderate and high risk of stroke.

Obesity and blood pressure in 17-year-old offspring of mothers with gestational diabetes: insights from the Jerusalem Perinatal Study.

OBJECTIVE: Gestational diabetes mellitus (GDM) influences fetal development and offspring's metabolic risk. We evaluated this association in 17-year-old offspring adjusting for birth weight (BW) and prepregnancy maternal BMI (mBMI). STUDY DESIGN: The JPS birth cohort contains extensive data on 92,408 births from 1964 to 1976. Offspring's BMI and blood pressure (BP) were obtained from military records. For a subcohort born between 1974 and 1976, prepregnancy mBMI was available. Offspring were classified as born to mothers with GDM (n = 293) or born to mothers without recorded GDM (n = 59,499). RESULTS: GDM offspring had higher mean BMI and systolic and diastolic BP compared to no-recorded-GDM offspring. After adjusting for BW, GDM remained significantly associated with offspring BMI and diastolic BP (ß = 1.169 and 1.520, resp.). In the subcohort, when prepregnancy mBMI was entered to the models, it markedly attenuated the associations with GDM. CONCLUSIONS: Maternal characteristics have long-term effects on cardiometabolic outcomes of their offspring aged 17 years.

The Cohen diabetic rat as a model for fetal growth restriction: vitamins C and E reduce fetal oxidative stress but do not restore normal growth.

UNLABELLED: Fetal growth restriction (FGR) describes newborns that were born small for gestational age. The etiology of FGR is unknown, but it is assumed that it is the consequences of both genetic and environmental factors, and that one of the important environmental factors is oxidative stress. In this study we used the Cohen diabetic (CD) rats (sensitive and resistant strains) and the original Sabra strain fed either high sucrose low copper diet-HSD or regular diet-RD to evaluate the genetic and environmental factors contributing to FGR. In addition, we treated the pregnant rats with antioxidants (vitamins C and E added to their food) to evaluate the effects of antioxidants in the prevention of FGR and in changing the redox state of the fetuses. METHODS: The study was performed on term 21-day-old fetuses of the three strains fed RD or HSD. Fetal and placental weight and fetal crown rump length were measured. Heart, kidneys, brain and liver were also weighted and studied. The fetal and placental redox status was investigated by studying the levels of Malondialdehyde (MDA) to determine the lipid peroxidation damage and by measuring the activity of catalase (CAT) and superoxide dismutase (SOD) enzymes. Similar studies were performed following the addition of 0.1% of vitamins C and E to the diet. RESULTS: FGR in the Cohen diabetic rats is a consequence of genetic (6-20% reduction in fetal weight in the CDr and CDs compared to Sabra) and environmental (11-36% reduction in fetal weight while on HSD) factors, with greater susceptibility in the CDs diabetic rats. Increased lipid peroxidation was observed in some of the organs only in HSD, however not only in the sensitive strain. In each organ, different patterns of anti oxidant capacity were observed. The addition of antioxidants to the food significantly reduced the signs of enhanced oxidative stress in all animals but partially restored normal fetal growth only in the diabetic CDs rats. This may imply that in this model oxidative stress is apparently not a major contributor to FGR. CONCLUSIONS: Cohen diabetic rats are a good model for the study of the interaction of genetic and environmental factors in the development of FGR. Maternal nutrition can influence the antioxidant capacity of the fetal organs which is modified by antioxidants. However, FGR in our model does not seem to result primarily from enhanced oxidative stress, as it is only partially affected by the antioxidant treatment. Thus, the repeated observations of oxidative stress in SGA infants may be a resulting metabolic alteration of FGR and not the main cause.