Ayala Burger

Associations of Maternal Prepregnancy Body Mass Index and Gestational Weight Gain With Adult Offspring Cardiometabolic Risk Factors The Jerusalem Perinatal Family Follow-Up Study

Background— Accumulating evidence demonstrates that both maternal prepregnancy body mass index (mppBMI) and gestational weight gain (GWG) are associated with adult offspring adiposity. However, whether these maternal attributes are related to other cardiometabolic risk factors in adulthood has not been comprehensively studied. Methods and Results— We used a birth cohort of 1400 young adults born in Jerusalem who had extensive archival data and clinical information at 32 years of age to prospectively examine the associations of mppBMI and GWG with adiposity and related cardiometabolic outcomes. Greater mppBMI, independently of GWG and confounders, was significantly associated with higher offspring BMI, waist circumference, systolic and diastolic blood pressures, insulin, and triglycerides and with lower high-density lipoprotein cholesterol. For example, the effect sizes were translated to nearly 5 kg/m2 higher mean BMI, 8.4 cm higher waist circumference, 0.13 mmol/L (11.4 mg/dL) higher triglycerides, and 0.10 mmol/L (3.8 mg/dL) lower high-density lipoprotein cholesterol among offspring of mothers within the upper mppBMI quartile (mppBMI >26.4 kg/m2) compared with the lower quartile (mppBMI <21.0 kg/m2). GWG, independently of mppBMI, was positively associated with offspring adiposity; differences of 1.6 kg/m2 in BMI and 2.4 cm in waist were observed when offspring of mothers in the upper (GWG >14 kg) and lower (GWG <9 kg) quartiles of GWG were compared. Further adjustment for offspring adiposity attenuated the observed associations to the null. Conclusions— Maternal size both before and during pregnancy is associated with cardiometabolic risk factors in young adult offspring. The associations appear to be driven mainly by offspring adiposity. Future studies that explore mechanisms underlying the intergenerational cycle of obesity are warranted to identify potentially novel targets for cardiometabolic risk-reduction interventions.

Association between number of children and mortality of mothers: results of a 37-year follow-up study

PURPOSE To examine the association between parity and long-term, all-cause mortality and mortality owing to specific causes in women. METHODS This prospective population-based study included 40,454 mothers who gave birth in Western Jerusalem, Israel, to 125,842 children and were followed for an average of 37 years after the birth of their first child. Cox proportional hazards models were used to evaluate long-term total and specific-cause mortality of women by their parity. RESULTS We found a U-shaped relationship between the number of offspring and risk of all-cause mortality in mothers. After adjustment for sociodemographic characteristics and maternal health and obstetric conditions, higher mortality rates were observed for mothers of 1 child (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.04-1.4), mothers of 5 to 9 children (HR, 1.21; 95% CI, 1.09-1.33), and mothers of 10 or more children (HR, 1.49; 95% CI, 1.12-1.99) compared with mothers of 2 to 4 children. Mortality risk from specific causes including coronary disease, circulatory disease, and cancer were increased for multiparous women. CONCLUSIONS In this long-term follow-up study, there was an association between number of children and mortality risk for mothers. These findings suggest that maternal pregnancies and postnatal characteristics as reflected by number of children may have consequences for long-term maternal health.

Delineation of C12orf65-related phenotypes: a genotype–phenotype relationship

C12orf65 participates in the process of mitochondrial translation and has been shown to be associated with a spectrum of phenotypes, including early onset optic atrophy, progressive encephalomyopathy, peripheral neuropathy, and spastic paraparesis.We used whole-genome homozygosity mapping as well as exome sequencing and targeted gene sequencing to identify novel C12orf65 disease-causing mutations in seven affected individuals originating from two consanguineous families. In four family members affected with childhood-onset optic atrophy accompanied by slowly progressive peripheral neuropathy and spastic paraparesis, we identified a homozygous frame shift mutation c.413_417 delAACAA, which predicts a truncated protein lacking the C-terminal portion. In the second family, we studied three affected individuals who presented with early onset optic atrophy, peripheral neuropathy, and spastic gait in addition to moderate intellectual disability. Muscle biopsy in two of the patients revealed decreased activities of the mitochondrial respiratory chain complexes I and IV. In these patients, we identified a homozygous splice mutation, g.21043 T>A (c.282+2 T>A) which leads to skipping of exon 2. Our study broadens the phenotypic spectrum of C12orf65 defects and highlights the triad of optic atrophy, axonal neuropathy and spastic paraparesis as its key clinical features. In addition, a clear genotype–phenotype correlation is anticipated in which deleterious mutations which disrupt the GGQ-containing domain in the first coding exon are expected to result in a more severe phenotype, whereas down-stream C-terminal mutations may result in a more favorable phenotype, typically lacking cognitive impairment.

Associations of maternal pre‐pregnancy and gestational body size with offspring longitudinal change in BMI

Studies demonstrate associations between changes in obesity‐related phenotypes and cardiovascular risk. Although maternal pre‐pregnancy BMI (mppBMI) and gestational weight gain (GWG) may be associated with adult offspring adiposity, no study has examined associations with obesity changes. Associations of mppBMI and GWG with longitudinal change in offsprings BMI (ΔBMI) were examined, and whether associations are explained by offspring genetics was assessed.

The Association of Maternal Intrapartum Subfebrile Temperature and Adverse Obstetric and Neonatal Outcomes

BACKGROUND Subfebrile intrapartum maternal temperature is very common, yet there is sparse evidence regarding its causes or its effects on perinatal outcomes. We examined whether mild temperature elevation during labour is a risk marker for adverse obstetric and neonatal outcomes. METHODS A retrospective cohort analysis including 42 601 term, singleton live-births in two medical centres between 2003 and 2010 was performed. This study compared women who experienced a maximal intrapartum temperature of ≤37°C with women who experienced subfebrile intrapartum temperature (37.1-37.9°C). Adjusted risks for adverse obstetric and neonatal outcomes were calculated by using multivariable logistic regression models. RESULTS Compared with maternal temperature ≤ 37°C, subfebrile temperature was associated with higher rates of primary caesarean deliveries {adjusted odds ratios [aOR] = 1.36 [95% confidence interval (CI) 1.25, 1.49])} and assisted vaginal deliveries (aOR = 1.20 [95% CI 1.11, 1.30]), as well as with greater risks of early neonatal sepsis (aOR = 2.66 [95% CI 1.88, 3.77]), neonatal intensive care unit admissions (aOR = 1.40 [95% CI 1.08, 1.83]), and neonatal asphyxia or seizures (aOR = 3.18 [95% CI 1.51, 6.70]). Mildly elevated maternal intrapartum temperature (37.1-37.5°C) was also associated with adverse outcomes. CONCLUSIONS Maternal intrapartum subfebrile temperature may be an indicator of operative delivery and neonatal morbidity. Further research is needed to confirm these findings and to reveal underlying mechanisms.

Maternal genetic variation accounts in part for the associations of maternal size during pregnancy with offspring cardiometabolic risk in adulthood.

Background Maternal pre-pregnancy body-mass index (ppBMI) and gestational weight gain (GWG) are associated with cardiometabolic risk (CMR) traits in the offspring. The extent to which maternal genetic variation accounts for these associations is unknown. Methods/Results In 1249 mother-offspring pairs recruited from the Jerusalem Perinatal Study, we used archival data to characterize ppBMI and GWG and follow-up data from offspring to assess CMR, including body mass index (BMI), waist circumference, glucose, insulin, blood pressure, and lipid levels, at an average age of 32. Maternal genetic risk scores (GRS) were created using a subset of SNPs most predictive of ppBMI, GWG, and each CMR trait, selected among 1384 single-nucleotide polymorphisms (SNPs) characterizing variation in 170 candidate genes potentially related to fetal development and/or metabolic risk. We fit linear regression models to examine the associations of ppBMI and GWG with CMR traits with and without adjustment for GRS. Compared to unadjusted models, the coefficient for the association of a one-standard-deviation (SD) difference in GWG and offspring BMI decreased by 41% (95%CI −81%, −11%) from 0.847 to 0.503 and the coefficient for a 1SD difference in GWG and WC decreased by 63% (95%CI −318%, −11%) from 1.196 to 0.443. For other traits, there were no statistically significant changes in the coefficients for GWG with adjustment for GRS. None of the associations of ppBMI with CMR traits were significantly altered by adjustment for GRS. Conclusions Maternal genetic variation may account in part for associations of GWG with offspring BMI and WC in young adults.

Associations of Maternal Pre-pregnancy Body Mass Index and Gestational Weight Gain with Offspring Longitudinal Change in BMI

Studies demonstrate associations between changes in obesity‐related phenotypes and cardiovascular risk. Although maternal pre‐pregnancy BMI (mppBMI) and gestational weight gain (GWG) may be associated with adult offspring adiposity, no study has examined associations with obesity changes. Associations of mppBMI and GWG with longitudinal change in offsprings BMI (ΔBMI) were examined, and whether associations are explained by offspring genetics was assessed.

Leukocyte blood count during early puerperium and its relation to puerperal infection

Abstract Objective: To describe the white blood cell (WBC) and neutrophil counts in early puerperium and to investigate their contribution to the diagnosis of puerperal bacterial infection. Methods: A retrospective cohort analysis through which clinical and laboratory data were collected from 67 695 term live births. Total leukocyte and neutrophil blood count percentiles were established for febrile parturients (FP) with puerperal fever (≥38 °C) and for non-FP (NFP), and stratified by mode of delivery. Rates of positive bacterial cultures were compared according to the total leukocyte and neutrophil blood counts. Results: Mean WBC counts of parturients delivering vaginally and by cesarean section were 12.62 × 103 and 12.71 × 103/µL for NFP, and 14.38 × 103 and 12.74 × 103/µL for FP, respectively. The proportions of parturients with a WBC count of ≥15 × 103/µL were 36.4% for FP and 21.8% for NFP (p < 0.001). Neutrophils comprised 80% or more of the leukocyte count in 57.6% of FP and in 30.6% of NFP (p < 0.001). However, no statistically significant differences in the rates of positive bacterial cultures were observed between those with high and low levels of leukocytes and neutrophils. Conclusions: Leukocytosis and non-extreme neutrophilia were not found to reliably associate with bacterial infection, and their value in determining antibiotic therapy is questioned.

Associations of Maternal Prepregnancy Body Mass Index and Gestational Weight Gain With Adult Offspring Cardiometabolic Risk Factors

Background— Accumulating evidence demonstrates that both maternal prepregnancy body mass index (mppBMI) and gestational weight gain (GWG) are associated with adult offspring adiposity. However, whether these maternal attributes are related to other cardiometabolic risk factors in adulthood has not been comprehensively studied. Methods and Results— We used a birth cohort of 1400 young adults born in Jerusalem who had extensive archival data and clinical information at 32 years of age to prospectively examine the associations of mppBMI and GWG with adiposity and related cardiometabolic outcomes. Greater mppBMI, independently of GWG and confounders, was significantly associated with higher offspring BMI, waist circumference, systolic and diastolic blood pressures, insulin, and triglycerides and with lower high-density lipoprotein cholesterol. For example, the effect sizes were translated to nearly 5 kg/m2 higher mean BMI, 8.4 cm higher waist circumference, 0.13 mmol/L (11.4 mg/dL) higher triglycerides, and 0.10 mmol/L (3.8 mg/dL) lower high-density lipoprotein cholesterol among offspring of mothers within the upper mppBMI quartile (mppBMI >26.4 kg/m2) compared with the lower quartile (mppBMI <21.0 kg/m2). GWG, independently of mppBMI, was positively associated with offspring adiposity; differences of 1.6 kg/m2 in BMI and 2.4 cm in waist were observed when offspring of mothers in the upper (GWG >14 kg) and lower (GWG <9 kg) quartiles of GWG were compared. Further adjustment for offspring adiposity attenuated the observed associations to the null. Conclusions— Maternal size both before and during pregnancy is associated with cardiometabolic risk factors in young adult offspring. The associations appear to be driven mainly by offspring adiposity. Future studies that explore mechanisms underlying the intergenerational cycle of obesity are warranted to identify potentially novel targets for cardiometabolic risk-reduction interventions.

Associations of socioeconomic position in childhood and young adulthood with cardiometabolic risk factors: the Jerusalem Perinatal Family Follow-Up Study.

Background Several stages in the life course have been identified as important to the development of cardiovascular disease. This study aimed to assess the associations of childhood and adulthood socioeconomic position (SEP) and social mobility with cardiometabolic risk factors (CMRs) later in life. Methods We conducted follow-up examinations of 1132 offspring, aged 32, within a population-based cohort of all births in Jerusalem from 1974 to 1976. SEP was indicated by parents’ occupation and education, and adulthood SEP was based on offsprings occupation and education recorded at age 32. Linear regression models were used to investigate the associations of SEP and social mobility with CMRs. Results Childhood-occupational SEP was negatively associated with body mass index (BMI; β=−0.29, p=0.031), fat percentage (fat%; β=−0.58, p=0.005), insulin (β=−0.01, p=0.031), triglycerides (β=−0.02, p=0.024) and low-density lipoprotein cholesterol (LDL-C; β=−1.91, p=0.015), independent of adulthood SEP. Adulthood-occupational SEP was negatively associated with waist-to-hip ratio (WHR; β=−0.01, p=0.002), and positively with high-density lipoprotein cholesterol (HDL-C; β=0.87, p=0.030). Results remained similar after adjustment for smoking and inactivity. Childhood-educational SEP was associated with decreased WHR and LDL-C level (p=0.0002), and adulthood-educational SEP was inversely associated with BMI (p=0.001), waist circumference (p=0.008), WHR (p=0.001) and fat% (p=0.0002) and positively associated with HDL-C (p=0.030). Additionally, social mobility (mainly upward) was shown to have adverse cardiometabolic outcomes. Conclusions Both childhood and adulthood SEP contribute independently to CMR. The match–mismatch hypothesis may explain the elevated CMRs among participants experiencing social mobility. Identification of life-course SEP-related aspects that translate into social inequality in cardiovascular risk may facilitate efforts for improving health and for reducing disparities in cardiovascular disease.