Maternal Hemoglobin A1c in the Third-Trimester May Underestimate Maternal Hyperglycemia and Its Impact on Offspring in Perinatal Demise Associated With Gestational Diabetes Mellitus: An Autopsy Case Series.

INTRODUCTION: Gestational diabetes mellitus (GDM) is a common metabolic disorder linked to adverse pregnancy outcomes. Recent research indicates that HbA1c is reliable in detecting maternal glycemia during the first trimester but may underestimate glucose intolerance in the late second to third trimesters. Therefore, it is reasonable to hypothesize that mothers with GDM, despite apparently normal HbA1c levels in the third trimester, may give birth to infants displaying characteristic features often seen in infants of diabetic mothers with suboptimal glycemic control. This study aimed to describe a case series of autopsy cases involving stillborn or deceased neonates delivered in the third trimester to mothers diagnosed with GDM and having normal HbA1c levels at or around the time of delivery. The primary focus was on identifying and documenting the characteristic features commonly associated with "infants of diabetic mothers" with suboptimal glycemic control in this series of cases. MATERIALS AND METHODS: We conducted a retrospective review of autopsy reports from our institution spanning 7.5 years. The study included cases that met the following criteria: (1) stillborn or infants who died in the early neonatal period, delivered in the third trimester; (2) mothers diagnosed with GDM; (3) normal maternal HbA1c levels of ≤6.1% at or around the time of delivery; (4) birthweight or femoral length exceeding the 90th percentile for gestational age; and (5) absence of genetic aberrations. We also examined these cases for other characteristic features associated with "infants of diabetic mothers." RESULTS: Ten autopsy cases met our inclusion criteria, including 9 stillbirths and 1 neonatal death. Gestational age at delivery ranged from 32 to 39 weeks (mean: 35.7 weeks). Femoral length exceeded the 90th percentile in all cases, and 6 cases had birthweights above the 90th percentile. Puffy facies were observed in 6 cases. Among the 9 cases with complete autopsies including internal examination, 6 exhibited excess adipose tissue, 4 had cardiomegaly, and 3 showed pancreatic islet hyperplasia. Hypoxic-ischemic encephalopathy was detected in 7 cases. No structural abnormalities were noted. DISCUSSION: Our findings demonstrated that fetuses and neonates born to mothers with apparently normal HbA1c levels in the third trimester could still display characteristic features commonly observed in infants of diabetic mothers with poor glycemic control, also known as "infants of diabetic mothers." This study underscores the potential of third-trimester maternal HbA1c measurements to underestimate maternal glycemia and its consequential impact on fetal development, as well as the subsequent manifestation of features of "infants of diabetic mothers."

Vitelline Vessel Remnant-Derived Funisitis Is a Sensitive and Specific Predictor of Histological Evidence of Amniotic Fluid Infection.

BACKGROUND: 4-11% of umbilical cords contain vitelline vessel remnants (VVRs). A recent study has described neutrophilic inflammation arising from VVRs and suggested an association with amniotic fluid infection (AFI). METHODS: During routine placental pathology sign-out over a six month period, we identified 70 cords with VVRs. HE-stained sections were re-examined for "VVR-derived funisitis," which was classified as low or high grade/stage based upon whether neutrophils were present only in Wharton's jelly near the VVRs or whether neutrophils were also present near the cord's amniotic surface. The same placentas were also examined for histologic evidence of AFI (maternal response = acute chorionitis or chorioamnionitis vs. fetal response = chorionic vasculitis, umbilical vasculitis, or funisitis vs. both). RESULTS: Neutrophilic inflammation arising from VVRs was present in 54.3% (38/70); 15 and 23 lesions were low and high grade/stage, respectively. "VVR-derived funisitis" was strongly associated with histological evidence of AFI elsewhere in the placenta. Its overall sensitivity and specificity were 0.94 and 0.88; when VVR-derived funisitis was high grade/stage or diagnosed in the third trimester, specificity rose to 1.0. CONCLUSION: "VVR-derived funisitis" has a strong association with histological evidence of AFI.

Quantifying the contribution of modifiable risk factors to socio-economic inequities in cancer morbidity and mortality: a nationally representative population-based cohort study.

BACKGROUND: Compared with those with a higher socio-economic position (SEP), individuals with a lower SEP have higher cancer morbidity and mortality. However, the contribution of modifiable risk factors to these inequities is not known. This study aimed to quantify the mediating effects of modifiable risk factors to associations between SEP and cancer morbidity and mortality. METHODS: This study used a prospective observational cohort design. We combined eight cycles of the Canadian Community Health Survey (2000/2001-2011) as baseline data to identify a cohort of adults (≥35 years) without cancer at the time of survey administration (n = 309 800). The cohort was linked to the Discharge Abstract Database and the Canadian Mortality Database for cancer morbidity and mortality ascertainment. Individuals were followed from the date they completed the Canadian Community Health Survey until 31 March 2013. Dates of individual first hospitalizations for cancer and deaths due to cancer were captured during this time period. SEP was operationalized using a latent variable combining measures of education and household income. Self-reported modifiable risk factors, including smoking, excess alcohol consumption, low fruit-and-vegetable intake, physical inactivity and obesity, were considered as potential mediators. Generalized structural equation modelling was used to estimate the mediating effects of modifiable risk factors in associations between low SEP and cancer morbidity and mortality in the total population and stratified by sex. RESULTS: Modifiable risk factors together explained 45.6% of associations between low SEP and overall cancer morbidity and mortality. Smoking was the most important mediator in the total population and for males, accounting for 15.5% and 40.2% of the total effect, respectively. For females, obesity was the most important mediator. CONCLUSIONS: Modifiable risk factors are important mediators of socio-economic inequities in cancer morbidity and mortality. Nevertheless, more than half of the variance in these associations remained unexplained. Midstream interventions that target modifiable risk factors may help to alleviate inequities in cancer risk in the short term. However, ultimately, upstream interventions that target structural determinants of health are needed to reduce overall socio-economic inequities in cancer morbidity and mortality.