Pregnancy insulin, glucose, and BMI contribute to birth outcomes in nondiabetic mothers.

OBJECTIVE: We investigated the effects of normal variations in maternal glycemia on birth size and other birth outcomes. RESEARCH DESIGN AND METHODS: Women in two unselected birth cohorts, one retrospective (n = 3,158) and one prospective (n = 668), underwent an oral glucose challenge at 28 weeks of gestation. In the retrospective study, glycemia was linked to routine birth records. In the prospective study, offspring adiposity was assessed by skinfold thickness from birth to age 24 months. RESULTS: In the retrospective study, within the nondiabetic range (2.1-7.8 mmol/l), each 1 mmol/l rise in the mother's 60-min glucose level was associated with a (mean +/- SEM) 2.1 +/- 0.8% (P = 0.006) rise in absolute risk of assisted vaginal delivery, a 3.4 +/- 0.8% (P 90th centile) was independently related to the mother's fasting glucose (odds ratio 2.61 per +1 mmol/l [95% CI 1.15-5.93]) and prepregnancy BMI (1.10 per +1 kg/m(2) [1.04-1.18]). The mother's higher fasting glycemia (P = 0.004), lower insulin sensitivity (P = 0.01), and lower insulin secretion (P = 0.02) were independently related to greater offspring adiposity at birth. During postnatal follow-up, the correlation between the mother's glycemia and offspring adiposity disappeared by 3 months, whereas prepregnancy BMI was associated with offspring adiposity that was only apparent at 12 and 24 months (both P < 0.05). CONCLUSIONS: Prepregnancy BMI, pregnancy glycemia, insulin sensitivity, and insulin secretion all contribute to offspring adiposity and macrosomia and may be separate targets for intervention to optimize birth outcomes and later offspring health

Modifying effect of dual antiplatelet therapy on incidence of stent thrombosis according to implanted drug-eluting stent type

Aim To investigate the putative modifying effect of dual antiplatelet therapy (DAPT) use on the incidence of stent thrombosis at 3 years in patients randomized to Endeavor zotarolimus-eluting stent (E-ZES) or Cypher sirolimus-eluting stent (C-SES). Methods and results Of 8709 patients in PROTECT, 4357 were randomized to E-ZES and 4352 to C-SES. Aspirin was to be given indefinitely, and clopidogrel/ticlopidine for ≥3 months or up to 12 months after implantation. Main outcome measures were definite or probable stent thrombosis at 3 years. Multivariable Cox regression analysis was applied, with stent type, DAPT, and their interaction as the main outcome determinants. Dual antiplatelet therapy adherence remained the same in the E-ZES and C-SES groups (79.6% at 1 year, 32.8% at 2 years, and 21.6% at 3 years). We observed a statistically significant (P = 0.0052) heterogeneity in treatment effect of stent type in relation to DAPT. In the absence of DAPT, stent thrombosis was lower with E-ZES vs. C-SES (adjusted hazard ratio 0.38, 95% confidence interval 0.19, 0.75; P = 0.0056). In the presence of DAPT, no difference was found (1.18; 0.79, 1.77; P = 0.43). Conclusion A strong interaction was observed between drug-eluting stent type and DAPT use, most likely prompted by the vascular healing response induced by the implanted DES system. These results suggest that the incidence of stent thrombosis in DES trials should not be evaluated independently of DAPT use, and the optimal duration of DAPT will likely depend upon stent type (Clinicaltrials.gov number NCT00476957

Maternal and fetal fatty acid profile in normal and intrauterine growth restriction pregnancies with and without preeclampsia

The aim of this study was to evaluate maternal and fetal lipid profile in intrauterine growth restriction (IUGR) pregnancies with and without preeclampsia (PE). Thirteen normal pregnancies studied during the third trimester (control M) and 29 at elective cesarean section (control CS) were compared with 18 pregnancies complicated by IUGR (IUGR only) and with seven pregnancies complicated by both IUGR and PE (IUGR-PE). Total plasma fatty acids, triglycerides,cholesterol, and nonesterified fatty acids (NEFA) were determined in maternal and fetal plasma. Nutritional intake was analyzed. IUGR only mothers had lower percentage of linoleic acid (LA) and higher arachidonic acid (AA) than controls, partly explained by higher AA dietary intake. Higher levels of NEFA were observed both in IUGR only and in IUGR-PE mothers whereas triglyceride levels were increased in IUGR-PE mothers only. In IUGR-PE fetuses, LA and AA were significantly decreased, whereas triglyceride and NEFA concentrations were significantly increased compared with normal fetuses. In conclusion, IUGR only is associated with altered fatty acids profile not completely accounted by dietary changes. We hypothesize that the differences observed in IUGR with PE for triglycerides and other lipids could be related to a difference in maternal phenotype

Convergence in insulin resistance between very severely obese and lean women at the end of pregnancy

AIMS: Disrupted intermediary metabolism may contribute to the adverse pregnancy outcomes in women with very severe obesity. Our aim was to study metabolism in such pregnancies. METHODS: We recruited a longitudinal cohort of very severely obese (n = 190) and lean (n = 118) glucose-tolerant women for anthropometric and metabolic measurements at early, mid and late gestation and postpartum. In case–control studies of very severely obese and lean women we measured glucose and glycerol turnover during low- and high-dose hyperinsulinaemic–euglycaemic clamps (HEC) at early and late pregnancy and in non-pregnant women (each n = 6–9) and body fat distribution by MRI in late pregnancy (n = 10/group). RESULTS: Although greater glucose, insulin, NEFA and insulin resistance (HOMA-IR), and greater weight and % fat mass (FM) was observed in very severely obese vs lean participants, the degree of worsening was attenuated in the very severely obese individuals with advancing gestation, with no difference in triacylglycerol (TG) concentrations between very severely obese and lean women at term. Enhanced glycerol production was observed in early pregnancy only in very severely obese individuals, with similar intrahepatic FM in very severely obese vs lean women by late gestation. Offspring from obese mothers were heavier (p = 0.04). CONCLUSIONS/INTERPRETATION: Pregnancies complicated by obesity demonstrate attenuation in weight gain and insulin resistance compared with pregnancies in lean women. Increased glycerol production is confined to obese women in early pregnancy and obese and lean individuals have similar intrahepatic FM by term. When targeting maternal metabolism to treat adverse pregnancy outcomes, therapeutic intervention may be most effective applied early in pregnancy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-015-3708-3) contains peer-reviewed but unedited supplementary material, which is available to authorised users

Obesity rates in two generations of Swedish women entering pregnancy, and associated obesity risk among adult daughters

We examined changes in obesity rates in two generations of Swedish women entering pregnancy, and assessed the effects of maternal body mass index (BMI) on the risk of overweight or obesity among adult daughters. This study covered an intergenerational retrospective cohort of 26,561 Swedish mothers and their 26,561 first-born daughters. There was a 4-fold increase in obesity rates, which rose from 3.1% among women entering pregnancy in 1982-1988 to 12.3% among their daughters in 2000-2008 (p &lt; 0.0001) when entering pregnancy. The greater the maternal BMI, the greater the odds of overweight and/or obesity among daughters. Underweight mothers had half the odds of having an overweight or obese daughter in comparison to mothers of normal BMI (p &lt; 0.0001). In contrast, the odds ratio of obese mothers having obese daughters was 3.94 (p &lt; 0.0001). This study showed a strong association between maternal obesity and the risk of obesity among their first-born daughters. In addition, we observed a considerable increase in obesity rates across generations in mother-daughter pairs of Swedish women entering pregnancy. Thus, it is important to have preventative strategies in place to halt the worsening intergenerational cycle of obesity