Andree Gruslin

Adverse Fetal and Neonatal Outcomes Associated with a Life-Long High Fat Diet: Role of Altered Development of the Placental Vasculature

Maternal obesity results in a number of obstetrical and fetal complications with both immediate and long-term consequences. The increased prevalence of obesity has resulted in increasing numbers of women of reproductive age in this high-risk group. Since many of these obese women have been subjected to hypercaloric diets from early childhood we have developed a rodent model of life-long maternal obesity to more clearly understand the mechanisms that contribute to adverse pregnancy outcomes in obese women. Female Sprague Dawley rats were fed a control diet (CON - 16% of calories from fat) or high fat diet (HF - 45% of calories from fat) from 3 to 19 weeks of age. Prior to pregnancy HF-fed dams exhibited significant increases in body fat, serum leptin and triglycerides. A subset of dams was sacrificed at gestational day 15 to evaluate fetal and placental development. The remaining animals were allowed to deliver normally. HF-fed dams exhibited a more than 3-fold increase in fetal death and decreased neonatal survival. These outcomes were associated with altered vascular development in the placenta, as well as increased hypoxia in the labyrinth. We propose that the altered placental vasculature may result in reduced oxygenation of the fetal tissues contributing to premature demise and poor neonatal survival.

First-Trimester Levels of Pregnancy-Associated Plasma Protein A2 (PAPP-A2) in the Maternal Circulation Are Elevated in Pregnancies That Subsequently Develop Preeclampsia

Recent studies have consistently found pregnancy-associated plasma protein A2 (PAPP-A2) to be upregulated in preeclamptic placentae at term. We tested whether first-trimester circulating PAPP-A2 levels differed between complicated and uncomplicated pregnancies. We measured maternal PAPP-A2 levels at 10 to 14 weeks of gestational age in 17 pregnancies resulting in small-for-gestational-age (SGA) infants, 6 which developed preeclampsia (PE), 1 which developed PE and resulted in an SGA infant, and 37 gestational age-matched controls. The concentration of the PAPP-A2 isoform corresponding to the full-length protein was significantly higher in pregnancies that developed PE (35 ng/mL) compared with those that did not (23 ng/mL; P < .044). In contrast, we found no difference in PAPP-A2 levels between pregnancies that did or did not result in an SGA infant. The upregulation of PAPP-A2 that has previously been observed in PE at term appears to begin early in pregnancy, well before the symptoms develop.

5.6 The Control of Hypertension In Pregnancy Study (CHIPS) randomised controlled trial

Background Most obstetricians believe that BP normalisation in pregnancy reduces maternal complications, but may increase adverse perinatal outcomes. No adequately powered trials of differential BP control have been performed. Objective Determine best management of non-severe pregnancy hypertension. Methods In an open pragmatic international multicentre trial, women at 14+0–33+6 wk gestation with non-proteinuric pre-existing or gestational hypertension, office diastolic blood pressure (dBP) 90–105 mmHg (or 85–105 mmHg if on antihypertensives) and a live fetus were randomised to ‘less tight’ (target dBP 100 mmHg) or ‘tight’ control (target dBP 85 mmHg). The composite primary outcome was pregnancy loss or high level neonatal care for >48 h in the first 28d of life, and the secondary one/more serious maternal complications before 6wks. Outcomes were compared between groups using logistic regression adjusted for key prognostic factors (alpha = 0.05, two-sided, intention-to-treat). Results Of 1030 women randomised, 987 (94 sites) were included in the analysis. 74.6% had pre-existing hypertension. Women in ‘less tight’ (n=497) [vs. ‘tight’ (n = 490)] control had higher mean dBP by 4.5 mmHg (95% CI 3.6, 5.4), but similar rates of the primary (perinatal) outcome [31.4% vs. 30.7%; aOR 1.03, 95% CI 0.78, 1.36] and secondary (maternal) outcome [3.7% vs. 2.0%; aOR 1.74, 95% CI 0.79, 3.84]. Women receiving ‘less tight’ control more frequently developed BP ≥160/110mmHg) (40.4% vs. 27.5%; aOR 1.78, 95% CI 1.35, 2.36). Interpretation ‘Tight’ control is safer for the mother. These data reassure that it has no adverse effects for the baby. A target dBP of 85mmHg should be aimed for. Funding Canadian Institutes of Health Research.