Background: Severe food restriction (sFR) due to various psychological, environmental, and economic reasons can have adverse consequences on cardiovascular functioning and health. Inadequate caloric intake during pregnancy can lead to adverse effects for both the mother and the developing baby. Less well understood are the chronic effects of undernutrition on pregnancies that occur long after body weight (BW) has recovered following refeeding. Aim: To determine how a prior period of severe food restriction impacts maternal heart and kidney function and pup development during pregnancy, even when BW and caloric intake have been restored months before conception. Methods: Female Sprague-Dawley rats (3 months old) were fed normal chow ad libitum (Ctrl) or a 60% food-restricted diet for 2 weeks (sFR), followed by 3 months ad libitum access to the food (sFR-Refed). In both groups, breeding commenced at the beginning of the second month of refeeding. Once the pregnancy was confirmed, glomerular filtration rate (GFR) was assessed in the Ctrl and sFR-Refed pregnant animals on pregnancy day 15 utilizing transdermal sensors and FITC-sinistrin to measure fluorescent tracer clearance. Cardiac, renal, and uterine vasculature function and flow were analyzed by precision ultrasound during the late pregnancy period (day 20). On day 21, the animals were infused with Evans blue for plasma volume determination, and the maternal blood pressure was recorded through femoral catheterization. Maternal tissue weight, placental weight, fetal body weight (BW), and fetal head and chest circumference were measured to assess placental efficiency and fetal growth restriction. Results: After 2 weeks of sFR, rats lost approximately 20% of their initial BW DFinal/Initial (g): Ctrl, 8.0±2.3, n=9 vs sFR, -46.9±1.0, n=9; p< 0.0001. BW recovered to match Ctrl levels within 2 weeks of refeeding however sFR-Refed tended to gain less BW during pregnancy DFinal/Initial (g): Ctrl, 95.7±5.6, n=7 vs sFR-Refed, 71.2±9.9, n=5; p=0.07. Renal artery blood flow (RABF) was significantly reduced mL/min: Ctrl, 259.3±17.1, n=14 vs sFR-Refed, 207.6±11.1, n=17 p=0.01 and there was also a trend toward lower cardiac output in sFR-Refed pregnant rats compared to the Ctrl group despite there being no difference in maternal heart and kidney weights. Plasma volume was also significantly reduced in the sFR-Refed mL/100g BW: Ctrl, 3.4±0.15, n=6 vs sFR-Refed, 2.9±0.15; n=9 p=0.04. Despite reduced RABF and plasma volume, GFR was not significantly different between groups. Although resistance index (RI) of the placental artery significantly decreased RI: Ctrl, 0.72±0.06, n=4 vs sFR-Refed, 0.54±0.03, n=5; p=0.01, placental efficiency placenta: pup ratio (g): Ctrl, 9.6±0.35, n=3 vs sFR-Refed, 8.6±0.22, n=5; p=0.01 was still reduced, and pup head:chest ratios AU: Ctrl, 0.92±0.03, n=3 vs sFR-Refed, 1.0±0.003, n=5; p=0.01 was higher in the pups of the sFR-Refed group. Conclusion: Exposure to sFR followed by months of refeeding has chronic adverse effects on the kidneys and cardiovascular system in pregnant rats. Although pregnancy occurred months after severe food restriction ended and BW normalized, adverse effects on pup development were still evident. Additional research is necessary to understand how previous food restriction, either voluntarily (e.g., crash diets) or involuntarily (e.g., very low food security), increases the risk for maternal cardiovascular and renal disease as well as poor pregnancy outcomes and fetal development. Funding: AHA: 940246 (AS); KL2: KL2TR001432 (AS); Marriott Award: EG400066 (AS); DOD: W81XWH2110201 (AS). This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Mackie et al. (Fri,) studied this question.