Effect of Roux-en-Y Gastric Bypass (RYGB) Surgery on Pregnancy and Offspring in Rhesus Macaques

Background: Two-thirds of women of reproductive age are overweight or obese leading to decreased conception rates, and increased maternal and fetal morbidity and mortality. Bariatric surgeries, like Roux-en-Y gastric bypass (RYGB), are successful treatments for weight loss. RYGB partially limits the absorption of nutrients, which can include vitamins and minerals. The objective of our study was to test the impact of RYGB in obese females, specifically on fertility, placental function, and prenatal and offspring outcomes in a nonhuman primate model. Methods: Female rhesus macaques were assigned to three cohorts: controls (C; n = 9), obese on a western style diet (WSD; n = 10) and RYGB (n = 8). Animals were bred, allowed to deliver naturally, and infants followed through 6 months of age. Metabolic studies were performed in all animals prior to breeding and throughout pregnancy and lactation. In RYGB animals, metabolic studies were also performed before and after surgery. Placental function and fetal growth were assessed by prenatal ultrasound. Postnatally, offspring assessments of weight and metabolism occurred through 6 months of age. Results: RYGB resulted in 26 ± 0.1% body weight loss that was maintained for 6 months prior to breeding. Despite effective weight loss, RYGB did not improve fecundity, but was associated with increased perinatal morbidity. RYGB significantly decreased levels of Vitamin B12 (p < 0.001) and folate (p < 0.05) post-RYGB. Weight gain during pregnancy was lower in HFD dams (p < 0.05), but similar in RYGB and C animals. RYGB animals had improved glucose homeostasis after surgery compared to WSD, except for elevated fasting glucose levels (p < 0.05) in the third trimester. There was no difference in placental function across all three animal cohorts. Offspring from RYGB pregnancies experienced more rapid weight gain after birth, especially in males (p < 0.05). Conclusions: RYGB improved pre-pregnancy weight in obese females, but did not improve fertility, pregnancy outcomes, placental function, or insulin resistance compared to HFD. Multivitamin supplementation was required to support pregnancies, although malabsorption persisted. Offspring of RYGB pregnancies, especially males, also have an accelerated growth curve trend.