Bariatric surgery And consequences for Mother and Baby In pregnancy: The BAMBI study

Roux-en-Y gastric bypass improves fertility and decreases obesity-relatedrisks in pregnancy. However, gastric bypass is also associated withalterations in glucose metabolism. Following meals, a rapid secretion ofglucagon-like peptide 1 (GLP-1) causes an increased insulin release thatcan result in a disproportion in glucose and insulin levels with risk ofpostprandial hypoglycemia. On the other hand, insulin sensitivitydecreases during pregnancy. Evidence is limited on how these effectsinteract on glucose metabolism in pregnancy following gastric bypass.A higher risk of restricted fetal growth is evident in pregnancies followinggastric bypass with an increase in the number of small-for-gestationalage (SGA) neonates and a lower mean birthweight as compared tocontrols. Insufficient maternal gestational weight gain has beenassociated with SGA neonates, but does not account for all cases.

The aims of the Bariatric surgery And consequences for Mother and Baby In pregnancy (BAMBI) study were to investigate glucose profiles during pregnancy as assessed by mixed meal test (MMT) and continuous glucose monitoring (CGM). Furthermore, to investigate risk factors associated with hypoglycemia, and the association between fetal growth and hypoglycemia in pregnant women previously treated with gastric bypass compared to matched controls.

The BAMBI cohort consisted of pregnant women treated with gastric bypass, and BMI- and parity-matched controls who were recruited from April 2019 to November 2021. All participants were prospectively followed from the first trimester until 4-6 weeks postpartum. Glucose and enteropancreatic hormone profiles were studied with a liquid MMT in the first and third trimester of pregnancy. Additionally, glucose profiles were studied with CGM in the first, second, and third trimester, as well as 4-6 weeks postpartum. Time in range (TIR) was defined as time with interstitial glucose of 3.5-7.8 mmol/L (63-140 mg/dL). Fetal growth was examined by ultrasound in gestational week 28, 32, and 36. At birth, anthropometric measures were obtained as well as neonatal dual energy X-ray absorption (DXA) scans and skinfold measurements.

A 2 hour 75 g oral glucose tolerance test was performed at 24 weeks of gestation among the matched controls to screen for gestational diabetes mellitus.

Twenty-three pregnant women with gastric bypass and 23 BMI- and parity-matched pregnant controls were included in the BAMBI cohort. Women with gastric bypass were 4 years (IQR: 0–7) older than controls. Pregnancies occurred 30 months (IQR: 15-98) following gastric bypass, which reduced their BMI from 45 kg/m2
(IQR: 42-54) pre-surgery to 32 kg/m2 (IQR: 27-39) pre- regnancy.
During MMT, fasting plasma glucose levels were lower, peak plasma glucose levels were higher and nadir plasma glucose levels lower among the women with gastric bypass in both early and late pregnancy. Furthermore, peak and nadir plasma glucose occurred earlier among the women with gastric bypass compared to the matched controls. Despite an increase in insulin resistance among women with gastric bypass from the first to the third trimester, hypoglycemia occurred in both first and third trimester of pregnancy. In the first trimester, GLP-1 was positively and
glucagon negatively associated with nadir plasma glucose, while only glucagon was negatively associated with nadir plasma glucose in the third trimester. During CGM, Women with gastric bypass had decreased TIR (87.3-89.5% vs. 93.3-96.1%, plower nadir weight, and greater weight loss following gastric bypass. While six neonates born of women with gastric bypass were SGA, one was SGA among the controls (p=0.10). As assessed by ultrasound and clinical examinations, weight and abdominal circumference tended to be lower throughout pregnancy and at birth for the offspring of the women with gastric bypass compared to matched controls. In addition, the offspring of women with gastric bypass and increased time in hypoglycemia had further reduced weight and abdominal circumference compared to the women with gastric bypass with acceptable time in hypoglycemia. While the differences in birthweight were not statistically significant, the abdominal circumference percentile was significantly lower among the women with increased time in hypoglycemia compared to those with acceptable time in hypoglycemia in the gastric bypass group (20th (IQR 0- 30) vs. 55th (IQR: 27-91) percentile, p=0.01).

In conclusion, women with gastric bypass were more exposed to both hypo- and hyperglycemia during pregnancy compared to matched pregnant controls. While the risk of hypoglycemia was unchanged during pregnancy according to the MMT results, it aggravated during pregnancy judged from the CGM results. This difference may be explained partly by physical activity during the measurements and the food ingested. While the women were not physical active before and during the MMT, they could be physical active during the CGM. Regarding the food ingested, the women ingested a standardized meal during the MMT, while they ate food
of their own choice during CGM. The ingested food during the CGM may have contained more simple carbohydrates, which in turn could provoke hypoglycemia. Increased intake of simple carbohydrates could explain the twofold increase in TAR among the women with gastric bypass. These results of the BAMBI study warrant evidence based guidelines for the screening of gestational diabetes mellitus in pregnancy following gastric bypass as well as further studies including information on diet and physical activity during CGM measurements. To reduce the number of SGA neonates born of women treated with gastric bypass, the etiology must be clarified. Achieving appropriate gestational weight gain has been suggested. The results of the BAMBI study suggest glycemic monitoring and optimization as another target of intervention. However, the results should be confirmed in a larger study population.