Muscle sympathetic nerve activity during pregnancy: A systematic review and meta-analysis

We conducted a systematic review and meta-analysis to quantify the impact of healthy and complex pregnancy on muscle sympathetic nerve activity (MSNA) at rest, and in response to stress. Structured searches of electronic databases were performed until February 23, 2022. All study designs (except reviews) were included: population (pregnant individuals); exposures (healthy and complicated pregnancy with direct measures of MSNA); comparator (individuals who were not pregnant, or with uncomplicated pregnancy); and outcomes (MSNA, BP, and heart rate). Twenty-seven studies (N = 807) were included. MSNA burst frequency was higher in pregnancy (n = 201) versus non-pregnant controls (n = 194) (Mean Differences [MD], MD: 10.6 bursts/min; 95% CI: 7.2, 14.0; I²  = 72%). Accounting for the normative increase in heart rate with gestation, burst incidence was also higher during pregnancy (Pregnant N = 189, non-pregnant N = 173; MD: 11 bpm; 95% CI: 8, 13 bpm; I²  = 47%; p < 0.0001). Meta-regression analyses confirmed that although sympathetic burst frequency and incidence are augmented during pregnancy, this was not significantly associated with gestational age. Compared to uncomplicated pregnancy, individuals with obesity, obstructive sleep apnea, and gestational hypertension exhibited sympathetic hyperactivity, while individuals with gestational diabetes mellitus or preeclampsia did not. Uncomplicated pregnancies exhibited a lesser response to head-up tilt, but an exaggerated sympathetic responsiveness to cold pressor stress compared to non-pregnant individuals. MSNA is higher in pregnant individuals and further increased with some, but not all pregnancy complications. PROSPERO registration number: CRD42022311590.