Abstract 018: High Stillbirth Rate and Altered Maternal Renal Function and Water Balance are Associated With Spontaneous Gestational Hypertension in Nonhuman Primates

Abstract

Gestational hypertension (GH) is new-onset hypertension specific to pregnancy (PG) that may precede preeclampsia (PE). While the specific etiology of PE is unclear, defective fluid and electrolyte balances have been implicated. The African Green Monkey (AGM; Chlorocebus aethiops sabaeus ) is a novel model of spontaneous GH with pathophysiological consequences of PE. Systolic blood pressure (SBP; forearm plethysmography) was measured in AGMs pre-PG, during each trimester, and postpartum (PP). Gestational age was estimated by fetal lengths at 7 weeks/trimester (21 week gestation). Animals were characterized as normotensive (NT; SBP < 120 mmHg in PG and PP) or gestational hypertensive (GH; SBP ≥ 140 mmHg during PG). SBP was unchanged in NT PG (pre-PG 110 ± 5 mmHg; 1 st trimester 101± 6 mmHg; 3 rd 107 ± 7 mmHg; n = 27). In GH AGMs, SBP increased in the 3 rd trimester from 115 ± 6 mmHg (1 st ) and 117 ± 25 mmHg (2 nd ) to 152 ± 7 mmHg (3 rd ; p<0.05; n = 16). Plasma osmolality did not change during PG for NT AGMs but declined in GH (NT pre-PG 305 ± 5 mOsm/kg; PG 299 ± 5 mOsm/kg; n = 6; GH pre-PG 313 ± 6; PG 293 ± 4 mOsm/kg; p<0.05 ANOVA; n = 15). Maternal body weight increased in GH by the 1 st trimester, while NT body weight did not change until the 3 rd trimester (NT pre-PG 3.8 ± 0.2 kg; 1 st trimester 3.8 ± 0.3 kg; 3 rd 4.4 ± 0.2 kg; GH pre-PG 3.7 ± 0.1 kg; 1 st trimester 4.4 ± 0.2 kg; 3 rd 4.7 ± 0.1 kg; p<0.05). Protein excretion was unchanged in NT AGMs but increased with GH compared to pre-PG and NT PG (NT pre-PG 365 ± 45 mg/day; 3 rd trimester 466 ± 84 mg/day; GH pre-PG 346 ± 138 mg/day; 3 rd trimester 702 ± 69 mg/day; p<0.05). Third trimester estimated GFR (eGFR) did not change in NT AGMs but declined in GH (NT 5.0 ± 0.7 ml/min vs GH 2.5 ± 0.5 ml/min; p<0.05). Infants from GH pregnancies were smaller (NT 327.4 ± 13.7 g, n = 5, vs GH 290.0 ± 8.5 g n = 15; p<0.05) and GH increased fetal stillbirth rate to 40% (6/15). Thus, GH in AGMs has early PG water retention, decreased plasma osmolality and excess weight gain preceding GH. GH AGMs have smaller infants and increased stillbirth rates, showing fetal growth restriction. Elevated SBP during GH may lead to renal dysfunction, proteinuria and reduced eGFR. Thus, the AGM is a novel, translational model of hypertensive pregnancy disorders for the study of acute and long-term effects on fetal development.