Circulating Angiogenic Factors and the Risk of Adverse Outcomes among Haitian Women with Preeclampsia

Abstract

Objective: Angiogenic factors are strongly associated with adverse maternal and fetal outcomes among women with preterm preeclampsia (PE) in developed countries. We evaluated the role of angiogenic factors and their relationship to adverse outcomes among Haitian women with PE.

Material and methods: We measured plasma antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt1) and proangiogenic placental growth factor (PlGF) levels in women with PE (n=35) compared to controls with no hypertensive disorders (NHD) (n=43) among subjects with singleton pregnancies that delivered at Hospital Albert Schweitzer (HAS) in Haiti. We divided the preeclamptic women into two groups, early onset (≤ 34 weeks) and late onset (>34 weeks) and examined relationships between sFlt1/PlGF ratios on admission and adverse outcomes (abruption, respiratory complications, stroke, renal insufficiency, eclampsia, maternal death, birth weight <2500 grams, or fetal/neonatal death) in women with PE subgroups as compared to NHD groups separated by week of admission. Data are presented as median (25th-75th centile), n (%), and proportions.

Results: Among patients with PE, most (24/35) were admitted at term. Adverse outcome rates in PE were much higher among the early onset group compared to the late onset group (100.0% vs. 54.2%, P=0.007). Plasma angiogenic factors were dramatically altered in both subtypes of PE. Angiogenic factors also correlated with adverse outcomes in both subtypes of PE. The median sFlt1/PlGF ratios for subjects with early onset PE with any adverse outcome vs. NHD <=34 weeks with no adverse outcome were 703.1 (146.6, 1614.9) and 9.6 (3.5, 58.6); P<0.001). Among late onset group the median sFlt1/PlGF ratio for women with any adverse outcome was 130.7 (56.1, 242.6) versus 22.4 (10.2, 58.7; P=0.005) in NHD >34 weeks with no adverse outcome.

Conclusion: PE-related adverse outcomes are common in women in Haiti and are associated with profound angiogenic imbalance regardless of gestational age at presentation.

Fig 1. Frequency and number of adverse outcomes among early onset (≤34 weeks) and late onset (>34 weeks) preeclampsia at Hospital Albert Schweitzer in Haiti.

(A) Percentage of pregnant patients with early onset and late onset preeclampsia with adverse outcomes (Category I- Severe hypertension (BP ≥160/110), Category II- abruption or respiratory complications or stroke or renal failure or birth weight <2500 grams, Category III- Antepartum Eclampsia, Category IV- Maternal, Fetal and neonatal death, Cat V- any of the above adverse outcomes (Category I to IV)). All outcomes were ascertained only in presence of HTN (SBP> = 140 or DBP> = 90). (B) The x-axis shows the number of adverse outcomes and the y-axis shows each patient among different gestational age groups. Early onset PE = preeclampsia diagnosis at presentation at ≤34 weeks, Late onset PE = preeclampsia diagnosis at presentation at >34 weeks.

Fig 2. Preeclampsia diagnosis and angiogenic factors at Hospital Albert Schweitzer in Haiti.

Ratio of soluble fms-like tyrosine kinase 1 (sFlt1) to placental growth factor (PlGF) at presentation. The distribution of Natural log of sFlt1/PlGF ratio in pregnant women with no hypertensive disorder, early onset preeclampsia (≤34 weeks), and late onset preeclampsia (>34 weeks). Diagnoses were ascertained at the time of presentation. PE = preeclampsia, HTN = hypertension.

Fig 3. Adverse outcomes and angiogenic factors among patients with preeclampsia at Hospital Albert Schweitzer in Haiti.

The distribution of natural log transformed sFlt1/PlGF ratios at initial presentation by adverse outcomes is shown. Category I- Severe hypertension (BP ≥160/110), Category II- abruption or respiratory complications or stroke or renal failure or birth weight <2500 grams, Category III- Antepartum Eclampsia, Category IV- Maternal, Fetal and neonatal death, Cat V- any of the above adverse outcomes (Category I to IV). All outcomes were ascertained only in presence of HTN (SBP> = 140 or DBP> = 90). (A) Distribution among early onset preeclampsia (≤34 weeks). Control = women with no hypertensive disorder with no adverse outcome at ≤34 weeks on admission. (B) Distribution among late onset preeclampsia (>34 weeks). Control = women with no hypertensive disorder with no adverse outcome at >34 weeks on admission. P value compared to controls.

Fig 4. Correlation of angiogenic factor ratio with birth weight, highest systolic blood pressure (SBP) and highest diastolic blood pressure (DBP) and gestational age (GA) at delivery.

Pearson correlation with ln (sFlt1/PIGF Ratio) and birth weight (r = -0.25, P = 0.04), highest SBP (r = 0.50, P<0.001), highest DBP (r = 0.57, P<0.001), and GA of delivery (r = -0.30, P = 0.01).