Table 1.
Randomized studies of omega-3 supplementation and hypertensive disorders of pregnancy.
| Author(-s) and Year | Supplementation Per Day According to Methods | Population and Sample with Adjustments for Exclusion, Dropout and Missing Information Where Possible | Gestational Age at Randomization/Baseline and Treatment Duration | Preeclampsia and Hypertension Criteria According to Methods Section |
|---|---|---|---|---|
| Moodley and Norman, 1989 [6] | Evening primrose oil 400 mg (LA 73% and 8% GLA) vs. placebo | 47 (23 + 24) primigravidae pregnancies, singleton or twins not mentioned | Mean 35 (range 30–36) weeks in main group and mean 34 (range 32–36) weeks in control group Duration: minimum 2 weeks | Study included women with established preeclampsia at BP 140/90 mm Hg or more after 24 h of hospital bed rest. Authors mention proteinuria evaluation, but do not disclose details. |
| D’Almeida et al., 1992 [7] | Evening primrose oil (GLA 296 mg) plus fish oil (DHA 80 mg and EPA 144 mg) vs. placebo | 100 (50 + 50) primigravidae and multigravidae singleton pregnancies, 21% had a history of PIH or other hypertensive disorder | First 4 months of pregnancy Duration: 30 days | Preeclampsia defined as simultaneous occurrence of: (1) hypertension: a rise in SBP greater 30 mm Hg and/or a rise in DBP greater than 15 mm Hg; either one or both, during the course of the pregnancy; (2) proteinuria: protein greater than one determined by test tape; (3) edema: visible fluid accumulation in the ankles and feet; indentation produced by pressure applied by the thumb over the anterior surface of the tibia. |
| Onwude et al., 1995 [8] | EPA 1620 mg and DHA 1080 g vs. placebo | 232 singleton pregnancies, including: −35 + 37 primigravidae with abnormal Doppler at 24 weeks −34 + 34 multigravidae with previous birthweight < 3rd centile −36 + 40 multigravidae with history of proteinuric or nonproteinuric PIH −8 + 8 multigravidae with history of unexplained stillbirth | Mean 24.0 (range 18–32) weeks in main group and 24.4 (range 18–32) weeks in control group. Majority of patients 19–26 weeks. Duration: not reported Women obtained 140 capsules and were supposed to take 9 per day. However, 50% of women in fish oil group and 57% in control group took less than 70% of capsules. | Hypertension: diastolic blood pressure of at least 90 mm Hg on two consecutive occasions at least 4 h apart. Proteinuria: two clean-catch-midstream specimens of urine collected > 4 h apart with 1 g/L albumin or 2+ more on reagent strip. |
| Bulstra-Ramakers et al., 1995 [9] | Mixture of DHA and EPA, approximately 3000 mg of the latter daily vs. placebo | 70 multigravidae with 63 completing the study, including: −24 + 15 with history of PIH and IUGR −1 + 1 with history of IUGR and renal disease −7 + 15 with history of IUGR | 12–14 weeks Duration: not reported 78% women in fish oil group and 75% in control group reported, that they usually took 4 capsules per day | Hypertension: an increase in diastolic blood pressure of a t least 25 mm Hg in the course of pregnancy, with a final diastolic pressure >90 mm Hg. Proteinuria: albuminuria >0.5 g/24 h. |
| Salvig et al., 1996 [10] | EPA 1280 mg and DHA 920 mg vs. olive oil vs. placebo | 533 (266 + 136 + 131) singleton pregnancies | 30 weeks Duration: until delivery | Hypertension: BP greater than 140/90 mm Hg after rest at two subsequent measurements with a 6 h interval. Proteinuria: (>0.3 g/L). |
| Herrera et al., 1998 [11] | LA 450 mg and calcium 600 mg vs. placebo | 86 (43 + 43) primigravidae with high risk of PE: biopsychosocial risk score above 3, positive roll-over test and mean BP > 85 mm Hg. | 28–32 weeks Duration: 4 weeks | Hypertension: acute development of hypertension in a woman whose blood pressure was normal in the early stages of pregnancy and who had persistent elevation of blood pressure to at least 140/90 mm Hg, that must have represented an increase in the diastolic pressure of no less than 20 mmHg determined in at least two occasions six or more hours apart. Proteinuria: 24-h proteinuria (more than 0.3 g/L) in the absence of urinary tract infection. |
| Olsen et al. [12] “Earl-PIH” | EPA 1300 mg and DHA 900 mg vs. olive oil | 350 (167 + 183) singleton pregnancies with history of PIH defined as DBP > 100 mm Hg in earlier pregnancy | Mean 18.4 ± 3.05 weeks in main group and 18.9 ± 3.8 weeks in control group *. Duration: until delivery | Hypertension: one or more recorded measurements of a DBP > 90 mmHg at rest. Proteinuria: urinary measurement of > 1+ in albustix, 0.3 g protein/L, 0.3 g protein/24 h, or 300 mmol protein/L. |
| Olsen et al. [12] “Twins” | EPA 1300 mg and DHA 900 mg vs. olive oil | 553 (274 + 279) twin pregnancies, with nulliparity at 52.5% at both groups. Analysis for preeclampsia included 497 (246 + 251) pregnancies due to missing data on proteinuria | Mean 20.2 ± 3.0 weeks in main group and 20.2 ± 3.04 weeks in control group *.Duration: until delivery | Hypertension as one or more recorded measurements of a DBP > 90 mmHg at rest. Proteinuria as a urinary measurement of > 1+ in albustix, 0.3 g protein/L, 0.3 g protein/24 h, or 300 mmol protein/L. |
| Smuts et al., 2003 [13] | DHA-enriched eggs DHA 133 ± 15 mg median 7.3 eggs/week hence appr. 139 mg vs. simple eggs | 291 (149 + 142) singleton pregnancies without any-cause hypertension | Mean 26.0 ± 1.4 weeks in main group and 26.1 ± 1.5 in control group Duration: until delivery | Criteria not listed since PIH and preeclampsia were secondary outcomes |
| Zhou et.al., 2012 [14] “DOMInO” | DHA 800 mg | 2399 (1197 + 1202) singleton pregnancies, preeclampsia data was available for 96% cases | Median 19 (IQR 19–20) weeks in both groups Duration: until delivery | Hypertension: as either (1) one SBP reading of ≥160 mm Hg or DBP reading of ≥110 mm Hg or (2) 2 consecutive SBP readings of ≥140 mm Hg and/or DBP readings of ≥90 mm Hg 4 h apart after 20 wk gestation. Proteinuria as (1) a spot urine protein to creatinine ratio of ≥30 mg/mmol; (2) one 24-h urine specimen with a total protein content of ≥0.3 g/L on a dipstick test; or (3) a total protein content of ≥1 g/L from 2 random urine samples |
* Data originally reported as means days. LA—linoleic acid, GLA—gamma-linolenic acid, EPA—eicosopentaenoic acid, DHA—docosohexaenoic acid, BP—blood pressure, SBP—systolic blood pressure, DBP—diastolic blood pressure, PIH—pregnancy-induced hypertension.