Low sodium diet and pregnancy-induced hypertension: a multi-centre randomised controlled trial
Correspondence: Dr M. Knuist, Academic Medical Centre, University of Amsterdam, Department of Obstetrics and Gynaecology, PO Box 22700, 1100 DE Amsterdam, The Netherlands
Objective To examine the effectiveness of the standard policy in the Netherlands to prescribe a sodium restricted diet to prevent or to treat mild pregnancy-induced hypertension.
Design Multi-centre randomised controlled trial between April 1992 and April 1994.
Setting Seven practices of independent midwives and one university hospital.
Participants The experimental group comprised 184 women given a low sodium diet (≤ 50 mmol sodium/day) and a control group of 177 women given a normal diet. Eligible women for inclusion had had a rise of blood pressure, or excessive weight gain or oedema during the antenatal period. The 361 women in the trial were recruited from 2020 nulliparae, of whom 1512 (75%) gave informed consent at the beginning of their pregnancy to participate in the study.
Main outcome measures The difference between highest diastolic blood pressure after randomization and diastolic blood pressure at the moment of randomisation; referral and admission to hospital for hypertension.
Results There was no difference in increase of diastolic blood pressure after randomisation, the percentage of referral and admission to hospital for hypertension, or in obstetric outcome between the two groups. Urinary sodium excretion after randomisation in the normal diet group was significantly higher than in the low sodium group.
Conclusion Prescribing a sodium-restricted diet to prevent or to treat mild pregnancy-induced hypertension is not effective. Therefore there is no need to introduce a salt restricted diet in prenatal care, although increasing evidence shows that a low sodium diet prevents hypertension in non pregnant individuals.
Ever since De Snoo1 suggested that a salt-reduced diet may prevent eclampsia, this diet has been prescribed widely by Dutch midwives, general practitioners and obstetricians. His study, however, was not a randomised trial, and the decrease in the rate of eclampsia could be explained by other factors. Since then, the value of sodium restriction in pregnancy has been debated. Some investigators considered the use of a sodium-restricted diet to treat pregnancy-induced hypertension essential2–4, others held the opposite opinion5–7, or feared an adverse effect on birthweight8. Prophylactic dietary sodium restriction from 14 weeks of pregnancy has been investigated in small groups of healthy pregnant women8,9. In these studies blood pressure was not different in the low sodium group compared with women acting as controls. In non pregnant individuals it is well established that sodium excretion is significantly related to blood pressure10, and a difference in sodium intake of 100 mmol/24 h is associated with an average difference in diastolic blood pressure that ranged from 2 to 4 mmHg11.
Because lowering the blood pressure of a pregnant woman by even a few mmHg may have important consequences for prenatal care, including the avoidance of referral of pregnant women to the obstetrician as a high risk patient, or even admission to hospital, further investigation of the use of a sodium restricted diet in the treatment of pregnancy-induced hypertension is justified.
At present Dutch midwives care for low risk pregnant women and prescribe a sodium restricted diet to prevent and to treat pregnancy-induced hypertension. Usually a sodium restricted diet is prescribed if during the second half of pregnancy the blood pressure rises or if excessive weight gain occurs or oedema becomes apparent. If severe pregnancy-induced hypertension supervenes they refer the woman to the obstetrician12. Midwives are not allowed to prescribe anti-hypertensive drugs or diuretics. There have been no randomised trials to investigate the effectiveness of this policy. Previous studies investigating the use of a sodium restricted diet to prevent or to treat pregnancy-induced hypertension included only healthy pregnant women5,8,9 women with pre-eclampsia7, or they did not differentiate between nulliparous and multiparous women1,3,4,6,7.
We conducted a randomised controlled trial to assess the current policy of prescribing a sodium-restricted diet. The study involved only nulliparous women because the risk of pregnancy-induced hypertension is much higher in these women than in multiparae.
The study protocol was approved by the ethical committee of the hospital. At the first prenatal visit nulliparae who agreed to the trial gave written informed consent. Those women who were eligible for the trial again gave informed consent before randomisation.
We recruited women from seven groups of independent midwives and from one group of midwives in a university hospital. All participants were Dutch-speaking nulliparous women, with a diastolic blood pressure < 90 mmHg at their first prenatal visit, which took place before 20 weeks of gestation. Women planning to move to another city and those with conditions associated with an increased risk of pregnancy-induced hypertension (eg, twin pregnancy, diabetes, pre-existing hypertension or renal disease) were ineligible.
Standard prenatal care involved approximately 12 visits. If during one of the prenatal visits a rise of blood pressure was detected, or if excessive weight gain or oedema became apparent, the woman was randomly assigned a low sodium diet or a normal diet. The inclusion criteria for randomisation were: two diastolic blood pressure recordings ≥ 85 mmHg; weight gain > 1 kg/week for three successive weeks; or excessive oedema (not defined). Randomisation lists were devised for each practice with the use of random numbers in blocks of ten; the treatment allocations were placed in numbered, opaque, sealed envelopes, opened by the midwives.
The primary outcomes measured were 1. The difference between highest diastolic blood pressure after randomisation and the diastolic blood pressure at randomisation; 2. The rates of referral and admission to hospital for hypertension. Two consecutive readings of at least four hours apart were required to assign the highest diastolic blood pressure, because a single, isolated reading of blood pressure could have lead to erroneously high blood pressure values. Compliance with the low sodium diet and obstetric outcomes were also studied.
Blood pressure was measured with the woman in the sitting position, using the same arm (left or right depending on the setting of the equipment) with a portable oscillometric sphygmomanometer (BOSO Prestige ‘automatic’; Bosch and Sohn, Juningen, Germany), a device which meets the criteria of the Assocation for the Advancement of Medical Instrumentation for Korotkoff phase I and V, but not for Korotkoff phase IV13. After referral to the obstetrician, standardised blood pressure measurements with the BOSO Prestige sphygmomanometer were not always obtained since very many obstetricians were involved who did not have access to the machine.
In order to measure compliance with the low sodium diet, 24–hour urine samples were collected during early pregnancy by all nulliparae who agreed to take part in the trial. Women who were randomised were also asked to collect a 24–hour sample of urine as soon as possible after enrollment and before every subsequent prenatal visit. After instruction the participating women measured the volume of urine they collected and took a sample. The urine samples were kept in a domestic freezer until sodium and creatinine measurements could take place. Sodium was measured in order to measure compliance with low sodium diet. Creatinine was measured in order to compare completeness of the 24–hour urine sampling in the two groups enrolled in the trial. Urine sodium and creatinine were measured simultaneously in a multichannel continuous flow analysis system (Technicon SMA II, Technicon, Tarrytown, New York), according to usual procedures.
The women allocated to a low sodium diet were asked to take c 50 mmol sodium a day until delivery. Written dietary instructions were given by the mid- wives. The women allocated to a normal diet were asked not to change their eating habits until delivery. The midwives were blinded to the results of the urine measurements.
Analysis was by intention-to-treat. To compare two means Student's t-test was used and to compare two percentages the χ2 test was used. Probability values were considered to be significant at the 5% level. Data were analysed using EpiInfo 5.1.
Between 1 April 1992 and 1 April 1994 2020 nulliparous women were booked for prenatal care; 1512 (75%) gave informed consent to participate in the study. Of these 15 12 women 361 met the criteria for randomisation in the course of their prenatal care. A low sodium diet was assigned to 184: 177 were asked to continue their normal diet. The baseline characteristics at the first visit of the participants and those who declined the study were similar with regard to age, diastolic blood pressure and weight at first visit; previous miscarriage (< 16 weeks gestation); cigarette smoking and consumption of alcohol. The percentage of Caucasian women was higher among participants (80%) compared with non-participants (71 %) (data not shown). The baseline characteristics at first visit and at randomisation of the women enrolled in the trial did not show important clinical differences between the two groups (Table 1). The main criterion for entry into the trial was equally distributed in both groups (Table 2).
Table 1. Baseline characteristics of the women enrolled in the trial. Values are shown as mean [SD] or n (%), as appropriate.
|At first visit|
| Maternal age (years)||27.6 [4.2]||27.5 [4.8]|
| Diastolic blood pressure (mmHg)||74.5 [8.0]||75.0 [8.2]|
| Maternal weight (kg)||70.4 ||69.7 [12.1]|
| Previous miscarriage*||42 (23)||31 (18)|
| Smokers||62 (34)||55 (31)|
| Takes alcohol||27 (15)||23 (13)|
| Caucasian||159 (86)||153 (86)|
| Diastolic blood pressure (mmHg)||84.4 [9.6]||84.4 [9.0]|
| Maternal weight (kg)||80.7 [12.6]||80.2 [12.1]|
| Urinary sodium excretion (mmol/24 h)||117 ||127 |
| Urinary creatinine excretion (mmol/24 h)||9.08 [2.50]||9.12 [2.48]|
Table 2. Main criterion for entry into the trial. Values are numbers of women.
|Diastolic blood pressure ≥ 85 mmHg|
|Weight gain > 1 kg/week|
The highest diastolic blood pressure after randomisation could not be obtained in 67 women, because of delivery before a blood pressure could be measured (35 low sodium, 32 controls). In the remaining women there was no difference in the change in diastolic blood pressure between the low sodium group and the controls. There was no difference in the highest diastolic blood pressure after randomisation, or in the distribution of the highest diastolic blood pressure (Table 3).
Table 3. Diastolic blood pressure after randomisation. Values are shown as n or mean [SD], as appropriate.
|Change in dbp (mmHg)||+6.5 [9.6]||+6.5 [10.4]|
|Highest dbp (mmHg)||89.9 [10.7]||90.6 [11.5]|
|Distribution of highest dbp (mmHg)|
| ≥90 to <95||28||24|
| ≥95 to <100||19||12|
There was no difference in the number of referrals and admission to hospital for hypertension (Table 4). There was also no difference in the median duration between randomisation and delivery [low sodium: 35 days (range 1–168); controls: 34 days (range 2–156)].
Table 4. Referral and admission to hospital for hypertension. Values are shown as n (%).
|No referral||136 (74)||124 (70)|
|Referral without admission to hospital||12 (7)||11 (6)|
|Admission to hospital||36 (20)||42 (24)|
Urine was collected before randomisation by 320 women who were enrolled in the study (89%) and by 283 women (78%) after randomisation. One hundred and twenty-three women (67%) on the low sodium diet and 137 controls (77%) collected urine both before and after randomisation. The mean urinary sodium excretion after randomisation was significantly lower in the low sodium group (Table 5). The decrease in urinary sodium excretion (Urinary sodium excretion before randomisation minus urinary sodium excretion after randomisation) in the women taking the low sodium diet was significantly greater than in the controls, there was no difference in the mean and in the decrease in urinary creatinine excretion in both groups (Table 5).
Table 5. Urinary sodium and creatinine excretion after randomisation. Values are shown as numbers of women or mean [SD], as appropriate.
|Urinary sodium excretion (mmol/24 h)||84 ||124 *|
|Urinary creatinine excretion (mmol/24 h)||10.00 [2.24]||9.89 [2.50]|
|Complete data before and after randomisation||123||137|
|Change in urinary sodium excretion (mmol/24 h)||−33 ||−5 *|
|Change in urinary creatinine excretion (mmol/24 h)||+1.05 [2.44]||+0.63 [2.87]|
In the low sodium group the urinary sodium excretion before randomisation was significantly higher than after randomisation (117 mmol compared with 84 mmol; P = 0.003). In the women taking a normal diet no difference was found (127 mmol compared with 124 mmol).
In the low sodium group 32 women (24%) had a urinary sodium excretion of ≤ 50 mmol/24 h after randomisation, implying strict observance of the diet. A sodium excretion of ≤80 mmol/24 h was found in 77 women (57%), suggesting partial compliance. In women with a normal diet, urinary sodium excretion of ≤50 mmol/24 h after randomisation was found in four (3%) and ≤80 mmol/24 h in 24 women (16%). The mean change in diastolic blood pressure was not different in those women who kept strictly to their diet, compared with the women who were not compliant [4.7 mmHg (SD 9.7) compared with 7.4 mmHg (SD 9.5)]. There was no difference between these women as regards their highest diastolic blood pressure [91 mmHg (SD 11) compared with 89 mmHg (SD 11)].
There was also no difference in the obstetric outcomes. In both groups eight women developed pre-eclampsia (hypertension and significant proteinuria in two specimens of urine), but there were no cases of eclampsia. There were two cases of placental abruptio in the control group. There were no differences in the gestational age at delivery, mode of delivery, birthweight, percent-age of infants with an Apgar score at 5 min ≤7, admission to the paediatric department and perinatal mortality (Table 6). All three cases of perinatal mortality were due to major congenital malformations.
Table 6. Obstetric outcomes. Values are shown as n (%) or mean [SD], as appropriate.
|Gestational age at delivery (days)||280 ||277 |
|Mode of delivery|
| Spontaneous||127 (69)||117 (66)|
| Instrumental vaginal||36 (20)||33 (19)|
| Caesarean section||21 (11)||27 (15)|
|Birthweight (g)||3320 ||3295 |
|Birthweight < 2500 g||14(8)||16(9)|
|Apgar score at 5 min ≤ 7*||10(5)||7(4)|
|Admission to paediatric department*||47 (26)||46 (26)|
|Perinatal mortality||2(1)||1 (0.6)|
This study is the first randomised trial of a sodium-restricted diet during pregnancy in the prevention of pregnancy-induced hypertension and the treatment of mild pregnancy-induced hypertension. The trial was carried out in nulliparous women in eight midwives’ practices, with a standardised method of recording the blood pressure at the prenatal clinics. Approximately one-quarter of all nulliparae at booking satisfied the criteria for randomisation, which agrees with our expectation based on previous observations in a low risk population14. The groups in the trial showed a similar change in diastolic blood pressure after randomisation and highest diastolic blood pressure recorded, and similar rates of referral and admission to hospital for hypertension.
The urinary sodium excretion after randomisation in the women taking the low sodium diet was significantly lower than in the controls, but only 24% of the women in the low sodium group kept strictly to the diet: presumably, maintaining a low sodium diet is difficult. We analysed our results by intention-to-treat, because this approach is consistent with clinical practice; when the analysis is confined to the women who kept strictly to the diet, the results were not different from those in the low sodium group as a whole.
We conclude that the standard policy in The Netherlands to prescribe a sodium restricted diet in nulliparous women at risk of pregnancy-induced hypertension, to prevent pregnancy-induced hypertension, or to treat mild pregnancy-induced hypertension is not effective and should be abandoned. There is no need to introduce a salt restricted diet in prenatal care, although increasing evidence shows that a low sodium diet prevents hypertension in non pregnant individuals15.
The authors would like to thank all the participants and midwives for their help in the succesful completion of this study. Funding was provided by Praeventie Fonds, The Netherlands (Grant no. 28–1971).