Dietary sodium restriction in the prophylaxis of hypertensive disorders of pregnancy: effects on the intake of other nutrients.

Dietary sodium restriction is used in the Netherlands in the prophylaxis of preeclampsia. To study the effects of long-term sodium restriction on the intake of other nutrients and the outcome of pregnancy, 68 healthy nulliparous pregnant women were randomly assigned to either a low-sodium diet (20 mmol/24 h) or an unrestricted diet. The diet was consumed between week 14 of gestation and delivery. The dietary intakes of energy, fat, protein, carbohydrate, sodium, potassium, and calcium were estimated with the dietary-history technique. A low-sodium diet reduced the intake of protein (by approximately 15 g/24 h), fat (by 20 g/24 h), and calcium (by 350 mg/24 h) and tended to decrease the energy intake (by approximately 0.7 MJ/24 h). The intakes of carbohydrate and potassium did not differ between the groups. The maternal weight gain was less in the low-sodium group (6.0 +/- 3.7 compared with 11.7 +/- 4.7 kg). Mean birth weight was not significantly different (3.2 +/- 0.5 compared with 3.4 +/- 0.5 kg).

Haematological and biochemical profile of uncomplicated pregnancy in nulliparous women; a longitudinal study.

BACKGROUND: Most laboratory parameters change during pregnancy. A serial study of a large number of routine haematological and biochemical blood parameters and biochemical urine parameters was conducted in a group of 66 healthy nulliparous pregnant women, who had an uncomplicated pregnancy. METHODS: Blood samples and 24-h urine samples were obtained at four weeks intervals during pregnancy and at 1 (1P) and 6 (6P) weeks after delivery. RESULTS: During pregnancy, haemoglobin concentration, haematocrit and erythrocyte count were lower, mean cell volume was not different, and mean cell haemoglobin and mean cell haemoglobin concentration were enhanced. The platelet count during pregnancy was not different from the level at 6P but increased 60% at 1P. Serum ferritin decreased 50% whereas plasma fibrinogen increased 100%. Serum creatinine (-28%), uric acid (-35%) and urea (-40%) concentrations were reduced during pregnancy. The serum concentrations of sodium (-4 mmol/l) and potassium (-0.2 mmol/l) were lower, but serum chloride was unaltered. Serum protein and albumen concentrations declined by 7.8 and 9.4 g/l respectively. The serum concentrations of bilirubin, ALAT, ASAT and gamma-GT remained unaltered. Serum LDH was 30% above normal non-pregnant values at 1P. The heat-stable alkaline phosphatase level increased in the third trimester. Heat-stable and heat-labile fractions were both elevated at 1P. The serum osmolality was 9 mosmol/kg lower and urine volume was about 25% higher during pregnancy. The creatinine excretion was unaltered but creatinine clearance increased by 25%. CONCLUSIONS: The concentrations of most components change during pregnancy. The interpretation of results of laboratory tests in pregnant women should be made with caution.

(Patho)physiological implications of chronic dietary sodium restriction during pregnancy; a longitudinal prospective randomized study.

OBJECTIVE: To study the possible pathophysiological implications of long continued dietary sodium restriction in pregnancy. DESIGN: Longitudinal prospective randomized study of the effects of a low sodium diet compared with unrestricted sodium intake in pregnancy. SETTING: Academic Department of Obstetrics and Gynaecology at Sint Radboud Hospital, Nijmegen, The Netherlands. SUBJECTS: 42 healthy nulliparous women. INTERVENTION: A low sodium diet (20 mmol sodium daily) started in the 14th week of pregnancy and stopped after delivery. MAIN OUTCOME MEASURES: Maternal weight gain, food intake, blood pressure, cardiac output, systemic vascular resistance, haematocrit and birthweight. RESULTS: Total maternal weight gain and dietary energy intake during pregnancy and weight at 1 and 6 weeks postpartum were significantly lower in the low sodium group. Blood pressure during pregnancy did not show major differences. Stroke volume and cardiac output during pregnancy were significantly lower in the low sodium group whereas systemic vascular resistance was significantly higher. Haematocrit values in the low sodium group tended to be lower during pregnancy, but were significantly lower at 1 and 6 weeks postpartum than in the unrestricted group. Placental and birthweights were not significantly different between the two groups. CONCLUSIONS: Chronic dietary sodium restriction during pregnancy is characterized by a diminished body fat accumulation and a reduction in circulating volume, due to a decrease in both plasma and red cell volume, in combination with a high systemic vascular resistance without major effects on blood pressure and birthweight.

Dietary sodium restriction during pregnancy; a historical review.

This article reviews the major milestones in obstetric research in the past 90 years, which have lead to the wide-spread use of salt restriction during pregnancy. Possibly the most ardent advocate of the view that salt plays a crucial role in eclampsia was De Snoo (1877-1949), a Dutch obstetrician. However, despite many enthusiastic clinical reports, no convincing evidence has ever been produced that salt restriction helps in the prevention of hypertension during pregnancy.

Atrial natriuretic peptide and atrial size during normal pregnancy.

Plasma atrial natriuretic peptide (ANP), right and left atrial areas and the diameter of the left atrium were studied serially during normal pregnancy and at 6 weeks post partum in 21 nulliparous women. Concentrations of ANP in plasma were significantly elevated during mid-pregnancy. Thereafter ANP levels were not significantly different from those at 6 weeks after delivery. All atrial measurements were significantly increased in the third trimester of pregnancy, but none was significantly correlated with the plasma ANP concentrations. This might point at an altered mechanism of ANP secretion, which may be part of a physiological adaptive process to sustain the hypervolaemia of pregnancy.

The effect of chronic oral methadone treatment on monkey chorionic gonadotropin, estradiol, dehydroepiandrosterone sulfate, progesterone, prolactin and cortisol levels during pregnancy in the cynomolgus monkey (Macaca fascicularis).

The effect of chronic methadone treatment upon the serum levels of Estradiol (E2), Progesterone (P), Prolactin (Prl), monkey chorionic gonadotropin (mCG), dehydroepiandrosterone sulfate (DHEAS) and Cortisol (C) in pregnant Cynomolgus monkeys (Macaca fascicularis) is described in comparison with the hormone levels in a control group. Only DHEAS was significantly decreased in late pregnancy in the methadone group. From these data it can not be concluded that methadone treatment compromises (feto)placental function. The observed intra-uterine growth retardation in the methadone treated group might be a result of a direct influence of methadone upon growth.

Effects of dietary sodium restriction and posture on plasma levels of atrial natriuretic peptide, aldosterone and free aldosterone in normal human pregnancy.

The effects of dietary sodium restriction and posture on plasma concentrations of atrial natriuretic peptide (ANP), aldosterone and free aldosterone were investigated in ten women between weeks 29 and 33 of normal pregnancy. Hormone levels were studied during unrestricted sodium intake and on day 6 of a low sodium diet. On both occasions venous blood was obtained in the sitting as well as in the left lateral tilt position. Plasma concentrations of ANP during the unrestricted sodium intake were not raised compared with control values in healthy non-pregnant females. Recovery experiments showed no differences in the degradation of ANP in blood from pregnant and non-pregnant women. Plasma concentrations of ANP significantly decreased (by 32%) in response to the low sodium regime in both positions. Concentrations of aldosterone and free aldosterone (in women in the sitting position) increased twofold after sodium restriction. Mean values of ANP were higher in women in the left lateral tilt position that in those in the sitting position, but the difference was not significant. Concentrations of aldosterone and free aldosterone were significantly lower (by around 30%) in women in the left lateral tilt position compared with those in the sitting posture.

Atrial natriuretic peptide and progesterone in ovarian follicular fluid.

Synthesis and secretion of atrial natriuretic peptide (ANP) is not confined to the heart, but also present in other tissues. ANP is known to affect steroidogenesis in the ovary. To assess the possibilities that (a) the human ovary is a source of ANP secretion as well, and (b) ovarian ANP stimulates progesterone secretion, we investigated ANP as well as progesterone concentrations in preovulatory ovarian follicular fluid form women in an in vitro fertilization program. In all women detectable ANP immunoreactivity was found in ovarian follicular fluid (range 3.3-60.1 pg/ml). Follicular fluid concentrations were low in all but 1 women who demonstrated a higher ANP level in follicular fluid than in plasma. Follicular ANP and progesterone concentrations were not significantly correlated. These preliminary results suggest that the ovary could well be a site of ANP secretion. If and how ovarian ANP activity affects progesterone secretion remains as yet unknown.

Uterine and umbilical artery blood flow velocity waveforms and their validity in the prediction of fetal compromise.

The maternal and fetal placental circulation was studied by recording of the blood flow velocity waveforms (FVW) of the uterine and umbilical artery (UFVW and UmbFVW) in 99 pregnant women. The FVW was quantitated by the Pulsatility-Index (PI). By analysing the UFVWs as well as the UmbFVWs, it was possible to define four groups of patients, based on normal versus abnormal PI on either side of the placenta. The group with abnormal FVWs on both sides of the placental bed showed the highest percentage of pathological phenomena. Uterine and/or umbilical artery FVW analysis was not sensitive in the prediction of small for gestational age (SGA), whereas it was a sensitive method for the prediction of fetal distress (FD) during pregnancy. For the latter, our data suggested that at a chosen specificity of 95%%. FVW analysis on both sides of the placental bed was more sensitive than separate UFVW or UmbFVW analysis.

Serum hormone levels in pregnant cynomolgus monkeys.

Serum levels of estradiol (E2), progesterone (P), prolactin (Prl), monkey chorionic gonadotropin (mCG), dehydroepiandrosterone sulfate (DHEAS), and cortisol (C) in pregnant cynomolgus monkeys are described. mCG, E2, and Prl patterns resembled those of pregnant rhesus monkeys. P patterns differed from data from the literature. DHEAS patterns did not follow E2 patterns. C levels did not change during pregnancy.

The uterine artery blood flow velocity waveform in pathological pregnancy.

Uterine artery blood flow velocity waveforms (FVW) were recorded longitudinally in 41 women with undisturbed pregnancy as well as in 32 women with complicated pregnancy at 4-week intervals from a gestational age of 18 weeks onwards. Of these women, four did not complete the study. In a second group of 76 patients at least one FVW was recorded after admission to the obstetrical department because of complicated pregnancy. The Pulsatility-Index (PI) for normal pregnancy was based on the results of the 41 women with undisturbed pregnancy (Mulders et al. (1988) Early Hum. Dev., 17, 55-70). The complete study group (n = 145) was divided in two groups, based on the value of the last measured uterine artery PI before delivery in the abnormal PI group (PI greater than or equal to 1.02 before 32 weeks or PI greater than or equal to 0.91 after 32 weeks, n = 38) hypertension, fetal distress during pregnancy, premature delivery, small for gestational age babies (SGA) and lower placental weight were all significantly increased. In each of the groups of patients with either SGA, fetal distress during pregnancy, pre-existing hypertension with proteinuria and pregnancy-induced hypertension with or without proteinuria the mean PI was significantly increased as compared to the results in normal pregnancy. Sensitivity and specificity of the last uterine artery PI for the detection of SGA and/or fetal distress during pregnancy were 48.8% and 82.7%, respectively. The longitudinally studied women (n = 73) were divided in two groups, based on uterine artery PI before 32 weeks of gestation; in the abnormal PI group (PI greater than or equal to 1.02, n = 12) pregnancy was more complicated by premature delivery and low birth weight. Sensitivity for the early prediction of pathological pregnancies (at least one pathological phenomenon as mentioned above) was 30.4%, whereas specificity was 90.0%.

The uterine artery blood flow velocity waveform: reproducibility and results in normal pregnancy.

Uterine artery blood flow velocity waveforms (FVW) were recorded longitudinally in normal pregnancies (n = 41) at 4-week intervals from a gestational age of 18 weeks onwards. Furthermore, reproducibility of the uterine artery FVWs and the relation with maternal heart rate (MHR) was studied. The uterine artery FVW showed a low resistance flow pattern already from 18 weeks onwards, with high diastolic flow velocity relative to systolic flow velocity. Mean values (+/- S.D.) for the Pulsatility-Index (PI) before and after 32 weeks of normal pregnancy were 0.73 (+/- 0.17) and 0.67 (+/- 0.15) respectively; for the A/B ratio these values were 1.98 (+/- 0.30) and 1.85 (+/- 0.25) respectively. Intra- and interobserver reproducibility could be established for uterine artery FVW analysis. A varying time-period between the FVWs (0-4 min), repositioning of the flow probe and different observers did not cause any systematic effect on the PI, although variation increased in case of a longer time-period between the FVWs. Overall variation of the PI in the reproducibility experiments appeared to be caused more by inter- than intrapatient variance. Inter- and intrapatient variance were in the same range for the results of the longitudinal study. A statistically significant, inverse relationship between uterine artery PI and MHR could be established in a majority of cases. The mean regression coefficient for all patients of the reproducibility study was -0.0061; PI decreases with 0.0061 when maternal heart rate increases 1 beats/min.

The influence of maternal exercise on the uteroplacental vascular bed resistance and the fetal heart rate during normal pregnancy.

The effects of maternal exercise were studied in 20 healthy women with uncomplicated pregnancies. A continuous-wave Doppler ultrasound system was used to record arterial flow velocity waveforms from the ascending vasculature downstream from the uterine artery. The fetal heart rate was monitored with a Doppler ultrasound cardiotocograph. No significant change was found in the uterine blood flow velocity waveform post-exercise, as expressed by the pulsatility index, suggesting absence of change in the uterine vascular bed resistance. The fetal heart rate significantly increased after exercise.

The effect of chronic methadone treatment on intra-uterine growth of the cynomolgus monkey (Macaca fascicularis).

A generally accepted management of heroin addiction during pregnancy is treatment with methadone, which reduces the complications of heroin addiction considerably. Reports in the literature are still contradictory, however, about the influence of methadone upon birthweight. In pregnant Cynomolgus monkeys (Macaca fascicularis) the effect of chronic treatment with rather high dosages of methadone upon birthweight was studied under standardized conditions. Birthweights were significantly lower in the methadone-treated animals.

Plasma atrial natriuretic peptide (ANP) in late pregnancy and puerperium.

Plasma concentrations of atrial natriuretic peptide (ANP) were determined ante- and post-partum in 7 healthy primiparous women. ANP was measured at weekly intervals from the 35th week of pregnancy onwards and throughout the puerperium up to the sixth week post-partum. In all seven patients the mean of the ANP values during the first four days post-partum was higher than in late pregnancy. The mean ANP level from the 6th day up to the 42nd day showed a marked decrease compared with the first four days after birth, which, however, did not differ significantly from the mean plasma concentration in late pregnancy. In conclusion, ANP is markedly elevated during the first few days post-partum compared with plasma levels in the normal late pregnancy and the subsequent puerperium.

Lethal lung hypoplasia in infants after prolonged rupture of membranes.

A retrospective study to detect the frequency of lethal lung hypoplasia in 48 cases with prolonged rupture of membranes (greater than 7 days) before 34 weeks' gestation was made. Fourteen infants died (29%), but only four deaths (8.3%) were due to lung hypoplasia. Three infants with lung hypoplasia had their membranes ruptured before 20 weeks' gestation and showed echoscopically a persistent oligohydramnios, as did the one with rupture at 26 weeks. Neither the duration of rupture of membranes nor the gestational age at the time of rupture showed any influence on the occurrence of lung hypoplasia. The rupture of membranes before 20 weeks' gestational age with resulting persistent oligohydramnios will certainly lead to lung hypoplasia.

A comparative study of three indices of umbilical blood flow in relation to prediction of growth retardation.

The literature reporting Doppler ultrasound flow velocity waveform analysis of the umbilical artery and its applications for detecting intrauterine growth retardation (IUGR) is growing rapidly. Several indices originally introduced to evaluate different vascular beds in adults, are used to assess the vascular bed resistance downstream the umbilical artery (i.e. the placental bed). A higher resistance in this placental bed causes a decreased end-diastolic flow, which is described in combination with IUGR. The three most commonly used flow indices are: A/B ratio, Resistance Index (RI = (A-B)/A) and Pulsatility Index (PI = (A-B)/mean). In this study we evaluated which of these indices correlated best with IUGR. We calculated the three above mentioned indices from the same recordings of the blood flow (at a gestational age of 34 +/- 2 weeks) and correlated the results with the subsequent birthweight of the child. In the studied group (n = 48) 15 children were small for gestational age (SGA = less than P 10) and 33 children were appropriate for gestational age (AGA = greater than or equal to P 10). All three indices showed a significant difference in value between AGA and SGA children (see table III). The Spearman correlation-coefficients were calculated and were approximately one. So there was a high correlation between all three indices. This indicates that the different indices have the same relation to IUGR. Thus, no arguments were found to prefer one index above the other. In the second part of the study we investigated the validity of these indices to predict IUGR. The validity can be estimated from two components: the sensitivity and specificity. Both sensitivity and specificity are determined by the value of the index which discriminates between AGA and SGA. Changes in this discriminating value (the so-called cut-off point) will change both sensitivity and specificity. This last effect can be visualized in the Receiver-Operating-Characteristic (ROC) curve, which plots sensitivity against specificity for different cut-off points (see figures 4 and 5). Arbitrarily sensitivity and specificity were calculated for the cut-off points PI = 1.1 and A/B ratio = 3.0. Choosing these cut-off points, the same specificity of 87.9% with a sensitivity of 53.3% were found (table IV). It is concluded, that the sensitivity of the PI of the umbilical artery in predicting growth retardation with acceptable specificity is rather disappointing. A possible reason for this is discussed.(ABSTRACT TRUNCATED AT 400 WORDS)

A study of maternal ECG characteristics before and during intravenous tocolysis with beta-sympathicomimetics. Effects of i.v. tocolysis on maternal ECG characteristics.

Severe maternal complications during beta-mimetic therapy have been reported. In a study of maternal complications related to intravenous tocolysis, which covering a period of 2 years, we paid special attention to the maternal ECG before and during treatment. There was a high prevalence of pretreatment ECG changes: tachycardia (23.6%), disorders of impulse conduction (43.6%), ST-depression (14.5%) and disorders of repolarization (43.6%). During intravenous beta-mimetic therapy there was an increase in the prevalence of tachycardia, prolonged QT-time and disorders of repolarization. We also studied the course in time of the different ECG characteristics during treatment. With regard to the ST-depression, a possible physiological adaptation to the beta-mimetic drug is described. We could not find this possible adaptation with regard to the other ECG characteristics. None of the women in the studied group showed clinical signs of myocardial ischemia, notwithstanding the high prevalence of ECG changes. We conclude that the ECG criteria for discontinuation of tocolytic therapy need re-evaluation.