Maternal thromboxane and prostacyclin levels in relation to fetal birth weight.

OBJECTIVE: To analyse whether pregnancies resulting in a small for gestational age neonate are preceded by a prostacyclin deficiency or an imbalance between thromboxane and prostacyclin. STUDY DESIGN: At five fixed time points during pregnancy, 24-h urine samples were collected for the measurement of thromboxane and prostacyclin metabolites thromboxane-B(2) (TXB(2)) and 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)). In order to study trend differences between pregnancies with appropriate (AGA; n=26) and small for gestational age neonates (SGA; n=17), trend analysis with simple contrasts were accomplished for TXB(2), 6-keto-PGF(1alpha) and the TXB(2)/6-keto-PGF(1alpha) ratio. RESULTS: Trend analysis showed higher TXB(2) levels and higher TXB(2)/6-keto-PGF(1alpha) ratios in patients with SGA versus AGA newborns. No statistically significant difference in 6-keto-PGF(1alpha) excretion between patients with SGA and AGA newborns was detected. CONCLUSION: The birth of an SGA neonate is not preceded by prostacyclin deficiency. With ongoing pregnancy an imbalance between thromboxane and prostacyclin becomes more obvious in pregnancies with SGA newborns.

Customized fetal weight limits for antenatal detection of fetal growth restriction.

OBJECTIVE: To define cut-off limits for individually adjustable fetal weight standards for the detection of intrauterine growth restriction. DESIGN: Retrospective study, with the outcome measures small-for-gestational age (SGA) birth weight, operative delivery for fetal distress, umbilical artery pH < 7.15, and admission to the neonatal intensive care unit. SUBJECTS AND METHODS: Two hundred and fifteen women considered to be at increased risk of uteroplacental insufficiency were recruited to a study of serial ultrasound scans. Fetal weights were derived using standard formulae and, retrospectively, weight percentiles were calculated after individual adjustment for maternal height, weight in early pregnancy, ethnic group, parity and fetal sex. INTRODUCTION: One or more antenatal scans indicative of fetal weight below the 10th customized percentile were predictive for a SGA neonate at birth (P < 0.001), operative delivery for fetal distress (P < 0.01) and admission to neonatal intensive care (P < 0.01) but not for a low umbilical artery pH (P = 0.6). Receiver-operator curves showed the optimal customized fetal weight percentile limit for predicting an SGA neonate to be the 18th percentile (sensitivity 83%, specificity 79%, positive predictive value 63% and negative predictive value 92%). For the prediction of operative delivery for fetal distress and admission to neonatal intensive care, the optional customized cut-off value was the 8th percentile. CONCLUSIONS: The assessment of fetal weight using ultrasound and an individually-adjusted standard is predictive of growth restriction and perinatal events associated with hypoxia or diminished reserve. The optimal cut-off value for predicting operative delivery for fetal distress or admission to the neonatal intensive care unit suggests that the 10th customized percentile is a good limit for clinical use.

Fetal growth rate and adverse perinatal events.

OBJECTIVE: To study fetal weight gain and its association with adverse perinatal events in a serially scanned high-risk population. SUBJECTS AND METHODS: A total of 200 pregnant women considered at increased risk of uteroplacental insufficiency had a total of 1140 scans in the third trimester, with a median of six scans in each pregnancy. The average fetal growth rate was retrospectively calculated for the last 6 weeks to birth, and expressed as daily weight gain in grams per day. Adverse pregnancy outcome was defined as operative delivery for fetal distress, acidotic umbilical artery pH (< 7.15), or admission to the neonatal intensive care unit (NICU). RESULTS: Fetuses with normal outcome in this high-risk pregnancy population had an average antenatal growth rate of 24.2 g/day. Compared to pregnancies with normal outcome, the growth rate was slower in those that required operative delivery for fetal distress (20.9 g/day, p < 0.05) and those that required admission to the NICU (20.3 g/day, p < 0.05). The growth rate in pregnancies resulting in acidotic umbilical artery pH also seemed lower, but this did not reach statistical significance. CONCLUSIONS: Impaired fetal weight gain prior to birth is associated with adverse perinatal events suggestive of growth failure.

Vasoactive mediators in pregnancy-induced hypertensive disorders: a longitudinal study.

OBJECTIVE: The objective of this study was to evaluate the extent to which endothelin and the eicosanoids prostacyclin and thromboxane A2 are involved in the pathophysiology of gestational hypertension and preeclampsia. STUDY DESIGN: In a longitudinal design, venous blood samples and 24-hour urine specimens were collected from 396 women in each trimester of pregnancy. After delivery of all patients, venous plasma endothelin was assessed in 20 subjects with identified preeclampsia, 48 subjects with gestational hypertension, and 59 normotensive subjects. Urinary excretions of the thromboxane A2 and of the prostacyclin metabolites thromboxane B2 and 6-keto-prostaglandin F1 alpha were assessed in 16 subjects with preeclampsia, 35 subjects with gestational hypertension, and 31 normotensive subjects. RESULTS: Endothelin levels showed a second-trimester drop in all groups. In all 3 gestational trimesters a high correlation was found between the excretion of thromboxane B2 and that of 6-keto-prostaglandin F1 alpha (P <.001). The overall thromboxane B2 and 6-keto-prostaglandin F1 alpha urinary excretions increased throughout pregnancy and the overall thromboxane B2 /6-keto-prostaglandin F1 alpha ratio decreased. No significant differences in endothelin, thromboxane B2, and 6-keto-prostaglandin F1 alpha excretion levels or in thromboxane B2 /6-keto-prostaglandin F1 alpha ratios were found between women with preeclampsia, gestational hypertension, and normotension. Only in a small group of patients with severe preeclampsia (n = 2) and severe gestational hypertension (n = 2) were increased second-trimester endothelin values and increased thromboxane B2 /6-keto-prostaglandin F1 alpha ratios found. CONCLUSION: In this longitudinal study we found no evidence for prostacyclin deficiency or increased endothelin levels in preeclampsia. Only women with severe preeclampsia and severe gestational hypertension expressed increased endothelin levels and thromboxane dominance over prostacyclin.

Application of a customised birthweight standard in the assessment of perinatal outcome in a high risk population.

OBJECTIVE: Physiological as well as pathological variables influence birthweight. The aim of the present study was to examine perinatal outcome in relation to birthweight centiles applying a customised birthweight standard. METHODS: Two hundred and seventeen babies from high risk pregnancies were evaluated and classified as small or not small for gestational age according to two standards: 1. conventional Dutch birthweight centiles and 2. customised centiles which adjust individually for physiological variables like maternal booking weight, height and ethnic origin. RESULTS: Customisation of the weight standards resulted in identification of an additional group of infants who were small for gestational age, but not by the Dutch standards. These babies were associated with significantly more adverse perinatal events than those who were not small for gestational age as defined by a customised standard. CONCLUSIONS: Adjustment of birthweight centiles for physiological variables significantly improves the identification of infants who have failed to reach the expected birthweight and who are at increased risk for adverse perinatal events.

Total plasma fibronectin as a marker of pregnancy-induced hypertensive disorders: a longitudinal study.

OBJECTIVE: To determine normal values of total plasma fibronectin in all three gestational trimesters and to examine 1) whether total plasma fibronectin levels differ between normotensive, hypertensive, and preeclamptic women; and 2) whether total plasma fibronectin may serve as an early marker of pregnancy-induced hypertensive disorders. METHODS: Total plasma fibronectin was measured in 376 nulliparous women once in each trimester of pregnancy. Normotensive controls (n = 222) and subjects with pregnancy-induced hypertensive disorders (n = 154) were identified after delivery. The group with pregnancy-induced hypertensive disorders was subdivided into a gestational hypertensive group (n = 125) and a preeclamptic group (n = 29). A complete total plasma fibronectin data set was obtained from 347 subjects. Trends in total plasma fibronectin values were compared for the different groups and relative risks (RRs) were calculated after optimal cutoff levels had been determined by receiver operating characteristic curves. RESULTS: Total plasma fibronectin values (+/- standard error of the mean) were 227 +/- 3 mg/L in the first, 219 +/- 3 mg/L in the second, and 260 +/- 5 mg/L in the third trimesters in normotensive pregnancies. In the first trimester and persisting throughout pregnancy, total plasma fibronectin levels were significantly higher in patients with pregnancy-induced hypertensive disorders than in controls and showed a sharper increase throughout pregnancy. Increased first-trimester total plasma fibronectin levels result in an RR of 1.4 (95% confidence interval [CI] 1.1, 1.8) of developing a pregnancy-induced hypertensive disorder in general. The RR for the development of preeclampsia was 1.7 (95% CI 0.9, 3.4), which was not significant, when the first-trimester total plasma fibronectin level was above the cutoff level of 240 mg/L. The RR for developing preeclampsia was 3.8 (95% CI 1.8, 8.0) when the second-trimester total plasma fibronectin level increased above 230 mg/L. CONCLUSION: The findings of the present study confirm those of previous studies that have found increased total plasma fibronectin levels in pregnancy-induced hypertensive disorders. This study discovered that in these women, total plasma fibronectin levels are elevated in the first trimester. Total plasma fibronectin appears to be a poor predictor of preeclampsia when measured in a general pregnant population. Therefore, total plasma fibronectin should not be used as a routine screening test in a low-risk population. However, obstetricians may use total plasma fibronectin values to help determine the relative risk of developing pregnancy-induced hypertensive disorders.

Fetal weight gain in a serially scanned high-risk population.

Physiological as well as pathological variables influence fetal growth. This study was undertaken to assess the influence of physiological variables on fetal weight gain in a high-risk population with normal outcome. A total of 121 pregnancies had 3-13 (median 8) ultrasound scans in the third trimester. Estimated fetal weight was calculated according to standard formulae. The estimated fetal weight at 30, 34 and 38 weeks and growth per day in the last 2 weeks prior to delivery were calculated and compared between subgroups defined on physiological characteristics, such as maternal height, maternal weight, parity and fetal sex. There were differences in growth curves for each of the physiological parameters studied. Maternal height and weight were significantly related to the estimated fetal weight throughout the third trimester but there were no significant differences in growth per day in the last 2 weeks before birth. In contrast, subgroups defined by parity and fetal sex did not show significant fetal weight differences in the third trimester, but the daily growth rate prior to birth was significantly higher for multiparae and male fetuses. Physiological factors affect fetal weight gain and need to be taken into account when fetal growth is monitored in high-risk pregnancies.

Decreased first trimester uric acid production in future preeclamptic patients.

The relationship between first trimester uric acid production and later development of pregnancy induced hypertensive disorders (PIHD) was investigated. An anti-oxidant role for uric acid has been mentioned. Since uric acid and fibronectin (PF) are both markers of preeclampsia, the relationship between these two substances was also studied. Controls (n = 72) and patients with PIHD (n = 120) were selected. Uric acid was measured in serum and 24-hours urine samples (uric acid excretion) and PF in blood plasma in 270 nulliparous women at 13 +/- 2 weeks of gestation. Uric acid excretion was significantly lower in the first trimester in a group of patients who later develop PIHD as compared to patients who remain normotensive (p < 0.05), especially when corrected for body weight (p < 0.01). Patients with elevated PF levels in the first trimester showed a significantly lower uric acid excretion than patients with normal PF levels (p < 0.05). The data show diminished uric acid production in patients who will likely develop preeclampsia suggesting an impaired anti-oxidant production in the first trimester. This observation fits well with the hypothesis that an imbalance between anti-oxidant and oxidants plays an important role in the pathogenesis of preeclampsia.

The effect of flecainide acetate on fetal heart rate variability: a case report.

BACKGROUND: Fetal supraventricular tachycardia is most often treated by maternal application of digoxin. A drug used for second-choice therapy is flecainide acetate. CASE: For a case in which maternal digoxin therapy failed, flecainide caused a lowering of the fetal heart rate (FHR) but, simultaneously, variability and accelerations nearly disappeared. The fetus demonstrated a normal movement pattern. Fetal well-being during delivery was assessed by regular ultrasound observations of fetal movements. Flecainide was not continued after birth, and digoxin therapy was started when tachycardia reappeared. The heart rate changed into a reactive pattern 5 days after birth. Around that time, flecainide levels in the neonatal serum were below the limit of detection. CONCLUSION: Flecainide use can cause the absence of accelerations and poor variability in the FHR.

The renin-angiotensin-aldosterone system in preeclampsia. A review.

The renin-angiotensin-aldosterone system plays an integral role in the (patho)physiology of pregnancy and pregnancy-induced hypertensive disease. The current review concerns the renin-angiotensin-aldosterone system in relation to other vasoactive substances in normal pregnancy and preeclampsia.