Per Olofsson

Cardiotocography only versus cardiotocography plus ST analysis of fetal electrocardiogram for intrapartum fetal monitoring: a Swedish randomised controlled trial

BACKGROUND Previous studies indicate that analysis of the ST waveform of the fetal electrocardiogram provides information on the fetal response to hypoxia. We did a multicentre randomised controlled trial to test the hypothesis that intrapartum monitoring with cardiotocography combined with automatic ST-waveform analysis results in an improved perinatal outcome compared with cardiotocography alone. METHODS At three Swedish labour wards, 4966 women with term fetuses in the cephalic presentation entered the trial during labour after a clinical decision had been made to apply a fetal scalp electrode for internal cardiotocography. They were randomly assigned monitoring with cardiotocography plus ST analysis (CTG+ST group) or cardiotocography only (CTG group). The main outcome measure was rate of umbilical-artery metabolic acidosis (pH <7.05 and base deficit >12 mmol/L). Secondary outcomes included operative delivery for fetal distress. Results were first analysed according to intention to treat, and secondly after exclusion of cases with severe malformations or with inadequate monitoring. FINDINGS The CTG+ST group showed significantly lower rates of umbilical-artery metabolic acidosis than the cardiotocography group (15 of 2159 [0.7%] vs 31 of 2079 [2%], relative risk 0.47 [95% CI 0.25-0.86], p=0.02) and of operative delivery for fetal distress (193 of 2519 [8%] vs 227 of 2447 [9%], 0.83 [0.69-0.99], p=0.047) when all cases were included according to intention to treat. The differences were more pronounced after exclusion of 291 in the CTG+ST group and 283 in the CTG group with malformations or inadequate recording. INTERPRETATION Intrapartum monitoring with cardiotocography combined with automatic ST-waveform analysis increases the ability of obstetricians to identify fetal hypoxia and to intervene more appropriately, resulting in an improved perinatal outcome.

A high uterine artery pulsatility index reflects a defective development of placental bed spiral arteries in pregnancies complicated by hypertension and fetal growth retardation

INTRODUCTION The development of PIH is associated with a defective trophoblast invasion and conversion of spiral arteries into low-resistance uteroplacental arteries. Hypertension may then be a compensatory response to a defective uteroplacental perfusion. Similar mechanisms may operate in IUGR. AIM To compare uterine artery Doppler blood flow measurements with placental bed histology. The hypothesis was that placental bed vessel pathology plays a role for a raised flow resistance. MATERIALS AND METHODS After blood flow measurements, a placental bed biopsy was taken at CS in 26 complicated (study group) and 29 uncomplicated pregnancies (control group). RESULTS The uterine artery PI was significantly more often abnormally high in the study group compared with the control group, and also in hypertensive pregnancies compared with normotensive IUGR pregnancies. Physiological vessel changes were found in all controls but were absent in 76% of study cases. Physiological changes were significantly more often absent in SGA than in AGA newborns. Absence of physiological changes were significantly more often found in cases with an abnormally high PI. DISCUSSION The results link together circulatory and structural pathophysiological changes of the uteroplacental unit. A defective physiological conversion of the spiral arteries was associated with an increased uterine flow resistance. CONCLUSION This study gave further support for the existence of a triad of defective placental bed vessel maturation, increased uteroplacental flow resistance, and hypertension.

Delayed umbilical cord clamping at birth has effects on arterial and venous blood gases and lactate concentrations

Objective  To estimate the influence of delayed umbilical cord clamping at birth on arterial and venous umbilical cord blood gases, bicarbonate (), base excess (BE) and lactate in vigorous newborns.

Glomerular filtration rate in pregnancy: a study in normal subjects and in patients with hypertension, preeclampsia and diabetes

We have studied renal function during pregnancy using plasma clearance of iohexol to determine the glomerular filtration rate (GFR). In normal pregnancy, GFR was elevated by 40% throughout pregnancy and during the first week post partum, and fell to levels similar to those in non-pregnant women within 1 month. The development of GFR in diabetic pregnant women and in women with gestational hypertension was similar to that recorded in normal pregnancy. In subjects with preeclampsia the rise in GFR observed in normal pregnancy was absent, and no change in GFR was recorded after delivery. We conclude that the development of proteinuria and fluid retention typical of preeclampsia is paralleled by a deterioration of GFR.

Increased uterine artery vascular impedance is related to adverse outcome of pregnancy but is present in only one-third of late third-trimester pre-eclamptic women.

Signs of increased uterine artery vascular impedance in mid‐gestation are strongly related to pre‐eclampsia later in pregnancy. Whether this is true for the late third trimester is, however, unclear. The aim of the present study was to analyze the frequency of increased uterine artery vascular impedance in the third trimester, and its relationship to abnormal umbilical artery Doppler and adverse outcome of pregnancy.

New score indicating placental vascular resistance.

Background.  Umbilical artery Doppler velocimetry is a routine method for fetal surveillance in high‐risk pregnancy. Uterine artery Doppler seems to give comparable information, but it can be difficult to interpret as there are two arteries, which might show notching and/or increased pulsatility index (PI) as signs of increased vascular impedance. Combining the information on vascular resistance on both sides in a new score might simplify and improve evaluation of placental circulation.

Twin delivery: how should the second twin be delivered?

In a series of 803 pairs of twins born between 1973 and 1982, 0.33% of second twins were delivered by cesarean section after vaginal delivery of the first twin. During the last year the frequency has increased to 7%, calling attention to the problem of declining obstetric skills and experience. This has caused us to update the routines of intrapartum management of twin gestations. In the present program only commonly available obstetric techniques are used. The potentially hazardous twin delivery is excluded from a trial of vaginal delivery. Hopefully, the program will help other obstetricians to decide in favor of vaginal delivery in selected twin gestations.

Swedish randomized controlled trial of cardiotocography only versus cardiotocography plus ST analysis of fetal electrocardiogram revisited: analysis of data according to standard versus modified intention-to-treat principle

Objective. To undertake a renewed analysis of data from the previously published Swedish randomized controlled trial on intrapartum fetal monitoring with cardiotocography (CTG‐only) vs. CTG plus ST analysis of fetal electrocardiogram (CTG+ST), using current standards of intention‐to‐treat (ITT) analysis and to compare the results with those of the modified ITT (mITT) and per protocol analyses. Methods. Renewed extraction of data from the original database including all cases randomized according to primary case allocation (n=5 049). Main outcome measure. Metabolic acidosis in umbilical artery at birth (pH <7.05, base deficit in extracellular fluid >12.0mmol/l) including samples of umbilical vein blood or neonatal blood if umbilical artery blood was missing. Results. The metabolic acidosis rates were 0.66% (17 of 2 565) and 1.33% (33 of 2 484) in the CTG+ST and CTG‐only groups, respectively [relative risk (RR) 0.50; 95% confidence interval (CI) 0.28–0.88; p=0.019]. The original mITT gave RR 0.47, 95%CI 0.25–0.86 (p=0.015), mITT with correction for 10 previously misclassified cases RR 0.48, 95%CI 0.24–0.96 (p=0.038) and per protocol analysis RR 0.40, 95%CI 0.20–0.80 (p=0.009). The level of significance of the difference in metabolic acidosis rates between the two groups remained unchanged in all analyses. Conclusion. Re‐analysis of data according to the ITT principle showed that regardless of the method of analysis, the Swedish randomized controlled trial maintained its ability to demonstrate a significant reduction in metabolic acidosis rate when using CTG+ST analysis for fetal surveillance in labor.

Relation between umbilical cord blood pH, base deficit, lactate, 5-minute Apgar score and development of hypoxic ischemic encephalopathy

Objective. Umbilical cord acid–base analysis is fundamental for assessing intrapartum hypoxia. The accuracy of arterial umbilical cord blood lactate, pH and base deficit to reflect a low 5‐minute Apgar score and hypoxic ischemic encephalopathy (HIE) stage 2–3 was assessed, and new gestational age‐adjusted reference standards were compared with traditional stationary reference values. Design and sample. A total of 13,735 pH‐validated routine cord acid–base values from singleton deliveries were tested with stationary and gestational age‐adjusted reference values using receiver operating characteristic curves and calculation of area under curve. Setting. University hospital. Main outcome measures. Accuracy of low pH, high base deficit and high lactate, alone or in combination, to imply 5‐minute Apgar score < 7 or < 4 or HIE. Results. Gestational age‐adjusted values were for all parameters significantly better than crude values to indicate Apgar score < 7. For Apgar score < 4, the differences were not significant. The frequency of HIE was 0.046%, making statistical analyses pointless. Gestational age‐adjusted lactate had the overall best accuracy and among combinations; a low age‐adjusted pH plus high age‐adjusted lactate was slightly better than a low age‐adjusted pH plus high age‐adjusted base deficit. The sensitivity and positive predictive value were low for all parameters. Conclusions. Lactate in cord arterial blood at birth is at least as good as base deficit to reflect an impaired condition at birth, and best when gestational age‐adjusted values are used. Due to methodological confounding involved in calculation of base deficit, lactate may replace base deficit as an acid–base outcome parameter at birth.

Fetal exposure to perfluorinated compounds and attention deficit hyperactivity disorder in childhood.

Background The association between exposure to perfluorinated compounds (PFCs) and attention deficit hyperactivity disorder (ADHD) diagnosis has been sparsely investigated in humans and the findings are inconsistent. Objectives A matched case-control study was conducted to investigate the association between fetal exposure to PFCs and ADHD diagnosis in childhood. Methods The study base comprised children born in Malmö, Sweden, between 1978 and 2000 that were followed up until 2005. Children with ADHD (n = 206) were identified at the Department of Child and Adolescent Psychiatry. Controls (n = 206) were selected from the study base and were matched for year of birth and maternal country of birth. PFC concentrations were measured in umbilical cord serum samples. The differences of the PFC concentrations between cases and controls were investigated using Wilcoxons paired test. Possible threshold effects (above the upper quartile for perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) and above limit of detection [LOD] for perfluorononanoic acid (PFNA)) were evaluated by conditional logistic regression. Results The median umbilical cord serum concentrations of PFOS were 6.92 ng/ml in the cases and 6.77 ng/ml in the controls. The corresponding concentrations of PFOA were 1.80 and 1.83 ng/ml. No associations between PFCs and ADHD were observed. Odds ratios adjusted for smoking status, parity, and gestational age were 0.81 (95% confidence interval [CI] 0.50 to 1.32) for PFOS, 1.07 (95% CI 0.67 to 1.7) for PFOA, and 1.1 (95% CI 0.75 to 1.7) for PFNA. Conclusions The current study revealed no support for an association between fetal exposure to PFOS, PFOA, or PFNA and ADHD.