Fetal blood sampling in addition to intrapartum ST-analysis of the fetal electrocardiogram: evaluation of the recommendations in the Dutch STAN® trial.

OBJECTIVES: To evaluate the recommendations for additional fetal blood sampling (FBS) when using ST-analysis of the fetal electrocardiogram. DESIGN: Prospective cohort study. SETTING: Three academic and six non-academic teaching hospitals in the Netherlands. POPULATION: Labouring women with a high-risk singleton pregnancy in cephalic position beyond 36 weeks of gestation. METHODS: In labouring women allocated to the STAN® arm of a previously published randomised controlled trial who underwent one or more FBS during delivery, we assessed whether FBS was performed according to the trial protocol and how fetal acidosis, defined as an FBS pH < 7.20, was related to ST-waveform analysis. MAIN OUTCOME MEASURES: The number of FBS showing fetal acidosis, related to the different STAN® criteria where additional FBS is recommended. RESULTS: Among 2827 women monitored with STAN®, 297 underwent FBS, of whom 171 (57.6%) were performed according to the predefined criteria and 126 were performed in absence of these criteria. In the first group, rates of fetal acidosis (pH < 7.20) were two of 18, none of nine, 12 of 111 and three of 33 when FBS was taken for abnormal cardiotocogram (CTG) at the start, intermediary CTG at the start, abnormal CTG >60 minutes, and poor electrocardiogram quality, respectively. When the predefined criteria were not met and ST-analysis showed no ST-events, only two incidents of fetal acidosis were seen. CONCLUSIONS: The performance of FBS is valuable in the advised STAN® criteria. When these criteria are not met, performance of FBS does not seem helpful in the detection of fetal acidosis.

Changes in echogenicity in the fetal brain: a prevalence study in fetuses at risk for preterm delivery.

OBJECTIVES: To study the incidence of echodensities in the periventricular white matter, ventricular system, basal ganglia and thalamus of the brain in fetuses at risk for preterm delivery. METHODS: This was a prospective study of 124 fetuses with a gestational age between 26 and 34 weeks in pregnancies affected by either pregnancy-induced hypertensive disorders or preterm labor. Transvaginal ultrasound examination of the fetal brain in coronal and sagittal planes was performed weekly until delivery and the neonatal brain was examined within 24 h after delivery. RESULTS: In 66% of all fetuses, echodensities were found in one or more areas of the brain. They were present in the periventricular area in 52% of cases, the intraventricular area in 18% and in the basal ganglia and thalamus area in 28%. Changes in echogenicity were seen throughout the entire gestational-age period studied. Of the periventricular echodensities that exceeded in echodensity that of the choroid plexus, at least 50% persisted after delivery; at least 38% of the intraventricular echodensities and at least 32% of the basal ganglia and thalamus echodensities persisted after delivery. CONCLUSIONS: In high-risk fetuses, echodensities are a frequent finding in several areas in the brain. How far these echodensities are related to future outcome of the infant needs to be investigated.

Haemodynamic changes in the second half of pregnancy: a longitudinal, noninvasive study with thoracic electrical bioimpedance.

OBJECTIVE: Maternal cardiovascular adaptations to pregnancy are necessary for an adequate fetomaternal circulation. However, the time course of physiological haemodynamic changes during the second half of pregnancy remains unclear. Various methods, invasive and noninvasive, are described to measure these changes. The thoracic electrical bioimpedance (TEB) technique is a method which is especially suitable to measure haemodynamic changes over time. The aim of the study was to determine both individual and group trends of haemodynamic changes in healthy pregnant women during the second half of pregnancy by means of TEB. Outcome variables are heart rate (HR), stroke volume (SV), cardiac output (CO) and blood pressure. DESIGN: Longitudinal study. SETTING: Outpatient antenatal care clinic of university hospital. POPULATION: A total of 22 healthy nonsmoking women with an uncomplicated singleton pregnancy and without pre-existing vascular disorders were invited. METHODS: TEB and blood pressure measurements were performed at each regular visit from about 24 weeks of gestation through term age. MAIN OUTCOME MEASURES: Trends were calculated with the random effects model. RESULTS: Data obtained from 19 women were analysed, with a median of eight (range 3-11) measurements. HR showed a linear increase (P < 0.0005) and a quadratic trend (P < 0.0005). SV decreased linearly (P = 0.046), without a quadratic course. CO remained stable over time. CONCLUSION: During the second half of physiological pregnancy, significant trends could be determined. An increase in HR, a decrease in SV, a stable CO and an increase in systolic and diastolic blood pressures were found.

Elevated uterine activity increases the risk of fetal acidosis at birth.

OBJECTIVE: The objective of the study was to assess the role of uterine activity on fetal outcome. STUDY DESIGN: Intrauterine pressure (IUP) recordings from consecutive term singleton, vaginal deliveries collected between June 1, 1993, and July 1, 2004, were analyzed. One thousand four hundred thirty-three recordings were included. IUP data were obtained using HP 8040A and HP M1350 cardiotocographs. For each recording the uterine contraction curve was analyzed, and the following contraction parameters were determined: relaxation time; contraction duration, frequency, amplitude, and surface; Montevideo units; and active planimeter units and contraction frequency. IUP recordings and contraction parameters from deliveries ending with an umbilical artery pH of 7.11 or less were compared with those ending with an umbilical artery pH of 7.12 or greater. Statistical analyses were performed using Student's t test and logistic regression. RESULTS: An umbilical artery pH 7.11 or less at birth is associated with significant more uterine activity during the first and second stage of labor. CONCLUSION: Increased uterine activity is significantly associated with a higher incidence of an umbilical artery pH of 7.11 or less.

[Indications for respiratory complications during the use of oral nifedipine as a tocolytic agent, especially in patients with multiple pregnancies]. / Aanwijzingen voor respiratoire complicaties bij gebruik van oraal nifedipine als tocolyticum, met name bij patiënten met een meerlingzwangerschap.

In 7 women with premature labour pains, severe dyspnoea developed that was possibly related to the use of nifedipine as an 'off-label' tocolytic. 6 of these women had a twin pregnancy. Diuretics and oxygen therapy had little effect, but the patients recovered after the administration of nifedipine was stopped. The efficacy and safety of nifedipine as a tocolytic agent has been investigated in a number of well-designed randomised studies. However, these studies were performed in a selected group of pregnant women and women with multiple pregnancies or prematurely ruptured membranes were mostly excluded. It can be hypothesised that the respiratory complications in these cases are due to unequal ventilation/perfusion of the lungs in the presence of a physiologically elevated diaphragm due to the pregnancy. These changes are more pronounced in multiple pregnancies. After administration ofnifedipine, there is perfusion of atelectatic areas of the lung that are not or not well ventilated, resulting in ventilation-perfusion discrepancy and hence dyspnoea. Although case reports permit only limited extrapolation, these observations warrant caution with regard to the safety ofnifedipine as a tocolytic agent in patients with multiple pregnancies. The use of medication in groups of patients for which the agent has not been investigated, or which were explicitly excluded from the study, should be done with extreme caution. One should in any case be aware of the possible risks.

Long-term follow up of children exposed in utero to nifedipine or ritodrine for the management of preterm labour.

OBJECTIVE: To compare the long-term psychosocial and motor effects on children exposed in utero to nifedipine or ritodrine for the management of preterm labour. DESIGN: Randomised controlled trial. SETTING: Multicentre study in two university and one primary hospital in the Netherlands. POPULATION: In the original trial, 185 women were randomised to either nifedipine (n = 95) or ritodrine (n = 90). Of the 185 liveborn children, 171 survived (92%), and of these 102 (61%) were followed up at age 9-12 years. METHODS: Age-specific questionnaires were administered to the parent and teacher. Additional data were obtained from medical records. MAIN OUTCOME MEASURES: Questionnaires were used to assess the child's behavioural-emotional problems, quality of life (QoL), motor functioning, parenting distress and the child's education. RESULTS: Of the 171 eligible families, 102 (61%) agreed to participate and completed the questionnaires. Response was equal in the ritodrine group (n = 54 of 83 surviving children, 65%) compared with the nifedipine group (n= 48 of 88 surviving children, 55%). After controlling for differing perinatal characteristics at birth, no significant differences between the groups were detected with respect to long-term behaviour-emotional outcome, QoL, education, motor functioning or parenting distress. Psychosocial outcome was slightly better in the nifedipine group. CONCLUSIONS: The results do not support any differential postnatal effect of the tocolytic agents ritodrine or nifedipine on the child's long-term psychosocial and motor functioning. The slightly better outcome of children randomised in the nifedipine group is most likely due to more favourable perinatal outcomes in this group. These results merit further investigation in a larger group of survivors.

Pharmacological and surgical therapy for primary postpartum hemorrhage.

Early postpartum hemorrhage remains a significant cause of maternal morbidity and mortality. Postpartum hemorrhage is most commonly due to uterine atony and often responds to medical treatments such as administration of uterotonic drugs, alone or in combination with uterine massage or bimanual compression. As the incidence of cesarean section continues to rise, the problem of placenta previa and accreta is likely to become more common. For first-line management of postpartum hemorrhage adequate blood and fluid replacement is mandatory. In recent years new therapeutic measures to control the bleeding have gained attention. Although, these newer therapies focus on avoiding the need for emergency hysterectomy and preservation of reproductive function, reports of subsequent pregnancies are still scarce. Established management options are shortly reviewed and novel medical and surgical treatments are more extensively discussed.

Quality of intrapartum cardiotocography in twin deliveries.

OBJECTIVE: Intrapartum fetal heart rate (FHR) recordings in twins were compared for fetal signal loss during both stages of labor to assess the quality of these recordings by the method that had been used: external ultrasound or directly via a scalp electrode. STUDY DESIGN: Analysis of recordings collected between January 1, 1994, and January 1, 2002, from consecutive twin deliveries at the Vrije Universiteit Medical Center in Amsterdam. One hundred seventy-two twins that delivered via the vaginal route were included in the study. FHR recordings had a duration of at least 1 hour before the birth of the second twin. Subdivision took place on the basis of the recording technique, ie, ultrasound or scalp electrode. FHR data was obtained with HP-M1350 cardiotocographs. The status (pen on, pen off, maternal signal) and the mode of the signals were acquired. The duration of pen lifts and maternal signals was divided by the total duration of the recording. Statistical analyses were performed with the Mann-Whitney U test and the Wilcoxon signed ranks test. RESULTS: Recordings obtained via ultrasound demonstrated significantly more fetal signal loss than those obtained via the direct mode, particularly in the second stage. Approximately 26% to 33% of first stage and 41% to 63% of second stage ultrasound intrapartum FHR recordings in twins exceeded the International Federation of Gynecology and Obstetrics (FIGO) criteria for fetal signal loss. CONCLUSION: Intrapartum FHR monitoring via ultrasound provides far poorer quality FHR signals than the direct mode. The direct mode deserves a more prominent position in fetal surveillance than it currently has.

The quality of intrapartum fetal heart rate monitoring.

OBJECTIVE: To determine the quality of fetal heart rate (FHR) recordings during the first and second stage of labor by quantifying the amount of fetal signal loss in relation to the method of monitoring: external ultrasound or directly via a scalp electrode. STUDY DESIGN: Analysis of 239 intrapartum recordings stored between 1 January 2001 and 1 July 2001 from consecutive deliveries at the Vrije Universiteit Medical Center in Amsterdam. Singletons delivered via the vaginal route were included in the study. FHR recordings had duration of at least 1h prior to birth of the infant. Subdivision in three groups took place on the basis of the recording technique which had been used; i.e. ultrasound, scalp electrode or a combination of both methods. FHR data was obtained using HP-M1350 cardiotocographs. The status (pen on, pen off, maternal signal) and the mode of the signals were acquired. The duration of pen lifts and maternal signals was divided by the total duration of the recording. Statistical analyses were performed with the Mann-Whitney U-test and the Wilcoxon signed ranks test. RESULTS: Recordings obtained via ultrasound demonstrated significantly more fetal signal loss than those obtained via the direct mode, particularly in the second stage. The FIGO criteria for fetal signal loss with external ultrasound were not fulfilled during this stage for about half the cases. CONCLUSION: Intrapartum FHR monitoring via a scalp electrode provides far better quality FHR signals than external ultrasound and deserves a more prominent position in fetal surveillance than it currently has.

Peri- and intraventricular cerebral sonography in second- and third-trimester high-risk fetuses: a comparison with neonatal ultrasound and relation to neurological development.

OBJECTIVES: To determine whether periventricular leukomalacia (PVL) and peri- and intraventricular hemorrhages can be detected in fetuses at risk for preterm birth and to establish the clinical significance of this finding. METHODS: Prenatal cerebral sonography was performed in 26 fetuses at risk for uteroplacental insufficiency on the day of inclusion into the study and weekly until delivery. Neonatal cerebral ultrasound examination was performed within 24 h of birth and biweekly until discharge. The infants underwent standardized neurological examinations. RESULTS: During 30 observations, 21/26 fetuses presented in a cephalic position. Successful visualization in the coronal and sagittal planes was significantly correlated with that of a control population (r = 0.615; 95% CI, 0.390-0.771). In 20/21 fetuses at least one observation was adequate for analysis. Eleven cerebral abnormalities were found in nine fetuses, periventricular echodensities in four, intraventricular hemorrhage in two, and localized thalamic densities in five. In six of these infants ultrasound abnormalities persisted after birth. Neurological follow-up at 24 months demonstrated abnormalities in three infants, two infants were normal and one was lost to follow-up. The three infants with normal ultrasound results after birth had a normal follow-up. Five infants with normal antenatal ultrasound results showed ultrasound abnormalities during the neonatal period; four of them developed PVL Grade 1 and one developed PVL Grade 2. The follow-up of two of these infants was normal, two died and one developed spastic tetraplegia. Abnormal antenatal brain sonography was significantly correlated with gestational age at birth (r = 0.487; P = 0.029). CONCLUSION: Peri- and intraventricular echodensities can be detected reliably before birth in fetuses at high risk for uteroplacental insufficiency. When abnormalities persist, there is a high risk for an adverse outcome.

Hemodynamic and metabolic effects after nifedipine and ritodrine tocolysis.

OBJECTIVES: The purpose of this study is to compare the hemodynamic and metabolic changes after ritodrine and nifedipine tocolysis. METHODS: For an open randomized study, patients with preterm labor (N=185) were allocated to groups to receive ritodrine intravenously (N=90) or nifedipine orally (N=95). RESULTS: The mean diastolic blood pressure was significantly lower in the ritodrine group 24 h (65+/-12 vs. 70+/-8, P=0.001) and 48 h (65+/-12 vs. 71+/-8, P=0.004) after starting tocolysis compared with the nifedipine group. Mean maternal heart rate was significantly higher in the ritodrine group 24 h (105+/-17 vs. 86+/-13, P<0.0001) and 48 h (100+/-21 vs. 85+/-12, P<0.0001) after starting tocolysis compared with the nifedipine group. Mean fasting glucose levels were higher (6.68+/-2.53 vs. 4.93+/-1.23, P=0.0016), while mean potassium levels were lower (3.52+/-0.84 vs. 3.81+/-0.45, P=0.04) in the ritodrine group 48 h after starting tocolysis compared with the nifedipine group. CONCLUSIONS: Use of nifedipine for preterm labor is associated with a lower incidence of adverse hemodynamic and metabolic changes compared with ritodrine after 24 and 48 h of tocolysis. In our opinion nifedipine is the preferred drug of choice for the treatment of preterm labor.

[Nifedipine first choice in management of threatening preterm labor]. / Nifedipine eerste keus bij de behandeling van dreigende vroeggeboorte.

Preterm birth is the most important cause of perinatal mortality in Europe and North America. Tocolytic agents named beta 2-sympathicomimetics postpone delivery for 24-48 hours, but do not reduce perinatal mortality or morbidity. Calcium antagonists, in particular nifedipine, are more effective tocolytic agents than beta 2-sympathicomimetics in terms of delaying delivery. Meta-analyses have found that calcium antagonists statistically significantly reduced perinatal morbidity and that the number of maternal side effects was statistically significantly lower compared with beta 2-sympathicomimetics. Nifedipine also has the benefit of oral administration, in contrast with beta 2-sympathicomimetics which are administered intravenously. Nifedipine is therefore the first choice in the management of threatening preterm labour.

Fetal handedness and head position preference: a developmental study.

Hand-head contacts were observed by means of serial ultrasound recordings in 10 healthy fetuses from 12 to 38 weeks of gestational age. Contacts were distinguished as being unimanual or bimanual, and if unimanual, whether they were made with the right or left hand. Both types of contact and ones made unimanually with the right or left hand were identified at each age as to whether they were associated with a preferential head position. A strong unimanual bias was evident at each age except for Week 36. At this age, there was a bimanual bias. Unimanual contacts did not develop a lateralized preference, and neither type of contact established a stable relationship with head position. Furthermore, there was no evidence to support the suggestion that hand contact and head position codevelop to form a preferred ipsilateral synergy. Findings are discussed relative to contradictory evidence from other fetal and neonatal studies.

Final results of the Cervical Incompetence Prevention Randomized Cerclage Trial (CIPRACT): therapeutic cerclage with bed rest versus bed rest alone.

OBJECTIVE: To compare preterm delivery rates (before 34 weeks of gestation) and neonatal morbidity and mortality in patients with risk factors or symptoms of cervical incompetence managed with therapeutic McDonald cerclage and bed rest versus bed rest alone. STUDY DESIGN: Cervical length was measured in patients with risk factors or symptoms of cervical incompetence. Risk factors for cervical incompetence included previous preterm delivery before 34 weeks of gestation that met clinical criteria for the diagnosis of cervical incompetence, previous preterm premature rupture of membranes before 32 weeks of gestation, history of cold knife conization, diethylstilbestrol exposure, and uterine anomaly. When a cervical length of <25 mm was measured before a gestational age of 27 weeks, a randomization for therapeutic cerclage and bed rest (cerclage group) or bed rest alone (bed rest group) was performed. The analysis is based on intention to treat. RESULTS: Of the 35 women who met the inclusion criteria, 19 were allocated randomly to the cerclage group and 16 to the bed rest group. Both groups were comparable for mean cervical length and mean gestational age at time of randomization, mean overall 20 mm and 21 weeks. Preterm delivery before 34 weeks was significantly more frequent in the bed rest group than in the cerclage group (7 of 16 vs none, respectively; P =.002). There was no statistically significant difference in neonatal survival between the groups (13 neonates survived in the bed rest group vs all in the cerclage group). The compound neonatal morbidity, defined as admission to the neonatal intensive care unit or neonatal death, was significantly higher in the bed rest group than in the cerclage group (8 of 16 vs 1 of 19, respectively; P =.005; RR = 9.5, 95% CI, 1.3-68.1). CONCLUSIONS: Therapeutic cerclage with bed rest reduces preterm delivery before 34 weeks of gestation and compound neonatal morbidity in women with risk factors and/or symptoms of cervical incompetence and a cervical length of <25 mm before 27 weeks of gestation.

Neonatal respiratory morbidity following elective caesarean section in term infants. A 5-year retrospective study and a review of the literature.

Respiratory morbidity is an important complication of elective caesarean section. The presence of labour preceding caesarean section reduces the risk of neonatal respiratory morbidity. Recently, it has been shown that the incidence of respiratory morbidity is lower in infants with a gestational age of at least 39(+0) weeks at elective caesarean section compared to infants with a gestational age less than 39(+0) weeks.This article describes the results of a 5-year retrospective study on the incidence of respiratory distress in term neonates delivered by elective caesarean section in relation to gestational age and provides a literature review on neonatal respiratory morbidity following elective caesarean section.

Maternal serum Ca125 and Ca15-3 antigen levels in normal and pathological pregnancy.

OBJECTIVE: To evaluate the value of maternal serum CA125 and CA15-3 concentrations for discriminating pathological from normal pregnancies. METHODS: Serum samples from 120 women, in whom pregnancy outcome was pathological, i.e. spontaneous abortion, fetal death, intrauterine growth retardation, chromosomal and structural abnormalities, and (pre)eclampsia, were assessed for CA125 and CA15-3 and compared with levels found in 350 women with a normal pregnancy outcome matched for age and duration of pregnancy. RESULTS: Maternal CA125 serum values were significantly higher in the first and the third trimester of pregnancy (median 23.0 and 21.0 U/ml; p < 0.00001 and p < 0.001, respectively), compared to those in the second trimester (median 14.0 U/ml), but not significantly different from those obtained in pathological pregnancies. Maternal serum CA15-3 values were significantly higher during the third trimester (median 26.0 U/ml) compared to the first and second trimester of pregnancy (median 14.0 and 15.0 U/ml; p < 0.0001); CA15-3 serum levels in normal and pathological pregnancies showed no significant difference. CONCLUSION: Maternal serum levels of CA125 are higher during the first and third trimester of pregnancy. CA15-3 maternal serum levels are higher during the third trimester compared to the first and second trimester. Maternal CA125 and CA15-3 serum levels showed no relation with a pathological outcome of pregnancy.

Management and monitoring of severe preeclampsia.

Preeclampsia is associated with increased maternal and perinatal morbidity and mortality. Preeclampsia is more than pregnancy-induced hypertension. The hypertension is only one manifestation of an underlying multifactorial, multisystem disorder, initiated early in pregnancy. In established severe disease there is volume contraction, reduced cardiac output, enhanced vascular reactivity, increased vascular permeability and platelet consumption. Medical treatment of severe hypertension in pregnancy is required. The more controversial issues are the role of pharmacological treatment in conservative management of severe preeclampsia aiming at prolongation of pregnancy, the ability of such therapy to modify the course of the underlying systemic disorder and the effects on fetal and maternal outcome. This paper presents an overview concerning the current developments in management and monitoring of severe preeclampsia. Controversial topics such as the role of plasma volume expansion in preeclampsia, expectant versus aggressive management of severe preeclampsia remote from term, and pharmacological interventions in the management of eclampsia and the HELLP syndrome are addressed.

Pathophysiology of preeclampsia and the role of serotonin.

Hypertensive disorders constitute the most common medical complications of pregnancy. In normal pregnancy, impressive physiological changes take place in the maternal cardiovascular system. Morphological changes are the result of invasion of migratory trophoblast cells into the walls of the spiral arteries. After destruction of elastic, muscular and neural tissue in the media, the trophoblast cells get incorporated into the vessel wall and the endothelial lining of the spiral arteries is restored. The physiological changes create a low-resistance, low-pressure, high-flow system with the absence of maternal vasomotor control. Biochemical adaptations in maternal vasculature include changes in the prostaglandin system, the renin-angiotensin-aldosteron system and the kallikrein-kinin system. In preeclampsia, physiological changes in the spiral arteries are confined to the decidual portion of the arteries. Myometrial segments remain anatomically intact and fail to dilate. In addition, the adrenergic nerve supply is left intact. The cause of this impaired endovascular trophoblast invasion is not yet elucidated. But in combination with the imbalance between vasodilator and vasoconstrictor eicosanoids, it gives rise to reduced perfusion of the intervillous space. In the absence of an adequate production of antiaggregatory prostacyclin (PGI(2)), nitric oxide, or both, surface-mediated platelet activation is supposed to occur on the surface of the spiral arteries. Because platelets are the principal source of circulating serotonin, the increased platelet aggregation in preeclampsia causes an increase in serotonin levels. Interaction of serotonin with serotonin(1)- or serotonin(2)-receptors depends on the state of the endovascular trophoblast or endothelium in the spiral arteries and has opposite effects with regard to vasodilating and vasoconstrictive influences.

Pharmacological treatment of severe hypertension in pregnancy and the role of serotonin(2)-receptor blockers.

Hypertensive disorders of pregnancy are the leading cause of maternal and perinatal mortality and morbidity in developing and developed countries. The etiology of preeclampsia is still unknown. Delivering the baby is the only definite treatment. The benefits of acute pharmacological control of severe hypertension prior to and/or post-delivery are generally accepted. Most drugs commonly used in the management of severe hypertension in pregnancy have significant maternal and/or neonatal adverse side effects. Furthermore, some are not effective to acutely lower the blood pressure in patients with a hypertensive crisis. Until recently not one of the commonly used antihypertensive drugs has been tailored to the pathophysiology of severe preeclampsia, being a clinical syndrome characterized by endothelial cell dysfunction, vasospasm and platelet aggregation. Ketanserin, a serotonin(2)-receptor blocker, is a drug that appears to be tailored for treating this pregnancy-associated enthothelial cell dysfunction. The results of several prospective trials show that there is a definite place for serotonin(2)-receptor blockers in the treatment of pregnancy-induced hypertensive disorders. This review provides a summary on the more established drugs as well as on some of the newer antihypertensive drugs used in pregnancy with emphasis on the existing experience with ketanserin.