European Association of Perinatal Medicine (EAPM), European Board and College of Obstetricians and Gynaecologists (EBCOG), European Midwives Association (EMA). Joint position statement: Substandard and disrespectful care in labour - because words matter.

Substandard or disrespectful care during labour should be of serious concern for healthcare professionals, as it can affect one of the most important events in a woman's life. Substandard care refers to the use of interventions that are not considered best-practice, to the inadequate execution of interventions, to situations where best-practice interventions are withheld from patients, or there is lack of adequate informed consent. Disrespectful care refers to forms of verbal and non-verbal communication that affect patients' dignity, individuality, privacy, intimacy, or personal beliefs. There are many possible underlying causes for substandard and disrespectful care in labour, including difficulties in modifying behaviours, judgmental or paternalistic attitudes, personal interests and individualism, and a human tendency to make less arduous, less difficult, or less stressful clinical decisions. The term "obstetric violence" is used in some parts of the world to describe various forms of substandard and disrespectful care in labour, but suggests that it is mainly carried out by obstetricians and is a serious form of aggression, carried out with the intent to cause harm. We believe that this term should not be used, as it does not help to identify the underlying problem, its causes, or its correction. In addition, it is generally seen by obstetricians and other healthcare professionals as an unjust and offensive term, generating a defensive and less collaborative mindset. We reach out to all individuals and institutions sharing the common goal of improving women's experience during labour, to work together to address the underlying causes of substandard and disrespectful care, and to develop common strategies to deal with this problem, based on mutual comprehension, trust and respect.

EUROPEAN ASSOCIATION OF PERINATAL MEDICINE (EAPM) Position statement: Use of appropriate terminology for situations related to inadequate fetal oxygenation in labor.

In high-resource countries, adverse perinatal outcomes are currently rare in term, non-malformed fetuses, undergoing labor, but they remain a leading cause of medico-legal dispute. Precise terminology is important to describe situations related to inadequate fetal oxygenation in labor, to ensure appropriate communication between healthcare professionals and adequate transmission of information to parents. This position statement provides consensus definitions from European perinatologists and midwives regarding the most appropriate terminology to describe situations related to inadequate fetal oxygenation in labor: suspected fetal hypoxia, severe newborn acidemia, newborn metabolic acidosis, and hypoxic-ischemic encephalopathy. It also identifies terms that are imprecise or nonspecific to this situation, and should therefore be avoided by healthcare professionals: fetal well-being, fetal stress, fetal distress, non-reassuring fetal state, and birth asphyxia.

Is the fetus fit for labor? Introducing fast-and-frugal trees (FFTrees) to simplify triage of women for STAN monitoring: An interobserver agreement comparison with traditional classification.

INTRODUCTION: It is a shortcoming of traditional cardiotocography (CTG) classification table formats that CTG traces are frequently classified differently by different users, resulting in poor interobserver agreements. A fast-and-frugal tree (FFTree) flow chart may help provide better concordance because it is straightforward and has clearly structured binary questions with understandable "yes" or "no" responses. The initial triage to determine whether a fetus is suitable for labor when utilizing fetal ECG ST analysis (STAN) is very important, since a fetus with restricted capacity to respond to hypoxic stress may not generate STAN events and therefore may become falsely negative. This study aimed to compare physiology-focused FFTree CTG interpretation with FIGO classification for assessing the suitability for STAN monitoring. MATERIAL AND METHODS: A retrospective study of 36 CTG traces with a high proportion of adverse outcomes (17/36) selected from a European multicenter study database. Eight experienced European obstetricians evaluated the initial 40 minutes of the CTG recordings and judged whether STAN was a suitable fetal surveillance method and whether intervention was indicated. The experts rated the CTGs using the FFTree and FIGO classifications at least 6 weeks apart. Interobserver agreements were calculated using proportions of agreement and Fleiss' kappa (κ). RESULTS: The proportions of agreement for "not suitable for STAN" were for FIGO 47% (95% confidence interval [CI] 42%-52%) and for FFTree 60% (95% CI 56-64), ie a significant difference; the corresponding figures for "yes, suitable" were 74% (95% CI 71-77) and 70% (95% CI 67-74). For "intervention needed" the figures were 52% (95% CI 47-56) vs 58% (95% CI 54-62) and for "expectant management" 74% (95% CI 71-77) vs 72% (95% CI 69-75). Fleiss' κ agreement on "suitability for STAN" was 0.50 (95% CI 0.44-0.56) for the FIGO classification and 0.57 (95% CI 0.51-0.63) for the FFTree classification; the corresponding figures for "intervention or expectancy" were 0.53 (95% CI 0.47-0.59) and 0.57 (95% CI 0.51-0.63). CONCLUSIONS: The proportion of agreement among expert obstetricians using the FFTree physiological approach was significantly higher compared with the traditional FIGO classification system in rejecting cases not suitable for STAN monitoring. That might be of importance to avoid false negative STAN recordings. Other agreement figures were similar. It remains to be shown whether the FFTree simplicity will benefit less experienced users and how it will work in real-world clinical scenarios.

European guidelines on perinatal care- Peripartum care Episiotomy.

OF RECOMMENDATIONS1. Episiotomy should be performed by indication only, and not routinely (Moderate quality evidence +++-; Strong recommendation). Accepted indications for episiotomy are to shorten the second stage of labor when there is suspected fetal hypoxia (Low quality evidence ++-; Weak recommendation); to prevent obstetric anal sphincter injury in vaginal operative deliveries, or when obstetric sphincter injury occurred in previous deliveries (Moderate quality evidence +++-; Strong recommendation)2. Mediolateral or lateral episiotomy technique should be used (Moderate quality evidence +++-; Strong recommendation). Labor ward staff should be offered regular training in correct episiotomy techniques (Moderate quality evidence +++-; Strong recommendation).3. Pain relief needs to be considered before episiotomy is performed, and epidural analgesia may be insufficient. The perineal skin needs to be tested for pain before an episiotomy is performed, even when an epidural is in place. Local anesthetics or pudendal block need to be considered as isolated or additional pain relief methods (Low quality evidence ++-; Strong recommendation).4. After childbirth the perineum should be carefully inspected, and the anal sphincter palpated to identify possible injury (Moderate quality evidence +++-; Strong recommendation). Primary suturing immediately after childbirth should be offered and a continuous suturing technique should be used when repairing an uncomplicated episiotomy (High quality evidence ++++; Strong recommendation).

European Guidelines on Perinatal Care - Oxytocin for induction and augmentation of labor[Formula: see text].

OF RECOMMENDATIONS1. Oxytocin for induction or augmentation of labor should not be started when there is a previous scar on the body of the uterus (such as previous classical cesarean section, uterine perforation or myomectomy when uterine cavity is reached) or in any other condition where labor or vaginal delivery are contraindicated. (Moderate quality evidence +++-; Strong recommendation).2. Oxytocin should not be started before at least 1 h has elapsed since amniotomy, 6 h since the use of dinoprostone (30 min if vaginal insert) and 4 h since the use of misoprostol (Low quality evidence ++- -; Moderate recommendation).3. Cardiotocography (CTG) should be performed and a normal pattern without tachysystole should be documented for at least 30 min before oxytocin is used. Continuous CTG, with adequate monitoring of both fetal heart rate and uterine contractions, should be maintained for as long as oxytocin is used, and thereafter until delivery (Low ++- - to moderate +++- quality evidence; Strong recommendation).4. For labor induction, at least 1-h should be allowed after amniotomy before oxytocin infusion is started, to evaluate whether adequate uterine contractility has meanwhile ensued. For augmentation of labor, if the membranes are intact and there are conditions for a safe amniotomy, the latter should be considered before oxytocin is started (Very low quality evidence +- --; Weak recommendation).5. Oxytocin should be administered intravenously using the following regimen: 5 IU oxytocin diluted in 500 mL of 0.9% normal saline (NaCl) (each mL contains 10 mIU of oxytocin), in an infusion pump at increasing rates, as shown in Table 1, until a frequency of 3-4 contractions per 10 min is reached, a non-reassuring CTG pattern ensues, or maximum rates are reached (Low quality evidence ++ - -; Strong recommendation). If the frequency of contractions exceeds 5 in 10 min, the infusion rate should be reduced, even if a normal CTG pattern is present. With a non-reassuring CTG pattern, urgent clinical assessment by an obstetrician is indicated, and strong consideration should be given to reducing or stopping the oxytocin infusion. The minimal effective dose of oxytocin should always be used. (Low ++- - to Moderate +++- - quality evidence; Strong recommendation).[Table: see text]6. Use of oxytocin for induction and augmentation of labor should be regularly audited (Low quality evidence ++--; Strong recommendation).

A multi-centre, open label, randomised, parallel-group, superiority Trial to compare the efficacy of URsodeoxycholic acid with RIFampicin in the management of women with severe early onset Intrahepatic Cholestasis of pregnancy: the TURRIFIC randomised trial.

BACKGROUND: Severe early onset (less than 34 weeks gestation) intrahepatic cholestasis of pregnancy (ICP) affects 0.1% of pregnant women in Australia and is associated with a 3-fold increased risk of stillbirth, fetal hypoxia and compromise, spontaneous preterm birth, as well as increased frequencies of pre-eclampsia and gestational diabetes. ICP is often familial and overlaps with other cholestatic disorders. Treatment options for ICP are not well established, although there are limited data to support the use of ursodeoxycholic acid (UDCA) to relieve pruritus, the main symptom. Rifampicin, a widely used antibiotic including in pregnant women, is effective in reducing pruritus in non-pregnancy cholestasis and has been used as a supplement to UDCA in severe ICP. Many women with ICP are electively delivered preterm, although there are no randomised data to support this approach. METHODS: We have initiated an international multicentre randomised clinical trial to compare the clinical efficacy of rifampicin tablets (300 mg bd) with that of UDCA tablets (up to 2000 mg daily) in reducing pruritus in women with ICP, using visual pruritus scores as a measuring tool. DISCUSSION: Our study will be the first to examine the outcomes of treatment specifically in the severe early onset form of ICP, comparing "standard" UDCA therapy with rifampicin, and so be able to provide for the first-time high-quality evidence for use of rifampicin in severe ICP. It will also allow an assessment of feasibility of a future trial to test whether elective early delivery in severe ICP is beneficial. TRIAL IDENTIFIERS: Australian New Zealand Clinical Trials Registration Number (ANZCTR): 12618000332224p (29/08/2018). HREC No: HREC/18/WCHN/36. EudraCT number: 2018-004011-44. IRAS: 272398. NHMRC registration: APP1152418 and APP117853.

Fetal electrocardiography ST-segment analysis for intrapartum monitoring: a critical appraisal of conflicting evidence and a way forward.

BACKGROUND: In the past century, some areas of obstetric including intrapartum care have been slow to benefit from the dramatic advances in technology and medical care. Although fetal heart rate monitoring (cardiotocography) became available a half century ago, its interpretation often differs between institutions and countries, its diagnostic accuracy needs improvement, and a technology to help reduce the unnecessary obstetric interventions that have accompanied the cardiotocography is urgently needed. STUDY DESIGN: During the second half of the 20th century, key findings in animal experiments captured the close relationship between myocardial glycogenolysis, myocardial workload, and ST changes, thus demonstrating that ST waveform analysis of the fetal electrocardiogram can provide information on oxygenation of the fetal myocardium and establishing the physiological basis for the use of electrocardiogram in intrapartum fetal surveillance. RESULTS: Six randomized controlled trials, 10 meta-analyses, and more than 20 observational studies have evaluated the technology developed based on this principle. Nonetheless, despite this intensive assessment, differences in study protocols, inclusion criteria, enrollment rates, clinical guidelines, use of fetal blood sampling, and definitions of key outcome parameters, as well as inconsistencies in randomized controlled trial data handling and statistical methodology, have made this voluminous evidence difficult to interpret. Enormous resources spent on randomized controlled trials have failed to guarantee the generalizability of their results to other settings or their ability to reflect everyday clinical practice. CONCLUSION: The latest meta-analysis used revised data from primary randomized controlled trials and data from the largest randomized controlled trials from the United States to demonstrate a significant reduction of metabolic acidosis rates by 36% (odds ratio, 0.64; 95% confidence interval, 0.46-0.88) and operative vaginal delivery rates by 8% (relative risk, 0.92; 95% confidence interval, 0.86-0.99), compared with cardiotocography alone.

The efficacy of misoprostol vaginal insert compared with oral misoprostol in the induction of labor of nulliparous women: A randomized national multicenter trial.

INTRODUCTION: Our objective was to compare the efficacy of a 200-µg misoprostol vaginal insert vs oral misoprostol regarding the cesarean section rate and the time interval to vaginal delivery in nulliparous women with unfavorable cervix. MATERIAL AND METHODS: In this prospective multicenter trial, 283 nulliparous women at term with Bishop score <6 were randomized to induction of labor with either a misoprostol vaginal insert (n = 140) or oral misoprostol (n = 143). In the oral misoprostol group, a 50-µg dose of oral misoprostol was administered every 4 hours up to three times during the first day; during the second day, the dose was increased to 100-µg every 4 hours up to three times during the first day, if necessary. Primary outcome was the cesarean section rate. Secondary outcomes were the time from induction of labor to vaginal delivery, the rate of other induction methods needed, labor augmentation with oxytocin and/or amniotomy, use of tocolytics and adverse neonatal and maternal events. RESULTS: In the misoprostol vaginal insert group, median time to vaginal delivery was shorter (24.5 hours vs 44.2 hours, P < 0.001), whereas no difference was found in the cesarean section rate (33.8% vs 29.6%, odds ratio [OR] 1.21, 95% confidence interval [CI] 0.66-1.91, P = 0.67). Other induction methods and labor augmentation with oxytocin and/or amniotomy were less frequent in the misoprostol vaginal insert group (OR 0.32, 95% CI 0.18-0.59 and OR 0.56, 95% CI 0.32-0.99, respectively). Need for tocolysis and meconium-stained amniotic fluid were more common in the misoprostol vaginal insert group (OR 3.63, 95% CI 1.12-11.79 and OR 2.38, 95% CI 1.32-4.29, respectively). Maternal and neonatal adverse events did not differ between groups. CONCLUSIONS: Misoprostol vaginal insert proved to shorten the time to vaginal delivery and to reduce the use of other methods of labor induction and augmentation, but it did not reduce the cesarean section rate compared with oral misoprostol. The benefit of more rapid delivery associated with misoprostol vaginal insert should be weighed against the greater risks for uterine hyperstimulation and meconium-stained amniotic fluid.

Waveform analysis of the fetal ECG in labor in patients with intrahepatic cholestasis of pregnancy.

AIM: Intrahepatic cholestasis of pregnancy (ICP) is reported to be associated with an increased risk of sudden fetal death. The possible mechanism is thought to be cardiac arrhythmia. Prolonged QT interval of the electrocardiogram (ECG) is associated with arrhytmogenic events. The aim of the study was to compare the fetal ECG QT interval during labor in pregnancies complicated with ICP to healthy controls. METHODS: The fetal ECG and QT interval was reviewed retrospectively. The intrapartum QT interval was measured in 61 fetuses born to mothers with ICP and in a control group of similar size. The corrected QT interval (QTc) was calculated using Bazett's formula: QT/√RR. The occurrence of ST segment depression was also included in the analysis. RESULTS: The groups were similar regarding to maternal age, parity, BMI, gestational age and smoking habits. The rate of labor induction was significantly higher in ICP patients (P < 0.001). The QTc at the beginning and the end of recording was analyzed and there were no significant differences in these values between the ICP patients and healthy controls (P = 0.467). Most ICP patients used ursodeoxycholic acid (UDCA) for mediation. We analyzed separately patients who had elevated liver enzymes before labor. No significant differences in the QTc were noted in these patients either. Nor were there any significant ST depressions in ICP patients. CONCLUSIONS: The etiology of adverse perinatal outcome and even sudden fetal death in ICP is still controversial. No differences in QTc intervals and ST waveforms during labor were found in our study material.

The importance of the learning process in ST analysis interpretation and its impact in improving clinical and neonatal outcomes.

BACKGROUND: Intrapartum fetal heart rate monitoring was introduced with the goal to reduce fetal hypoxia and deaths. However, continuous fetal heart rate monitoring has been shown to have a high sensitivity but also a high false-positive rate. To improve specificity, adjunctive technologies have been developed to identify fetuses at risk for intrapartum asphyxia. Intensive research on the value of ST-segment analysis of the fetal electrocardiogram as an adjunct to standard electronic fetal monitoring in lowering the rates of fetal metabolic acidosis and operative deliveries has been ongoing. The conflicting results in randomized and observational studies may partly be due to differences in study design. OBJECTIVE: This study aims to determine the significance of the learning process for the introduction of ST analysis into clinical practice and its impact on initial and subsequent obstetric outcomes. STUDY DESIGN: This was a prospective observational study with the primary objective to evaluate the importance of the learning period on the rates of metabolic acidosis and operative deliveries after the implementation of ST analysis. The study was conducted at the Turku University Hospital, Turku, Finland, with 3400-4200 annual deliveries. The whole study population consisted of all 42,146 deliveries during the study period 2001 through 2011. The ST analysis usage rate was 18%. The data were collected prospectively from labors monitored with ST analysis as an adjunct to conventional intrapartum fetal heart rate monitoring. Primary endpoints were the rates of metabolic acidosis (cord artery pH <7.05 and an extracellular fluid compartment base deficit >12.0 mmol/L), fetal scalp blood sampling, and operative deliveries. Comparisons of these outcomes were made between the initiation period (the first 2 years) and the subsequent usage period (the next 9 years). RESULTS: In the whole study population the prevalence of cord pH <7.05 decreased from 1.5-0.81% (relative risk, 0.54; 95% confidence interval, 0.43-0.67), the rate of cesarean deliveries from 17.2-14.1% (relative risk, 0.82; 95% confidence interval, 0.89-0.97), and the rate of fetal scalp blood sampling from 1.75-0.82% (relative risk, 0.47; 95% confidence interval, 0.38-0.58) when the 2 study periods were compared. In the ST analysis group, the frequency of cord metabolic acidosis rate was reduced from 1.0-0.25% (relative risk, 0.33; 95% confidence interval, 0.15-0.72). CONCLUSION: We provide evidence that the results improve over time and there is a learning curve in the introduction of the ST analysis method. This was demonstrated by the lower rates of metabolic acidosis and operative deliveries after the initial implementation period.

The pregnancy in neurofibromatosis 1: A retrospective register-based total population study.

The objective of this retrospective total population study was to form a view of the pregnancies of the patients with neurofibromatosis type 1 (NF1). A cohort of 1,410 Finnish patients with NF1 was acquired by searching NF1-related inpatient and outpatient hospital visits and confirming the diagnoses by reviewing the medical records. Ten matched control persons per patient with NF1 were collected from Population Register Centre. Study persons were linked to data from Medical Birth Register and Care Register for Health Care through the personal identity code. Cesarean deliveries, hypertension/preeclampsia, and placental abruptions were more common among mothers with NF1 with adjusted odds ratios of 2.24 (95%CI 1.63-3.07), 1.96 (95%CI 1.18-3.24), and 13.40 (95%CI 4.26-42.13), respectively. The adjusted mean pregnancy duration was 0.65 (95%CI 0.42-0.88) weeks shorter among the mothers with NF1 than in the control group consisting of non-NF1 mothers giving birth to a non-NF1 child. The pregnancies of non-NF1 mothers giving birth to a NF1 child were 0.43 (95%CI 0.24-0.62) weeks shorter than in the control group. In summary, NF1 of the mother was associated with a shortened pregnancy and increased pregnancy complications. Also, the NF1 of the fetus slightly shortened pregnancy. Since mothers with NF1 are at increased risk for pregnancy complications, careful evaluation of their pregnancies is warranted.

First-Trimester Maternal Serum Amino Acids and Acylcarnitines Are Significant Predictors of Gestational Diabetes.

BACKGROUND: Current screening methods for gestational diabetes mellitus (GDM) are insufficient in detecting the risk of GDM in the first trimester of the pregnancy. Recent metabolomic studies have detected altered amino acid and acylcarnitine concentrations in type 2 diabetes (T2D). Because of the similarities between T2D and GDM, the determination of these metabolites may be useful in early screening for GDM. AIM: To evaluate the association between GDM and first-trimester maternal serum concentrations of ten amino acids and 31 acylcarnitines. METHODS: This retrospective case-control study included data from pregnant women screened at Oulu University Hospital between 1.1.2008 and 31.12.2011. A total of 31,146 women participated voluntarily in a first-trimester combined screening (for chromosomal abnormalities). The study population included 69 women who developed GDM during pregnancy and 295 women without diabetes before or after pregnancy. The serum concentrations of ten amino acids and 31 acylcarnitines were analyzed from frozen serum samples taken in the first-trimester screening. Multiple of median (MoM) values were compared between the two groups. RESULTS: In the GDM group, serum levels of arginine were significantly higher (1.13 MoM vs. 0.97 MoM), and those of glycine (0.93 MoM vs. 1.03 MoM) and 3-hydroxy-isovalerylcarnitine (0.86 MoM vs. 1.03 MoM) significantly lower compared to the control group (all p < 0.01). In each case, arginine, glycine, and 3-hydroxy-isovaleryl-carnitine would have detected 46%, 32%, and 39% of GDM cases, with a false-positive rate of 20%. Combining these three metabolites with the first-trimester serum marker pregnancy-associated plasma protein A (PAPP-A) and prior risk (age, BMI, and smoking) achieved a detection rate of 72%. CONCLUSION: There are significant differences in the serum levels of arginine, glycine, and 3-hydroxy-isovalerylcarnitine between controls and women who subsequently develop GDM. These differences were already existent in the first trimester of the pregnancy. The use of metabolites in combination with prior risk and first-trimester PAPP-A represents a reliable method to identify women at risk of GDM.

Monitoring the condition of the fetus during delivery.

Uterine contractions during delivery increase the resistance to flow in the blood vessels of the placenta and decreases placental blood circulation, possibly subjecting the fetus to hypoxia. Several methods have been developed for monitoring the condition of the fetus during delivery. Cardiotocography is used to monitor the fetus's heart rate and variability in relation to the mother's contractions. A change in cardiotocography recording due to stimulation of the presenting part is an indication of a healthy fetus. ST analysis of fetal ECG depicts the oxygenation of fetal cardiac muscle during delivery. In addition to cardiotocography and ST analysis, analysis of blood gases and lactate determination are used in assessing the condition of the fetus.

Intrahepatic cholestasis of pregnancy: observational study of the treatment with low-dose ursodeoxycholic acid.

BACKGROUND: To exam the biochemical, obstetric management and pregnancy outcome in women with intrahepatic cholestasis of pregnancy (ICP) and treatment with ursodeoxycholic acid (UDCA). METHODS: Pregnancy outcome in patients with ICP (N = 307) was studied and patients treated with UDCA (N = 208) vs. no UDCA were compared. The data of the antenatal visits, deliveries and neonatal outcome of 307 pregnancies with ICP was collected from the hospital computerized delivery room log book. UDCA was used in 208 pregnancies. The diagnosis was made by maternal pruritus and elevation of total fasting bile acid (BA) (>6 µmol/l) and elevation of serum alanine aminotransferases (ALT) (>45 U/l). Maternal and neonatal data was analysed and data of the patients who used UDCA during pregnancy was analysed separately and compared with the data from patients without medication. RESULTS: UDCA was well tolerated. Mothers receiving UDCA had ICP diagnosed five weeks earlier than mothers without medication. At the diagnosis, levels of total BA and ALT were higher in the group using UDCA compared to the group without medication. Most deliveries were induced and perinatal outcome was good. Apgar scores at 5 min were significantly lower in UDCA group (p < 0.05), but fetal umbilical artery pH values were similar in both groups (p > 0.05). There were 30 patients with total BA > 40 µmol/l at diagnosis, 24 with UDCA and 6 without medication and those deliveries were induced soon after diagnosis. The preterm labour was also more common in these patents (p < 0.05). Women with preterm babies had significantly early onset pruritus and ICP was diagnosed earlier. Serum ALT and total BA levels were significantly higher in those pregnancies at diagnosis and also at first control. CONCLUSIONS: Preterm labour was associated in severe ICP (total BA > 40 µmol/l), ALT levels were also significantly higher and ICP was diagnosed earlier (p < 0.05). Apgar scores were lower in preterm babies (p < 0.05), but umbilical artery pHvalues were not significantly lower. UDCA was well tolerated by pregnant women. With low-dose UDCA treatment the obstetric outcome was good. We still recommend careful obstetrical follow-up.

Early pregnancy cerebral venous thrombosis and status epilepticus treated with levetiracetam and lacosamide throughout pregnancy.

Cerebral venous thrombosis (CVT) is an uncommon cause of stroke, accounting to less than 1% of all strokes. We describe a pregnant woman with a massive CVT in early pregnancy, complicated by status epilepticus. The mother was treated with levetiracetam, lacosamide, and enoxaparin throughout pregnancy. A male infant was born on pregnancy week 36, weighing 2.2kg. Both levetiracetam and and lacosamide were present in cord blood in levels similar to those in maternal blood. The infant was partially breast-fed and experienced poor feeding and sleepiness, starting to resolve after two first weeks. Milk samples were drawn 5 days after the delivery and a blood sample from the infant 3 days later. Lacosamide level in milk was low, resulting in an estimated relative infant dose of 1.8% of the maternal weight-adjusted daily dose in a fully breast-fed infant. This is the first case describing lacosamide use during pregnancy and lactation.

Ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy: a randomized controlled trial.

PURPOSE: To test the efficacy and safety of ursodeoxycholic acid (UDCA) in the treatment of patients with intrahepatic cholestasis of pregnancy (ICP). METHODS: In the randomized (double-blind, placebo-controlled) study 20 pregnant women with ICP received (random allocation of) either 450 mg/day UDCA or placebo for 14 days during the third trimester of pregnancy. The severity of pruritus was registered and itching scores were assessed before the treatment and weekly thereafter. The effects of UDCA on liver function and fetoplacental hormone production were measured with covering laboratory testing: serum levels of alanine aminotransferase (ALAT), total bile acids (TBA), estradiol, progesterone, prolactin, cholesterol, HDL-cholesterol, triglycerides, activated partial thromboplastin time, fibrinogen D-dimers (FIDD) and platelet count were assessed before the treatment and weekly thereafter. Data on pregnancy and delivery outcome were recorded and analyzed. RESULTS: UDCA was well tolerated. A significant improvement in itching scores was detected in 2 weeks in the group receiving UDCA. Serum levels of ALAT and TBA fell after 2 weeks treatment. The other laboratory values were not modified by the treatment. CONCLUSIONS: UDCA improves maternal itching scores and liver function tests without interfering with the fetoplacental estrogen production in patients with ICP. UDCA is well tolerated by pregnant women. No fetal or neonatal side-effects could be detected.

[When the expected date of delivery is overdue]. / Kun laskettu aika on ohi.

When pregnancy has continued past the expected date of delivery, the capacity of the placenta to transport oxygen and nutrients will decrease, whereby the condition of the fetus may be endangered with concomitantly increasing intrapartum problems. In addition, the mother's risk of complications of labor will increase, which is partly due to the increasing size of the child. The pregnancy is closely followed at the maternity and prenatal clinic, and induction of active labor will usually be conducted no later than two weeks after the expected date.

Hepatocellular enzyme glutathione S-transferase alpha and intrahepatic cholestasis of pregnancy.

OBJECTIVE: To evaluate and compare plasma glutathione S-transferase alpha (GSTA) concentrations in the third trimester of pregnancy in patients with intrahepatic cholestasis of pregnancy (ICP) and in healthy pregnant women. DESIGN: Non-randomized clinical study. SETTING: Maternity unit and Department of Clinical Chemistry, Turku University Central Hospital, Turku, Finland. POPULATION: Twenty-seven women with ICP and 49 healthy pregnant women. METHODS: GSTA concentrations were assessed in plasma samples in the third trimester of pregnancy using an enzyme-linked immunoassay (HEPKIT Alpha, Biotrin, Sinsheim-Reihen, Germany). MAIN OUTCOME MEASURES: Plasma GSTA, serum alanine and bile acid concentrations were compared between study and control group. Correlation between plasma GSTA levels and serum alanine aminotransferase and bile acid levels in the ICP patients were tested by Spearman correlation coefficients. Main perinatal outcome was compared between the groups. RESULTS: GSTA concentration in the control group was 1.62 microg/l (range: 0.25-6.1). In the ICP patients, the mean plasma GSTA concentration was 51.0 microg/l (range: 2.1-183.5), the mean serum alanine aminotransferase concentration was 145.70 U/l (range: 6-393) and the mean bile acid concentration was 19.2 micromol/l (range: 3-63). There was a statistically significant correlation in ICP patients between plasma GSTA concentration and serum alanine aminotransferase concentration (r=0.694, p=0.0001), but not with serum bile acid concentration. Nor was there any statistically significant correlation between gestational weeks and plasma GSTA concentration in the study group. CONCLUSION: Plasma GSTA measurements may provide a more sensitive and specific diagnostic tool for diagnosis of ICP than the evaluation of transaminases or bile acid concentrations alone. Further studies are needed to evaluate the role of GSTA in the follow-up of patients with ICP and its prognostic value for threatening fetal distress in patients with ICP.