[The effect of maternal HBV DNA levels on HBV intrauterine transmission and fetal distress].

Aim: To identify the key risk factors of intrauterine hepatitis B virus transmission (HBV) and its effect on the placenta and fetus. Methods: 425 infants born to hepatitis B surface antigen (HBsAg)-positive pregnant women who received combined immunization with hepatitis B immunoglobulin and hepatitis B vaccine between 2009 to 2015 were prospectively enrolled in this study. The intrauterine transmission situation was assessed by dynamic monitoring of infants HBV DNA load and quantitative HBsAg. Univariate and multivariate regression analysis was used to determine the high risk factors for intrauterine transmission. Stratified analysis was used to determine the relationship between maternal HBV DNA load and fetal distress. Transmission electron microscopy was used to observe HBV Effects on placental tissue. Results: HBV intrauterine infection rate was 2.6% (11/425). Multivariate analysis result showed that the maternal HBV DNA load was an independent risk factor for intrauterine infection among infants (P=0.011). Intrauterine infection and distress rate was significantly higher in infants with with maternal HBV DNA>106 IU/ml than those with HBV DNA <106 IU/ml (12.2% vs. 1.8%; χ2=11.275, P=0.006), and (24.4% vs. 16.0%, χ2=3.993, P=0.046). Transmission electron microscopy showed that mitochondrial edema, endoplasmic reticulum expansion and thicker basement membrane were apparent when the maternal HBV DNA>106 IU/ml than that of maternal HBV DNA<106 IU/ml (960 nm vs. 214 nm, Z=-2.782, P=0.005) in the placental tissue. Conclusion: Maternal HBV DNA>106 IU/ml is associated not only with intrauterine infection, but also with increased incidence of intrauterine distress and placental sub-microstructural changes, providing strong clinical and histological evidence for pregnancy avoidance and treatment in this population.

Acute tocolysis for uterine tachysystole or suspected fetal distress.

BACKGROUND: Uterine tachysystole (more than 5 contractions per 10 minutes in 2 consecutive intervals) is common during labour, particularly with use of labour-stimulating agents. Tachysystole may reduce fetal oxygenation by interrupting maternal blood flow to the placenta during contractions. Reducing uterine contractions may improve placental blood flow, improving fetal oxygenation. This review aimed to evaluate the use of tocolytics to reduce or stop uterine contractions for improvement of the condition of the fetus in utero. This new review supersedes an earlier Cochrane Review on the same topic. OBJECTIVES: To assess the effects of the use of acute tocolysis during labour for uterine tachysystole or suspected fetal distress, or both, on fetal, maternal and neonatal outcomes. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (2 February 2018), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating acute tocolysis for uterine tachysystole, intrapartum fetal distress, or both. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. MAIN RESULTS: We included eight studies (734 women), conducted in hospital settings, predominantly in high-income countries (USA, Austria, Uruguay). Two trials were conducted in upper and lower middle-income countries (South Africa, Sri Lanka). The hospital facilities all had the capacity to perform caesarean section. Overall, the studies had a low risk of bias, except for methods to maintain blinding. All of the trials used a selective beta2 (ß2)-adrenergic agonist in one arm, however the drug used varied, as did the comparator. Limited information was available on maternal outcomes.Selective ß2-adrenergic agonist versus no tocolytic agent, whilst awaiting emergency deliveryThere were two stillbirths, both in the no tocolytic control group (risk ratio (RR) 0.23, 95% confidence interval (CI) 0.01 to 4.55; 2 studies, 57 women; low-quality evidence). One had gross hydrocephalus and the second occurred with vaginal delivery after waiting 55 minutes for caesarean section. The decision for caesarean section delivery was an inclusion criterion in both studies so we could not assess this as an outcome under this comparison. Abnormal fetal heart trace is probably lower with tocolytic treatment (RR 0.28, 95% CI 0.08 to 0.95; 2 studies, 43 women; moderate-quality evidence). The effects on the number of babies with Apgar score below seven were uncertain (low-quality evidence).Intravenous (IV) atosiban versus IV hexoprenaline (1 study, 26 women) One infant in the hexoprenaline group required > 24 hours in the neonatal intensive care unit (NICU) following a forceps delivery (RR 0.33, 95% CI 0.01 to 7.50; low-quality evidence). There were no fetal or neonatal mortalities and no Apgar scores below seven. There was one caesarean delivery in the IV hexoprenaline group (RR 0.33, 95% CI 0.01 to 7.50; low-quality evidence), and one case of abnormal fetal heart score in the atosiban group (RR 3.00, 95% CI 0.13 to 67.51; very low-quality evidence).IV fenoterol bromhydrate versus emergency delivery (1 study, 390 women) No data were reported for perinatal death, severe morbidity or fetal or neonatal mortality. IV fenoterol probably increases the risk of caesarean delivery (RR 1.12, 95% CI 1.04 to 1.22; moderate-quality evidence). Fenoterol may have little or no effect on the risk of Apgar scores below seven (RR 1.28, 95% CI 0.35 to 4.68; low-quality evidence).IV hexoprenaline versus no tocolytic agent, whilst awaiting emergency delivery (1 study, 37 women) No data were reported for perinatal death or severe morbidity. There were two fetal deaths in the no tocolytic control group (RR 0.23, 95% CI 0.01 to 4.55; low-quality evidence). The rate of caesarean delivery was not reported. There were two babies with Apgar scores below seven in the control group and none in the hexoprenaline group (RR 0.24, 95% CI 0.01 to 4.57; 35 women; low-quality evidence).Subcutaneous terbutaline versus IV magnesium sulphate (1 study, 46 women)No data were reported for perinatal death, severe morbidity or fetal or neonatal mortality. The decision for caesarean section was an inclusion criterion, so we could not assess this. The effects on abnormal fetal heart trace are uncertain (very low-quality evidence).Subcutaneous terbutaline with continuation of oxytocic infusion versus cessation of oxytocic infusion without tocolytic agent (1 study, 28 women) No data were reported for perinatal death, severe morbidity or fetal or neonatal mortality. There may be little or no difference in the rates of caesarean delivery in the subcutaneous terbutaline (8/15) and control groups (4/13) (RR 1.73, 95% CI 0.68 to 4.45; low-quality evidence). There were no cases of Apgar scores below seven or abnormal fetal heart trace.Subcutaneous terbutaline versus no tocolytic agent, whilst awaiting emergency delivery (1 study, 20 women) No data were reported for perinatal death or severe morbidity. There were no fetal or neonatal mortalities. The decision for caesarean section was an inclusion criterion, so we could not assess this. There were two babies with Apgar scores below seven in the control group and none in the terbutaline group (RR 0.17, 95% CI 0.01 to 3.08; low-quality evidence).IV terbutaline versus IV nitroglycerin (1 study, 110 women)No data were reported for perinatal death or severe morbidity or fetal or neonatal mortality. There may be little or no difference in the rates of caesarean delivery between the IV terbutaline (30/57) and control groups (29/53) (RR 0.96, 95% CI 0.68 to 1.36; low-quality evidence). There were no cases of Apgar scores below seven. AUTHORS' CONCLUSIONS: There is insufficient evidence to determine the effects of tocolytics for uterine tachysystole or suspected fetal distress during labour. The clinical significance for some of the improvements in measures of fetal well-being with tocolytics is unclear. The sample sizes were too small to detect effects on neonatal morbidity, mortality or serious adverse effects. The majority of studies are from high-income countries in facilities with access to caesarean section, which may limit the generalisability of the results to lower-resource settings, or settings where caesarean section is not available.Further well-designed and adequately powered RCTs are required to evaluate clinically relevant indicators of maternal and neonatal morbidity and mortality.

Reducing the risk of fetal distress with sildenafil study (RIDSTRESS): a double-blind randomised control trial.

BACKGROUND: Labour is perhaps the most hazardous time in pregnancy. As many as 20 % of cerebral palsy cases in term infants result from intrapartum events and up to 63 % of babies who develop intrapartum compromise have no prior risk factors. Sildenafil citrate (SC), a phosphodiesterase 5 inhibitor, improves uterine blood supply through vasodilatation and potentially could improve placental perfusion and hence reduce the risk of intrapartum fetal hypoxia. The aim of this study is to evaluate the efficacy of SC to reduce the risk of intrapartum fetal compromise and the need for emergency operative delivery. METHODS/DESIGN: This is a single centre, double-blind, randomised, phase II clinical trial of SC or placebo given during labour to women (18-50 years of age) with a single, appropriately grown, non-anomalous baby at term (37-42 weeks gestation). Those with cardiovascular, renal, hepatic, ocular or hypertensive disease or contraindication to SC will be excluded. Participants will be randomised to either SC 50 mg or placebo capsules eight hourly (SC maximum 150 mg) to commence when admitted to birth suite for management of labour. Within 3 h of the first dose, a repeat ultrasound scan will be performed to measure any changes in uteroplacental and fetal Doppler indices. Labour will continue otherwise in accordance with hospital clinical guidelines. The primary outcome is emergency caesarean section for intrapartum fetal compromise. Secondary outcomes include the effect of SC on fetal and uteroplacental blood flow, meconium liquor, fetal heart rate abnormalities and neonatal outcomes (admission to neonatal intensive care, Apgar <7 at 5 min, cord pH <7.1 or lactate >4.0 mmol/L, neonatal encephalopathy, death). CONCLUSION: This is the first reported study evaluating the efficacy of SC on reducing the risk intrapartum fetal compromise. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ACTRN12615000319572.

Safe extubation of a parturient using an airway exchange technique.

The difficult obstetric airway is a well-recognised anaesthetic challenge but little emphasis is placed on the difficulty of performing a safe tracheal extubation. We report the use of an airway exchange technique to extubate a difficult obstetric airway and discuss the role of these techniques in the obstetric population.

Medications in neonatal resuscitation: epinephrine and the search for better alternative strategies.

Epinephrine remains the primary vasopressor for neonatal resuscitation complicated by asystole or prolonged bradycardia not responsive to adequate ventilation and chest compressions. Epinephrine increases coronary perfusion pressure primarily through peripheral vasoconstriction. Current guidelines recommend intravenous epinephrine administration (0.01-0.03 mg/kg). Endotracheal epinephrine administration results in unpredictable absorption. High-dose intravenous epinephrine poses additional risks and does not result in better long-term survival. Vasopressin has been considered an alternative to epinephrine in adults, but there is insufficient evidence to recommend its use in newborn infants. Future research will focus on the best sequence for epinephrine administration and chest compressions.

Piracetam for fetal distress in labour.

BACKGROUND: Piracetam is thought to promote the metabolism of brain cells when they are hypoxic. It has been used to prevent adverse effects of fetal distress. OBJECTIVES: The objective of this review was to assess the effects of piracetam for suspected fetal distress in labour on method of delivery and perinatal morbidity. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (15 February 2012). SELECTION CRITERIA: Randomised trials of piracetam compared with placebo or no treatment for suspected fetal distress in labour. DATA COLLECTION AND ANALYSIS: Both review authors assessed eligibility and trial quality. MAIN RESULTS: One study of 96 women was included. Piracetam compared with placebo was associated with a trend to reduced need for caesarean section (risk ratio 0.57, 95% confidence interval 0.32 to 1.03). There were no statistically significant differences between the piracetam and placebo group for neonatal morbidity (measured by neonatal respiratory distress) or Apgar score. AUTHORS' CONCLUSIONS: There is not enough evidence to evaluate the use of piracetam for fetal distress in labour.

Time to delivery after the first course of antenatal corticosteroids: a cohort study.

The optimal time interval between administration of antenatal corticosteroids and delivery is 1 to 7 days. This study evaluates the timing of the first course of antenatal corticosteroids in clinical practice. We performed a retrospective cohort study of consecutive women who had received antenatal corticosteroids and/or delivered between 24 and 34 weeks of gestation. Time between administration of corticosteroids and delivery was compared between women with different causes of anticipated preterm deliveries: symptomatic preterm labor with intact membranes; preterm premature rupture of the membranes; (pre)eclampsia; hemolysis, elevated liver enzymes, and low platelet count; intrauterine growth restriction; vaginal blood loss; and suspected fetal distress. We included 439 women of whom 348 (79%) completed the course of corticosteroids. In women with a complete course, 143 (41%) delivered within 7 days. The median interval between the course and delivery was 11 days and varied between 41 days in women with vaginal blood loss, 25 days in women with spontaneous preterm labor with intact membranes, and 8 days in women with preeclampsia ( P < 0.001). In women with spontaneous preterm labor with intact membranes and in women with vaginal blood loss, we can benefit substantially from a more accurate discrimination of women who need corticosteroids immediately and women who do not.

In utero beta 2 adrenergic agonist exposure and adverse neurophysiologic and behavioral outcomes.

Beta 2 adrenergic receptor overstimulation during critical periods of prenatal development can induce a permanent shift in the balance of sympathetic-to-parasympathetic tone. This is a biologically plausible mechanism whereby beta 2 adrenergic agonists can induce functional and behavioral teratogenesis, which explains their association with increases in autism spectrum disorders, psychiatric disorders, poor cognitive, motor function and school performance, and changes in blood pressure in the offspring. The use of beta 2 adrenergic agonists should be limited to proven indications when alternate drugs are ineffective or unavailable; the risks of untreated disease to the mother and fetus are greater than the risk of the beta 2 adrenergic agonist.

Randomized comparison of intravenous terbutaline vs nitroglycerin for acute intrapartum fetal resuscitation.

OBJECTIVE: The purpose of this study was to compare terbutaline and nitroglycerin for acute intrapartum fetal resuscitation. STUDY DESIGN: Women between 32-, 42 weeks' gestation were assigned randomly to 250 microg of terbutaline or 400 microg nitroglycerin intravenously for nonreassuring fetal heart rate tracings in labor. The rate of successful acute intrapartum fetal resuscitation and the maternal hemodynamic changes were compared. Assuming a 50% failure rate in the terbutaline arm, we calculated that a total of 110 patients would be required to detect a 50% reduction in failure in the nitroglycerin group (50% to 25%), with an alpha value of .05, a beta value of .20, and a power of 80%. RESULTS: One hundred ten women had nonreassuring fetal heart rate tracings in labor; 57 women received terbutaline, and 53 women received nitroglycerin. Successful acute resuscitation rates were similar (terbutaline 71.9% and nitroglycerin 64.2%; P = .38). Terbutaline resulted in lower median contraction frequency per 10 minutes (2.9 [25-75 percentile, 1.7- 3.3] vs 4 [25-75 percentile, 2.5- 5]; P < .002) and reduced tachysystole (1.8% vs 18.9%; P = .003). Maternal mean arterial pressures decreased with nitroglycerin (81-76 mm Hg; P = .02), but not terbutaline (82-81 mm Hg; P = .73). CONCLUSION: Although terbutaline provided more effective tocolysis with less impact on maternal blood pressure, no difference was noted between nitroglycerin and terbutaline in successful acute intrapartum fetal resuscitation.

[Assessment of fetus' hypoxia treatment with actovegin].

The condition of fetus dramatically impairs in the case of pregnancy pathologies, when uterine-placental blood circulation impairment reveals, as it happens during placental presentation followed by bleeding, chronic anemia, heart and lung diseases of mother and pneumonia. Fetus' hypoxia develops when blood circulation in the vessels of cord is impaired, placental blood circulation disorders reveal. Preventive measures of fetus intra-natal hypoxia lay in elimination of obstetric and extra-genital causes. For the treatment of fetus hypoxia the solution Actovegin 4.0+5% glucose 400.0+vitamin "C" 4.0 in dosage of 15-20 drops per minute was applied. Out of 36 pregnant patients treatment was effective in 24 cases. In 12 cases a Caesarean section was performed. In cases of fetus hypoxia Actovegin allows to transfer metabolic processes in the form of anaerobic glycolysis, thus protecting vital centers from oxygen deprivation.

[Significance of infusion of sodium bicarbonate in amniotic cavity under continuous internal fetal heart rate monitoring for management of fetal distress during labor].

OBJECTIVE: To investigate the effect of infusion of sodium bicarbonate in amniotic cavity and exchange of amniotic fluid for fetus with distress and acidosis. METHODS: The patients included 40 cases of oligohydramnios with mild and serious abnormality of fetal heart rate and amniotic fluid contamination of degree II or more during the labor. The 40 cases had exchange of amniotic fluid with infusion under continuous monitoring. Twenty of them had infusion with 5% sodium bicarbonate into amniotic cavity; the other 20 cases received 5% sodium bicarbonate intravenous in fusion. After the labor all the patients had test of arterial blood gas in umbilical cord and the fetuses were evaluated with Apgar score. RESULTS: (1) the effective rate was 88% in the group of infusion into amniotic cavity and 85% in the group of exchange of amniotic fluid. (2) The arterial blood pH, PO(2), HCO(3)(-), ABE, SBE in the group of amniotic cavity infusion with 5% sodium bicarbonate were all higher than group of IV infusion, however PCO(2) was significantly lower than the group of IV (P < 0.05). CONCLUSION: Infusion into amniotic cavity and exchange of amniotic fluid is effective therapy for fetal distress due to oligohydramnios and can prevent meconium aspiration syndrome; infusion of antacids medicine (5% sodium bicarbonate) into amniotic cavity is effective and safe therapy for fetus with acidosis.

[Combination therapy for fetal supraventricular tachycardia with flecainide and digoxin]. / Kombinationstherapie einer fetalen supraventrikulären Tachykardie mit Flecainid und Digoxin.

Persistent fetal supraventricular tachycardia (SVT) with more than 210 bpm frequently leads to congestive heart failure. We report on a case with SVT and congestive heart failure that converted into sinus rhythm within 19 days of therapy with flecainide and beta-acetyldigoxin. A 32-year-old II gravida I para (25 + 1 weeks of gestation) presented with fetal SVT of 267 bpm. A non-immunologic hydrops fetalis was diagnosed by ultrasound showing ascites, pleural and pericardial effusion and tricuspid regurgitation. Within 19 days of combination therapy with flecainide and digoxin, cardioversion was achieved. After 36 days of therapy no more signs of cardiac failure could be detected. A healthy boy was born at 38 + 6 weeks of gestation. Although cardioversion is expected after 72 h of therapy according to the literature, this fetus converted into sinus rhythm on day 19 of therapy. This indicates that patients should not be considered resistant to treatment within the first 3 - 4 days.

A prospective randomised trial of atosiban versus hexoprenaline for acute tocolysis and intrauterine resuscitation.

OBJECTIVE: The aim of this study was to compare the efficacy and side effect profile of atosiban with hexoprenaline when used for intrauterine resuscitation of intrapartum fetal distress. STUDY DESIGN: Women in labour with acute intrapartum fetal distress detected by cardiotocography were randomly assigned to receive intravenous atosiban or hexoprenaline. SETTING: Department of Obstetrics and Gynecology, Karl Franzens University of Graz and General Hospital Graz, Austria. POPULATION OR SAMPLE: One thousand and four hundred and thirty-one women with singleton pregnancy at term and cephalic presentation were enrolled in the study during October 2000 and May 2001. METHODS: A prospective, randomised, pilot study with no a priori sample size calculation. MAIN OUTCOME MEASURE: Efficacy of treatment for stopping uterine contractions and the resumption of contractions determined by fetal heart rate monitoring. RESULTS: Tocolysis was achieved in 92% (12/13) of the women receiving atosiban and 100% (13/13) of those receiving hexoprenaline. Maternal tachycardia developed in 1/13 women, receiving atosiban and 10/13 women hexoprenaline. Hypertension occurred in 1/13 on atosiban and 3/13 women on hexoprenaline. Palpitations were only reported by 10/13 women receiving hexoprenaline. Uterine contractions resumed after 8 minutes (+/-3) in the atosiban group and 14 minutes (+/-4) in the hexoprenaline group (P < 0.001). CONCLUSION: Atosiban and hexoprenaline were similarly effective for stopping uterine contractions. Women receiving atosiban had significantly fewer adverse events than those receiving hexoprenaline. Uterine contractions resumed more promptly in the atosiban group. Considering the low incidence of mild maternal adverse events, atosiban may be an option for acute intrapartum tocolysis for fetal distress.

[The therapeutic role of tocolysis]. / Tocolyse dans les situations pathologiques particulières.

In twin pregnancies, the use of beta-adrenergics is associated with a significantly higher incidence of cardiovascular complications, and calcium channel blockers as well as oxytocin antagonists currently appear as first line agents. After extreme preterm delivery of the first twin and in selected patients, the birth of second twin may be delayed with a mean gain of 10-50 days. In cases of symptomatic placenta previa with mild-to-moderate bleeding, tocolytic agents may be associated with a prolongation of pregnancy and increased birth weight without significant impact on frequency or severity of bleeding. Calcium channel blockers are the drugs of choice in the event of diabetes. Indomethacin is a potent tocolytic, in particular in patients with polyhydramnios. However, it may cause oligohydramnios, premature closure of the ductus arteriosus and intrauterine fetal death when high doses are administered for a duration exceeding 48 to 72 hours, particularly beyond 32 weeks' gestation. The neonatal complications of indomethacin occur frequently. Tocolysis appears to reduce the failure rate of external cephalic version at term.

Fetal supraventricular tachycardia diagnosed and treated at twenty-four weeks of gestation and after birth: a case report.

Supraventricular tachycardia is the most common clinically significant fetal tachycardia. The diagnosis is usually made at routine sonographic workup during the second-third trimester of pregnancy. Treatment goals are cardioversion to sinus rhythm and reversal of cardiac dysfunction. We describe a case of fetal supraventricular tachycardia diagnosed at 24 weeks of gestation. The first-line treatment was oral maternal digoxin and sotalol. This therapy was not sufficient for complete control of the tachycardia. Hence, second-line treatment with digoxin and flecainide was started and successfully achieved conversion to sinus rhythm. No adverse maternal side effects were noted during the 14 weeks of therapy. A normal male infant was delivered at elective cesarean section performed for obstetric indications at 38 weeks of gestation. A persistent junctional reciprocating tachycardia with a ventriculo-atrial/atrioventricular ratio > 1 was diagnosed following delivery at transesophageal electrophysiological study. At the age of 8 months the child is on therapy with sotalol (4 mg/kg/day) and flecainide (3 mg/kg/day) and is in good clinical conditions.

Successful management of pregnancy in a patient with eisenmenger syndrome with epoprostenol.

Pregnancy in the setting of pulmonary hypertension and Eisenmenger physiology is associated with a substantial maternal and fetal risk. Such patients are advised against pregnancy. We report a case of a woman with an Eisenmenger atrial septal defect diagnosed during the last trimester of pregnancy. On presentation, she was critically ill and there was evidence of fetal distress. She was emergently treated with IV epoprostenol, and her status improved. She underwent cesarean section and delivered a male infant with Apgar scores of 8 and 9. Her dyspnea improved, and she was characterized as World Health Organization functional class II on a subsequent clinical visit. Although pregnancy should be discouraged in women with Eisenmenger syndrome, we have demonstrated that IV epoprostenol successfully treated a woman with Eisenmenger syndrome diagnosed in the third trimester.

Piracetam for fetal distress in labour.

BACKGROUND: Piracetam is thought to promote the metabolism of brain cells when they are hypoxic. It has been used to prevent adverse effects of fetal distress. OBJECTIVES: The objective of this review was to assess the effects of piracetam for suspected fetal distress in labour on method of delivery and perinatal morbidity. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register (The Cochrane Library Issue 3, 2001) were searched. Date of last search: September 2001. SELECTION CRITERIA: Randomised trials of piracetam compared with placebo or no treatment for suspected fetal distress in labour. DATA COLLECTION AND ANALYSIS: Both reviewers assessed eligibility and trial quality. MAIN RESULTS: One study of 96 women was included. Piracetam compared with placebo was associated with a trend to reduced need for caesarean section (relative risk 0.57, 95% confidence interval 0.32 to 1.03). There were no statistically significant differences in relative risk between the piracetam and placebo group for neonatal morbidity (measured by neonatal respiratory distress) or Apgar score. REVIEWER'S CONCLUSIONS: There is not enough evidence to evaluate the use of piracetam for fetal distress in labour.

Drug treatment of fetal tachycardias.

The pharmacological treatment of fetal tachycardia (FT) has been described in various publications. We present a study reviewing the necessity for treatment of FT, the regimens of drugs used in the last two decades and their mode of administration. The absence of reliable predictors of fetal hydrops (FH) has led most centers to initiate treatment as soon as the diagnosis of FT has been established, although a small minority advocate nonintervention. As the primary form of pharmacological intervention, oral maternal transplacental therapy is generally preferred. Digoxin is the most common drug used to treat FT; however, effectiveness remains a point of discussion. After digoxin, sotalol seems to be the most promising agent, specifically in atrial flutter and nonhydropic supraventricular tachycardia (SVT). Flecainide is a very effective drug in the treatment of fetal SVT, although concerns about possible pro-arrhythmic effects have limited its use. Amiodarone has been described favorably, but is frequently excluded due to its poor tolerability. Verapamil is contraindicated as it may increase mortality. Conclusions on other less frequently used drugs cannot be drawn. In severely hydropic fetuses and/or therapy-resistant FT, direct fetal therapy is sometimes initiated. To minimize the number of invasive procedures, fetal intramuscular or intraperitoneal injections that provide a more sustained release are preferred. Based on these data we propose a drug protocol of sotalol 160 mg twice daily orally, increased to a maximum of 480 mg daily. Whenever sinus rhythm is not achieved, the addition of digoxin 0.25 mg three times daily is recommended, increased to a maximum of 0.5 mg three times daily. Only in SVT complicated by FH, either maternal digoxin 1 to 2mg IV in 24 hours, and subsequently 0.5 to 1 mg/day IV, or flecainide 200 to 400 mg/day orally is proposed. Initiating direct fetal therapy may follow failure of transplacental therapy.

Effects of antenatal corticosteroid administration on mortality and long-term morbidity in early preterm, growth-restricted infants.

OBJECTIVE: To evaluate the effect of antenatal corticosteroids on mortality, morbidity, and disability or handicap rate in early preterm, growth-restricted infants. METHODS: This case-control study in two tertiary care centers included all live-born singleton infants with growth-restriction due to placental insufficiency, who were delivered by cesarean because of cardiotocographic signs of fetal distress before the beginning of labor at a gestational age of 26-32 weeks during the years 1984-1991. Infants who had been treated antenatally with corticosteroids more than 24 hours and less than 7 days before birth were matched by birth weight, sex, and year of birth with infants whose mothers had been admitted more than 24 hours before delivery but were not treated antenatally with steroids. The main outcome measure was survival without disability or handicap at 2 years corrected age. A sample of 60 case-control pairs would give 81% power to demonstrate 50% increase of this outcome [odds ratio (OR) 3.0] by corticosteroid treatment. Behavior and physical growth were evaluated at school age by questionnaire. RESULTS: The study group and control group consisted of 62 infants each. Survival without disability or handicap at 2 years' corrected age was more frequent in the corticosteroid group [OR 3.2, confidence interval (CI) 1.1, 11.2]. In the long-term follow-up at school age there was a statistically significant negative effect on physical growth (OR 5.1, CI 1.4, 23.8), but no differences in behavior were detected. CONCLUSION: Benefits from antenatal corticosteroids for early preterm, growth-restricted infants appear to outweigh possible adverse effects.

Update in Sjögren syndrome.

Sjögren syndrome (SS), the second most common autoimmune rheumatic disease, refers to keratoconjunctivitis sicca and xerostomia resulting from immune lymphocytes that infiltrate the lacrimal and salivary glands. However, differential diagnosis remains confusing due to the high prevalence of vague symptoms of dryness, fatigue, and myalgias in the general population. The problems of diagnosis are further compounded by the finding of "positive" antinuclear antibodies in a high percent of the general population. Unless minor salivary gland biopsies are read by experienced observers, nonspecific changes of sialadenitis are frequently confused with the focal lymphocytic infiltrates that are characteristic of SS. The distinction between fibromyalgia patients with low titer antinuclear antibodies and primary SS remains difficult. Even in patients fulfilling strict criteria for SS, the genomic search for critical genes has proven difficult due to the multigenic pattern of inheritance and strong role of currently undefined environmental factors. No single environmental factor has been detected in the majority of SS patients. SS-like syndrome has been detected in certain patients with HTLV-1 and hepatitis C infection, providing clues to pathogenesis. Even in SS patients with marked sicca symptoms, minor salivary gland biopsy shows that almost 50% of glandular cells are still detected on biopsy. These results imply the importance of immune factors such as cytokines and autoantibodies in decreasing neuro-secretory circuits and induction of glandular dysfunction. Of potential importance, an antibody against muscarinic M3 receptor that can decrease secretory function when injected into rodents is frequently found in the sera of SS patients. Newly developed topical and oral therapies can ease the oral and ocular dryness. Orally administered agonists of the muscarinic M3 receptor (pilocarpine and cevimeline) have recently been approved by the US Food and Drug Administration to increase salivary secretion. Topical ocular use of low-dose corticosteroids or cyclosporin may decrease conjunctival surface inflammation. In a Phase II double-blind study, orally administered interferon alpha (150 U) led to improved saliva flow and symptoms. In pregnant patients with evidence of fetal distress, oral dexamethasone is preferred because this agent crosses the placenta effectively. In animal models, antagonists of tumor necrosis factor and inhibitors of de novo pyrimidine synthesis appear promising.