Transdermal clonidine in the treatment of severe hyperemesis. A pilot randomised control trial: CLONEMESI.

OBJECTIVE: To study the efficacy of transdermal clonidine in the treatment of severe refractory hyperemesis gravidarum (HG), the most severe illness of pregnancy. DESIGN: The study had a randomised, double -blind, placebo-controlled, cross-over design (RCT). SETTING: Single tertiary referral hospital after admission of patients. SAMPLE: Twelve women of gestational age 6-12 weeks and a major grade of HG clinical severity who were unresponsive to standard antiemetic treatment. METHODS: The patients were randomly treated with and without the active drug (5 mg patch) for two consecutive periods of 5 days. The patients were allocated to a random list to receive first placebo and then active drug or the other way round. Other antiemetic drugs were administered on a scheduled or as-needed basis. All patients received intravenous hydration and thiamine supplementation. MAIN OUTCOME MEASURES: Pregnancy Unique Quantification of Emesis (PUQE) and visual analog scale (VAS) clinical scores, positive morning urine ketonuria, number of doses of standard antiemetic drugs required, and number of days off intravenous therapy were compared in the two periods. RESULTS: Transdermal clonidine led to a significantly greater improvement compared with placebo of the primary (PUQE score P = 0.026 CI 0.43-3.24; VAS score P = 0.010 CI 2.17-12.83) and secondary outcome measures. A reduction of blood pressure was reported for systolic 6 mmHg P = 0.01 and diastolic 3 mmHg P = 0.055. CONCLUSIONS: This preliminary RCT demonstrates the efficacy of transdermal clonidine in the treatment of severe HG, leading to a significant reduction of symptoms and reducing the need for other supportive measures and medications.

Neurological examination at 6 to 9 months in infants with cystic periventricular leukomalacia.

The Hammersmith Infant Neurological Examination was performed in 24 infants with cystic periventricular leukomalacia whose gestational age ranged between 26-38 weeks. The infants were examined between 6 and 9.5 months corrected age. The aim of the study was to establish the different patterns of neurological abnormality as well as the optimality scores that predict the severity of motor sequelae at 2 years. Increased neck and trunk extensor tone, and a posture of flexed arms and extended legs between 6 and 9 months were always associated with the inability to sit unsupported at 2 years, whilst truncal hypotonia and extended arms and legs were associated with unsupported sitting but not walking. Optimality scores between 41 and 60 were generally associated with sitting but not walking at 2 years whilst scores below 40 were always associated with the inability to sit independently at 2 years. All infants who did not develop cerebral palsy at 2 years had scores > 60. Our results suggest that the pattern of findings on neurological examination performed between 6 and 9 months as well as the calculated optimality score helps to predict motor impairment in infants with PVL.

Severe abnormalities of the pons in two infants with goldenhar syndrome.

We describe 2 cases of Goldenhar syndrome with severe abnormalities of the pons. The first case is a 10-month-old Caucasian female infant. At birth the girl showed polydactyly, labiopalatoschisis, right ear agenesis, left eye coloboma and vertebral anomalies. She also had marked hypotonia, severely reduced movements and respiratory and feeding abnormalities. She required gastrostomy at 5 months and tracheostomy at 7 months. Brain MRI scans showed moderate cerebellar hypoplasia and severe abnormalities of the pons with a congenital cleft. The child died at age 12 months. Case 2 is a Caucasian boy. Clinical signs and presentation were similar to case 1. The child also had severely reduced lacrimation, sweating, with thermoregulation abnormalities. He also underwent gastrostomy at 18 months. The child is now 3 years old and is able to sit only with support. Brain MRI was similar to case 1. The association of Goldenhar syndrome and pons abnormalities in 2 subjects suggests that this is more than a mere coincidence. Further studies and characterization of the genes involved in Goldenhar syndrome are needed to establish an adequate genotype-phenotype correlation.

Observation of continuous spike-waves during slow sleep in children with myelomeningocele.

CASES: Two patients with myelomeningoceles (MMC) and shunt-treated hydrocephalus are reported. At 5 and 7 years respectively, when they began presenting mental deterioration and behavioural disorders, sleep EEG showed continuous spike-waves during slow sleep (CSWS). DISCUSSION: These are the first cases of CSWS described in patients with MMC. The mechanisms of CSWS are considered. The role of hydrocephalus and the thalamic injuries found in one of the patients is discussed in detail. The usefulness of monitoring sleep EEG in patients with hydrocephalus or thalamic lesions is stressed, considering the effects of CSWS on the cognitive competencies and the soft or subclinical course that epilepsy complicated with CSWS may follow.

Low-molecular-weight heparin during pregnancy.

Thromboembolism is an infrequent, yet serious cause of both maternal and fetal morbidity and death during pregnancy and the puerperium. Pregnancy itself increases the risk of thromboembolic complications probably owing to a combination of hypercoagulability and venous stasis due to venous dilation. Recent studies have indicated that some serious obstetric complications are correlated with inherited or acquired thrombophilia. The prevalence of venous thromboembolism (VTE) has been extimated to be 1 per 1000-2000 pregnancies in retrospective studies. Anticoagulant treatment and prophylaxis both before and during pregnancy are based on unfractionated heparin (UH), low-molecular-weight heparin (LMWH) and warfarin. Warfarin is teratogenous if administered between the 6th and the 12th week. LMWH is replacing UH in the prevention and treatment of VTE both outside and more recently during pregnancy with the same indications, and also for obstetric complications. This paper assesses the safety and efficacy of heparin therapy during pregnancy and the puerperium. Its cardiovascular and obstetric indications and regimens and maternal and fetal side-effects are also discussed.

Spontaneous ovarian hyperstimulation syndrome and deep vein thrombosis in pregnancy: case report.

This report describes a case of spontaneous ovarian hyperstimulation syndrome (OHSS) occurring in a pregnant woman carrying the factor V Leiden mutation. Even though prophylactic treatment for thrombo-embolism was adopted by administering low molecular weight heparin, the pregnancy was complicated by thromboses of the left subclavian, axillary, humeral and internal jugular veins during the second trimester of gestation. The pregnancy was managed conservatively and a healthy newborn was delivered at term. In order to avoid unnecessary laparotomy, we emphasize the importance of careful diagnosis in order to differentiate spontaneous OHSS from ovarian carcinoma, as well as the necessity to look for the presence of coagulation disorders in women affected by OHSS.