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Maternal Administration (maternal + administration)

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Medical Sciences	100%

Selected Abstracts

Maternal antecedents for cerebral palsy in extremely preterm babies: a case-control study

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 9 2001
Peter H Gray MD FRCPI FRACP FRCPCH
The study aimed to identify significant antenatal risk factors for cerebral palsy (CP) among extremely preterm infants with a matched case-control design. Infants born between 1989 and 1996 at 24 to 27 weeks'gestation who survived to hospital discharge were evaluated: 30 with a proven diagnosis of CP at 2 years corrected for prematurity and 120 control children matched for gestational age without CP. Information on maternal obstetric risk factors and medication was obtained. Matched analyses were performed and odds ratios (OR) and 95% confidence intervals (CI) were calculated. An antenatal diagnosis of intrauterine growth restriction was associated with an increased risk of CP (OR 6.6; 95% CI 1.8 to 25.2), while maternal administration of corticosteroids was associated with a reduced risk of CP (OR 0.4; 95% CI 0.1 to 0.98). A high rate of placental histopathology was achieved but no relation between clinical or histological chorioamnionitis or funisitis and CP was demonstrated. Maternal preeclampsia was not associated with a statistically significant reduction in the risk of CP. It is concluded that a reduced risk of CP in extremely preterm infants is associated with the antenatal use of corticosteroids. [source]

Embryonic Arrhythmia by Inhibition of HERG Channels: A Common Hypoxia-related Teratogenic Mechanism for Antiepileptic Drugs?

EPILEPSIA, Issue 5 2002
Faranak Azarbayjani
Summary: ,Purpose: There is evidence that drug-induced embryonic arrhythmia initiates phenytoin (PHT) teratogenicity. The arrhythmia, which links to the potential of PHT to inhibit a specific potassium channel (Ikr), may result in episodes of embryonic ischemia and generation of reactive oxygen species (ROS) at reperfusion. This study sought to determine whether the proposed mechanism might be relevant for the teratogenic antiepileptic drug trimethadione (TMO). Methods: Effects on embryonic heart rhythm during various stages of organogenesis were examined in CD-1 mice after maternal administration (125,1,000 mg/kg) of dimethadione (DMO), the pharmacologically active metabolite of TMO. Palatal development was examined after administration of a teratogenic dose of DMO and after simultaneous treatment with DMO and a ROS-capturing agent (,-phenyl- N -tert-butyl-nitrone; PBN). The Ikr blocking potentials of TMO and DMO were investigated in HERG-transfected cells by using voltage patch-clamping tests. Results: DMO caused stage-specific (gestation days 9,13 only) and dose-dependent embryonic bradycardia and arrhythmia at clinically relevant maternal plasma concentrations (3,11 mM). Hemorrhage in the nasopharyngeal part of the embryonic palate (within 24 h) preceded cleft palate in fetuses at term. Simultaneous treatment with PBN significantly reduced the incidence of DMO-induced cleft palate, from 40 to 13%. Voltage patch-clamping studies showed that particularly DMO (70% inhibition), but also TMO, had Ikr blocking potential at clinically relevant concentrations. Conclusions: TMO teratogenicity, in the same way as previously shown for PHT, was associated with Ikr -mediated episodes of embryonic cardiac arrhythmia and hypoxia/reoxygenation damage. [source]

Selective neuronal nitric oxide synthase inhibitors and the prevention of cerebral palsy,

ANNALS OF NEUROLOGY, Issue 2 2009
Haitao Ji PhD
Objective To design a new class of selective neuronal nitric oxide synthase (NOS) inhibitors, and demonstrate that administration in a rabbit model for cerebral palsy (CP) prevents hypoxia-ischemia,induced deaths and reduces the number of newborn kits exhibiting signs of CP. Methods We used a novel computer-based drug design method called fragment hopping to identify new chemical entities, synthesized them, and conducted in vitro enzyme inhibition studies with the three isozymes of NOS and in vivo experiments to monitor cardiovascular effects on pregnant rabbit dams, NOS activity, and NOx (NO and NO2) concentration in fetal brain, and assess neurobehavioral effects on kits born to saline- and compound treated dams. Results The computer-based design led to the development of powerful and highly selective compounds for inhibition of neuronal NOS over the other isozymes. After maternal administration in a rabbit model of CP, these compounds were found to distribute to fetal brain, to be nontoxic, without cardiovascular effects, inhibit fetal brain NOS activity in vivo, reduce NO concentration in fetal brain, and dramatically ameliorate deaths and number of newborn kits exhibiting signs of CP. Interpretation This approach may lead to new preventive strategies for CP. Ann Neurol 2008 [source]

Cervical occlusion in women with cervical insufficiency: protocol for a randomised, controlled trial with cerclage, with and without cervical occlusion,

BJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 5 2007
NJ Secher
Objective, To evaluate the effect of double cerclage compared with a single cerclage. Design, Randomised, controlled multicentre trial. Setting, Ten different countries are participating with both secondary and tertiary centres. The countries participating are Denmark, Sweden, Germany, United Kingdom, Spain, South Africa, Australia and India. This gives both a broad spectrum of diversity global and local. We expect a total of 242 women enrolled per year. Population, Prophylactic study: 1History of cervical incompetence/insufficiency. (Delivery 15 to <36 weeks.) 2Congenital short cervix (secondary to maternal administration of diethyl stilbestrol) or traumatic/surgical damage rendering the vaginal approach difficult (e.g. conisation). 3Cervical suture applied in previous pregnancy, successful outcome. 4Previous failed cerclage. Therapeutic study: 5Secondary cerclage: Short cervix, without the membranes being exposed to the vagina. 6Tertiary cerclage: Short cervix, membranes exposed to the vagina. Observational study: Eligible women who refuse to be randomised will participate in an observational study. 7Repeat/requested cervical occlusion. Methods, The women will be randomised between a single (vaginal or abdominal) and a double cerclage. The cervical cerclage (McDonald or Shirodkar) as well as the abdominal suture will be performed with the same material and technique normally used by the participating department. Those randomised to the double cerclage will have their external os closed with a continuous nylon 2-0/3-0 suture, in addition to the standard single cerclage. Local guidelines concerning antibiotics, Heparin, bed rest, tocolytics etc. are followed and recorded in the follow-up form. Main outcome measures, Primary endpoint is take home baby rate. The secondary endpoints are gestational age at delivery, incidence of preterm birth (<34+0 days) and number of days in neonatal unit. [source]