Maternal safety of the delayed-release doxylamine and pyridoxine combination for nausea and vomiting of pregnancy; a randomized placebo controlled trial

Background: Nausea and vomiting of pregnancy (NVP) is the most common medical condition in pregnancy, affecting up to 80% of expecting mothers. In April 2013 the FDA approved the delayed release combination of doxylamine succinate and -pyridoxine hydrochloride (Diclegis®) for NVP, following a phase 3 randomized trial in pregnant women. The fetal safety of this medication has been proven by numerous studies. However, because it is the only FDA-approved medication for NVP that is likely to be used by a large number of pregnant women, its maternal safety is an important public health question. The Objective is to evaluate the maternal safety of doxylamine succinate -pyridoxine hydrochloride delayed-release preparation (Diclegis® as compared to placebo. Methods: We randomized women suffering from NVP to receive Diclegis® (n = 131) or placebo (n = 125) for 14 days at doses ranging from 2-4 tablets a day, based on a pre-specified titration protocol response to symptoms. Adverse events were collected through patient diaries, clinical examination and laboratory testing. Results: Doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg use was not associated with an increased rate of any adverse event over placebo, including CNS depression, gastrointestinal or cardiovascular involvement. Conclusions: Doxylamine succinate-pyridoxine hydrochloride delayed release combination is safe and well tolerated by pregnant women when used in the recommended dose of up to 4 tablets daily in treating nausea and vomiting of pregnancy. Trial Registration: Clinical Trial Registration No: NCT00614445

Cesarean section rate in Iran, multidimensional approaches for behavioral change of providers: a qualitative study

<p>Abstract</p> <p>Background</p> <p>The cesarean section rate has been steadily rising from 35% in 2000 to 40% in 2005 in Iran. The objective of this study was to identify barriers of reduce the cesarean section rate in Iran, as perceived by obstetricians and midwives as the main behavioral change target groups.</p> <p>Methods</p> <p>A qualitative study with purposive sampling was designed in which data were collected through in-depth interviews and document analyses. Hospitals were selected on the bases of being public and or private and their response to the ministry's C-section reduction interventions. The hospital director, obstetricians and midwives from each hospital were included in the study. The classification of barriers suggested by Grol and Wensing was used for the thematic analysis.</p> <p>Results</p> <p>After 26 in-depth interviews and document analyses, the barriers were identified as: financial, insurance and judicial problems at the <it>economic and political context </it>level; the type and ownership of hospitals, absence of an on call physician, absence of clear job-descriptions for obstetricians and midwives, too many interventions in the delivery process and shortage of human resources and facilities at the <it>organizational context </it>level; distrust and insufficient collaborations between obstetricians and midwives from macro to micro level at the <it>social context </it>level; attitudes toward complications of C-section, reduced capabilities of obstetricians, midwives and residents at the <it>individual professional </it>level; and finally, at the <it>innovation </it>level, vaginal delivery is time consuming, imposes high stress levels and is unpredictable.</p> <p>Conclusion</p> <p>Changing service providers' behavior is not possible through presentation of scientific evidence alone. A multi-level and multidisciplinary approach using behavior change theories is unavoidable. In future studies, the effect of the barriers should be determined to help policy makers recognize the most effective interventional package.</p

Cesarean delivery on maternal request: Can the ethical problem be solved by the principlist approach?

In this article, we use the principlist approach to identify, analyse and attempt to solve the ethical problem raised by a pregnant woman's request for cesarean delivery in absence of medical indications

Enhanced growth and improved vascular function in offspring from successive pregnancies in endothelial nitric oxide synthase knockout mice

Objective: Transgenic mice that lack endothelial nitric oxide synthase have offspring with growth deficiency and abnormal vascular reactivity in later life. Our objective was to evaluate the role of parity in the modulation of the fetal programming of growth and vascular responses in these transgenic mice. Study design: Oligoparous (0-2 previous pregnancies) and multiparous (5-9 previous pregnancies) nitric oxide synthase knockout (-/-KO) female mice were bred with nitric oxide synthase(-/-KO) and wild type (+/+WT) male mice to produce nitric oxide synthase-/-KO and maternally derived heterozygous (+/-Mat) litters. The pups were weighed weekly. Carotid arteries of the adult females from these litters were used for in vitro vascular reactivity studies. Results: Nitric oxide synthase knockout and nitric oxide synthase maternal litters that were born to oligoparous mothers had significant growth lag compared with corresponding multiparous litters. Length-tension characteristics were not different between the groups. However, optimal diameter, which is a measure of vascular tensile properties and resistance, was decreased in oligoparous compared with multiparous female offspring. Acetylcholine-mediated vasorelaxation was abolished, and contraction by phenylephrine and Ca++ was increased in oligoparous, but not multiparous, female offspring (P <.05). Conclusion: These data support the role of abnormal uterine environment in the fetal programming of postnatal growth and vascular function in later life. Successive pregnancies may lead to maternal uterine adaptations that bypass the lack of a functional nitric oxide synthase, which leads to improvement in postnatal growth and vascular function in the offspring. Given the reported effect of parity on the risk of preeclampsia, similar mechanisms may be operative in human pregnancy. (C) 2004 Elsevier Inc. All rights reserved