While prescribing in pregnancy, the physician is confronted with the problem of alleviating the mothers symptoms and ensuring that no or minimal harm is produced in the unborn. Unfortunately, the rising trend of drug consumption during this period appears often to be in near-disregard to the unintended recipient “the unborn baby”. This article examines various aspects that have to be considered before deciding on the appropriate therapy in a pregnant (possibly pregnant) woman as well as in lactating mothers.
This review presents basic aspects of placental morphology with particular reference to the regional specialization of human placental tissues. Intrauterine visualization of the placenta is now possible with new non-invasive methods. Echotomographic ultrasound images of the placenta in vivo and in vitro are of the greatest value for clinical and pathological diagnosis. X-ray computed tomography, though it cannot be applied to pregnant women, is invaluable for the study of circulatory and pathologic changes in the placenta isolated post partum. Nuclear magnetic resonance imaging is another useful adjunct not only for placental localization but also to detect changes of placental morphology with an accuracy almost as good as ultrasonography. Fourier-transform spectroscopy now offers a unique opportunity to obtain computed biochemical data on the metabolic evolution of the human placenta.
Recent interest in biofuels and bio-refineries has been building upon the technology of biomass gasification. This technology developed since the 1980s in three periods, but failed to break through. We try to explain this by studying the technological development from a quasi-evolutionary perspective, drawing upon the concepts of technological paradigms and technological trajectories. We show that the socio-economic context was most important, as it both offered windows of opportunity as well as provided direction to developments. Changes in this context resulted in paradigm shifts, characterized by a change in considered end-products and technologies, as well as a change in companies involved. Other influences on the technological trajectory were firm specific differences, like the focus on a specific feedstock, scale and more recently biofuels to be produced. These were strengthened by the national focus of supporting policies, as well as specific attention for multiple technologies in policies of the USA and European Commission. Over each period we see strong variation that likely benefitted the long term development of the technology. Despite policy efforts that included variation and institutionalization, our case shows that the large changes in socio-economic context and the technological challenges were hard to overcome.
Although few psychotropic drugs are known to be teratogenic or to have adverse effects on the developing fetus or neonate, no psychotropic drug is of proven safety. It is therefore very important that psychotropic medication should not be prescribed lightly during pregnancy or lactation and that such drugs should be prescribed only where there are positive indications for their use. Close collaboration between obstetrician and psychiatrist is recommended before treatment of a mental illness with psychotropic medication. Breast feeding should not routinely be suspended in mothers who require psychotropic medication. There is an adequate range of psychotropic drugs available to safely treat the pregnant or lactating woman who is mentally ill.
DNA-damage response of cutaneous interfollicular melanocytes to fractionated radiotherapy was investigated by immunostaining of tissue sections from punch biopsies collected before, during, and after the treatment of patients for breast cancer. Our clinical assay with sterilized hair follicles, excluded the migration of immature melanocytes from the bulge, and highlighted interfollicular melanocytes as an autonomous self-renewing population. About thirty percent are immature. Surrounding keratinocytes induced and maintained melanocyte differentiation as long as treatment was ongoing. Concomitant with differentiation, melanocytes were protected from apoptosis by transient upregulation of Bcl-2 and CXCR2. CXCR2 upregulation also indicated the instigation of premature senescence, preventing proliferation. The stem cell factor BMI1 was constitutively expressed exclusively in interfollicular melanocytes and further upregulated upon irradiation. BMI1 prevents apoptosis, terminal differentiation, and premature senescence, allowing dedifferentiation post-treatment, by suppressing the p53/p21-and p16-mediated response and upregulating CXCR2 to genotoxic damage. The pre-treatment immature subset of interfollicular melanocytes was restored after the exposure ended.
Hypertensive diseases are among the most common of all pregnancy complications. Significant elevations of blood pressure can be missed if inflexible criteria are used. There is now very strong evidence to support the use of antihypertensive agents in all forms of hypertension. The antihypertensive drugs in current use have a good safety record with regard to both mother and baby. The management of hypertension during pregnancy ideally requires the close cooperation of obstetrician and physician.
When treating thyroid disease, as with other conditions in pregnancy, one is concerned with the welfare of both mother and developing child. Thyroid disease causes few maternal problems; thyrotoxicosis in fact tends to improve in pregnancy, allowing medical management with lower drug doses than usual. Relapse of thyroid disease may occur postpartum, when transient hypo- and hyperthyroidism are relatively common.
Chorion villus biopsy answers the pressing need for early prenatal diagnosis. The technique is carried out at about 10 weeks gestation and in most instances this tissue is amenable to direct analysis without culture. This technique is particularly suitable for gene probe diagnosis. However, it is now widely offered for cytogenetic diagnosis on the basis of maternal age and some 10 000 patients have been reported to a Central Registry. The procedure-related abortion rate in skilled hands would seem to be about 2-3%, although this is probably lower with the new transabdominal route. Despite the great deal of attention which is focused on this technique, it is still too early to tell whether chorion villus biopsy will replace amniocentesis as the standard method of prenatal diagnosis.
The placenta has a considerable functional reserve capacity, easily repairs ischaemic damage, is able to compensate for toxic injury and does not appear to age. Most of the macroscopically visible abnormalities of the placenta are of no functional significance, the major exception to this general banality being the uncommon large haemangioma which can cause complications in the mother, fetus and neonate. Most of the histological abnormalities seen in the placental villi represent a reaction to alterations in either maternal or fetal blood flow through the placenta, but a failure of adequate maturation of the villous tree may impair the functional efficiency of the placenta, as may defective trophoblastic differentiation. Infections of the placenta are important but do not influence placental function, whilst there is currently no firm evidence that the placenta ever suffers immune-mediated damage. Intrinsic placental 'insufficiency' is extremely rare and it is becoming increasingly clear that this clinical syndrome is usually due to a restricted supply of maternal oxygen and nutrients as a result of inadequate transformation of the spiral arteries into uteroplacental vessels. This failure of placentation represents an abnormality of the relationship between fetal and maternal tissues at a relatively early stage of pregnancy, and it is only by gaining a better understanding of this relationship that the problems posed by such conditions as pre-eclampsia and idiopathic intrauterine growth retardation will be answered.
When treating thyroid disease, as with other conditions in pregnancy, one is concerned with the welfare of both mother and developing child. Thyroid disease causes few maternal problems; thyrotoxicosis in fact tends to improve in pregnancy, allowing medical management with lower drug doses than usual. Relapse of thyroid disease may occur postpartum, when transient hypo- and hyperthyroidism are relatively common. In contrast, the fetus and neonate are threatened in a number of ways by drugs given to the mother and by transplacental passage of maternal antibodies capable of inducing thyroid disease. Antithyroid drugs may cause fetal goitre with airway obstruction, and are associated with mild neonatal hypothyroidism. Thyroid antibodies in primary myxoedema and Hashimoto's thyroiditis are occasionally implicated in neonatal hypothyroidism and may even cause thyroid dysgenesis. Neonatal hyperthyroidism has a high morbidity and mortality and may have long-term skeletal effects such as craniosynostosis. Fetal problems may not be apparent at birth but may emerge in the next eight to ten days, especially in hyperthyroidism when the mother has been on treatment. Close monitoring throughout pregnancy and for the first ten days postpartum is required to minimize risks to the fetus and neonate. Most pregnancies associated with thyroid disease will have a successful outcome. If the occasional at-risk fetus is to be identified and treated successfully there should ideally be close cooperation between obstetrician, endocrinologist and paediatrician.
Current treatment for severe hemophilia A is replacement of deficient factor. Although replacement therapy has improved life expectancy and quality, limitations include frequent infusions and high costs. Gene therapy is a potential alternative that utilizes an adeno‐associated virus (AAV) vector containing the human genetic code for factor 8 (FVIII) that transduces the liver, enabling endogenous production of FVIII. Individuals with preexisting immunity to AAV serotypes may be less likely to benefit from this treatment.This study measured seroprevalence of antibodies to AAV5 and 8 in an UK adult hemophilia A cohort.Patients were recruited from seven hemophilia centres in the UK. Citrated plasma samples from 100 patients were tested for preexisting activities against AAV5 and 8 using AAV transduction inhibition and total antibodies assays.Twent‐one percent of patients had antibodies against AAV5 and 23% had antibodies against AAV8. Twenty‐five percent and 38% of patients exhibited inhibitors of AAV5 or AAV8 cellular transduction respectively. Overall seroprevalence using either assay against AAV5 was 30% and against AAV8 was 40% in this cohort of hemophilia A patients. Seropositivity for both AAV5 and AAV8 was seen in 24% of participants.Screening for preexisting immunity may be important in identifying patients most likely to benefit from gene therapy. Clinical studies may be needed to evaluate the impact of preexisting immunity on the safety and efficacy of AAV mediated gene therapy.
1.In women with epilepsy, seizure control during pregnancy can be improved by maintaining the serum anticonvulsant drug concentration within the therapeutic range.2.Treatment with one anticonvulsant drug plus folic acid supplementation 5 mg per day seems appropriate in most cases. This should be achieved before conception whenever possible.3.No anticonvulsant drug seems free of teratogenic risk. With the commonly used anticonvulsant drugs—phenytoin, phenobarbitone, carbamazepine and sodium valproate—the risk is relatively low and represents less potential harm to the fetus than might occur with uncontrolled seizures.
Aims: To assess the efficacy and fetomaternal safety of atosiban among Indian pregnant women presenting with preterm labor. Study Design: Prospective, open-label, multicentric, non-comparative, phase-IV clinical study. Place and Duration of Study: Department of Obstetrics and Gynaecology at nine hospitals across India from October 2016 to December 2019. Methodology: A total of 212 pregnant women admitted with preterm labour between 24 and 36 weeks of gestation were administered intravenous atosiban up to 48 hours. Efficacy was defined as the successful delay of delivery without the need of an additional or alternative tocolytic agent for 72 hours. Safety was evaluated by recording the occurrence of adverse events in the mother, fetus and neonate. Results: Tocolytic efficacy of Atosiban was 84.88% at 48 hours and 74.15% at day 7 without additional tocolytic agent or retreatment after 48 hours. The mean number of days gained after the start of atosiban tocolysis were 29.15 ± 1.82 days with mean gestational age at delivery of 35.1 ± 3.33 weeks. Atosiban reduced the frequency of contractions from 4.3 ± 1.47 to 0.67 ± 1.13 contractions/30 min at 72 hours. The proportion of neonates with birth weights more than 2,500 gm was 41.67%. A total of 205 neonates out of 216 (94.95%) had APGAR score more than 7 after 5 minute. Atosiban successfully delayed the labour in 92.31% (n=13) of “Twin pregnancy” patients for 48 hours and beyond 7 days in 9 patients (69.2%). There were no serious adverse events reported. Conclusions: In patients with threatened preterm birth, 48 hour tocolysis with atosiban was found to be safe and effective in preventing imminent preterm birth even when it was a twin pregnancy or associated with co-morbidities. Atosiban showed favorable side effects profile and improved the perinatal outcomes. Clinical Trial Registry of India Number: CTRI/2017/03/008065;
