Current Women's Health Reviews - Volume 7, Issue 1, 2011

Unfortunately, pregnancy and puerperium are not protective against the onset or recurrence of psychiatric disorders. Concordant information drawn from scientific literature has also demonstrated that antenatal and puerperal mental problems impact severely on the physiological progress of pregnancy, the developing fetus, the infant, and even the future psychological and neurocognitive development of their offspring. Hence, focusing our attention more closely on perinatal psychiatry may be an effective strategy for reducing the prevalence of psychiatric disorder. In the light of the impact of untreated maternal mental disorder on children's mental health, treating mentally-ill women safely and effectively may reduce the risk of future compromise in their offspring's psychological development. Obviously, effective treatment of maternal mental disorder does not reduce the genetic risk of suffering from mental problems. However, as genetic predisposition acts in conjunction with specific external influences, restoring a healthy family environment may reduce future risk of developing mental problems during adolescence and young adulthood. Briefly, it would also be useful to remember that maternal depression may complicate pregnancy progression by increasing the probability of unhealthy life-styles and inadequate self-care, both of which lead to an increase in the risk of fetal and placental anomalies, pre-eclampsia, and antepartum bleeding. Impaired intrauterine growth has been also associated with the occurrence of depressive symptoms during the gestational period. Moreover, antenatal depression induces significant effects on neonatal physiology: elevated cortisol and norepinephrine levels, lower dopamine levels, and greater relative right-frontal electroencephalographic asymmetry. All have been reported in infants born to mothers who suffered from mood disorders while pregnant [1]. Such infants are also likely to show depressive-like behaviors [2]. The impact of untreated bipolar disorder on expecting mothers and their fetuses is also likely to be devastating. Indeed, maternal bipolar disorder is associated with an increased frequency of birth defects, perinatal mortality, preterm birth, low birth weight/Apgar scores, and different typologies of perinatal complications, whose occurrence is facilitated by the difficulty of these mothers to adhere to healthy lifestyle changes [3]. Infants born to bipolar mothers are also at increased risk of developing emotional problems, impairments in affective/behavioral responses and social functioning, deficits in spatial memory and attention, as well as suffering from various psychiatric disorders during childhood (preschool offspring of parents with bipolar disorder have an elevated risk for ADHD and have greater levels of subthreshold manic and depressive symptoms), adolescence, or young adulthood [4, 5]. Women with schizophrenia are significantly more likely to have placental abruption, to give birth to newborns in the lowest weight/growth decile, and to have children with cardiovascular congenital anomalies [6]. This background justifies a special journal issue focused on assembling up-to date information on the safety of pharmacological management of antenatal and puerperal psychiatric disorders. Indeed, this information may help clinicians to balance the potential risks for the fetus and the newborn (associated with exposure to psychotropic medications through placenta and/or maternal milk) with the ascertained detrimental effects of untreated maternal mental illness. An interesting update of Australian epidemiological data about the prevalence of schizophrenia in female patients is provided by McCauley-Elsom, Elsom, and Cross, who also discussed the repercussion on fertility of the increasing use of atypical antipsychotics. Unfortunately, however, no psychotropic agents seem to be totally devoid of risks for the developing fetus and the neonate. Although Carlos De las Cuevas and Emilio J. Sanz report in this issue that only a few studies have shown a slight increase in the presence of malformations associated with prenatal use of antidepressants, and that such data are not fully concordant, reviewed literature information conversely demonstrate that late in utero exposure to all classes of antidepressants is likely to induce a spectrum of neonatal complication which resembles, to some extent, the profile of adverse events that such medications may induce in adult patients [7]. Recently, the whole spectrum of neonatal associated with late pregnancy exposure to antidepressants has been labeled “Prenatal antidepressant exposure syndrome” [8]. However, as reported by Jan Oystein Berle and Olav Spigset, antidepressant treatment does not contraindicate breastfeeding. This reassuring information may facilitate the pharmacological approach of women who develop postpartum depression [9, 10]. Christina Wichman is forced to conclude that, at this time, available data are still insufficient to confirm or exclude a potential structural teratogenic risk associated with intrauterine exposure to both typical and atypical antipsychotic agents, despite being reported elsewhere that there is more reassuring published information regarding typical antipsychotics and, especially, chlorpromazine [11]. Moreover, all antipsychotic agents are likely to induce neonatal adverse reactions if used during late pregnancy [12]. On the other hand, Jacques Dayan, Rozenn Graignic-Philippe, and Gwenaelle Andro, following a comprehensive review of pertinent scientific literature, conclude that, for some of the antipsychotics (haloperidol, risperidone, and quetiapine), there are no signals of adverse effect in the suckling infant. Hence, it is confirmed that the possibility exists that mothers who need antipsychotic medications during puerperium may safely breastfeed their own babies [13]. As regards mood stabilizing agents, our Spanish colleagues rightly highlight that available evidence indicates that, at therapeutic serum levels, lithium poses only a small (albeit measurable) structural teratogenic hazard to human reproduction. Moreover, it appears that the risk of lithium-induced serious adverse events in the breastfed infant is relatively low. The risk of major structural malformations is conversely significantly increased by exposure to either carbamazepine or valproate, whereas it seems negligible during exposure to lamotrigine. All these three antiepileptic drugs show anecdotal information regarding their use during late pregnancy or by lactating women. However, as reported by Angelika Wieck, the high serum levels of lamotrigine in breastfed infants and the theoretical risk of severe skin reactions has lead national guidelines to advise against breast feeding during medication with this drug. Regrettably, apart from reassuring results regarding antidepressants [14] (which, however, require urgently further confirmation [15]) and worrying results regarding valproate, [16, 17] the potential impact of prenatal exposure to most psychotropic drugs on the infant’s later neurodevelopment remains substantially unknown. Given these considerations, we are forced to completely turn upside-down our approach to pharmacological treatment of mental disorders during pregnancy and puerperium. Clinicians should abandon any attempt to individuate the safest option, and should re-channel their attention toward individuating the least worrying option, since it is irresponsible to leave severely mental ill women untreated, even if pregnant or lactating. However, whatever the choice, obtaining a full informed consent, warranting careful gynecologic monitoring, ensuring that delivery happens in hospitals equipped with Neonatal Intensive Care Units, and providing strict pediatric surveillance of infants up to school age are all indispensable tools for optimizing maternal treatment and reducing the risks for the fetus and the newborn as much as possible.

While the treatment of schizophrenia and other psychotic disorders has advanced over the past decades, the management of women with this serious mental illness, who become pregnant, and their babies remains a concern. The use of psychotropic medications is necessary in a large number of women of childbearing potential who have a serious mental illness however the use of psychotropics, particularly antipsychotics, may interfere with the reproductive process. The literature regarding the effect of psychotropic medications on the reproductive ability of women is presented in this article. The authors have found varied reports regarding fertility rates and outcomes for this group of women including a lower rate of fertility, fewer children, despite being less likely to use contraceptives. That atypical antipsychotic medications effect fertility is outlined. Implications for the women and clinicians are discussed. Coinciding with the developments in medication management have been many changes in the delivery of mental health care and social changes which have led to women developing and maintaining relationships and wanting to have children. Many factors may influence the fertility of women. Women generally prefer not to take medications if they are wishing or trying to become pregnant. Adherence to medication treatment may have implications in relation to this. There is little consistency in the literature around this, and little is really known about the fertility rates of women with serious mental illness.

Since 1993 there have been numerous published reports on teratogenic risks of antidepressants. Most of the studies indicate that the risk of major malformations associated to the use of antidepressants in early pregnancy is not greater than the risk of major malformations in the general population without known risk factors. Few studies have shown a slight increase in the presence of malformations associated with the use of antidepressants, especially septal heart defects, as compared with general population. These data are not consistent enough, and are in contrast with most of other studies. In any case, if there were an increased risk of septal heart malformations, this would be very limited. Furthermore, an overestimated perception of risks would impede the needed treatment of mothers with psychiatric disorders requiring antidepressants. The risk of untreated moderate -severe psychiatric disorders is far more dangerous for the foetus and the mother than the possible increased risk of septal heart malformations. As with any medication, a careful and personalized evaluation of the treatment is required, but with the available data at hand, in most occasions the decision should incline towards adequate treatment of the psychiatric problems.

Late in utero exposure to antidepressants has been suspected of compromising neonatal adaptation. Objectives: To analyze published information on the risk of neonatal withdrawal phenomena associated with antidepressant use during late pregnancy. Methods: Computerized searches on MEDLINE, PsycINFO, ENBASE, and Cochrane Library (up to October 2010) were performed for selecting literature information published in English and investigating the safety of antidepressants when used during late pregnancy (50 articles). Results: Antidepressant treatment during late pregnancy may significantly increase the rate of neonatal discontinuation symptoms of various degree of severity. Conclusions: Further, prospective, large cohort studies are needed to clarify whether such symptoms can be prevented by suspending antidepressant treatment within the final month before parturition.

Background: The treatment of breastfeeding mothers with depression raises several dilemmas, including the possible risk of drug exposure through breast milk for the infant. This article provides background information and presents practical advice and recommendations for the clinician dealing with the treatment of depression and related disorders in the postpartum period. Methods: An electronic search for relevant articles was performed. As the use of tricyclic antidepressants has considerably decreased during the last decade and no new information on breastfeeding has emerged for the tricyclics in this period, this review exclusively focuses on the newer, non-tricyclic compounds. Results: Most newer antidepressants produce very low or undetectable plasma concentrations in nursing infants. The highest infant plasma levels have been reported for fluoxetine, citalopram and venlafaxine. Suspected adverse effects have been reported in a few infants, particularly for fluoxetine and citalopram. Conclusions: Infant exposure of antidepressants through breast milk is generally low to very low. We consider that when antidepressant treatment is indicated in women with postpartum depression, they should not be advised to discontinue breastfeeding. Paroxetine and sertraline are most likely suitable first-line agents. Although some concern has been expressed for fluoxetine, citalopram and venlafaxine, we nevertheless consider that if the mother has been treated with one of these drugs during pregnancy, breast-feeding could also be allowed during continued treatment with these drugs in the postpartum period. However, an individual risk-benefit assessment should always be performed.

The management of psychiatric illness during pregnancy requires a risk-benefit analysis; physicians must weigh the benefits of treating severe psychiatric illness in pregnant patients with the possible risks to the mother of non-treatment and the risks to the developing fetus secondary to exposure to psychotropic medication. Unfortunately for many pregnant women, discontinuation of their antipsychotic medication is not an option; the risk of relapse, recurrent illness, suicide and difficulty in returning to a non-psychotic state if relapse were to occur is too great. Treating physicians will often advise these women to continue their medications throughout pregnancy. Unfortunately, there has not been clear evidence on which antipsychotic medication is safest in pregnancy and lactation. Two articles have recently reviewed the safety of antipsychotic drugs in pregnancy. And even review articles have highly different outcomes, despite, for the most part, utilizing the same source of articles. What is needed at this time is guidance in choosing an antipsychotic medication in a medication naive pregnant patient or a woman contemplating pregnancy. Prospective cohort studies are attractive studies to contribute to a better understanding in the selection of effective drugs to afford this problem.

Background: Post partum psychosis, mainly first episodes and relapses of either bipolar or schizophrenic disorders, entail severe risks for both mother and infant during postpartum, including suicide and infanticide. Although antipsychotics are now generally considered as a first line treatment for these disorders, there are no randomized controlled trials (RCTs) examining their efficacy during postpartum and there are only sparse data about their safety during breastfeeding. Methods: After a brief recall of the main indications of antipsychotics during post-partum we examined the risks and benefits of breastfeeding in that context. We reviewed the question by performing an electronic search from 1957 to January 2009. This procedure yielded a total of 28 papers reporting 18 single case reports and 13 small samples case series. Results: No adverse effect has been reported with Haloperidol, Risperidone and Quetiapine when prescribed alone and there are no published reports for Aripiprazole or Ziprasidone. One case of drowsiness and lethargy has been reported with Chlorpromazine, an infant developing agranulocytosis with Clozapine and four adverse events in case of infants exposed to Olanzapine. Mild developmental delay was noted with Clozapine alone and with a combination of Quetiapine and Paroxetine and a combination of Haloperidol and Chlorpromazine. Conclusion: Few adverse effects have been reported for first and second generation of antipsychotic drugs during lactation but only sparse data have been gathered. Meanwhile, taking into account some precautions that we summarize in proposed guidelines, it seems to be no reason in most cases to prevent a mother using antipsychotics from breastfeeding, if she wishes to do so.

Lithium salts are regularly used in the treatment for bipolar disorder, both as a prophylactic and as an episodic treatment agent. Bipolar affective disorder is most common in women of childbearing age. The available evidence indicate that lithium at therapeutic dose levels poses only a small but measurable teratogenic hazard to human reproduction being the main teratogenic target the cardiovascular system. The specific defect associated with lithium exposure, the Ebstein anomaly, may be serious or life threatening. In addition, the continuous use throughout gestation is associated with perinatal complications including toxicity and transient neurodevelopment deficits in the neonatal period. Since there is no controlled data in human pregnancy, lithium should only be given during pregnancy when there are no alternatives and benefit outweighs risk. Whenever lithium is the drug of choice in women with bipolar disorder it may be continued during pregnancy although these lithium-treated women should be considered high risk and need to be monitored during pregnancy including fetal echocardiography and serum Li levels throughout pregnancy.

Valproate, carbamazepine and lamotrigine are used in psychiatry mainly for the treatment of bipolar disorder. Increasing evidence from studies in women with epilepsy indicate that valproate in higher doses is toxic to the susceptible fetus and can cause anomalies in several organ systems as well as widespread deficits in later cognitive development. This agent should not now be prescribed in psychiatry to women during the entire pregnancy and not to women with childbearing potential unless they use highly reliable contraception. Carbamazepine is associated with a relatively small increase in the risk of neural tube defects and together with the uncertainty about it's antidepressant and preventative efficacy in bipolar disorder it's use in pregnancy should be limited only to special cases who have a history of a particularly favourable therapeutic response to this agent but not others. Whether lamotrigine is associated with a small increase in oral clefts is at present uncertain but the absolute risk is relatively small. Breastfeeding is not contraindicated when women are prescribed valproate or carbamazepine. In contrast, the high serum levels of lamotrigine in breastfed infants and the theoretical risk of severe skin reactions has lead national guidelines to advise against breast feeding during medication with lamotrigine. Pregnancy does not protect from new episodes of bipolar disorder and the early postpartum period is an extremely potent trigger for recurrences. It is therefore essential that reproductive issues are discussed with premenopausal women with affective disorders and that preconception consultations are offered to women who plan a pregnancy. In many countries, advice in these complex situations is available from specialists in perinatal psychiatry.

Efforts to prevent cervical cancer in the developed world have largely been successful, with cervical cancer rates showing a decline over time. The Great Britain age-standardised (European) incidence rate for cervical cancer has decreased by around 44% since 1975. In the UK the age-standardised (European) incidence rate for cervical cancer has decreased by 29% since 1993 [1]. This has been achieved largely through successful screening programs [2]. It is estimated that screening can prevent up to 75% of cervical cancer. The introduction of vaccination against the high risk human papilloma viruses may lead to a further decline in cervical cancer incidence. Treatment for cervical cancer in the developed world is largely successful and with improving survival, efforts are being directed to minimising treatment-related morbidity and improving quality of life after treatment. Radical hysterectomy is now a relatively well tolerated procedure and minimally invasive and nerve-sparing techniques improve the safety profile even more (ref). Surgical staging (Hadwin ref) ensures that the treatment field for chemoradiation can be defined, with inclusion of the para-aortic area if these nodes are affected. In addition, as the peak age for cervical cancer is now in the third decade, and with the majority of these women desirous of fertility, fertility-sparing options should be considered where appropriate. The contrast with the developing world is significant. One in ten female cancers diagnosed worldwide are cancers of the cervix and it is the most commonly diagnosed cancer among women in Southern Africa and Central America. There is a sevenfold variation in the incidence of cervical cancer between the different regions of the world [3]. The reality for women from less developed countries who develop cervical cancer is that the majority will die of their disease. Therefore all efforts to introduce low cost cervical screening to these countries should be applauded. Agrawal discusses the challenges associated with establishing a screening program. Researchers in the developing world have called for cervical cancer to be given the same priority and funding as HIV malaria and TB and only then can there be an impact on this disease that causes a health, social and economic burden in these countries [4].

Cervical cancer is the most common gynaecological cancer in developing countries. It is the single largest cause of life years lost to cancer in these settings, despite the existence of technology that could almost entirely prevent these deaths. Low-income countries face multiple challenges that prevent them achieving a reduction in burden of disease similar to that of the industrialised countries. Cytology-based programs are difficult to provide in resourcelimited settings, further compounded by socio-cultural factors such as lack of awareness amongst public, providers and politicians; cultural practices of child marriage and polygamy; as well as low levels of female literacy. However, despite these hurdles, there has been no better time to act than now. Widespread distribution of the HPV (Human Papillomavirus) vaccine and the adoption of new tools that enable a screen-and-treat approach have the potential to dramatically reduce the burden of cervical cancer. Increased recognition of the growing cancer burden, international resource-mobilisation and global collaboration will be necessary to stop women in developing countries dying of a wholly preventable disease.

Cervical cancer presents a significant challenge for the clinician in choosing the optimal therapy. The majority of disease burden remains in the resource poor developing world, where sophisticated surgical or radiological staging is generally not available. In the developed world, surgery remains the mainstay of treatment for early invasive disease, but surgical staging is of controversial importance in the management of later stage disease. Evolution of minimal access techniques have reduced the mortality and morbidity for the techniques, and may shift the emphasis from radiological to surgical approaches. We discuss the available methods used for surgical staging for cervical cancer, the evidence supporting these techniques and their relative merits.

Women between ages 30-40 have the highest incidence of cervical cancer in the UK and survival rates in this group are over 85%. Traditional treatments for both early and more locally advanced disease render women infertile but treatments which allow them to maintain the potential for having children are now available and should be discussed prior to the commencement of definitive cancer treatment. Fertility-sparing surgery is now widely available for early stage disease and ovarian preservation with transposition out of the radiotherapy field should be considered in more advanced disease. Assisted reproductive techniques can be used prior to treatment or after ovarian transposition to allow embryo, egg or ovarian tissue storage with ever-improving success rates.

A diagnosis of cervical cancer during pregnancy often requires difficult management decisions. This review focuses on the current literature and practice with regards to diagnosis and management. We explore the role of surgery, chemoradiation and neo-adjuvant chemotherapy. Treatment decisions are influenced by the stage of the cancer, the histological type, the stage of the pregnancy and the patient's wishes. Both maternal and fetal safety and wellbeing has to be taken into account. Termination of pregnancy is not indicated in all cases. Pregnancy preservation in tumours diagnosed during early gestation is feasible in carefully selected cases. Discussion with the patient and her family is essential and treatment has to be individualised. .

As diagnostic, screening and treatment options for cervical cancer become more efficient, more people will benefit from treatment and therefore survive longer. Modern treatment options for cervical cancer, despite advantages in survival, carry a broad spectrum of morbidities, leaving survivors with chronic treatment related conditions, the management of which requires complex multidisciplinary expert approaches. It is of utmost importance for health care providers to recognize that aspects of cancer survivorship continue to require attention and complex follow-up care. The United Kingdom National Cancer Survivorship Initiative (NCSI) group, created in the UK in 2009 has highlighted the following principles of care for cancer survivors: a personalised assessment and care plan, access to specialist medical care for complications that occur after cancer, support to self-management of their condition by patients and information on the long-term effects of living with and beyond cancer. This article provides a brief overview of treatment related morbidity for cervical cancer and rises awareness of health professionals of the need to address these complications.

Obstetric anaesthesia can be potentially hazardous. The physiological changes of pregnancy place an extra burden on the pregnant patient, particularly on the respiratory and cardiovascular systems, which may then be further strained by the introduction of general or regional anaesthesia in the peripartum period. Many of these physiological changes can be exacerbated by obesity, and the care of obese parturients can present extra challenges to anaesthetists. Obesity is increasing in prevalence globally, and these patients are presenting for antenatal care with increasing frequency. This article reviews the changes in physiology associated with obesity and pregnancy, considers some of the hazards of providing anaesthesia to obese parturients and suggests some techniques which may help to provide safer care to these challenging patients.