Neurosurgical considerations on highly eloquent brainstem cavernomas during pregnancy

Objective

Cerebral cavernous malformations (CCMs) and especially cavernous malformations (CMs) in highly eloquent brain areas such as brainstem CMs are rare but possible events during pregnancy. Due to the few published cases in literature clear recommendations regarding the management are rare. In this study we evaluate the proceeding decision in pregnant patients with highly eloquent brainstem CMs.

Methods

In our series 43 patients with CMs in highly eloquent brain areas, including 39 patients with brainstem CMs, were surgically treated by the senior author between July 2007 and July 2010. Out of these, 29 patients were female and three of them presented with a symptomatic brainstem CMs during pregnancy and were included in this study. According to our experiences and to the available literature we analyzed demographic and clinical variables to provide recommendations for the management of pregnant patients with highly eloquent brainstem CMs.

Results

Only one patient was operated during pregnancy the other two patients were surgically treated after delivery, respectively. A thorough review of the literature revealed 12 patients with brainstem cavernomas during pregnancy there of only two patients were operated during pregnancy.

Conclusion

Surgical treatment during pregnancy is rarely required, but needs to be performed right away in life-threatening and rapidly progressive clinical situations. Pregnant women with CMs in highly eloquent brain areas such as brainstem CMs need to be treated in specialized centers to assess the best point of time for surgery. Our study offers a useful tool to support the proceeding decision in this rare but important situation.     

A prospective study of postpartum psychoses in a high-risk group. 4. Relationship to life situation and experience of pregnancy

Within a sample of 88 pregnant women with a history of nonorganic psychosis, the woman's life situation and experience of pregnancy, assessed through interviews during pregnancy, were studied in relationship to the development of 25 postpartum psychotic episodes (PPPs) occurring during the first 6 months postpartum. Neither Early nor Later Onset PPPs were associated with more current material situational problems, interpersonal difficulties, lack of relatives' support for the pregnancy, the woman's negative attitude toward the pregnancy or her experience of somatic health complaints. Contrary to expectation, PPP cases reported several more positive situational, attitudinal and experiential characteristics than did risk cases not developing PPPs. A number of different possible explanations for this finding are discussed.     

Stress and salivary cortisol during pregnancy

The purpose of this study was to determine whether exposure to stressful life events was associated with changes in levels of circulating cortisol during pregnancy in a population of 603 pregnant women. The participating pregnant women filled out a questionnaire and collected a morning and evening sample of saliva in early pregnancy (median 14th gestational week) and in late pregnancy (median and 30th gestational week). They were asked to report the number of life events experienced during first and second trimester, respectively, and were asked to rate the intensity of the experienced events. Complications related to the pregnancy such as vaginal bleeding and suspected growth retardation were registered and the women were asked about concerns about their pregnancy. The salivary samples were analyzed for cortisol and the levels were higher in late than in early pregnancy. In late pregnancy women exposed to more than one life event or were concerned about pregnancy complications during second trimester had a higher evening cortisol level, whereas morning values were unaffected. After adjustment for smoking women who experienced more than one very stressful life event had 27% higher evening cortisol concentrations (95% confidence intervals: 1-59%). Women with worries about pregnancy complications had 27% (95% confidence intervals: 2-57%) higher levels. In early pregnancy women reporting stressful life events did not have higher evening cortisol levels, but tended to have a blunted morning HPA response. In conclusion, we found differences in the associations between chronic stress in early and late pregnancy and cortisol levels indicating that the response to chronic stress is dependent on the stage of the pregnancy.     

Psychological factors in pregnancy and mixed-handedness in the offspring

Animal studies suggest that psychological factors may interfere with the development of brain asymmetry during gestation. We evaluated whether psychological exposure in pregnancy was associated with mixed-handedness in the offspring. In a follow-up design study, 824 Danish-speaking women with singleton pregnancies provided information on psychological distress and the occurrence of life events in the early second and third trimesters of pregnancy. Handedness of the children was based on maternal reports when the children were 3 years of age. Among the 419 males and 405 females, 7% and 5% respectively were mixed-handed whereas mixed-handedness was found in 3% of the parents. Psychological distress in the third trimester as well as higher levels of stressful life events were related to a higher prevalence of mixed-handedness in the offspring. About 16% of the women reported more than one life event in the third trimester of pregnancy and among the offspring of these women 11% were mixed-handed (odds ratio = 2.3; 95% confidence interval 1.2 to 4.4). Women who at the same time reported a high level of distress and stressful life events, had a three- to four-fold higher prevalence of mixed-handedness in their offspring.     

Maternal smoking during pregnancy and offspring psychiatric disorder: a longitudinal birth cohort study

Background

There is evidence that prenatal stress and smoking during pregnancy both independently increase the risk of offspring psychopathology. Here we examine whether increased levels of self-reported stress is associated with increased smoking in a population of pregnant women, and whether prenatal smoking is associated with offspring psychiatric diagnoses independent of prenatal stress exposure.

Method

Using a longitudinal birth cohort, we used ordered logistic regressions to examine associations between maternal stress and smoking during pregnancy. We then used logistic regression analyses to examine associations between prenatal smoking and later offspring psychiatric disorders.

Results

A dose–response relationship was found between maternally reported stress and smoking during pregnancy. Pregnant women reporting severe stress were more likely to smoke compared to both the moderate stress and no stress groups, and those reporting moderate stress were significantly more likely to smoke compared to the no stress group. Smoking more than 5 cigarettes daily during pregnancy increased the risk of offspring personality disorder (OR 3.08, 95% CI 1.60–5.94) as well as developing any Axis 1 psychiatric disorder, inclusive of mood, anxiety and psychotic disorders (OR 1.45, 95% CI 1.04–2.04). After adjusting for parental psychiatric history and maternal self-reported stress during pregnancy, associations between smoking more than 5 cigarettes daily when pregnancy and offspring personality (OR 2.58 95% CI 1.32–5.06) disorder remained.

Conclusion

Exposure to cigarette smoking during gestation could impact a child’s mental health. Smoking during pregnancy is a prime target for preventative interventions as unlike most other environmental risk factors, it is very amenable to change.

     

Offspring of women with nonorganic psychoses

ABSTRACT– This article describes the development of a prospective, longitudinal study of 88 “high-risk” offspring of pregnant index women with a history of nonorganic psychoses and 104 offspring of demographically-similar pregnant control women. The maternal psychoses represented the diagnostic categories, Schizophrenia, Cycloid Psychosis, Affective Illness, Psychogenic Psychosis, Postpartum Psychosis and Other (remaining) Psychoses. The first phase of the study began during pregnancy and continued until the offspring reached 2 years of age. Selected characteristics of the mothers, the offspring and their environments were investigated during this project phase.     

Cortisol awakening response in pregnant women

In this study, basal saliva cortisol was determined in women at 32 weeks of pregnancy and again at 9 months post-partum. During pregnancy, the cortisol levels of the 119 subjects were found to be elevated, with noon and evening levels more than twice as high as during the non-pregnant state. Despite the hypercortisolism, the cortisol awakening response was still present during pregnancy. Although the absolute mean increase in cortisol at 30 min post-awakening was larger during pregnancy, the relative mean increase was around 40% of the awakening level in both cases. The cortisol awakening response was not correlated between pregnancy and the post-partum, showing a lack of stability over the 11-month period. Finally, both in the pregnant and non-pregnant states, the magnitude of the cortisol awakening response was not related to time of awakening, nor to anticipation of a working vs. non-working day. In conclusion, the free cortisol awakening response is present during pregnancy, and is potentially a useful marker to study the association between prenatal psychosocial stress and offspring development.     

A prospective study of postpartum psychoses in a high-risk group. 7. Relationship to later offspring characteristics

Among the offspring of 88 pregnant index women with a history of nonorganic psychosis, offspring whose mothers developed postpartum psychotic episodes (PPPs) following birth (maximum n = 17) were compared with the remaining index offspring on emotional development during the first year of life, temperament characteristics during the first 2 years, and mental characteristics at 6 years of age. The maternal PPPs were not associated with any negative consequences for offspring development, and the offspring of PPP cases evidenced a number of more positive mental developmental characteristics than did other index offspring. Further comparison with offspring of normal-risk controls also supported the conclusion of no negative effect caused by maternal PPPs. Choice of an appropriate comparison group for PPP cases is discussed.     

Women with nonorganic psychosis: factors associated with pregnancy's effect on mental health

Pregnancy's effect on mental health during pregnancy was studied in relation to 17 variables representing the pregnant woman's demographic, social, material, physical and attitudinal characteristics, in an attempt to explain the highly varied effect of pregnancy on mental health which had been observed both among 88 index women with a history of nonorganic psychosis and among 104 demographically similar pregnant control women. Little explanation or predictability was found for the varied effect of pregnancy. Among index cases, only maternal age and the experienced effect of pregnancy on physical health were significantly related to its effect on mental health. In controls, the presence of material-situational problems and a negative/ambivalent initial reaction to pregnancy were each related to increased change in mental health, i.e. to both improvement and worsening in mental health associated with pregnancy.     

Do hypertension and diuretic treatment in pregnancy increase the risk of schizophrenia in offspring?

OBJECTIVE: Diuretics prescribed after the first trimester for treatment of hypertension in pregnant women may interfere with normal plasma volume expansion and cause volume depletion. The authors hypothesized that prenatal exposure to diuretics and maternal hypertension might disrupt fetal neurodevelopment and increase the risk of schizophrenia in offspring. METHOD: Using data from the Copenhagen Perinatal Cohort of individuals born between 1959 and 1961, the authors studied the relationship of maternal hypertension and diuretic treatment during pregnancy with the risk of schizophrenia (ICD-8 code 295) in the offspring. Prenatal medical information was linked to the Danish National Psychiatric Register. The effects of maternal hypertension and diuretic treatment were adjusted for the maternal history of schizophrenia, social status of the family breadwinner, mother's age, and concomitant drug treatment during pregnancy. RESULTS: In a risk set of 7,866 individuals, 84 cases of schizophrenia were found (1.1% prevalence). Logistic multiple regression analysis identified the following independent risk factors: maternal hypertension (odds ratio=1.69 [95% CI=1.02-2.80]), diuretic treatment in the third trimester (odds ratio=2.55 [95% CI=1.21-5.37]), and maternal schizophrenia (odds ratio=11.12 [95% CI=4.60-29.91]). Prenatal exposure to both hypertension and diuretic treatment in the third trimester conferred a 4.01-fold (95% CI=1.41-11.40) elevated risk. CONCLUSIONS: Children of mothers with hypertension in pregnancy plus diuretic treatment in the third trimester were at significantly increased risk of developing schizophrenia. In pregnancies complicated by hypertension, diuretics may interfere with aspects of fetal neurodevelopment and thus increase the vulnerability of offspring to the development of schizophrenia later in life.     

Maternal distress and congenital malformations: do mothers of malformed fetuses have more problems?

As compared with 580 randomly chosen pregnant women without malformed offspring. 161 women with malformed offspring at the index pregnancy had a more frequent history of previous multiple offspring deaths and somewhat increased maternal age but were not different on social class, marital or cohabitation status or parity. As compared with demographically similar reproducing women (n = 54) interviewed, malformation cases (n = 98) reported having had significantly more strong stress before identification of the malformation, as well as a clear tendency toward less appropriate timing of the pregnancy. Women with malformed offspring represent a psychosocially vulnerable group and should receive special clinical and personal support.     

A prospective study of postpartum psychoses in a high-risk group. 3. Relationship to mental health characteristics during pregnancy

Within a sample of 88 pregnant women with a history of nonorganic psychosis, mental health characteristics during pregnancy, assessed prospectively through interviews and psychiatric records, were studied in relationship to the development of 25 postpartum psychotic episodes (PPPs) occurring during the first 6 months postpartum. Cases with PPP onset within 3 weeks of delivery (mostly affective or cycloid psychoses) evidenced more frequent tension-anxiety and excitement at interviews during pregnancy than did diagnostically comparable cases not developing PPPs. Cases with PPP onset later than 3 weeks postpartum (mostly schizophrenic-like psychoses) were not more frequently disturbed than were diagnostically comparable cases not developing PPPs. An absence of both affective symptoms and common fears represented a sign of increased PPP-risk in these later onset cases. The subsample of actively disturbed cases who were in contact with a psychiatrist during pregnancy were at notably increased risk for a PPP during the total 6-month period.     

Positive life events predict salivary cortisol in pregnant women

Maternal stress during pregnancy has been repeatedly associated with problematic child development. According to the fetal programming hypothesis adverse experiences during pregnancy increase maternal cortisol, which is then assumed to exert a negative effect on fetal development. Recent studies in non-pregnant women report significant associations between positive emotionality and low cortisol levels. We tested in a sample of 60 pregnant women whether both negative and positive life events independently predicted third-trimester baseline awakening cortisol levels. While the effect of negative life events proved unrelated positive life events significantly predicted lower cortisol levels. These findings suggest that positive experiences are of relevance regarding maternal morning cortisol levels in pregnancy reflecting a resource with potentially beneficial effects for the mother and the developing fetus. It might be promising for psychological intervention programs to focus on increasing positive experiences of the expecting mother rather than exclusively trying to reduce maternal stress during pregnancy.     

Sexual function may be impaired during pregnancy in adolescent women

Prevalence of sexual dysfunctions is reported as high as 70% during pregnancy. However, there are limited data about the burden of sexual dysfunction in pregnant adolescents. This cross-sectional study was conducted in the outpatient antenatal clinic of our institution between October and December 2014. The total female sexual function index scores and domain scores were compared between adolescent and adult pregnant women. A total of 121 pregnant women participated in the study. Of those women, 29 (24.0%) were 21 years old or younger (Group 1), whereas the remaining were older (Group 2). The sexual dysfunction ratios were 41.4% and 23.9% in Groups 1 and 2, respectively (p = 0.068). The desire (3.29 vs. 2.79, p = 0.024) and arousal (3.48 vs. 2.71, p = 0.008) domain scores of adolescent pregnant women were significantly higher whereas the remaining domain scores (i.e. lubrication, orgasm, satisfaction and pain) were not significantly different. The adolescent women seem to be more prone to sexual dysfunctions during the course of pregnancy, especially in the third trimester. The health care providers should consider discussing the sexual life during pregnancy as a part of routine antenatal visit to improve sexual function and quality of life, especially among adolescent pregnant population.     

Pregnancy of the early-career psychiatrist

OBJECTIVE: Since the 1970s the number of women physicians has steadily increased and is expected to continue to climb into the next century. Psychiatry is a medical specialty that has been successful in attracting women. As more young women enter psychiatry, more colleagues will be pregnant in the workplace. This paper explores some of the practical issues that pregnancy poses for the early-career psychiatrist, her colleagues, and her patients. METHODS: A MEDLINE search was conducted. Literature on the pregnant physician, the pregnant therapist, and the pregnant resident was reviewed. Recommendations found in these resources were combined with the author's observations to create a single resource paper that outlines common problems and practical strategies for the psychiatrist who is pregnant. RESULTS: The integration of the psychiatrist's maternal identity with her professional identity is a task that often begins during pregnancy. The fear of abandonment is a common theme for patients under her care. Relationships with colleagues are sometimes strained. The medical workplace has been slow to accommodate the needs of women, who make up a growing percentage of professional employees. CONCLUSIONS: The reproductive years and the early years of practice overlap for a growing number of women in psychiatry. The life experience of motherhood can be an important part of one's growth as a psychiatrist. Relationships with coworkers and patients can be eased if potential problems are recognized and dealt with early on. Employers and medical organizations are challenged to make an investment in women professionals through the development of family-oriented policies.     

Pregnancy and epilepsy

The management of women with epilepsy who are planning a pregnancy or who are currently pregnant remains one of the most perplexing and engaging clinical issues for neurologists. A refinement of surveillance methods, along with a greater understanding of teratogenesis, has provided us with better information regarding specific antiepileptic drug (AED)-associated teratogenic risk than in the past. A recent finding from multiple worldwide AED pregnancy registries is an increased teratogenic risk with valproate compared with the other AEDs, supporting previous retrospective reports. Valproate use and independently having more than five convulsive seizures during pregnancy are associated with a risk of decreased verbal intelligence quotient (IQ) in the offspring. The European pregnancy register confirms that most women who are seizure-free early in pregnancy have an excellent chance of maintaining seizure freedom throughout pregnancy. The management of AEDs during pregnancy continues to be explored, and considerations for dosing and therapeutic monitoring are discussed herein. The metabolism of both lamotrigine and oxcarbazepine is induced during pregnancy, and careful clinical monitoring and frequent level assessment are emerging as important for these AEDs.     

Pregnancies of Women with Epilepsy: A Population-Based Study in Iceland

Summary: Purpose : Women with epilepsy who become pregnant are commonly considered to be at high risk for complications during pregnancy or delivery. The offspring are also considered o have increased risk of perinatal mortality, congenital malformations, and maturational delay. Because few of these studies are population based, potential bias exists because of selection.
Methods: We performed a historical population-based cohort study in Iceland to determine the prevalence of epilepsy among pregnant women, to identify pregnancy and delivery complications in women with epilepsy, and to determine the outcome of their pregnancies as compared with that in the general population of Iceland. We identified all women with active epilepsy who gave birth during a 19-year period in Iceland.
Results: In this population, 3.3 in 1,000 pregnancies involve mothers with active epilepsy. The frequency of adverse events (AE) during pregnancy in the women with epilepsy is similar to that observed among all live births in the population, but cesarean section was performed twice as frequently as in the general population. Perinatal mortality rate and mean birth weight are not significantly different in the offspring of women with epilepsy as compared with rest of the population. The risk of major congenital malformations (MGM) is increased 2.7- fold over that expected when a mother is treated with antiepileptic drugs (AEDs) during a pregnancy.
Conclusions: Our study indicates that the rate of complications of pregnancy in mothers with active epilepsy is low and similar to that of the general population with epilepsy. Use of AEDs by the mother during pregnancy significantly increases the risk of MGM in the offspring.     

Elevated risk of tobacco dependence among offspring of mothers who smoked during pregnancy: a 30-year prospective study

OBJECTIVE: The authors' goal was to investigate whether maternal smoking during pregnancy is associated with an increased risk of nicotine dependence among adult offspring. METHOD: Prospective data from two samples of offspring in the National Collaborative Perinatal Project, a long-term prospective investigation from pregnancy through adulthood, were combined (N=1,248). Maternal smoking during pregnancy was assessed during each prenatal visit. Offspring smoking behavior and lifetime risk of nicotine dependence were obtained by structured interview with the Diagnostic Interview Schedule; the mean age of the offspring at the time of interview was 29 years. RESULTS: Offspring whose mothers reported smoking a pack or more of cigarettes during their pregnancy were significantly more likely to meet DSM criteria for lifetime tobacco dependence than offspring of mothers who reported that they never smoked during pregnancy. The odds of progressing from smoking to nicotine dependence were almost twice as great for offspring whose mothers smoked heavily during pregnancy. These significant differences remained after adjustments for participants' gender and age and maternal socioeconomic status and age at pregnancy. Results were comparable for men and women. The findings were specific for tobacco dependence; odds of marijuana dependence were not significantly elevated among the offspring of tobacco smokers. CONCLUSIONS: Offspring of mothers who smoked a pack or more of cigarettes during pregnancy are at elevated risk of developing nicotine dependence but not marijuana dependence as adults. Maternal smoking during pregnancy is a risk factor for subsequent nicotine dependence among offspring.     

Duration of antidepressant use during pregnancy and risk of major congenital malformations

BACKGROUND: Antidepressant use during the gestational period is a controversial topic. AIMS: To determine whether duration of antidepressant use during the first trimester increases the risk of major congenital malformations in offspring of women diagnosed with psychiatric disorders. METHOD: A case-control study was performed among women who had been pregnant between January 1998 and December 2002. Data were obtained from a Medication and Pregnancy registry, built by linking three databases from the province of Quebec, and a self-administered questionnaire. Women eligible for this study had to be 15-45 years old at the beginning of pregnancy, have at least one diagnosis of psychiatric disorder before pregnancy, have used antidepressants for > or =30 days in the year prior to pregnancy and have a pregnancy ending with a delivery. Cases were defined as any major congenital malformation diagnosed in the offspring's first year of life. Odds ratios, adjusted for relevant confounders, were estimated using logistic regression. RESULTS: Among the 2329 women meeting the inclusion criteria, 189 (8.1%) infants were born with a major congenital malformation. Duration of antidepressant use during the first trimester of pregnancy was not associated with an increased risk of major congenital malformations: 1-30 days v. 0 day, adjusted OR=1.23 (95% CI 0.77-1.98); 31-60 days v. 0 day, adjusted OR=1.03 (95% CI 0.63-1.69); > or =61 days v. 0 day, adjusted OR=0.92 (95% CI 0.50-1.69). CONCLUSIONS: These data do not support an association between duration of antidepressant use during the first trimester of pregnancy and major congenital malformations in the offspring of women with psychiatric disorders. These findings should help clinicians decide whether to continue antidepressant therapy during pregnancy.     

Strain-dependent effects of prenatal maternal immune activation on anxiety- and depression-like behaviors in offspring

There is converging evidence that prenatal maternal infection can increase the risk of occurrence of neuropsychiatric disorders like schizophrenia, autism, anxiety and depression in later life. Experimental studies have shown conflicting effects of prenatal maternal immune activation on anxiety-like behavior and hypothalamic–pituitary–adrenal (HPA) axis development in offspring. We investigated the effects of maternal immune activation during pregnancy on anxiety- and depression-like behaviors in pregnant mice and their offspring to determine whether these effects are dependent on strain. NMRI and C57BL/6 pregnant mice were treated with either saline or lipopolysaccharide on gestational day 17 and then interleukin (IL)-6 and corticosterone (COR) levels; anxiety or depression in the pregnant mice and their offspring were evaluated. The results indicate that maternal inflammation increased the levels of COR and anxiety-like behavior in NMRI pregnant mice, but not in C57BL/6 dams. Our data also demonstrate that maternal inflammation elevated the levels of anxiety-and depression-like behaviors in NMRI offspring on the elevated plus-maze, elevated zero-maze, tail suspension test and forced swimming test respectively, but not in the open field and light–dark box. In addition, we did not find any significant change in anxiety- and depression-like behaviors of adult C57BL/6 offspring. Our findings suggest that prenatal maternal immune activation can alter the HPA axis activity, anxiety- and depression-like behaviors in a strain- and task-dependent manner in offspring and further comprehensive studies are needed to prove the causal relationship between the findings found here and to validate their relevance to neuropsychiatric disorders in humans.