A prospective cohort study of antipsychotic medications in pregnancy: the first 147 pregnancies and 100 one year old babies

BACKGROUND: Many women diagnosed with varying psychiatric disorders take antipsychotic medications during pregnancy. The safety of antipsychotic medications in pregnancy is largely unknown.

METHODS: We established the National Register of Antipsychotic Medications in Pregnancy in 2005. Women who are pregnant and taking an antipsychotic medication are interviewed every 6 weeks during pregnancy and then followed until their babies are one year old. The baby's progress is closely followed for the first year of life.

FINDINGS: As of April 18 2012, 147 pregnancies had been followed through to completion. There were 142 live births and data is available for 100 one year old babies. 18% of babies were born preterm, with a higher dose of antipsychotic medication correlating to an increased likelihood of premature delivery; 43% of babies required special care nursery or intensive care after birth; 37% had any degree of respiratory distress and 15% of babies developed withdrawal symptoms. Congenital anomalies were seen in eight babies. Most pregnancies resulted in the birth of live, healthy babies. The use of mood stabilisers or higher doses of antipsychotics during pregnancy increased the likelihood of babies experiencing respiratory distress or admission to Special Care Nursery or Neonatal Intensive Care Units.

CONCLUSION: There is a great need for safety and efficacy information about the use of antipsychotic medications in pregnancy. Live, healthy babies are the most common outcome following the use of antipsychotic medication in pregnancy, but clinicians should be particularly mindful of neonatal problems such as respiratory distress.

Three-dimensional kinetic adaptations of gait throughout pregnancy and postpartum

Biomechanical adaptations that occur during pregnancy can lead to changes on gait pattern. Nevertheless, these adaptations of gait are still not fully understood. The purpose was to determine the effect of pregnancy on the biomechanical pattern of walking, regarding the kinetic parameters. A three-dimensional analysis was performed in eleven participants. The kinetic parameters in the joints of the lower limb during gait were compared at the end of the first, second, and third trimesters of pregnancy and in the postpartum period, in healthy pregnant women. The main results showed a reduction in the normalized vertical reaction forces, throughout pregnancy, particularly the third peak. Pregnant women showed, during most of the stance phase, medial reaction forces as a motor response to promote the body stability. Bilateral changes were observed in hip joint, with a decrease in the participation of the hip extensors and in the eccentric contraction of hip flexors. In ankle joint a decrease in the participation of ankle plantar flexors was found. In conclusion, the overall results point to biomechanical adjustments that showed a decrease of the mechanical load of women throughout pregnancy, with exception for few unilateral changes of hip joint moments.

Three-dimensional kinetic adaptations of gait throughout pregnancy and postpartum

Biomechanical adaptations that occur during pregnancy can lead to changes on gait pattern. Nevertheless, these adaptations of gait are still not fully understood. The purpose was to determine the effect of pregnancy on the biomechanical pattern of walking, regarding the kinetic parameters. A three-dimensional analysis was performed in eleven participants. The kinetic parameters in the joints of the lower limb during gait were compared at the end of the first, second, and third trimesters of pregnancy and in the postpartum period, in healthy pregnant women. The main results showed a reduction in the normalized vertical reaction forces, throughout pregnancy, particularly the third peak. Pregnant women showed, during most of the stance phase, medial reaction forces as a motor response to promote the body stability. Bilateral changes were observed in hip joint, with a decrease in the participation of the hip extensors and in the eccentric contraction of hip flexors. In ankle joint a decrease in the participation of ankle plantar flexors was found. In conclusion, the overall results point to biomechanical adjustments that showed a decrease of the mechanical load of women throughout pregnancy, with exception for few unilateral changes of hip joint moments.

Pregnancy in Spanish elite sportswomen: A qualitative study

Pregnancy and motherhood have been historically considered as reasons why elite sportswomen may end their sport careers. During pregnancy, the safety of both mother and baby has been identified as a key reason for ceasing sport participation. Recent “official” statistics on how many elite athletes are mothers suggest that pregnancy, motherhood, and sport could be no longer mutually exclusive. The aim of this qualitative phenomenological study was to describe the lived pregnancy of Spanish elite sportswomen. Spanish elite sportswomen (n = 20) aged between 18 and 65 years that had been pregnant during their sporting professional career and after the end of their pregnancy had taken up again their professional sporting career for at least one year were included. Data were collected from May 2010 to April 2012 using in-depth personal interviews, investigator’s field notes, and extracts from the participants’ personal letters. Identified themes included: choosing the right moment; fears and doubts; and justifying physical exercise. By giving voice to these elite Spanish sportswomen, their pregnancy experiences are made visible, which might help to gain a better understanding into their expectations and develop policies and practices focused on elite sportswomen during and after pregnancy.

Perinatal maternal depression and cortisol function in pregnancy and the postpartum period : a systematic literature review

BACKGROUND: Perinatal depression has a significant impact on both mother and child. However, the influence of hormonal changes during pregnancy and the postpartum period remains unclear. This article provides a systematic review of studies examining the effects of maternal cortisol function on perinatal depression. METHOD: A systematic search was conducted of six electronic databases for published research on the relationship between cortisol and perinatal depression. The databases included; MEDLINE complete, PsychINFO, SCOPUS, Psychology and Behavioural Sciences, Science Direct and EBSCO, for the years 1960 to May 2015. Risk of bias was assessed and data extraction verified by two investigators. RESULTS: In total, 47 studies met criteria and studies showed considerable variation in terms of methodology including sample size, cortisol assays, cortisol substrates, sampling processes and outcome measures. Those studies identified as higher quality found that the cortisol awakening response is positively associated with momentary mood states but is blunted in cases of major maternal depression. Furthermore, results indicate that hypercortisolemia is linked to transient depressive states while hypocortisolemia is related to chronic postpartum depression. DISCUSSION AND CONCLUSION: Future research should aim to improve the accuracy of cortisol measurement over time, obtain multiple cortisol samples in a day and utilise diagnostic measures of depression. Future studies should also consider both antenatal and postnatal depression and the differential impact of atypical versus melancholic depression on cortisol levels, as this can help to further clarify the relationship between perinatal depression and maternal cortisol function across pregnancy and the postpartum period.

"My midwife said that having a glass of red wine was actually better for the baby": a focus group study of women and their partner's knowledge and experiences relating to alcohol consumption in pregnancy.

BACKGROUND: While it is well established that alcohol can cross the placenta to the foetus and can affect an infant's development, many women continue to drink during pregnancy. For this reason it is important to determine what information is being provided, what information may be missing, and the preferred sources of information on this issue. In order to improve prevention strategies, we sought to understand the knowledge and experiences of pregnant women and their partners regarding the effects of alcohol consumption during pregnancy. METHODS: The current study utilised a qualitative study design in order to gain insight into the views and experiences of pregnant women, newly delivered mothers and their partners. Focus groups examined the participant's knowledge about the effects of alcohol consumption during pregnancy, the sources of information on this issue, and the psycho-social influences on their drinking behaviour. Five focus groups were conducted involving a total of 21 participants (17 female). A six-stage thematic analysis framework was used to analyse all focus group discussions in a systematic way. RESULTS: Seven major themes were identified from the focus group data: 1) knowledge of Foetal Alcohol Spectrum Disorders; 2) message content and sources; 3) healthcare system; 4) society and culture; 5) partner role; 6) evaluation of risk; and 7) motivation. The findings indicated that although the majority of participants knew not to drink alcohol in pregnancy they had limited information on the specific harmful effects. In addition, routine enquiry and the provision of information by health care professionals were seen as lacking. CONCLUSIONS: The findings of this research provide important insights in to the relationship between pregnant women, their partners, and their healthcare providers. Several recommendations can be made on the basis of these findings. Firstly, public health messages and educational materials need to provide clear and consistent information about the effects of alcohol consumption on the developing baby. Additionally, more thorough and consistent routine enquiry for alcohol consumption in pregnant women needs to occur. Finally, it is important to ensure ongoing education for health professionals on the issue of alcohol consumption during pregnancy.

A public health intervention to change knowledge, attitudes and behaviour regarding alcohol consumption in pregnancy

Aim. To evaluate the effectiveness of a public health intervention aimed at changing knowledge, attitudes and behaviour. Methods. A non-blinded parallel group randomised controlled trial of pregnant women over 18 years of age. Women were recruited in the second trimester and assigned to one of two treatment groups. Both groups completed an initial questionnaire assessing knowledge, attitudes, and practices relating to alcohol consumption during pregnancy. The intervention group then received a mocktail recipe booklet and participants were asked to share the information with their partner. The control group received standard antenatal care. A follow-up questionnaire was conducted four weeks post birth. Primary outcome measures were a knowledge score of the health risks associated with alcohol consumption during pregnancy and an attitude score toward drinking during pregnancy. Secondary outcome measures included whether or not the woman and her partner abstained from drinking. Ethical approval was granted by the Women’s and Children’s Health Network and the University of South Australia. Results. A total of 161 participants were recruited at baseline (intervention = 82, control = 79) and 96 participants completed the trial (intervention = 49, control = 47). The findings suggest that the mocktail booklet was effective at improving knowledge (p<0.001; effect size 0.80) and improving attitudes towards drinking during pregnancy (p=0.017; effect size 0.43) in the intervention group compared to the control group. Although women in the intervention group were 30% more likely to abstain from drinking than in the control group (RR=1.3, 95% CI 0.97 – 1.75), this result was not statistically significant (p=0.077). Conclusions. Knowledge regarding the effects of alcohol consumption as well as attitudes towards drinking significantly improved as a result of a mocktail recipe booklet. Improving knowledge and changing attitudes has the potential to change health behaviour. Therefore, this intervention may reduce the percentage of women who continue to drink alcohol while they are pregnant and improve outcomes for infants and children.

The role of inflammation in vascular function and pregnancy outcome in the pregnant stroke prone spontaneously hypertensive rat

During pregnancy, the maternal cardiovascular system undergoes major adaptation. One of these changes is a 40-50 % increase in circulating blood volume which requires a systemic remodelling of the vasculature in order to regulate maternal blood pressure and maximise blood supply to the developing placenta and fetus. These changes are broadly conserved between humans and rats making them an appropriate pre-clinical model in which to study the underlying mechanisms of pregnancy-dependent cardiovascular remodelling. Whilst women are normally protected against cardiovascular disease; pregnancy marks a period of time where women are susceptible to cardiovascular complications. Cardiovascular disease is the leading cause of maternal mortality in the United Kingdom; in particular hypertensive conditions are among the most common complications of pregnancy. One of the main underlying pathologies of these pregnancy complications is thought to be a failure of the maternal cardiovascular system to adapt. The remodelling of the uterine arteries, which directly supply the maternal-fetal interface, is paramount to a healthy pregnancy. Failure of the uterine arteries to remodel sufficiently can result in a number of obstetric complications such as preeclampsia, fetal growth restriction and spontaneous pregnancy loss. At present, it is poorly understood whether this deficient vascular response is due to a predisposition from existing maternal cardiovascular risk factors, the physiological changes that occur during pregnancy or a combination of both. Previous work in our group employed the stroke prone spontaneously hypertensive rat (SHRSP) as a model to investigate pregnancy-dependent remodelling of the uterine arteries. The SHRSP develops hypertension from 6 weeks of age and can be contrasted with the control strain, the Wistar Kyoto (WKY) rat. The phenotype of the SHRSP is therefore reflective of the clinical situation of maternal chronic hypertension during pregnancy. We showed that the SHRSP exhibited a deficient uterine artery remodelling response with respect to both structure and function accompanied by a reduction in litter size relative to the WKY at gestational day (GD) 18. A previous intervention study using nifedipine in the SHRSP achieved successful blood pressure reduction from 6 weeks of age and throughout pregnancy; however uterine artery remodelling and litter size at GD18 was not improved. We concluded that the abnormal uterine artery remodelling present in the SHRSP was independent of chronic hypertension. From these findings, we hypothesised that the SHRSP could be a novel model of spontaneously deficient uterine artery remodelling in response to pregnancy which was underpinned by other as yet unidentified cardiovascular risk factors. In Chapter 1 of this thesis, I have characterised the maternal, placental and fetal phenotype in pregnant (GD18) SHRSP and WKY. The pregnant SHRSP exhibit features of left ventricular hypertrophy in response to pregnancy and altered expression of maternal plasma biomarkers which have been previously associated with hypertension in human pregnancy. I developed a protocol for accurate dissection of the rat uteroplacental unit using qPCR probes specific for each layer. This allowed me to make an accurate and specific statement about gene expression in the SHRSP GD18 placenta; where oxidative stress related gene markers were increased in the vascular compartments. The majority of SHRSP placenta presented at GD18 with a blackened ring which encircled the tissue. Further investigation of the placenta using western blot for caspase 3 cleavage determined that this was likely due to increased cell death in the SHRSP placenta. The SHRSP also presented with a loss of one particular placental cell type at GD18: the glycogen cells. These cells could have been the target of cell death in the SHRSP placenta or were utilised early in pregnancy as a source of energy due to the deficient uterine artery blood supply. Blastocyst implantation was not altered but resorption rate was increased between SHRSP and WKY; indicating that the reduction in litter size in the SHRSP was primarily due to late (>GD14) pregnancy loss. Fetal growth was not restricted in SHRSP which led to the conclusion that SHRSP sacrifice part of their litter to deliver a smaller number of healthier pups. Activation of the immune system is a common pathway that has been implicated in the development of both hypertension and adverse pregnancy outcome. In Chapter 2, I proposed that this may be a mechanism of interest in SHRSP pregnancy and measured the pro-inflammatory cytokine, TNFα, as a marker of inflammation in pregnant SHRSP and WKY and in the placentas from these animals. TNFα was up-regulated in maternal plasma and urine from the GD18 SHRSP. In addition, TNFα release was increased from the GD18 SHRSP placenta as was the expression of the pro-inflammatory TNFα receptor 1 (Tnfr1). In order to investigate whether this excess TNFα was detrimental to SHRSP pregnancy, a vehicle-controlled intervention study using etanercept (a monoclonal antibody which works as a TNFα antagonist) was carried out. Etanercept treatment at GD0, 6, 12 and 18 resulted in an improvement in pregnancy outcome in the SHRSP with an increased litter size and reduced resorption rate. Furthermore, there was an improved uterine artery function in GD18 SHRSP treated with etanercept which was associated with an improved uterine artery blood flow over the course of gestation. In Chapter 3, I sought to identify the source of this detrimental excess of TNFα by designing a panel for maternal leukocytes in the blood and placenta at GD18. A population of CD3- CD161+ cells, which are defined as rat natural killer (NK) cells, were increased in number in the SHRSP. Intracellular flow cytometry also identified this cell type as a source of excess TNFα in blood and placenta from pregnant SHRSP. I then went on to evaluate the effects of etanercept treatment on these CD3- CD161+ cells and showed that etanercept reduced the expression of CD161 and the cytotoxic molecule, granzyme B, in the NK cells. Thus, etanercept limits the cytotoxicity and potential damaging effect of these NK cells in the SHRSP placenta. Analysing the urinary peptidome has clinical potential to identify novel pathways involved with disease and/or to develop biomarker panels to aid and stratify diagnosis. In Chapter 4, I utilised the SHRSP as a pre-clinical model to identify novel urinary peptides associated with hypertensive pregnancy. Firstly, a characterisation study was carried out in the kidney of the WKY and SHRSP. Urine samples from WKY and SHRSP taken at pre-pregnancy, mid-pregnancy (GD12) and late pregnancy (GD18) were used in the peptidomic screen. In order to capture peptides which were markers of hypertensive pregnancy from the urinary peptidomic data, I focussed on those that were only changed in a strain dependent manner at GD12 and 18 and not pre-pregnancy. Peptide fragments from the uromodulin protein were identified from this analysis to be increased in pregnant SHRSP relative to pregnant WKY. This increase in uromodulin was validated at the SHRSP kidney level using qPCR. Uromodulin has previously been identified to be a candidate molecule involved in systemic arterial hypertension but not in hypertensive pregnancy thus is a promising target for further study. In summary, we have characterised the SHRSP as the first model of maternal chronic hypertension during pregnancy and identified that inflammation mediated by TNFα and NK cells plays a key role in the pathology. The evidence presented in this thesis establishes the SHRSP as a pre-clinical model for pregnancy research and can be continued into clinical studies in pregnant women with chronic hypertension which remains an area of unmet research need.

Intimate partner violence in pregnancy: planning and pregnancy monitoring

The intimate partner violence (IPV) in pregnancy results in risk factors with an impact on maternal and fetal health. There is a tendency to unwanted pregnancies, unplanned and poor adherence to health services, increasing the risk of complications during pregnancy. The aim is describe the prevalence rates of IPV during pregnancy in the Central Region of Portugal and analyse their association with pregnancy planning and frequency of prenatal consultations. There was prevalence of IPV during pregnancy with a significant association to pregnancy planning. Although most women have attended prenatal consultations in the last pregnancy, the late start is associated with the probability of frequency of some type of IPV.

Intimate partner violence in pregnancy: Communicate better to unveil the problem.

The intimate partner violence (IPV) is defined as any behavior within an intimate relationship that causes physical, psychological or sexual damage to members of relationship (Organización Panamericana de la Salud, Oficina Regional para las Américas de la Organización Mundial de la Salud 2003). Exposure to the IPV during pregnancy leads to a number of risk factors with significant impact on the physical, mental and social well-being of women, as well in perinatal outcomes. The prevalence rates, existing throughout the world, have demonstrated the importance of further enhance the attention given to the woman / couple / family, from prenatal care to the postpartum. (World Health Organization, WHO Collaborating Centre for Violence Prevention 2010), challenges the health professionals to monitor the phenomenon of IPV and compare national and international indicators in order to adjust and qualify interventions. This requires awareness of health professionals in the early identification of these indicators using appropriate communication strategies and safe environments.

Intimate partner violence in pregnancy: planning and pregnancy monitoring.

The aim is describe the prevalence rates of IPV during pregnancy in the Central Region of Portugal and analyse their association with pregnancy planning and frequency of prenatal consultations.

Intimate partner violence in pregnancy: Communicate better to unveil the problema.

Describe the prevalence of IPV during pregnancy in the Central Region of Portugal. Reflect on the need to improve the effectiveness of communication between nurse or midwife and pregnant woman or couple, for easier identification of violence exposure during pregnancy.

Determinants of infant and young child feeding practices in Sri Lanka : secondary data analysis of demographic and health survey 2000

Background: Poor feeding practices in early childhood contribute to the burden of childhood malnutrition and morbidity. Objective: To estimate the key indicators of breastfeeding and complementary feeding and the determinants of selected feeding practices in Sri Lanka. Methods: The sample consisted of 1,127 children aged 0 to 23 months from the Sri Lanka Demographic and Health Survey 2000. The key infant feeding indicators were estimated and selected indicators were examined against a set of individual-, household-, and community- level variables using univariate and multivariate analyses. Results: Breastfeeding was initiated within the first hour after birth in 56.3% of infants, 99.7% had ever been breastfed, 85.0% were currently being breastfed, and 27.2% were being bottle-fed. Of infants under 6 months of age, 60.6% were fully breastfed, and of those aged 6 to 9 months, 93.4% received complementary foods. The likelihood of not initiating breastfeeding within the first hour after birth was higher for mothers who underwent cesarean delivery (OR = 3.23) and those who were not visited by a Public Health Midwife at home during pregnancy (OR = 1.81). The rate of full breastfeeding was significantly lower among mothers who did not receive postnatal home visits by a Public Health Midwife. Bottlefeeding rates were higher among infants whose mothers had ever been employed (OR = 1.86), lived in a metropolitan area (OR = 3.99), or lived in the South-Central Hill country (OR = 3.11) and were lower among infants of mothers with secondary education (OR = 0.27). Infants from the urban (OR = 8.06) and tea estate (OR = 12.63) sectors were less likely to receive timely complementary feeding than rural infants. Conclusions: Antenatal and postnatal contacts with Public Health Midwives were associated with improved breastfeeding practices. Breastfeeding promotion strategies should specifically focus on the estate and urban or metropolitan communities.

Maternal exposure to ambient temperature and the risk of preterm birth and stillbirth in Brisbane, Australia

Almost 10% of all births are preterm and 2.2% are stillbirths globally. Recent research has suggested that environmental factors may be a contributory cause to these adverse birth outcomes. The authors examined the relationship between ambient temperature and preterm birth and stillbirth in Brisbane, Australia between 2005 and 2009 (n = 101,870). They used a Cox proportional hazard model with live birth and stillbirth as competing risks. They also examined if there were periods of the pregnancy where exposure to high temperatures had a greater effect. Exposure to higher ambient temperatures during pregnancy increased the risk of stillbirth. The hazard ratio for stillbirth was 0.3 at 12 °C relative to the reference temperature at 21 °C. The temperature effect was greatest for fetuses of less than 36 weeks of gestation. There was an association between higher temperature and shorter gestation, as the hazard ratio for live birth was 0.96 at 15 °C and 1.02 at 25 °C. This effect was greatest at later gestational ages. The results provide strong evidence of an association between increased temperature and increased risk of stillbirth and shorter gestations.

The factor V HR2 haplotype: Prevalence and association of the A4070G and A6755G polymorphisms

Recently, a polymorphism was identified in exon 25 of the factor V gene that is possibly a functional candidate for the HR2 haplotype. This haplotype is characterized by a single base substitution named R2 (A4070G) in the B domain of the protein. A mutation (A6755G; 2194Asp→Gly) located near the C terminus has been hypothesized to influence protein folding and glycosylation, and might be responsible for the shift in factor V isoform (FV1 / FV2) ratio. This study investigated the prevalence of these two factor V HR2 haplotype polymorphisms in a cohort of normal blood donors, patients with osteoarthritis and women with complications during pregnancy, and in families of factor V Leiden individuals. A high allele frequency for the two polymorphisms was found in the blood donor group (6.2% R2, 5.6% A6755G). No significant difference in allele frequency was observed in the clinical groups (obstetric complications and osteoarthritis, 4.1-4.9% for the two polymorphisms) when compared with that of healthy blood donors. We confirm that the factor V A6755G polymorphism shows strong linkage to the R2 allele, although it is not exclusively inherited with the exon 13 A4070G variant and can occur independently. © 2001 Lippincott Williams & Wilkins.