Depression occurs in approximately 20% of pregnant women, and up to 25% of them experience anxiety. Several pregnancy complications and labour and delivery outcomes have been associated with antenatal depression and anxiety, such as higher rates of nausea and vomiting, bleeding, psychosomatic complaints, preterm labour and delivery complications. Neonatal outcomes include lower Apgar scores, shorter gestation, smaller head circumference, and increased admissions to the neonatal intensive care unit. Research Questions: 1. To examine the prevalence of pregnancy complications and neonatal outcomes in this study sample. 2. To examine whether there is a difference in the association between observed pregnancy complications and neonatal outcomes and major depression, when depression is episodic compared to when the depression is continuous. 3. To examine whether there is a difference in the association between observed pregnancy complications and neonatal outcomes and mild depression, when the mild depression is episodic compared to when it is continuous. 4. To examine whether there is a difference in the association between observed pregnancy complications and neonatal outcomes and anxiety, when anxiety is episodic compared to when it is continuous. Methods: The data for this study was collected for the Feelings in Pregnancy and Motherhood Study (FIP). This population-based study interviewed 649 participants three times: in the second trimester, the third trimester, and in the early postpartum. Participants were screened for depression and anxiety with the Edinburgh Postnatal Depression Scale (EPDS), using the validated cut-off scores of >12 and >4 respectively. Sociodemographic data as well as detailed risk behaviours, and sources of stress and coping, were explored. Finally, pregnancy, labour and delivery and neonatal complications were collected. Descriptive and multivariate logistic regression analyses were completed. Results: Major depression in the second trimester was significantly associated with gestational diabetes (OR: 3.518; 95% CI 1.56, 7.93) and swelling/edema (OR: 2.099; 95% CI 1.13, 3.89). Major depression that occurred continuously throughout pregnancy was significantly associated with induced labour (2.417; 95% CI 0.99, 5.92) and antenatal bleeding/abruption (OR: 2.099; 95% CI 1.13, 3.89). Anxiety in the second trimester was significantly associated with caesarean birth (OR: 0.522; 95% CI 0.29, 0.95). Anxiety occurring continuously throughout pregnancy was significantly associated with swelling/edema (OR: 1.816; 95% CI 1.19, 2.77) and there was a significant interaction between age and anxiety that predicted epidural use during pregnancy: while age decreased in the participants who had anxiety in both trimesters, the likelihood of using an epidural increased. Finally, mild depression in the second trimester was significantly associated with antenatal bleeding/abruption (OR: 2.124; 95% CI 1.09, 4.14) and PROM (OR: 2.504; 95% CI 1.04, 6.05). Mild depression in the third trimester was associated with caesarean birth (OR: 0.298; 95% CI 0.10, 0.86). Mild depression that occurred continuously throughout pregnancy was significantly associated with the use of vacuum/forceps in delivery or an operative delivery (OR: 4.820; 95% CI 1.10, 21.16). Conclusions: These results show that episodic depression and anxiety can have a more profound impact on pregnancy complications and labour and delivery outcomes than continuous depression and anxiety. Furthermore, the results demonstrate that even mild depression can have a significant negative impact on pregnancy complications and labour and delivery outcomes. These results further highlight the imperative need for women to be screened and treated for depression and anxiety during pregnancy.

The discovery of the Aschheim Zondek test for pregnancy resulted in a large amount of research work which had been performed in the investigation of the hormones concerned in the physiology of the female reproductive system. This work has been carried out by an almost countless number of investigators, in all parts of the the world. I shall make no attempt to view the literature on this subject since it has alreacy been done in the monographs by Parkes and Frank, and moreover it would serve no useful purpose in a thesis of this kind. It is my intention to merely point out the chief evenats which led up to the foundation of the Aschheim Zondek reaction as a test for pregnancy.

Daily changes in body temperature as well as physical activeness from mating to pregnancy were illustrated in MF1 mice.  Body temperature and physical activity gradually declined as pregnancy advanced while energy intake and body mass increased in late pregnancy.  Diurnal and nocturnal locomotor activity and body temperature were significantly lower in late pregnancy than in non-reproductive and mating phases. Despite low physical activity, inactive body temperature was relatively high through late pregnancy.  This suggests that pregnant mice tend to increase thermogenesis against a drop of body temperature. Energy intake increased remarkably after parturition and reached a plateau in late lactation suggesting a limit of energy intake.  Litter size and litter mass significantly influenced maternal energy intake and body mass (<i>P</i>&lt;0.05). However, daily pup mass gain declined at the peak lactation when maternal energy intake was limited.  Body temperature rose sharply after parturition.  Body temperature during the day considerably increased.  Consequently, lactating mice faced a constantly high body temperature through the day despite lower activity levels. There were no trends that litter size and litter mass stimulated maternal body temperature and physical activity on average through lactation. Body temperature during suckling inside the nest increased towards the end of suckling.  However, no significant increase in body temperature was found between 20 and 1 minutes before terminating suckling bouts. Dams that raised larger litters encountered higher body temperature while suckling inside the nest, suggesting that suckling offspring considerably contributed to heat retention in mothers.  Suckling offspring appeared to prevent mothers from releasing cumulative heat, although the significance of suckling behaviour on overheating was smaller than that of metabolic heat generation.

This thesis investigates possible mechanisms underlying the decreased kidney size and the development of high blood pressure in the offspring of our model of maternal iron deficiency. This study has demonstrated that a maternal iron deficient diet has no effect on gene expression of either markers of vasculogenesis/angiogenesis or regulators of apoptosis and cell proliferation in the kidneys of the offspring. The effect of maternal iron deficiency on well documented mechanisms involved in blood pressure regulation were investigated in the offspring. The data showed that neither renal sodium transport nor nephron number are involved in hypertension development in our model of maternal iron deficiency. The renin angiotensin system showed significant increase in the renal renin mRNA expression, and pulmonary ACE1 mRNA and activity levels in newborn offspring of iron deficient mothers.  These changes are unique for maternal iron deficiency as they have not been seen in the other models of nutritional programming.  However, they are also temporary and disappear by two weeks after birth and at this stage it is unknown if and how the renin angiotensin system contributes to hypertension development in the offspring of iron deficient mothers. Finally, the whole rat genome arrays were used to identify new genes and pathways affected by maternal iron deficiency in fetal kidneys.  The results of the microarray experiment suggested renal inflammation and increased collagen cross-linking leading to stiffening of vascular walls, as possible causes of hypertension in the offspring of iron deficient mothers.  Further analysis showed, however, that both mechanisms do not appear to be involved.  The microarray study also identified CD36 scavenger receptor as being significantly up-regulated in the kidneys of the fetuses of iron deficient mothers, but its expression significantly decreased in adult animals compared to controls. The data presented in this thesis indicate that the effect of an iron deficient diet on offspring blood pressure is multifactorial and complex.

The impact of a termination on subsequent pregnancy outcomes has been widely studied. It has been suggested that women who terminate a pregnancy are more likely to have an adverse outcome of a subsequent pregnancy, either miscarriage, or a preterm or low birthweight baby. However, the evidence to date is inconclusive and in some cases contradictory. Hypothesis: It is hypothesised that those who had terminated their first pregnancy are more likely to have an adverse outcome of a subsequent pregnancy, (either miscarriage, preterm delivery (<37 weeks), or low birthweight ((<2500g) as a proxy for gestation). They are also more likely to have shorter gestation at miscarriage, and the gestation at miscarriage is associated with method of termination. Also, women are more likely to show a dose-response in three-pregnancy series, with increasing numbers of consecutive terminations associated with increasingly poorer outcomes. Data and Methodology: Setting and Sample: Aberdeen maternity hospital (AMH) is the level III consultant-led maternity unit for NHS North of Scotland Region. It provides care for pregnant women both with and without complications and for sick neonates. The data were extracted from the Aberdeen Maternity and Neonatal Databank (AMND), with the sample restricted to Aberdeen city women in 1970-1999, and only singleton pregnancy events were included. Outcomes The study group was Termination-Birth (TB) and this group was compared to three comparison pregnancy history groups, Miscarriage-Birth (MB), Birth-Birth (BB) and Birth (B). The outcomes are preterm and low birthweight deliveries and the sub-categories of preterm and low birthweight. In addition, miscarriage on the index event is also considered as an outcome. Methods: The distributions of gestation and birthweight were examined between and within study groups for outcomes of preterm and low birthweight deliveries, and logistic and multinomial regression was used to assess the impact of selected potentially confounding socio-demographic and pregnancy related characteristics on the odds of delivering at different levels of preterm and low birthweight by pregnancy history. The gestation at miscarriage of the index subsequent event is also examined between study groups, as is the method of termination for women whose first pregnancy was terminated. In addition, two and three pregnancy sequences are examined to determine if there was a ‘dose-response’ effect of termination of pregnancy. Results: For women from group TB, the overall difference in average adjusted gestation at delivery is approximately 1 day less for women from group TB compared to women from group MB, and only 2 days from women with only a history of births, these results could be considered clinically insignificant. This thesis has shown that compared with women with a previous birth, and after adjusting for possible confounding factors, births after a previous termination were consistently more likely to result in a preterm delivery. Women who terminated a first pregnancy have an increased likelihood of preterm delivery from a public health perspective, with an overall 40% increase in risk for preterm birth for women from group TB when compared to women from group B (OR 1.35 95%CI 1.15, 1.58). These increased odds of preterm delivery for group TB are very similar to those for women from group MB (OR 1.45, 95%CI 1.18, 1.79). Similarly, after adjustment for potential confounding factors, women from group TB were consistently more likely to deliver a low birthweight baby, when compared to women with from group B, (OR 1.18 95%CI 1.00, 1.38). Women from group MB were also significantly more likely to deliver a low birthweight baby after adjustment for possible confounding factors (OR 1.42 95%CI 1.16, 1.72). Few if any of the explanatory variables are directly modifiable, and the PAF associated with women from group TB is relatively small, when compared to other significant potential risk factors. Women who terminated a first pregnancy were significantly more likely, after adjustment for socio-demographic characteristics to miscarry late (OR 1.74, 95%CI 1.07, 2.84), but there was no difference between medical and surgical terminations. Finally, there was no evidence of a dose response of termination for either preterm or low birthweight deliveries, although there was marked evidence of a dose response of miscarriage. Conclusions The results from a clinical and public health point of view may appear to be contradictory, in that there is an approximate 40% increase in relative risk for preterm delivery, but only an adjusted absolute difference of two days lower gestation at birth for women from group TB. PAF findings indicate only a small overall reduction in the number of preterm deliveries if the exposure to the risk factor of a previous termination was eliminated. Women who undergo a termination should therefore receive full information on factors which might have an influence on the outcome of a subsequent pregnancy, and in addition medical information given to the women should cover details about the termination process, including methods of termination, possible complications, post termination follow up and future contraception.

Class of 2010 Abstract / OBJECTIVES: The purpose of the study was to determine the knowledge of third year pharmacy students about the safety of certain medications during pregnancy and to assess their awareness of an important resource available on medication safety. METHODS: The study used an analytical cross-­‐sectional design. A pre-­‐test was administered to determine baseline knowledge. Dee Quinn provided a presentation on teratogens. The same test was then administered as a post-­‐test to assess the amount of knowledge gained from the presentation. The pre and post-­‐tests were matched for data analysis. A mean and standard deviation were developed for pre and post-­‐test data and the results were compared to each other using a t-­‐test for dependent groups. RESULTS: Students showed a significant increase in knowledge after the presentation (p<0.0001). 78% of students had improved scores after the presentation. 100% of students felt that pharmacists could help make a difference in preventing malformations due to teratogen exposure. There was no significant difference between men and women or students with children and without children. Work experience did not affect knowledge scores. 64% of students felt more comfortable counseling pregnant patients after the presentation. Awareness of the Teratology Information Service improved after the presentation. CONCLUSIONS: After the presentation, students rated themselves as more comfortable speaking with pregnant patients and showed improved knowledge of teratogens. Gender, being a parent and work experience had no relevance on knowledge scores. The investigators recommend that this presentation be given to all students at the College of Pharmacy to improve knowledge in this area.

Class of 2009 Abstract / OBJECTIVES: The objectives of this study were 1) to review the University of Arizona College of Pharmacy’s curriculum to assess if courses cover pertinent topics in the use of prescription and over-the-counter (OTC) medications by pregnant and lactating women based on The American Association of Colleges of Pharmacy (AACP) Gender and Sex-Related Health Care Pharmacy Curriculum Guide and 2) to assess pharmacy students’ knowledge and abilities to counsel women during pregnancy and breastfeeding. METHODS: The curriculum review was a retrospective, descriptive analysis to assess how well the required curriculum addressed eight pertinent topics in the use of prescription and OTC medications by pregnant and lactating women. The self-assessment questionnaire was a cross-sectional, descriptive analysis that measured student pharmacists’ comfort level with counseling pregnant and lactating women, their perception of how well pharmacy school has prepared them for this role, and their familiarity with and use of available resources. RESULTS: The College of Pharmacy was not in compliance with AACP’s Pharmacy Curriculum Guide. This was reinforced by the questionnaire, which showed that the majority of students, regardless of year in school, did not feel they had been adequately prepared to counsel or to make recommendations to this population. CONCLUSIONS: It is recommended that the curriculum be amended by adding a lecture on teratogenicity. A list of gender and sex- related topics should be provided as well as a handout with available resources. In addition, case studies in each course should be revised to include critical decision-making, recommendations, and counseling if the patient were pregnant or breastfeeding.

Findings are presented from matched case-control studies of risk factors for diabetes, cryptorchidism and inguinal hernia in children using routine data collected by the Oxford Record Linkage Study since 1965. There were 315 cases born 1965-85 in the diabetes study, 947 and 1449 cases in studies of cryptorchidism diagnosed at birth and at orchidopexy respectively, and 1701 male and 347 female cases in the study of inguinal hernia. Each case was individually matched with up to eight controls on sex, year, and hospital or place of birth. A potential bias caused by differential migration of cases and controls was identified. A sample of 753 controls born in Oxfordshire was checked against the Oxfordshire Family Health Services Authority register to determine migration out of the study area in relation to perinatal risk factors. A general procedure was developed to estimate the strength of the migration bias. Pre-eclampsia was identified as a significant pre-natal risk factor for diabetes. The studies of cryptorchidism identified significantly raised risks with low birth weight, low social class and breech presentation. The results suggested that asymmetric growth retardation in the third trimester may be involved in the aetiology of undescended testes that do not spontaneously descend in later life. Analysis of risk factors among siblings of cases and controls suggested that permanent changes to the mother may occur around the time of the pregnancy involving the affected child. Low birth weight, short gestation and smoking during pregnancy were associated with significantly raised risks of inguinal hernia among boys. Among girls the results were similar, suggesting that mechanisms independent of the sex of the child may be important in the aetiology of this condition. Estimates of disease risk in siblings showed a strong familial aggregation, especially among girls.

Background Preterm birth is a leading cause of perinatal morbidity and mortality worldwide, resulting in a pressing need to identify risk factors leading to effective interventions. Limited evidence suggests potential relationships between maternal sleep or vital exhaustion and preterm birth, yet the literature is generally inconclusive. Methods We examined the relationship between maternal sleep duration and vital exhaustion in the first six months of pregnancy and spontaneous (non-medically indicated) preterm birth among 479 Peruvian women who delivered a preterm singleton infant (<37 weeks gestation) and 480 term controls who delivered a singleton infant at term (≥37 weeks gestation). Maternal nightly sleep and reports of vital exhaustion were ascertained through in-person interviews. Spontaneous preterm birth cases were further categorized as those following either spontaneous preterm labor or preterm premature rupture of membranes. In addition, cases were categorized as very (<32 weeks), moderate (32–33 weeks), and late (34- <37 weeks) preterm birth for additional analyses. Logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results After adjusting for confounders, we found that short sleep duration (≤6 hours) was significantly associated with preterm birth (aOR = 1.56; 95% CI 1.11-2.19) compared to 7–8 hours of sleep. Vital exhaustion was also associated with increased odds of preterm birth (aOR = 2.41; 95% CI 1.79-3.23) compared to no exhaustion (Ptrend <0.001). These associations remained significant for spontaneous preterm labor and preterm premature rupture of membranes. We also found evidence of joint effects of sleep duration and vital exhaustion on the odds of spontaneous preterm birth. Conclusions The results of this case–control study suggest maternal sleep duration, particularly short sleep duration, and vital exhaustion may be risk factors for spontaneous preterm birth. These findings call for increased clinical attention to maternal sleep and the study of potential intervention strategies to improve sleep in early pregnancy with the aim of decreasing risk of preterm birth.

Eclampsia is defined as de novo seizure in a woman with the hypertensive complication of pregnancy known as preeclampsia (PE), and is a leading cause of maternal and fetal morbidity and mortality worldwide. The pathogenesis of eclamptic seizure remains unknown, but is considered a form of hypertensive encephalopathy where an acute rise in blood pressure causes loss of cerebral blood flow (CBF) autoregulation and hyperperfusion of the brain that results in vasogenic edema formation and subsequent seizure. However, eclamptic seizure can occur during seemingly uncomplicated pregnancies, in the absence of hypertension and PE, suggesting that normal pregnancy may predispose the brain to hypertensive encephalopathy or seizure, independently of PE. The overall goal of this dissertation was to investigate the effect of pregnancy and PE on the cerebrovasculature and neurophysiological properties that may promote brain injury and eclamptic seizure. For this dissertation project, a rat model of PE was established that combined placental ischemia, induced by restricting blood flow to the uteroplacental unit, and maternal endothelial dysfunction that was induced by a prolonged high cholesterol diet. Rats with PE developed several PE-like symptoms, including elevated blood pressure, fetal growth restriction, placental dysfunction, and were in a state of oxidative stress and endothelial dysfunction. We found that pregnancy had an overall protective effect on the maintenance of CBF that was potentially due to a nitric-oxide dependent enhancement of the vasodilation of cerebral arteries to decreased intravascular pressure. Further, maintenance of CBF during acute hypertension was similar in pregnancy and PE. Thus, it does not appear that pregnancy and PE are states during which CBF autoregulation is compromised in a manner that would promote the development of hypertensive encephalopathy. However, the brain was found to be in a hyperexcitable state during normal pregnancy that was augmented in PE, and could contribute to onset of eclamptic seizure. Under chloral hydrate anesthesia, generalized seizure was induced by timed infusion of the convulsant pentylenetetrazole (PTZ), with simultaneous electroencephalography that was stopped at the first onset of spikewave discharge indicative of electrical seizure. Seizure threshold was determined as the amount of PTZ required to elicit seizure. Compared to the nonpregnant state, seizure threshold was ~44% lower in pregnant rats and ~80% lower in rats with PE. Further, pregnant rats were more susceptible to seizure-induced vasogenic edema formation than the nonpregnant state. Mechanisms by which pregnancy and PE lowered seizure threshold appeared to be through pregnancy-associated decreases in cortical gamma-aminobutyric acid type A receptor (GABAAR) subunits and PE-induced disruption of the blood-brain barrier (BBB) and microglial activation, indicative of neuroinflammation. Magnesium sulfate (MgSO4), the leading treatment for seizure prophylaxis in women with PE, restored seizure threshold to control levels by reversing neuroinflammation in PE rats, without affecting BBB permeability. Overall, this dissertation provides evidence that pregnancy increases susceptibility of the brain to seizure and vasogenic edema formation that likely contribute to the onset of eclampsia during seemingly uncomplicated pregnancies. Further, the pathogenesis of eclampsia during PE likely involves breakdown of the BBB and subsequent neuroinflammation, resulting in a state of greater seizure susceptibility that is ameliorated by MgSO4 treatment.