A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master of Science in Epidemiology & Biostatistics. Johannesburg, February 2015 / Background Anaemia in pregnancy is a major public health and economic problem worldwide, that contributes to both maternal and fetal morbidity and mortality. Clinical manifestations of anaemia in pregnancy include fetal growth restriction, preterm delivery, low birth weight, impaired lactation, poor maternal/infant behavioural interactions and post partum depression. Objective The aim of the study was to calculate the prevalence of anaemia in early pregnancy in a cohort of ‘low risk’ women participating in a large international multicentre prospective study (n = 5 609), to identify the modifiable risk factors for anaemia in pregnancy in this cohort, and to compare the birth outcomes between pregnancies with and without anaemia in early gestation. Methods The study is an analysis of data that were collected prospectively during the Screening for Pregnancy Endpoints (SCOPE) study. Anaemia was defined according to the World Health Organization’s definition of anaemia in pregnancy (haemoglobin < 11g/dL). Binary logistic regression with adjustment for potential confounders (country, maternal age, having a marital partner, ethnic origin, years of schooling, and having paid work) was the main method of analysis. Results The hallmark findings were the low prevalence of anaemia (2.2%), that having no marital partner was an independent risk factor for having anaemia (OR 1.34, 95% CI 1.01-1.78), and that there was no statistically significant effect of anaemia on adverse pregnancy outcomes (small for gestational age, pre-tem birth, mode of delivery, low birth weight, APGAR score < 7 at one and five minutes). Adverse pregnancy outcomes were however more common in those with anaemia than in those without. Conclusion The absence of a marital partner is an important non-modifiable factor that should be added to the conceptual framework of anaemia’s determinants. Although not statistically significant, clinically, a trend towards a higher risk of adverse pregnancy outcomes was observed in women that were anaemic in early pregnancy.

Preeclampsia (PE) is a major cause of perinatal and maternal morbidity and mortality. In the United Kingdom, the National Institute for Clinical Excellence (NICE) has issued guidelines on routine antenatal care recommending that at the booking visit a woman’s level of risk for PE should be determined and the subsequent intensity of antenatal care should be based on this risk assessment. This method relies on a risk scoring system derived from maternal characteristics and medical history; the performance of screening by this method is poor with detection of less than 50% of cases of preterm-PE and term-PE. The objective of this thesis is to develop a method for the estimation of the patient-specific risk for PE by combining the a priori risk based on maternal characteristics and medical history with the results of biophysical and biochemical markers obtained at 11-13 weeks’ gestation. Such early identification of high-risk pregnancies could lead to the use of pharmacological interventions, such as low-dose aspirin, which could prevent the development of the disease. The data for the thesis were derived from two types of studies: First, prospective screening in 65,771 singleton pregnancies, which provided data for maternal factors and serum pregnancy associated plasma protein-A (PAPP-A). In an unselected sequential process we also measured uterine artery pulsatility index (PI) in 45,885 of these pregnancies, mean arterial pressure (MAP) in 35,215 cases and placental growth factor (PLGF) in 14,252 cases. Second, cases-control studies for evaluating the ten most promising biochemical markers identified from search of the literature; for these studies we used stored serum or plasma samples obtained during screening and measured PLGF, Activin-A, Inhibin-A, placental protein-13 (PP13), P-selectin, Pentraxin-3 (PTX-3), soluble Endoglin (sEng), Plasminogen activator inhibitor-2 (PAI-2), Angiopoietin-2 (Ang-2) and soluble fms-like tyrosine kinase-1 (s-Flt-1). A competing risk model was developed which is based on Bayes theorem and combines the prior risk from maternal factors with the distribution of biomarkers to derive patient-specific risk for PE at different stages in pregnancy. The prior risk was derived by multiple regression analysis of maternal factors in the screening study. The distribution of biophysical and biochemical markers was derived from both the screening study and the case-control studies. The prior risk increased with advancing maternal age, increasing weight, was higher in women of Afro-Caribbean and South-Asian racial origin, those with a previous pregnancy with PE, conception by in vitro fertilization and medical history of chronic hypertension, type 1 diabetes mellitus and systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APS). The estimated detection rate (DR) of PE requiring delivery at < 34, < 37 weeks’ gestation and all PE, at false positive rate (FPR) of 10%, in screening by maternal factors were 51, 43 and 40%, respectively. The addition of biochemical markers to maternal factors, including maternal serum PLGF and PAPPA, improved the performance of screening with respective DRs of 74, 56 and 41%. Similarly, addition of biophysical markers to maternal factors, including uterine artery PI and MAP, improved the performance of screening with respective DRs of 90, 72 and 57%. The combination of maternal factors with all the above biophysical and biochemical markers improved the respective DRs to 96, 77 and 54%. The findings of these studies demonstrate that a combination of maternal factors, biophysical and biochemical markers can effectively identify women at high-risk of developing PE.

This study examines the impact of successive versus non-successive scheduling of mathematics courses on the achievement of ninth-grade students in a suburban Oregon high school. The Oregon Assessment of Knowledge and Skills and student performance on the geometry course final exam were employed to compare the achievement of intact groups of students who had geometry scheduled for two successive trimesters and students who had geometry in two non-successive trimesters. An ANCOVA provides a comparison of students on pre-test and post-test performance. The results show no differences in student mathematics achievement as a result of scheduling differences after the covariate pre-test is examined. The implications are that schools may choose schedules for reasons other than improving student achievement and that scheduling does not impact student achievement.

published_or_final_version / abstract / Obstetrics and Gynaecology / Doctoral / Doctor of Philosophy

Regulation of the growth and differentiation of trophoblast cells is critical for successful embryo implantation and placentation. Cytokines are key players in these processes, as well as modulating the maternal immune response to prevent rejection of the conceptus. This thesis focused on the investigation of the cytokine interleukin (IL) - 33 and its receptor, ST2. ST2 has two isoforms, a functional cell surface receptor (ST2L) and a soluble decoy receptor (sST2). Previous work in this laboratory had shown that the human placenta expresses both IL-33 and sST2 at term. The aim of this thesis was to investigate IL-33 and ST2 in early pregnancy, the time when trophoblast is at its most active, with a view to better understanding their role. IL-33 and ST2 mRNA and protein were examined in 14 first trimester placentas from 6-12 weeks of gestation. IL-33 was localized to cells in the villous stroma, whereas ST2 was present in the syncytiotrophoblast, villous cytotrophoblast and the invasive extravillous cytotrophoblast of the cell columns. Secretion of sST2, but not IL-33, by the placenta was found. Investigation of pre-implantation embryos showed the presence of ST2, but not IL-33 protein. Decidualized endometrium was investigated as a potential source of IL-33 and sST2 at the maternal-fetal interface and, although mRNA for both was present, no protein could be found. The key finding was that sST2, rather than ST2L, was the predominant isoform in the placenta. This led us to reconsider the hypothesis that IL-33/ST2 interactions in the placenta are important for successful pregnancy and raised the possibility that they may have independent roles. Using trophoblast cell lines as a model, it was shown that sST2 binds to trophoblast cells, significantly inhibits their proliferation and stimulates their invasion in vitro. This is the first report of this novel role for sST2 in pregnancy. Thus these studies have shown that sST2 may play an important role in implantation and placentation through controlling trophoblast invasion.

Leung Yee Fong, Vivian. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (leaves 159-169). / Acknowledgments --- p.i / Legend for figures --- p.ii / Legend for tables --- p.v / List of abbreviations --- p.vii / Abstract --- p.viii / Chapter Ch 1 --- Introduction --- p.1 / Chapter 1.1 --- Embryology --- p.1 / Chapter 1.1.1 --- Embryology of amniotic cavity --- p.1 / Chapter 1.1.2 --- Embryology of kidney and bladder --- p.3 / Chapter Ch 2 --- Background: What is already known about amniotic fluid volume? --- p.7 / Chapter 2.1 --- Normal physiology --- p.7 / Chapter 2.1.1 --- The origin of amniotic fluid: Where does it come from? --- p.8 / Chapter 2.1.2 --- Where does the amniotic fluid go? How reabsorbed? --- p.14 / Chapter 2.1.3 --- How is amniotic fluid volume controlled? --- p.18 / Chapter 2.2 --- Abnormal physiology --- p.26 / Chapter 2.2.1 --- Too much liquor: polyhydramnios --- p.26 / Chapter 2.2.2 --- Too little liquor: oligohydramnios --- p.28 / Chapter 2.2.3 --- Diseases and gender differences that may be related to parity and amniotic fluid volume --- p.30 / Chapter 2.3 --- Techniques of measuring amniotic fluid volume --- p.32 / Chapter 2.3.1 --- History --- p.32 / Chapter 2.3.2 --- Current most popular technique: amniotic fluid index --- p.38 / Chapter 2.4 --- Summary of what is known and not yet known about amniotic fluid volume --- p.48 / Chapter Ch 3 --- Aims of this study --- p.49 / Chapter Ch4 --- Method --- p.50 / Chapter 4.1 --- Equipment --- p.50 / Chapter 4.2 --- Subject selection criteria --- p.50 / Chapter 4.2.1 --- Criteria --- p.50 / Chapter 4.2.2 --- Total number of subjects studied --- p.51 / Chapter 4.2.3 --- Total number of subjects selected fulfilling all criteria --- p.51 / Chapter 4.2.4 --- Subject preparation --- p.52 / Chapter 4.3 --- Technique --- p.53 / Chapter 4.3.1 --- "Standard measurement of BPD， AC, FL and EFW" --- p.53 / Chapter 4.3.2 --- Standard measurement of Doppler --- p.54 / Chapter 4.3.3 --- Amniotic fluid index --- p.55 / Chapter 4.3.4 --- Bladder volume --- p.59 / Chapter 4.3.5 --- Fetal renal pelvis --- p.61 / Chapter 4.3.6 --- Intra-observer error techniques and calculation --- p.63 / Chapter 4.4 --- Techniques used in analysis --- p.65 / Chapter Ch5 --- Results --- p.67 / Chapter 5.1 --- Fetal parameters --- p.68 / Chapter 5.1.1 --- Fetal biparietal diameter (BPD) --- p.68 / Chapter 5.1.2 --- Fetal abdominal circumference (AC) --- p.69 / Chapter 5.1.3 --- Fetal femur length (FL) --- p.70 / Chapter 5.1.4 --- Pulsatility index values of umbilical artery --- p.71 / Chapter 5.1.5 --- Birth weight (BW) --- p.74 / Chapter 5.1.6 --- Estimated fetal weight --- p.76 / Chapter 5.2 --- Amniotic fluid index --- p.79 / Chapter 5.2.1 --- Amniotic fluid index-overall --- p.79 / Chapter 5.2.2 --- Amniotic fluid index-male and female --- p.81 / Chapter 5.2.3 --- The ten segments of amniotic fluid index distribution --- p.83 / Chapter 5.2.4 --- Amniotic fluid index relationship to estimated fetal weight --- p.86 / Chapter 5.2.5 --- Amniotic fluid index with gravidity and parity --- p.89 / Chapter 5.2.6 --- Amniotic fluid index with estimated fetal weight of different parity (best fit line) for both male and female --- p.93 / Chapter 5.3 --- Fetal urinary bladder volume (BV) --- p.96 / Chapter 5.3.1 --- Bladder volume-overall --- p.96 / Chapter 5.3.2 --- Bladder volume-male and female --- p.97 / Chapter 5.3.3 --- Bladder volume with estimated fetal weight- overall --- p.100 / Chapter 5.3.4 --- Bladder volume with estimated fetal weight in both male and female --- p.101 / Chapter 5.3.5 --- Bladder volume with gravidity and parity --- p.103 / Chapter 5.3.6 --- Bladder volume with amniotic fluid index --- p.105 / Chapter 5.4 --- Anteroposterior diameter of the fetal renal pelvis --- p.106 / Chapter 5.5 --- Hydronephrosis index values --- p.107 / Chapter Ch 6 --- Discussion --- p.108 / Chapter 6.1 --- Review of the study --- p.108 / Chapter 6.2 --- Discussion on subject --- p.111 / Chapter 6.2.1 --- Gestational age chosen --- p.111 / Chapter 6.2.2 --- Subject preparation --- p.112 / Chapter 6.3 --- Discussion of method --- p.114 / Chapter 6.3.1 --- Equipment --- p.114 / Chapter 6.3.2 --- Technique --- p.117 / Chapter 6.4 --- Discussion on results --- p.128 / Chapter 6.4.1 --- Normality of population --- p.128 / Chapter 6.4.2 --- Low birth weight/ IUGR in Chinese and Caucasian --- p.129 / Chapter 6.4.3 --- Cut-off points to detect oligohydramnios and polyhydramnios --- p.132 / Chapter 6.4.4 --- Amniotic fluid index-relationship with fetal weight --- p.143 / Chapter 6.4.5 --- Amniotic fluid index-relationship to parity --- p.145 / Chapter 6.4.6 --- "Relationship between gender, estimated fetal weight and amniotic fluid index" --- p.147 / Chapter 6.4.7 --- Parity and cut-off points for oligohydramnios and polyhydramnios --- p.150 / Chapter 6.4.8 --- Relationship of amniotic fluid volume to urinary function --- p.152 / Chapter Ch 7 --- Conclusions --- p.157 / References --- p.159

Purpose: To determine the step count accuracy of three pedometers and one accelerometer in pregnant women during treadmill walking. Methods: Subjects were 30 women in the second or third trimester (20-36 weeks) who were screened for pregnancy-related risk factors. Each subject was fitted with a belt containing three physical activity monitors: Yamax Digiwalker SW-200 (DW), New Lifestyles NL 2000 (NL), and GT3X Actigraph accelerometer (ACT). The Omron HJ-720 (HJ) was placed in the pants pocket. Subjects walked at 54, 67, 80, and 94 m•min-1 for two minutes each. Actual steps were determined by an investigator using a hand-tally counter. Percentage of actual steps was calculated for each device at each speed and compared. Results: There was a significant interaction between speed and device (F9,20=7.574,P<0.001). At all speeds, the NL and HJ were most accurate. At 54 m•min-1, the DW was significantly less accurate (P<0.001) than all other devices and the ACT was significantly less accurate (P<0.001) than the NL and HJ. At 67 m•min-1, the ACT and DW were significantly less accurate (P<0.001) than the NL and HJ. At 80 m•min-1, the DW was significantly less accurate (P=0.024) than the NL and HJ. At 94 m•min-1, the ACT was significantly less accurate (P=0.001) than the NL and HJ. No significant differences were found at any speed for the NL (P=0.996) and HJ (P=0.298). Trimester did not significantly affect device accuracy. Conclusion: In pregnant women, the ACT and DW are less accurate than the NL and HJ. The HJ appeared to be the most accurate. These results can be useful in developing further research studies and physical activity programs that focus on walking during pregnancy.

Purpose: To determine the step count accuracy of three pedometers and one accelerometer in pregnant women during treadmill walking. Methods: Subjects were 30 women in the second or third trimester (20-36 weeks) who were screened for pregnancy-related risk factors. Each subject was fitted with a belt containing three physical activity monitors: Yamax Digiwalker SW-200 (DW), New Lifestyles NL 2000 (NL), and GT3X Actigraph accelerometer (ACT). The Omron HJ-720 (HJ) was placed in the pants pocket. Subjects walked at 54, 67, 80, and 94 m•min-1 for two minutes each. Actual steps were determined by an investigator using a hand-tally counter. Percentage of actual steps was calculated for each device at each speed and compared. Results: There was a significant interaction between speed and device (F9,20=7.574,P<0.001). At all speeds, the NL and HJ were most accurate. At 54 m•min-1, the DW was significantly less accurate (P<0.001) than all other devices and the ACT was significantly less accurate (P<0.001) than the NL and HJ. At 67 m•min-1, the ACT and DW were significantly less accurate (P<0.001) than the NL and HJ. At 80 m•min-1, the DW was significantly less accurate (P=0.024) than the NL and HJ. At 94 m•min-1, the ACT was significantly less accurate (P=0.001) than the NL and HJ. No significant differences were found at any speed for the NL (P=0.996) and HJ (P=0.298). Trimester did not significantly affect device accuracy. Conclusion: In pregnant women, the ACT and DW are less accurate than the NL and HJ. The HJ appeared to be the most accurate. These results can be useful in developing further research studies and physical activity programs that focus on walking during pregnancy.

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2009. / Härtill 4 uppsatser.

Hensikt: Hensikten med studien er å fordype kunnskapen om hvordan gravide kvinner opplever en tidlig ultralydundersøkelse med risikovurdering for kromosomavvik, og hvordan de resonnerer omkring resultatet. Nytteverdien blir å løfte frem denne kunnskapen, og ta den med i den videre debatten omkring dette tema. Metode: Det ble gjort en kvalitativ intervjuundersøkelse med ti gravide kvinner som skulle få utført en risikovurdering for kromosomavvik. Kvinnene ble intervjuet både før og etter undersøkelsen. Grounded theory ble benyttet som analysemetode. Resultater: I studien ble det ble generert en kjernekategori; Jeg vil ha valget, men ikke ta det, og fem hovedkategorier: Eksistensielle valg, Trygghetsfølelse, Engstelse, Skyldfølelse og Veiledning / Ivaretakelse. Kjernekategorien beskriver kvinnenes konflikt mellom å ville ha muligheten til denne undersøkelsen, og samtidig ha vanskeligheter med å ta de påfølgende valgene. Noen av faktorene som gjorde valgene så vanskelige var engstelse, tap av kontroll / mestring, tilknytning til fosteret, skyldfølelse og sosialt press. Siden kvinnene ønsket selvstendige valg uten påvirkning fra andre, følte de også en større ansvarlighet for de valg som ble tatt. Forståelsen av den kalkulerte risikoen varierte mellom kvinnene, og de benyttet ulike metoder for å lette vurderingen og valget. Gravide kvinner har et stort informasjonsbehov når det gjelder prenatal diagnostikk, og de ønsker en lett tilgjengelighet til spesialisthelsetjenesten. For å få tid til refleksjon over egne verdier og holdninger, er det viktig at informasjonen blir gitt på et så tidlig tidspunkt i svangerskapet som mulig. Konklusjon: Studien viser kompleksiteten av følelser som gravide kvinner kan oppleve i forbindelse med en tidlig ultralydundersøkelse og risikovurdering for kromosomavvik. Disse stressrelaterte følelsene kan sammen med beslutninger på komplisert risikoinformasjon, og på et sterkt ansvarlig og moralsk område vanskeliggjøre beslutningsprosessen. En bedre informasjonsformidling og kontakt med helsevesenet er nødvendig for at kvinnene skal ta informerte valg, som er i tråd med deres verdier og holdninger. / Purpose: This qualitative study aimed to increase understanding of how pregnant women experience early ultrasound examination that includes risk assessment for chromosomal anomalies. Moreover, this study examined how such women rationalize test results. Method: I conducted pre- and post-examination interviews of ten pregnant women undergoing risk assessment for chromosomal anomolies, and used grounded theory to analyze the results. Results: The study generated a core category (I want a choice, but I don’t want to decide) and five main categories (existential choices, feeling of safety, anxiety, guilt, and counselling and care). Factors contributing to choice difficulty included anxiety, loss of control or coping, emotional connection to the fetus, feelings of guilt, and social pressures. The core category describes the conflict between choice and decision. Since the women sought independent choices without external influence, they also felt greater responsibility. The women’s understanding of actual risk varied, and they used different logic and methods to evaluate risk and reach a decision. Conclusion: Pregnant women need for prenatal diagnostic information and want easy access to specialty services. This study shows the complex feelings pregnant women experience regarding early ultrasound examination that includes risk assessment for chromosomal defects. Stress, non-transparent information about actual and perceived risks, and personal moral judgments further complicate the decision-making process. Therefore, improved distribution of information and frequent contact with health professionals will help women to make informed choices in accordance with their values and beliefs. / <p>ISBN 978-91-5-85721-47-4</p>