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Title: Maternal, obstetric, biochemical and ultrasonic associations of normal and abnormal human pregnancy
Author: Smith, Gordon Campbell Sinclair
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2010
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The work in this thesis describes a series of studies utilising diverse data sources which were analysed using a number of regression methods (logistic, linear, Cox, Poisson), to address the factors associated with normal and abnormal pregnancy outcome. A series of maternal characteristics were related to adverse pregnancy outcome. Teenage pregnancy was not associated with an increased risk of any adverse outcome among first births, but was strongly associated with adverse outcome among second births [8]. Parity also interacted with body mass index: maternal obesity was associated with an increased risk of preterm birth among nulliparous but not multiparous women. This was explained by higher rates of elective preterm deliveries among obese nullipara [31]. There was a linear relationship between maternal age and the duration of labour, and the risk of operative vaginal and caesarean delivery [37]. It was hypothesised that age-related deterioration in obstetric performance was due to prolonged hormonal stimulation prior to the first birth. This hypothesis was supported by the observation that later menarche was independently associated with a decreased risk of operative delivery [38]. A short inter-pregnancy interval was associated with an increased risk of spontaneous preterm birth, but not stillbirth or intra-uterine growth restriction [16]. The risk of unexplained stillbirth at term was increased among nulliparous women [5] and nulliparous women also had slightly longer pregnancies [7]. A U-shaped relationship between birth weight and caesarean risk was observed at term. There was an interaction between fetal sex and caesarean risk: small boys were at increased risk of emergency caesarean [3]. The same interaction was observed for antepartum stillbirth [4]. Previous pregnancy outcome was predictive of the outcome of subsequent pregnancies. Women who were delivered by caesarean section in their first pregnancy had an increased risk of unexplained stillbirth in their second [17]. This finding was confirmed in a separate cohort and associations were also observed between previous complicated livebirths and the subsequent risk of unexplained stillbirth [32]. Some specific situations were also studied (vaginal birth after caesarean section (VBAC) and twins). Among women attempting VBAC, the absolute risk of delivery-related perinatal death was comparable to primiparous women but was significantly higher than women delivered by elective caesarean section [11]. The risk of perinatal death associated with uterine rupture was increased in low throughput obstetric units and among women induced with prostaglandins [19]. Using simple maternal characteristics, approximately 50% of women attempting VBAC could be classified into having a high (>40%) or low (<10%) risk of emergency caesarean [24]. This was better discrimination than could be achieved using similar characteristics among nulliparous women being induced at term [21]. The risk of delivery related perinatal death was increased among second twins, although this was only evident among births at term [13]. The association was observed among sex discordant twins, but was not observed among twins delivered by elective caesarean section [23]. The association between birth order and the risk of death due to anoxia was confirmed in data from England and Wales [33]. Ultrasonic measurements of the fetus were related to eventual birth weight. The range of error associated with such estimates was quantified and abdominal circumference on its own was as predictive as models using abdominal circumference and femur length [1]. Estimating fetal weight using ultrasound was not found to be a better measure of human fetal blood volume than simply using gestational age [10]. A series of ultrasonic measurements in the first and second trimester were predictive of pregnancy outcome, including smaller than expected crown rump length and intra-uterine growth restriction, preterm birth and low birth weight [2]; a long cervix in mid gestation and caesarean section [36]; and, high resistance patterns of uterine artery Doppler flow velocimetry and stillbirth [30]. Biochemical measurements performed in early pregnancy were also predictive of later adverse outcome: low maternal levels of pregnancy-associated plasma protein A (PAPP-A) were associated with an increased of pre-eclampsia, preterm birth and growth restriction [9]; low PAPP-A prior to 13 weeks was associated with birth weight at term in healthy pregnancies [12] and with a dramatically increased risk of stillbirth due to placental dysfunction [22]. Low first trimester levels of placenta growth factor were associated with increased risks of pre-eclampsia and growth restriction, whereas there was no association between elevated levels of the soluble fms-like receptor and adverse outcome [35]. Measurements of biochemical variables in the second trimester were also predictive of outcome, with elevated maternal serum alphafetoprotein (AFP) being associated with an increased risk of stillbirth [34] and spontaneous preterm birth [29]. Women with the combination of low first trimester PAPP-A and high second trimester AFP were at particularly high risk of complications, reflecting the synergistic predictive ability of the two measures [27]. Given proposed similarities between stillbirth and sudden infant death syndrome (SIDS), this outcome was also studied. Elevated second trimester levels of AFP were also associated with an increased subsequent risk of SIDS [20]. Women with a pregnancy resulting ultimately in SIDS were found to be more likely to have had complications in past and future pregnancies [25]. The risk of SIDS declined with advancing gestational age at term following spontaneous, but not elective birth [15]. Obstetric characteristics were used to generate a predictive model for SIDS [26]. Pregnancy outcome was also predictive of other aspects of child health, specifically, respiratory morbidity following birth at term was associated with an increased risk of hospital admission for asthma [18]. Pregnancy complications were also related to long term maternal health. Elective caesarean delivery for breech presentation did not appear to have an independent effect on fertility [28]. However, pregnancy complications were associated with the mother’s subsequent experience of cardiovascular disease. Women experiencing growth restriction, preterm birth or pre-eclampsia were at increased risk of subsequent ischaemic heart disease (IHD) [6] and the risk of this was also related to the number of miscarriages experienced prior to the first birth [14]. The parents of women who had experienced pregnancy complications or recurrent miscarriage had an increased incidence of IHD [39 & 40, respectively].
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (D.Sc.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RB Pathology ; RG Gynecology and obstetrics