Thesis (M.Sc.(Med.))--University of the Witwatersrand, Faculty of Health, 2013.

xi, 283 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D. 1972) from the Dept. of Obstetrics and Gynaecology, University of Adelaide

Thesis (M.D. 1972) from the Dept. of Obstetrics and Gynaecology, University of Adelaide.

A Research Report submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master of Medicine in Paediatrics. 8 May 2014 / Background: Perinatal asphyxia is a significant cause of death and disability. Aim: To determine the outcomes (survival to discharge and morbidity post discharge) of neonates with perinatal asphyxia at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH). Methods: This was a descriptive retrospective study. Patient information was obtained from the computerised neonatal database of neonates admitted to CMJAH within 24 hours of birth between 1 January 2006 and 31 December 2011 with a birth weight of >1800 grams and a 5 minute Apgar score <6. Results: 450 babies were included in the study; 185 females (41.1%). Mean birth weight was 3034.80 grams (SD 484.936) and mean gestational age was 39.11 weeks (SD 2.2). Most babies were inborn 391/450 (86.9%) and most were delivered by normal vaginal delivery 270/450 (60%). The overall survival was 390/450 (86.6%). There were 42 babies admitted to ICU. The ICU survival was 37/42 (88.1%). Significant predictors of survival were place of birth (p value 0.006), mode of delivery (p value 0.007) and bag mask ventilation at birth (p value 0.040). The duration of stay (p value 0.000) was significantly longer in survivors (6.49 days SD 6.6). The remaining factors were not significantly different between the two groups. The rate of perinatal asphyxia (Apgar score <6) was 4.68 per 1000 live births; while 3.61 per 1000 live births had evidence of hypoxic ischaemic encephalopathy (HIE). Of the 390 babies discharged from CMJAH, 113 had follow up records (28.97%) to a mean corrected age of 5.88 months (SD 5.03). The majority (90/113 – 79.64%) had normal development. Conclusion: i) The high overall survival and survival after ICU admission provides a benchmark for further care. ii) Obtaining adequate data for long term follow up was not possible with the existing resources and surrogate early markers of outcome and / or more resources to ensure accurate follow-up are needed and iii) the high incidence of HIE suggest that a therapeutic hypothermia service including long-term follow-up component would be beneficial.

This study addresses the problem of asphyxia neonatorum in a developing African community in the Mdantsane region of Ciskei. It also documents asphyxia as a prominent cause of childhood handicap, examines aspects of its epidemiology and evaluates the effectiveness of a regimen of phenobarbitone and dexamethasone in limiting subsequent neurological deficit in asphyxiated neonates. Analysis of neonatal deaths at Cecilia Makiwane Hospital over an 18-month period showed that asphyxia accounted for one third of all neonatal deaths. In particular, asphyxia caused two thirds of deaths in infants over 2 Kg birth weight. From a hospital register of handicapped children, 211 had cerebral palsy. Asphyxia was the cause of cerebral palsy in 33% of these children. Spastic quadriplegia, the type of cerebral palsy most often resulting from the cerebral damage associated with asphyxial hypoxic-ischaemic insults, was by far the largest diagnostic category (57%). Asphyxia therefore appears to be the single largest cause of significant handicap in Ciskei. In view of the underdeveloped support services to parents in most developing areas, the problem of asphyxia is of considerable importance. In the study of the epidemiology of asphyxia, details of pregnancy and labour were obtained for 163 asphyxiated term infants and 2758 non- asphyxiated term infants whose mothers had delivered in the hospital. The factors positively associated with asphyxia were: low gravidity and parity, failure to book for antenatal care, the occurrence of antenatal disorders, the occurrence of fetal distress, a prolonged first stage of labour and delivery by caesarean section or vacuum extraction. Maternal age and the actual number of antenatal visits were not associated with asphyxia. The causes of asphyxia assigned by the specialist obstetrician in charge were cephalopelvic disproportion (CPD) (39%), utero-placental pathologies (22%), other (8%), and "unknown" where he could find no abnormality in pregnancy and labour (27%). From these findings it appears that the steps that need to be taken for prevention include: active recruitment of patients to book for antenatal care, more active detection and management of cephalopelvic disproportion and basic research to elucidate the causes of the "unknown" group whom it is speculated have undetected utero-placental pathology.

To investigate the relationship between birth asphyxia and neurological impairment a cohort of 184 infants with a low (≤3) one-minute Apgar score was studied. All were singletons, apparently normally formed, and born at term (≥37 weeks' gestation) in the John Radcliffe Hospital, between January 1984 and September 1985. The 181 cohort survivors were traced at the age of five years; 159 were assessed by a paediatrician on a battery of neurodevelopmental tests, and information about a further eight was obtained from other sources. Three infants in the cohort died neonatally with a diagnosis of birth asphyxia, and three had spastic quadriplegia, profound developmental delay and visual impairment. Examination of the perinatal histories of these six children, including their fetal heart rate patterns in labour and acid-base status at delivery, found convincing evidence of birth asphyxia. Only one other child in the cohort exhibited similar signs of birth asphyxia; he was unimpaired at the age of five. To assess the impact of birth asphyxia on the overall rate of cerebral palsy, all cases of cerebral palsy born to Oxford residents in the study period were identified. Of 30 cases of cerebral palsy, the three identified in the follow-up study were the only ones whose impairment could be attributed to birth asphyxia in a full-term birth. Birth asphyxia therefore accounted for 10% of all cases of cerebral palsy, a fraction that agrees with previous estimates. The frequency of cerebral palsy due to birth asphyxia was estimated as 1 in 3800 full-term livebirths. A detailed analysis of the test scores of the 159 children assessed by the paediatrician failed to show any association between their acid-base values at delivery and test scores, or between their fetal heart rate patterns in labour and test scores. These results conform with the view that birth asphyxia has an "all or nothing" effect, and that it presents as a cluster of abnormal neonatal signs, including persistent cerebral depression, severe acidaemia, neonatal encephalopathy, and multiorgan dysfunction.

Thesis (Ph.D.) - University of Queensland, 2004. / Includes bibliography.

[Truncated abstract] In this thesis the role of lactate measurement has been evaluated in intrapartum assessment of fetal wellbeing. Specifically, I have addressed the question of whether fetal lactate measurement is better than the assessment of fetal heart rate patterns or the measurement of pH at predicting fetal brain injury after intrapartum asphyxia. Using an ovine model of repeated umbilical cord occlusion designed to mimic events which may occur during human labour, I have shown that the measurement of fetal lactate levels after repeated cord occlusion is significantly associated with the severity of brain injury after the asphyxial insult. No significant associations were identified with fetal pH measurements or with the duration of decelerative or compound fetal heart rate patterns; however, this is the first study to describe an association between the duration of both increased fetal heart rate variability and fetal heart rate overshoot with the severity of subsequent brain injury. Although no significant association was identified between fetal arterial pressure measured between umbilical cord occlusions and the grade of brain injury, the studies performed in this thesis are the first to show a strong correlation between the duration of specific arterial pressure responses during cord occlusions and the grade of brain injury, accounting for approximately 90% of the variability seen in the severity of injury. The mechanism responsible for the improved ability of lactate measurement to predict fetal brain injury is unknown. It may be because fetal lactate levels are a more stable marker of anaerobic metabolism of glucose than fetal pH levels, which are influenced by both increasing levels of carbon dioxide and anaerobic metabolism of amino-acids and fatty acids. In addition fetal pH levels can be rapidly normalised through placental exchange of carbon dioxide whereas fetal lactate levels are slow to normalise across the placenta as they rely on facilitated diffusion.

O Magnésio é o segundo cátion intracelular mais comum e desempenha importante papel na modulação de funções de transporte e receptores, atividades enzimáticas, metabolismo energético, síntese de proteínas e ácidos nucleicos e proteção de membranas biológicas. Apesar de sua importância, o conhecimento de sua homeostase não é completo, principalmente por dificuldade de acesso a seus estoques intracelulares e da ausência de métodos laboratoriais confiáveis para medida da fração iônica. O desenvolvimento recente de um eletrodo íon-seletivo permitiu a determinação das concentrações de Mg iônico(Mgi), em pequenas amostras de sangue, o que possibilitou a realização de estudos para determinação desta fração no período neonatal. A presença de alguns distúrbios, como o Crescimento Intra-uterino Restrito(CIUR) e a Asfixia Perinatal, poderiam potencialmente levar a desvios da homeostase do Mg, ainda não totalmente esclarecidos. O objetivo deste estudo foi descrever, em Recém-nascidos de termo(RNT) sem CIUR, os níveis de Mgi e total (MgT) em sangue de cordão umbilical, 3o e 7o dias de vida e comparar os valores obtidos entre os RNT, com e sem CIUR e asfixia perinatal. Realizou-se um estudo prospectivo, no qual foram incluídos 95 RNT, divididos em dois grupos de estudo: Grupo I - sem CIUR(50 RN - 52,6%) e Grupo II - com CIUR(45 RN - 47,4%). A presença de CIUR foi determinada por um peso de nascimento abaixo do percentil 10 para a curva de Ramos(1983), associado a uma relação P/P50 < 0,85. Cada um desses grupos foi subdividido em 2 subgrupos : Grupo Ia - 30 RN (31,6%), sem CIUR e sem asfixia perinatal; Grupo Ib - 20 RN(21,0%), sem CIUR e com asfixia perinatal; Grupo IIa - 40 RN(42,1%), com CIUR e sem asfixia perinatal; Grupo IIb - 5 RN(5,3%), com CIUR e asfixia perinatal. A presença de asfixia perinatal foi indicada por um Apgar de 5o minuto < 6 associada a presença de um dos seguintes critérios: pH de sangue de cordão umbilical < 7,2 , disfunção de um ou mais órgãos, sequelas neurológicas no período neonatal imediato. Foram realizadas determinações de Mgi, Cálcio iônico(Cai), Uréia(U), pH, MgT, Fósforo(P) e Creatinina(Cr), em sangue de cordão umbilical, no 3o e no 7o dias de vida. Verificou-se que nos RNT sem CIUR(Grupo Ia), as concentrações médias de MgT, ao nascimento, foram menores do que as de RN com CIUR e elevaram-se, de forma significante, até o 7o dia de vida, enquanto as de Mgi mantiveram-se. As concentrações de Mgi neste grupo, foram significativamente menores do que as de RN com CIUR(Grupo IIa) durante a 1a semana de vida e do que as de RN com asfixia perinatal(Grupo Ib) no 3o e 7o dias de vida. Concluiu-se que, em RNT sem CIUR, há um aumento dos níveis de MgT durante a 1a semana de vida, sem alteração das concentrações de Mgi. A presença de CIUR, bem como a asfixia perinatal, podem influenciar as concentrações neonatais de Mg, através de seus efeitos de modulação da homeostase deste íon, durante os períodos fetal e neonatal / Magnesium is the second most abundant intracellular cation and plays an important role in regulation of transporting and receptors functions, enzymatic activities, energy metabolism, protein and nucleic acid synthesis and biologic membranes protection. In spite of this, the knowledge of its homeostasis is still limited, mainly due to inacessibility of its intracellular stores and the absence of a reliable methodology to measuring the ionized fraction. The recent development of an ion-selective electrode has allowed not only the determination of ionized magnesium(iMg) concentrations in a small blood sample volume, but also an increasing number of researches as to this fraction in neonatal period. The presence of some disorders,i.e. like Intrauterine Growth Restriction (IUGR) and Perinatal Asphyxia, could lead to an unclear imbalance of magnesium homeostasis, in a way not yet clear. The aim of this study was to describe, in term newborns without IUGR, iMg and Total Mg (TMg) concentrations in umbilical cord blood, third and seventh days of life and to compare the results among term newborns with and without IUGR and perinatal asphyxia. Ninety-five term newborn infants were enrolled in a prospective study and were divided into two study groups: Group I : without IUGR(50RN - 52.6%) and Group II - with IUGR(45RN - 47.4%). Intrauterine growth restriction was defined as a birth weight below the 10th percentil for Ramos Curve(1983) besides to a birth weight ratio <0,85. Each one of these groups were divided in two subgroups: Group Ia :30 RN (31,6%), without IUGR or perinatal asphyxia; Group Ib : 20 RN (21,0%), without IUGR, with perinatal asphyxia ; Group IIa : 40 RN (42,1%), with IUGR, without perinatal asphyxia; Group IIb: 5 RN(5,3%), with perinatal asphyxia and IUGR. Perinatal asphyxia was defined as a 5 minutes Apgar score < 6 besides to one of the following: umbilical cord blood pH < 7,2, disfunction of one or more organs, neonatal neurologic manifestations. iMg, TMg, ionized calcium, urea, pH, phosphorus and creatinine concentrations were determined in umbilical cord blood, third and seventh days of life. We observed that in term newborns without IUGR (Group Ia), TMg concentrations increased significantly during the first week of life, while iMg concentrations remained unchanged. iMg levels in this group, were significantly lower than in the group with IUGR (Group IIa) from birth to 7th day of life and than in the group without IUGR, with perinatal asphyxia (Group Ib) in the third and seventh days of life. We concluded that in term newborns without IUGR, TMg levels increased during the first week of life, while iMg levels remained unchanged. The presence of IUGR, as well as, perinatal asphyxia, may influence neonatal levels of magnesium, through their effect on the modulation of this ion homeostasis, during fetal and neonatal periods

O Magnésio é o segundo cátion intracelular mais comum e desempenha importante papel na modulação de funções de transporte e receptores, atividades enzimáticas, metabolismo energético, síntese de proteínas e ácidos nucleicos e proteção de membranas biológicas. Apesar de sua importância, o conhecimento de sua homeostase não é completo, principalmente por dificuldade de acesso a seus estoques intracelulares e da ausência de métodos laboratoriais confiáveis para medida da fração iônica. O desenvolvimento recente de um eletrodo íon-seletivo permitiu a determinação das concentrações de Mg iônico(Mgi), em pequenas amostras de sangue, o que possibilitou a realização de estudos para determinação desta fração no período neonatal. A presença de alguns distúrbios, como o Crescimento Intra-uterino Restrito(CIUR) e a Asfixia Perinatal, poderiam potencialmente levar a desvios da homeostase do Mg, ainda não totalmente esclarecidos. O objetivo deste estudo foi descrever, em Recém-nascidos de termo(RNT) sem CIUR, os níveis de Mgi e total (MgT) em sangue de cordão umbilical, 3o e 7o dias de vida e comparar os valores obtidos entre os RNT, com e sem CIUR e asfixia perinatal. Realizou-se um estudo prospectivo, no qual foram incluídos 95 RNT, divididos em dois grupos de estudo: Grupo I - sem CIUR(50 RN - 52,6%) e Grupo II - com CIUR(45 RN - 47,4%). A presença de CIUR foi determinada por um peso de nascimento abaixo do percentil 10 para a curva de Ramos(1983), associado a uma relação P/P50 < 0,85. Cada um desses grupos foi subdividido em 2 subgrupos : Grupo Ia - 30 RN (31,6%), sem CIUR e sem asfixia perinatal; Grupo Ib - 20 RN(21,0%), sem CIUR e com asfixia perinatal; Grupo IIa - 40 RN(42,1%), com CIUR e sem asfixia perinatal; Grupo IIb - 5 RN(5,3%), com CIUR e asfixia perinatal. A presença de asfixia perinatal foi indicada por um Apgar de 5o minuto < 6 associada a presença de um dos seguintes critérios: pH de sangue de cordão umbilical < 7,2 , disfunção de um ou mais órgãos, sequelas neurológicas no período neonatal imediato. Foram realizadas determinações de Mgi, Cálcio iônico(Cai), Uréia(U), pH, MgT, Fósforo(P) e Creatinina(Cr), em sangue de cordão umbilical, no 3o e no 7o dias de vida. Verificou-se que nos RNT sem CIUR(Grupo Ia), as concentrações médias de MgT, ao nascimento, foram menores do que as de RN com CIUR e elevaram-se, de forma significante, até o 7o dia de vida, enquanto as de Mgi mantiveram-se. As concentrações de Mgi neste grupo, foram significativamente menores do que as de RN com CIUR(Grupo IIa) durante a 1a semana de vida e do que as de RN com asfixia perinatal(Grupo Ib) no 3o e 7o dias de vida. Concluiu-se que, em RNT sem CIUR, há um aumento dos níveis de MgT durante a 1a semana de vida, sem alteração das concentrações de Mgi. A presença de CIUR, bem como a asfixia perinatal, podem influenciar as concentrações neonatais de Mg, através de seus efeitos de modulação da homeostase deste íon, durante os períodos fetal e neonatal / Magnesium is the second most abundant intracellular cation and plays an important role in regulation of transporting and receptors functions, enzymatic activities, energy metabolism, protein and nucleic acid synthesis and biologic membranes protection. In spite of this, the knowledge of its homeostasis is still limited, mainly due to inacessibility of its intracellular stores and the absence of a reliable methodology to measuring the ionized fraction. The recent development of an ion-selective electrode has allowed not only the determination of ionized magnesium(iMg) concentrations in a small blood sample volume, but also an increasing number of researches as to this fraction in neonatal period. The presence of some disorders,i.e. like Intrauterine Growth Restriction (IUGR) and Perinatal Asphyxia, could lead to an unclear imbalance of magnesium homeostasis, in a way not yet clear. The aim of this study was to describe, in term newborns without IUGR, iMg and Total Mg (TMg) concentrations in umbilical cord blood, third and seventh days of life and to compare the results among term newborns with and without IUGR and perinatal asphyxia. Ninety-five term newborn infants were enrolled in a prospective study and were divided into two study groups: Group I : without IUGR(50RN - 52.6%) and Group II - with IUGR(45RN - 47.4%). Intrauterine growth restriction was defined as a birth weight below the 10th percentil for Ramos Curve(1983) besides to a birth weight ratio <0,85. Each one of these groups were divided in two subgroups: Group Ia :30 RN (31,6%), without IUGR or perinatal asphyxia; Group Ib : 20 RN (21,0%), without IUGR, with perinatal asphyxia ; Group IIa : 40 RN (42,1%), with IUGR, without perinatal asphyxia; Group IIb: 5 RN(5,3%), with perinatal asphyxia and IUGR. Perinatal asphyxia was defined as a 5 minutes Apgar score < 6 besides to one of the following: umbilical cord blood pH < 7,2, disfunction of one or more organs, neonatal neurologic manifestations. iMg, TMg, ionized calcium, urea, pH, phosphorus and creatinine concentrations were determined in umbilical cord blood, third and seventh days of life. We observed that in term newborns without IUGR (Group Ia), TMg concentrations increased significantly during the first week of life, while iMg concentrations remained unchanged. iMg levels in this group, were significantly lower than in the group with IUGR (Group IIa) from birth to 7th day of life and than in the group without IUGR, with perinatal asphyxia (Group Ib) in the third and seventh days of life. We concluded that in term newborns without IUGR, TMg levels increased during the first week of life, while iMg levels remained unchanged. The presence of IUGR, as well as, perinatal asphyxia, may influence neonatal levels of magnesium, through their effect on the modulation of this ion homeostasis, during fetal and neonatal periods