Intrauterine foetal and child growth in the context of Ethiopian Health system: Implications for Prenatal care : Intrauterine foetal growth and child linear growth in Ethiopia

Fostervekst og vekst hos små barn på den etiopiske landsbygd. Etiopia er fortsatt et av verdens fattigste land, og bruken av helsetjenester er lav. Mødre dødeligheten er også høy. Og, mange barn har både akutt og kronisk underernæring. Det er derfor behov for studier til å bedre forståelsen av fostervekst og barns vekst. Bedre innsikt av intrauterin fostervekst er en viktig for tidlig identifisering av normal og unormal fostervekst, noe som kan påvirke fødselsvekt ved fødselen og vekst i tidlig barndom. Målsetningen med denne avhandlingen var å måle intrauterin fostervekst, og se hvorledes barns lengdevekst var i de første to leveår. Avhandlingen vurderer også hvorledes slike mål kan brukes i den eksisterende mødre- og barnehelsetjenesten på den etiopiske landsbygd. Studien ble utført i den sentrale delen av Riftdalen i Etiopia. Omtrent 700 gravide kvinner ble undersøkt, og deres barn ble fulgt opp til de var omtrent to år. Studieområdet er et typisk landbruksområde, har gjentatte ganger vært rammet av tørke og hungersnød. Selv om det har vært matmangel i området, viser studien at intrauterin vekst er sammenlignbart med Verdens helseorganisasjon (WHO) og INTERGROWTH-21st referansene. Imidlertid er det mange barn som får en lav lengdevekst de først to år. Dette kan forklares både med faktorer under graviditeten og årsaker som oppstår i de tidlige barneårene. I den siste artikkelen i avhandlingen beskrives og analyseres hvorledes svangerskapsomsorgen fungerer sammenlignet med de nasjonale og WHOs retningslinjer. Det er betydelige mangler med dagens graviditetskontroller. Det er derfor viktig å styrke mor-barn helsearbeidet.Introduction Ethiopia is a country with a low coverage of antenatal care services. In 2019, only 43% of pregnant women had the recommended four antenatal care (ANC) visits during their pregnancy while 24% of women in Ethiopia had no ANC visits at all. Different national initiatives are underway to expand and improve maternal health services utilization. These are aligned with international and national agendas and goals. In the first 1000 days of life, starting from the time of conception, growth is viewed as a continuum between the foetal period, infancy, and early childhood. Foetal growth is dynamic. Defining normal or abnormal foetal growth requires the taking of serial measurements. If the foetal growth is abnormal, it can result in low birth weight or prematurity. Low birth weight and prematurity are major contributors of neonatal and infant mortality and morbidity. ANC is an important care point that has a positive influence in identifying pregnancy-related complications. It can also contribute to improved pregnancy outcomes. Ethiopia implemented the World Health Organization’s (WHO) focused ANC (FANC) model at all health facilities until February 2022, which was a goal orientated approach to delivering evidence-based interventions carried out at four critical times during pregnancy. Population specific foetal growth charts that can be used to monitor foetal growth patterns are lacking, particularly in areas affected by food insecurity and drought such as are found in Ethiopia. Moreover, the influence of intrauterine uterine growth on birth weight and early childhood growth has not been examined in this country. In addition, even though ANC is taken as an opportunity for influencing the well-being of pregnant mothers and growing foetus, the evidence supporting a relationship between ANC and adverse pregnancy outcomes is unclear in Ethiopia.   Objective The overall objective of this thesis was to examine intrauterine and child growth in a drought-affected rural area of Ethiopia in the context of the country’s health system. The first objective was to assess intrauterine uterine growth patterns in comparison to the WHO and the INTERGROWTH 21st intrauterine uterine growth standards. The second objective was to examine the influence of intrauterine foetal growth on length-for-age Z-score and weight-for-length Z-score in early childhood 11–24 months of age. The third objective was to assess the compliance of ANC utilization with national and WHO guidelines and whether adverse pregnancy outcomes were associated with the use of antenatal care services. Methods We conducted a prospective cohort study in the rural community of Adami Tullu district in the Oromia Regional State in south central Ethiopia from July 2016 to November 2018. We included 704 pregnant women, with a gestational age of less than 24 weeks and followed them to delivery. We followed the children until they were 24 months postnatal. At enrolment, we collected data on maternal, sociodemographic and household characteristics. We also collected data on maternal weight, blood pressure, mid upper arm circumference (MUAC), haemoglobin, and malaria test results at 26, 30, and 36 weeks of gestation. We obtained foetal biometric measurements (head circumference, biparietal diameter, abdominal circumference, and femoral length) and estimated foetal weight using ultrasound at each visit. We subsequently followed the new-borns postnatally and measured their lengths and weights once at the age of 11-24 months. Foetal weight was estimated using the Hadlock algorithm, and the 5th, 10th, 25th, 50th, 75th, 90th, and 95th centiles were generated from this model. We compared the Z-scores and percentiles of biometric measurements and estimated foetal weight with the INTERGROWTH 21st and WHO multicentre foetal growth reference standards (Paper I). After birth, we measured the weights and lengths of 554 children at age of 11–24 months. The birth-weight-for-gestational-age Z-score was calculated using INTERGROWTH 21st international new-born birth standards. We determined Z-scores of length-for-age, weight-for-age and weight-for-length of the children using the 2006 WHO child growth standards. We used a multilevel mixed effect linear regression model to examine the influence of foetal biometric measurements, new-born (birth weight, gestational age at delivery, sex), maternal (age, height, education, occupation, parity) and household (household wealth, family size) characteristics on birth weight, child length-for-age and weight-for-age (Paper II). We used the WHO and national ANC guidelines to compare the service utilization patterns, and collected data on ANC utilization among 704 pregnant women at three prescheduled visits during pregnancy and at birth. Data on the extent of antenatal care content received, timing of antenatal care, location of antenatal care, and location and mode of delivery were obtained by interviewing the pregnant women. Adverse pregnancy outcomes was computed as the sum of preterm birth, intrauterine foetal deaths, and stillbirths (Paper III). Results The distribution of biometric measurements and estimated foetal weight in our study were similar to the WHO and INTERGROWTH-21st references. Most measurements were between -2 and +2 of the reference Z-scores. Based on the smoothed percentiles, the 5th, 50th, and 95th percentiles, our study had similar distribution patterns to the WHO chart, and the 50th percentile was similar to the INTERGROWTH-21st chart (Paper I). We found that foetal factors, duration of pregnancy, child age, maternal height and family size were the main predictors of linear growth. Both birth weights and linear growth were influenced by early intrauterine foetal growth. Birth weight was also influenced by foetal growth during late pregnancy. Environmental factors had more influence on the child’s linear growth compared to their effect on birth weight. We observed a large variation in length-for-age Z-score (30%) and weight-for-length Z-score (22%) among kebeles (local wards) than in the birth weight of new-borns (11%) indicating more heterogeneity in clusters for length-for-age Z-score and weight-for-length Z-score than for birth weight (Paper II). We found that pregnant mothers had a poor compliance of ANC utilization compared to the national and the WHO guidelines. In addition, we found that the current FANC utilization status were not associated with the adverse pregnancy outcomes that we measured (Paper III). Conclusions In conclusion, this thesis demonstrated that; (i) foetal growth patterns were similar to the INTERGROWTH-21st and the WHO multicentre foetal growth reference standards, (ii) early intrauterine foetal growth affected both birth weight and linear growth while foetal growth during late pregnancy influenced birth weight only. In addition, there was more influence of environmental factors on child linear growth compared to their effects on birth weight and, (iii) ANC service utilization is low in the context of national and WHO guidelines. In addition, there was no association between the current focused antenatal health care service and adverse pregnancy outcomes.  Doktorgradsavhandlin

Effectiveness of routine third trimester ultrasonography to reduce adverse perinatal outcomes in low risk pregnancy (the IRIS study): nationwide, pragmatic, multicentre, stepped wedge cluster randomised trial

Objectives To investigate the effectiveness of routine ultrasonography in the third trimester in reducing adverse perinatal outcomes in low risk pregnancies compared with usual care and the effect of this policy on maternal outcomes and obstetric interventions. Design Pragmatic, multicentre, stepped wedge cluster randomised trial. Setting 60 midwifery practices in the Netherlands. Participants 13 046 women aged 16 years or older with a low risk singleton pregnancy. Interventions 60 midwifery practices offered usual care (serial fundal height measurements with clinically indicated ultrasonography). After 3, 7, and 10 months, a third of the practices were randomised to the intervention strategy. As well as receiving usual care, women in the intervention strategy were offered two routine biometry scans at 28-30 and 34-36 weeks’ gestation. The same multidisciplinary protocol for detecting and managing fetal growth restriction was used in both strategies. Main outcome measures The primary outcome measure was a composite of severe adverse perinatal outcomes: perinatal death, Apgar score <4, impaired consciousness, asphyxia, seizures, assisted ventilation, septicaemia, meningitis, bronchopulmonary dysplasia, intraventricular haemorrhage, periventricular leucomalacia, or necrotising enterocolitis. Secondary outcomes were two composite measures of severe maternal morbidity, and spontaneous labour and birth. Results Between 1 February 2015 and 29 February 2016, 60 midwifery practices enrolled 13 520 women in mid-pregnancy (mean 22.8 (SD 2.4) weeks’ gestation). 13 046 women (intervention n=7067, usual care n=5979) with data based on the national Dutch perinatal registry or hospital records were included in the analyses. Small for gestational age at birth was significantly more often detected in the intervention group than in the usual care group (179 of 556 (32%) v 78 of 407 (19%), P<0.001). The incidence of severe adverse perinatal outcomes was 1.7% (n=118) for the intervention strategy and 1.8% (n=106) for usual care. After adjustment for confounders, the difference between the groups was not significant (odds ratio 0.88, 95% confidence interval 0.70 to 1.20). The intervention strategy showed a higher incidence of induction of labour (1.16, 1.04 to 1.30) and a lower incidence of augmentation of labour (0.78, 0.71 to 0.85). Maternal outcomes and other obstetric interventions did not differ between the strategies. Conclusion In low risk pregnancies, routine ultrasonography in the third trimester along with clinically indicated ultrasonography was associated with higher antenatal detection of small for gestational age fetuses but not with a reduced incidence of severe adverse perinatal outcomes compared with usual care alone. The findings do not support routine ultrasonography in the third trimester for low risk pregnancies. Trial registration Netherlands Trial Register NTR4367

Clinical impact of the methodological quality of fetal doppler standards in the management of fetal growth restriction

Esta tesis, que lleva por título “Clinical impact of the methodological quality of fetal Doppler standards in the management of fetal growth Restriction”, es un trabajo realizado en la Universidad de Zaragoza con colaboración de la Universidad de Oxford por lo que opta a la mención internacional. Además, está elaborada según la normativa de la Universidad de Zaragoza como tesis por compendio de publicaciones, con 4 artículos publicados en revistas de elevado factor de impacto.El crecimiento intrauterino restringido (CIR) es una de las enfermedades con mayor repercusión médica, social y económica en obstetricia. Estos fetos pueden interrumpir su crecimiento como consecuencia de una insuficiencia placentaria, apareciendo alteraciones en el Doppler fetal, lo que conlleva un riesgo elevado de resultado perinatal adverso. Para que una herramienta como el Doppler fetal sea fiable, los valores obtenidos deben ser adecuados y reproducibles, la medición del Doppler debe estar estandarizada y así, maximizaremos su potencial en la evaluación del CIR en la práctica clínica. Con este objetivo se desarrolló la primera de las publicaciones que propone un sistema de puntuación objetiva para evaluar imágenes Doppler de la arteria cerebral media (ACM), demostrando que los controles de calidad de imágenes son esenciales, así como el uso de sistemas objetivos que hagan que las imágenes sean reproducibles.Por otro lado, la secuencia de progresión del Doppler fetal ha sido descrita claramente y hay evidencia de que los cambios cualitativos en el Doppler de la arterial umbilical (AU), como la presencia, ausencia o inversión del flujo diastólico, indican un mayor riesgo de muerte fetal. Sin embargo, la asociación entre los cambios semi-cuantitativos en el Doppler de AU y ACM (medidos con el índice de pulsatilidad) y los resultados perinatales y a largo plazo no se han establecido claramente. Como consecuencia, se han publicado multitud de valores de referencia del índice de pulsatilidad del Doppler fetal. Esta falta de evidencia podría explicarse, al menos parcialmente, por la calidad metodología utilizada para establecer estos valores, lo que podría tener importantes implicaciones para la práctica clínica. Con esta hipótesis, en el segundo trabajo se realizó una revisión sistemática de todos los estudios publicados con el objetivo de crear curvas de referencia para la AU, ACM e índice cerebroplacentario (ICP). Tras utilizar una lista de verificación ya validada y evaluar 38 estudios, se llegó a la conclusión de que todos los estudios en los que se basan los valores de referencia que se usan en la práctica clínica tienen numerosos sesgos metodológicos, haciendo que las diferencias entre los valores sean importantes. Además, en el tercer estudio, se comparó todos estos valores demostrando su gran variabilidad y se realizó una simulación clínica en la que se observó que el manejo de un feto con crecimiento intrauterino restringido puede variar en dependencia del valor de referencia que se elija, decidiendo finalizar la gestación o no y produciendo en algunos casos prematuridad iatrogénica y en otros, aumento del riesgo de muerte fetal intrauterina.Finalmente, como solución a todos los problemas planteados y a la falta de estudios de alta calidad metodológica en los que basar nuestras actuaciones médicas, se propone el estudio FETHUS, un estudio de cohortes, longitudinal, multicéntrico, internacional y prospectivo, con el objetivo de crear unos valores de referencia basados en un estudio con alta calidad metodológica que sirvan de referencia universal para el Doppler fetal, unificando así el manejo del feto con crecimiento intrauterino restringido.1. Alfirevic Z, Stampalija T, Dowswell T. Fetal and umbilical Doppler ultrasound in high-risk pregnancies. Vol. 2017, Cochrane Database of Systematic Reviews. John Wiley and Sons Ltd; 2017. 2. Alfirevic Z, Stampalija T, Medley N. Fetal and umbilical Doppler ultrasound in normal pregnancy. Vol. 2015, Cochrane Database of Systematic Reviews. John Wiley and Sons Ltd; 2015. 3. Fetal Growth Restriction. Practice Bulletin No. 134. American College of Obstetricians & Gyncologists. Obstet Gynecol. 2013;4. Gordijn SJ, Beune IM, Thilaganathan B, Papageorghiou A, Baschat AA, Baker PN, et al. Consensus definition of fetal growth restriction: a Delphi procedure. Ultrasound Obstet Gynecol [Internet]. 2016 Sep [cited 2019 Aug 3];48(3):333–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/269096645. RCOG Green-top Guideline, 2nd Edition J 2014. Investigation and Management of the Small for Gestational Age Fetus. R Coll Obstet Gynaecol (RCOG) [Internet]. Available from: http://www.rcog.org.uk/files/rcog-corp/6. Conde-Agudelo A, Villar J, Kennedy SH, Papageorghiou AT. Predictive accuracy of cerebroplacental ratio for adverse perinatal and neurodevelopmental outcomes in suspected fetal growth restriction: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2018; 7. Oros D, Figueras F, Cruz-Martinez R, Padilla N, Meler E, Hernandez-Andrade E, et al. Middle versus anterior cerebral artery Doppler for the prediction of perinatal outcome and neonatal neurobehavior in term small-for-gestational-age fetuses with normal umbilical artery Doppler. Ultrasound Obstet Gynecol [Internet]. 2010 Apr [cited 2019 Aug 22];35(4):456–61. Available from: http://www.ncbi.nlm.nih.gov/pubmed/201781158. DeVore GR. The importance of the cerebroplacental ratio in the evaluation of fetal well-being in SGA and AGA fetuses. Vol. 213, American Journal of Obstetrics and Gynecology. Mosby Inc.; 2015. p. 5–15. 9. Arduini D, Rizzo G. Normal values of Pulsatility Index from fetal vessels: a cross-sectional study on 1556 healthy fetuses. J Perinat Med [Internet]. 1990 [cited 2019 Aug 3];18(3):165–72. Available from: http://www.ncbi.nlm.nih.gov/pubmed/220086210. Morales-Roselló J, Diaz García-Donato J. Study of fetal femoral and umbilical artery blood flow by Doppler ultrasound throughout pregnancy.11. Figueras F, Gardosi J. Intrauterine growth restriction: New concepts in antenatal surveillance, diagnosis, and management. Vol. 204, American Journal of Obstetrics and Gynecology. Mosby Inc.; 2011. p. 288–300.12. Royston P, Wright EM. How to construct “normal ranges” for fetal variables. Ultrasound Obstet Gynecol. 1998;11(1):30–8.13. Ruiz-Martinez S, Volpe G, Vannuccini S, Cavallaro A, Impey L, Ioannou C. An objective scoring method to evaluate image quality of middle cerebral artery Doppler. J Matern Fetal Neonatal Med [Internet]. 2018 Jun 27 [cited 2019 Sep 12];1–181. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2995015614. Salomon LJ, Bernard JP, Duyme M, Buvat I, Ville Y. The impact of choice of reference charts and equations on the assessment of fetal biometry. Ultrasound Obstet Gynecol. 2005 Jun;25(6):559–65.<br /

Optimising perinatal outcome in fetal growth restriction using doppler velocimetry

INTRODUCTION: Ante partum fetal surveillance is the corner stone of preventive obstetric management aimed at reducing maternal and perinatal mortality and morbidity. Ante partum detection of fetus at risk of death or compromise in utero remains the major challenge in modern obstetrics. Specific and accurate methods for detection of fetus at risk can result in early appropriate intervention and hence reduce fetal loss. Diagnostic ultrasound is the main stay in the evaluation and management of obstetric patients. Antenatal test of fetal well being depends indirectly on changes in fetal physiology, an aspect of fetus, which until recently, has been relatively inaccessible to study. There has been a paucity of techniques to measure the placental function - the critical organ through which the transfer of nutrients occur. Fetal growth and development rely on normal uteroplacental and fetoplacental circulation to supply oxygen and nutrients from the maternal circulation. New technologies have now become available in the clinical assessment of placental function. Doppler ultrasound offers a non - invasive evaluation of the feto-placental circulation and can identify placental circulatory failure. There are specific abnormalities in Doppler parameters in asymmetric intrauterine growth retardation, which occurs as a result of utero - placental insufficiency . Hence doppler ultrasound plays a key role in antenatal fetal surveillance of high risk pregnancies like evaluation of growth restricted fetuses. AIMS AND OBJECTIVES: 1. To detect any abnormalities in fetoplacental unit and fetal circulation in IUGR. 2. To identify the hypoxemic fetus & time the delivery before the occurrence of acidemia. 3. To correlate the occurrence of adverse perinatal outcome with degree of abnormality in doppler indices. MATERIALS AND METHODS This study was conducted jointly at the Institute of Obstetrics and Gynecology and Barnard Institute of Radiology, Chennai both coming under the Madras Medical College, Chennai. Two hundred documented IUGR cases confirmed by clinical evaluation and serial ultrasound biometry were selected for the study and it was done on singleton pregnant women with welldocumented period of gestation beyond 34 weeks. Known congenital anomalies were excluded from the study. The machine used for Doppler was an Aloka 3500 color Doppler machine with a 3.5 to 5 MHz curvilinear probe. Name, Age, Unit, Registration number and Address of the patients were noted. Detailed obstetric history including the history of pregnancy induced hypertension; gestational diabetes and chronic hypertension were obtained. History of previous pregnancies including birth weight of previous babies, perinatal deaths, and mode of delivery were elicited. Details of present pregnancy were asked, including the date of last menstrual period, details of scan in the first trimester and clinical examination noting, if available, were scrutinized. SUMMARY: Diagnosis of IUGR was done by clinical assessment and serial sonography. • The routine use of SFH measurement together with the use of serial ultrasound examinations in the 3rd trimester of high risk pregnancies detected majority of IUGR cases. • With the use of Doppler of umbilical and middle cerebral arteries, it is possible to predict that an IUGR fetus is not hypoxic. • With ductus venosus alteration, detection of fetal acidemia is possible. • Negative predictive value of normal Doppler is 100%. It means that if the Doppler is normal in an IUGR fetus the possibility of an abnormal perinatal outcome is very rare. So, unnecessary intervention can be reduced in those pregnancies with normal Doppler and normal amniotic fluid volume. • There is a strict co-relation between abnormal umbilical Doppler velocimetry and an increased incidence of perinatal complications in an IUGR fetus. • Incidence of perinatal mortality and morbidity are increased with the worsening of Doppler velocimetry. • In cases with absent and reversed diastolic flow in umbilical artery the perinatal morbidity is nearly100%. • The perinatal mortality in cases of ductus venosus alteration is 100%. • In cases with differential shunting of blood flow to the fetal brain, frequent monitoring and early delivery should be done. • The Doppler ultrasound finding of increased resistance of umbilical artery and decreased resistance of middle cerebral artery, detects the fetus at risk of complications 2 weeks earlier than the conventional methods like NST. • After identifying those fetuses at risk of complications, close monitoring is done by non stress test and bio-physical scoring for planning the delivery so as to improve the perinatal outcome. • Since ductus venosus has been shown to cause irreversible fetal compromise and inevitably leads to fetal demise, close monitoring should be done so as to deliver before the fetus becomes acidotic which is shown by the increase in ductus PI values. CONCLUSIONS: The diagnosis of utero-placental insufficiency causing fetal growth restriction identifies a group of fetuses who are prone for perinatal complications. • Many fetuses with FGR are hypoxemic and some are acidemic even prior to the onset of labor. • The role of antenatal surveillance is identification of the hyproxemic fetus, since the sequelae of hypoxemia can only be altered by iatrogenic intervention. Delivery is timed to precede acidemia. • Doppler ultrasound velocimetry is a noninvasive, repeatable and simple method for antepartum fetal surveillance which holds great promise in this area. • There is a strong correlation between fetal hypoxemia and Doppler measured flow indices of the fetal arterial and venous circulations. • Grading of the Doppler abnormalities can accurately predict the perinatal outcome of the potentially compromised FGR baby much earlier than NST and thus it can be used as a prognostic tool as proved in our study. • So, Doppler ultrasound should be used in all patients with fetal growth restriction, to identify impending hypoxia, to optimise the time of delivery, and hence to optimise the perinatal outcome in these patients

Development of multivariate quality control and quality assurance models for antenatal care service in Indonesia

Neonatal mortality rate (NMR) is an increasingly important public health issue in many developing countries. With an estimated 154 preterm births per 1,000 live births in 2010, Indonesia was ranked 5th highest for preterm births in the world. Estimated birth weight is a significant indicator of the optimal growth, survival and future well-being of newborns. Low birth weight (LBW) is well documented as one of the factors that contributes most to neonatal mortality and it can be caused by preterm birth. Access to routine data on estimated foetal weight (EFW) at a given gestation age (GA) is required to develop a foetal growth chart. Lack of access to such data is one of the reasons for the absence of a standard foetal growth chart in Indonesian antenatal care (ANC) practices. Consistent monitoring of&amp;nbsp; EFW using a foetal growth chart allows early detection of growth abnormalities and can initiate interventions to ensure safe delivery. Low performance of ANC services in measuring and documenting the key performance indicators (KPIs) for maternal and foetal risk assessment is one of the major barriers to reducing NMR in Indonesia. This research has developed statistical quality assurance systems to assess the efficacy of the current performance of ANC services in reducing NMR, particularly among Indonesian rural primary health care centres. This includes identification of the most significant KPIs during pregnancy. To optimise the practical applicability of the research outcomes, a data measuring and recording model that provides a more reliable medical database for the national health system was developed. This was followed by initiating scientific and technical training among urban and rural midwives to improve the quality of routine ANC data collection tasks for maternal and foetal risk assessment and development of a foetal growth chart. The training has equipped nineteen urban and rural midwives in South Kalimantan province with the scientific knowledge and technical abilities to carry out routine collection of ANC data. The ANC information on 4,946 women (retrospective cohort study) and 381 women (prospective cohort study) has been used to assess the impact of the scientific and technical training, particularly its impact on the ability of midwives in settings with limited resources to collect and record the KPIs for maternal and foetal risk assessment and the data for developing the proposed foetal growth chart. The results show that the training has significantly improved the average amount of recorded data for maternal and foetal risk assessment (from 17.5 to 62.1%, p-value &amp;lt; 0.0005) and for developing the foetal growth chart (from 33.4 to 89.1%, p-value &amp;lt; 0.0005). Midwives&#039; views regarding factors which affect their ability to successfully complete the data documentation tasks have also been explored. Lack of awareness, high workload and insufficient skills and facilities are the main reasons for gaps in the data. This research has developed reliable regression models that can easily be implemented in rural primary health care centres to accurately predict EFW at a given GA in the absence of ultrasound facilities. Multiple comparison criteria showed that the proposed models are more accurate than the existing clinical and ultrasound models in predicting foetal weight between 35 and 41 weeks of GA, and much more accurate at earlier GAs. The results also indicate that foetal weight can be best predicted by the measurement of maternal fundal height (FH). The model based on FH can be utilised in rural areas where advanced health equipment such as ultrasound is not always accessible. Prior to the development of a new foetal growth chart, the research reviewed the existing growth charts for EFW. The potential challenges in utilising such surveillance tools in Indonesia were also investigated. The results showed that the customised and standard foetal growth charts for EFW used internationally had been developed and highly recommended for use without local data being available. Moreover, limited access to ultrasound measurement of foetal biometric characteristics hindered foetal weight estimation using the existing models. Low levels of recording of the minimum database requirements on individual maternal, foetal and neonatal characteristics also made the existing customised charts less applicable in the local setting.&amp;nbsp;&amp;nbsp; For the first time an alternative foetal growth chart for EFW, which only requires information on FH, has been developed to monitor and identify unusual growth of a foetus. The efficacy of the proposed chart has been assessed by using it to look for abnormal patterns of foetal growth in the data recorded for normal and LBW newborns. The results highlighted the effectiveness of the developed growth chart for risk assessment during pregnancy to prevent the occurrence of LBW delivery. Using prospective data, it was shown that the proposed chart can effectively detect signs of abnormality between 20 and 41 weeks of GA. It was also shown that the existing foetal growth chart does not fit Indonesian data in the absence of ultrasound information. This research has also evaluated the prediction accuracy of the ultrasound-based prediction models used in the development of the existing foetal growth charts for EFW and compared them with the proposed clinical-based prediction model using the Indonesian data. The results showed that the proposed model has comparable ability, and is even more effective at earlier GAs in predicting foetal weight than the existing models. This justifies the utilisation of the proposed prediction model in the development of the new foetal growth chart. The outcome of this research provides a useful administrative and scientific guideline for the expansion of health services programs and for the more effective distribution of limited government resources in rural area. It includes analysis of where further aid investments are likely to best impact on reducing the NMR. The outcome also aids midwives in identifying the key risk factors and types of clinical interventions required prior to delivery to reduce the mortality rate

Optimisation of gestational age estimates in low-income settings

Accurate estimates of gestational age are fundamental to the provision of obstetric care, helping to facilitate appropriate antenatal care schedules and the identification and management of high-risk pregnancies. At a population level, accurate estimates of gestational age are required for the global reporting of obstetric and neonatal outcomes, for example, the rates of pre-term birth, and are a key component of strategies to reduce neonatal morbidity and mortality. Early pregnancy ultrasound is considered the most accurate way to determine gestational age and is undertaken as part of routine care in high-income settings. However, despite the recommendation from the World Health Organisation that all women receive at least one ultrasound prior to 24 weeks’ gestation, this remains unavailable to the majority of women in low-income settings. Instead, gestational age is derived from the last menstrual period or by measurement of the symphysis fundal height, methods known to be considerably less accurate. There are a number of barriers to the widespread provision of ultrasound as part of routine care in low- and middle- income settings, not least the lack of trained practitioners. Although effective, the length and complexity of many previous training programmes has been prohibitive, with practitioners struggling to secure cover for their clinical duties in order to provide or attend training. Furthermore, few initiatives have explored the widespread implementation of these programmes and how they may be sustained within pre-existing healthcare structures. Ultrasound determination of gestational age relies on the assumption that the size of the fetus is consistent with its age and is therefore best performed prior to 14 weeks’ gestation, when natural variation in fetal size is least apparent. Unfortunately, the majority of women in low- and middle- income countries do not seek antenatal care until later and would therefore require dating by different biometric parameters. In high-income settings the gold standard would be a combination of measurements, however there are concerns about the time investment required to develop such skills. The work in this Thesis explores the development of a novel strategy to optimise estimates of gestational age in Malawi, through the development and implementation of a bespoke education package to teach midwives how to date pregnancies using ultrasound measurement of the fetal femur length. A systematic review investigated the previous initiatives that had been undertaken to train practitioners in low- and middle- income countries to determine gestational age using ultrasound, finding major inconsistences in the current provision of ultrasound training and highlighting the need for a more consistent and robust approach. Less than half of the programmes met international recommendations for the delivery of safe and sustainable training, and many had not considered how ultrasound may be integrated into clinical practice thereafter. The evidence synthesised went on to inform the development of a new programme, where it was hypothesised that ultrasound-naive midwives could be taught to date pregnancies using fetal femur length. Pilot work helped to shape and refine the programme, which was delivered by local teams across six sites in Malawi in 2021. All but one midwife completed the course, with all demonstrating significant increases in their knowledge, confidence, and practical skills, achieving the criteria specified for competency within the specified two weeks. Skills were sustained at a 3-month follow up, and of the images submitted for remote image review, over 87% were deemed acceptable. These results suggest that femur length is a sufficiently simple measurement to be taught effectively over a short timescale, making it a potentially viable option for the upscale of ultrasound to date pregnancies in this setting. A mixed methods study, run by the wider collaborative group, evaluated the implementation of ultrasound into routine services, however the work in this Thesis focused more specifically on the provision of the programme itself. Outcomes were reported in the context of an implementation framework, providing valuable insight into factors influencing the longterm sustainability of such endeavours. It is clear this is an important area for ongoing research. In conclusion, this Thesis proposes that measurement of fetal femur length should be considered a potential option for the determination of gestational age in low- and middle- income settings. Not only is it considerably more accurate than the current standard of care, but midwives with no prior experience of ultrasound can be trained to perform these measurements, confidently and competently, after just two weeks of training, a substantially shorter training duration than many previous initiatives. Although many implementation challenges persist, this programme provides a potentially more sustainable means by which to provide a greater number of women more accurate estimates of gestational age

Brain growth and development in fetuses with congenital heart disease

Introduction and Objectives: In the current era of excellent surgical results for congenital heart disease (CHD), focus has become directed on quality of life for these children. Previous studies have shown that neurodevelopmental outcome in CHD is impaired. The mechanisms are incompletely understood but there is increasing evidence that the origins of this are in fetal life. This thesis aims to describe the in utero brain growth in a cohort of fetuses with CHD and relate this to the circulatory abnormalities and fetal Doppler parameters. Methods: Pregnant women with a fetus with CHD were prospectively recruited. The congenital heart defect was phenotyped using fetal echocardiography and patients subdivided into three physiological groups on the basis of the anticipated abnormality of cerebral blood flow and oxygen delivery: (1) isolated reduced flow to the brain; 2) reduced oxygen saturation of cerebral blood flow; (3) combination of reduced oxygen and flow. Fetal brain MRI was performed. In addition to standard biometric measurements, snapshot to volume reconstruction (SVR) was used to construct a 3D data set from the oversampled raw data. From these 3D volumes the total brain volume and ventricular volumes were measured by manual segmentation. Serial measurements of fetal growth were also made and umbilical artery and middle cerebral artery Doppler parameters were analysed. Results: 29 women were included; comparison was made with 83 normal MRI controls. Fetuses with CHD were found to have smaller brain volumes compared to controls when adjusting for advancing gestation (p<0.01). This difference becomes more pronounced with advancing gestation, suggesting a slower rate of in utero brain growth. Measurements of growth found that the fetuses with CHD were smaller throughout gestation with a highly significant difference at the later growth scan. (p<0.001). Cerebral and umbilical artery Doppler data showed evidence of reduced cerebrovascular resistance in fetuses with CHD but did not show a difference in the umbilical artery Doppler. Conclusion: Fetuses with CHD have evidence of impaired brain growth with advancing pregnancy and an increased rate of overall growth restriction. Doppler evidence of cerebral vasodilation supports the mechanism of reduced oxygen delivery as an underlying cause.Open Acces

Preventing term stillbirth: benefits and limitations of using fetal growth reference charts.

PURPOSE OF REVIEW: This review examines the variation in clinical practice with regards to ultrasound estimation of fetal weight, as well as calculation of fetal weight centiles. RECENT FINDINGS: Placental dysfunction is associated with fetal smallness from intrauterine malnutrition as well as fetal disability and even stillbirth from hypoxemia. Although estimating fetal weight can be done accurately, the issue of which fetal weight centile chart should be used continues to be a contentious topic. The arguments against local fetal growth charts based on national borders and customization for variables known to be associated with disease are substantial. As for other human diseases such as hypertension and diabetes, there is a rationale for the use of an international fetal growth reference standard. Irrespective of the choice of fetal growth reference standard, a significant limitation of small for gestational age (SGA) detection programs to prevent stillbirth is that the majority of stillborn infants at term were not SGA at the time of demise. SUMMARY: Placental dysfunction can present with SGA from malnutrition and/or stillbirth from hypoxemia depending on the gestational age of onset. Emerging data show that at term, fetal Doppler arterial redistribution is associated more strongly with perinatal death than fetal size. Properly conducted trials of the role for maternal characteristics, fetal size, placental biomarkers, and Doppler assessing fetal well-being are required urgently

Prediction of Adverse Perinatal Outcome in Growth Restricted Fetuses with Antenatal Doppler Study.

Ante Partum Fetal Surveillance Is The Corner Stone Of Preventive Obstetric Management Aimed At Reducing Maternal And Perinatal Mortality And Morbidity. Ante Partum Detection Of Fetus At Risk Of Death Or Compromise In Utero Remains The Major Challenge In Modern Obstetrics. Specific And Accurate Methods For Detection Of Fetus At Risk Can Result In Early Appropriate Intervention And Hence Reduce Fetal Loss. Antenatal Test Of Fetal Well Being Depends Indirectly On Changes In Fetal Physiology, An Aspect Of Fetus, Which Until Recently, Has Been Relatively Inaccessible To Study By The Paucity Of Techniques To Measure The Placental Function - The Critical Organ Through Which The Transfer Of Nutrients Occur. New Technologies Have Now Become Available In The Clinical Assessment Of Placental Function. Doppler Measurement Of The Pulsatile Blood Velocity In Umbilical Artery Gives Direct Information On Feto-Placental Circulation And Hence Identifies Placental Circulatory Failure. Diagnostic Ultrasound Is The Main Stay In The Evaluation And Management Of Obstetric Patients. Fetal Growth And Development Rely On Normal Uteroplacental And Fetoplacental Circulation To Supply Oxygen And Nutrients From The Maternal Circulation. Doppler Sonography Offers A Unique Tool For The Noninvasive Evaluation Of Physiological Hemodynamic Fetoplacental Blood Flow Information. There Are Specific Abnormalities In Doppler Parameters In Asymmetric Intrauterine Growth Retardation. Fetal Growth Restriction (FGR), Otherwise Known As Intrauterine Growth Restriction Is Defined As A Pathologic Decrease In The Rate Of Fetal Growth. Here The Fetus Does Not Achieve Its Inherent Growth Potential, Thereby Increasing Perinatal Morbidity And Mortality. Small For Gestational Age (SGA) Is Conceptually Not The Same Entity As FGR. It Is Defined As Fetus Which Has Failed To Achieve Specific And Arbitrary Anthropometric Measurements Or Weight Threshold By A Specific Gestational Age, Whereas In FGR, The Infant Has Not Achieved Its Genetic Growth Potential In Utero (Rajan. R. 2001). All FGR Fetuses Don't Suffer From In Utero Compromise In Terms Of Hypoxia Or Acidemia. Fetal Growth Restriction Only Means That The Fetus Has Not Grown Appropriately For The Corresponding Gestational Age, And Does Not Necessarily Mean It Is A Situation Of Uteroplacental Respiratory Insufficiency Causing Fetal Hypoxia Or Acidemia. But Many IUGR Fetuses Could Sooner Or Later Become Hypoxemic, Hypoxic And Acidotic As A Progressive Event Of The Pathophysiology. Diagnosis Of IUGR Is Based On B-Mode Ultrasound. Estimation Of Fetal Weight In Utero Using Multiple Ultrasound Parameters Remains The Mainstay In Screening For FGR. Use Of Various Fetal Morphometric Ratios And/Or Measurements Of Other Fetal Parameters May Provide Additional Useful Information. Serial Evaluation To Assess Interval Growth May Be Necessary To Clarify The Diagnosis. Doppler Velocimetry Has Poor Sensitivity In Detecting IUGR, Whereas It Is Helpful In Assessing The Hemodyanmic State. Doppler Indices Change If The Fetus Is Compromised Due To Hypoxemia. Doppler Flow Velocimetry, Particularly Of The Middle Cerebral And Umbilical Arteries Is An Earlier Predictor Of Hypoxemia, When Compared To BPP Or NST. Ductus Venosus Flow Study Is An Accurate Predictor For Acidemia. The Relationship Between The Size Of Fetal Abdominal Circumference And Fetal Head Is Used To Characterize The Pattern Of FGR As Being Either Symmetric Or Asymmetric. Symmetric IUGR Refers To A Growth Pattern In Which The Growth Of Both The Fetal Abdomen And Head Are Decreased Proportionally. Asymmetric IUGR Refers To The Growth-Retarded Fetus In Which A Disproportionate Decrease In The Size Of Fetal Abdomen With Respect To The Fetal Head Is Seen. Symmetric IUGR May Result From An Early Insult Such As Genetic Or Infective Pathology That Impairs Fetal Cellular Hyperplasia And Therefore Causes A Proportionate Decrease In Size Of All Fetal Organs. By Contrast, Asymmetric IUGR May Be Caused By A Later Insult That Impairs Cellular Hypertrophy, Causes A Disproportionate Decrease In The Size Of Fetal Abdomen In Relation To That Of The Fetal Head. Progressive Uteroplacental Insufficiency May Be Associated With This Asymmetric Growth Pattern. Nearly 70% Of Patients With IUGR May Be Classified As Having An Asymmetrical Growth Pattern. These Cases May Be At Greater Risk For Perinatal Hypoxia And Neonatal Hypoglycemia. However, Their Long-Term Prognosis With Appropriate Management Is Good. Symmetric IUGR Results From An Early Insult And Is Characterized By A Long Period Of Subnormal Growth. These Infants Usually Do Not Have Perinatal Hypoxia, But They Are At Risk Of Long-Term Neurodevelopmental Dysfunction, Resulting From A Deficit In The Total Number Of Brain Cells