Objetivos: avaliar a contribuição do fluxo anormal no ducto venoso de 11 a 13 6/7 semanas no rastreamento de anomalias cromossômicas, defeitos estruturais e prognóstico gestacional. Método: 1221 gestações únicas foram submetidas a Dopplervelocimetria do ducto venoso após o rastreamento pela translucência nucal (TN). Resultados: os defeitos cromossômicos foram diagnosticados em 22 fetos. O fluxo no ducto venoso estava anormal em 84 fetos, a TN estava acima do 95o percentil em 160 casos e ambos marcadores estiveram anormais em 41 fetos. A sensibilidade, especificidade, valores preditivos positivo e negativo para defeitos cariotípicos corresponderam respectivamente a 86,4%, 86,9%, 11,9% e 99,7% considerando a TN aumentada, 68,2%, 96,9%, 31,3%, 99,3% para anomalias do fluxo do ducto venoso e 68,2%, 97,6%, 36,6%, 99,3% analisando ambos os marcadores. Investigando malformações estruturais, esses valores foram de 43,8%, 92,9%, 8,3%, 99,1% para uma TN aumentada, 25%, 92,6%, 4,8%, 98,8% para anomalias do fluxo do ducto venoso e 25%, 97,9%, 15,4%, 98,9% para ambos os marcadores. Nos casos com TN aumentada, a proporção de nascidos vivos morfológica e cariotipicamente normais diminui de 93,8% nos fetos com fluxo no ducto venoso normal para 77,3%, quando anormal. Conclusão: a avaliação do ducto venoso de 11 a 13 6/7 semanas de gestação pode ser utilizada no rastreamento de anomalias cromossômicas fetais e pode ajudar a reduzir a taxa de falso-positivo quando combinado com a medida da TN. Em fetos com TN aumentada o fluxo anormal no ducto venoso aumenta a probabilidade de resultados gestacionais adversos / Objective: To evaluate the association between abnormal ductus venosus at 11 - 13 6/7 weeks\' gestation and chromosomal abnormalities, structural defects and fetal outcome. Methods: Ductus venosus waveform (DVFVW) and nuchal translucency (NT) thickness were prospectively evaluated in 1221 singleton pregnancies. Results: The DVFVW was abnormal in 84 cases, NT was above the 95th centile in 160 cases and both markers were observed in 41 fetuses. Chromosomal defects were diagnosed in 22 fetuses. The sensitivity, specificity and positive predictive values for an abnormal karyotype were respectively 86.4%, 86.9%, 11.9% for an increased NT; 68.2%, 96.9%, 31.3% for DVFVW abnormalities and 68.2%, 97.6%, 36.6% for both markers. Regarding structural defects, this values were 43.8%, 92.9%, 8.3% for an abnormal NT, 25%, 92.6%, 4.8% for DVFVW abnormalities and 25%, 97.9%, 15.4% for both. Considering those cases of unexplained fetal demise, the percentages were 44.4%, 85.9%, 5% for NT abnormalities, 22.2%, 92.6%, 4.8% for an abnormal DVFVW and 22.2%, 98%, 15.4% for both. In cases with increased NT measurement, the percentage of livebirths with normal karyotype and no major fetal structural defects decreased from 93.8% in normal DVFVW fetuses to 77.3%, when abnormal. Conclusion: Ductus venosus assessment at 11 - 13 6/7 weeks\' gestation is useful in screening for fetal chromosomal abnormalities and may help to reduce the false-positive rate when combining with NT thickness measurement. Abnormal DVFVW is also associated with an increase of adverse perinatal outcome in fetuses with enlarged NT. However, the value of DVFVW assessment in cases with normal NT measurement is unclear

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Abstract not available

Thesis (MNutr (Interdisciplinary Health Sciences. Human Nutrition))--University of Stellenbosch, 2006. / INTRODUCTION: The objective of the study was to determine the prevalence of certain known risk factors for intra-uterine growth restriction (IUGR) in women who gave premature birth to growth-restricted infants at a large regional hospital (Kalafong) in the Gauteng province of South Africa and to investigate the possible associations between the presence of various risk factors and the severity of growth restriction found in these infants. METHOD: The study was designed as cross-sectional, descriptive and observational. The subjects included singleton growth-restricted premature infants (n=80), without congenital abnormalities and their mothers (n=80). Anthropometric data [weight, height, mid-upper arm circumference (MUAC) and triceps skinfold thickness (TSF)] were collected from these mothers three to four days post-partum. Infant birth weights were recorded at birth, while the lengths and head circumferences were recorded within 2 days post-partum. Additional information, such as birth spacing, maternal age, smoking habits and alcohol use, was collected by personal interview and blood pressure data and HIV status was obtained from medical records. Data capturing and descriptive statistics were done using Microsoft Excel and comparative analytical statistics were performed with the Statistical Package for the Social Sciences (SPSS), version 12.0. RESULTS: The study demonstrated a high prevalence (69%) of infants born with a birth weight <3rd percentile. In the sample, 81% of the mothers were aged 17-34 years and most (93%) had their children 18 months or longer apart. Malnutrition prevalence was moderate. In 58% of the mothers the BMI was normal (18.5-24.9 kg/m2) and in 47% the upper arm muscle area (UAMA) was between the 10th-85th percentile. Grade III overweight occurred in 3% and TSF ≤5th percentile occurred in 35% of the mothers. About half (51%) of the mothers in the sample population had hypertension during the second trimester of pregnancy. Smoking and alcohol use during pregnancy was rare (1% and 6% respectively) and the prevalence of HIV infection in the mothers was 26%. The prevalence (16%) of Grade II overweight among the mothers of symmetric growth-restricted (SGR) infants was higher than among the mothers of asymmetric growth-restricted (AGR) infants (7%). Of the hypertensive mothers, 55% had infants with SGR compared to 45% with AGR (p=0.47). Although rare, smoking occurred only in mothers with AGR infants (3%). No significant differences were found between the smoking and non-smoking group (p=0.21). Although the use of alcohol was more prevalent at 6% in mothers with SGA infants and 7% in mothers with AGR infants, no significant associations were found (p=0.95). Although not significant (p=0.76), there was a higher prevalence of HIV infection in mothers with SGR infants at 29%, compared to 23% of mothers of AGR infants. CONCLUSION: Although further studies are needed before intervention strategies can be planned and implemented, the findings of this study suggest that apart from the usual factors (maternal age and nutritional status, smoking and alcohol use during pregnancy and birth spacing) that may influence intra-uterine growth, hypertension may contribute greatly to IUGR in this study population.

Objetivo: Comparar o desempenho de diferentes curvas de referência de crescimento fetal em gestações gemelares com insuficiência placentária grave. Método: Estudo retrospectivo envolvendo gestações gemelares (n=47), com fluxo diastólico zero ou reverso, no estudo dopplervelocimétrico da artéria umbilical de um dos fetos, e ambos os fetos vivos no momento do diagnóstico. Não foram incluídas gestações com anomalia fetal \"major\", síndrome de transfusão feto-fetal, ou de ordem maior. Em ambos os fetos (acometido, FA; e cogemelar, CG), as estimativas de peso fetal foram convertidas em escore zeta de acordo com os critérios de Hadlock, Liao e Araújo. As medidas de circunferência abdominal foram convertidas de acordo com as curvas de Hadlock, Liao, Araújo, Ong e STORK. A análise estatística foi realizada segundo modelos de equações de estimação generalizada. Resultados: A idade materna média foi 27,8 ± 7,4 anos, 24 (51%) pacientes eram primigestas, 12 (25,5%) apresentavam antecedentes clínicos significativos e 61,7% (n=29) eram monocoriônicas. A idade gestacional média no momento do diagnóstico da diástole zero ou reversa foi de 27,4 ± 4,7 semanas. A idade gestacional média do parto foi de 32,9 ± 2,9 semanas e o peso médio ao nascimento dos fetos acometidos foi de 1075 ± 469 g, e dos cogemelares, 1749 ± 544 g. No modelo investigado, foram preditores significativos do escore-zeta: sexo fetal (p < 0,001) e a interação sub-grupo (feto acometido/cogemelar) e critério (p < 0,001). As estimativas do escore zeta médio (erro padrão) para o peso fetal estimado segundo cada critério examinado foram Hadlock FA: -2.98 (0,18), CG: -1,16 (0,15), Liao FA: -2,89 (0,24), CG: -0,58 (0,19), Araújo FA: -3,05 (0,29), CG: - 0,75 (0,18). Para circunferência abdominal, Hadlock FA: -3,14 (0,26), CG: - 1,13 (0,19), Liao FA: -2,63 (0,27), CG: -0,42 (0,19), Araújo FA: -2,44 (0,22), CG: -0,71 (0,14), Ong FA: -3,36 (0,34), CG: -1,48 (0,23) e STORK FA: -2,36 (0,14), CG: -1,18 (0,10). Conclusão: Em gestações gemelares, com diástole zero ou reversa em um dos fetos, as curvas que melhor diferenciaram os fetos acometidos de seus cogemelares foram as curvas nacionais, publicadas por Liao et al. e Araújo et al / Objectives: To compare the performance of different fetal growth reference curves in twin pregnancies with severe placental insufficiency. Methods: Retrospective analysis of 47 twin pregnancies with absent or reverse end diastolic flow in the umbilical artery in one fetus, and both twins alive at diagnosis. Pregnancies with major fetal abnormality, twin-twin transfusion and higher order were not included. At each ultrasound evaluation, estimated fetal weight zeta-scores were calculated for both fetuses (abnormal Doppler, AD; co-twin, CT) according to the following criteria: Hadlock, Liao and Araújo. Abdominal circumference zeta-scores were calculated according to Hadlock, Liao, Araújo, Ong and STORK. Statistical analysis was performed with generalized estimating equation regression. Results: Mean maternal age was 27.8 ± 7.4 years, 24 (51%) women were primigravida, 12 (25.5%) had a previous clinical history and 29 (61.7%) were monochorionic. Gestational age at abnormal Doppler diagnosis was 27.4 ± 4.7 weeks. Gestational age at delivery was 32.9 ± 2.9 weeks and mean birthweight was 1075 ± 469 g for AD twin, and 1749 ± 544 g in CT group. Zeta-score values were significantly related to fetal sex (p < 0.001) and subgroup (abnormal Doppler/co-twin) versus criteria interaction (p < 0.001). Estimated fetal weight mean zeta-score (standard error) according to each criteria were: Hadlock AD: -2.98 (0.18), CT: -1.16 (0.15), Liao AD: -2.89 (0.24), CT: -0.58 (0.19), Araújo AD: -3.05 (0.29), CT: -0.75 (0.18). Values for abdominal circumference were: Hadlock AD: -3.14 (0.26), CT: -1.13 (0.19), Liao AD: -2.63 (0.27), CT: -0.42 (0.19), Araújo AD: -2.44 (0.22), CT: -0.71 (0.14), Ong AD: -3.36 (0.34), CT: -1.48 (0.23) and STORK AD: -2.36 (0.14), CT: -1.18 (0.10). Conclusion: In twin pregnancies with absent or reversed end diastolic flow in the umbilical artery of one fetus, affected fetuses and their co-twins are best differentiated by Liao et al. and Araújo et al. reference ranges

Objetivo: Comparar o desempenho de diferentes curvas de referência de crescimento fetal em gestações gemelares com insuficiência placentária grave. Método: Estudo retrospectivo envolvendo gestações gemelares (n=47), com fluxo diastólico zero ou reverso, no estudo dopplervelocimétrico da artéria umbilical de um dos fetos, e ambos os fetos vivos no momento do diagnóstico. Não foram incluídas gestações com anomalia fetal \"major\", síndrome de transfusão feto-fetal, ou de ordem maior. Em ambos os fetos (acometido, FA; e cogemelar, CG), as estimativas de peso fetal foram convertidas em escore zeta de acordo com os critérios de Hadlock, Liao e Araújo. As medidas de circunferência abdominal foram convertidas de acordo com as curvas de Hadlock, Liao, Araújo, Ong e STORK. A análise estatística foi realizada segundo modelos de equações de estimação generalizada. Resultados: A idade materna média foi 27,8 ± 7,4 anos, 24 (51%) pacientes eram primigestas, 12 (25,5%) apresentavam antecedentes clínicos significativos e 61,7% (n=29) eram monocoriônicas. A idade gestacional média no momento do diagnóstico da diástole zero ou reversa foi de 27,4 ± 4,7 semanas. A idade gestacional média do parto foi de 32,9 ± 2,9 semanas e o peso médio ao nascimento dos fetos acometidos foi de 1075 ± 469 g, e dos cogemelares, 1749 ± 544 g. No modelo investigado, foram preditores significativos do escore-zeta: sexo fetal (p < 0,001) e a interação sub-grupo (feto acometido/cogemelar) e critério (p < 0,001). As estimativas do escore zeta médio (erro padrão) para o peso fetal estimado segundo cada critério examinado foram Hadlock FA: -2.98 (0,18), CG: -1,16 (0,15), Liao FA: -2,89 (0,24), CG: -0,58 (0,19), Araújo FA: -3,05 (0,29), CG: - 0,75 (0,18). Para circunferência abdominal, Hadlock FA: -3,14 (0,26), CG: - 1,13 (0,19), Liao FA: -2,63 (0,27), CG: -0,42 (0,19), Araújo FA: -2,44 (0,22), CG: -0,71 (0,14), Ong FA: -3,36 (0,34), CG: -1,48 (0,23) e STORK FA: -2,36 (0,14), CG: -1,18 (0,10). Conclusão: Em gestações gemelares, com diástole zero ou reversa em um dos fetos, as curvas que melhor diferenciaram os fetos acometidos de seus cogemelares foram as curvas nacionais, publicadas por Liao et al. e Araújo et al / Objectives: To compare the performance of different fetal growth reference curves in twin pregnancies with severe placental insufficiency. Methods: Retrospective analysis of 47 twin pregnancies with absent or reverse end diastolic flow in the umbilical artery in one fetus, and both twins alive at diagnosis. Pregnancies with major fetal abnormality, twin-twin transfusion and higher order were not included. At each ultrasound evaluation, estimated fetal weight zeta-scores were calculated for both fetuses (abnormal Doppler, AD; co-twin, CT) according to the following criteria: Hadlock, Liao and Araújo. Abdominal circumference zeta-scores were calculated according to Hadlock, Liao, Araújo, Ong and STORK. Statistical analysis was performed with generalized estimating equation regression. Results: Mean maternal age was 27.8 ± 7.4 years, 24 (51%) women were primigravida, 12 (25.5%) had a previous clinical history and 29 (61.7%) were monochorionic. Gestational age at abnormal Doppler diagnosis was 27.4 ± 4.7 weeks. Gestational age at delivery was 32.9 ± 2.9 weeks and mean birthweight was 1075 ± 469 g for AD twin, and 1749 ± 544 g in CT group. Zeta-score values were significantly related to fetal sex (p < 0.001) and subgroup (abnormal Doppler/co-twin) versus criteria interaction (p < 0.001). Estimated fetal weight mean zeta-score (standard error) according to each criteria were: Hadlock AD: -2.98 (0.18), CT: -1.16 (0.15), Liao AD: -2.89 (0.24), CT: -0.58 (0.19), Araújo AD: -3.05 (0.29), CT: -0.75 (0.18). Values for abdominal circumference were: Hadlock AD: -3.14 (0.26), CT: -1.13 (0.19), Liao AD: -2.63 (0.27), CT: -0.42 (0.19), Araújo AD: -2.44 (0.22), CT: -0.71 (0.14), Ong AD: -3.36 (0.34), CT: -1.48 (0.23) and STORK AD: -2.36 (0.14), CT: -1.18 (0.10). Conclusion: In twin pregnancies with absent or reversed end diastolic flow in the umbilical artery of one fetus, affected fetuses and their co-twins are best differentiated by Liao et al. and Araújo et al. reference ranges

L’alpha-foetoprotéine (AFP) est la protéine majoritaire du sérum fœtal de mammifère. C’est une glycoprotéine produite et sécrétée par l’endoderme viscéral du sac vitellin, les hépatocytes fœtaux et dans une moindre mesure, par l’intestin fœtal. Son profil d’expression est onco-fœtal :la synthèse de cette protéine chute fortement après la naissance mais peut reprendre en cas de régénération hépatique ou en cas de tumeurs diverses. Cette protéine est capable de fixer les oestrogènes et jouerait un rôle dans la différenciation sexuelle du cerveau femelle.<p>\ / Doctorat en sciences, Spécialisation biologie moléculaire / info:eu-repo/semantics/nonPublished

Impaired intrauterine growth, inability of the fetus to achieve the required growth potential, contributes to a higher burden of neonatal morbidity and mortality. Intrauterine growth is an inferred process and small for gestational age is considered a rough estimate of impaired intrauterine growth that requires reliable gestational age data. Due to sparse data and measurement errors in gestational age, researchers rely on markers such as birth weight, birth length, and birth head circumference to infer fetal growth. While the etiology of impaired fetal growth is multifactorial, maternal anemia and undernutrition contribute substantially to impaired fetal growth and are prioritized in 2030 global nutrition goals by the World Health Assembly. Nutrition supplements such as lipid-based nutrient supplements, multiple micronutrients, and iron or folic acid during pregnancy are presumed to improve maternal anemia. But the effect of the supplements during pregnancy on fetal growth appears to be small to negligible, which has shifted the researcher’s focus to the pre-conception period. However, prior reviews on the preconception period have either synthesized the evidence from observational studies, or have explored outcomes such as congenital anomalies (e.g., neural tube defects), neurodevelopment disorders, or only birth weight. Hence the evidence from existing randomized controlled trials (RCTs) evaluating the effect of preconception nutrition supplements on maternal anemia and all markers of fetal growth including birth weight, birth length, and birth head circumference has not been systematically summarized and synthesized. We bridged this knowledge gap in the current dissertation (Aim 1). The Women First (WF) Preconception Nutrition Trial found that lipid-based nutrient supplementation started preconception or during pregnancy conferred greater benefits for birth weight and birth length among mothers who were anemic (Hemoglobin (Hb) < 12 g/dL) than among mothers who were non-anemic (Hb ≥ 12 g/dL) pre-pregnancy. However, by dichotomizing women into anemic and non-anemic women, we may miss high-risk women with specific Hb levels who may obtain greater benefits for intrauterine growth associated with the supplements. Assessing the effect of preconception nutrient supplements across a range of pre-pregnancy Hb levels will help us identify women with specific Hb cut-offs who may have the greatest potential to respond to the supplements (Aim 2). Additionally, there are major gaps in understanding the mechanisms of how nutrient supplements, consumed either before or during pregnancy, improve intrauterine growth. A better understanding of the underlying mechanisms would allow for fine-tuning of nutrition interventions for greater efficacy. Here, we examined whether Hb during pregnancy could be a potential mechanism through which nutrition supplements improve intrauterine growth (Aim 3). For Aim 1, we undertook a systematic review and meta-analysis of the RCTs evaluating the effect of preconception nutrition supplements on maternal hemoglobin and markers of intrauterine growth including birth weight, birth length, birth head circumference, and small for gestational age. Additionally, we examined preterm birth as an important perinatal outcome. We searched electronic databases including PubMed, Web of Science, Embase, CINAHL, and Cochrane Central. We computed pooled mean differences and risk ratios (RR) with 95% confidence intervals (CIs) using random-effect models. We employed I2 and Cochran’s Q test statistics to assess heterogeneity. We used the GRADE (grading of recommendations, assessment, development, and evaluations) tool to assess the quality of evidence. For Aim 2 and Aim 3, we leveraged the existing data from a large multi-country Women First (WF) Preconception Nutrition Trial conducted in Pakistan, India, Guatemala, and the Democratic Republic of Congo. Women in the WF trial were randomized to consume a lipid-based nutrient supplement (LNS) at least three months before and during pregnancy (Arm 1- preconception), only during pregnancy (Arm 2- during), or not at all (Arm 3 - control). The outcome was weight, length, and head circumference within 48 hours of birth expressed as Z-scores. For Aim 2, we analyzed the WF trial data on 2443 women-newborn dyads. For each site, we computed adjusted mean differences in these Z-scores between the randomized arms across six pre-pregnancy Hb categories (8-8.9, 9-9.9, 10-10.9, 11-11.9, 12-12.9, and ≥13g/dL) based on Hb distributions. We pooled site-specific effect measures using meta-analysis. For Aim 3, hemoglobin measured at 12 (n=2075) and 32 weeks of gestation (n=2157) was a mediator. We employed causal mediation analysis under a counterfactual approach to estimate direct and indirect effects. For Aim 1, we identified 20 eligible RCTs (n=27,659 women). Preconception nutrition supplements (iron and folic acid, multiple micronutrients, and a lipid-based nutrient supplement) increased maternal hemoglobin by 0.30g/dL ((0.03, 0.57); I2=79%). However, we did not find a significant effect of the supplements on birth weight (12.47gm ((-33.14, 58.08); I2=58%)), birth length (0.15cm (-0.26, 0.56); I2=68%; n=5), birth head circumference (-0.23cm (-0.88, 0.43); I2=84%), small for gestational age (RR: 0.91 (0.80,1.04); I2=31%), or preterm birth (RR: 0.93 (0.69,1.25); I2=57%). Overall, the quality of evidence was assessed as moderate and very low for maternal hemoglobin and three markers of intrauterine growth including birth weight, birth length, and birth head circumference, respectively. In Aim 2, we found that the effect of LNS on birth weight, length, and head circumference varied by pre-pregnancy Hb categories. Pooled mean differences in the Z-scores for birth length (0.60 (0.03, 1.23)), birth weight (0.50, (0.11, 0.89)), and birth head circumference ((0.26, (0.02, 0.51)) were greatest for Arm 1-preconception vs. Arm 3-control women with Hb 9-9.9g/dL. Women with Hb 10-10.9g/dL also benefited from preconception LNS. However, compared to controls, the effects of preconception LNS on birth weight, birth length, and birth head circumference attenuated for women with Hb 10-10.9g/dL. Compared to Arm 3-control, LNS during pregnancy (Arm 2) improved birth length, birth weight, and birth head circumference for women with Hb 8-10.9g/dL. Preconception LNS (Arm1) vs. LNS during pregnancy (Arm 2) improved the three markers of intrauterine growth only for women with Hb 9-9.9g/dL. Women with nearly normal (11-11.9 g/dL) and normal Hb (≥12g/dL) did not appreciably benefit from LNS, offered before and or during pregnancy. For Aim 3, Hb at 12 or 32 weeks of gestation did not mediate the relationship between the LNS and intrauterine growth. Indirect effects of preconception LNS (Arm 1) vs. Arm 3, mediated by Hb at 12 weeks, were 0.02 (-0.02, 0.01), 0.01 (-0.01, 0.02), and 0.01 (-0.01, 0.02) for length, weight, and head circumference Z-scores, respectively. The corresponding direct effects, not mediated by Hb, were 0.18 (0.09, 0.33), 0.12 (0.03, 0.23), and 0.06 (-0.03, 0.20), respectively. Site-specific and gestational age-adjusted data analyses both at 12 and 32 weeks of gestation confirmed the findings of negligible mediation by Hb during pregnancy. All types of preconception nutrition supplements studied to date appear to reduce maternal anemia. However, it is uncertain whether there are beneficial effects of preconception nutrition supplements on markers of intrauterine growth. Low quality of evidence from the RCTs examining the markers of intrauterine growth warrants future well-designed RCTs to produce solid scientific data, particularly on the benefits of a more comprehensive package of preconception nutrition supplements that include both macro- and micronutrients. The findings from the WF trial suggest that the benefits of preconception LNS on fetal growth are mainly confined to women with pre-pregnancy Hb 9-9.9g/dL. Compared to controls, women with Hb 10-10.9g/dL also benefited from preconception LNS, albeit the magnitude of effect on three markers of intrauterine growth was modest for women with Hb 10-10.9g/dL. However, LNS, started during pregnancy, appeared to improve markers of intrauterine growth for women with a wider range of Hb 8-10.9g/dL. Women with Hb ≥ 11g/dL did not benefit from LNS started either pre-conception or during pregnancy. These findings suggest that prioritizing women with specific pre-pregnancy Hb categories for targeted nutrition interventions may be advisable. This would target limited resources most efficiently in LMICs. Lastly, negligible mediation by Hb during pregnancy suggests that alternative pathways that potentially mediate the relationship between LNS and intrauterine growth need to be investigated.