OBJETIVO: Avaliar o comportamento alimentar de recém-nascidos (RN) pequenos (PIG) e grandes (GIG) para a idade gestacional através de questionário específico e comparar com RN adequados para a idade gestacional (AIG). METODOLOGIA: Estudo de coorte prospectivo, cuja primeira fase consistiu na realização de uma entrevista para coleta de dados da mãe da gestação e do parto, bem como de dados socioeconômicos, com mães que tiveram seus filhos a termo no Hospital de Clínicas de Porto Alegre. Na segunda fase do estudo foi aplicado o questionário Baby Eating Behaviour Questionnaire (BEBQ) através de contato por telefone, com 1 mês do nascimento. RESULTADOS: Foram avaliados 126 RN (43 AIG, 43 PIG e 40 GIG). As análises não demonstraram diferenças significativas nos principais dados demográficos e perinatais em relação aos diferentes grupos de estudo. No entanto, foi observada uma maior escolaridade em mães de RN PIG (p=0,004) e uma menor prevalência de aleitamento materno exclusivo até a alta hospitalar em RN GIG (p=0,002). A análise de variância não encontrou diferença significativa entre os grupos em relação aos domínios do BEBQ, mesmo quando corrigido por sexo do RN. CONCLUSÃO: O estudo demonstrou que alterações do comportamento alimentar ainda não estão presentes com 1 mês de vida, sugerindo que não são inatas, e sim desenvolvidas com o passar do tempo. O estudo tem como limitação as avaliações do crescimento baseadas em registros de terceiros. / OBJECTIVE: To evaluate feeding behavior of infants born small (SGA) and large (LGA) for gestational age using a questionnaire, and compare them with infants born adequate for gestational age (AGA). METHODS: Prospective cohort study was carried out in which the first phase consisted of an interview about gestation and delivery, as well as socioeconomic data, with mothers who had their babies born at term in the Hospital de Clínicas de Porto Alegre. In the second phase of the study, the Baby Eating Questionnaire (BEBQ) was applied through telephone interview 1 month of birth. RESULTS: 126 infants (43 AGA, 43 SGA and 40 LGA) with a mean gestational age of 39.4 weeks were assessed. The analyses did not show significant differences in the main demographic and perinatal data between the different study groups. However, a higher level of schooling was observed in mothers of SGA infants (p = 0.004) and a lower prevalence of exclusive breastfeeding in the LGA (p = 0.002). The analysis of variance found no significant difference between the groups in any of the BEBQ domains, even when corrected for the sex of the baby. CONCLUSION: This study demonstrated that changes in feeding behavior are not yet present at 1 month of age, suggesting that they are not innate, but developed over time. The study is limited to growth assessments based on third-party records.

Introdução: Sabe-se que os fatores angiogênicos e antiangiogênicos encontram-se alterados nas gestações com pré-eclâmpsia (PE), mas se desconhece seu comportamento nestes recém-nascidos (RNs). Objetivo: Dosagem do vascular endothelial growth factor (VEGF), soluble fms-like tyrosine kinase-1 (sFtl-1) e heterodímero vascular endothelial growth factor/placental growth factor (VEGF/PlGF) em pré-termos filhos de mães com PE. Métodos: Incluídos: RNs com peso de nascimento < 2.000 g e idade gestacional (IG) ≤ 34 semanas, divididos em dois grupos: filhos de mães com e sem PE. Excluídos: RNs transferidos de outra instituição com mais de 72 horas de vida, óbito antes da coleta dos exames, malformação congênita maior, erros inatos de metabolismo, gestações múltiplas, mães com infecção do grupo sífilis, toxoplasmose, rubéola, citomegalovírus, herpes (STORCH) ou vírus da imunodeficiência humana (HIV) e doença autoimune. Coletado sangue nas primeiras 72 horas de vida, e nos RNs que permaneceram internados, foi realizada uma segunda coleta com 28 dias. Foi utilizado método ELISA para a dosagem do VEGF, sFlt-1 e VEGF/PlGF. Resultados: Incluídos: 88 pacientes (37 filhos de mães com PE, 51 sem PE) com IG de 29,12 ± 2,96 semanas e peso de nascimento de 1223,80 ± 417,48 g. O VEGF foi menor no grupo com PE [32,45 (6,36-85,75) x 82,38 (35-130,03) pg/mL], p = 0,001 e o sFlt-1 foi maior no grupo com PE [1338,57 (418,8-3472,24) x 318,13 (182,03-453,66) pg/mL], p < 0,001. Na análise multivariada, o VEGF foi 80% menor e sFlt-1 13,48 vezes maior no grupo com PE. O sFlt-1 foi maior nos RNs pequenos para idade gestacional (PIG) do que nos adequados para idade gestacional (AIG) [1044,94 (290,64-3472,24) x 372,67 (236,75-860,14) pg/mL], p = 0,013. No grupo com PE, houve um aumento [≠ 151,71 (76,55-226,86); p < 0,001] entre as dosagens do VEGF entre a primeira e a segunda coleta com 28 dias, já o sFlt-1 diminuiu [≠ 1941,44 (2757,01-1125,87); p < 0,001] entre as duas dosagens. O VEGF/PlGF foi maior nos filhos de mães com PE [20,69 pg/mL (12,79-52,86) x 12,19 pg/mL (0,03 -21,58)], p = 0,003. Esses achados mantiveram-se na análise multivariada, com o VEGF/PlGF 1,05 vezes maior nos filhos de mães com PE. Os níveis de VEGF/PlGF foram inversamente proporcionais ao peso de nascimento, com p < 0,001 e r = - 0,418. Na segunda coleta com 28 dias de vida não houve diferença entre os dois grupos. Conclusão: Os maiores níveis de sFlt-1 e VEGF/PlGF e menores níveis de VEGF no grupo com PE, assim como maiores concentrações de sFlt-1 nos PIG refletem uma predominância dos mecanismos antiangiogênicos na PE e na restrição de crescimento. Os níveis de VEGF/PlGF também foram relacionados ao peso de nascimento, sendo inversamente proporcionais. O estado antiangiogênico da PE tende à normalização com 28 dias de vida. / Background: It is known that angiogenic and antiangiogenic factors are altered in pregnant women with preeclampsia (PE), but the pattern of expression of these factors in their newborn infants remains unknown. Objective: To measure vascular endothelial growth factor (VEGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and vascular endothelial growth factor/placental growth factor (VEGF/PlGF) heterodimer levels in preterm neonates born to mothers with PE. Methods: Neonates with birth weight < 2,000 g and gestational age ≤ 34 weeks were included and divided into two groups: born to mothers with and without PE. Exclusion criteria were as follows: the neonate was transferred from another institution after 72 hours of life; the neonate died before blood collection; major congenital anomalies; inborn errors of metabolism; congenital infections (STORCH screen); HIV-positive mothers; multiple pregnancies; and mothers with autoimmune disease. Blood was collected from neonates within the first 72 hours of life, and a second sample was collected at 28 days of life from those who remained hospitalized. VEGF, sFlt-1 and VEGF/PlGF levels were measured using the ELISA method. Results: A total of 88 neonates were included (37 born to mothers with and 51 without PE), with mean gestational age of 29.12 ± 2.96 weeks and birth weight of 1223.80 ± 417.48 g. VEGF was lower in the group with PE [32.45 (6.36-85.75) vs. 82.38 (35-130.03) pg/mL] (p = 0.001), and sFlt-1 was higher in the group with PE [1338.57 (418.8-3472.24) vs. 318.13 (182.03-453.66) pg/mL] (p < 0.001). In the multivariate analysis, VEGF was 80% lower and sFlt-1 was 13.48 times higher in the group with PE. sFlt-1 concentration was higher in neonates small for gestational age (SGA) than in those appropriate for gestational age (AGA) [1044.94 (290.64-3472.24) vs. 372.67 (236.75-860.14) pg/mL] (p = 0.013). In the group with PE, VEGF levels increased [≠151.71 (76.55-226.86); p < 0.001) between the first and second collection (at 28 days), while sFlt-1 levels decreased [≠1941.44 (2757.01-1125.87); p < 0.001] between the two measurements. Median VEGF/PlGF levels were significantly higher among infants born to mothers with PE (20.69 pg/mL [12.79-52.86] vs. 12.19 pg/mL [0.03-21.58], p = 0.003). These findings held on multivariate analysis, with VEGF/PlGF levels 1.05-fold higher in the PE group. VEGF/PlGF levels were inversely proportional to birth weight (p < 0.001, r = - 0.418). There were no between-group differences in blood samples collected at age 28 days. Conclusion: Higher sFlt-1 and VEGF/PlGF and lower VEGF levels in the group with PE, as well as higher sFlt-1 levels in SGA neonates, reflect a predominance of antiangiogenic mechanisms in PE and growth restriction. The VEGF/PlGF levels also affected the weight at birth, with VEGF/PlGF levels inversely proportional to birth weight. This antiangiogenic state of PE shows a trend toward normalization within 28 days of life.

OBJETIVO: Avaliar o comportamento alimentar de recém-nascidos (RN) pequenos (PIG) e grandes (GIG) para a idade gestacional através de questionário específico e comparar com RN adequados para a idade gestacional (AIG). METODOLOGIA: Estudo de coorte prospectivo, cuja primeira fase consistiu na realização de uma entrevista para coleta de dados da mãe da gestação e do parto, bem como de dados socioeconômicos, com mães que tiveram seus filhos a termo no Hospital de Clínicas de Porto Alegre. Na segunda fase do estudo foi aplicado o questionário Baby Eating Behaviour Questionnaire (BEBQ) através de contato por telefone, com 1 mês do nascimento. RESULTADOS: Foram avaliados 126 RN (43 AIG, 43 PIG e 40 GIG). As análises não demonstraram diferenças significativas nos principais dados demográficos e perinatais em relação aos diferentes grupos de estudo. No entanto, foi observada uma maior escolaridade em mães de RN PIG (p=0,004) e uma menor prevalência de aleitamento materno exclusivo até a alta hospitalar em RN GIG (p=0,002). A análise de variância não encontrou diferença significativa entre os grupos em relação aos domínios do BEBQ, mesmo quando corrigido por sexo do RN. CONCLUSÃO: O estudo demonstrou que alterações do comportamento alimentar ainda não estão presentes com 1 mês de vida, sugerindo que não são inatas, e sim desenvolvidas com o passar do tempo. O estudo tem como limitação as avaliações do crescimento baseadas em registros de terceiros. / OBJECTIVE: To evaluate feeding behavior of infants born small (SGA) and large (LGA) for gestational age using a questionnaire, and compare them with infants born adequate for gestational age (AGA). METHODS: Prospective cohort study was carried out in which the first phase consisted of an interview about gestation and delivery, as well as socioeconomic data, with mothers who had their babies born at term in the Hospital de Clínicas de Porto Alegre. In the second phase of the study, the Baby Eating Questionnaire (BEBQ) was applied through telephone interview 1 month of birth. RESULTS: 126 infants (43 AGA, 43 SGA and 40 LGA) with a mean gestational age of 39.4 weeks were assessed. The analyses did not show significant differences in the main demographic and perinatal data between the different study groups. However, a higher level of schooling was observed in mothers of SGA infants (p = 0.004) and a lower prevalence of exclusive breastfeeding in the LGA (p = 0.002). The analysis of variance found no significant difference between the groups in any of the BEBQ domains, even when corrected for the sex of the baby. CONCLUSION: This study demonstrated that changes in feeding behavior are not yet present at 1 month of age, suggesting that they are not innate, but developed over time. The study is limited to growth assessments based on third-party records.

Introdução: Sabe-se que os fatores angiogênicos e antiangiogênicos encontram-se alterados nas gestações com pré-eclâmpsia (PE), mas se desconhece seu comportamento nestes recém-nascidos (RNs). Objetivo: Dosagem do vascular endothelial growth factor (VEGF), soluble fms-like tyrosine kinase-1 (sFtl-1) e heterodímero vascular endothelial growth factor/placental growth factor (VEGF/PlGF) em pré-termos filhos de mães com PE. Métodos: Incluídos: RNs com peso de nascimento < 2.000 g e idade gestacional (IG) ≤ 34 semanas, divididos em dois grupos: filhos de mães com e sem PE. Excluídos: RNs transferidos de outra instituição com mais de 72 horas de vida, óbito antes da coleta dos exames, malformação congênita maior, erros inatos de metabolismo, gestações múltiplas, mães com infecção do grupo sífilis, toxoplasmose, rubéola, citomegalovírus, herpes (STORCH) ou vírus da imunodeficiência humana (HIV) e doença autoimune. Coletado sangue nas primeiras 72 horas de vida, e nos RNs que permaneceram internados, foi realizada uma segunda coleta com 28 dias. Foi utilizado método ELISA para a dosagem do VEGF, sFlt-1 e VEGF/PlGF. Resultados: Incluídos: 88 pacientes (37 filhos de mães com PE, 51 sem PE) com IG de 29,12 ± 2,96 semanas e peso de nascimento de 1223,80 ± 417,48 g. O VEGF foi menor no grupo com PE [32,45 (6,36-85,75) x 82,38 (35-130,03) pg/mL], p = 0,001 e o sFlt-1 foi maior no grupo com PE [1338,57 (418,8-3472,24) x 318,13 (182,03-453,66) pg/mL], p < 0,001. Na análise multivariada, o VEGF foi 80% menor e sFlt-1 13,48 vezes maior no grupo com PE. O sFlt-1 foi maior nos RNs pequenos para idade gestacional (PIG) do que nos adequados para idade gestacional (AIG) [1044,94 (290,64-3472,24) x 372,67 (236,75-860,14) pg/mL], p = 0,013. No grupo com PE, houve um aumento [≠ 151,71 (76,55-226,86); p < 0,001] entre as dosagens do VEGF entre a primeira e a segunda coleta com 28 dias, já o sFlt-1 diminuiu [≠ 1941,44 (2757,01-1125,87); p < 0,001] entre as duas dosagens. O VEGF/PlGF foi maior nos filhos de mães com PE [20,69 pg/mL (12,79-52,86) x 12,19 pg/mL (0,03 -21,58)], p = 0,003. Esses achados mantiveram-se na análise multivariada, com o VEGF/PlGF 1,05 vezes maior nos filhos de mães com PE. Os níveis de VEGF/PlGF foram inversamente proporcionais ao peso de nascimento, com p < 0,001 e r = - 0,418. Na segunda coleta com 28 dias de vida não houve diferença entre os dois grupos. Conclusão: Os maiores níveis de sFlt-1 e VEGF/PlGF e menores níveis de VEGF no grupo com PE, assim como maiores concentrações de sFlt-1 nos PIG refletem uma predominância dos mecanismos antiangiogênicos na PE e na restrição de crescimento. Os níveis de VEGF/PlGF também foram relacionados ao peso de nascimento, sendo inversamente proporcionais. O estado antiangiogênico da PE tende à normalização com 28 dias de vida. / Background: It is known that angiogenic and antiangiogenic factors are altered in pregnant women with preeclampsia (PE), but the pattern of expression of these factors in their newborn infants remains unknown. Objective: To measure vascular endothelial growth factor (VEGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and vascular endothelial growth factor/placental growth factor (VEGF/PlGF) heterodimer levels in preterm neonates born to mothers with PE. Methods: Neonates with birth weight < 2,000 g and gestational age ≤ 34 weeks were included and divided into two groups: born to mothers with and without PE. Exclusion criteria were as follows: the neonate was transferred from another institution after 72 hours of life; the neonate died before blood collection; major congenital anomalies; inborn errors of metabolism; congenital infections (STORCH screen); HIV-positive mothers; multiple pregnancies; and mothers with autoimmune disease. Blood was collected from neonates within the first 72 hours of life, and a second sample was collected at 28 days of life from those who remained hospitalized. VEGF, sFlt-1 and VEGF/PlGF levels were measured using the ELISA method. Results: A total of 88 neonates were included (37 born to mothers with and 51 without PE), with mean gestational age of 29.12 ± 2.96 weeks and birth weight of 1223.80 ± 417.48 g. VEGF was lower in the group with PE [32.45 (6.36-85.75) vs. 82.38 (35-130.03) pg/mL] (p = 0.001), and sFlt-1 was higher in the group with PE [1338.57 (418.8-3472.24) vs. 318.13 (182.03-453.66) pg/mL] (p < 0.001). In the multivariate analysis, VEGF was 80% lower and sFlt-1 was 13.48 times higher in the group with PE. sFlt-1 concentration was higher in neonates small for gestational age (SGA) than in those appropriate for gestational age (AGA) [1044.94 (290.64-3472.24) vs. 372.67 (236.75-860.14) pg/mL] (p = 0.013). In the group with PE, VEGF levels increased [≠151.71 (76.55-226.86); p < 0.001) between the first and second collection (at 28 days), while sFlt-1 levels decreased [≠1941.44 (2757.01-1125.87); p < 0.001] between the two measurements. Median VEGF/PlGF levels were significantly higher among infants born to mothers with PE (20.69 pg/mL [12.79-52.86] vs. 12.19 pg/mL [0.03-21.58], p = 0.003). These findings held on multivariate analysis, with VEGF/PlGF levels 1.05-fold higher in the PE group. VEGF/PlGF levels were inversely proportional to birth weight (p < 0.001, r = - 0.418). There were no between-group differences in blood samples collected at age 28 days. Conclusion: Higher sFlt-1 and VEGF/PlGF and lower VEGF levels in the group with PE, as well as higher sFlt-1 levels in SGA neonates, reflect a predominance of antiangiogenic mechanisms in PE and growth restriction. The VEGF/PlGF levels also affected the weight at birth, with VEGF/PlGF levels inversely proportional to birth weight. This antiangiogenic state of PE shows a trend toward normalization within 28 days of life.

Introdução: Sabe-se que os fatores angiogênicos e antiangiogênicos encontram-se alterados nas gestações com pré-eclâmpsia (PE), mas se desconhece seu comportamento nestes recém-nascidos (RNs). Objetivo: Dosagem do vascular endothelial growth factor (VEGF), soluble fms-like tyrosine kinase-1 (sFtl-1) e heterodímero vascular endothelial growth factor/placental growth factor (VEGF/PlGF) em pré-termos filhos de mães com PE. Métodos: Incluídos: RNs com peso de nascimento < 2.000 g e idade gestacional (IG) ≤ 34 semanas, divididos em dois grupos: filhos de mães com e sem PE. Excluídos: RNs transferidos de outra instituição com mais de 72 horas de vida, óbito antes da coleta dos exames, malformação congênita maior, erros inatos de metabolismo, gestações múltiplas, mães com infecção do grupo sífilis, toxoplasmose, rubéola, citomegalovírus, herpes (STORCH) ou vírus da imunodeficiência humana (HIV) e doença autoimune. Coletado sangue nas primeiras 72 horas de vida, e nos RNs que permaneceram internados, foi realizada uma segunda coleta com 28 dias. Foi utilizado método ELISA para a dosagem do VEGF, sFlt-1 e VEGF/PlGF. Resultados: Incluídos: 88 pacientes (37 filhos de mães com PE, 51 sem PE) com IG de 29,12 ± 2,96 semanas e peso de nascimento de 1223,80 ± 417,48 g. O VEGF foi menor no grupo com PE [32,45 (6,36-85,75) x 82,38 (35-130,03) pg/mL], p = 0,001 e o sFlt-1 foi maior no grupo com PE [1338,57 (418,8-3472,24) x 318,13 (182,03-453,66) pg/mL], p < 0,001. Na análise multivariada, o VEGF foi 80% menor e sFlt-1 13,48 vezes maior no grupo com PE. O sFlt-1 foi maior nos RNs pequenos para idade gestacional (PIG) do que nos adequados para idade gestacional (AIG) [1044,94 (290,64-3472,24) x 372,67 (236,75-860,14) pg/mL], p = 0,013. No grupo com PE, houve um aumento [≠ 151,71 (76,55-226,86); p < 0,001] entre as dosagens do VEGF entre a primeira e a segunda coleta com 28 dias, já o sFlt-1 diminuiu [≠ 1941,44 (2757,01-1125,87); p < 0,001] entre as duas dosagens. O VEGF/PlGF foi maior nos filhos de mães com PE [20,69 pg/mL (12,79-52,86) x 12,19 pg/mL (0,03 -21,58)], p = 0,003. Esses achados mantiveram-se na análise multivariada, com o VEGF/PlGF 1,05 vezes maior nos filhos de mães com PE. Os níveis de VEGF/PlGF foram inversamente proporcionais ao peso de nascimento, com p < 0,001 e r = - 0,418. Na segunda coleta com 28 dias de vida não houve diferença entre os dois grupos. Conclusão: Os maiores níveis de sFlt-1 e VEGF/PlGF e menores níveis de VEGF no grupo com PE, assim como maiores concentrações de sFlt-1 nos PIG refletem uma predominância dos mecanismos antiangiogênicos na PE e na restrição de crescimento. Os níveis de VEGF/PlGF também foram relacionados ao peso de nascimento, sendo inversamente proporcionais. O estado antiangiogênico da PE tende à normalização com 28 dias de vida. / Background: It is known that angiogenic and antiangiogenic factors are altered in pregnant women with preeclampsia (PE), but the pattern of expression of these factors in their newborn infants remains unknown. Objective: To measure vascular endothelial growth factor (VEGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and vascular endothelial growth factor/placental growth factor (VEGF/PlGF) heterodimer levels in preterm neonates born to mothers with PE. Methods: Neonates with birth weight < 2,000 g and gestational age ≤ 34 weeks were included and divided into two groups: born to mothers with and without PE. Exclusion criteria were as follows: the neonate was transferred from another institution after 72 hours of life; the neonate died before blood collection; major congenital anomalies; inborn errors of metabolism; congenital infections (STORCH screen); HIV-positive mothers; multiple pregnancies; and mothers with autoimmune disease. Blood was collected from neonates within the first 72 hours of life, and a second sample was collected at 28 days of life from those who remained hospitalized. VEGF, sFlt-1 and VEGF/PlGF levels were measured using the ELISA method. Results: A total of 88 neonates were included (37 born to mothers with and 51 without PE), with mean gestational age of 29.12 ± 2.96 weeks and birth weight of 1223.80 ± 417.48 g. VEGF was lower in the group with PE [32.45 (6.36-85.75) vs. 82.38 (35-130.03) pg/mL] (p = 0.001), and sFlt-1 was higher in the group with PE [1338.57 (418.8-3472.24) vs. 318.13 (182.03-453.66) pg/mL] (p < 0.001). In the multivariate analysis, VEGF was 80% lower and sFlt-1 was 13.48 times higher in the group with PE. sFlt-1 concentration was higher in neonates small for gestational age (SGA) than in those appropriate for gestational age (AGA) [1044.94 (290.64-3472.24) vs. 372.67 (236.75-860.14) pg/mL] (p = 0.013). In the group with PE, VEGF levels increased [≠151.71 (76.55-226.86); p < 0.001) between the first and second collection (at 28 days), while sFlt-1 levels decreased [≠1941.44 (2757.01-1125.87); p < 0.001] between the two measurements. Median VEGF/PlGF levels were significantly higher among infants born to mothers with PE (20.69 pg/mL [12.79-52.86] vs. 12.19 pg/mL [0.03-21.58], p = 0.003). These findings held on multivariate analysis, with VEGF/PlGF levels 1.05-fold higher in the PE group. VEGF/PlGF levels were inversely proportional to birth weight (p < 0.001, r = - 0.418). There were no between-group differences in blood samples collected at age 28 days. Conclusion: Higher sFlt-1 and VEGF/PlGF and lower VEGF levels in the group with PE, as well as higher sFlt-1 levels in SGA neonates, reflect a predominance of antiangiogenic mechanisms in PE and growth restriction. The VEGF/PlGF levels also affected the weight at birth, with VEGF/PlGF levels inversely proportional to birth weight. This antiangiogenic state of PE shows a trend toward normalization within 28 days of life.

Introdução: A restrição de crescimento intrauterino (RCIU) é uma intercorrência obstétrica de prevalência relevante e altas taxas de morbimortalidade. A ultrassonografia (US) obstétrica ainda é limitada para diagnosticar comprometimento cerebral na RCIU. Por isso, com o intuito de aumentar a acurácia diagnóstica de lesões no encéfalo e comprometimento da criança acometida, surgiram alguns trabalhos utilizando a ressonância magnética (RM), mas com dificuldades técnicas. Sendo assim, são necessários estudos que avaliem o encéfalo de fetos com RCIU e que identifiquem biomarcadores simples de hipóxia crônica e/ou aguda. Objetivos: comparar parâmetros morfométricos mensurados por RM do crânio e encéfalo de fetos com crescimento normal e de fetos com RCIU. Métodos: trata-se de um estudo de coorte prospectivo que incluiu 13 fetos de gestações únicas, com crescimento adequado e 13 fetos de gestações únicas com RCIU, na relação 1 caso:1 controle, de 26 a 38 semanas de idade gestacional (IG) que foram submetidos à avaliação ultrassonográfica para determinação da biometria, volume de líquido amniótico e Dopplervelocimetria fetal e à RM para avaliação de medidas encefálicas e cranianas. Variáveis relacionadas ao tipo de parto, condições do nascimento e resultados perinatais adversos foram obtidas de prontuários médicos. Para análise estatística foram empregados os testes de Wilcoxon e Chi-quadrado. Resultados: as medidas do diâmetro biparietal (DBP) ósseo e cerebral e do diâmetro occipitofrontal (DOF) ósseo de fetos restritos foram menores que as de controles, assim como os percentis desses diâmetros, da circunferência craniana e do DOF cerebral. Observou-se também que a mediana da relação DBP cerebral/cerebelo da população de fetos restritos tendeu a ser menor que a de controles. Além disso, as medidas do líquor cerebroespinhal (LCE) extracerebral e seus percentis também foram menores nos fetos restritos. Também há diferenças nas relações DOF ósseo/LCE, DOF cerebral/LCE, DBP ósseo/LCE e DBP cerebral/LCE entre os grupos de fetos estudados. Além disso, as medidas das distâncias interoperculares axiais direita e esquerda foram significativamente menores nos fetos restritos. Conclusões: podemos concluir que fetos com RCIU possuem medidas cranianas e encefálicas menores que fetos com crescimento adequado, além de haver redução do LCE extracerebral. Estudos de RM fetal com casuística maior, que permitam análise com regressão logística multivariada e aqueles que avaliem comprometimento neurológico das crianças acometidas são necessários. / Introduction: intrauterine growth restriction (IUGR) is an obstetric intercurrence of relevant prevalence and high morbidity and mortality rates. Obstetrical ultrasonography is still limited to diagnose brain impairment in IUGR. Therefore, in order to increase the diagnostic accuracy of brain lesions and impairment of the affected child, some studies using magnetic resonance imaging (MRI) have emerged, but with technical difficulties. Hence, studies that evaluate the brain of fetuses with IUGR and that identify simple biomarkers of chronic and/or acute hypoxia are needed. Objectives: to compare morphometric parameters measured by MRI of the skull and brain of fetuses with normal growth and fetuses with IUGR. Methods: this was a prospective cohort study that included 13 fetuses with normal growth and 13 fetuses with IUGR from singleton pregnancies, in the ratio 1 case: 1 control, from 26 to 38 weeks of gestational age (GI) who underwent ultrasound evaluation to determine the biometry, amniotic fluid volume and fetal Doppler velocimetry and MRI for evaluation of brain and cranial measurements. Variables related to the type of delivery, birth conditions and adverse perinatal outcomes were obtained from medical records. Wilcoxon and Chi-square tests were used for statistical analysis. Results: the measurements of skull and brain biparietal diameter (BPD) and skull occipitofrontal diameter (OFD) of IUGR fetuses were lower than those of controls, as well as the percentiles of these diameters, head circumference and the brain OFD. It has also been observed that the median of the brain BPD/cerebellar diameter ratio of the IUGR fetuses tended to be lower than that of the controls. In addition, measurements of the extracerebral cerebrospinal fluid (CSF) and their percentiles were also lower in IUGR fetuses. There are also differences in the skull OFD/ CSF, brain OFD/ CSF, skull BPD/ CSF and brain BPD/ CSF and extracerebral CSF ratios between the groups of fetuses studied. In addition, measurements of right and left axial interopercular distances were significantly lower in the IUGR fetuses. Conclusions: we can conclude that IUGR fetuses have smaller cranial and brain measures than fetuses with normal growth, besides having reduction of extracerebral CSF. Fetal MRI studies with larger number of subjects, allowing analysis with multivariate logistic regression and those which assess neurological impairment of affected children are needed.

La distinction entre les fœtus constitutionnellement petits de ceux qui présentent une réelle restriction de croissance liée à une insuffisance placentaire n’est pas aisée avec les mesures échographiques utilisées en pratique courante. Le retard de croissance intra-utérin (RCIU) est responsable d’une part importante de la prématurité induite, et d’une augmentation du risque de mortalité et de morbidité néonatales. C’est pourquoi, l’amélioration de la connaissance de la vascularisation placentaire est indispensable pour mieux identifier et prendre en charge les situations d’hypoxie chroniques foetales associées à l’insuffisance placentaire.Pour quantifier la vascularisation les modalités d’imagerie de perfusion disponibles sont l’échographie et l’IRM. Les études évaluant la quantification de la perfusion placentaire par échographie de contraste sont peu nombreuses. Les avantages et les limites de cet examen ont été évalués sur un modèle murin de RCIU par ligature vasculaire. Ainsi, l’échographie de contraste permettait de quantifier une baisse de la perfusion placentaire sur un modèle de RCIU sans que l’on puisse observer de passage d’agents de contraste ultrasonores au travers la barrière placentaire. Les résultats obtenus ont été comparés aux données obtenues par l’IRM de perfusion. Les paramètres quantitatifs obtenus à partir des courbes de cinétiques du contraste pour chacune des deux modalités d’imagerie étaient comparables sur un modèle identique de RCIU murin. Enfin, une méthode d’étude de l’oxygénation placentaire par imagerie photoacoustique a été évaluée. Cette modalité d’imagerie non invasive permettait d’obtenir en temps réel l’oxygénation placentaire, avec cependant une profondeur limitée d’exploration. Le placenta semblait se comporter comme une réserve en oxygène au cours de l’étude d’une séquence hypoxie – hyperoxygénation maternelle avec une désaturation moins importante que celle observée dans les autres tissus maternels. / To identify fetuses small for their gestational-age who have reached their appropriate growth potential from growth-restricted fetuses due to placental insufficiency is uneasy. Intra Uterine Growth Restriction (IUGR) increases the risk for indicated preterm delivery, neonatal mortality and morbidity. Therefore, improving the knowledge of the placental perfusion is essential to better identify and manage fetal chronic oxygen deprivation associated with placental insufficiency.Contrast Enhanced Ultrasound (CEUS) and MRI are two imaging modalities available to quantify placental perfusion. However, few studies focus on the quantification of placental perfusion with CEUS. First, the advantages and limitations of CEUS were presented in an IUGR rat model by uterine ligation. The placental perfusion observed by CEUS was significantly decreased in the ligated horn. No contrast enhancement was observed in the umbilical vein or the fetus. Then, we compared the CEUS parameters to results obtained by MRI perfusion. Perfusion parameters were obtained from the signal intensity decay curve for the two imaging modalities. Results of such perfusion parameters were comparable in the same IUGR rat model. Finally, we evaluated the response of the placenta to oxygenation by photoacoustic imaging. PA imaging is a real-time, non-invasive method to evaluate placental oxygenation without contrast agents. Our results suggesting that placenta is less affected than maternal tissue by the decline in maternal oxygenation. The placenta may play an important role in protecting the feus against hypoxia.

Le retard de croissance intra-utérin (RCIU) est une complication responsable d’une importante mortalité et morbidité périnatales. Son dépistage représente un enjeu important de la surveillance prénatale. Les objectifs de la thèse étaient d’évaluer la performance du dépistage anténatal du RCIU, d’identifier ses déterminants et de mesurer son impact sur les issues périnatales. Dans une première partie, nous avons utilisé les données de l’Enquête Nationale Périnatale de 2010 (N=14 100 enfants uniques) : 21,7% des enfants de poids <10ème percentile étaient suspectés avec un RCIU en anténatal tandis que la moitié des enfants suspectés avait un poids normal à la naissance (faux positifs). Le risque de naissance induite était élevé en cas de suspicion, indépendamment de l’existence d’un faible poids, suggérant des interventions iatrogènes. Les issues néonatales n’étaient pas différentes selon la suspicion. Dans une seconde partie, nous avons utilisé les données d’une cohorte nationale d’enfants nés avant 32 SA en 2011, EPIPAGE 2 (N=3698 enfants uniques sans anomalie congénitale). La prise en charge active pour indication fœtale en cas de RCIU était initiée à partir de 26 SA. Pour 14% des enfants, il existait une discordance entre la suspicion d’un RCIU en anténatal et un faible poids à la naissance. En cas de discordance, le poids de naissance était le paramètre le plus important pour évaluer le pronostic néonatal. Nos travaux soulèvent des questions sur l’efficacité du dépistage du RCIU en France. Ils montrent la nécessité de développer de nouvelles stratégies de dépistage et de poursuivre les recherches pour mesurer leur impact sur les décisions médicales et sur la santé. / Fetal growth restriction (FGR) is a pregnancy complication that is responsible for significant perinatal mortality and morbidity. Screening for FGR is a key component of prenatal care. The objectives of this thesis were to evaluate the performance of prenatal screening for FGR, to identify the determinants of antenatal suspicion of FGR and to measure its impact on perinatal outcomes. For the first part of the thesis, we used data from the nationally representative French National Perinatal Survey of births (N=14,100 singleton pregnancies): 21.7% of infants with a low birthweight <10th percentile were suspected with FGR during pregnancy and half of infants suspected with FGR had a normal birthweight (false positives). The risk of indicated delivery was higher when FGR was suspected, regardless of the existence of low birthweight, suggesting possible iatrogenic effects. Outcomes were not different for suspected versus unsuspected low birthweight infants. In the second part of the thesis, we used data from the EPIPAGE 2 national cohort of children born before 32 weeks of GA in 2011 (N=3698 singleton non-anomalous infants). Active management for fetal indications in cases of suspected FGR was initiated at 26 weeks. Antenatal and postnatal assessments of FGR were discordant for 14% of infants. When assessments were discordant, birthweight was a better predictor of adverse neonatal outcome. Our results raise questions about the effectiveness of screening strategies for FGR in France. New strategies for the detection of FGR are needed as well as research to measure the impact of screening on medical decisions and health.

Vielfältige Studien haben bereits Zusammenhänge zwischen niedrigem Geburtsgewicht und der Entwicklung von Adipositas und eines metabolischen Syndroms im späteren Lebensalter dargestellt. Umfangreiche Daten liegen vor allem für frühgeborene Neonaten vor. Ziel dieser Arbeit ist deshalb die Bewertung perinataler Parameter und der frühen Entwicklung reifer SGA – Neugeborener. Für die vorliegende prospektive Studie wurden 50 Neugeborene mit einem Geburtsgewicht < 10. Perzentile und 50 eutrophe Neugeborene erfasst. Bei allen Kindern wurden anamnestische Befunde zum Schwangerschaftsverlauf, die Biometrie der Eltern sowie Daten zur Geburt und zum stationären Verlauf erfasst. Mit Hilfe eines standardisierten Fragebogens an die niedergelassenen Kinderärzte erfolgte die Nachbeobachtung der Kinder hinsichtlich der Gewichts–, Längen– und Kopfumfangsentwicklung sowie der Ernährung bis zur 15. Lebenswoche. Die Ergebnisse der Studie zeigen, dass nur 13% der SGA – Kinder ein genetisch vermindertes Wachstumspotential haben. Demnach liegt bei der Mehrzahl der SGA – Geborenen ein pathologischer Mechanismus zugrunde. Während der Schwangerschaft waren in der SGA – Gruppe häufiger uterine Perfusionsstörungen bei einem erhöhten Auftreten von Präeklampsien oder Nikotinabusus darstellbar. Die SGA – Kinder wurden häufiger per sectionem geboren und zeigten zu einem erhöhten Anteil Dysmaturitätszeichen als Ausdruck einer intrauterinen Stress– oder Mangelsituation. Aufgrund der perinatalen Risiken sollte die Geburt dieser Kinder in einem Perinatalzentrum erfolgen. In der SGA – Gruppe bestand eine signifikante Korrelation zwischen Gestationsalter und Geburtsgewicht, deshalb ist eine individuelle Abwägung des Geburtszeitpunktes zur Nutzung des noch vorhandenen intrauterinen Wachstumspotentials erforderlich. Kinder der SGA – Gruppe bedurften häufiger einer intensivmedizinischen Betreuung und hatten einen längeren stationären Aufenthalt als Kinder der Vergleichsgruppe; Säurebasenstatus, APGAR – Werte und Blutdruck unterschieden sich nicht. Während des stationären Aufenthaltes wurden die SGA – Neonaten vermehrt zugefüttert und zeigten eine geringere postnatale Gewichtsabnahme. Nach der Entlassung kam es, bezogen auf die Körperlänge, zu einer stärkeren und rascheren Gewichtszunahme bei SGA – Kindern, während die Längendifferenz zunächst bestehen blieb. Ein frühes Aufholwachstum, welches sich in dieser Studie isoliert auf das Gewicht bezieht, ist hinsichtlich späterer metabolischer Störungen als möglicher Risikofaktor zu werten.

Children descending from pregnancy complicated by gestational hypertension, preeclampsia or fetal growth restriction have a lifelong increased risk of development of cardiovascular disease. This study investigates the expression profile of 29 cardiovascular and cerebrovascular microRNAs in children at the age of 3 to 11 years. MicroRNAs are short non-coding RNA molecules affecting gene expression by posttranscriptional modifications of mRNA, which affects biological processes. Abnormal microRNA levels can lead to pathological conditions of the individual. This study explores the relationship between dysregulated microRNA levels in whole peripheral venous blood of children and the presence of complications during pregnancy. Furthermore, this study looks at expression profile specificities depending on the presence of pathology in the child's cardiovascular system, as found in a clinical examination consisting of BMI assessment and evaluation, blood pressure testing and ultrasound examination of the heart. Dysregulated profile was present in children with gestational hypertension in miR-1-3p, miR-17-5p, miR-20a-5p, miR-21-5p, miR-26a-5p, miR-29a-3p, miR-126-3p, miR-133a-3p, miR-181a-5p, miR-199a-5p, miR-342-3p and miR-499-5p. In children with preeclampsia, dysregulation was found with miR-1-3p and...