THESIS SUMMARY:BACKGROUND: Abnormal ductus venosus flow at 11-13 weeks has been associated to fetal chromosomal abnormalities and cardiac defects.The hypothesis of the studies is that flow through the ductus venosus can be assessed routinely at 11-13 weeks of gestation and that abnormal flow at this scan can help identify fetal chromosomal and structural defects as well as adverse pregnancy outcome.STUDIES:In the first study, ten sonographers received practical training in accurate assessment of the ductus venosus and performed 300 examinations each. The sonographers required an average of 80 examinations before they could successfully examine the ductus venosus flow. In the second study ductus venosus flow was assessed immediately before chorion villous sampling (CVS) in fetuses with nuchal translucency (NT) thickness of 3.5 mm or more. A fetal echocardiography was performed in euploid fetuses at 11-13 weeks and/or 18-22 weeks. Reverse or absent flow during atrial contraction was observed in 68.8% of the fetuses with cardiac defects and in 22.9% with no cardiac defects. In the third study screening by the combined test was performed in singleton pregnancies, including 19,614 with euploid fetuses, 122 with trisomy 21, 36 with trisomy 18, 20 with trisomy 13 and 8 with Turner syndrome. We examined the performance of two screening strategies: firstly, assessment of the a-wave in all patients and secondly, first-stage screening using the combined test in all patients followed by second-stage assessment of the a-wave only in those with an intermediate risk of 1 in 51 to 1 in 1,000 after the first-stage. Reversed a-wave was observed in 3.2% of the euploid fetuses and in 66.4%, 58.3%, 55.0% and 75.0% of fetuses with trisomies 21, 18 and 13 and Turner syndrome, respectively. Inclusion of ductus venosus flow in all pregnancies would detect 96%, 92%, 100% and 100% of trisomies 21, 18 and 13 and Turner syndrome, respectively, at a false positive rate of 3%. The same detection rates were achieved with the two-stage strategy at a false positive rate of 2.6%.In the fourth study the patients were subdivided into five groups: normal outcome (n=10,120), miscarriage or fetal death (n=185), abnormal karyotype (n=95), major cardiac (n=20) or non-cardiac defect (n=70). The prevalence of reversed a-wave was significantly higher in the groups with miscarriage or fetal death (10.8%), abnormal karyotype (62.1%) and fetal cardiac defect (25.0%) but not non-cardiac defect (4.3%) than in the normal outcome group (3.7%). The fifth study was a prospective study in 516 dichorionic and 179 monochorionic twin pregnancies. The prevalence of reversed a-wave in the fetal ductus venosus was compared between monochorionic and dichorionic pregnancies and between those with and without pregnancy complications. The prevalence of reversed a-wave in at least one of the fetuses was significantly higher in monochorionic than in dichorionic pregnancies (18.4% vs. 8.3%, p<0.001) and in pregnancies complicated by miscarriage (28.6%, p=0.005), fetal aneuploidy (70.0%, p<0.001) and twin-to-twin-transfusion syndrome (TTTS) (38.5%, p<0.001) compared to the pregnancies with two healthy live births (7.7%). Pregnancy outcome was normal in 76.7% dichorionic and in 42.4% monochorionic twins with reversed a-wave in at least one of the fetuses.CONCLUSIONS: After an extensive supervised training, ductus venosus flow assessment can be incorporated into the first trimester scan, where it improves the performance of screening for chromosomal defects and cardiac defects, and it helps to identify the fetuses with a higher risk of death. Similarly, in twin pregnancies ductus venosus assessment identifies the pregnancies with a higher risk of having a fetus with an aneuploidy, those with a higher risk of miscarriage, and those that will subsequently develop TTTS.KEY WORDS: Ductus venosus, First trimester, Chromosomal abnormality, Cardiac effect, Adverse outcome, Twin pregnancy

Aquesta tesi (mitjançant cinc estudis) va ser destinada a investigar factors que tenen un efecte potencial sobre la salut materna durant la gestació i el postpart temprà, tenint en compte la melatonina com una possible millora de la salut i el rendiment de les vaques. En el primer estudi, els factors que afecten els leucòcits perifèrics de la mare, com un indicador d'estat immune, entre els dies 90-210 de gestació van ser, la interacció entre l'edat de la vaca i Neospora caninum, l'estació, la gestació gemelar, la producció de llet i el temps de mostreig. Seguint el sistema immune matern més enllà en la seva fase més crítica, el segon i el tercer estudis resumeixen els diferents factors que afecten el sistema immunològic de la mare des del dia 220 de gestació fins a 30 dies postpart. El toro d'IA, les glicoproteïnes associades a la gestació (PAG), la interacció N. caninum-C. burnetii, l'estació, l'edat, la gestació gemelar i el temps de mostreig afectaven significativament els leucòcits materns. L'objectiu del quart estudi va ser avaluar la dosi adequada de la melatonina, per provar els seus possibles efectes en la millora de la salut de la mare durant el peripart i la dosi de 332 mg / kg era la més adequada. Finalment, els possibles efectes de la melatonina en millorar la salut materna durant el peripart van ser avaluats en el cinquè estudi. Les vaques tractades amb melatonina tenien menys probabilitat de ser repetidores i de perdre la gestació, i, per tant, tenien menys dies oberts. / Esta tesis (mediante cinco estudios) fue destinada a investigar factores que tienen un efecto potencial sobre la salud materna durante la gestación y el posparto temprano, teniendo en cuenta la melatonina como una posible mejora de la salud y el rendimiento de las vacas. En el primer estudio, los factores que afectan a los leucocitos periféricos de la madre, como un indicador de estado inmune, entre los días 90-210 de gestaion fueron, la interacción entre la edad de la vaca y Neospora caninum, la estación, la gestación gemelar, la producción de leche y el tiempo de muestreo. Siguiendo el sistema inmune materno más allá en su fase más crítica, el segundo y el tercer estudios resumen los diferentes factores que afectan al sistema inmunológico de la madre desde el día 220 de gestación hasta 30 días posparto. El toro de IA, las glicoproteínas asociadas a la gestación (PAG), la interacción N. caninum-C. burnetii, la estación, la edad, la gestación gemelar y el tiempo de muestreo afectaban significativamente los leucocitos maternos. El objetivo del cuarto estudio fue evaluar la dosis adecuada de la melatonina, para probar sus posibles efectos en la mejora de la salud de la madre durante el periparto y la dosis de 332 mg/kg era la más adecuada. Por último, los posibles efectos de la melatonina en mejorar la salud materna durante el periparto fueron evaluados en el quinto estudio. Las vacas tratadas con melatonina tenian menos probabilidad de ser repetidoras y de perder la gestación, y, por lo tanto, tenian menos días abiertos. / This thesis (by means of five studies) aimed at investigating factors that have potential effect on the maternal health during gestation and the early postpartum, plus considering melatonin for improving cows’ health and performance. In the first study, factors affecting maternal peripheral leukocytes, as an indicator to immune status, between Days 90-210 of gestaion were, the interaction between cows’ age and Neospora caninum-seropositivity, season, twin-pregnancy, milk production and time. Following the maternal immune system further in its most critical phase, the second and third studies summarize different factors affecting maternal immune system from gestation Day 220 till 30 days postpartum. Artificial inseminating bull, plasma pregnancy associated glycoproteins (PAGs), N. caninum-C. burnetii interaction, season, age, twin-pregnancy and time were found to significantly affect maternal peripheral leukocytes during that stage. The aim of the forth study was to evaluate proper melatonin dose as subcutaneous implants, for testing its possible effects in enhancing maternal health during the peripartum. Melatonin dose of 332 μg/kg was the most adequate. Finally, possible melatonin effects on enhancing maternal health during the peripartum were evaluated in the fifth study. Melatonin treated cows were found to have less likelihood of repeat breeding syndrome and pregnancy loss, and, therefore, less days open.