In 70% of identical twin pregnancies, the twins share a single placenta in the womb that provides them with nutrients. This shared placenta can be unequaly shared. This means that one of the twins... Show moreIn 70% of identical twin pregnancies, the twins share a single placenta in the womb that provides them with nutrients. This shared placenta can be unequaly shared. This means that one of the twins has a much smaller share of the placenta compared to the other twin, resulting in a large growth discrepancy during pregnancy, also known as 'selective fetal growth restriction'. At birth, a large difference in birth weight ensues. Sometimes one twin can be almost twice the size of the other twin.These twins are considered a vulnerable patient group in which perinatal complications are prevalent. Nevertheless, a large gap in knowledge persists, impeding proper parent counseling and risk assessment by health care providers. Simultaneously, these twins can also be considered a unique natural 'experiment' to uncover the early origins of health and disease following an adverse environment in the womb. The growth-restricted twin can be compared to a genetically identical, normally-grown twin who has been in the same womb of the same mother at the same time.In this thesis, Sophie Groene has investigated the placental mechanisms and the short- and long-term outcomes of this special group of twins. Show less
Bos, M.; Koenders, M.J.M.; Dijkstra, K.L.; Meeren, L.E. van der; Nikkels, P.G.J.; Bloemenkamp, K.W.M.; ... ; Hoorn, M.L.P. van der 2023
Introduction: Chronic histiocytic intervillositis (CHI) is a rare histopathological lesion in the placenta that is associated with poor reproductive outcomes. The intervillous infiltrate consists... Show moreIntroduction: Chronic histiocytic intervillositis (CHI) is a rare histopathological lesion in the placenta that is associated with poor reproductive outcomes. The intervillous infiltrate consists mostly of maternal mononuclear cells and fibrin depositions, which are both indicators for the severity of the intervillous infiltrate. The severity of the intervillous infiltrate as well as the clinical outcomes of pregnancy differ between cases. Our objective is to determine the relation between the severity of the intervillous infiltrate and the clinical outcomes of CHI. Methods: Cases of CHI were semi-quantitatively graded based on histopathological severity scores. Hereto, CD68 positive mononuclear cells were quantified, fibrin depositions visualized by both a PTAH stain and an immuo-histochemical staining, and placental dysfunction was assessed via thrombomodulin staining. Results: This study included 36 women with CHI. A higher CD68 score was significantly associated with a lower birthweight. Loss of placental thrombomodulin was associated with lower gestational age, lower birthweight, and a lower placenta weight. The combined severity score based on CD68 and PTAH was significantly associated with fetal growth restriction, and the joint score of CD68 and fibrin was associated with birthweight and placental weight. Discussion: More severe intervillous infiltrates in CHI placentas is associated with a lower birth weight and placental weight. Furthermore, this study proposes thrombomodulin as a possible new severity marker of placental damage. More research is needed to better understand the pathophysiology of CHI. Show less
The aim was to reflect on the unexpected finding of persistent pulmonary hypertension of the neonate (PPHN) and pulmonary hypertension in infants born within the Dutch STRIDER trial, its definition... Show moreThe aim was to reflect on the unexpected finding of persistent pulmonary hypertension of the neonate (PPHN) and pulmonary hypertension in infants born within the Dutch STRIDER trial, its definition and possible pathophysiological mechanisms. The trial randomly assigned pregnant women with severe early-onset fetal growth restriction to sildenafil 25 mg three times a day versus placebo. Sildenafil use did not reduce perinatal mortality and morbidity, but did result in a higher rate of neonatal pulmonary hypertension (PH). The current paper reflects on the used definition, prevalence, and possible pathophysiology of the data on pulmonary hypertension. Twenty infants were diagnosed with pulmonary hypertension (12% of 163 live born infants). Of these, 16 infants had PPHN shortly after birth, and four had pulmonary hypertension associated with sepsis or bronchopulmonary dysplasia. Four infants with PPHN in the early neonatal period subsequently developed pulmonary hypertension associated with bronchopulmonary dysplasia in later life. Infants with pulmonary hypertension were at lower gestational age at delivery, had a lower birth weight and a higher rate of neonatal co-morbidity. The infants in the sildenafil group showed a significant increase in pulmonary hypertension compared to the placebo group (relative risk 3.67; 95% confidence interval 1.28 to 10.51, P = 0.02).Conclusion: Pulmonary hypertension occurred more frequent among infants of mothers allocated to antenatal sildenafil compared with placebo. A possible pathophysiological mechanism could be a "rebound" vasoconstriction after cessation of sildenafil. Additional studies and data are necessary to understand the mechanism of action. Show less
