BackgroundPregnancy is a known trigger of novel and pre-existing supraventricular tachyarrhythmias. We present a case of a stable pregnant patient presenting with atrioventricular nodal reentry... Show moreBackgroundPregnancy is a known trigger of novel and pre-existing supraventricular tachyarrhythmias. We present a case of a stable pregnant patient presenting with atrioventricular nodal reentry tachycardia (AVNRT) and application of the ‘facial ice immersion technique’.Case summaryA 37-year-old pregnant woman presented with recurrent AVNRT. Due to unsuccessful attempts of conventional vagal manoeuvres (VMs) and refusal of pharmacological agents, we successfully performed a non-conventional VM with the ‘facial ice immersion technique’. This technique was applied successfully at repeated clinical presentation.DiscussionThe role of non-pharmacological interventions remains pivotal and may lead to desired therapeutical effects without the use of any costly pharmacological agents with possible adverse events. However, non-conventional VMs such as the ‘facial ice immersion technique’ are less commonly known but appear to be easy and a safe option for both mother and foetus in the management of AVNRT during pregnancy. Clinical awareness and understanding of treatment options are imperative in contemporary patient care. Show less
Recent studies have suggested that the fetus is capable of exhibiting a stress response to intrauterine needling, resulting in alterations in fetal stress hormone levels. Intrauterine transfusions... Show moreRecent studies have suggested that the fetus is capable of exhibiting a stress response to intrauterine needling, resulting in alterations in fetal stress hormone levels. Intrauterine transfusions are performed by inserting a needle either in the umbilical cord root at the placental surface (PCI), or in the intrahepatic portion of the umbilical vein (IHV). Aim of our study was to test the hypothesis that fetal hormonal changes during intrauterine transfusion are more pronounced when the needle is inserted in the fetal abdomen. Furthermore we aimed to evaluate the effect of fetal analgesia with remifentanil on the fetal stress hormone changes. Exploring the hemodynamic changes following a noxious stimulus, we saw no differences in transfusions through the IHV or the PCI. Remifentanil did not influence the stress hormone changes. We concluded that the stress hormone changes are independent of both site of transfusion and the use of remifentanil. Our results do not confirm nor deny that the fetus is capable to react to a potential painful stimulus, or to show signs of stress or even pain. However, previous research has suggested that presumably painful fetal conditions can lead to alterations in stress reactions after birth. This phenomenon is called ‘fetal programming’. Fetal programming could possibly lead to life-long changes in stress responses and even to increased susceptibility for certain diseases. With the current understanding of fetal pain and fetal analgesia we would advocate the following: 1. Fetal analgesia for invasive procedures should be provided from at least 20 weeks gestation onwards 2. All invasive fetal procedures warrant fetal analgesia, but in procedures involving more than just a single puncture with a thin needle it is obligatory. 3. Analgesics should be given intravenously to the mother. The drug of choice should be ultra-short working (like remifentanil) therefore minimising possible undesirable side-effects to both fetus and mother. Show less
In summary, in this thesis it becomes clear that the intrauterine environment created by the mother during pregnancy not only has beneficial effects on the developing embryo / fetus. Although it is... Show moreIn summary, in this thesis it becomes clear that the intrauterine environment created by the mother during pregnancy not only has beneficial effects on the developing embryo / fetus. Although it is too early to draw definite conclusions, the first results of this research line show that maternal apoE-deficiency, in contrast to maternal Ldlr-deficiency, adversely affects the offspring, not only in late fetal stages but also in adult life. Our data indicate that the inflammatory status of the mother and the lack of maternal apoE itself may attribute to the increased cardiovascular disease risk observed in the adult offspring. Hypercholesterolemia and oxidative stress possibly play a more regulatory role. In a first attempt to elucidate the underlying mechanism we show that maternal apoE-deficiency leads to changes in the histone triple-methylation modifications in the vascular wall of the offspring. Thi s can be considered an important lead that needs to be investigated further. It does not mean, however, that we are close to complete elucidation of the underlying mechanism. A lot of research is needed to accomplish this and it is needed. Why? The fact that a hit so early in life exerts negative effects on cardiovascular disease risk in adulthood is worrisome. If we could succeed in elucidating the exact role of epigenetics in this process and are able to translate these data to the human situation, possibly we could reduce the incidence of cardiovascular disease. Show less
Diagnosing and treating hypercalcemia during pregnancy can be challenging due to both the physiological changes in calcium homeostasis and the underlying cause for the hypercalcemia. During... Show moreDiagnosing and treating hypercalcemia during pregnancy can be challenging due to both the physiological changes in calcium homeostasis and the underlying cause for the hypercalcemia. During pregnancy and lactation there is increased mobilization of calcium in the mother to meet the fetus' calcium requirements. Here we discuss the diagnostic challenges, management, and patient perspective of hypercalcemia during pregnancy in two particular cases and in other rare conditions causing hypercalcemia. Show less
Aim: To examine whether maternal angiogenic factors in the first half of pregnancy are associated with offspring left and right cardiac development. Methods: In a population-based prospective... Show moreAim: To examine whether maternal angiogenic factors in the first half of pregnancy are associated with offspring left and right cardiac development. Methods: In a population-based prospective cohort among 2,415 women and their offspring, maternal first and second trimester plasma PlGF and sFlt-1 concentrations were measured. Cardiac MRI was performed in their offspring at 10 years. Results: Maternal angiogenic factors were not associated with childhood cardiac outcomes in the total population. In children born small-for-their-gestational-age, higher maternal first trimester PlGF concentrations were associated with a lower childhood left ventricular mass (-0.24 SDS [95a/aCI-0.42,-0.05 per SDS increase in maternal PlGF]), whereas higher sFlt-1 concentrations were associated with higher childhood left ventricular mass (0.22 SDS [95a/aCI 0.09, 0.34 per SDS increase in maternal sFlt-1]). Higher second trimester maternal sFlt-1 concentrations were also associated with higher childhood left ventricular mass (P-value > .05). In preterm born children, higher maternal first and second trimester sFlt-1/PlGF ratio were associated with higher childhood left ventricular mass (0.30 SDS [95a/aCI 0.01, 0.60], 0.22 SDS [95a/aCI-0.03, 0.40]) per SDS increase in maternal sFlt-1/PlGF ratio in first and second trimester respectively). No effects on other childhood cardiac outcomes were present within these higher-risk children. Conclusions: In a low-risk population, maternal angiogenic factors are not associated with childhood cardiac ventricular structure, and function within the normal range. In children born small for their gestational age or preterm, an imbalance in maternal angiogenic factors in the first half of pregnancy was associated with higher childhood left ventricular mass only. Show less
Preeclampsia is a pregnancy-specific condition that originates in the placenta. Despite decades of research, its pathogenesis remains largely unknown. However, several risk factors for preeclampsia... Show morePreeclampsia is a pregnancy-specific condition that originates in the placenta. Despite decades of research, its pathogenesis remains largely unknown. However, several risk factors for preeclampsia have been identified, including a (family) history of preeclampsia, autoimmune disease and conditions associated with endothelial damage, including hypertension, diabetes mellitus and preexistent renal disease. This thesis aims to further investigate through which mechanisms these risk factors increase the risk for preeclampsia. It deals with both the genetic background of preeclampsia, as well as the role of complement activation in its pathogenesis. Finally, it touches upon the role of angiogenic factors in the development of preeclampsia. Show less
Thromboembolic complications remain a major public health burden, making antithrombotic agents one of the most widely prescribed groups of medication, but the treatment is often challenging as it... Show moreThromboembolic complications remain a major public health burden, making antithrombotic agents one of the most widely prescribed groups of medication, but the treatment is often challenging as it at the same time increases risk of bleeding. With nationwide data from Statistics Netherlands, antithrombotic therapy and relevant clinical outcomes were comprehensively examined in the patient population of atrial fibrillation, overall or among those with comorbid cancer. The results suggest the patient population was increasingly receiving anticoagulants, driven by the newly introduced medication- direct oral anticoagulant and guided by the CHA2DS2-VASc score, and meanwhile the patient population experienced fewer ischemic stroke and major bleeding. In spite of these promising changes, suboptimal medication adherence and potential underuse of anticoagulants remain directions for further improvement. Antithrombotic agent use during pregnancy was also examined in the general Dutch pregnant population, which featured a surge in antiplatelet prescriptions, and risk of preeclampsia/eclampsia decreased and several newborn outcomes improved simultaneously. Together, the studies presented in this thesis provide an overview of antithrombotic therapy in the Netherlands in recent years, providing insights for further improving this treatment and relevant patient outcomes. Show less
Craenmehr, M.H.C.; Egmond, A. van; Haasnoot, G.W.; Eikmans, M.; Roelen, D.L.; Heidt, S.; ... ; Claas, F.H.J. 2019
Pregnancy can be seen as an immunologic paradox. Even though the fetus expresses paternally inherited alloantigens it is protected from rejection by a proper regulation of the maternal immune... Show morePregnancy can be seen as an immunologic paradox. Even though the fetus expresses paternally inherited alloantigens it is protected from rejection by a proper regulation of the maternal immune system. With the studies described in this thesis, we want to get more insight in the immunologic mechanisms that play a role in pregnancy. The results of this research can help to identify underlying etiologies in patients with unexplained pregnancy complications, such as recurrent miscarriage. Identifying these causes is important for providing answers and taking away anxiety in these couples, and eventually for the development of effective therapies. Furthermore, elucidating the mechanism leading to survival or rejection of the fetal allograft is not only essential for our understanding of processes leading to normal and abnormal pregnancies, but may also result in important concepts in the field of transplantation and autoimmunity. Show less
Recurrent pregnancy loss (RPL) is a poorly understood condition that comes with many uncertainties, both for affected couples and healthcare providers. Important goals are to provide answers to... Show moreRecurrent pregnancy loss (RPL) is a poorly understood condition that comes with many uncertainties, both for affected couples and healthcare providers. Important goals are to provide answers to these couples and to improve their pregnancy outcomes. To achieve this, we need a better understanding of contributing and predictive factors. Until now, the male role in RPL has been underexposed. In this thesis, we aimed to expand our knowledge regarding the ‘forgotten father’ in RPL. We have found strong clues that in RPL, male contribution really matters.The main conclusions are that advanced paternal age and paternal smoking are associated with an increased risk of pregnancy loss, that inclusion of paternal factors into a prediction model improves the accuracy of predicting ongoing pregnancy after RPL, and that impaired immunomodulatory effects of seminal plasma may play a role in RPL. At the same time, our studies have led to new questions and uncovered new challenges, which are excellent opportunities for further research. Show less
Fosse, N.A. du; Bronsgeest, K.; Arbous, M.S.; Zlei, M.; Myeni, S.K.; Kikkert, M.; ... ; Akker, T. van den 2021
A primigravid woman with Covid-19 related respiratory insufficiency was admitted into a tertiary Intensive Care Unit at 23 3/7 weeks' gestation. Highly sensitive flow cytometry of peripheral... Show moreA primigravid woman with Covid-19 related respiratory insufficiency was admitted into a tertiary Intensive Care Unit at 23 3/7 weeks' gestation. Highly sensitive flow cytometry of peripheral leukocytes indicated significantly suppressed naive T- and B-cell compartments. The suppressed immune cell responses led us keep the initially started administration of corticosteroids for fetal and maternal indication at a low dose. After three weeks her B-cell response peaked, SARS-CoV-2 was cleared and clinical improvement ensued a week later. At 28 weeks' gestation, a son of 1570 g was born by cesarean section. She was extubated two days postpartum and discharged from hospital 5.5 weeks postpartum. Show less
Understanding maternal mental health and cortisol regulation across pregnancy and the relationship to the development of the offspring's stress regulation Is critical to a range of health outcomes.... Show moreUnderstanding maternal mental health and cortisol regulation across pregnancy and the relationship to the development of the offspring's stress regulation Is critical to a range of health outcomes. The aim of this study was to investigate infant and maternal cortisol in women with depression. Data were obtained from 241 pregnant women within the Mercy Pregnancy and Emotional Wellbeing Study (MPEWS), a selected pregnancy cohort study. Depression was measured using the Structured Clinical Interview for DSM-IV (SCID-IV) and repeat Edinburgh Postnatal Depression Scale (EPDS). Repeated measures of antidepressant use, stressful events, anxiety symptoms and maternal hair cortisol concentrations (HCC) and infant cortisol at 12 months postpartum in saliva and hair. Socio-emotional outcomes were measured at 12 months by maternal report on the Brief Infant and Toddler Socio-emotional Assessment (BITSEA). This study found that maternal depression was not associated with maternal HCC. Anxiety, stress and antidepressant use were not associated with maternal HCC. Independently, higher maternal 3rd trimester maternal depressive and anxiety symptoms were associated with lower infant cortisol response at 12 months of age. A higher number of postpartum stressful events was associated with lower infant cortisol response. Lower infant stress reactivity was associated with higher externalizing symptoms at 12 months of age. Future studies are required to understand implications for later mental health. Show less
Galbally, M.; Watson, S.J.; Lappas, M.; Kloet, E.R. de; Rossum, E. van; Wyrwoll, C.; ... ; Lewis, A.J. 2021
Placental 11fl-HSD2 has been a focus of research for understanding potential fetal programming associated with maternal emotional disorders. This study examined the pathway from antenatal mental... Show morePlacental 11fl-HSD2 has been a focus of research for understanding potential fetal programming associated with maternal emotional disorders. This study examined the pathway from antenatal mental health via placental 11flHSD2 mRNA to cortisol regulation in the infant offspring. This study reports on data obtained from 236 participants in the Mercy Pregnancy and Emotional Wellbeing Study (MPEWS). At term, placental tissue was collected within 30 min of birth from 52 participants meeting current criteria for a depressive disorder, and 184 control participants. Depressive disorders were diagnosed using the SCID-IV. In addition, antidepressant use, depressive and anxiety symptoms were measured in early and late pregnancy. Placental 11fl-HSD2 mRNA expression was measured using qRT-PCR. Infant salivary cortisol samples were taken at 12 months of age. Women on antidepressant medication and with higher trait anxiety had higher placental 11fl-HSD2 expression compared to women not taking medication. Furthermore, the offspring of women taking an antidepressant and who also had a current depressive disorder and high trait anxiety had high cortisol reactivity at 12 months of age and this was mediated through 11fl-HSD2 mRNA expression. In contrast, offspring of women not taking antidepressant medication with depressive disorder and high anxiety there was low cortisol reactivity observed. Our findings suggest that the relationship between maternal antenatal depression and anxiety and infant cortisol reactivity is mediated through placental 11fl-HSD2 mRNA expression. Furthermore, the direction differed for women taking antidepressants, where infant cortisol reactivity was high whereas when compared to those with unmedicated depression and anxiety, where infant cortisol reactivity was low. Show less
