Sicco Scherjon - Academia.edu (original) (raw)
Papers by Sicco Scherjon
International Journal of Environmental Research and Public Health
With postpartum hemorrhage (PPH) continuing to be the leading cause of maternal mortality in most... more With postpartum hemorrhage (PPH) continuing to be the leading cause of maternal mortality in most low-resource settings, an audit of the quality of care in health facilities is essential. The purpose of this study was to identify areas of substandard care and establish recommendations for the management of PPH in Hiwot Fana Specialized University Hospital, eastern Ethiopia. Using standard criteria (n = 8) adapted to the local hospital setting, we audited 45 women with PPH admitted from August 2018 to March 2019. Four criteria were agreed as being low: IV line-setup (32 women, 71.1%), accurate postpartum vital sign monitoring (23 women, 51.1%), performing typing and cross-matching (22 women, 48.9%), and fluid intake/output chart maintenance (6 women, 13.3%). In only 3 out of 45 women (6.7%), all eight standard criteria were met. Deficiencies in the case of note documentation and clinical monitoring, non-availability of medical resources and blood for transfusion, as well as delays in...
Obstetrical & Gynecological Survey
Frontiers in Immunology
Preeclampsia is one of the leading causes of maternal and neonatal mortality and morbidity worldw... more Preeclampsia is one of the leading causes of maternal and neonatal mortality and morbidity worldwide, affecting 2-8% of all pregnancies. Studies suggest a link between complement activation and preeclampsia. The complement system plays an essential role in the innate immunity, leading to opsonization, inflammation, and elimination of potential pathogens. The complement system also provides a link between innate and adaptive immunity and clearance of immune complexes and apoptotic cells. During pregnancy there is increased activity of the complement system systemically. However, locally at the placenta, complement inhibition is crucial for the maintenance of a normal pregnancy. Inappropriate or excessive activation of the complement system at the placenta is likely involved in placental dysfunction, and is in turn associated with pregnancy complications like preeclampsia. Therefore, modulation of the complement system could be a potential therapeutic target to prevent pregnancy complications such as preeclampsia. This review, based on a systematic literature search, gives an overview of the complement system and its activation locally in the placenta and systemically during healthy pregnancies and during complicated pregnancies, with a focus on preeclampsia. Furthermore, this review describes results of animal and human studies with a focus on the complement system in pregnancy, and the role of the complement system in placental dysfunction. Various clinical and animal studies provide evidence that dysregulation of the complement system is associated with placental dysfunction and therefore with preeclampsia. Several drugs are used for prevention and treatment of preeclampsia in humans and animal models, and some of these drugs work through complement modulation. Therefore, this review further discusses these studies examining pharmaceutical interventions as treatment for preeclampsia. These observations will help direct research to generate new target options for prevention and treatment of preeclampsia, which include direct and indirect modulation of the complement system.
European Journal of Obstetrics & Gynecology and Reproductive Biology
Objective: To compare effects of immediate delivery vs expectant monitoring on neurodevelopmental... more Objective: To compare effects of immediate delivery vs expectant monitoring on neurodevelopmental and behavioral outcomes at 5 [ 1 2 7 _ T D $ D I F F ] years of age in offspring of women with mild late preterm hypertensive disorders. Study design: We studied children born during the HYPITAT-II trial, in which 704 women with a hypertensive disorder between 34 and 37 weeks of gestation were randomized to immediate delivery or expectant monitoring. Participating women were asked to complete the Ages and Stages Questionnaire (ASQ) for developmental outcome and the Child Behavior Checklist (CBCL) for behavioral problems when their child was 5 [ 1 2 7 _ T D $ D I F F ] years old. Outcomes were dichotomized and analyzed by logistic regression analysis. We also assessed factors influencing development and behavior at both 2 and 5 [ 1 2 7 _ T D $ D I F F ] years after a hypertensive pregnancy. Results: Five years after the original study 322(46%) women were contacted for follow-up, of whom 148 (46%) responded. In the delivery group 22%(n = 14/65) of the children had an abnormal ASQ score compared to 21% (n = 13/62) in the expectant monitoring group (p = 0.9). Abnormal CBCL-scores were found in 19% (n = 14/72) of the children in the delivery group versus in 27% (n = 20/75) in the expectant monitoring group (p = 0.3). The main predictor of development and behavior at 2 and 5 [ 1 2 7 _ T D $ D I F F ] years was fetal growth restriction (for abnormal development OR 2.1, CI 1.0-4.4; for behavior problems OR 2.2, CI 1.1-5.5). Higher maternal education decreased abnormal behavior outcomes (OR 0.5, CI 0.2-0.9) and a similar tendency was observed for developmental problems (OR 0.6, CI 0.3-1.1). Conclusion: We did not find different developmental and behavior outcomes at 5 [ 1 2 7 _ T D $ D I F F ] years of age between a management policy of immediate delivery and expectant management in preterm hypertensive disorders. The increased risk of developmental delay at 2 years of age after immediate delivery, we found in the 2 year follow up study, did not persist at 5
Journal of Reproductive Immunology
American Journal of Obstetrics and Gynecology
American journal of physiology. Regulatory, integrative and comparative physiology, Jan 12, 2018
Intrauterine growth restriction (IUGR) is an accepted risk factor for metabolic disorders in late... more Intrauterine growth restriction (IUGR) is an accepted risk factor for metabolic disorders in later life, including obesity and type 2 diabetes. The level of metabolic dysregulation can vary between subjects and is dependent on the severity and the type of IUGR insult. Classical IUGR animal models involve nutritional deprivation of the mother or uterine artery ligation. The latter aims to mimic a placental insufficiency, which is the most frequent cause of IUGR. In this study, we investigated whether IUGR due to placental insufficiency impacts the glucose and lipid homeostasis at advanced age. Placental insufficiency was achieved by deletion of the transcription factor AP-2y (Tfap2c), which serves as one of the major trophoblast differentiation regulators. TdelT-IUGR mice were obtained by crossing mice with a floxed Tfap2c allele and mice with Cre recombinase under the control of the Tpbpa promoter. In advanced adulthood (9-12 months) female and male IUGR mice are respectively 20% an...
Journal of reproductive immunology, 2018
Disturbances in fetal neurodevelopment have extensively been related to neurodevelopmental disord... more Disturbances in fetal neurodevelopment have extensively been related to neurodevelopmental disorders in early and later life. Fetal neurodevelopment is dependent on adequate functioning of the fetal immune system. During pregnancy, the maternal immune system is challenged to both tolerate the semi-allogenic fetus and to protect the mother and fetus from microbes. The fetal immune system is influenced by maternal immune disturbances; therefore, perturbations in maternal immunity likely do not only alter pregnancy outcome but also alter fetal neurodevelopment. A possible common pathway could be modulating the functioning of tissue macrophages in the placenta and brain. Maternal immune tolerance towards the fetus involves several complex adaptations. In this active maternal immune state, the fetus develops its own immunity. As cytokines and other players of the immune system -which can pass the placenta- are involved in neurodevelopment, disruptions in immune balance influence fetal ne...
Hypertension (Dallas, Tex. : 1979), 2018
Diabetic pregnancy is correlated with increased risk of metabolic and neurological disorders in t... more Diabetic pregnancy is correlated with increased risk of metabolic and neurological disorders in the offspring putatively mediated epigenetically. Little is known about epigenetic changes already present in fetuses of diabetic pregnancies. We aimed at characterizing the perinatal environment after preexisting maternal diabetes mellitus and at identifying relevant epigenetic changes in the fetus. We focused on the transcription factor (sterol regulatory element binding transcription factor 2), a master gene in regulation of cholesterol metabolism. We tested whether diabetic pregnancy induces epigenetic changes in the promoter and if they become manifest in altered gene expression. We worked with a transgenic rat model of type 2 diabetes mellitus (Tet29) in which the insulin receptor is knocked down by doxycycline-induced RNA interference. Doxycycline was administered preconceptionally to Tet29 and wild-type control rats. Only Tet29 doxycycline dams were hyperglycemic, hyperinsulinemic...
European Journal of Obstetrics & Gynecology and Reproductive Biology
To assess the underlying risk factors for perinatal mortality in term born small for gestational ... more To assess the underlying risk factors for perinatal mortality in term born small for gestational age infants. We performed a population based nationwide cohort study in the Netherlands of 465,532 term born infants from January 2010 to January 2013. Logistic regression analyses were performed. Also audit results were studied for detailed care information. We studied 162 small for gestational age infants who died in the perinatal period. Risk factors were: gestational age at 37completed weeks (adjusted Odds Ratio (aOR) 2.6, 95% Confidence Interval (CI) 1.6-4.3), male gender (aOR 1.4, 95% CI 1.01-1.9), South Asian ethnicity (aOR 3.6, 95% CI 1.6-8.4), African (aOR 3.5, 95% CI 1.9-6.5) and other non-Western ethnicity (aOR 1.9, CI 1.2-3.1). At 37 completed weeks gestation audit results showed that 26% of the women smoked, 91% were boys and in all but one case death occurred before birth. In 61% of all deceased SGA infants born at 37 completed weeks gestation referral from primary care by independent midwives to the obstetrician took place because of antepartum death before labor. Gestational age of 37 completed weeks, male gender, South Asian, African or other non-Western ethnicity and smoking are associated with perinatal mortality in SGA infants. These risk factors concern the complete term population starting at 37 weeks or even earlier. Therefore, it is of utmost importance to develop accurate diagnostic tests to screen for SGA before 36 weeks gestation to prevent perinatal mortality at term in SGA infants.
Scientific Reports, 2016
During pregnancy, the mother provides multiple nutrients and substances to the foetus, with mater... more During pregnancy, the mother provides multiple nutrients and substances to the foetus, with maternal immunoglobulin G (IgG) being actively transported to the foetus. Newborns depend on maternal IgG for immune-protection in their first months. The glycosylation of IgG has been shown to influence its dynamics, e.g. receptor binding. While minor differences in IgG glycosylation have been found between IgG derived from maternal blood and umbilical cord blood (UC) of newborn children, the differential glycosylation of maternal and UC plasma has hitherto not been studied. Here, we studied the Nglycosylation of IgG and total plasma proteome of both maternal and UC plasma of 42 pairs of mothers and newborn children. A total of 37 N-glycans were quantified for IgG and 45 for the total plasma Nglycome (TPNG). The study showed slightly higher levels of galactosylation for UC IgG than maternal IgG, confirming previous results, as well as lower bisection and sialylation. Furthermore, the TPNG results showed lower values for galactosylation and sialylation, and higher values for fucosylation in the UC plasma. In conclusion, this study presents some novel insights into IgG glycosylation differences as well as the first broad overview of the differential plasma glycosylation between mothers and newborns.
Journal of Reproductive Immunology, 2016
Early Human Development, Apr 30, 2009
Background: Antenatal corticosteroid administration to premature, growth restricted fetuses may n... more Background: Antenatal corticosteroid administration to premature, growth restricted fetuses may not be beneficial and even have adverse effects on neonatal outcome. Aims: To determine if preterm growth restricted fetuses benefit from antenatal corticosteroids. Study design: Retrospective cohort study. Methods: All singleton pregnancies with growth restricted fetuses delivered at our department before 34 weeks' gestation or weighing less than 1500 g, between January 2001 and December 2005, were retrospectively reviewed. Neonatal outcome was compared between growth restricted fetuses (defined as abnormal flow patterns in umbilical and middle cerebral arteries) that received antenatal CST (CST group) and those who did not receive antenatal CST (no CST group). The administration of CST appeared to be quasi randomized. Results: A total of 88 pregnancies fulfilled the inclusion criteria (CST group, n = 54; no CST group, n = 34). The incidence of neonatal respiratory distress syndrome in the CST and no CST group was 42% (22/54) and 50% (17/34), respectively (p = 0.44). Neonatal mortality in the CST and no CST group was 9% (5/54) and 12% (4/34), respectively (p = 0.73). The prevalence of adverse neonatal outcome (neonatal mortality, major neonatal morbidity or severe cerebral lesions) in the CST and no CST group was 28% (15/54) versus 24% (8/34), (p = 0.62). Conclusions: Administration of CST to growth restricted preterm fetuses does not appear to be beneficial with respect to short term neonatal outcome.
Prenatal Diagnosis, Dec 15, 2005
To describe the use of fetal MRI as an adjunct to high-resolution ultrasound in parental counsell... more To describe the use of fetal MRI as an adjunct to high-resolution ultrasound in parental counselling in a family with a central nervous system (CNS) abnormality, resembling the agyria-pachyria complex, of probably autosomal recessive inheritance. Description of the use of fetal MRI as an adjunct to high-resolution ultrasound in three consecutive pregnancies in a family with a CNS abnormality. Fetal MRI, by showing more detailed abnormalities of the CNS, proved to be very useful in parental counselling because of the definitive diagnosis available early in pregnancy. In the first two pregnancies, ultrasound examination revealed mild pyelectasis, megacystis and an enlarged posterior fossa with small cerebellum. MRI at 22-33 weeks confirmed these abnormalities, but also showed pachygyria. In the third pregnancy, MRI at 19 weeks showed no abnormalities, a finding of decisive importance for counselling. Fetal MRI was useful both for early diagnosis and prenatal management in this family with an agyria-pachyria complex CNS abnormality.
Nederlands Tijdschrift Voor Geneeskunde, 2009
To determine the prognostic value of foetal fibronectin and cervical length for predicting immine... more To determine the prognostic value of foetal fibronectin and cervical length for predicting imminent preterm labour among Dutch women, who in the Netherlands normally undergo a digital examination of the cervix prior to referral to a hospital or university medical centre. Prospective observational cohort study. Pregnant women with symptoms of preterm labour and a gestational age between 24 and 34 weeks were included. A fibronectin smear was taken from them and the cervical length was measured. Primary outcome was delivery within 7 days after inclusion. Sensitivity, specificity and a receiver-operating characteristics (ROC) curve were calculated. 13 (12%) of the 108 included patients delivered spontaneously within 7 days after inclusion. The fibronectin test had a sensitivity of 92% and specificity of 60%. The positive and negative predictive values were 27% and 98% respectively. For women who had undergone a digital examination prior to testing, the predictive value was slightly less but the difference was not significant. Although measurement of the cervical length scarcely had a predictive value, none of the patients with a cervical length above 35 mm delivered within 7 days. In women with an imminent preterm labour, a negative fibronectin test virtually ruled out delivery within 7 days. The fibronectin test can therefore also be used in the Dutch situation. In women with a cervix length greater than 35 mm, the chance of a preterm labour within 7 days is very small and a fibronectin test does not need to be performed in their case.
Acta Obstetricia Et Gynecologica Scandinavica, Sep 19, 2009
There are no randomized studies on the effect of antenatal corticosteroids in preterm intrauterin... more There are no randomized studies on the effect of antenatal corticosteroids in preterm intrauterine growth restricted (IUGR) fetuses. Fetal lung maturation has been postulated to be enhanced in these fetuses, which may result in little benefit of steroid treatment. Furthermore, corticosteroid treatment may be detrimental, as has been shown in IUGR animal models. The objective of this study was to review the available literature on antenatal steroid treatment of the IUGR fetus. All available reports on antenatal steroid treatment of IUGR and small for gestational age (SGA) fetuses published prior to October 2007 were included in this review. IUGR fetuses are a subgroup of SGA fetuses that are small due to placental insufficiency, which is reflected in abnormal Doppler examination of the umbilical artery. The main outcome measures were respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and neonatal mortality. No difference in neonatal mortality was seen in any of the reviewed studies and RDS, IVH, and NEC incidence did not differ between treated and untreated IUGR fetuses. In SGA fetuses, results on RDS incidence and intracranial outcome were inconclusive. Antenatal steroid treatment does not seem to have an effect on neonatal mortality or morbidity in IUGR fetuses. In SGA fetuses, it remains unclear if antenatal steroid treatment is beneficial due to heterogeneous populations and treatment regimes. A randomized controlled trial should be performed to confirm prior results and answer further questions regarding antenatal steroid treatment of these fetuses.
Journal of Reproductive Immunology, May 1, 2009
Specific receptors enable NK cells to discriminate between cells with normal expression of MHC cl... more Specific receptors enable NK cells to discriminate between cells with normal expression of MHC class I and cells that have low or absent expression of MHC class I molecules. In addition to NK cells, these receptors can be expressed on T cell subsets, mainly on CD8+ T cells but also on gammadeltaTCR+ T cells and CD4+ T cells. Although the function of NK cell receptor expression on T cells is not completely understood, various studies have shown that they are involved in down regulation of T cell receptor (TCR)-mediated activation and influence effector functions, like cytotoxicity and cytokine production. The aim of this study was to analyze expression of NK cell receptors on peripheral blood and decidual T cells during human pregnancy using flow cytometry. We demonstrate that a proportion of decidual T cells express HLA-C specific killer immunoglobulin-like receptors (KIRs). Furthermore, a small proportion of decidual T cells express the HLA-E specific CD94-NKG2A inhibitory and CD94-NKG2C activating receptors. Decidual KIR+ and CD94-NKG2+ T cells mainly display a CD3+CD4-CD8- phenotype. However, decidual tissue also contains higher percentages of KIR and CD94-NKG2 expressing CD4+ and CD8+ T cells compared to peripheral blood. So far, the functional capacities of decidual T cells expressing the NK cell receptors are unknown but NK cell receptor expression on decidual T cells may provide an alternative means by which decidual T cells distinguish self (maternal) cells from allogeneic fetal cells, and act to modulate the decidual immune response.
American Journal of Obstetrics and Gynecology, Jan 31, 2005
The purpose of this study was to establish the true procedure-related complication rate of intrau... more The purpose of this study was to establish the true procedure-related complication rate of intrauterine transfusion therapy. A cohort study of 254 fetuses treated with 740 intrauterine blood transfusions for red-cell alloimmunization in a single center in the years 1988 to 2001. Our database was searched for perinatal deaths, emergency deliveries, infections, and preterm rupture of membranes associated with intrauterine blood transfusion. Complications were categorized by two independent obstetricians as procedure-related (PR) or not procedure-related (NPR). Logistic regression analysis was used to identify risk factors for complications. Overall survival was 225/254 (89%). Fetal death occurred in 19 cases (7 PR) and neonatal death in 10 cases (5 PR). There were two cases of intrauterine infection with Escherichia coli (both PR) and two other cases of preterm premature rupture of membranes (1 PR) within a week of a procedure. Emergency delivery after a transfusion was performed in 18 pregnancies (15 PR). The total PR complication rate was 3.1%, resulting in an overall PR loss rate of 1.6% per procedure. Arterial puncture, transamniotic cord puncture, refraining from fetal paralysis, and advancing gestational age were associated with the occurrence of PR complications. Our study shows that intrauterine transfusion is a safe procedure, with a relatively low PR perinatal loss rate. Arterial puncture and transamniotic cord needling carry a high risk for serious complications, whereas fetal paralysis improves the safety of the procedure. This information on risks of intrauterine transfusion therapy may help to further improve the safety of intrauterine transfusions. Data on complication rates of intrauterine transfusions are essential in counseling patients.
International Journal of Environmental Research and Public Health
With postpartum hemorrhage (PPH) continuing to be the leading cause of maternal mortality in most... more With postpartum hemorrhage (PPH) continuing to be the leading cause of maternal mortality in most low-resource settings, an audit of the quality of care in health facilities is essential. The purpose of this study was to identify areas of substandard care and establish recommendations for the management of PPH in Hiwot Fana Specialized University Hospital, eastern Ethiopia. Using standard criteria (n = 8) adapted to the local hospital setting, we audited 45 women with PPH admitted from August 2018 to March 2019. Four criteria were agreed as being low: IV line-setup (32 women, 71.1%), accurate postpartum vital sign monitoring (23 women, 51.1%), performing typing and cross-matching (22 women, 48.9%), and fluid intake/output chart maintenance (6 women, 13.3%). In only 3 out of 45 women (6.7%), all eight standard criteria were met. Deficiencies in the case of note documentation and clinical monitoring, non-availability of medical resources and blood for transfusion, as well as delays in...
Obstetrical & Gynecological Survey
Frontiers in Immunology
Preeclampsia is one of the leading causes of maternal and neonatal mortality and morbidity worldw... more Preeclampsia is one of the leading causes of maternal and neonatal mortality and morbidity worldwide, affecting 2-8% of all pregnancies. Studies suggest a link between complement activation and preeclampsia. The complement system plays an essential role in the innate immunity, leading to opsonization, inflammation, and elimination of potential pathogens. The complement system also provides a link between innate and adaptive immunity and clearance of immune complexes and apoptotic cells. During pregnancy there is increased activity of the complement system systemically. However, locally at the placenta, complement inhibition is crucial for the maintenance of a normal pregnancy. Inappropriate or excessive activation of the complement system at the placenta is likely involved in placental dysfunction, and is in turn associated with pregnancy complications like preeclampsia. Therefore, modulation of the complement system could be a potential therapeutic target to prevent pregnancy complications such as preeclampsia. This review, based on a systematic literature search, gives an overview of the complement system and its activation locally in the placenta and systemically during healthy pregnancies and during complicated pregnancies, with a focus on preeclampsia. Furthermore, this review describes results of animal and human studies with a focus on the complement system in pregnancy, and the role of the complement system in placental dysfunction. Various clinical and animal studies provide evidence that dysregulation of the complement system is associated with placental dysfunction and therefore with preeclampsia. Several drugs are used for prevention and treatment of preeclampsia in humans and animal models, and some of these drugs work through complement modulation. Therefore, this review further discusses these studies examining pharmaceutical interventions as treatment for preeclampsia. These observations will help direct research to generate new target options for prevention and treatment of preeclampsia, which include direct and indirect modulation of the complement system.
European Journal of Obstetrics & Gynecology and Reproductive Biology
Objective: To compare effects of immediate delivery vs expectant monitoring on neurodevelopmental... more Objective: To compare effects of immediate delivery vs expectant monitoring on neurodevelopmental and behavioral outcomes at 5 [ 1 2 7 _ T D $ D I F F ] years of age in offspring of women with mild late preterm hypertensive disorders. Study design: We studied children born during the HYPITAT-II trial, in which 704 women with a hypertensive disorder between 34 and 37 weeks of gestation were randomized to immediate delivery or expectant monitoring. Participating women were asked to complete the Ages and Stages Questionnaire (ASQ) for developmental outcome and the Child Behavior Checklist (CBCL) for behavioral problems when their child was 5 [ 1 2 7 _ T D $ D I F F ] years old. Outcomes were dichotomized and analyzed by logistic regression analysis. We also assessed factors influencing development and behavior at both 2 and 5 [ 1 2 7 _ T D $ D I F F ] years after a hypertensive pregnancy. Results: Five years after the original study 322(46%) women were contacted for follow-up, of whom 148 (46%) responded. In the delivery group 22%(n = 14/65) of the children had an abnormal ASQ score compared to 21% (n = 13/62) in the expectant monitoring group (p = 0.9). Abnormal CBCL-scores were found in 19% (n = 14/72) of the children in the delivery group versus in 27% (n = 20/75) in the expectant monitoring group (p = 0.3). The main predictor of development and behavior at 2 and 5 [ 1 2 7 _ T D $ D I F F ] years was fetal growth restriction (for abnormal development OR 2.1, CI 1.0-4.4; for behavior problems OR 2.2, CI 1.1-5.5). Higher maternal education decreased abnormal behavior outcomes (OR 0.5, CI 0.2-0.9) and a similar tendency was observed for developmental problems (OR 0.6, CI 0.3-1.1). Conclusion: We did not find different developmental and behavior outcomes at 5 [ 1 2 7 _ T D $ D I F F ] years of age between a management policy of immediate delivery and expectant management in preterm hypertensive disorders. The increased risk of developmental delay at 2 years of age after immediate delivery, we found in the 2 year follow up study, did not persist at 5
Journal of Reproductive Immunology
American Journal of Obstetrics and Gynecology
American journal of physiology. Regulatory, integrative and comparative physiology, Jan 12, 2018
Intrauterine growth restriction (IUGR) is an accepted risk factor for metabolic disorders in late... more Intrauterine growth restriction (IUGR) is an accepted risk factor for metabolic disorders in later life, including obesity and type 2 diabetes. The level of metabolic dysregulation can vary between subjects and is dependent on the severity and the type of IUGR insult. Classical IUGR animal models involve nutritional deprivation of the mother or uterine artery ligation. The latter aims to mimic a placental insufficiency, which is the most frequent cause of IUGR. In this study, we investigated whether IUGR due to placental insufficiency impacts the glucose and lipid homeostasis at advanced age. Placental insufficiency was achieved by deletion of the transcription factor AP-2y (Tfap2c), which serves as one of the major trophoblast differentiation regulators. TdelT-IUGR mice were obtained by crossing mice with a floxed Tfap2c allele and mice with Cre recombinase under the control of the Tpbpa promoter. In advanced adulthood (9-12 months) female and male IUGR mice are respectively 20% an...
Journal of reproductive immunology, 2018
Disturbances in fetal neurodevelopment have extensively been related to neurodevelopmental disord... more Disturbances in fetal neurodevelopment have extensively been related to neurodevelopmental disorders in early and later life. Fetal neurodevelopment is dependent on adequate functioning of the fetal immune system. During pregnancy, the maternal immune system is challenged to both tolerate the semi-allogenic fetus and to protect the mother and fetus from microbes. The fetal immune system is influenced by maternal immune disturbances; therefore, perturbations in maternal immunity likely do not only alter pregnancy outcome but also alter fetal neurodevelopment. A possible common pathway could be modulating the functioning of tissue macrophages in the placenta and brain. Maternal immune tolerance towards the fetus involves several complex adaptations. In this active maternal immune state, the fetus develops its own immunity. As cytokines and other players of the immune system -which can pass the placenta- are involved in neurodevelopment, disruptions in immune balance influence fetal ne...
Hypertension (Dallas, Tex. : 1979), 2018
Diabetic pregnancy is correlated with increased risk of metabolic and neurological disorders in t... more Diabetic pregnancy is correlated with increased risk of metabolic and neurological disorders in the offspring putatively mediated epigenetically. Little is known about epigenetic changes already present in fetuses of diabetic pregnancies. We aimed at characterizing the perinatal environment after preexisting maternal diabetes mellitus and at identifying relevant epigenetic changes in the fetus. We focused on the transcription factor (sterol regulatory element binding transcription factor 2), a master gene in regulation of cholesterol metabolism. We tested whether diabetic pregnancy induces epigenetic changes in the promoter and if they become manifest in altered gene expression. We worked with a transgenic rat model of type 2 diabetes mellitus (Tet29) in which the insulin receptor is knocked down by doxycycline-induced RNA interference. Doxycycline was administered preconceptionally to Tet29 and wild-type control rats. Only Tet29 doxycycline dams were hyperglycemic, hyperinsulinemic...
European Journal of Obstetrics & Gynecology and Reproductive Biology
To assess the underlying risk factors for perinatal mortality in term born small for gestational ... more To assess the underlying risk factors for perinatal mortality in term born small for gestational age infants. We performed a population based nationwide cohort study in the Netherlands of 465,532 term born infants from January 2010 to January 2013. Logistic regression analyses were performed. Also audit results were studied for detailed care information. We studied 162 small for gestational age infants who died in the perinatal period. Risk factors were: gestational age at 37completed weeks (adjusted Odds Ratio (aOR) 2.6, 95% Confidence Interval (CI) 1.6-4.3), male gender (aOR 1.4, 95% CI 1.01-1.9), South Asian ethnicity (aOR 3.6, 95% CI 1.6-8.4), African (aOR 3.5, 95% CI 1.9-6.5) and other non-Western ethnicity (aOR 1.9, CI 1.2-3.1). At 37 completed weeks gestation audit results showed that 26% of the women smoked, 91% were boys and in all but one case death occurred before birth. In 61% of all deceased SGA infants born at 37 completed weeks gestation referral from primary care by independent midwives to the obstetrician took place because of antepartum death before labor. Gestational age of 37 completed weeks, male gender, South Asian, African or other non-Western ethnicity and smoking are associated with perinatal mortality in SGA infants. These risk factors concern the complete term population starting at 37 weeks or even earlier. Therefore, it is of utmost importance to develop accurate diagnostic tests to screen for SGA before 36 weeks gestation to prevent perinatal mortality at term in SGA infants.
Scientific Reports, 2016
During pregnancy, the mother provides multiple nutrients and substances to the foetus, with mater... more During pregnancy, the mother provides multiple nutrients and substances to the foetus, with maternal immunoglobulin G (IgG) being actively transported to the foetus. Newborns depend on maternal IgG for immune-protection in their first months. The glycosylation of IgG has been shown to influence its dynamics, e.g. receptor binding. While minor differences in IgG glycosylation have been found between IgG derived from maternal blood and umbilical cord blood (UC) of newborn children, the differential glycosylation of maternal and UC plasma has hitherto not been studied. Here, we studied the Nglycosylation of IgG and total plasma proteome of both maternal and UC plasma of 42 pairs of mothers and newborn children. A total of 37 N-glycans were quantified for IgG and 45 for the total plasma Nglycome (TPNG). The study showed slightly higher levels of galactosylation for UC IgG than maternal IgG, confirming previous results, as well as lower bisection and sialylation. Furthermore, the TPNG results showed lower values for galactosylation and sialylation, and higher values for fucosylation in the UC plasma. In conclusion, this study presents some novel insights into IgG glycosylation differences as well as the first broad overview of the differential plasma glycosylation between mothers and newborns.
Journal of Reproductive Immunology, 2016
Early Human Development, Apr 30, 2009
Background: Antenatal corticosteroid administration to premature, growth restricted fetuses may n... more Background: Antenatal corticosteroid administration to premature, growth restricted fetuses may not be beneficial and even have adverse effects on neonatal outcome. Aims: To determine if preterm growth restricted fetuses benefit from antenatal corticosteroids. Study design: Retrospective cohort study. Methods: All singleton pregnancies with growth restricted fetuses delivered at our department before 34 weeks' gestation or weighing less than 1500 g, between January 2001 and December 2005, were retrospectively reviewed. Neonatal outcome was compared between growth restricted fetuses (defined as abnormal flow patterns in umbilical and middle cerebral arteries) that received antenatal CST (CST group) and those who did not receive antenatal CST (no CST group). The administration of CST appeared to be quasi randomized. Results: A total of 88 pregnancies fulfilled the inclusion criteria (CST group, n = 54; no CST group, n = 34). The incidence of neonatal respiratory distress syndrome in the CST and no CST group was 42% (22/54) and 50% (17/34), respectively (p = 0.44). Neonatal mortality in the CST and no CST group was 9% (5/54) and 12% (4/34), respectively (p = 0.73). The prevalence of adverse neonatal outcome (neonatal mortality, major neonatal morbidity or severe cerebral lesions) in the CST and no CST group was 28% (15/54) versus 24% (8/34), (p = 0.62). Conclusions: Administration of CST to growth restricted preterm fetuses does not appear to be beneficial with respect to short term neonatal outcome.
Prenatal Diagnosis, Dec 15, 2005
To describe the use of fetal MRI as an adjunct to high-resolution ultrasound in parental counsell... more To describe the use of fetal MRI as an adjunct to high-resolution ultrasound in parental counselling in a family with a central nervous system (CNS) abnormality, resembling the agyria-pachyria complex, of probably autosomal recessive inheritance. Description of the use of fetal MRI as an adjunct to high-resolution ultrasound in three consecutive pregnancies in a family with a CNS abnormality. Fetal MRI, by showing more detailed abnormalities of the CNS, proved to be very useful in parental counselling because of the definitive diagnosis available early in pregnancy. In the first two pregnancies, ultrasound examination revealed mild pyelectasis, megacystis and an enlarged posterior fossa with small cerebellum. MRI at 22-33 weeks confirmed these abnormalities, but also showed pachygyria. In the third pregnancy, MRI at 19 weeks showed no abnormalities, a finding of decisive importance for counselling. Fetal MRI was useful both for early diagnosis and prenatal management in this family with an agyria-pachyria complex CNS abnormality.
Nederlands Tijdschrift Voor Geneeskunde, 2009
To determine the prognostic value of foetal fibronectin and cervical length for predicting immine... more To determine the prognostic value of foetal fibronectin and cervical length for predicting imminent preterm labour among Dutch women, who in the Netherlands normally undergo a digital examination of the cervix prior to referral to a hospital or university medical centre. Prospective observational cohort study. Pregnant women with symptoms of preterm labour and a gestational age between 24 and 34 weeks were included. A fibronectin smear was taken from them and the cervical length was measured. Primary outcome was delivery within 7 days after inclusion. Sensitivity, specificity and a receiver-operating characteristics (ROC) curve were calculated. 13 (12%) of the 108 included patients delivered spontaneously within 7 days after inclusion. The fibronectin test had a sensitivity of 92% and specificity of 60%. The positive and negative predictive values were 27% and 98% respectively. For women who had undergone a digital examination prior to testing, the predictive value was slightly less but the difference was not significant. Although measurement of the cervical length scarcely had a predictive value, none of the patients with a cervical length above 35 mm delivered within 7 days. In women with an imminent preterm labour, a negative fibronectin test virtually ruled out delivery within 7 days. The fibronectin test can therefore also be used in the Dutch situation. In women with a cervix length greater than 35 mm, the chance of a preterm labour within 7 days is very small and a fibronectin test does not need to be performed in their case.
Acta Obstetricia Et Gynecologica Scandinavica, Sep 19, 2009
There are no randomized studies on the effect of antenatal corticosteroids in preterm intrauterin... more There are no randomized studies on the effect of antenatal corticosteroids in preterm intrauterine growth restricted (IUGR) fetuses. Fetal lung maturation has been postulated to be enhanced in these fetuses, which may result in little benefit of steroid treatment. Furthermore, corticosteroid treatment may be detrimental, as has been shown in IUGR animal models. The objective of this study was to review the available literature on antenatal steroid treatment of the IUGR fetus. All available reports on antenatal steroid treatment of IUGR and small for gestational age (SGA) fetuses published prior to October 2007 were included in this review. IUGR fetuses are a subgroup of SGA fetuses that are small due to placental insufficiency, which is reflected in abnormal Doppler examination of the umbilical artery. The main outcome measures were respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and neonatal mortality. No difference in neonatal mortality was seen in any of the reviewed studies and RDS, IVH, and NEC incidence did not differ between treated and untreated IUGR fetuses. In SGA fetuses, results on RDS incidence and intracranial outcome were inconclusive. Antenatal steroid treatment does not seem to have an effect on neonatal mortality or morbidity in IUGR fetuses. In SGA fetuses, it remains unclear if antenatal steroid treatment is beneficial due to heterogeneous populations and treatment regimes. A randomized controlled trial should be performed to confirm prior results and answer further questions regarding antenatal steroid treatment of these fetuses.
Journal of Reproductive Immunology, May 1, 2009
Specific receptors enable NK cells to discriminate between cells with normal expression of MHC cl... more Specific receptors enable NK cells to discriminate between cells with normal expression of MHC class I and cells that have low or absent expression of MHC class I molecules. In addition to NK cells, these receptors can be expressed on T cell subsets, mainly on CD8+ T cells but also on gammadeltaTCR+ T cells and CD4+ T cells. Although the function of NK cell receptor expression on T cells is not completely understood, various studies have shown that they are involved in down regulation of T cell receptor (TCR)-mediated activation and influence effector functions, like cytotoxicity and cytokine production. The aim of this study was to analyze expression of NK cell receptors on peripheral blood and decidual T cells during human pregnancy using flow cytometry. We demonstrate that a proportion of decidual T cells express HLA-C specific killer immunoglobulin-like receptors (KIRs). Furthermore, a small proportion of decidual T cells express the HLA-E specific CD94-NKG2A inhibitory and CD94-NKG2C activating receptors. Decidual KIR+ and CD94-NKG2+ T cells mainly display a CD3+CD4-CD8- phenotype. However, decidual tissue also contains higher percentages of KIR and CD94-NKG2 expressing CD4+ and CD8+ T cells compared to peripheral blood. So far, the functional capacities of decidual T cells expressing the NK cell receptors are unknown but NK cell receptor expression on decidual T cells may provide an alternative means by which decidual T cells distinguish self (maternal) cells from allogeneic fetal cells, and act to modulate the decidual immune response.
American Journal of Obstetrics and Gynecology, Jan 31, 2005
The purpose of this study was to establish the true procedure-related complication rate of intrau... more The purpose of this study was to establish the true procedure-related complication rate of intrauterine transfusion therapy. A cohort study of 254 fetuses treated with 740 intrauterine blood transfusions for red-cell alloimmunization in a single center in the years 1988 to 2001. Our database was searched for perinatal deaths, emergency deliveries, infections, and preterm rupture of membranes associated with intrauterine blood transfusion. Complications were categorized by two independent obstetricians as procedure-related (PR) or not procedure-related (NPR). Logistic regression analysis was used to identify risk factors for complications. Overall survival was 225/254 (89%). Fetal death occurred in 19 cases (7 PR) and neonatal death in 10 cases (5 PR). There were two cases of intrauterine infection with Escherichia coli (both PR) and two other cases of preterm premature rupture of membranes (1 PR) within a week of a procedure. Emergency delivery after a transfusion was performed in 18 pregnancies (15 PR). The total PR complication rate was 3.1%, resulting in an overall PR loss rate of 1.6% per procedure. Arterial puncture, transamniotic cord puncture, refraining from fetal paralysis, and advancing gestational age were associated with the occurrence of PR complications. Our study shows that intrauterine transfusion is a safe procedure, with a relatively low PR perinatal loss rate. Arterial puncture and transamniotic cord needling carry a high risk for serious complications, whereas fetal paralysis improves the safety of the procedure. This information on risks of intrauterine transfusion therapy may help to further improve the safety of intrauterine transfusions. Data on complication rates of intrauterine transfusions are essential in counseling patients.