Nico Hartwig - Academia.edu (original) (raw)
Papers by Nico Hartwig
Vaccine, 2013
Objective: A phase IV interventional study with a combined hepatitis A and B vaccine was conducte... more Objective: A phase IV interventional study with a combined hepatitis A and B vaccine was conducted in HIV-infected children and children receiving immunosuppressive medication for treatment of rheumatic diseases to evaluate immune responses. Methods: Both groups (1-16 years of age) received combined (inactivated) HAV and (rDNA) HBV vaccine Ambirix ® at months 0 and 6. Serum samples were taken at four time points and tested for anti-HAV and anti-HBs antibodies. Anti-HAV concentrations ≥20 mIU/mL or anti-HBs concentrations ≥10 mIU/mL were considered protective. Seropositivity percentages were calculated and geometric mean concentrations (GMCs) were compared by nonparametric Mann-Whitney U-test or Kruskal-Wallis one-way-analysisof-variance. Results: Of 80 HIV-infected children who completed the study, 67 were HAV-susceptible and 68 HBVsusceptible at enrolment. Of 80 children with rheumatic diseases who completed the study, 65 were HAV-susceptible and 74 HBV-susceptible at enrolment. Immune responses to HAV after first dose of vaccine in both study groups were low: 71% and 55% respectively, whereas immune responses after the second dose were 99% and 100% respectively. Immune response to HBV after first dose of vaccine in both groups was also low: 27% and 17% respectively. Immune responses after the second dose were 97% and 93%, respectively. A larger proportion of children on combination antiretroviral therapy (cART) and of children with viral load <50 copies/mL responded to HBV, and also showed a significantly higher GMC. Conclusions: Although immune response after full series of combined HAV and HBV vaccine in both groups was excellent and comparable to healthy children, a substantial proportion of both groups was not protected for HAV after first dose of vaccine. This protection gap is especially important for HAV in travel health and postexposure prophylactic treatment: both groups of children should be serologically tested for anti-HAV prior to travel to ensure protection if there is no time to await second dose of vaccine.
Tijdschrift voor kindergeneeskunde, 2004
... Toediening van immunoglobulinen zou enig effect hebben gehad bij patie¨nten met agammaglobuli... more ... Toediening van immunoglobulinen zou enig effect hebben gehad bij patie¨nten met agammaglobuline-mie met een chronische enterovirusinfectie.18 Voor ... Antimicrob Agents Chemother 1999;43:2109-15. Kearns G, Abdel-Rahman S, James L, et al. ...
Tijdschrift Voor Kindergeneeskunde, 2002
... CMR Weemaes NG Hartwig I. van der Burgt Summary In 'classical' immunodefici... more ... CMR Weemaes NG Hartwig I. van der Burgt Summary In 'classical' immunodeficiencies only the function of phagocytes or lymphocytes is disturbed. ... 13 Page 2. palatoschisis, kleine teruggetrokken kin en laag inge-plante kleine oren. ...
Tijdschrift Voor Kindergeneeskunde, 2005
Tijdschrift Voor Kindergeneeskunde, 2010
Seminars in Pediatric Surgery
Congenital abdominal wall defects, frequently associated with other anomalies, are found in many ... more Congenital abdominal wall defects, frequently associated with other anomalies, are found in many forms. Consequently, there is still controversy in the literature concerning nomenclature, classification, and pathogenesis. Recently, we proposed a new nomenclature and classification of abdominal wall defects based on the early development of the umbilical cord and of the ventral body wall. According to this classification the complete spectrum of abdominal wall defects, including cloacal exstrophy, bladder exstrophy, and epispadias, can be subdivided into four types: primary (thoraco-)abdominoschisis, omphalocele, body wall dysplasia, and secondary (thoraco-)abdominoschisis. Each type is characterized by its specific configuration of the placenta, the membranes, the umbilical cord, and the fetus. Anomalies such as urachal remnants and omphalomesenteric duct malformations can be explained by disturbances during later stages of umbilical cord development.
Nederlands tijdschrift voor geneeskunde
In a 6-week-old male infant who was referred because of an umbilical hernia and a non-purulent om... more In a 6-week-old male infant who was referred because of an umbilical hernia and a non-purulent omphalitis, type-I leukocyte-adhesion deficiency was diagnosed. Additional clues were persisting leukocytosis upon clinical improvement under antibiotic treatment and a late falling off of the umbilical remnant in the patient's history. After cure by antibiotic therapy, life-long antibiotic prophylaxis was prescribed. Leukocyte-adhesion deficiency syndromes are rare, autosomal recessive, hereditary immunological disorders. The basis of these disorders is found in the absence or defective function of adhesion molecules that are needed for an interaction between the leukocytes, especially neutrophilic granulocytes, and endothelial surfaces. On the basis of clinical signs and symptoms and laboratory findings, two types of leukocyte-adhesion deficiency can be distinguished. Type I is marked by a disorder in the migration of granulocytes through the endothelium, in which integrins are involved. In type II, there is a disorder in the first step in the adhesion of granulocytes to the endothelium, in which selectins are involved. These conditions already become manifest in childhood. Therapy is generally symptomatic and consists mainly of the prevention and treatment of infection. Cure is sometimes possible by means of allogenic bone-marrow transplantation.
Nederlands tijdschrift voor geneeskunde
The multidisciplinary guideline &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;... more The multidisciplinary guideline &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Varicella&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; provides guidelines for diagnosis, therapy, and prevention of chickenpox. At the first pregnancy check, patients should be questioned about previous chickenpox; in case of a negative or doubtful history varicella zoster virus (VZV) serology is indicated. VZV antibody determination is also indicated in patients considered for immunosuppressive therapy and for healthcare workers with a negative VZV history who are in contact with immunocompromised patients. Administration of VZV immunoglobulin within 96 hours following VZV contact can mitigate the infection in pregnant women and patients with T-cell deficiency. VZV immunoglobulin treatment should be considered for newborn infants of mothers who developed chickenpox in the period from five days before to two days after delivery. Antivirals can reduce the severity of infection and are safe during pregnancy. Varicella vaccine protects against chickenpox, but is contraindicated in immunocompromised patients and pregnant women.
Tijdschrift voor kindergeneeskunde, 2002
... CMR Weemaes NG Hartwig I. van der Burgt Summary In 'classical' immunodefici... more ... CMR Weemaes NG Hartwig I. van der Burgt Summary In 'classical' immunodeficiencies only the function of phagocytes or lymphocytes is disturbed. ... 13 Page 2. palatoschisis, kleine teruggetrokken kin en laag inge-plante kleine oren. ...
BMC infectious diseases, Jan 30, 2014
The incidence of pertussis has been increasing worldwide. In the Netherlands, the seroprevalence ... more The incidence of pertussis has been increasing worldwide. In the Netherlands, the seroprevalence has risen higher than the reported cases, suggesting that laboratory tests for pertussis are considered infrequently and that even more pertussis cases are missed. The objective of our study was to determine the frequency of pertussis in clinically unsuspect cases compared to suspect cases with the intention of finding clinical predictors. The present prospective cohort study was part of a controlled clinical trial evaluating the impact of molecular diagnostics on clinical decision making in pediatric respiratory infections, performed during 2 winter seasons. For this study, in the first season pertussis was only tested in case of clinical suspicion, in the second season, pertussis was also tested without clinical suspicion. Multivariate and univariate analysis were performed using SPSS 18 and Statistical software 'R'. In the two seasons respectively 22/209 (10,5%) and 49/373 (13...
Paediatric respiratory reviews, 2015
Acute respiratory tract infection (ARI) is a frequently occurring disease in children. It is a cl... more Acute respiratory tract infection (ARI) is a frequently occurring disease in children. It is a clinical diagnosis for which no internationally accepted diagnostic test is available. The majority of ARI is viral in origin, though diagnostic tests for viruses were rarely performed in the past. In the past 2 decades, new molecular techniques have been introduced in many hospitals. They are capable of generating a high yield of viral and bacterial diagnoses, but their impact upon clinical practices is still questionable. In this paper, we discuss the difficulties of diagnosing ARI in children, the indications for conventional and new diagnostics and their implications.
Advances in experimental medicine and biology, 2006
Timely diagnosis of musculoskeletal infections is essential to prevent severe complications of th... more Timely diagnosis of musculoskeletal infections is essential to prevent severe complications of this disease. Important symptoms that lead to the diagnosis include high fever, malaise, local pain and loss of function of the involved extremity. In the case of arthritis, swelling of the affected joint may develop quickly in the course of disease. Imaging techniques include ultrasound and MRI. Both are useful in determining the exact site of infection. Infectious parameters, C-reactive protein and/or sedimentation rate of erythrocytes (ESR) are used in following disease activity during treatment. The gold standard for diagnosing musculoskeletal infection is microbiological isolation of the organism. Bone-biopsy of an involved metaphysis or aspiration of joint-fluid gives the highest chance of a positive culture. Usually S. aureus is the causative micro-organism, although specific underlying diseases may predispose to other bacterial infections. Antibiotic treatment is aimed at the most ...
Current Urology, 2007
ABSTRACT Renal candidiasis in neonates and young infants is a potentially life threatening condit... more ABSTRACT Renal candidiasis in neonates and young infants is a potentially life threatening condition. It occurs mainly in neonates and young infants with secondary risk factors and underlying congenital urinary tract abnormalities. The diagnosis can easily be established and is usually followed by antifungal therapy with fluconazole. However, fluconazole therapy might fail and there seems to be no consensus on best second-line therapy. We describe 4 patients with renal candidiasis, which illustrate the different aspects to be considered during treatment. A literature study was performed to search for the best therapeutic modality to achieve cure. Based on the few papers that describe the management of invasive candidiasis and the experience with the 4 cases, a therapy protocol is proposed in which systemic antifungal therapy is combined with an irrigation procedure.
Human pathology, 1989
Four human fetuses with the limb body wall malformation complex, also known as the amniotic band ... more Four human fetuses with the limb body wall malformation complex, also known as the amniotic band syndrome, were examined. Besides malformations of the body wall and the limb(s), anomalies of the internal organs were found in three fetuses, suggesting a disturbance of normal morphogenesis before the fifth week of development. When analyzing the observed data in relation to their etiology, no support was found for either the amniotic band or the vascular disruption theory. New insights into morphogenesis suggest that the limb body wall malformation complex results from a malfunction in the ectodermal placodes and that it can be considered to be an embryonic dysplasia.
American journal of clinical pathology, 1991
Three stillborn fetuses are reported in which an abdominal wall defect was associated with defect... more Three stillborn fetuses are reported in which an abdominal wall defect was associated with defects in the urogenital and anal region. Autopsy of these fetuses provided clues indicative of how and where the embryonic development went wrong. The malformation involved a disturbance of the cell deposition process, occurring in the caudal part of the embryo. During the cell deposition process, which takes place in the neural crest and the body wall placode, ectodermal cells are added to the mesodermal compartment of the embryo, thus contributing to the anlagen of several structures, including the ventral body wall. In addition, a change in the shape of the embryo is generated. The sequence of events resulting from a disturbance of the cell deposition process is explained.
Tijdschrift Voor Kindergeneeskunde, 2005
Summary A recent study by De Gans and Van de Beek in the nejm entitled ‘Dexamethasone in adults ... more Summary A recent study by De Gans and Van de Beek in the nejm entitled ‘Dexamethasone in adults with bacterial meningitis’ made the question relevant if children suspected of bacterial meningitis should be treated with dexamethasone. Based on the literature available we advise dexamethasone treatment for children older than two months of age who are suspected of acute bacterial meningitis. Dexamethasone
Tijdschrift voor kindergeneeskunde, 2006
Tijdschrift voor Kindergeneeskunde, 2010
Abstract Al meer dan dertig jaar is bekend dat Chlamydia, Ureaplasma en Mycoplasma geïsoleerd ku... more Abstract Al meer dan dertig jaar is bekend dat Chlamydia, Ureaplasma en Mycoplasma geïsoleerd kunnen worden uit materiaal verkregen uit de luchtwegen van pasgeborenen met respiratoire klachten. 1 Echter, in de literatuur is geen consensus of deze micro-organismen werkelijk een belangrijke rol spelen bij ziekteverschijnselen van de pasgeborene.
Vaccine, 2013
Objective: A phase IV interventional study with a combined hepatitis A and B vaccine was conducte... more Objective: A phase IV interventional study with a combined hepatitis A and B vaccine was conducted in HIV-infected children and children receiving immunosuppressive medication for treatment of rheumatic diseases to evaluate immune responses. Methods: Both groups (1-16 years of age) received combined (inactivated) HAV and (rDNA) HBV vaccine Ambirix ® at months 0 and 6. Serum samples were taken at four time points and tested for anti-HAV and anti-HBs antibodies. Anti-HAV concentrations ≥20 mIU/mL or anti-HBs concentrations ≥10 mIU/mL were considered protective. Seropositivity percentages were calculated and geometric mean concentrations (GMCs) were compared by nonparametric Mann-Whitney U-test or Kruskal-Wallis one-way-analysisof-variance. Results: Of 80 HIV-infected children who completed the study, 67 were HAV-susceptible and 68 HBVsusceptible at enrolment. Of 80 children with rheumatic diseases who completed the study, 65 were HAV-susceptible and 74 HBV-susceptible at enrolment. Immune responses to HAV after first dose of vaccine in both study groups were low: 71% and 55% respectively, whereas immune responses after the second dose were 99% and 100% respectively. Immune response to HBV after first dose of vaccine in both groups was also low: 27% and 17% respectively. Immune responses after the second dose were 97% and 93%, respectively. A larger proportion of children on combination antiretroviral therapy (cART) and of children with viral load <50 copies/mL responded to HBV, and also showed a significantly higher GMC. Conclusions: Although immune response after full series of combined HAV and HBV vaccine in both groups was excellent and comparable to healthy children, a substantial proportion of both groups was not protected for HAV after first dose of vaccine. This protection gap is especially important for HAV in travel health and postexposure prophylactic treatment: both groups of children should be serologically tested for anti-HAV prior to travel to ensure protection if there is no time to await second dose of vaccine.
Tijdschrift voor kindergeneeskunde, 2004
... Toediening van immunoglobulinen zou enig effect hebben gehad bij patie¨nten met agammaglobuli... more ... Toediening van immunoglobulinen zou enig effect hebben gehad bij patie¨nten met agammaglobuline-mie met een chronische enterovirusinfectie.18 Voor ... Antimicrob Agents Chemother 1999;43:2109-15. Kearns G, Abdel-Rahman S, James L, et al. ...
Tijdschrift Voor Kindergeneeskunde, 2002
... CMR Weemaes NG Hartwig I. van der Burgt Summary In 'classical' immunodefici... more ... CMR Weemaes NG Hartwig I. van der Burgt Summary In 'classical' immunodeficiencies only the function of phagocytes or lymphocytes is disturbed. ... 13 Page 2. palatoschisis, kleine teruggetrokken kin en laag inge-plante kleine oren. ...
Tijdschrift Voor Kindergeneeskunde, 2005
Tijdschrift Voor Kindergeneeskunde, 2010
Seminars in Pediatric Surgery
Congenital abdominal wall defects, frequently associated with other anomalies, are found in many ... more Congenital abdominal wall defects, frequently associated with other anomalies, are found in many forms. Consequently, there is still controversy in the literature concerning nomenclature, classification, and pathogenesis. Recently, we proposed a new nomenclature and classification of abdominal wall defects based on the early development of the umbilical cord and of the ventral body wall. According to this classification the complete spectrum of abdominal wall defects, including cloacal exstrophy, bladder exstrophy, and epispadias, can be subdivided into four types: primary (thoraco-)abdominoschisis, omphalocele, body wall dysplasia, and secondary (thoraco-)abdominoschisis. Each type is characterized by its specific configuration of the placenta, the membranes, the umbilical cord, and the fetus. Anomalies such as urachal remnants and omphalomesenteric duct malformations can be explained by disturbances during later stages of umbilical cord development.
Nederlands tijdschrift voor geneeskunde
In a 6-week-old male infant who was referred because of an umbilical hernia and a non-purulent om... more In a 6-week-old male infant who was referred because of an umbilical hernia and a non-purulent omphalitis, type-I leukocyte-adhesion deficiency was diagnosed. Additional clues were persisting leukocytosis upon clinical improvement under antibiotic treatment and a late falling off of the umbilical remnant in the patient's history. After cure by antibiotic therapy, life-long antibiotic prophylaxis was prescribed. Leukocyte-adhesion deficiency syndromes are rare, autosomal recessive, hereditary immunological disorders. The basis of these disorders is found in the absence or defective function of adhesion molecules that are needed for an interaction between the leukocytes, especially neutrophilic granulocytes, and endothelial surfaces. On the basis of clinical signs and symptoms and laboratory findings, two types of leukocyte-adhesion deficiency can be distinguished. Type I is marked by a disorder in the migration of granulocytes through the endothelium, in which integrins are involved. In type II, there is a disorder in the first step in the adhesion of granulocytes to the endothelium, in which selectins are involved. These conditions already become manifest in childhood. Therapy is generally symptomatic and consists mainly of the prevention and treatment of infection. Cure is sometimes possible by means of allogenic bone-marrow transplantation.
Nederlands tijdschrift voor geneeskunde
The multidisciplinary guideline &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;... more The multidisciplinary guideline &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Varicella&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; provides guidelines for diagnosis, therapy, and prevention of chickenpox. At the first pregnancy check, patients should be questioned about previous chickenpox; in case of a negative or doubtful history varicella zoster virus (VZV) serology is indicated. VZV antibody determination is also indicated in patients considered for immunosuppressive therapy and for healthcare workers with a negative VZV history who are in contact with immunocompromised patients. Administration of VZV immunoglobulin within 96 hours following VZV contact can mitigate the infection in pregnant women and patients with T-cell deficiency. VZV immunoglobulin treatment should be considered for newborn infants of mothers who developed chickenpox in the period from five days before to two days after delivery. Antivirals can reduce the severity of infection and are safe during pregnancy. Varicella vaccine protects against chickenpox, but is contraindicated in immunocompromised patients and pregnant women.
Tijdschrift voor kindergeneeskunde, 2002
... CMR Weemaes NG Hartwig I. van der Burgt Summary In 'classical' immunodefici... more ... CMR Weemaes NG Hartwig I. van der Burgt Summary In 'classical' immunodeficiencies only the function of phagocytes or lymphocytes is disturbed. ... 13 Page 2. palatoschisis, kleine teruggetrokken kin en laag inge-plante kleine oren. ...
BMC infectious diseases, Jan 30, 2014
The incidence of pertussis has been increasing worldwide. In the Netherlands, the seroprevalence ... more The incidence of pertussis has been increasing worldwide. In the Netherlands, the seroprevalence has risen higher than the reported cases, suggesting that laboratory tests for pertussis are considered infrequently and that even more pertussis cases are missed. The objective of our study was to determine the frequency of pertussis in clinically unsuspect cases compared to suspect cases with the intention of finding clinical predictors. The present prospective cohort study was part of a controlled clinical trial evaluating the impact of molecular diagnostics on clinical decision making in pediatric respiratory infections, performed during 2 winter seasons. For this study, in the first season pertussis was only tested in case of clinical suspicion, in the second season, pertussis was also tested without clinical suspicion. Multivariate and univariate analysis were performed using SPSS 18 and Statistical software 'R'. In the two seasons respectively 22/209 (10,5%) and 49/373 (13...
Paediatric respiratory reviews, 2015
Acute respiratory tract infection (ARI) is a frequently occurring disease in children. It is a cl... more Acute respiratory tract infection (ARI) is a frequently occurring disease in children. It is a clinical diagnosis for which no internationally accepted diagnostic test is available. The majority of ARI is viral in origin, though diagnostic tests for viruses were rarely performed in the past. In the past 2 decades, new molecular techniques have been introduced in many hospitals. They are capable of generating a high yield of viral and bacterial diagnoses, but their impact upon clinical practices is still questionable. In this paper, we discuss the difficulties of diagnosing ARI in children, the indications for conventional and new diagnostics and their implications.
Advances in experimental medicine and biology, 2006
Timely diagnosis of musculoskeletal infections is essential to prevent severe complications of th... more Timely diagnosis of musculoskeletal infections is essential to prevent severe complications of this disease. Important symptoms that lead to the diagnosis include high fever, malaise, local pain and loss of function of the involved extremity. In the case of arthritis, swelling of the affected joint may develop quickly in the course of disease. Imaging techniques include ultrasound and MRI. Both are useful in determining the exact site of infection. Infectious parameters, C-reactive protein and/or sedimentation rate of erythrocytes (ESR) are used in following disease activity during treatment. The gold standard for diagnosing musculoskeletal infection is microbiological isolation of the organism. Bone-biopsy of an involved metaphysis or aspiration of joint-fluid gives the highest chance of a positive culture. Usually S. aureus is the causative micro-organism, although specific underlying diseases may predispose to other bacterial infections. Antibiotic treatment is aimed at the most ...
Current Urology, 2007
ABSTRACT Renal candidiasis in neonates and young infants is a potentially life threatening condit... more ABSTRACT Renal candidiasis in neonates and young infants is a potentially life threatening condition. It occurs mainly in neonates and young infants with secondary risk factors and underlying congenital urinary tract abnormalities. The diagnosis can easily be established and is usually followed by antifungal therapy with fluconazole. However, fluconazole therapy might fail and there seems to be no consensus on best second-line therapy. We describe 4 patients with renal candidiasis, which illustrate the different aspects to be considered during treatment. A literature study was performed to search for the best therapeutic modality to achieve cure. Based on the few papers that describe the management of invasive candidiasis and the experience with the 4 cases, a therapy protocol is proposed in which systemic antifungal therapy is combined with an irrigation procedure.
Human pathology, 1989
Four human fetuses with the limb body wall malformation complex, also known as the amniotic band ... more Four human fetuses with the limb body wall malformation complex, also known as the amniotic band syndrome, were examined. Besides malformations of the body wall and the limb(s), anomalies of the internal organs were found in three fetuses, suggesting a disturbance of normal morphogenesis before the fifth week of development. When analyzing the observed data in relation to their etiology, no support was found for either the amniotic band or the vascular disruption theory. New insights into morphogenesis suggest that the limb body wall malformation complex results from a malfunction in the ectodermal placodes and that it can be considered to be an embryonic dysplasia.
American journal of clinical pathology, 1991
Three stillborn fetuses are reported in which an abdominal wall defect was associated with defect... more Three stillborn fetuses are reported in which an abdominal wall defect was associated with defects in the urogenital and anal region. Autopsy of these fetuses provided clues indicative of how and where the embryonic development went wrong. The malformation involved a disturbance of the cell deposition process, occurring in the caudal part of the embryo. During the cell deposition process, which takes place in the neural crest and the body wall placode, ectodermal cells are added to the mesodermal compartment of the embryo, thus contributing to the anlagen of several structures, including the ventral body wall. In addition, a change in the shape of the embryo is generated. The sequence of events resulting from a disturbance of the cell deposition process is explained.
Tijdschrift Voor Kindergeneeskunde, 2005
Summary A recent study by De Gans and Van de Beek in the nejm entitled ‘Dexamethasone in adults ... more Summary A recent study by De Gans and Van de Beek in the nejm entitled ‘Dexamethasone in adults with bacterial meningitis’ made the question relevant if children suspected of bacterial meningitis should be treated with dexamethasone. Based on the literature available we advise dexamethasone treatment for children older than two months of age who are suspected of acute bacterial meningitis. Dexamethasone
Tijdschrift voor kindergeneeskunde, 2006
Tijdschrift voor Kindergeneeskunde, 2010
Abstract Al meer dan dertig jaar is bekend dat Chlamydia, Ureaplasma en Mycoplasma geïsoleerd ku... more Abstract Al meer dan dertig jaar is bekend dat Chlamydia, Ureaplasma en Mycoplasma geïsoleerd kunnen worden uit materiaal verkregen uit de luchtwegen van pasgeborenen met respiratoire klachten. 1 Echter, in de literatuur is geen consensus of deze micro-organismen werkelijk een belangrijke rol spelen bij ziekteverschijnselen van de pasgeborene.