Summary minor challenges in women and child’s healthcare N. Smit - 2023
Summary minor
‘Challenges in Women and Child
healthcare’ part 2
Inhoudsopgave
Colleges week 9 – Challenges in (prevention of) neonatal infections...............................................................3
Microbiota: friend or enemy................................................................................................................................3
Obstetric profylactic antibiotics and the infant microbiome................................................................................3
Predicting NEC and sepsis using microbiota analyses in extremely preterm infants...........................................4
PREN Amsterdam: the importance of evaluating healthcare..............................................................................4
Research in children: is it allowed?......................................................................................................................5
Sepsis in neonates: diagnostic challenges............................................................................................................5
Neonatal sepsis: Presepsin...................................................................................................................................7
RCTs: standard and advanced analyses...............................................................................................................7
Colleges week 10 – infection and the immune system....................................................................................9
Invasive Group B streptococcus infections in infants...........................................................................................9
Feeding and IGF-1 in preterm newborns..............................................................................................................9
Interaction of human milk (glycans) with the immune system..........................................................................12
Nutrition and immunology.................................................................................................................................13
Upper gastrointestinal motility disorders in children: diagnostics and therapeutic..........................................14
Colleges week 11 – Food and growth............................................................................................................ 15
Human milk response to COVID 19....................................................................................................................15
Neonatal nutrition..............................................................................................................................................15
ABCD study: results............................................................................................................................................16
Failure to thrive..................................................................................................................................................17
Food allergies.....................................................................................................................................................18
Colleges week 12 – Pediatric oncology.......................................................................................................... 19
Introduction........................................................................................................................................................19
Retinoblastoma..................................................................................................................................................19
Retinoblastoma and genetics.............................................................................................................................21
Imaging in retinoblastoma.................................................................................................................................22
Hematologic malignancies.................................................................................................................................22
Pediatric brain tumors........................................................................................................................................25
,Summary minor challenges in women and child’s healthcare N. Smit - 2023
Solid tumors.......................................................................................................................................................27
Radiology in workup and follow-up...................................................................................................................29
Infectiology.........................................................................................................................................................29
Malignancy in pregnancy...................................................................................................................................29
Medical pedagogic healthcare professional......................................................................................................30
Acute pediatric oncology....................................................................................................................................30
Patient lecture Leukemia....................................................................................................................................31
Neurosurgical aspects of pediatric brain tumors...............................................................................................32
Lectures week 13 – (psychiatric) problems in adolescence............................................................................33
Trauma in children and adolescents...................................................................................................................33
Trauma and research.........................................................................................................................................34
Depression in adolescents..................................................................................................................................34
Secure residential youth care.............................................................................................................................35
Antisocial behaviour from a neurodevelopmental perspective.........................................................................35
Transgender care for minors, a developmental perspective..............................................................................36
Prevention in youth mental health.....................................................................................................................36
Psychological impact of COVID-19 on child mental health................................................................................37
Anorexia nervosa................................................................................................................................................37
ADHD..................................................................................................................................................................39
Colleges week 14 – Child public healthcare................................................................................................... 42
Introduction to prevention.................................................................................................................................42
Determinants of child (physical) health.............................................................................................................43
Health and care inequalities..............................................................................................................................43
Youth health care in the Dutch health care system: policy and legislation........................................................44
Youth health care in practice..............................................................................................................................44
Early diagnosis of celiac disease........................................................................................................................44
Lifestyle and health: physical activity.................................................................................................................45
Colleges week 15......................................................................................................................................... 47
Health advocacy for refugee children................................................................................................................47
HPV vaccination.................................................................................................................................................47
Child abuse prevention.......................................................................................................................................48
Global adolescent health....................................................................................................................................49
,Summary minor challenges in women and child’s healthcare N. Smit - 2023
Colleges week 9 – Challenges in (prevention of)
neonatal infections
Microbiota: friend or enemy
Multiple AB cures in the first 3 years of the child can increase the chance on obesity later in
life. AB cures during pregnancy increases the risk on diseases for the child. Last decennia a
decrease has been seen in infectional diseases, but an increase in the auto-immune diseases.
Might be caused by: diet, medication (looking at the short dure it has to be something else
than a genetic cause) ‘dysbiotic drift’ in modern society
Functions intestional microbiota
- Metabolic: fermentation, production vitamins and essential aminoacids
- Protective role against infections: prevention colonization pathogens (low pH by
production fatty acids, production antimicrobial factors, anti-oxidants and pro-
inflammatory cytokins (TNF-alfa, IL-6)
- Immunity: IgA induction, cellular and mucosal immunity, lymfoid organogenesis
Diseases linked to microbiota IBD, allergic rhinitis, eczema, celiac disease, intestinal
cancer, obesity, diabetes mellitus, asthma
Vertical transmission evidence for shared strains between mother and child. Family
members have more similar microbiota than unrelated people.
Environmental acquisition not extensively studied in humans, in pigs this is important in
shaping the gut microbiota. The assumption that is important forms the basis of hygiëne.
Horizontal transmission pathogens are spread to other members of the same or different
species through non-hereditary means. For example via a dog.
Manipulation of the microbiota: inserting the microbiota of an obese person in another
person can increase adiposity.
Fecal transplantation has been shown to be effective in a C. difficile infection. Via this
treatment a whole new microbiota is entered into the body.
Obstetric profylactic antibiotics and the infant microbiome
Colonization of the infant gut microbiota starts around birth. Perinatal factors influencing the
microbiota are way of feeding, skin contact, gestational age, perinatal antibiotics and way of
delivery.
Antibiotics and C-section are associated with clinical conditions later in life. Antibiotics result
in less diversity, more pathogens and less commensals. A C-section circumvents the birth
canal, this results in more skin microbes and less GI-microbes, less diversity. Differences
between VB and CS can be seen up to two years post-partum.
, Summary minor challenges in women and child’s healthcare N. Smit - 2023
Discussion about when to administer the maternally prophylactic antiobiotics (1 dose of
cefuroxime 1500mg) in a C-section. Former guidelines it was after clamping the umbilical
cord. Adjusted guidelines is prior to C-section. MAMI study to compare these methods
- Group A (30 min prior CS): less infectious complications in the mother
- Group B (after clamping umbilical cord): disturbance in microbial colonization;
possible long-term consequences?
Predicting NEC and sepsis using microbiota analyses in extremely
preterm infants
A child is preterm when born before a GA of 37 weeks. This is 10% of all pregnancies.
Extremely preterm is <28 weeks (0,3%). Premature children may have respiratory problems,
congenital anomalies, intracranial hemorrhage, infections and bowel diseases.
Early onset neonatal sepsis (EOS): vertical transmission (1-3.5%)
Late onset neonatal sepsis (LOS): horizontal transmission (11-32%) or vertical
When EOS/LOS is suspected blood/CSF/urine culture and broad-spectrum AB
Necrotizing enterocolitis (NEC) has an incidence of around 7% <28 weeks. A mortality of 10-
50%. Causes severe morbidity, such as short bowel syndrome, developmental delay etc. is a
quickly progressive disease.
eMINDS study: predict NEC and sepsis with fecal biomarkers (AD<28 weeks), effects of
probiotica and antibiotics on preterm microbiota and NEC&sepsis in the first 28 days of life.
To predict long term health associated with microbiome. Study found that the microbiome
changed 1 day before the NEC diagnosis and LOS was predictable 3 days prior to diagnosis. 1
to 3 days before NEC diagnosis a unique smell pattern was found. 1-3 prior specific
aminoacids elevated. Less NEC was found in baby’s who have only had breastfeeding.
PREN Amsterdam: the importance of evaluating healthcare
Mission of PREN (Pediatric research and evaluation network) is to ensure that health care
evaluation is part of general pediatric patient care. By using education and training to actively
disseminate care evaluation.
Health care evaluation via the traffic light model
- Proven effective care (Green) implementation
- Prove ineffective care (red) de-implementation
- Unknown/knowledge gap (orange) evaluate (de-)implementation
EOS: 0,5-1,0 per 1000 live births; empiric antibiotic therapy 5-8% with NNT 50-80. Too many
children received AB. Therefore the EOS calculator was made. Calculates the risk for an
individual newborn using 5 maternal risk factors (GBS status, GA, duration of ROM (gebroken
vliezen), highest intrapartum temperature and broad spectrum AB usage) + newborn’s
clinical condition postpartum. EOS calculator led to significant less antibiotic usage. On short
term this resulted in start breastfeeding and intravascular acces. On long term on a better
microbiota. On population level less resistance. Also significant reduction health care related
costs.
Summary minor
‘Challenges in Women and Child
healthcare’ part 2
Inhoudsopgave
Colleges week 9 – Challenges in (prevention of) neonatal infections...............................................................3
Microbiota: friend or enemy................................................................................................................................3
Obstetric profylactic antibiotics and the infant microbiome................................................................................3
Predicting NEC and sepsis using microbiota analyses in extremely preterm infants...........................................4
PREN Amsterdam: the importance of evaluating healthcare..............................................................................4
Research in children: is it allowed?......................................................................................................................5
Sepsis in neonates: diagnostic challenges............................................................................................................5
Neonatal sepsis: Presepsin...................................................................................................................................7
RCTs: standard and advanced analyses...............................................................................................................7
Colleges week 10 – infection and the immune system....................................................................................9
Invasive Group B streptococcus infections in infants...........................................................................................9
Feeding and IGF-1 in preterm newborns..............................................................................................................9
Interaction of human milk (glycans) with the immune system..........................................................................12
Nutrition and immunology.................................................................................................................................13
Upper gastrointestinal motility disorders in children: diagnostics and therapeutic..........................................14
Colleges week 11 – Food and growth............................................................................................................ 15
Human milk response to COVID 19....................................................................................................................15
Neonatal nutrition..............................................................................................................................................15
ABCD study: results............................................................................................................................................16
Failure to thrive..................................................................................................................................................17
Food allergies.....................................................................................................................................................18
Colleges week 12 – Pediatric oncology.......................................................................................................... 19
Introduction........................................................................................................................................................19
Retinoblastoma..................................................................................................................................................19
Retinoblastoma and genetics.............................................................................................................................21
Imaging in retinoblastoma.................................................................................................................................22
Hematologic malignancies.................................................................................................................................22
Pediatric brain tumors........................................................................................................................................25
,Summary minor challenges in women and child’s healthcare N. Smit - 2023
Solid tumors.......................................................................................................................................................27
Radiology in workup and follow-up...................................................................................................................29
Infectiology.........................................................................................................................................................29
Malignancy in pregnancy...................................................................................................................................29
Medical pedagogic healthcare professional......................................................................................................30
Acute pediatric oncology....................................................................................................................................30
Patient lecture Leukemia....................................................................................................................................31
Neurosurgical aspects of pediatric brain tumors...............................................................................................32
Lectures week 13 – (psychiatric) problems in adolescence............................................................................33
Trauma in children and adolescents...................................................................................................................33
Trauma and research.........................................................................................................................................34
Depression in adolescents..................................................................................................................................34
Secure residential youth care.............................................................................................................................35
Antisocial behaviour from a neurodevelopmental perspective.........................................................................35
Transgender care for minors, a developmental perspective..............................................................................36
Prevention in youth mental health.....................................................................................................................36
Psychological impact of COVID-19 on child mental health................................................................................37
Anorexia nervosa................................................................................................................................................37
ADHD..................................................................................................................................................................39
Colleges week 14 – Child public healthcare................................................................................................... 42
Introduction to prevention.................................................................................................................................42
Determinants of child (physical) health.............................................................................................................43
Health and care inequalities..............................................................................................................................43
Youth health care in the Dutch health care system: policy and legislation........................................................44
Youth health care in practice..............................................................................................................................44
Early diagnosis of celiac disease........................................................................................................................44
Lifestyle and health: physical activity.................................................................................................................45
Colleges week 15......................................................................................................................................... 47
Health advocacy for refugee children................................................................................................................47
HPV vaccination.................................................................................................................................................47
Child abuse prevention.......................................................................................................................................48
Global adolescent health....................................................................................................................................49
,Summary minor challenges in women and child’s healthcare N. Smit - 2023
Colleges week 9 – Challenges in (prevention of)
neonatal infections
Microbiota: friend or enemy
Multiple AB cures in the first 3 years of the child can increase the chance on obesity later in
life. AB cures during pregnancy increases the risk on diseases for the child. Last decennia a
decrease has been seen in infectional diseases, but an increase in the auto-immune diseases.
Might be caused by: diet, medication (looking at the short dure it has to be something else
than a genetic cause) ‘dysbiotic drift’ in modern society
Functions intestional microbiota
- Metabolic: fermentation, production vitamins and essential aminoacids
- Protective role against infections: prevention colonization pathogens (low pH by
production fatty acids, production antimicrobial factors, anti-oxidants and pro-
inflammatory cytokins (TNF-alfa, IL-6)
- Immunity: IgA induction, cellular and mucosal immunity, lymfoid organogenesis
Diseases linked to microbiota IBD, allergic rhinitis, eczema, celiac disease, intestinal
cancer, obesity, diabetes mellitus, asthma
Vertical transmission evidence for shared strains between mother and child. Family
members have more similar microbiota than unrelated people.
Environmental acquisition not extensively studied in humans, in pigs this is important in
shaping the gut microbiota. The assumption that is important forms the basis of hygiëne.
Horizontal transmission pathogens are spread to other members of the same or different
species through non-hereditary means. For example via a dog.
Manipulation of the microbiota: inserting the microbiota of an obese person in another
person can increase adiposity.
Fecal transplantation has been shown to be effective in a C. difficile infection. Via this
treatment a whole new microbiota is entered into the body.
Obstetric profylactic antibiotics and the infant microbiome
Colonization of the infant gut microbiota starts around birth. Perinatal factors influencing the
microbiota are way of feeding, skin contact, gestational age, perinatal antibiotics and way of
delivery.
Antibiotics and C-section are associated with clinical conditions later in life. Antibiotics result
in less diversity, more pathogens and less commensals. A C-section circumvents the birth
canal, this results in more skin microbes and less GI-microbes, less diversity. Differences
between VB and CS can be seen up to two years post-partum.
, Summary minor challenges in women and child’s healthcare N. Smit - 2023
Discussion about when to administer the maternally prophylactic antiobiotics (1 dose of
cefuroxime 1500mg) in a C-section. Former guidelines it was after clamping the umbilical
cord. Adjusted guidelines is prior to C-section. MAMI study to compare these methods
- Group A (30 min prior CS): less infectious complications in the mother
- Group B (after clamping umbilical cord): disturbance in microbial colonization;
possible long-term consequences?
Predicting NEC and sepsis using microbiota analyses in extremely
preterm infants
A child is preterm when born before a GA of 37 weeks. This is 10% of all pregnancies.
Extremely preterm is <28 weeks (0,3%). Premature children may have respiratory problems,
congenital anomalies, intracranial hemorrhage, infections and bowel diseases.
Early onset neonatal sepsis (EOS): vertical transmission (1-3.5%)
Late onset neonatal sepsis (LOS): horizontal transmission (11-32%) or vertical
When EOS/LOS is suspected blood/CSF/urine culture and broad-spectrum AB
Necrotizing enterocolitis (NEC) has an incidence of around 7% <28 weeks. A mortality of 10-
50%. Causes severe morbidity, such as short bowel syndrome, developmental delay etc. is a
quickly progressive disease.
eMINDS study: predict NEC and sepsis with fecal biomarkers (AD<28 weeks), effects of
probiotica and antibiotics on preterm microbiota and NEC&sepsis in the first 28 days of life.
To predict long term health associated with microbiome. Study found that the microbiome
changed 1 day before the NEC diagnosis and LOS was predictable 3 days prior to diagnosis. 1
to 3 days before NEC diagnosis a unique smell pattern was found. 1-3 prior specific
aminoacids elevated. Less NEC was found in baby’s who have only had breastfeeding.
PREN Amsterdam: the importance of evaluating healthcare
Mission of PREN (Pediatric research and evaluation network) is to ensure that health care
evaluation is part of general pediatric patient care. By using education and training to actively
disseminate care evaluation.
Health care evaluation via the traffic light model
- Proven effective care (Green) implementation
- Prove ineffective care (red) de-implementation
- Unknown/knowledge gap (orange) evaluate (de-)implementation
EOS: 0,5-1,0 per 1000 live births; empiric antibiotic therapy 5-8% with NNT 50-80. Too many
children received AB. Therefore the EOS calculator was made. Calculates the risk for an
individual newborn using 5 maternal risk factors (GBS status, GA, duration of ROM (gebroken
vliezen), highest intrapartum temperature and broad spectrum AB usage) + newborn’s
clinical condition postpartum. EOS calculator led to significant less antibiotic usage. On short
term this resulted in start breastfeeding and intravascular acces. On long term on a better
microbiota. On population level less resistance. Also significant reduction health care related
costs.
