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In de eerste week na de geboorte worden enkele druppels bloed uit de hiel van het kind onderzocht op een aantal ernstige, zeldzame aangeboren ziektes. In 2015 heeft de Gezondheidsraad de minister van VWS geadviseerd om de hielprik met veertien aandoeningen uit te breiden. Het RIVM heeft in een zogeheten uitvoeringstoets onderzocht of deze uitbreiding haalbaar is. Dit blijkt het geval te zijn, mits de uitbreiding gefaseerd wordt doorgevoerd. Ook blijkt dat de uitbreiding alleen onder een aantal randvoorwaarden kan plaatsvinden, zoals voldoende personeel en financiële middelen, beschikbaarheid van flexibele ICT-functionaliteiten, en een goede aansluiting op de zorg. In 2017 zijn inmiddels de eerste twee (alfa- en bèta-thalassemie) van de veertien aandoeningen toegevoegd aan het programma. De uitbreiding is een complex proces, onder meer vanwege het grote aantal aandoeningen, de logistiek en organisatie in de laboratoria, de beschikbaarheid en kwaliteit van testmethodes, de aanvullende onderzoeken die nog moeten plaatsvinden, en de aansluiting op de zorg. Het betreft bovendien zeldzame aandoeningen die nog niet door veel landen zijn opgenomen in het screeningspakket. Hierdoor is ook op internationaal niveau slechts beperkte kennis beschikbaar. Na elk van de onderzoeken is sprake van een go/no go-moment. Dan moet de minister besluiten of de aandoening de implementatiefase in kan gaan of dat eerst verder onderzoek nodig is. Ook kan het zijn dat het nog niet haalbaar is om de aandoening (op dat moment) toe te voegen aan de hielprikscreening. Onder de betrokken beroepsgroepen, patiëntenorganisaties en andere stakeholders bestaat voldoende draagvlak voor de verdere uitbreiding. De huidige neonatale hielprikscreening mag echter niet onder druk komen te staan door de (voorbereidingen voor de) uitbreiding.

In de eerste week na de geboorte worden enkele druppels bloed uit de hiel van het kind onderzocht op een aantal ernstige, zeldzame aangeboren ziektes. In 2015 heeft de Gezondheidsraad de minister van VWS geadviseerd om de hielprik met veertien aandoeningen uit te breiden. Het RIVM heeft in een zogeheten uitvoeringstoets onderzocht of deze uitbreiding haalbaar is. Dit blijkt het geval te zijn, mits de uitbreiding gefaseerd wordt doorgevoerd. Ook blijkt dat de uitbreiding alleen onder een aantal randvoorwaarden kan plaatsvinden, zoals voldoende personeel en financiële middelen, beschikbaarheid van flexibele ICT-functionaliteiten, en een goede aansluiting op de zorg. In 2017 zijn inmiddels de eerste twee (alfa- en bèta-thalassemie) van de veertien aandoeningen toegevoegd aan het programma. De uitbreiding is een complex proces, onder meer vanwege het grote aantal aandoeningen, de logistiek en organisatie in de laboratoria, de beschikbaarheid en kwaliteit van testmethodes, de aanvullende onderzoeken die nog moeten plaatsvinden, en de aansluiting op de zorg. Het betreft bovendien zeldzame aandoeningen die nog niet door veel landen zijn opgenomen in het screeningspakket. Hierdoor is ook op internationaal niveau slechts beperkte kennis beschikbaar. Na elk van de onderzoeken is sprake van een go/no go-moment. Dan moet de minister besluiten of de aandoening de implementatiefase in kan gaan of dat eerst verder onderzoek nodig is. Ook kan het zijn dat het nog niet haalbaar is om de aandoening (op dat moment) toe te voegen aan de hielprikscreening. Onder de betrokken beroepsgroepen, patiëntenorganisaties en andere stakeholders bestaat voldoende draagvlak voor de verdere uitbreiding. De huidige neonatale hielprikscreening mag echter niet onder druk komen te staan door de (voorbereidingen voor de) uitbreiding.

When formulating recommendations, guideline developers have opportunities to use systematic reviews (SRs), which are widely considered to be the best available evidence. However, in practice the use of SRs by guideline developers is limited. Recent research has shown that only 22% (60/279) of the recommendations on screening of newborns for rare diseases were based on SRs. Moreover, the non-use of SRs was correlated with positive recommendations. This commentary discusses the reasons for limited SR use and the influence of wishful thinking on decision making. Although standards for guideline development are evolving, differing methods can still be used without compromising quality. Expert opinion is always needed to weigh the benefits and harms of the available management options. As long as potential conflicts of interest and considerations as well as choices made during the process are explicitly described, guidelines and policy decisions can be considered to be trustworthy.

Het Beleidskader Pre- en Neonatale Screeningen geeft een overzicht van de wettelijke en beleidsmatige kaders voor vijf screeningen die tijdens de zwangerschap en kort na de geboorte preventief worden aangeboden. Deze kaders zijn door het ministerie van Volksgezondheid, Welzijn en Sport (VWS) vastgesteld. Er zijn drie screeningen voor het ongeboren kind: op het syndroom van down, op enkele infectieziekten zoals hiv, en lichamelijke afwijkingen. De screeningen vlak na de geboorte betreffen het gehoor van het kind en de hielprik. Het RIVM voert sinds 2006 de regie op de bevolkingsonderzoeken en bewaakt vanuit die rol de kwaliteit, bereikbaarheid en betaalbaarheid ervan. Het beleidskader is een instrument om de regie te voeren. De uitvoering ligt bij de uitvoeringsorganisaties. Het beleidskader beschrijft eveneens hoe partijen samenwerken die betrokken zijn bij de voorbereiding van, besluitvorming over en uitvoering van de pre- en neonatale screeningen. Voor een goede kwaliteit van de screening is het immers van belang dat alle logistieke en inhoudelijke processen goed op elkaar aansluiten. Vooral de 'overgang' van een uitslag van een bevolkingsonderzoek naar een diagnose en behandeling is een belangrijke stap, waarvoor partijen binnen het bevolkingsonderzoek en de zorg gezamenlijk verantwoordelijk zijn. Daarnaast worden de kaders weergegeven die relevant zijn voor de nadere uitwerking van de draaiboeken van de screeningen. Deze draaiboeken zijn vooral gericht op de wijze waarop de screeningen worden uitgevoerd. Het beleidskader zal regelmatig worden getoetst en indien nodig aangepast aan de actualiteit.

1089-1095 In onze maatschappij wordt een zwangerschap sterk gemedicaliseerd ondanks dat het een fysiologisch gegeven is. Er worden geregeld onderzoeken aangevraagd en uitgevoerd zonder voldoende evidentie. Naar aanleiding hiervan deed het Federaal Kenniscentrum voor de Gezondheidszorg (KCE) onderzoek naar de minimale vereisten om een zo goed mogelijke basiszorg in een laagrisicozwangerschap te kunnen verzekeren en publiceerde in 2015 een aangepaste klinische richtlijn. Deze richtlijn werd gefundeerd op de huidige wetenschappelijke evidentie en omvat een aantal klinische aanbevelingen. Deze klinische aanbevelingen kwamen tot stand door een systematische review van de literatuur voor tien onderwerpen en het ADAPTE-proces op basis van de Australische richtlijn 2015 voor 24 specifieke klinische vragen. Het GRADE-systeem werd gebruikt om vervolgens de sterkte van elke aanbeveling te definiëren. De aanbevelingen behelzen zowel het klinisch onderzoek, technische onderzoeken zoals echografie, serologische testen en de specifieke screening naar klinische maternale en zwangerschapsgerelateerde problemen.

The Health Council of the Netherlands recently issued a report advising adding 14 new disorders to the current neonatal screening programme: 11 metabolic conditions, severe combined immunodeficiency disease, beta-thalassaemia major and HbH disease. This recommendation was made because of the availability of new tests and treatments. The new criteria of availability and accessibility of treatment became relevant following discussions on reimbursement of enzyme replacement therapy for Pompe's disease. The potential for alternative or complementary measures for prevention are discussed, such as preconception and prenatal carrier screening. This report advises against reporting carrier information following newborn screening: advice that is not in line with earlier Health Council advice. A further recommendation is that newborn screening for untreatable conditions is not indicated now. Screening for untreatable conditions may not be the responsibility of national public health agencies, but alternative stakeholders have not been considered in the report.

Kernicterus is a severe neurological condition, caused by bilirubin-induced damage in the basal ganglia. The neurological outcome is often poor. In the past decades there seems to have been an increase in the number of reported cases of kernicterus. In order to raise awareness of this condition, we present two patients with kernicterus caused by different pathophysiological mechanisms. In both cases we make suggestions for the improvement of the medical care process. The first patient is a 7-day-old girl with kernicterus due to haemolysis caused by G6PD deficiency. Patient B is a 3-day-old boy with hyperbilirubinaemia based on 0/B blood group incompatibility. Kernicterus resulted in significant disabilities in these children. A proper diagnostic approach and precise treatment of hyperbilirubinaemia are essential to prevent major neurological damage. Awareness of this condition, education of health care professionals and changes in in- and outpatient care are needed to achieve this goal.

Kernicterus is a severe neurological condition, caused by bilirubin-induced damage in the basal ganglia. The neurological outcome is often poor. In the past decades there seems to have been an increase in the number of reported cases of kernicterus. In order to raise awareness of this condition, we present two patients with kernicterus caused by different pathophysiological mechanisms. In both cases we make suggestions for the improvement of the medical care process. The first patient is a 7-day-old girl with kernicterus due to haemolysis caused by G6PD deficiency. Patient B is a 3-day-old boy with hyperbilirubinaemia based on 0/B blood group incompatibility. Kernicterus resulted in significant disabilities in these children. A proper diagnostic approach and precise treatment of hyperbilirubinaemia are essential to prevent major neurological damage. Awareness of this condition, education of health care professionals and changes in in- and outpatient care are needed to achieve this goal.

Kernicterus is a severe neurological condition, caused by bilirubin-induced damage in the basal ganglia. The neurological outcome is often poor. In the past decades there seems to have been an increase in the number of reported cases of kernicterus. In order to raise awareness of this condition, we present two patients with kernicterus caused by different pathophysiological mechanisms. In both cases we make suggestions for the improvement of the medical care process. The first patient is a 7-day-old girl with kernicterus due to haemolysis caused by G6PD deficiency. Patient B is a 3-day-old boy with hyperbilirubinaemia based on 0/B blood group incompatibility. Kernicterus resulted in significant disabilities in these children. A proper diagnostic approach and precise treatment of hyperbilirubinaemia are essential to prevent major neurological damage. Awareness of this condition, education of health care professionals and changes in in- and outpatient care are needed to achieve this goal.

In a trial running since October 2003 in the Dutch provinces of Friesland, Groningen, Drenthe and Overijssel neonatal screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency has been added to the regular newborn screening programme for phenylketonuria, congenital hypothyroidism and adrenogenital syndrome. One of the questions to be answered by this trial is the cause of the strong variation in clinical expression of the disorder. Underdiagnosing is an important factor in this phenomenon, as shown by the data of a family of which the case histories of the two oldest children were discussed in this journal in 1965. Both children died at a very young age. Recently, MCAD deficiency was diagnosed in the youngest child of this family, now a 34-year-old woman. This family history illustrates the variable clinical expression of MCAD deficiency, which can cause death but can also run a milder or even subclinical course. Moreover, this family history shows that the underdiagnosis of MCAD deficiency in deceased children may be a cause of the apparently limited clinical detection rate of this disease, for which a simple treatment consisting of life-style and dietary measures is available after diagnosis.

To describe the Dutch neonatal screening programme for congenital hypothyroidism (CH).Descriptive study.Data on neonatal screening for CH in the period 1 January 1981 through 31 December 2011 were obtained from the Department for Vaccine Supply and Prevention Programmes of the Dutch National Institute for Public Health and the Environment (RIVM), laboratories and paediatricians to whom babies with abnormal screening results were referred. The screening procedure has been amended several times. In the period 1981-1994, only T4 and TSH were measured in heel prick blood, for example. From 1995, thyroxine-binding globulin (TBG) was added to the screening protocol.The participation rate was 99.7%. Before 1995 the sensitivity, specificity and positive predictive value were 94%, 99.51% and 6%, respectively. From 1995 these percentages were 98%, 99.85% and 21%, respectively. The total prevalence of CH was 1:2670 (prevalence of CH of thyroidal origin was 1:3100 and CH of central origin was 1:21,600). The percentages of patients with severe CH treated before day 15 in the periods 1981-1990, 1991-2000 and 2001-2011 were 24% (63/263), 63% (170/269) and 96% (176/184), respectively.The sensitivity and specificity of the screening procedure has considerably increased since 1995 compared with the period before 1995. In recent years patients with severe CH were treated considerably earlier than in the first years of the screening. Neonatal screening for CH may be considered as an important success for public health care.

In the first trimester of 1990, 49601 newborn babies were screened for congenital hypothyroidism. In 695 cases (1.40%) a second heel card was requested. In this group 103 babies were pre- or dysmature. For 50 children no data on birth weight or duration of pregnancy were provided. 391 children were screened according to the so called modified procedure. Of the 1187 samples mentioned in Table 2 in 52 cases the date of sampling and in 3 cases the date of birth was deleted. There is some variation between the laboratories with respect to the T4-level (Tables 3 and 4). The daily means in this trimester range from 122-146 pg/punch. In contrast the results obtained with the external quality control samples show a smaller range. After 37 trimesters of screening the general conclusion is that the program functions well.

In the Netherlands neonatal screening on congenital hypothyroidism (CHT) is based on the determination of thyroxine (T4) in dried bloodspots on filterpaper. In 20 percent of the samples, those with the lowest T4 concentration, also thyrotropin (TSH) is measured. The positive predictive value (PV) of this screening strategy is low, about 6-8%. The reason for this is the low PV for T4. On January 1st 1993 the "TBG-project", subsidized by "Het Praeventiefonds", started in the CHT laboratories. The aim of this project is to examine whether the determination of thyroxine-binding globulin (TBG), in addition to T4 and TSH, can improve the positive PV. A commercial available radioimmunoassay kit for TBG in serum was modified to determine TBG in bloodspots on filterpaper. To correct for matrix effects there was a need for bloodspot standards. Two batches of bloodspot standards were prepared: TBG-IS and TBG-BO3. TBG-IS was prepared by mixing bloodcells with TBG-free serum, enriched with the International Standard for TBG (WHO 88/638). In TBG-BO3 the TBG-source was serum with a high TBG concentration. After calibration of TBG-BO3 in terms of TBG-IS the following concentrations were stated: 0, 45, 90, 180, 360, 720 and 1440 nmol/l. The range of TBG-BO3 in the RIA was good: 45 and 1440 nmol/l displaced 10% respectively 85% from the I-125-TBG. Conclusion: TBG-BO3 is suited to serve as blootspot standard in the TBG-project. There is a stock for 1 year for the 5 laboratories involved in this project.

In de kwartaalrapportages van de PKU/CHT screeningslaboratoria wordt onder andere nagegaan of de hielprik conform de in het Draaiboek PKU en CHT gestelde eisen wordt uitgevoerd. Daarbij wordt gekeken naar de termijn tussen geboorte- en hielprikdatum, tussen hielprikdatum en datum van analyse en tussen geboortedatum en datum van analyse. Tevens wordt geregistreerd in hoeverre de voor de uitvoering van de screening van belang zijnde demografische gegevens op de setjes zijn ingevuld. Het probleem is echter dat de hielpriksetjes, waarop deze rapportages zijn gebaseerd, geen aselecte steekproef vormen. Daarom werd besloten in een aselecte steekproef een aantal van bovengenoemde aspecten te analyseren. Van in totaal 5000 setjes (1000 per laboratorium) werd een aantal gegevens geregistreerd. De gegevens werden vervolgens geanalyseerd per categorie uitvoerder van de hielprik, per provinciale entadministratie en per laboratorium. Per provincie bestaan grote verschillen tussen de categorieen uitvoerders van de hielprik. Op gemiddeld 6.9% van de setjes was niet pasgeborenen met een geboortegewicht < 2500 gram ontbrak de zwangerschapsduur. Op dag 7, de laatst aanbevolen dag, was 94% van de pasgeborenen geprikt. Op dag 3 na de hielprik zijn nog slechts 81% van alle setjes in het laboratorium ontvangen/geanalyseerd. Met name de regio Noord-West Nederland valt hierbij in negatieve zin. De bezorging van de setjes door de PTT laat overigens duidelijk te wensen over.

In the first trimester of 1990, 49601 newborn babies were screened for congenital hypothyroidism. In 695 cases (1.40%) a second heel card was requested. In this group 103 babies were pre- or dysmature. For 50 children no data on birth weight or duration of pregnancy were provided. 391 children were screened according to the so called modified procedure. Of the 1187 samples mentioned in Table 2 in 52 cases the date of sampling and in 3 cases the date of birth was deleted. There is some variation between the laboratories with respect to the T4-level (Tables 3 and 4). The daily means in this trimester range from 122-146 pg/punch. In contrast the results obtained with the external quality control samples show a smaller range. After 37 trimesters of screening the general conclusion is that the program functions well.

Dit rapport beschrijft in grote lijnen de automatisering van de gegevensverwerking van de screening op congenitale hypothyreoidie (CHT) en fenylketonurie (PKU) zoals toegepast bij de Bijzondere Afdeling Automatisering Serologisch Onderzoek (ASO). Het rapport is in hoofdzaak bedoeld als overzicht, naslagwerk en algemene "Standard Operational Procedure" (SOP) voor diegenen die zich (weer) vertrouwd moeten maken met de gang van zaken. Het is zeker niet geschreven als een volledige handleiding. Momenteel (oktober 1984) maakt alleen de Provinciale Ent Administratie (PEA) van Utrecht gebruik van de mogelijkheid rechtstreeks via het RIVM Computer systeem de uitslagen op te vragen. Dit zou gemakkelijk kunnen worden uitgebreid met de andere PEA's waarvoor ASO fungeert als CHT-laboratorium.

Dit rapport beschrijft in grote lijnen de automatisering van de gegevensverwerking van de screening op congenitale hypothyreoidie (CHT) en fenylketonurie (PKU) zoals toegepast bij de Bijzondere Afdeling Automatisering Serologisch Onderzoek (ASO). Het rapport is in hoofdzaak bedoeld als overzicht, naslagwerk en algemene "Standard Operational Procedure" (SOP) voor diegenen die zich (weer) vertrouwd moeten maken met de gang van zaken. Het is zeker niet geschreven als een volledige handleiding. Momenteel (oktober 1984) maakt alleen de Provinciale Ent Administratie (PEA) van Utrecht gebruik van de mogelijkheid rechtstreeks via het RIVM Computer systeem de uitslagen op te vragen. Dit zou gemakkelijk kunnen worden uitgebreid met de andere PEA's waarvoor ASO fungeert als CHT-laboratorium.

In the Netherlands neonatal screening on congenital hypothyroidism (CHT) is based on the determination of thyroxine (T4) in dried bloodspots on filterpaper. In 20 percent of the samples, those with the lowest T4 concentration, also thyrotropin (TSH) is measured. The positive predictive value (PV) of this screening strategy is low, about 6-8%. The reason for this is the low PV for T4. On January 1st 1993 the "TBG-project", subsidized by "Het Praeventiefonds", started in the CHT laboratories. The aim of this project is to examine whether the determination of thyroxine-binding globulin (TBG), in addition to T4 and TSH, can improve the positive PV. A commercial available radioimmunoassay kit for TBG in serum was modified to determine TBG in bloodspots on filterpaper. To correct for matrix effects there was a need for bloodspot standards. Two batches of bloodspot standards were prepared: TBG-IS and TBG-BO3. TBG-IS was prepared by mixing bloodcells with TBG-free serum, enriched with the International Standard for TBG (WHO 88/638). In TBG-BO3 the TBG-source was serum with a high TBG concentration. After calibration of TBG-BO3 in terms of TBG-IS the following concentrations were stated: 0, 45, 90, 180, 360, 720 and 1440 nmol/l. The range of TBG-BO3 in the RIA was good: 45 and 1440 nmol/l displaced 10% respectively 85% from the I-125-TBG. Conclusion: TBG-BO3 is suited to serve as blootspot standard in the TBG-project. There is a stock for 1 year for the 5 laboratories involved in this project.

Virginia Apgar (1909-1974), born in New Jersey, managed to continue medical school despite the financial crisis of 1929, continued for a brief time in surgery and subsequently became one of the first specialists in anaesthesiology. In 1949 she was appointed to a professorship, the first woman to reach this rank at Columbia University in New York. She then dedicated herself to obstetric anaesthesiology and devised the well known scale for the initial assessment of newborn babies, according to 5 criteria. From 1959 she worked for the National Foundation for Infantile Paralysis (now March of Dimes), to expand its activities from prevention of poliomyelitis to other aspects of preventive child care, such as rubella vaccination and testing for rhesus antagonism. She remained single; in her private life she enjoyed fly fishing, took lessons in aviation and was an accomplished violinist.

Two infants with congenital toxoplasmosis are presented. A girl born prematurely was treated postnatally after the mother had received antimicrobial treatment during pregnancy for acute toxoplasmosis. Apart from being small for gestational age, she remained without symptoms and treatment was ceased after 13 months. A 2-month-old boy presented with hydrocephalus and chorioretinitis, consistent with congenital toxoplasmosis. Despite antimicrobial treatment, at 12 months of age he suffered from epilepsy, cerebral palsy and vision impairment. Most infants with congenital toxoplasmosis (2 per 1000 live births in the Netherlands) are asymptomatic at birth. The education of pregnant women is crucial for the prevention of congenital toxoplasmosis. Awareness of antenatal and postnatal presenting signs and symptoms is important for clinicians, because early diagnosis and treatment may minimize sequelae. Untreated, the majority of affected infants will develop chorioretinitis, deafness and/or neurological symptoms.

Doel Evalueren van de uitkomsten van het eerste jaar na invoering van de uitbreiding van de landelijke hielprikscreening met sikkelcelziekte (SCZ). Opzet Prospectieve landelijke registratie van kinderen met vermoedelijk SCZ of een andere vorm van ernstige hemoglobinopathie. Methode De bloedspots werden geanalyseerd met een hemoglobinescheidingsmethode op basis van ‘high-performance liquid chromatography’ (HPLC). Kinderen met een afwijkende hielprikuitslag dienden te worden verwezen naar een kinderhematoloog in één van de 8 academische ziekenhuizen. Bevestiging van de diagnose gebeurde met een tweede HPLC-test, een DNA-test en een onderzoek naar hemoglobinopathie bij de ouders. De uiteindelijke diagnose werd vergeleken met de vermoedelijke diagnose uit de screening. Resultaten In het eerste jaar hadden 64 kinderen een afwijkende hielprikuitslag die wees op een hemoglobinopathie (prevalentie: 0,35‰). De vermoedelijke diagnose was bij 41 kinderen ‘SCZ’, bij 18 ‘α-thalassemie’, bij 4 ‘β-thalassemie’ en bij 1 een overige vorm van hemoglobinopathie (HbEE). De vermoedelijke diagnose kon bij alle kinderen bevestigd worden. Conclusie Het eerste jaar van de neonatale screening op SCZ was succesvol, aangezien het aantal kinderen bij wie een diagnose werd gesteld, overeenkwam met de verwachtingen. De positief voorspellende waarde van de hielprikuitslag voor SCZ was daarmee 100%. Het is nog te vroeg om een uitspraak te doen over eventuele foutnegatieve testresultaten.

To evaluate the effects of frequent latching versus supplementary feeding of breastfed infants with hypoglycaemia on blood glucose concentrations and breastfeeding.Retrospective study of patient files.All breastfed infants born in the period of investigation (June 1st 2004-April 30th 2005) by artificial or breech delivery were included. In the group with supplementary feeding (June 1st 2004 until December 12th 2004) mild neonatal hypoglycaemia, defined as glucose concentrations between 1.8 and 2.5 mmol/l, with symptoms, or between 1.3 and 1.7 mmol/l, without symptoms, was treated with supplementary feeding with formula. In the group with more frequent latching (December 13th 2004-April 30th 2005) mild neonatal hypoglycaemia (defined as glucose levels of 1.8-2.1 mmol/l) was treated with more frequent latching without supplementary feeding. The change in feeding policy (mid December 2004) was introduced because of excessive numbers of supplementary feedings, which jeopardized breastfeeding. Blood glucose determinations were carried out with the HemoCue B-glucose system. Risk factors for hypoglycaemia were listed, enabling the assessment of data of neonates who did not run an increased risk of hypoglycaemia, a kind of 'control group'.232 newborn infants were included: 158 in the supplementary feeding group and 74 in the group with more frequent latching. In the supplementary feeding group, 63% (100/158) of the children developed hypoglycaemia, versus 55% (41/77) in the group with more frequent latching. The latter had lower blood glucose concentrations than the supplementary feeding group. This difference was only significant for infants without risk factors: the mean difference in lowest glucose concentration between supplementary feeding and more frequent latching in the group without risk factors was 0.50 mmol/L (SD: 0.69; 95% CI: 0.06-0.93; p = 0.03) versus 0.20 mmol/l (SD: 0.79; 95% CI: -0.05-0.45; p = 0.14) in the group with risk factors. Supplementary feedings decreased by 39% (95% CI: 28-50). The number of infants discharged with breastfeeding only increased by 14% (95% CI: 2-26). Symptomatic hypoglycaemic episodes were not found in the group with supplementary feeding or in the group with more frequent latching.Frequent latching instead of supplementary (formula) feeding in infants with mild neonatal hypoglycaemia was associated with lower blood glucose concentrations but with higher percentages of breastfeeding only at discharge.

Neonatal screening in the Netherlands was extended in 2007. Twelve of the 17 diseases screened for are metabolic disorders. Only 2 of the metabolic diseases part of the neonatal screening programme in the Dutch population had been studied prior to the introduction of neonatal screening, namely galactosaemia and medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. Short-chain acyl-CoA dehydrogenase (SCAD) deficiency, a metabolic disease not added to the screening, was extensively studied recently. The authors concluded that SCAD deficiency did not meet screening criteria. The efficacy of screening should be investigated, as the screening test and genetic differences in populations make screening unique for each population. Clinical and biochemical phenotype do not always correlate with genotype. Differences in the disease population and the screening population can make decisions with respect to treatment difficult, especially when many more patients are found than expected. Some of these patients might never have become ill and should thus not be treated. Further studies are needed to differentiate between these patients.

Timely recognition of clinical signs and symptoms of sickle cell disease remains of great importance because the neonatal PKU screening program in The Netherlands that was introduced in January 1st 2007 will not reach all children with this disease. Of children that have been diagnosed in the Emma Children's Hospital AMC, Amsterdam, 20% would not have been reached by this new program: immigrant's children born abroad and adopted children. It goes without saying that also in children that have been born in the Netherlands before January 1st 2007 the diagnosis sickle cell disease should be considered in cases of disease-specific clinical symptoms. The initial clinical manifestation of sickle cell disease in children born in the Netherlands is potentially life-threatening in 8% (7/88), e.g. a pneumococcal infection or an acute splenic sequestration. Painful crisis, paleness and jaundice are the most common presenting symptoms. The median age at diagnosis of the group of Amsterdam children was 25 months. In view of the potential health benefit it is advised to test children from populations at risk, that are under the medical attention of a hospital for any reason, for the presence of sickle cell disease. This applies especially to children with a pneumococcal infection.

To evaluate the usefulness of transcutaneous bilirubinometry in determining the need for phototherapy in neonates with hyperbilirubinaemia and to assess whether this technique may be used as an alternative to blood tests.Prospective, descriptive.Serum bilirubin and both midfrontal and midsternal transcutaneous bilirubin were measured in icteric neonates admitted to the neonatal ward of the Kennemer Gasthuis, Haarlem, The Netherlands, between 1 March and 31 December 2005. The Minolta JM-103 jaundice meter was used for transcutaneous assessment. Data were interpreted with the aid ofa scatter plot, a 2-by-2 table and receiver operating characteristics (ROC) curve.A total of 70 matched transcutaneous-serum bilirubin measurements were taken from 50 patients, 22 girls and 28 boys. The mean gestational age was 66 hours (range: 12-164) and the mean birth weight was 2766 grams (range: 1680-4600). The mean duration of maternal amenorrhoea was 36.2 weeks (range: 32-41.3). The coefficient of correlation between serum bilirubin and mean transcutaneous midfrontal and midsternal bilirubin was o.88 and 0.91, respectively. The negative predictive value of mean transcutaneous midfrontal and midsternal bilirubin measurement was 0.91 and 0.87, respectively, indicating that phototherapy would be correctly avoided in 91 and 87% of children, respectively. Based on the area under the ROC curve, the transcutaneous midfrontal bilirubin measurement was more reliable than the midsternal measurement.Transcutaneous bilirubin measurement was useful in determining the need for phototherapy in neonates with hyperbilirubinaemia. Use of this non-invasive screening method may help to avoid unnecessary blood sampling in neonates.

A girl and a boy, who both presented with recurrent respiratory infections from birth, were referred to a paediatrician at the age of 2.5 years: they were diagnosed with cystic fibrosis (CF). The girl died from respiratory insufficiency at the age of 6 years and the boy at the age of 13 years from pulmonary aspiration. A further girl and boy who presented with abnormal faeces and failure to thrive were referred to the paediatrician at the ages of 2.5 months with haematomas and 2 weeks with anaemia respectively, as a result of vitamin deficiencies due to malabsorption. They too had CF. The girl had a brain haemorrhage in the meantime that left her with serious impairments. The boy recovered. A delay in diagnosing CF is not uncommon, as the symptoms of CF are hard to differentiate from those of common childhood diseases. However, this diagnostic delay can result in serious organ damage. Current treatment of CF has a predominantly prophylactic character and aims at maintaining normal growth and nutritional status as well as at preventing or postponing chronic bacterial infection of the lower respiratory tract. This treatment is most effective when it is started before any organ damage has occurred: a state that can only be achieved when patients with CF are identified shortly after birth. Therefore, it is important to add CF-screening to the neonatal screening program.

The Health Council of the Netherlands has published an advisory report on neonatal screening in view of developments in diagnostics, therapy and the prevalence of neonatal diseases. Currently it involves screening for phenylketonuria, congenital hypothyroidism and congenital adrenal hyperplasia. Because screening may lead to considerably better outcomes in affected newborns, the council recommends expanding current screening to include medium-chain acyl-CoA dehydrogenase deficiency, sickle-cell disease and 12 other rare disorders: biotinidase deficiency, galactosaemia, glutaricaciduria type I, HMG-CoA lyase deficiency, holocarboxylase-synthetase deficiency, homocystinuria, isovaleric-acidaemia, long-chain hydroxyacyl-CoA dehydrogenase deficiency, maple syrup urine disease, 3-methylcrotonyl-CoA carboxylase deficiency, tyrosinaemia I and very-long-chain acyl-CoA dehydrogenase deficiency. A better detection method for cystic fibrosis must be developed before it is included in screening to restrict the number of sweat-test referrals of unaffected newborns. The council recommends providing information on neonatal screening during pregnancy and gives special attention to the possibility of detecting carriership in the parents.

The Health Council of the Netherlands recently published a thorough report on neonatal screening, which recommends screening newborns for i8 treatable conditions. The report rightly stresses the importance of informing parents adequately, preferably during pregnancy. Issues that require further debate include neonatal screening for untreatable conditions and the relative advantages and disadvantages of screening newborns compared with screening prospective parents for carrier status, which may prevent the birth of a first-affected child.

In a trial running since October 2003 in the Dutch provinces of Friesland, Groningen, Drenthe and Overijssel neonatal screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency has been added to the regular newborn screening programme for phenylketonuria, congenital hypothyroidism and adrenogenital syndrome. One of the questions to be answered by this trial is the cause of the strong variation in clinical expression of the disorder. Underdiagnosing is an important factor in this phenomenon, as shown by the data of a family of which the case histories of the two oldest children were discussed in this journal in 1965. Both children died at a very young age. Recently, MCAD deficiency was diagnosed in the youngest child of this family, now a 34-year-old woman. This family history illustrates the variable clinical expression of MCAD deficiency, which can cause death but can also run a milder or even subclinical course. Moreover, this family history shows that the underdiagnosis of MCAD deficiency in deceased children may be a cause of the apparently limited clinical detection rate of this disease, for which a simple treatment consisting of life-style and dietary measures is available after diagnosis.

In a trial running since October 2003 in the Dutch provinces of Friesland, Groningen, Drenthe and Overijssel neonatal screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency has been added to the regular newborn screening programme for phenylketonuria, congenital hypothyroidism and adrenogenital syndrome. One of the questions to be answered by this trial is the cause of the strong variation in clinical expression of the disorder. Underdiagnosing is an important factor in this phenomenon, as shown by the data of a family of which the case histories of the two oldest children were discussed in this journal in 1965. Both children died at a very young age. Recently, MCAD deficiency was diagnosed in the youngest child of this family, now a 34-year-old woman. This family history illustrates the variable clinical expression of MCAD deficiency, which can cause death but can also run a milder or even subclinical course. Moreover, this family history shows that the underdiagnosis of MCAD deficiency in deceased children may be a cause of the apparently limited clinical detection rate of this disease, for which a simple treatment consisting of life-style and dietary measures is available after diagnosis.

The practice guideline on routine neonatal examination of the Dutch College of General Practitioners describes the examination of the newborn directly after birth, whether at home or in the hospital. It is proposed that examination be limited to inspection, without auscultation and palpation. If conducted strictly according to the guidelines given, this may be sufficient. However, auscultation of the heart is the most reliable way to determine the heart rate. Including auscultation and palpation in the routine examination after birth would contribute to the experience of general practitioners with these techniques in babies. This is of importance, since general practitioners are the first to be consulted in case of any health problems in this patient category. Previously, it was recommended that the general practitioner visit mother and child on the third, fourth or fifth day after delivery and examine the baby. In the new standard, this second examination is considered to be redundant, based on data in the literature. However, it remains the duty of the general practitioner to inform the parents about (non-specific) early signs of disease in newborns. Furthermore, the threshold for consultation of the general practitioner should be low for the early diagnosis and management of serious conditions, such as septicaemia or congenital heart disease.

Ortolani's manoeuvre is used to detect hip instability. It is intended to be used to establish the mobility of a dislocated femoral head with respect to the acetabulum in newly-born infants. Barlow's modification attempts to dislocate a reduced but unstable hip out of the acetabulum. Ortolani's manoeuvre is a primarily tactile, proprioceptive sensation and has nothing to do with the usually inconsequential audible and palpable clicks in infant hips. It has been found that widespread use of Ortolani's manoeuvre cannot prevent all late diagnoses of hip dysplasia. This is because neonatal hip instability is only part of the total spectrum of hip dysplasia, and because the examination requires a relaxed newly-born infant and an experienced examiner. In the Dutch situation, general screening with Ortolani's manoeuvre is not advisable as this will lead to many false-positive and false-negative outcomes due to this neonatal examination being carried out by various physicians and midwives with insufficient experience. Better results may be expected from ultrasound screening at child welfare clinics. This is presently being investigated in a large population study.

Early detection of children with sickle cell disease, determination of carriership frequency as well as evaluation of the knowledge regarding this haemoglobinopathy in various ethnic risk groups.Prospective.From 1 November 1998 through to 31 October 1999, the ethnic background was recorded for consecutive pregnant women under care of the Academic Medical Centre, Amsterdam, the Netherlands, and the presence of carriership for sickle cell disease was evaluated. Carriers were asked about their knowledge of sickle cell disease. A diagnostic blood test of cord blood was also performed using a PCR which could detect both haemoglobin S and C mutations.Fifty-five carriers were detected in a group of 1,016 investigated pregnant women (5.4%). The carriership frequencies in Surinam and African women were 12 and 15.7%, respectively. Knowledge of sickle cell disease, its occurrence in populations at risk, as well as the terms 'inheritance' and 'carriership', differed substantially between Surinam and African women, with awareness being lower in the latter group. In six cases informed consent was not asked. All other 49 carriers consented to a diagnostic test. Two intrauterine deaths occurred. Four children had sickle cell disease: three had HbSS, one had HbSC. Nineteen children proved to be carriers for sickle cell disease, 18 were heterozygotes for HbS, one for HbC.This targeted neonatal screening for sickle cell disease was feasible in a hospital setting. The number of children diagnosed with the disease supports the wider implementation of this method of early detection.

In the Netherlands, in contrast to England, no screening for carriership of haemoglobinopathy (sickle-cell anaemia and thalassaemia) is being carried out. The absolute prevalence is low, but the prevalence in proportion to birth figures is approximately the same in the two countries. The lack of knowledge of the professional groups involved can be rectified by adequate instruction. The question whether screening should be carried out before pregnancy or early prenatally proved not difficult to solve in England. Screening for carriership is technically possible and in England it is also cost-effective. This screening should be performed in the Netherlands, as well.

Two firstborn, breast-fed infants (delivery at home) were admitted to the hospital in a critical state of hypernatraemic dehydration. Case 1, a boy aged 13 days, had suffered 1220 g loss of weight since birth (31%), his serum sodium concentration was 180 mmol/l. Case 2, a girl aged 7 days, had lost 610 g since birth (18%); her serum sodium level was 159 mmol/l. In both cases poor professional support of lactation and lack of weight control had resulted in unnoticed severe malnutrition. After slow rehydration recovery was uneventful. Closer monitoring of babies' weight, e.g. twice a week, is advocated especially for breast-fed firstborns in the early weeks of life.

Evaluation of the Dutch screening programme for congenital hypothyroidism (CH).Descriptive.Nationwide.Data on the screening were obtained from the administration body for vaccination and screening results, laboratories and paediatricians to whom infants with positive screening values were referred, during the period from January 1st, 1981 to December 31st, 1990.Of all live births in the Netherlands, 99.5% (1,797,719) were screened for CH. During the study period, 10,165 children (0.57% of all screened infants) were referred. Of the referred children, 529 had primary CH and 53 had congenital thyrotropin deficiency syndrome (CTDS). The prevalences of primary CH and CTDS are 1:3,400 and 1:25,000, respectively. The sensitivity of the programme with respect to detection of primary CH and CTDS was 99% and 74%, respectively. For all forms of CH combined, the specificity of the programme was 99% and the positive predictive value 6%. The positive predictive value was especially low in the group of infants with low T4 and normal thyrotropin values. One of the goals of the programme is to realise the start of treatment in all patients before they reach the age of three weeks. Before the screening programme came into being, the cumulative proportion of patients treated on the 21st day was 6%. After the beginning of the programme, the proportion increased to 54%. In screened patients with a severe form of CH it is currently 72%.The screening programme has made a substantial and important contribution to early and effective identification of patients with CH. A number of measures to decrease the number of false-positive results have been taken and others are at present being investigated. Although patients are now treated much earlier than before the programme started, substantial improvement in this respect is still possible. This can only be achieved by a collective effort of performers of the heel puncture, laboratories, administration body for vaccination and screening results, general practitioners and pediatricians.

Doel. Evaluatie van de Nederlandse screening op congenitale hypothyreoïdie (CHT). Opzet. Descriptief. Plaats. Landelijk. Methoden. Gegevens over de screening in de periode 1 januari 1981-31 december 1990 werden verkregen van de entadministraties, van laboratoria en van kinderartsen naar wie kinderen met afwijkende uitslagen verwezen werden. Resultaten. Van alle levendgeborenen werden 1.797.719 (99,5) kinderen gescreend op congenitale hypothyreoïdie (CHT). Er kwamen 10.165 kinderen (0,57 van alle gescreenden) voor verwijzing in aanmerking. Van de verwezen kinderen hadden 529 primaire CHT en 53 congenitaal thyreotropinedeficiëntiesyndroom (CTDS). De prevalentie van primaire CHT en CTDS was respectievelijk 1:3400 en 1:25.000. De sensitiviteit van het programma ten aanzien van primaire CHT was 99 en ten aanzien van CTDS 74. De specificiteit en de voorspellende waarde ten aanzien van alle vormen van CHT waren respectievelijk 99 en 6. Een van de doelen van het screeningsprogramma is bij alle patiënten de behandeling te beginnen voor de leeftijd van 22 dagen. Vóór screening was het cumulatieve percentage patiënten dat op de 21e dag reeds werd behandeld 6, na introductie van de screening was dat 54. Gescreende patiënten met een ernstige vorm van CHT werden in 72 van de gevallen behandeld voor dag 22. Conclusie. De screening levert een belangrijke bijdrage aan een vroegtijdige en effectieve opsporing van CHT-patiënten. Maatregelen om het aantal fout-positieve uitslagen te beperken zijn inmiddels genomen of zijn nog in onderzoek. Hoewel patiënten dankzij de screening veel eerder worden behandeld dan voor de screening, valt hier nog een aanzienlijke winst te boeken. Alleen door een gezamenlijke inspanning van de uitvoerders van de hielprik, de laboratoria, de entadministraties, huisartsen en kinderartsen kan dit bereikt worden. Chemicals/CAS: Thyrotropin, 9002-71-5.

Doel. Evaluatie van de Nederlandse screening op congenitale hypothyreoïdie (CHT). Opzet. Descriptief. Plaats. Landelijk. Methoden. Gegevens over de screening in de periode 1 januari 1981-31 december 1990 werden verkregen van de entadministraties, van laboratoria en van kinderartsen naar wie kinderen met afwijkende uitslagen verwezen werden. Resultaten. Van alle levendgeborenen werden 1.797.719 (99,5) kinderen gescreend op congenitale hypothyreoïdie (CHT). Er kwamen 10.165 kinderen (0,57 van alle gescreenden) voor verwijzing in aanmerking. Van de verwezen kinderen hadden 529 primaire CHT en 53 congenitaal thyreotropinedeficiëntiesyndroom (CTDS). De prevalentie van primaire CHT en CTDS was respectievelijk 1:3400 en 1:25.000. De sensitiviteit van het programma ten aanzien van primaire CHT was 99 en ten aanzien van CTDS 74. De specificiteit en de voorspellende waarde ten aanzien van alle vormen van CHT waren respectievelijk 99 en 6. Een van de doelen van het screeningsprogramma is bij alle patiënten de behandeling te beginnen voor de leeftijd van 22 dagen. Vóór screening was het cumulatieve percentage patiënten dat op de 21e dag reeds werd behandeld 6, na introductie van de screening was dat 54. Gescreende patiënten met een ernstige vorm van CHT werden in 72 van de gevallen behandeld voor dag 22. Conclusie. De screening levert een belangrijke bijdrage aan een vroegtijdige en effectieve opsporing van CHT-patiënten. Maatregelen om het aantal fout-positieve uitslagen te beperken zijn inmiddels genomen of zijn nog in onderzoek. Hoewel patiënten dankzij de screening veel eerder worden behandeld dan voor de screening, valt hier nog een aanzienlijke winst te boeken. Alleen door een gezamenlijke inspanning van de uitvoerders van de hielprik, de laboratoria, de entadministraties, huisartsen en kinderartsen kan dit bereikt worden. Chemicals/CAS: Thyrotropin, 9002-71-5.