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Study question Does embryo vitrification affect children’s health including growth, up to 2 years of age when compared to fresh embryo transfer? Summary answer While embryo vitrification had an impact on birth parameters, no differences in growth or health outcomes were found up to 2 years of age. What is known already Vitrification has become the preferred cryopreservation method for embryos. Frozen embryo transfer has been repeatedly associated with altered health outcomes when compared with fresh transfer including a decreased risk for small-for gestational age (SGA) and an increased risk for large-for-gestational-age (LGA) and macrosomia. Not only there is uncertainty which factors are responsible for the observed differences, also the heterogeneity among studies limits overall conclusions. Notwithstanding the observed differences at birth, little is known about growth and health of children born after embryo vitrification beyond birth while aberrant growth trajectories have been linked to cardiometabolic morbidity later in life. Study design, size, duration This single-center cohort study compared anthropometry and health outcomes in singletons conceived after cleavage-stage or blastocyst-stage embryo vitrification with results after fresh embryo transfer between 2014 and 2018. Pregnancies after PGT, IVM, oocyte vitrification or oocyte/embryo donation were excluded. Eligible singletons living in Belgium and randomly selected for continued follow-up were invited for examination in our center at 2 months (infancy) and 2 years of age (early childhood). Participants/materials, setting, methods Birth characteristics were available for 1237 and 2063 children born after embryo vitrification and fresh embryo transfer, respectively. Follow-up data were available for 582 and 757 children at 2 months and for 233 and 296 children at 2 years. Growth parameters were adjusted for neonatal, treatment and maternal characteristics. Subgroup analysis according to cycle regimen (HRT versus NC) and strategy (freeze-all versus previous fresh cycle) was performed. In addition, outcomes restricted to blastocysts are presented. Main results and the role of chance Mothers giving birth to a child conceived after embryo vitrification presented more often with pregnancy-induced hypertensive disorders than controls (P Birthweight, height and head circumference SDS of children born after embryo vitrification were higher than for children born after fresh embryo transfer (all P Restricting the sample to blastocysts (n = 1795), we found a higher birthweight SDS and increased risks of LGA, macrosomia and pregnancy-induced hypertensive disorders after vitrification (all P At infancy, weight and height SDS were larger for children born after embryo vitrification, but not after adjustment for co-variates. At childhood, no differences in anthropometrics were found between the groups. Weight and height gain from birth to infancy and from infancy to early childhood were comparable between the groups. Until 2 years, comparable rates of severe developmental problems, hospital admissions, surgical interventions and of chronic medication intake were found between the groups. Subgroup analysis showed that growth parameters at all ages were not affected by cycle regimen or cycle strategy. Limitations, reasons for caution Participation rate at 2 years was lower than expected in both groups, probably due to cancellation/postponement of the visit related to the corona pandemic. Furthermore, although cycle strategy was not found to affect growth parameters, the sample size of the subgroup analysis remains rather small to draw firm conclusions. Wider implications of the findings When adjusted for co-variates including birthweight, the observed differences in anthropometrics at birth in children born after embryo vitrification attenuated by 2 years of age. This suggests that outcomes in early childhood are determined by size at birth. Trial registration number Not applicable

STUDY QUESTION Is there a relationship between karyotype abnormalities in fetuses and children conceived by ICSI and their father’s semen parameters? SUMMARY ANSWER The de novo chromosomal abnormality rate in pre- and postnatal karyotypes of ICSI offspring was higher than in the general population and related to fathers’ sperm parameters. WHAT IS KNOWN ALREADY Several studies have reported a higher rate of de novo chromosomal anomalies in ICSI fetuses but recent data from large cohorts are limited. Overall, reported prevalences of non-inherited karyotype aberrations are increased in fetuses conceived after ICSI and vary between 1.6% and 4.2%. Only a few studies focus on the relation between karyotype anomalies in ICSI offspring and semen parameters of their fathers. Furthermore, an increased incidence of abnormal karyotypes in ICSI neonates has been described, but the rates vary widely across studies. STUDY DESIGN, SIZE, DURATION We report on karyotype results from prenatal testing by means of chorionic villus sampling and amniocentesis and results from postnatal blood sampling in offspring conceived by ICSI in a single center. Ongoing pregnancies resulting from an oocyte retrieval between January 2004 and December 2012 and after transfer of fresh ICSI embryos obtained using ejaculated or non-ejaculated sperm (fresh or frozen-thawed) were considered. Pregnancies following frozen embryo transfer, oocyte or sperm donation, IVF, preimplantation genetic testing and IVM were excluded. All abnormal prenatal results after sampling are reported irrespective of the outcome of the pregnancy. PARTICIPANTS/MATERIALS, SETTING, METHODS From the 4816 ongoing ICSI pregnancies, information on pregnancy outcome was available for 4267 pregnancies. Prenatal testing was performed in 22.3% of the pregnancies, resulting in a diagnosis in 1114 fetuses. A postnatal karyotype was obtained in 29.4% of the pregnancies in which no invasive prenatal diagnosis was performed, resulting in a total of 1391 neonates sampled. The prevalence of chromosomal anomalies according to maternal age and semen quality was analyzed with logistic regression. For definitions of normal semen quality, the World Health Organization reference values for human semen characteristics were adopted. MAIN RESULTS AND THE ROLE OF CHANCE An abnormal fetal karyotype was found in 29 singletons and 12 multiples (41/1114; 3.7%; 95% CI 2.7–4.9%): 36 anomalies were de novo (3.2%; 95% CI 2.3–4.4), either numerical (n = 25), sex (n = 6) or structural (n = 5), and five were inherited. Logistic regression analysis did not show a significant association between maternal age and a de novo chromosomal fetal abnormality (odds ratio (OR) 1.05; 95% CI 0.96–1.15; P = 0.24). In all but one case, fetuses with an abnormal karyotype were conceived by ICSI using ejaculated sperm. Abnormal karyotypes were found in 14 (1.0%; 95% CI 0.6–1.7) out of 1391 postnatal samples of children born after ICSI who were not tested prenatally: 12 were de novo anomalies and two were inherited balanced karyotypes. The 14 abnormal karyotypes were all found in children born after ICSI using ejaculated sperm. The odds of a de novo karyotype aberration increased with maternal age when combining pre- and postnatal data (OR 1.11; 95% CI 1.04–1.19). A higher rate of de novo chromosomal abnormalities was found in fetuses and children of couples with men having a sperm concentration LIMITATIONS, REASONS FOR CAUTION We cannot exclude that the observation of a higher prevalence of karyotype anomalies in ICSI offspring compared to literature data in the general population is due to enhanced surveillance after ART given the lack of a control group. Although we did not find more chromosomal anomalies after ICSI with non-ejaculated sperm, the small numbers do not allow firm conclusions. WIDER IMPLICATIONS OF THE FINDINGS The observed increased risk of a de novo karyotype anomaly after ICSI conception in couples with poor sperm warrants continued counseling toward prenatal testing. The current and widespread use of innovative non-invasive prenatal testing will result in larger datasets, adding to a balanced estimation of the prevalence of karyotype anomalies in ICSI offspring. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the Methusalem grants issued by the Vrije Universiteit Brussel. All authors declared no conflict of interest related to this study. TRIAL REGISTRATION NUMBER N/A

STUDY QUESTION What is the likelihood of success of a single cycle of preimplantation genetic testing for monogenic disorders (PGT-M), measured as the cumulative live birth rate (CLBR) and based on various patient demographics? SUMMARY ANSWER For all women aged ≤40 years, the CLBR was at least 10% when the number of oocytes was ≥7 (range 10–30%) or was at least 5% when the number of oocytes was ≥3 (range 5–17%). WHAT IS KNOWN ALREADY The number of oocytes is significantly associated with the number of embryos for genetic testing and the clinical outcome in PGT-M. Embryos diagnosed as affected or embryos that remain without diagnosis cannot be used for embryo transfer. The size of the group of embryos non-suitable for transfer varies between 25% and 81%, depending on the indication. Thus, PGT-M is more likely to be more severely impacted by suboptimal ovarian response, poor fertilization and suboptimal embryo development than conventional IVF/ICSI schemes without PGT. STUDY DESIGN, SIZE, DURATION This was a single-centre retrospective comparative cohort study, of cycles between January 2011 and December 2015. A total number of 2265 PGT-M cycles were compared to 2833 conventional ICSI cycles. The principal aim of our study was the identification of the parameters of poor CLBR in couples undergoing PGT-M using multiplex short tandem repeat (STR) markers on blastomere biopsy DNA. The secondary aim was to compare the parameters of poor CLBR of the PGT-M population to those of couples undergoing ICSI without PGT. PARTICIPANTS/MATERIALS, SETTING, METHODS The baseline characteristics of the PGT-M group were compared to the conventional ICSI group. A multiple regression analysis was applied to account for the following potential confounding factors: female age, number of previous ART cycles, number of oocytes/suitable embryos for transfer and dosage of gonadotrophins used for ovarian stimulation. MAIN RESULTS AND THE ROLE OF CHANCE The PGT-M group was younger (female age 32.0 vs 34.5 years), had a higher number of previous ART cycles (1.1 vs 0.9 cycles) and used more gonadotrophins (2367 vs 1984 IU). Per cycle, the PGT-M group had more retrieved oocytes (11.8 vs 8.3 oocytes), fewer suitable embryos for transfer (1.7 vs 2.8 embryos) and a lower CLBR (29.4% vs 35.0%). Multiple regression analysis showed that the CLBR in the PGT-M group was significantly influenced by female age, the number of previous ART cycles, the number of oocytes and the dose of ovarian stimulation. In both groups, the predicted CLBR increased with increasing numbers of oocytes and suitable embryos. At least two retrieved oocytes or one embryo per single PGT-M cycle could confer an estimated CLBR above 10%. By assessing female age and the number of retrieved oocytes together, it was shown that for all women aged ≤40 years, the predicted CLBR per single PGT-M cycle was ≥10% when the number of oocytes was ≥7 or was ≥5% when the number of oocytes was ≥3. LIMITATIONS, REASONS FOR CAUTION Despite the large sample size, the findings are confined by limited confounder adjustment and the lack of specific PGT-M comparators. WIDER IMPLICATIONS OF THE FINDINGS This study aimed to describe the likelihood of success of PGT-M treatment, measured as CLBR, based on various patient demographics. In a PGT-M program, couples need to be informed of the prognosis more specifically when it is futile. The table of predicted CLBRs presented in this study is a useful tool in counselling PGT-M couples for making reproductive choices. STUDY FUNDING/COMPETING INTEREST(S) No funding was required and there are no competing interests. TRIAL REGISTRATION NUMBER N/A.

STUDY QUESTION: What are the factors influencing the success rate for couples undergoing preimplantation genetic testing (PGT) for polycystic kidney disease (PKD)? SUMMARY ANSWER: In our study cohort, the live birth delivery rate is significantly associated with female age while the male infertility accompanying autosomal dominant PKD (ADPKD) does not substantially affect the clinical outcome. WHAT IS KNOWN ALREADY: While women with ADPKD have no specific fertility problems, male ADPKD patients may present with reproductive system abnormalities and infertility. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study involves 91 PGT cycles for PKD for 43 couples (33 couples for PKD1, 2 couples for PKD2 and 8 couples for autosomal recessive PKD (ARPKD)) from January 2005 until December 2016 with follow-up of transfers until end of 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sixteen single-cell clinical tests for PKD based on multiplex PCR of short tandem repeat markers, with or without a specific mutation were developed and applied for diagnosis of 584 Day 3 cleavage stage embryos. In 18 couples, the male partner was affected with ADPKD (=Group A) and 12 of them had a documented infertility status. Group A underwent 52 cycles to oocyte retrieval. For 18 other couples, the female partner was affected with ADPKD (=Group B) and four male partners from this group had a documented history of infertility. This group underwent 31 cycles to OR. MAIN RESULTS AND THE ROLE OF CHANCE: Genetic analysis resulted in 545 embryos (93.3%) with a diagnosis, of which 215 (36.8%) were genetically transferable. Transfer of 74 embryos in 53 fresh cycles and of 34 cryopreserved embryos in 33 frozen-warmed embryo transfer cycles resulted in a live birth delivery rate of 38.4% per transfer with 31 singleton live births, two twin live births and one ongoing pregnancy. The observed cumulative delivery rate was 57.8% per couple after five treatment cycles. Thirty cryopreserved embryos still remain available for transfer. The clinical pregnancy rate per transfer (fresh + frozen; 45.9% in group A versus 60.0% in group B, P < 0.05) and the live birth delivery rate per transfer (fresh + frozen; 27.0% in group A versus 42.9% in group B, P < 0.05) was significantly lower for couples with the male partner affected with ADPKD compared with couples with the female partner affected with ADPKD. However, a multivariate logistic regression analysis showed that only female age was associated with live birth delivery rate (odds ratio = 0.87; 95% CI: 0.77-0.99; P = 0.032). LIMITATIONS, REASONS FOR CAUTION: This study is based on retrospective data from a single centre with Day 3 one-cell and two-cell biopsy. Further analysis of a larger cohort of PKD patients undergoing PGT is required to determine the impact of male infertility associated with ADPKD on the cumulative results. WIDER IMPLICATIONS OF THE FINDINGS: Knowledge about factors affecting the clinical outcome after PGT can be a valuable tool for physicians to counsel PKD patients about their reproductive options. Males affected with ADPKD who suffer from infertility should be advised to seek treatment in time to improve their chances of conceiving a child. STUDY FUNDING/COMPETING INTEREST(S): No funding was obtained. There are no competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

RESEARCH QUESTION: Can (mosaic) aneuploidy be reliably detected in preimplantation embryos after multiple displacement amplification and single nucleotide polymorphism detection, independent of haplotyping and copy number detection, with a new method 'analysis of parental contribution for aneuploidy detection' or 'APCAD'? DESIGN: This method is based on the maternal contribution, a parameter that reflects the proportion of DNA that is of maternal origin for a given chromosome or chromosome segment. A maternal contribution deviating from 50% for autosomes is strongly indicative of a (mosaic) chromosomal anomaly. The method was optimized using cell mixtures with varying ratios of euploid and aneuploid (47,XY,+21) lymphocytes. Next, the maternal contribution was retrospectively measured for all chromosomes from 349 Karyomapping samples. RESULTS: Retrospective analysis showed a skewed maternal contribution (63.6%) in 57 out of 59 autosome meiotic trisomies and all autosome monosomies (n = 57), with values close to theoretical expectation. Thirty-two out of 7436 chromosomes, for which no anomalies had been observed with Karyomapping, showed a similarly skewed maternal contribution. CONCLUSIONS: APCAD was used to measure the maternal contribution, which is an intuitive parameter independent of copy number detection. This method is useful for detecting copy number neutral anomalies and can confirm diagnosis of (mosaic) aneuploidy detected based on copy number. Mosaic and complete aneuploidy can be distinguished and the parent of origin for (mosaic) chromosome anomalies can be determined. Because of these benefits, the APCAD method has the potential to improve aneuploidy detection carried out by comprehensive preimplantation genetic testing methods.

Preimplantation genetic testing-human leukocyte antigen '(PGT-HLA) only' refers to the HLA typing of single or few cells biopsied from in vitro fertilized preimplantation embryos. The aim of the procedure is to establish a pregnancy, in which the fetus is HLA compatible with an affected sibling in need of a hematopoietic stem cell transplantation (HSCT). During PGT-M-HLA, the identification of a HLA-compatible embryo is combined with the detection of mutation(s) underlying immunodeficiencies and hemoglobinopathies. We report a combined retrospective and prospective cohort analysis of PGT-(M-)HLA procedures carried out from 1998 until 2017, with follow-up of transplantations to 2019. During the study period, 234 couples from 22 countries were invited for a multidisciplinary consultation. Two couples were rejected and 70 couples declined (various reasons), leaving 162 couples for which 414 clinical cycles were carried out. Cleavage stage biopsy followed by single-cell multiplex PCR for short tandem repeat-based haplotyping was applied in most cases (98.7%). The diagnostic efficiency was high (94.8%) but only 16.5% of the embryos was genetically suitable for transfer. Fresh and frozen-thawed embryo transfer resulted in 67 clinical pregnancies, 63 deliveries, and 74 live births, of which 60 children were HLA compatible. This yielded a live birth delivery rate of 30.3% per transfer. Information on neonatal characteristics of the matching PGT-(M-)HLA children showed reassuring outcomes. So far, HSCT was carried out successfully for 25 out of 26 cases. In conclusion, our data show that PGT-(M-)HLA is a valuable procedure: the high complexity and limited delivery rate are balanced by the successful HSCT outcome and the positive impact on families.

BACKGROUND: Trichothiodystrophy (TTD) describes a group of rare genetic disorders of DNA repair, characterized by sulphur-deficient hair, skin anomalies and systemic complications like preterm delivery, neurological impairment, haematological and ophthalmological abnormalities and life-threatening infections.OBJECTIVES: The aim of this case report was to investigate the contribution of the gene mutation to the phenotype.METHODS: We describe the clinical and molecular characteristics of a family with two TTD-affected siblings who died before the age of 2 years.RESULTS: The causal mutated gene is the ERCC2 gene, and one of the identified mutations is the c.2164C>T (p.Arg722Trp) variant. The association of this mutation with a severe TTD phenotype was suggested earlier in literature, and the present family adds further evidence to this hypothesis.CONCLUSION: Accurate identification of the underlying genetic defect can guide the clinical follow-up and counselling of patients and their families.

Objective Mutations in the X-linked gene Filamin A (FLNA) are known to be linked to a broad clinical phenotype ranging from otopalatodigital syndromes (OPD1, OPD2) to frontometaphyseal dysplasia, Melnick-Needles syndrome and periventricular nodular heterotopia (PVNH). In the present study we investigate the phenotype-genotype correlation in carriers of FLNA mutations in order to improve the counseling of these patients and their relatives. Methods Clinical and neuroloradiological data from 16 FLNA mutation carriers were collected through retrospective analysis of their hospital files and a standardized questionnaire sent to the referring physician. These data were reviewed by a neurologist, molecular geneticists and a clinical geneticist. Results Fifteen of the carriers were female, as expected in dominant X-linked disorders. Half of the carriers belonged to a mother-child pair, with the mother being diagnosed secondary to the diagnosis in the child. Four carriers had the clinical diagnosis of OPD and their mutations were clustered in exons 3 and 4, whereas the mutations associated with PVNH were scattered throughout the gene. Besides the PVNH other findings on brain MRI included mega cisterna magna, corpus callosum and white matter anomalies. Cardiac investigations revealed aortic valve insufficiency and dilatation of the aorta, even at young age. In the majority of the patients, the clinical work-up focused on the primary indications for FLNA mutation analysis whereby other organs were not systematically investigated. Conclusion Although a lot is already known on the manifestations caused by FLNA mutations, and phenotype-genotype correlations can be made to a certain extent, many patients could benefit from a more extensive work-up and follow-up. This will not only lead to further improvement of our knowledge and understanding of the FLNA-related disorders, but will also allow us to anticipate on certain complications.

The identification of all people with a diagnosis of Prader-Willi syndrome (PWS) confirmed by DNA methylation analysis living in Flanders was attempted through contact with the four genetic centres and the PWS Association. The birth incidence for the period 1993-2001 was 1:26 676, the minimum prevalence at 31 December 2001 was 1:76 574. A decreasing number of cases with age was found, which can be explained by a number of missing cases in the older population, a higher neonatal mortality in the past and an increasing mortality with age. Childhood death is usually sudden and associated with respiratory infection and high temperature, while the cause of death in adults is considered to be circulatory or respiratory in origin.

Background: Mutations in the TUBA1A gene have been reported in patients with lissencephaly and perisylvian pachygyria. Methods: Twenty-five patients with malformations of cortical development ranging from lissencephaly to polymicrogyria were screened for mutations in TUBA1A . Results: Two novel heterozygous missense mutations in TUBA1A were identified: c.629A>G (p.Tyr210Cys) occurring de novo in a boy with lissencephaly, and c.13A>C (p.Ile5Leu) affecting 2 sisters with polymicrogyria whose mother presented somatic mosaicism for the mutation. Conclusions: Mutations in TUBA1A have been described in patients with lissencephaly and pachygyria. We report a mutation in TUBA1A as a cause of polymicrogyria. So far, all mutations in TUBA1A have occurred de novo, resulting in isolated cases. This article describes familial recurrence of TUBA1A mutations due to somatic mosaicism in a parent. These findings broaden the phenotypic spectrum associated with TUBA1A mutations and have implications for genetic counseling.

To investigate indications, features and outcome of pediatric tracheotomy in our ENT department.A retrospective chart review of all pediatric patients who underwent tracheotomy between 1992 and 2006 in the Children's Hospital of the Universitair Ziekenhuis Brussel. The main parameters of the study were age, gender, indications, morbidity and mortality rate, time and success of decannulation.Twenty-nine children younger than 16 years of age, 21 males and 8 females, underwent tracheotomy. Indications for tracheotomy fell into two main groups: chronic diseases requiring ventilation support (55%) and relief of airway obstruction (45%). Tracheotomies were mainly performed in young children, 76% were under 3 years of age. In this age group, upper airway obstruction was the most frequent indication. The complication rate was 36%, and the nontracheotomy-related mortality rate was 25%. The tracheotomy-related mortality rate was 3.5%. Successful decannulation was possible in 28% after a mean duration of 24 months after surgery. Of the remaining 72% for whom decannulation was not performed, 35% died mainly because of the underlying disease. Those infants failing decannulation (65%) had neurologic disorders.In accord with the literature, where a shift towards very young patients and towards indications related to chronic ventilatory support is observed, in this series tracheotomies were mainly performed for the youngest children. Relief of upper airway obstruction was the most frequent indication. Morbidity and mortality rates among this specific patient population should not be ignored.

Objective Noonan syndrome is the most common Rasopathy, characterised by typical facial dysmorphism (hypertelorism, downslanting palpebral fissures, ptosis, low-set posteriorly rotated ears) and congenital heart defects. Other features include short stature, cryptorchidism, ectodermal abnormalities, intellectual impairment. The phenotype is variable. The disease is caused by mutations in genes encoding proteins interacting with the Ras-MAPK signaling pathway. How the clinical phenotype can orient the molecular analysis will be further illustrated with two patients. Methods Clinical and molecular data on two patients within the Noonan spectrum are presented. Results The first patient, a boy born with normal birth parameters, after pregnancy complicated by polyhydramnios. He presented typical dysmorphism, pectus excavatum and bilateral cryptorchidism. Billowing of the mitral valve was seen at cardiac evaluation. Evolution showes a relative macrocephaly and curly hair. Stature and psychomotor development are normal. Molecular analysis of the PTPN11 gene showed no mutations. Further analysis showed not earlier reported mutation in the SOS1 gene (c.1670_1687del). The second patient, a boy born with a birthweigth above the 95th centile, presented with typical dysmorphism, macrocephaly and atrial septal defect. Evolution shows slow growing, sparse, thin hair, pectus excavatum and severe eczema. He has short stature and intellectual disability. Molecular analysis of the most common genes in the RAS-MAPK pathway didn't reveal any mutation. Recently a mutation was found in the SHOC2 gene (p.Ser2Gly). Conclusion Noonan spectrum is a genetically heterogenous disorder but some distinctive characteristics are associated with particular genes as illustrated in our cases. SOS1 mutations are often associated with normal stature and normal cognition. Recently a recurrent mutation (p.Ser2Gly)in the SHOC2 gene has been associated with with loose anagen hair, short stature and more pronounced intellectual impairment. Knowledge of the phenotype–genotype correlation is helpful in clinical management and in choosing the best molecular tests.

Baron Clemens von Pirquet, an Austrian paediatrician, proposed in 1903 the terms allergy and allergen after observing that some of his patients had “altered responses” to certain substances. Allergic symptoms are not necessarily accompanied by sensitization or vice versa. Recently, nomenclature for allergy has been revised.

In 1987 Buttiens and Fryns [1987: Am J Med Genet 27:651-660] reported on two sibs, brother and sister, with severe distal limb defects, micrognathia, and mild to moderate mental retardation. The male also showed severe myopia and oligomeganephronia. To the best of our knowledge, no other similar patients have been described since. We report on a boy with a similar phenotype. .

We report 3 non related patients with severe hypoplasia/aplasia of the thumb with an ipsilateral synostosis of the fourth and fifth metacarpals. A review of few reports on this unusual association is presented and the possible pathogenetic mechanism is discussed.

In this report we describe the unusual manifestation of fibrous dysplasia of rays IV and V of the right hand and of rays III-IV of the left hand in a 12-year-old normal girl. The first symptoms of localised macrodactyly became progressively evident from the age of 8 years on.

We report on a girl with congenital scalp and acral reduction limb defects, consistent with the diagnosis of Adams-Oliver syndrome. The presence of constriction rings makes the limb anomalies in this case similar to those seen in the amniotic band disruption sequence. Vascular disruption--with or without secondary amniotic rupture--may be responsible for the observed anomalies. Therefore we believe that the present observation adds further evidence for the hypothesis that the Adams-Oliver syndrome is a vascular disruption sequence.

BACKGROUND: Hydrolysates are used in the treatment and prevention of cows milk protein allergy. Hydrolysis might alter the plasma level of amino acids. METHODS: Forty-five infants were included in a double-blind prospective study and were randomized in two groups: one receiving a whey predominant formula (n = 20) and the second group receiving a whey hydrolysate formula (n = 25). Weight and length gain was evaluated up to the age of 13 weeks, when blood was sampled for determination of fasting plasma amino acids. RESULTS: Four infants of the hydrolysate group dropped out because refusal to ingest the formula. Weight and length gain at 13 weeks of age were extremely comparable. Significant differences in plasma concentrations were observed for a number of nonessential and essential amino acids (p = .035 to .0001). Threonine and lysine were both higher in the hydrolysate group, and aspartic acid, cystine, methionine, tyrosine, phenylalanine, histidine, and arginine were lower in the hydrolysate group. CONCLUSIONS: These differences in plasma amino acid levels have to be regarded with care because all concentrations were within normal ranges, with the exception of threonine. Weight and length gain of the hydrolysate and the whey predominant formula were identical.

In a retrospective evaluation we reviewed the symptomatology of 143 children (age 2-15 years, mean 8.9 years) who were referred to us for upper gastrointestinal endoscopy because of recurrent abdominal pain with a duration of 6 weeks or longer. Helicobacter pylori infection was diagnosed in 36 out of 143 patients (25.2%). No statistically significant differences could be detected between the symptoms experienced by the 36 H. pylori-infected children and those experienced by the remaining 107 H. pylori-negative pediatric patients (p = 0.18-0.60). We conclude that no specific symptoms are associated with H. pylori gastritis in children. Our observations suggest that the recurrent abdominal complaints found in children with H. pylori infection seem to be caused by the secondary gastroduodenal pathology, rather than by H. pylori infection itself.

The programme "Europe against cancer" stimulated, among other activities, breast screening activities in the member states. From the beginning, it was clear that a rigorous and efficient approach required the highest possible quality of the three major components of a breast screening programme: the medical performance (correct positioning, training of the medical staff, double reading of the mammograms and feedback from the pathologist and the epidemiologist), the organisation (attendance rate, data base) and the quality of the imaging process (compliance of the image quality and the breast dose with the CEC document of 1990). The first part of this paper will be limited to the latter component and the second part to the subject of correct positioning of the breast.

We present an adult female patient with a so far unreported syndrome of severe short stature, severe mental retardation, facial dysmorphism and hyperphalangy of the index fingers. Parental consanguinity suggests an autosomal recessive inheritance.

In 1987 Buttiens and Fryns [1987: Am J Med Genet 27:651-660] reported on two sibs, brother and sister, with severe distal limb defects, micrognathia, and mild to moderate mental retardation. The male also showed severe myopia and oligomeganephronia. To the best of our knowledge, no other similar patients have been described since. We report on a boy with a similar phenotype. .

The etiology of allergy is multifactorial, with many variables contributing to the final expression of atopic disease. Three breeding grounds are needed to develop allergic disease: the appropriate genetic background, contact with the allergen(s) and environmental factors. Timing and dosing of allergen(s) are of major importance. Contact with (dietary) allergens and various agents such as tobacco smoke and infections occur not only during post-natal life, but also perinatally and even pre-natally. A critical review of published evidence regarding the impact of maternal exposure to antigens during pregnancy on later development of allergy in the offspring can only conclude that more research is urgently needed. Contact with multiple dietary allergens should be in general of benefit to the fetus to develop tolerance. Current knowledge suggests that pregnant women should have a normal diversified diet, avoiding toxic agents such as tobacco and alcohol. The role of maternal intake of poly-unsaturated fatty acids on the development of atopy in the infants needs to be further evaluated. If parental history would be insufficient to determine the fetal risk, preventive measurements would be advisable for all fetuses.