Severe Intrauterine Growth Retardation Research Articles

PHGDH-related microcephalic dwarfism in two fetuses: Expanding the phenotypical spectrum of L-serine biosynthesis defect

Defects in L-serine biosynthesis are a group of autosomal recessive diseases resulting in a wide phenotypic spectrum ranging from viable to lethal presentations and caused by variants in the three genes encoding the L-serine biosynthesis enzymes, PHGDH, PSAT1, and PSPH. Neu-Laxova syndrome (NLS) is the fetal form of this group, characterized by multiple congenital anomalies including severe intrauterine growth retardation, cutaneous lesions extending from ichthyosis to severe restrictive dermopathy with ectropion and eclabion, edema, microcephaly, central nervous system abnormalities, and flexion contractures. Here we report on two unrelated fetuses with an attenuated phenotype of NLS, that initially evoked Taybi-Linder syndrome. They carry biallelic pathogenic variants in the PHGDH gene. These observations expand the phenotypic continuum of L-serine biosynthesis defects, and illustrate the phenotypic overlap between NLS and microcephalic primordial dwarfism.

Response to growth hormone therapy in ring chromosome 15: Review and evidence from a new case on possible beneficial effect in neurodevelopment

Type 1 Insulin-like Growth Factor Receptor(IGF1R) plays a fundamental role in normal growth and development. Its disruption is usually characterized by severe intrauterine and postnatal growth retardation, microcephaly and neurodevelopmental delay.The efficacy of recombinant human growth hormone treatment remains a challenge for children with IGF1 resistance and pathogenic mutations of IGF1R, with limited data in patients carrying the most severe form of IGF1R defect, the ring chromosome 15. Subject and methodWe tested a high dose of rhGH in a new patient with ring chromosome 15, as confirmed by karyotype and CGH array. We performed a systematic review, and all published r(15) syndrome cases treated by growth hormone(GH) up to April 2023 were searched, and their response to GH therapy was recorded and summarized. ResultsTwelve patients with ring chromosome 15 received GH therapy according to a literature review. We expand the spectrum by the 13th case treated by GH, and we report an impressive improvement in intellectual performance and progressive catch-up growth after 5 and 20 months of follow-up. By introducing our new case in the analysis, the sex ratio was 3:10, and GH therapy was started at the age of 5.5 (3/9.4) (years) for an age of diagnosis of 4.75 (1.3/9.5) (years). The height before GH therapy was −5.1(−5.9/−4.1) SDS. The median duration of treatment was 1.7(0.9/2) (years), with a median height gain of 1(0.3/1.8) SDS and an improvement in growth velocity of 4.1(2.8/5.3) (cm/year). ConclusionGH seems to be effective for r(15) syndrome patients with short stature.

Management and survival of foetuses with trisomy 18 in a French retrospective cohort Prise en charge et survie des fœtus porteurs de trisomie 18 dans une cohorte française rétrospective.

The main objective of this study was to evaluate parents' current demands following the announcement of trisomy 18 and maternal risks. A single-centre retrospective study was performed in the Paris Saclay Foetal Medicine Department from 2018 to 2021. All patients followed up in the department who had cytogenetic confirmation of trisomy 18 were included. 89 patients were recruited. The most common malformations at ultrasound examination were cardiac or brain abnormalities, distal arthrogryposis as well as severe intrauterine growth retardation. 29% of foetuses with trisomy 18 had more than three malformations. 77.5% of patients requested medical termination of pregnancy. Among the 19 patients who chose to continue their pregnancy, 10 (52.6%) presented with obstetrical complications, of which 7 (41.2%) experienced stillbirth; five babies were born alive with no survival at 6 months. In France, in the case of foetal trisomy 18, most women request termination of pregnancy. In the post-natal period, the management of a newborn with trisomy 18 is oriented towards palliative care. The mother's risk of obstetrical complications should be part of counselling. Follow-up, support and safety should be the goal of management of these patients, regardless of the patient's choice.

Oral And Radiographic Features Of Majewski Osteodysplastic Dwarfism: A Case Report

Majewski osteodyplastic primordial dwarfism type II (MOPD II) is a rare, autosomal recessive disorder characterised by severe intrauterine and postnatal growth retardation. A case report with a distinct rare oral and radiographic feature with MOPD II is ...LAY ABSTRACTA description of a rare genetic disorder in a teenage male is provided with unique radiographic features that differ from what were previously documented in literature.

EP475: Long-term follow-up on fetuses diagnosed in second trimester with isolated single umbilical artery and normal chromosomal microarray

Fetuses diagnosed with isolated Fetal Single Umbilical Artery (iSUA), defined when no additional anatomical abnormalities are detected, and are not associated with significantly increased risk for chromosomal anomalies. However, information on their long-term outcome is lacking. The objective of the current study is to examine the long-term outcomes of fetuses diagnosed in second trimester with iSUA and normal chromosomal microarray assay (CMA). A retrospective review was conducted including all cases referred to our center with iSUA and a normal CMA between 2016 to 2020 (study group). Obstetrical and postnatal medical files were reviewed. Parents were contacted for a structured interview including neurodevelopment development assessment using Ages & Stages Questionary-3 (ASQ-3). A total of 282 cases of iSUA were referred for prenatal counseling, 48 (17%) opted to perform an invasive diagnostic test. The final study group consisted of 45 patients. Pregnancy follow-up was conducted in a dedicated clinic and included prenatal echocardiography and a 3rd-trimester malformation scan. Post-natal follow-up range was 3±2.2 years. In 9 (20%) cases of the study group additional findings were detected downstream: 4 (45%) cases prenatally (esophageal atresia, congenital anomaly of kidney, Severe Intrauterine growth retardation, and VACTERL association). Five cases (55%) showed abnormal findings only postnatally: 3 cases (6.6%) with malformations (brachial cyst and polydactyly and GLI1 pathogenic variant, sacral malformation and heterotopia due to FLNA pathogenic variant, and one case with coloboma - in assessment). 2 cases (4.4%) with functional abnormalities (one with recurrent meningitis and strabismus and one with prematurity and diplegic cerebral palsy) all being under evaluation. Two (4%) additional cases were diagnosed with neurodevelopment delay. ASQ-3 scores in all other study group participants were in the normal range. Fetuses diagnosed with iSUA and normal CMA in the second trimester are at increased risk for anatomical and functional complications including single-gene disorders. Additional findings might be disclosed in later stages of pregnancy but more importantly – can evolve postnatally only. Therefore, an extra risk should be given to the counselee and exome analysis should be considered. Further studies are required to reinforce this data

Seckel Syndrome: case report of functional motor recovery using proprioceptive neuromuscular facilitation/Kabat Method

Introduction: Seckel syndrome (SCKL) is a heterogeneous autosomal recessive disorder, the major characteristic of which is microcephalic osteodysplastic dwarfism, which is defined as severe intrauterine growth retardation, severe short stature, severe microcephaly, bird-like profile, retroverted chin and forehead, prominent nose, mental retardation and other congenital anomalies. Objective: Evaluate the therapeutic effect of proprioceptive neuromuscular facilitation/Kabat method (PNF/KM) for functional recovery in SCKL. Methods: A pre-treatment evaluation was performed, followed by an intervention involving PNF/KM. Sessions were held twice a week for ten weeks (total: 20 sessions), followed by a post-treatment evaluation. The evaluator and the therapist were blinded. The assessment instruments were Lawton & Brody's Activities of Daily Living (ADL) Scale, Disabilities of Arm, Shoulder and Hand (DASH), Short Physical Performance Battery, Timed Up and Go test and upper limb muscle strength using a digital dynamometer. Results: No significant changes were found regarding ADL Scale or DASH. However, functional gains were achieved in activities that require biomechanical and proprioceptive actions of the shoulder, arm and wrist. Regarding the Short Physical Performance Battery, improvement was found in variables that require stabilization, strength, balance and agility. An improvement was found in the execution speed of the Timed Up and Go test. An improvement in muscle strength was following the intervention. Conclusion: This study showed that the PNF/KM method was not able to improve the performance on activities of daily living, but improvements were found with regards to balance, stabilization, strength and agility of the upper limbs and lower limbs.

COVID-19 with peripartum cardiomyopathy: a case report

BackgroundThe world has been facing the novel coronavirus SARS-CoV-2 pandemic. The novel coronavirus primarily affects the lungs but also affects multiple organ systems including the cardiovascular system causing myocarditis, cardiomyopathy, and arrhythmias. Cardiomyopathy has been reported in patients with COVID-19; however, prognosis of peripartum cardiomyopathy in a patient with COVID-19 is still unexplored. More knowledge is required to understand the incidence of cardiomyopathy due to novel coronavirus SARS-CoV-2.Case presentationWe report a case of peripartum cardiomyopathy gravida 2 parity 2 COVID-19 confirmed patient who underwent an emergency preterm lower segment caesarean section (LSCS) for severe pre-eclampsia and intra-uterine growth retardation (IUGR) and landed up in acute congestive cardiac failure with pulmonary oedema. A postpartum 32 years female presented to our institute, a dedicated COVID-19 hospital with tachycardia, hypertension, anasarca, tachypnea with desaturation on room air. She had undergone emergency caesarean section for severe preeclampsia with intrauterine growth retardation. On post-operative day 2 (POD2), she complained of shortness of breath. On POD 3 she tested positive RT-PCR for COVID-19 infection. She responded to treatment with steroids. However, on POD6, She developed severe pulmonary oedema with poor ejection fraction necessitating endotracheal intubation and pressure control ventilation. Congestive cardiac failure was managed with diuretics and digoxin. Gradually oxygenation improved. She was electively ventilated for 3 days. Gradually, ejection fraction improved with the resolution of B lines. On the 9th POD, after a successful spontaneous breathing trial, she was extubated and non-invasive ventilation with bi-level positive airway pressure was attached. The patient was gradually tapered off of the non-invasive ventilation over 2 days. On the 11th post-operative day, she was maintaining oxygen saturation on nasal prongs and was sent to the ward.ConclusionsWe recommend early use of bedside lung ultrasonography; echocardiography and close cardiovascular monitoring in severe COVID-19 infected pregnant patients who present with shortness of breath, tachypnea, and hypertensive disorders of pregnancy and previous cardiac abnormalities for expedite management and improved prognosis. An ideal case scenario for extubation may not be present, non-invasive ventilation with bi-level positive airway pressure post-extubation helps in patients with peripartum cardiomyopathy.

A Case Study of Oxcarbazepine-induced Stevens-johnson Syndrome

Background: Stevens–Johnson syndrome is a rare potentially fatal disorder characterized by mucosal membrane erosions, bullous skin lesions and epidermal detachment.
 Objective: This case report discusses a case of a patient who developed seizures and macular rashes as a result of Stevens–Johnson syndrome induced by oxcarbazepine.
 Case presentation: An eight-year-old girl was admitted to hospital with complaints of seizure episodes that occurred during sleep, characterized by drooling, jerky stiff upper limbs, throat sounds, and blue lips. Patient was born with severe intrauterine growth retardation and microcephaly and was diagnosed with congenital cytomegalovirus (CMV). EEG results confirmed that focal epilepsy was the underlying cause of seizures. The patient was given oxcarbazepine as an anticonvulsant medication after confirming epilepsy diagnosis. However, after two weeks of treatment, patient developed rashes and skin lesions all over her body except hands. These skin lesions and rashes were red and tan in color, swollen, itchy, scaly, dry, popular, macular and patchy. The skin detachment was less than 10% of BSA (body surface area). The Naranjo algorithm was used to check the probability of a drug reaction and through the WHO-UMC criteria for causality, it was decided that oxcarbazepine induced the syndrome. Hence, patient was diagnosed as a case of Stevens-Johnson syndrome.
 Conclusion:Stevens–Johnson syndrome is a rare condition that can cause rashes and epidermal detachment. It can be caused by adverse effects of medications; however, exact pathogenesis is unknown. Therefore, studies on large number of patients are required to understand the pathogenesis of oxcarbazepine-induced SJS.

Epigenotype, Genotype, and Phenotype Analysis of Taiwanese Patients with Silver-Russell Syndrome.

Background: Silver–Russell syndrome (SRS) is a clinically and genetically heterogeneous disorder characterized by severe intrauterine growth retardation, poor postnatal growth, characteristic facial features, and body asymmetry. Hypomethylation of the imprinted genes of the chromosome 11p15.5 imprinting gene cluster and maternal uniparental disomy of chromosome 7 (mUPD7) are the major epigenetic disturbances. The aim of this study was to characterize the epigenotype, genotype, and phenotype of these patients in Taiwan. Methods: Two hundred and six subjects with clinically suspected SRS were referred for diagnostic testing, which was performed by profiling the methylation of H19-associated imprinting center (IC) 1 and the imprinted PEG1/MEST region using methylation-specific multiplex ligation-dependent probe amplification and high-resolution melting analysis with a methylation-specific polymerase chain reaction assay. We also applied a whole genome strategy to detect copy number changes and loss of heterozygosity. Clinical manifestations were recorded and analyzed according to the SRS scoring system proposed by Bartholdi et al. Results: Among the 206 referred subjects, 100 were classified as having a clinical diagnosis of SRS (score ≥ 8, maximum = 15) and 106 had an SRS score ≤ 7. Molecular lesions were detected in 45% (45/100) of the subjects with a clinical diagnosis of SRS, compared to 5% (5/106) of those with an SRS score ≤ 7. Thirty-seven subjects had IC1 hypomethylation, ten subjects had mUPD7, and three subjects had microdeletions. Several clinical features were found to be statistically different (p < 0.05) between the “IC1 hypomethylation” and “mUPD7” groups, including relative macrocephaly at birth (89% vs. 50%), triangular shaped face (89% vs. 50%), clinodactyly of the fifth finger (68% vs. 20%), and SRS score (11.4 ± 2.2 vs. 8.3 ± 2.5). Conclusions: The SRS score was positively correlated with the molecular diagnosis rate (p < 0.001). The SRS subjects with mUPD7 seemed to have fewer typical features and lower SRS scores than those with IC1 hypomethylation. Careful clinical observation and timely molecular confirmation are important to allow for an early diagnosis and multidisciplinary management of these patients.

A 24-Year-Old Woman First Diagnosed as a Sickle Cell Anemia during her Second Pregnancy: A Case Report

Introduction: Sickle cell anemia (SCA) is generally diagnosed in the early childhood and the disease is usually diagnosed in the first years of life by its clinical manifestations. The crises of this disease worsens during pregnancy. In this report, a 24-year-old pregnant woman with gestational age of 29 weeks and six days, G2P2A0L1, is presented. She complained of severe back and lower extremity pain. Considering the refractory pain, severe anemia, and absence of delivery process signs, further tests detected SCA for her. Preterm termination of pregnancy were performed by cesarean section regarding severe non-controlled pain, severe IUGR (intrauterine growth retardation), severe oligohydramnios, and previous caesarian section. A female baby was born with Apgar score of 8 and a birth weight of 1250 grams. Considering the high probability of vascular occlusion crisis and severe anemia associated with SCA during pregnancy, it is reasonable to seek sickle cells in all the pregnant patients with severe unexplained anemia or pain.

Pravastatin is useful for prevention of recurrent severe placenta-mediated complications – a pilot study

Background Preeclampsia with severe features and other severe placenta-mediated complications may be life threatening to mother and fetus, especially when they are recurrent. Recurrence of pregnancy complications is common, however, when combined treatment with low molecular weight heparin and low dose aspirin fails, there are not any proven therapeutic options for prevention of recurrence of obstetrical complications. Objective We aimed to determine the impact of adding pravastatin to low molecular weight heparin and low dose aspirin for improving pregnancy outcome in women with severe recurrent placenta-mediated complications. Design A retrospective study of 32 women with severe recurrent placenta-mediated complications (preeclampsia with severe features, placental abruption, severe intrauterine growth retardation or intra uterine fetal death) in spite of treatment with low molecular weight heparin and low dose aspirin in previous pregnancy. All women were treated in the index pregnancy with 20 mg pravastatin starting at 12 weeks, with low molecular weight heparin and low dose aspirin. Antiphospholipid syndrome was evident for 10 of the 32 women. Results In the index pregnancy, only one woman had recurrence of severe placenta-mediated complications. Gestational age at delivery in the index pregnancy compared to previous pregnancy when women were treated with low molecular weight heparin and low dose aspirin was 36.5 ± 1.7 vs. 32 ± 3.6 weeks, and mean birth weight 2691 ± 462 vs. 1436 ± 559 grams, compared to previous pregnancy when women were treated with low molecular weight heparin and low dose aspirin (p < .001 for both). Of the 17 women with previous preeclampsia with severe features, 15 had no recurrence of preeclampsia and 2 women had mild preeclampsia at term. Of the 8 women with previous severe intrauterine growth retardation, all delivered at significant higher gestational age compare to previous pregnancy, [37.0 ± 1 vs. 34 ± 3 weeks, (p < .05)] with higher mean birth-weight [2648 ± 212 vs. 1347 ± 465 grams, (p = .05)]. Of the 3 women with previous placental abruption, one delivered at 32 weeks due to non-reassuring fetal heart monitoring, one woman was delivered at 36 weeks due to mild preeclampsia, and one woman underwent elective induction of labor at 37 weeks with no intrauterine growth retardation. Of the 4 women with previous recurrent intrauterine fetal death, 3 women delivered at 37 weeks after elective induction, and one woman at 30 weeks with a birthweight of 960 grams due to severe intrauterine growth retardation. Conclusions Additive treatment with pravastatin to low molecular weight heparin and low dose aspirin may be a promising option in cases of previous severe recurrent placenta-mediated complications.

Use of infrared thermography to noninvasively assess neonatal piglet temperature.

Hypothermia is risk factor for piglet neonatal mortality, especially for low birth weight piglets. Piglets with intrauterine growth retardation (IUGR) also have a higher mortality risk at birth. This study aimed to validate infrared thermography (IRT) as an alternative to rectal temperature (RT) to measure piglet temperature in the hour postpartum, and to identify piglets with thermoregulation difficulties. At birth (6.3 ± 0.35 min postpartum), 67 piglets were dried, weighed, scored for growth retardation (IUGR; 0–3), and isolated in a plastic box where IRT images were taken, followed by RT. Piglets were then returned to the farrowing pen, and the process repeated at 15, 30, and 60 min postpartum. Piglets were ranked according to their weight (quartiles: 0.57–1.27 kg, 1.27–1.5 kg, 1.5–1.74 kg, 1.74–2.44 kg). Temperatures (ear base and tip; minimum, maximum and average of back) were extracted from IRT images (Thermacam Researcher Pro 2.0). Pearson correlations between temperature measures were calculated, and the effect of time, IUGR score, and weight were included in linear mixed models (SAS 9.4). RT was correlated with all IRT data across time points (P < 0.05); correlations were strongest with the ear base, and weakest with the ear tip and minimum back temperature. Both IUGR score and weight rank affected ear base (P < 0.05) and RTs (P < 0.05). The lightest piglets, and piglets with severe IUGR had the lowest temperature, relative to their counterparts. Indeed, differences between all weights categories were significant for RT. Piglets with the lowest weight (0.27–1.27 kg) had lower ear base temperatures than piglets in the third quartile (1.5–1.74 kg; 35.2 ± 0.36 °C vs. 36.5 ± 0.35 °C, t64.9 = −4.51, P < 0.001) and the heaviest piglets (1.74–2.44 kg; 35.2 ± 0.36 °C vs. 36.4 ± 0.36 °C, t70.4 = −3.97, P < 0.005). Overall, piglets with severe IUGR (score 3) had a lower RT than normal piglets (score 0; 35.8 ± 0.46 °C vs. 37.2 ± 0.42 °C, t43.1 = 3.16, P < 0.05) and piglets with mild IUGR (score 1; 35.8 ± 0.46 °C vs. 37.1 ± 0.40 °C, t45.3 = 2.92, P < 0.05); and they also had lower temperature at the base of the ear than normal piglets (35.1 ± 0.42 °C vs. 36.3 ± 0.36 °C, t63.1 = 3.01, P < 0.05). These results confirmed that IRT is an interesting noninvasive tool for assessing neonatal piglets’ thermoregulatory abilities and could be used in research investigating successful interventions for piglets at risk of hypothermia.

Maternal UPD of chromosome 7 in a patient with Silver‐Russell syndrome and Pendred syndrome

BackgroundSilver‐Russell syndrome (SRS) is a heterogeneous imprinting disorder featuring severe intrauterine and postnatal growth retardation and dysmorphic features. Pendred syndrome (PDS) is an autosomal recessive disorder caused by mutations in the SLC26A4 gene characterized by sensorineural hearing loss.MethodsKaryotyping analysis was performed to investigate any chromosomal abnormalities. Whole‐genome copy number variation and loss of heterozygosity were analyzed using an Affymetrix CytoScan 750 K Microarray. Variant screening was performed by targeted next‐generation sequencing on all known deafness‐causing genes.ResultsThe proband was a patient with SRS caused by maternal uniparental disomy 7. The PDS of the proband was caused by homozygous variant c.919‐2A > G of SLC26A4; both mutated alleles were inherited from his mother.ConclusionThis is the first report of uniparental disomy 7 leading to SRS and Pendred syndrome. Patients with intrauterine growth retardation or those born small for gestational age and exhibiting postnatal growth failure should undergo molecular testing to reach a clinical diagnosis.

Congenital diabetes mellitus.

Congenital diabetes mellitus is a rare disorder characterized by hyperglycemia that occurs shortly after birth. We define "Diabetes of Infancy" if hyperglycemia onset before 6 months of life. From the clinical point of view, we distinguish two main types of diabetes of infancy: transient (TNDM), which remits spontaneously, and permanent (PNDM), which requires lifelong treatment. TNDM may relapse later in life. About 50% of cases are transient (TNDM) and 50% permanent. Clinical manifestations include severe intrauterine growth retardation, hyperglycemia and dehydration. A wide range of different associated clinical signs including facial dysmorphism, deafness and neurological, cardiac, kidney or urinary tract anomalies are reported. Developmental delay and learning difficulties may also be observed. In this paper we review all the causes of congenital diabetes and all genes and syndromes involved in this pathology. The discovery of the pathogenesis of most forms of congenital diabetes has made it possible to adapt the therapy to the diagnosis and in the forms of alteration of the potassium channels of the pancreatic Beta cells the switch from insulin to glibenclamide per os has greatly improved the quality of life. Congenital diabetes, although it is a very rare form, has been at the must of research in recent years especially for pathogenesis and pharmacogenetics. The most striking difference compared to the more frequent autoimmune diabetes in children (type 1 diabetes) is the possibility of treatment with hypoglycemic agents and the apparent lower frequency of chronic complications.

Pregnancy during chronic hemodialysis. A series of cases

Pregnancies in women with end stage renal failure are uncommon. However, correction of anemia and improvement in dialysis techniques increases the rate of successful pregnancies. To describe a 16 years' experience treating pregnant women on hemodialysis and to analyze maternal-fetal outcomes. Observational study of a dialysis center historical cohort in a university hospital, between 2001 and 2016. Thirteen pregnancies were found in 11 women aged 23 to 32 years, 77% on dialysis prior to pregnancy. Residual diuresis was 1,300 [625-1,575] mL in 24 hrs. The baseline hemoglobin was 9.0 [7.6-9.9] g/dL and 92% of patients did not use contraception. The pre-dialysis blood urea nitrogen was 34 [29-36] mg /dL. An ultrasound to confirm pregnancy was done in all. At 23 [14-25] weeks of pregnancy, dialysis hours were increased, reaching 24 [19.5-24.0] hours per week. The most common complications were severe arterial hypertension (54%), severe anemia (46%), polyhydramnios (31%) and severe intrauterine growth retardation (IUGR) (23%). The median time of pregnancy at delivery was 34 [29-34] weeks. Neonatal median hospitalization length was 4 [4-32] days, with 18% of neonatal deaths. Pregnancies in dialysis are no longer exceptional. Despite better maternal and fetal outcomes, morbidity and mortality remains higher than in the normal population, which makes multidisciplinary management essential.

Search for cis-acting factors and maternal effect variants in Silver-Russell patients with ICR1 hypomethylation and their mothers.

Silver-Russell syndrome is an imprinting disorder characterized by severe intrauterine and postnatal growth retardation. The majority of patients show loss of methylation (LOM) of the H19/IGF2 IG-DMR (ICR1) in 11p15.5. In ~10% of these patients aberrant methylation of additional imprinted loci on other chromosomes than 11 can be observed (multilocus imprinting defect - MLID). Recently, genomic variations in the ICR1 have been associated with disturbed methylation of the ICR1. In addition, variants in factors contributing to the life cycle of imprinting are discussed to cause aberrant imprinting, including MLID. These variants can either be identified in the patients with imprinting disorders themselves or in their mothers. We performed comprehensive studies to elucidate the role of both cis-acting variants in 11p15.5 as well as of maternal effect variants in the etiology of ICR1 LOM. Whereas copy number analysis and next generation sequencing in the ICR1 did not provide any evidence for a variant, search for maternal effect variants in 21 mothers of patients with ICR1 LOM identified two carriers of NLRP5 variants. By considering our results as well as those from the literature, we conclude that the causes for epimutations are heterogeneous. MLID might be regarded as an own etiological subgroup, associated with maternal effect variants in NLRP and functionally related genes. In addition, these variants might also contribute to LOM of single imprinted loci. Furthermore, genomic variants in the patients themselves might result in aberrant methylation patterns and need further investigation.

LDL-apheresis to decrease sFlt-1 during early severe preeclampsia: Report of two cases from a discontinued phase II trial

ObjectiveSevere preeclampsia may require the delivery of the placenta to avoid life-threatening complications for the mother. Before 26 weeks of gestation, this often results in perinatal death. A decrease in soluble fms-like tyrosine kinase 1 (sFlt1), an anti-angiogenic factor central to the pathophysiology of the maternal syndrome, has been reported after LDL- apheresis. The present study tested whether LDL-apheresis could be used to allow women with early and severe preeclampsia to reach a gestational age where the baby had a viable chance of survival. Study DesignA phase II prospective study. Adult women were included if they had very early (<26 weeks of gestation) preeclampsia without severe (<5th percentile) intra-uterine growth retardation. Treatment consisted of two weekly sessions (90 min each) of LDL-apheresis of whole blood. The primary endpoint was the status of the baby (dead or living) at 6 months post-delivery. Sample size and stopping rules were calculated assuming a desired success rate of at least 90%. ResultsThe study was interrupted for safety reasons after the inclusion of two patients: both developed secondary uncontrolled hypertension and blurred vision during the first week of treatment. The first neonate, born at 25 + 3 weeks of gestation, died of sepsis at day 5; the second, born at 26 + 2 weeks of gestation, is still alive and well. In these two patients, the impact of apheresis sessions on sFlt1 concentrations was inconsistent. ConclusionLDL-apheresis did not result in the prolongation of pregnancy in this phase II trial. Further studies will be needed to delineate the appropriate contours of this therapeutic strategy.

Prenatal diagnosis of Wolf-Hirschhorn syndrome: Ultrasonography and molecular karyotyping results

ObjectiveTo present the experience on prenatal diagnosis of Wolf-Hirschhorn syndrome (WHS) to further delineate the fetal presentation of this syndrome. Study designThis was a retrospective analysis of ten pregnancies with fetal WHS identified by chromosomal microarray (CMA). Clinical data were reviewed for these cases, including maternal demographics, indications for invasive testing, sonographic findings, CMA results and pregnancy outcomes. ResultsThree cases were diagnosed at the first trimester because of an increased NT or cystic hygroma. The remaining seven cases were identified at late gestation for abnormal ultrasound findings. CMA revealed 4p deletions to be terminal in all of the ten cases. Deletion sizes ranged from 2.05 to 19.02 Mb. ConclusionPrenatal findings such as increased NT, severe and early onset intrauterine growth retardation, and renal dysplasia or oligohydramnios should warrant the diagnosis of WHS and invasive testing using CMA.

The ameliorative role of curcumin on the morphological and skeletal malformations induced by betamethasone in rat fetuses

Among the glucocorticoids, betamethasone has become very popular, being more commonly used for a number of diseases, to promote organ maturation and to prevent preterm delivery. This work aimed to examining the possible morphological and skeletal malformations induced by betamethasone in fetuses of albino rats and the role of curcumin as antioxidant against these adverse effects. Administration of betamethasone during the organogenesis phase at a dose equivalent to its human counterpart led to severe intrauterine growth retardation relative to the control group as it affected the growth parameters of the fetuses including reduction in length and weight. In addition, various malformations were detected in the skin, head, trunk, limbs and tail. Exencephaly, mandibular hypoplasia, and retarded ossification were the most evident endo-skeletal malformations observed in the fetuses maternally injected with betamethasone. A marked improvement in fetal growth in terms of shape, length, weight and skeleton was recorded in fetuses maternally injected with betamethasone followed by curcumin.

P 51 Improvement of utero-placental and feto-placental perfusion by Pentaerythrityltetranitrate (PETN) in pregnancies with impaired uterine perfusion in mid-gestion

Introduction In pregnancies complicated by impaired placental perfusion the NO-donor pentaeritrithyltetranitrate (PETN) has been shown to reduce the risk to develop severe intrauterine growth retardation and perinatal death by 39%. The shown effect is most likely based on the vasodilatative effect of PETN. Reduction of resistance in the uterine arteries alone might worthen fetal outcome when accompanied by low perfusion-pressure in the fetal circulation. Here we present the uterine and fetal Doppler parameters assessed during the PETN-trial. Patients and methods 111 pregnancies presenting with abnormal placental perfusion at mid-gestation have been included in the trial. 54 women received PETN while 57 received placebo. Doppler velocimetry measurements of uteroplacental and fetal vessels were monitored biweekly. Results Within the first week of intake, PETN improved uteroplacental perfusion (mean PI 1.26 + 0.36 vs. 1.49 + 0.44; p 0.01). In the PETN group the relative risk for absent or reverse flow in the umbilical artery was 0.565 (0.155-2.066) and 0.580 (0.129-2.606) respectively, for the development of brain sparing 0.488 (0,137-1,737) and for occurrence of a cerebrovascular ratio 1 0.425 (0.194-0.930). Conclusion The profound effect on uteroplacental and fetoplacental perfusion fortifies the positive impact of PETN in pregnancies complicated by impaired placental perfusion.