Abnormal Babies Research Articles

O-154 Chromosomal, gestational, and neonatal outcomes of mosaic embryos: analysis of 3074 cases from the international registry of mosaic embryo

Abstract Study question Which are the clinical outcomes and post-natal results of mosaic embryos with low and high-level of mosaicism? Summary answer The level of mosaicism negatively influences implantation and ongoing pregnancy rate. 6/7 cases in which mosaicism persisted in the foetuses were from low-level mosaic. What is known already Chromosomal mosaic embryos are characterized by the presence of chromosomally different cell lines within the same embryo. While the transfer of these embryos is now offered as an option for women who undergo in vitro fertilization (IVF), several concerns remain. For instance, the limited data on pregnancy outcome and the possibility that intra-biopsy mosaicism in the TE is a poor predictor of the ploidy status of the ICM. Therefore, some argue that mosaicism should be not reported until a clear classification of such embryos in relation to their reproductive potential has been defined. Study design, size, duration We collected the clinical outcomes of 3074 mosaic embryos transferred in women who underwent IVF between May 2019-May 2023. All embryos were cultured to blastocyst stage; trophectoderm (TE) biopsy was performed on Day-5 of development or Day6/7 for slow-growing embryos. The clinical outcome obtained after the transfer of mosaic embryos with the different chromosomal constitutions was compared with each other. Prenatal and post-natal outcomes were collected for available cases. Participants/materials, setting, methods Preimplantation genetic testing (PGT) was performed using high-resolution next-generation sequencing (NGS) methodology. TE biopsies were classified as mosaic if they had 20%-80% abnormal cells. For statistical analysis, mosaic embryos were divided into groups based on mosaic levels and chromosomal constitution detected in TE: single mosaic aneuploidy (monosomy/trisomy; SM), double mosaic chromosomes (monosomy/trisomy or combination, DM), complex mosaic aneuploidy (>2 different aneuploidies; CM) and mosaic segmental aneuploidy (single and double deletion/insertion >5Mb, MS). Main results and the role of chance Embryos classified as ‘low-mosaic’ by NGS-based PGT-A have a higher likelihood of achieving implantation compared to ‘high-mosaic’ embryos (48% vs. 39.%; p < 0.05 ), as well as ongoing pregnancy/live birth (40% vs. 29%; p < 0.05). Chromosomal composition of mosaicism abnormalities dictates the success rate of mosaic embryo transfers, with low and high segmental mosaics being preferable over low- and high-mosaics involving whole chromosomes. For 621/670 pregnancies, parental tests and post-natal data were available. The majority (99.75%) of the babies were largely healthy by routine physical inspection by neonatologists (no gross abnormalities in babies from mosaic embryos, n = 495). A combination of NIPT, CVS, and Amniocentesis prenatal testing results were collected for 552 pregnancies of mosaic embryo transfers, with predominantly normal findings. The mosaicism detected at the embryonic stage by PGT-A was reflected in prenatal testing in only 7 out of 552 pregnancies (0.9%), in which the mosaicism identified with PGT-A at the blastocyst stage was reflected in gestation by prenatal chromosomal testing as true fetal mosaicism. Limitations, reasons for caution Additional clinical data must be obtained to evaluate the contribution of each different chromosome before this approach can be evaluated as an additional tool to choose mosaic embryos for transfer. Wider implications of the findings The international registry of mosaic embryo transfers continues to grow in sample size, in turn increasing the power of analysis. The findings of the mosaic embryo transfer registry can help educate the management and selection of embryos in the clinic. Trial registration number no

Seroprevalence of Toxoplasma gondii among Aborted Women Admitted to Erbil Maternity Teaching Hospital

Background: Toxoplasma gondii is an obligate intracellular parasite responsible for causing congenital toxoplasmosis. Congenital infection during the first and second trimesters of pregnancy may result in spontaneous abortion, mental retardation, and cerebral calcifications, while the severity of fetal damage is decreased during the third trimester.
 
 Objectives: This study aimed to determine the seroprevalence of toxoplasmosis and its association with clinical-obstetric determinants and sociodemographic factors in aborted women.
 
 Materials and Methods: The present study was a Hospital-based Cross-sectional Study comprised 100 women who admitted to Erbil Maternity Hospital with a spontaneous abortion. A questionnaire was filled by the researchers after verbal consent, and 5 ml of venous blood was collected from each participant, centrifuged at 3500 rpm, and stored in 2 Eppendorf tubes, and tested by ELISA and Electrochemiluminescence Immunoassay by Cobas e 411 for Toxoplasma IgG and IgM according to Manufacturer’s instructions.
 
 Results: The highest seroprevalence for toxoplasmosis was observed in illiterate females aged 26-35 and living in Erbil City's urban areas. A statistically significant association was recorded regarding seropositivity to Toxoplasma IgG and having a history of abnormal babies (P=0.023), Toxoplasma IgG seropositivity and a history of having toxoplasmosis (P=0.016), and seropositivity to Toxoplasma IgM and parity of the females (P=0.037).
 
 Conclusions: Screening for toxoplasmosis during pregnancy is crucial for all women for the prevention of disease progression. Although there are various screening methods for the detection of toxoplasmosis, not all the methods are applicable and financially suitable for the patients.

Triple repeated fetal congenital heart disease linked to PLD1 mutation: a case report

BackgroundCongenital heart disease occurs in approximately 1 in 100 cases. Although sibling occurrence is high (3–9%), the causative genes for this disease are still being elucidated. PLD1 (Phospholipase D1) is a recently discovered gene; however, few case reports have been published on it. In this report, we describe a case of triplicate fetal congenital heart disease that was diagnosed as a PDL1 mutation. Our objective is to explore the clinical manifestations of PLD1 mutations in this particular case.Case presentationA 32-year-old Japanese woman (gravida, para 0) was introduced since fetus four chamber view was not clear and was diagnosed with ductus arteriosus-dependent left ventricular single ventricle and pulmonary atresia at 21 weeks and 1 day of gestation during her first pregnancy. Artificial abortion using Gemeprost was performed at 21 weeks and 5 days of gestation. The second pregnancy was diagnosed as pulmonary atresia with intact ventricular septum with cardiomegaly, a cardiothoracic area ratio of more than 35%, and a circulatory shunt at 13 weeks and 3 days of gestation. Subsequently, intrauterine fetal death was confirmed at 14 weeks and 3 days of gestation. Regarding the third pregnancy, fetal ultrasonography at 11 weeks and 5 days of gestation showed mild fetal hydrops and moderate tricuspid valve regurgitation. At 16 weeks and 5 days of gestation, the fetus was suspected to have a left ventricular-type single ventricle, trace right ventricle, pulmonary atresia with intact ventricular septum, or cardiomyopathy. Cardiac function gradually declined at 26 weeks of gestation, and intrauterine fetal death was confirmed at 27 weeks and 5 days of gestation. The fourth pregnancy resulted in a normal heart with good progression and no abnormal baby. We submitted the first and second fetuses’ umbilical cord, third fetus’ placenta, and the fourth fetus’ blood to genetic testing using whole exome analysis with next generation sequencing. Genetic analysis identified hemizygous PLD1 mutations in the first, second, and third fetuses. The fourth fetus was heterozygous. In addition, the parents were heterozygous for PLD1. This case is based on three consecutive cases of homozygosity for the PLD1 gene in the sibling cases and the fetuses with recurrent right ventricular valve dysplasia. This will elucidate the cause of recurrent congenital heart disease and intrauterine fetal death and may serve as an indicator for screening the next fetus. To date, homozygous mutations in PLD1 that repeat three times in a row are not reported, only up to two times. The novelty of this report is that it was repeated three times, followed by a heterozygous live birth.ConclusionsThis report is consistent with previous reports that mutations in PLD1 cause right ventricular valve dysplasia. However, there have been few case reports of PLD1 mutations, and we hope that this report will contribute to elucidate the causes of congenital heart disease, especially right ventricular valve dysplasia, and that the accumulation of such information will provide more detailed information on PLD1 mutations in heart disease.

O-076 Update on the International Registry of Mosaic Embryo Transfers

Abstract Study question Which are the results obtained by the International Registry of Mosaic Embryo Transfers? Summary answer An update of clinical outcomes and post-natal results of mosaic embryos with low and high-level of mosaicism is provided. What is known already Chromosomal mosaic embryos are characterized by the presence of chromosomally different cell lines within the same embryo. While the transfer of these embryos is now offered as an option for women who undergo in vitro fertilization (IVF), several concerns remain. For instance, the limited data on pregnancy outcome and the possibility that intra-biopsy mosaicism in the TE is a poor predictor of the ploidy status of the ICM. Therefore, some argue that mosaicism should be not reported until a clear classification of such embryos in relation to their reproductive potential has been defined. Study design, size, duration We collected the clinical outcomes of 2045 mosaic embryos transferred in women who undergoing IVF between May 2019-May 2022. All embryos were cultured to blastocyst stage; trophectoderm (TE) biopsy was performed on Day-5 of development or Day6/7 for slow-growing embryos. The clinical outcomes obtained after the transfer of mosaic embryos with the different chromosomal constitutions were compared. Prenatal and post-natal outcome was collected for available cases. Participants/materials, setting, methods Preimplantation genetic testing for aneuploidies (PGT-A) was performed using high-resolution next-generation sequencing (NGS) methodology. TE biopsies were classified as mosaic if they had 20%-80% abnormal cells. For statistical analysis, mosaic embryos were divided into groups based on mosaic levels and chromosomal constitution detected in TE: single mosaic aneuploidy (monosomy/trisomy; SM), double mosaic chromosomes (monosomy/trisomy or combination, DM), complex mosaic aneuploidy (>2 different aneuploidies; CM) and mosaic segmental aneuploidy (single and double deletion/insertion >5Mb, MS). Main results and the role of chance Embryos classified as ‘low-mosaic’ by NGS-based PGT-A have a higher likelihood of achieving implantation compared to ‘high-mosaic’ embryos (48% vs. 39.%; p < 0.05 ), as well as ongoing pregnancy/live birth (40% vs. 29%; p < 0.05). Chromosomal composition of mosaicism abnormalities dictates the success rate of mosaic embryo transfers, with low and high segmental mosaics being preferable over low- and high-mosaics involving whole chromosomes. For 550/670 pregnancies, parental tests and post-natal data were available. The majority (99.75%) of the babies were largely healthy by routine physical inspection by neonatologists (no gross abnormalities in babies from mosaic embryos, n = 495). Prenatal testing performed on pregnancies from mosaic embryo transfers were generally normal. The mosaicism detected at the embryonic stage by PGT-A was reflected in prenatal testing in only 5 out of 550 pregnancies (0.9%) in which the mosaicism identified with PGT-A at the blastocyst stage was reflected in gestation by prenatal chromosomal testing as true fetal mosaicism. Limitations, reasons for caution Additional clinical data must be obtained to evaluate the contribution of each different chromosome before this approach can be evaluated as an additional tool to choose mosaic embryos for transfer. Wider implications of the findings The International Registry of Mosaic Embryo transfers continues to grow in sample size, in turn increasing the power of analysis. The findings of the mosaic embryo transfer registry can help educate the management and selection of embryos in the clinic. Trial registration number Not applicable

Kerstin Hellwig: educating on multiple sclerosis and pregnancy

Kerstin Hellwig: educating on multiple sclerosis and pregnancy

The Relationship between Nutritional Status (Body Mass Index) of Three Pregnant Women with Estimated Fetal Weight

Many third trimester pregnant women experience problems related to nutritional status that affect the growth and development of their fetus. This study aims to determine the relationship between Body Mass Index (BMI) and Estimated Fetal Weight (TBJ). This research method uses an analytical survey method.Populationi in this study were third trimester pregnant women.Amount Samples were 72 third trimester pregnant women selected by accidental sampling who met the inclusion criteria. Using the Chi-Square test, the results obtained were p=0.004 (p<0.05). This shows that there is a significant relationship between body mass index and estimated fetal weight at UPT Puskesmas Watampone. The final conclusion of the researchers is that mothers pay more attention to fulfilling nutrition during pregnancy to prevent births with abnormal baby weights.

Prevalence and Pattern of Birth Defects in a Tertiary Care Hospital in Bangladesh

Background: Birth Defect is one of the most important causes of neonatal mortality and morbidity worldwide. The pattern and prevalence of Birth Defects may vary overtime or with geographic location. The objective of the study to determine the prevalence and pattern of Birth Defects in live newborn admitted in Hospital.
 Materials & Methods: This cross-sectional descriptive study was carried in Neonatology and OBS-gynae department of Sir Salimullah Medical college Hospital during the period of July 2016 to December 2019. A total 306 babies with Birth Defects were examined and detailed history for any risk factor was taken. A through physical examination was performed. Confirmation of internal defect was done by various imaging modalities; i.e, radiography, ultrasound, echocardiography and CT scan. A detailed history was taken regarding maternal age, gestational age and previous delivery of abnormal baby.
 Results: During this period total 27799 was born alive, of which 306 had Birth Defects, the prevalence of Birth Defects was 1.1%. The predominant system involved was Musculoskeletal system (30%) followed by CNS (19%), oro-facial clefts (13%), GIT, CVS, Ear-nosethroat( 7%) and least involved system was urinary system(4%). Talipes was most common one in musculo-skeletal system defect and Anencephaly in CNS defect.
 Conclusion: Prevalence of Birth Defects is common among newborn admitted in hospital and musculoskeletal system is most commonly affected system. Birth Defects is upcoming issue in current newborn situation which need to be prioritized.
 Sir Salimullah Med Coll J 2022; 30: 23-28

Adverse Short-Term Outcomes of Preterm Infants Born to Mothers with Preeclampsia by Doppler Cranial Ultrasound Investigation

Objective: In preeclampsia, abnormal fetal hemodynamics changes can be detected by Doppler ultrasound and predicted the perinatal outcome. But seldom studies focus on these preterm neonate’s hemodynamics changes during 72 hours after birth and the adverse short-term outcomes. The present study is planned to assess the parameters of middle cerebral arteries and associate the short-term outcome at 37 weeks early term age in pregnancies complicated by preeclampsia. Methods: A total of 114 preterm neonates were included. The Doppler cranial ultrasound was performed to bilateral middle cerebral arteries within 12 - 24 hours, 36 - 48 hours, 60 - 72 hours after birth for all the eligible study neonates. The parameters of resistive index (RI), resistive index (PI) and middle cerebral velocity (MBFV) were recorded by Doppler cranial ultrasound and 106 infants survived assessed by the Neonatal Behavioral Neurological Assessment (NBNA) at 37 weeks early term-equivalent age. Results: There were a total of 106 subjects that finally completed the NBNA examination at 37 weeks of early term-equivalent age. In the surviving infants, there were a total of 26 infants with abnormal NBNA scores, among them, 12 infants’ mothers were diagnosed with preeclampsia, accounting for up to 46.1%. In these preterm neonates, the lower velocity of bilateral middle cerebral arteries was observed in abnormal infants (p < 0.05) and the lowest velocity was observed in these abnormal babies with preeclampsia (p < 0.05). Conclusion: Velocity of middle cerebral artery is significantly abnormal in preeclampsia. The slower velocity in the 72 hours after birth, the higher associated with adverse perinatal short-term outcome.

A Detailed Biological Approach on Hormonal Imbalance Causing Depression in Critical Periods (Postpartum, Postmenopausal and Perimenopausal Depression) in Adult Women

Background:In today's global world, most women are experiencing midlife health problems which can affect their lives and mental status. Most of the diseases occurr after childbirth and during pregnancy or gestation period which can lead to severe problems such as postpartum depression (PPD), postmenopausal depression, perimenopausal depression which ultimately affects the mental health condition and develop various depressive episodes which ultimately lead to depression in women.Objective:The review paper gives the information that if there is untreated maternal depression then it can lead to anxiety, fear, negative effect on child development, disruption of the mother-infant relationship, and the occurrence of depressive symptoms in the early life of infants. Hormone levels are changed at the time of pregnancy.Methods:The data was collected by studying combination of research and review papers from different databases like PubMed, Medline, and Web of science by using search keywords like “Postpartum depression”, “Postmenopausal depression”, “Risk factors”, “Pathogenesis of PPD”, “Predictors of postpartum depression”.Results:This can lead to disrupting the quality of life of menopausal women like deficiency of nutrients, not properly regular physical activities, elevated Body Mass Index (BMI), loss of libido (loss of interest in sexual activities), due to the lack of education, and awareness among the people. Factors like increase in physical activity can naturally help in PPD condition. Mind body therapy, drug therapy and cognitive and mindfulness-based therapies help in hormonal imbalances.Conclusion:It was found that low birth weight and congenital abnormalities in babies lead to affect depression after delivery. It is recommended that health care providers and physicians are provided with information regarding factors contributing PPD and postmenopausal depression. Sleep timings and consumptions of nutraceuticals can help in natural healing with depression amongst women suffering from postpartum, postmenopausal and perimenopausal depression.

Disability and Normalcy as Constructs in Doris Lessing’s The Fifth Child

This paper aims to analyze Doris Lessing’s The Fifth Child as story with a special focus on abnormal child Ben who is born with Down’s syndrome and how society fear his difference and play an important role in constructing what is termed as disability. The young English couple, Harriet and David Lavatt move from a romanticized ideal to hazardous situations with the conception and birth of the fifth child, Ben who is described throughout the novel as an animal, an alien or a kind of monstrous baby or the baby of a monster. The disabled baby exercises an evil and destructive force upon the family. The novel ends with the formerly happy couple and family scattered across England and the family members have been physically and emotionally traumatized due to the birth of the abnormal baby ‘Ben’. The mother’s desire for a unconventionally large family is also a sign of abnormality. She refuses the social and class conventions that dictate small families. She also refuses medical technologies and interventions during conception and at birth. This serves to prove that concepts like normalcy and disability are socially constructed and can be challenged. For the purpose of theory the paper draws on the ideas related to normalcy and disability from The Disability Studies Reader edited by Lennard J Davis.

Oocyte Cryopreservation - Current Scenario and Future Perspectives: A Narrative Review.

Oocyte cryopreservation is a boon for women undergoing assisted reproductive technology. With the evolution in the technique of cryopreservation over the last three decades, there has been an exponential rise in the number of oocyte cryopreservation cycles for diverse indications. Apart from cancer patients, it has also been promoted as a mode of fertility insurance to overcome the age-related decline in fertility as well as post-surgical decline following endometriosis surgery. The objective of the review is to evaluate its clinical applications, ideal age at freezing, optimal oocyte number, freezing method of choice, efficacy, safety and recent advances. In the last decade, vitrification has surpassed slow freezing for oocyte cryopreservation. Although closed system of vitrification provides the aseptic environment, open vitrification is commonly followed in practice. Early to mid-thirties is a reasonable age group for planned oocyte cryopreservation, although it might be recommended at a younger age, in patients with diminished ovarian reserve. The patients should be motivated to preserve around 14–20 mature oocytes for successful live birth. Various studies have shown comparable fertilisation and pregnancy rates between Intracytoplasmic sperm injection with fresh and frozen-thawed oocytes. The available evidence has shown no increase in the incidence of congenital abnormalities in babies born through vitrified oocytes. In the future, image analysis using artificial intelligence, and spindle visualisation using poloscope may further enhance the outcome of oocyte cryopreservation.

ZIKV Infection Induces DNA Damage Response and Alters the Proteome of Gastrointestinal Cells.

The zika virus (ZIKV) is a neurotropic virus that causes congenital abnormalities in babies when they are infected in utero. Some studies have reported these congenital abnormalities result from ZIKV attacking neural progenitor cells within the brain which differentiate into neurons, oligodendrocytes, and astrocytes. Each of these glial cells play important roles during development of the fetal brain. In addition to ZIKV-induced congenital abnormalities, infected patients experience gastrointestinal complications. There are presently no reports investigating the role of this virus at the proteomic level in gastrointestinal associated cells, so we conducted an in vitro proteomic study of ZIKV-induced changes in Caco-2, a colon-derived human cell line which is known to be permissive to ZIKV infection. We used SomaScan, a new aptamer-based proteomic tool to identify host proteins that are dysregulated during ZIKV infection at 12, 24, and 48 h post-infection. Bioinformatic analyses predicted that dysregulation of differentially-regulated host proteins results in various gastrointestinal diseases. Validation of the clinical relevance of these promising protein targets will add to the existing knowledge of ZIKV biology. These potential proteins may be useful targets towards the development of therapeutic interventions.

Sero-prevalence of toxoplasmosis and Role of Cathepsin L-like and Cathepsin B-like Genes as Risk Factors for Abnormal Pregnancy Outcome

Background and objectives: Toxoplasma gondii (T. gondii) is a ubiquitous apicomplexan parasite. As an obligate intracellular parasite, T. gondii must invade host cells to survive and replicate. Five cathepsin proteases are encoded in the genome of T. gondii, cathepsin L like protein, cathepsin B like protein, and three cathepsin C like proteins. The present study was aimed to investigate the prevalence of toxoplasmosis among women in Erbil, and to study the role of cathepsin B and cathepsin L genes in the pathogenesis of toxoplasmosis as well as their role as risk factors for abnormal pregnancy outcome. Methods: This is a cross sectional study was carried out in Erbil from October 2018 to March 2019. A total of 230 women at their reproductive age and who attended Maternity Teaching Hospital and Nazdar Bamarni primary Health Center were enrolled. Anti- toxoplasma IgG and IgM antibodies were detected by cobas 6000. Toxoplasma cathepsin B and cathepsin L – like genes were selected to be targets in PCR. Results: Anti-toxoplasma IgG and IgM were seropositive in 105 (45.7%) and 18 (7.8%) women, respectively. Of those women who were seropositive for toxoplasmosis, only 15(6.5%) of them were carrying both anti-toxoplasma IgG and IgM. No significant association of toxoplasmosis and educational level, socioeconomic level, age, history of abortion, abnormal baby birth weight were observed. PCR targeting cathepsin L was more sensitive to be used in the diagnosis of toxoplasmosis. Conclusion: Sero-prevalence of toxoplasmosis is relatively high in Erbil and cathepsin L gene is an efficient target for PCR and could be used as risk factor for abnormal pregnancy outcome.

HUBUNGAN JENIS PERSALINAN DENGAN STATUS KESEHATAN BAYI BARU LAHIR DI KOTA BUKITTINGGI

&lt;p&gt;&lt;em&gt;Every woman wants her labor to run smoothly and can give birth to a baby perfectly. Childbirth can run normally, but it is not uncommon for labor to experience obstacles and must be done through surgery. This means the fetus and mother are in an emergency and can only be saved if labor is performed by surgery. The purpose of this study is to find out the related to the health status of newborn babies at delivery in the City of Bukittinggi.&lt;/em&gt;&lt;/p&gt;&lt;p&gt;&lt;em&gt;Type of analytic survey research with design cross-sectional&lt;/em&gt;&lt;em&gt;.&lt;/em&gt;&lt;em&gt;The object of the study was a newborn baby with Caesarean section and normal delivery at Bukittinggi City Hospital. The test used is thetest Chi-Square with a 95% confidence level.&lt;/em&gt;&lt;/p&gt;&lt;p&gt;&lt;em&gt;The results showed that as many as 65 people (54.2%) had the incidence of asphyxia. 65 people (54.2%) had normal respiratory conditions, 62 people (51.7%) had meconium aspiration&lt;/em&gt;&lt;em&gt;.&lt;/em&gt;&lt;em&gt;63 people (52.5%) had trauma to an abnormal baby&lt;/em&gt;&lt;em&gt;.&lt;/em&gt;&lt;em&gt;64 people (53.3%) had infectious diseases. 70 people (58.3%) had IMD.&lt;/em&gt;&lt;em&gt;72 people (60%) have joined care. 60 people (50%) with type of labor SC. Statistical tests showed that there was a relationship between apgar score (p = 0.003), respiratory conditions (p = 0.010), meconium aspiration (p = 0.0005), trauma in infants (p = 0.0005), joint care (p = 0.002 ) and IMD (p = 0.0005) for the type of labor. While infectious diseases do not have a relationship to the type of labor (p = 0.583).&lt;/em&gt;&lt;/p&gt;&lt;p&gt;&lt;em&gt;It was concluded that there was a relationship between apgar score, respiratory condition, meconium aspiration, admission and IMD with different types of delivery. Expected to health workers especially midwives can be used as input in order to improve health status in newborns.&lt;/em&gt;&lt;/p&gt;

62. SUCCESSFUL STRATEGY OF COMPREHENSIVE PRE-IMPLANTATION GENETIC TESTING FOR DUCHENNE MUSCULAR DYSTROPHY AND CHROMOSOME BALANCE USING KARYOMAPPING

Introduction Duchenne muscular dystrophy (DMD) is one of the most common muscular dystrophy in childhood. The patients suffer progressive proximal muscle weakness and die from respiratory failure and cardiomyopathy in their 30’s. Pre-implantation genetic testing (PGT) is an alternative traditional prenatal diagnosis (PND). However, extremely large size of the gene and the diversity of mutations cause molecular genetic testing difficult and labor intensive. Modern haplotyping using aSNP and Karyomapping algorithm would be useful for diagnosis of monogenic disease. This study applied Karyomapping for PGT-M of DMD in 2 clinical PGT cycles in comparison to standard PCR testing techniques. Material and methods Two families at risk of having DMD offspring joined the project following thoroughly counselling and inform consent was obtained. The patients underwent IVF procedures. Embryo biopsy was performed on Day-5 post-fertilization and biopsied trophectoderm underwent whole genome amplification. SNP array with Karyomapping analysis was carried out for haplotyping as well as copy number variation (CNV). Multiplex PCR with mini-sequencing was performed alongside for confirmation standard molecular mutation analysis. Multiple microsatellites within dystrophin gene were also analyzed for linkage analysis and contamination identification. Results Nine embryos with good morphology from each patient were chosen for PGT. Karyomapping results of family TZ (DMD c.895G>T) revealed three normal, two carriers, two affected and two with intragenic recombination. Standard mutation analysis using multiplex fluorescent PCR incorporation with mini-sequencing and microsatellites analysis for linkage analysis confirmed haplotyping results in all embryos. In addition, karyomapping demonstrated one embryo with chromosome unbalanced, i.e. 46,XX, -6q (intragenic recombination). Therefore, three normal (two male and one female) and two carrier (both female) embryos with chromosomally balanced were fulfilled for transfer. During the first embryo transfer, one normal female embryo was chosen, no pregnancy was resulted. In the second transfer, one normal male embryo was transferred, one ongoing pregnancy was resulted. Karyomapping results of family JM (DMD exon 8-9 duplication) revealed two normal, two carriers, two affected and one with intragenic recombination. Standard microsatellites analysis for linkage analysis confirmed haplotyping results in all embryos. Additionally, karyomapping demonstrated one embryo with chromosome unbalanced, i.e. 45,XX, +2P,-22 (normal) and one embryo with uniparental disomy (UPD), i.e. 46,XX (normal). Therefore, two normal (both female) and two carrier (both female) embryos with chromosomally balanced embryos were fulfilled for transfer. All are being frozen waiting for transfer. Polymorphic marker analysis revealed the absence of extraneous DNA contamination. Conclusions Two clinical PGT-M cycles using karyomapping were performed for two families at risk of having DMD offspring. This study exhibits that aSNP provides the benefit of extra information of chromosome balance and parental origins, i.e. uniparental disomy in one of the embryo. Therefore, kryomapping can omit the risk of transfer chromosomally unbalanced embryos, termination of abnormal chromosome pregnancy later and the birth of abnormal chromosome babies. Therefore, karyomapping provides an accurate, quick, time saving for protocol development, universal PGT-M method for every monogenic disease of various types of mutations and also the advantage of CNV and parental origin information which is common abnormalities in pre-implantation embryos.

65. SUCCESSFUL STRATEGY OF COMPREHENSIVE PRE-IMPLANTATION GENETIC TESTING FOR BETA-THALASSEMIA-HEMOGLOBIN E DISEASE AND CHROMOSOME BALANCE USING KARYOMAPPING

Introduction Thalassemia syndrome and hemoglobinopathy are the world commonest monogenic disease and cause health and economic burden worldwide. Pre-implantation genetic testing (PGT) is an alternative to traditional prenatal diagnosis (PND). However, the nature of a vast variety of mutations makes molecular genetic testing sophisticated and labor intensive. Modern haplotyping using SNP array (aSNP) and Karyomapping algorithm would omit molecular analysis development process and provide chromosome balance information at the same time. This study applied Karyomapping for PGT-M of beta-thalassemia-hemoglobin E (Hb E) disease in 2 clinical PGT cycles in comparison to PCR testing techniques. Material and methods: Two families at risk of having beta-thalassemia-Hb E disesase offspring decided to join the project following thoroughly counselling and inform consent was obtained. The patients underwent routine IVF procedures. Embryo biopsy was performed on Day-5 post-fertilization and the biopsied trophectoderm underwent whole genome amplification. SNP array with Karyomapping analysis was carried out for haplotyping as well as copy number variation (CNV). Multiplex PCR with mini-sequencing was performed alongside for confirmation standard molecular mutation analysis. Informative polymorphic marker was also included for contamination identification Results Thirteen and nine embryos with good morphology from families YW and CS were chosen for PGT, respectively. Karyomapping results of family YW (beta–thalassemia (c.17A>T)-Hb E (c.26G>A) disease) revealed four normal, two beta-thalassemia trait, one Hb E trait and six affected with beta-thalassemia-Hb E disease. Standard mutation analysis using multiplex fluorescent PCR and mini-sequencing confirmed haplotyping results in all embryos. In addition, Karyomapping demonstrated three embryos with chromosome unbalanced, i.e. 45,XY, -19 (affected), 47,XY, +16 (beta-thalassemia trait) and 47,XX, +21 (beta-thalassemia trait). Therefore, four normal (three male and one female) and one Hb E trait embryos were fulfilled for transfer. One normal male embryo was chosen for transfer and one normal male baby was delivered. Prenatal and postnatal DNA testing confirmed PGT results. Karyomapping results of family CS (beta–thalassemia (c.17A>T)-Hb E (c.26G>A) disease) revealed six Hb E trait and three affected with beta-thalassemia-Hb E disease. Standard mutation analysis using multiplex fluorescent PCR and mini-sequencing confirmed haplotyping results in all embryos. Additionally, Karyomapping demonstrated two embryos with chromosome unbalanced, i.e. 45,XY, -21 (affected) and 45,XY, -22 (Hb E trait). Therefore, five Hb E trait embryos were fulfilled for transfer. One Hb E trait embryo was chosen for transfer and one ongoing pregnancy was resulted. Polymorphic marker analysis revealed the absence of extraneous DNA contamination. Conclusions Two clinical PGT-M cycles using Karyomapping were performed for two families at risk of having beta–thalassemia (c.17A>T)-Hb E (c.26G>A) disease offspring. Additional standard multiplex PCR with mini-sequencing analysis confirmed haplotyping results of Karyomapping. However, aSNP provides the benefit of extra information of chromosome balance. This study demonstrated that kryomapping can omit the risk of transfer chromosomally unbalanced embryos, termination of abnormal chromosome pregnancy later and the birth of abnormal chromosome babies. Therefore, Karyomapping provides an accurate, quick, time saving for protocol development, universal PGT-M method for every monogenic disease, and also the advantage of CNV information which is common in pre-implantation embryos.

Pregnancy outcomes in patients with rheumatoid arthritis and systemic lupus erythematosus. Part II. Neonatal outcomes

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are the most common autoimmune rheumatic diseases (RD) that occur mostly in women of childbearing age, and the occurrence of pregnancy is an expected fact. Due to the ongoing disputes over the ethics of maintaining birth rates among an unhealthy population, modern researchers focus attention on studies of the mutual impact of RD and pregnancy, on the safety of pharmacotherapy during conception and gestation, and on the health of the offspring born to female patients with RD.Objective: to evaluate the neonatal outcomes of pregnancy in patients with RA and SLE.Subjects and methods. An investigation was conducted to study the health status of 73 babies born to 72 female patients with RD (76 cases of pregnancy), of whom 29 patients with RA (32 cases of pregnancy) and 43 with SLE (44 cases of pregnancy) were followed up prospectively at the V.A. Nasonova Research Institute of Rheumatology and the Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology. The health status of the babies was evaluated in the first year of their life. Supervising neonatologists and pediatricians recorded abnormalities in the newborns and subsequently analyzed using their medical records (extracts from maternity hospitals, children's hospitals, and outpatient cards).Results and discussion. Of the 76 supervised pregnancies, 72 (94.7%) resulted in 73 live births (one twin pregnancy in a patient with SLE). There were three (6.8%) cases of pregnancy loss in the second trimester in patients with SLE having antiphospholipid syndrome (APS) and one (3.1%) case of perinatal death (a boy and a girl from a monochorionic diamniotic twin with reversed arterial perfusion) in a patient with seropositive RA. The height and body weight of all the newborns conformed to gestational age. Patients with RA and SLE compared to the population more often gave birth to low birthweight babies (9.7 and 21.4% versus 60.9 per 1,000 live births in the Russian population). In the groups of mothers with RA and SLE, their infants had a high Apgar score of 8–9 at one and five minutes. Various abnormalities were detected in 5 (16.1%) and 15 (35.7%) babies born to mothers with RA and to those with SLE, respectively. Among the neonatal congenital anomalies (malformations), there was patent foramen ovale, patent ductus arteriosus, and hip joint dysplasia, which were more common in the babies born to mothers with SLE having APS and exceeded the population-based incidence of these anomalies. The babies were more commonly diagnosed with congenital pneumonia than those in the population; there were single cases of umbilical hernia, hemangioma, thrombocytopenia, hemorrhagic disease of the newborn, perinatal encephalopathy, and congenital hearing loss.Conclusion. The mothers with RA and SLE more often gave birth to low birthweight babies than did those in the population. The infants born to mothers with RA and SLE had significantly more frequently congenital heart defects (patent foramen ovale, patent ductus arteriosus) and congenital pneumonia. The detected abnormalities were more common in the newborns born to mothers with SLE having APS. Maternal RA and SLE activities and/or performed therapy were not found to have a negative impact on the incidence of abnormalities in babies.

William McBride: alerted the world to the dangers of thalidomide in fetal development

In December 1961, the Australian obstetrician William McBride warned in a letter to the Lancet that he had observed “multiple severe abnormalities” in babies delivered from women who had taken...

Congenital Anomalies among the Babies of Diabetic Mothers with Uncontrolled Blood Sugar -A Study in a Tertiary Hospital

Diabetes mellitus is a silent killer which affects at any stage of life. Worldwide incidence of major malformation among the offspring of diabetic mothers ranges from 5-10%. Though 65-75% of birth defects are multifactorial, poor diabetic control in pregnancy predisposes congenital malformation. The aim of this retrospective study is to see the actual picture of congenital anomalies among the babies of uncontrolled diabetic mothers. Cases are taken from the hospital records of the patients who delivered congenitally abnormal babies &amp; were admitted in SCABU of BIRDEM during the period of January, 2006 to December, 2010. After going through all records, patients were divided into DM/GDM/ND groups and different variables are studied. Among the patients (163), 57 (35%) were DM, 38 were (23.3%) GDM and 68 (41.7%) were ND. Major congenital anomalies were found 82.45% in DM and 71.05% in GDM and 83.82% in ND patients. Rests were minor anomalies. Among the anomalies maximum were congenital heart diseases, then CNS anomalies, then renalanomalies and then others. In this study congenital anomalies were found 1.4 times more in DM patients. Among DM and GDM patients maximum had uncontrolled blood sugar. Neonatal mortality was higher in DM and GDM groups. Both cardiac and CNS abnormalities were 1.2 times higher in diabetic groups. Renal anomalies were 2.8 times higher. Limb abnormalities were 7.15 times higher in diabetic groups. So it is concluded that pregnancy with uncontrolled diabetes increases the risk of birth defects, mainly CVS, CNS and Renal system related.Medicine Today 2017 Vol.29(1): 26-31

Fetal congenital abnormalities, types &amp; their relationshipwith age, prtity and recurrent abortions

Objective : To study fetal congenital abnormalities, types and theirrelationship with age , parity and number of abortions .Design : Prospective study .Setting :Alzahraa maternity teaching hospital in Al-Najaf city .Patient : 100mothers delivered normal babies &amp;100 mothersdelivered congenitally abnormal babies .Result : No significant relationship between fetal congenitalabnormalities with age and parity but there is a significant relationship between fetal congenital abnormalities and abortion especiallyrecurrent abortions. Conclusion : We find that there a significant relationship between fetal congenital abnormalities and abortion especially recurrent abortion and for that we adviseevery women with history of abortion for early prenatal screening and diagnostictests.