High Incidence Of Congenital Malformations Research Articles

Maternal and fetal factors for determining the cesarean section type (scheduled/emergency) in bitches

One hundred and forty bitches and their offspring (689 puppies) were involved in this study. The influence of different maternal features such as age, breed (brachycephalic/non-brachycephalic), previous births (primiparous/multiparous), health status (complete/incomplete) and litter size over the type of cesarean sections (scheduled/emergency), the neonatal survival, and the incidence of congenital malformations were also examined. Scheduled cesareans were predominant (104/140), of which 90 % were brachycephalic breeds and females were mostly between 2 and 4 years old (54.8 %), multiparous (88.4 %) and with a correct health status (67.3 %). Emergency cesarean sections mainly involved non-brachycephalic breeds (80 %) and were carried out mostly in females under 4 years of age (72.2 %), primiparous (77.7 %), with incomplete health status and a large litter size (47.2 %). Perinatal mortality was notably higher in emergency C-sections (3.25 % and 13.3 %, scheduled and emergency C-sections, respectively); the highest incidence of neonatal mortality was recorded in young females (<2, 2–4 years old), primiparous and with incomplete health status. Congenital anomalies were observed in 4.50 % (31/689) of the puppies, with anasarca (38.71 %) and cleft palate (29.03 %) being the most frequently observed malformations. A higher incidence of congenital malformations was detected in puppies from dams with incomplete sanitary health and from inbreeding cross. Overall, the study provides valuable insights into the complex interplay between maternal characteristics and cesarean outcomes. Appropriate genetic selection, good sanitary health conditions, and the age of the reproducers, are pivotal factors in planning for gestation and improving the survival of neonates.

Congenital cytomegalovirus infection: new answers to old problems

Congenital cytomegalovirus infection is one of the most common TORCH infections, characterized by a wide range of clinical manifestations, predominantly with multiple organ lesions and often a disabling course. The result of antenatal infection with cytomegalovirus is a high incidence of congenital malformations, often accompanied by disorders such as hearing loss, vision loss, motor and cognitive deficits. Despite the presence of modern domestic clinical recommendations, the study of this pathology remains relevant to the present day. Recently, significant progress has been made in the study of this disease. Every year, new research is conducted on topical issues of diagnosis, treatment and rehabilitation for congenital cytomegalovirus infection. This article provides a review of modern literature, covering the latest data on the molecular basis of pathogenesis, features of clinical manifestations, current approaches to the diagnosis and treatment of congenital cytomegalovirus infection.

CLINICAL, ULTRASOUND AND CYTOGENETIC CHARACTERISTICS OF FETUSES WITH INCREASED NUCHAL TRANSLUCENCY THICKNESS IN THE FIRST TRIMESTER OF PREGNANCY

Background: Improving programs for early prenatal detection of congenital malformations remains a relevant scientific and practical problem. The prevalence of congenital anomalies in Ukraine is 23.7:1000 among live-born babies, and there is no significant decrease in it. The aim of this study was to compare clinical, ultrasound and cytogenetic data in swollen fetuses with increased nuchal translucency (NT) thicknesses from the group of pregnant women in the first trimester at high genetic risk to optimize the algorithm of prenatal diagnostics.&#x0D; Materials and Methods: Clinical examinations, ultrasound diagnostics, invasive methods of prenatal diagnostics (chorion biopsy, amniocentesis), genetic testing techniques, such as karyotyping and FISH, genetic counseling and statistical analysis were carried out. The results of complex examinations of 127 fetuses with an increased NT thickness from the group of pregnant women were analyzed. Fetuses were divided into two groups with an NT thickness of 2.5–3.5 mm (group 1) (38 cases) and with an NT above 3.5 mm (group 2)(89 cases).&#x0D; Results: Among pregnancies with fetuses with an increased NT thickness, there were 65.4% cases of adverse outcomes with chromosomal pathology (69.9%), congenital malformations of non-chromosomal etiology (25.3%) and pregnancy loss (4.8%). The frequency of chromosomal abnormalities in fetuses of group 1 was 55.3% and 41.6% in group 2. Congenital malformations of various systems and organs in fetuses, the most frequent of which were cardiac defects, were diagnosed. The ratio of congenital heart defects in the fetuses of groups 1 and 2 was 23.7% and 43.8%, respectively (p=0.03; OR=0.40).&#x0D; Conclusion: There is no significant difference between the frequency of chromosomal abnormalities in the fetuses of group 1 compared to group 2, which indicates a high informative value of an increased NT thickness, including the thickness of 2.5–3.5 mm in fetuses in the first trimester as a marker of chromosomal pathology. A significantly higher incidence of congenital malformations of non-chromosomal etiology was found in fetuses with venous duct pathology and NT thickness over 3.5 mm compared to fetuses with the same pathology and NT thickness of 2.5–3.5 mm. Proposed changes to the management algorithm for pregnant women with swollen fetuses include mandatory congenital heart defects screening in the first trimester.

Analysis of the factors which may have influenced the incidence of congenital malformations in children born in the province of Warmia and Mazury between 1999 and 2000

&lt;b&gt;Introduction.&lt;/b&gt; Congenital malformations have been known about for ages, but the reasons for their development have always been shrouded in mystery. All efforts to explain such reasons as to relating to the natural forces of God’s revenge have not stood the test of time. Still, the knowledge concerning the aetiology of malformations is not complete; we know, however, about many factors which may contribute to their development during various stages of embryogenesis. &lt;b&gt;Aim.&lt;/b&gt; The aim of this paper is the analysis of specific factors which may have contributed to the development of congenital malformations in children born in the Province of Warmia and Mazury between the years 1999 and 2000. &lt;b&gt;Materials and methods.&lt;/b&gt; The author of this paper, who is involved in the creation of the Polish Register of Congenital Malformations (PRCM), evaluated case records of newborns who had been reported to have been born with congenital malformations. The data recorded in this Register, maintained by the Chair and Department of Medical Genetics at the Medical Academy (at present Medical University) in Poznań, was verified by specialists, and later analysed according to the methodological principles of this work. The analysis included: fetal age and birth weight, mother’s age and education, as well as mother’s place of residence. Statistical analysis was carried out by means of Statistica v.6.1 software. &lt;b&gt;Results and discussion.&lt;/b&gt; Congenital malformations were found in 276 boys, with a malformations incidence factor of 166.8/10000 for boys, and in 212 girls, the malformations incidence factor being 136.2/10000 for girls. The higher incidence of congenital malformations in boys was caused by a nearly 10 times higher incidence of urinary system defects. The incidence of congenital malformations in newborns whose mothers resided in cities amounted to 132.9/10000 of newborns born in cities. The incidence of congenital malformations in newborns of mothers residing in the country was 141.9/10 000 of newborns born in the country. It was also noted that the incidence of congenital malformations was 2–3 times higher in children with low birth weight in comparison to the general population. The highest incidence of congenital malformations was found in those children whose mothers were 35 years of age or older at the time of giving birth. Advanced maternal age was the most significant factor in the development of malformations caused by chromosome aberrations. Creating a district map presenting the incidence of malformations may be the first step to further research concerning those specific geographical regions at high risk of congenital malformations. The highest incidence, irrespective of the type of malformation, was observed in the districts of: Mrągowo, Ostróda and Braniewo, whereas the lowest was found in the districts of: Ełk, Olecko and Gołdap, and Giżycko. &lt;b&gt;Conclusions.&lt;/b&gt; Having analysed all pertinent data, it was then concluded that: 1. Male sex correlates with the incidence of congenital malformations of the genitals. 2. Low birth weight correlates with an increased incidence of congenital malformations. 3. The incidence of congenital malformations in particular districts is diversified, pointing to the significance of necessary further research in order to identify those specific geographical locations having the highest malformations incidence factors.

Hyperglycemia affects neuronal differentiation and Nestin, FOXO1, and LMO3 mRNA expression of human Wharton's jelly mesenchymal stem cells of children from diabetic mothers

Pregestational Diabetes Mellitus (PDM) during pregnancy constitutes an unfavorable embryonic and fetal development environment, with a high incidence of congenital malformations (CM). Neural tube defects are the second most common type of CM in children of diabetic mothers (CDM), who also have an elevated risk of developing neurodevelopmental disorders. The mechanisms that lead to these neuronal disorders in CDM are not yet fully understood. The present study aimed to know the effect of hyperglycemia on proliferation, neuronal differentiation percentage, and expression of neuronal differentiation mRNA markers in human umbilical cord Wharton's jelly mesenchymal stem cells (hUCWJMSC) of children from normoglycemic pregnancies (NGP) and PDM. We isolated and characterized hUCWJMSC by flow cytometry, immunofluorescence, RT-PCR and were induced to differentiate into adipocytes, osteocytes, and neurons. Proliferation assays were performed to determine the doubling time, and Nestin, TUBB3, FOXO1, KCNK2, LMO3, and MAP2 mRNA gene expression was assessed by semiquantitative RT-PCR. Hyperglycemia significantly decreased proliferation and neuronal differentiation percentage in NGP and PDM cells treated with 40 mM d-glucose. Nestin mRNA expression decreased under control glycemic conditions, while FOXO1, KCNK2, LMO3, and MAP2 mRNA expression increased during neuronal differentiation in both NGP and PDM cells. On the other hand, under hyperglycemic conditions, Nestin was significantly decreased in cells from NGP but not in cells from PDM, while mRNA expression of FOXO1 and LMO3 was significantly increased in cells from NGP, but not in cells from PDM. We found evidence that maternal PDM, with hyperglycemia in culture, affects the biological properties of fetal cells. All these results could be part of fetal programming.

Mild periconceptional hyperglycemia: predictor of adverse fetomaternal outcomes in gestational diabetes?

To clarify whether mild first trimester hyperglycaemia (characteristic of early-onset GDM) is associated with higher incidence of congenital malformations and other adverse fetomaternal outcomes compared to women with second trimester hyperglycaemia (later-onset GDM). We analyzed the Portuguese National GDM database, containing data collected between 2011 and 2017. Two study groups were defined: Group 1-Women with GDM diagnosed during the first trimester (with fasting glycemia ≥ 92 and < 126mg/dL); Group 2-Women with GDM diagnosed after the first 12weeks of gestation, with either fasting glycemia or oral glucose tolerance test, according to the International Association of Pregnancy and Diabetes Study Group criteria. The fetomaternal characteristics of each group were compared. A total of 18.518 pregnant women diagnosed with GDM were included which 34.4% of them belonged to Group 1. Pregnant women from this group were significantly younger and had a higher median BMI than the women from the other group. Overall, there was no significant differences in maternal morbidity parameters between groups. Non-evolutive pregnancies were significantly more frequent along the present gestation in the group 1 (1.1% vs. 0.1%, p < 0.001), as was fetal death (0.6% vs. 0.2%, p < 0.001). Congenital malformations did not differ significantly between groups (3.2% vs. 2.8%, p = 0.155). The mild near conceptional hyperglycaemic state characteristic of an early-onset GDM seems to be associated with an increased prevalence of non-evolutive pregnancies and foetal deaths when compared to later-onset GDM.

Anomalías congénitas de los embera-chamí en las reservas indígenas de Riosucio, Caldas, Colombia, de 2007 a 2012

Introducción: Tal como sucede a nivel mundial, en Colombia las malformaciones congénitas son causas importantes de mortalidad infantil, enfermedad crónica y discapacidad. Las poblaciones indígenas de Colombia no cuentan con estudios definidos a este respecto, por lo cual la presente investigación se desarrolla en la zona indígena. Objetivo general: Caracterizar las anomalías congénitas de los indígenas Embera-Chamí residentes en los resguardos del municipio de Riosucio, Caldas, entre los años 2007 y 2012. Métodos: Estudio descriptivo, retrospectivo, aplicado a 125 nacidos vivos con anomalías congénitas. Se aplicó el formato especializado de Instituto Nacional de Salud (INS) de Colombia y para el análisis de variables se utilizó el paquete estadístico SPSS. Resultados: De 3.382 nacimientos el 3,7 % (125) presentó anomalías congénitas. Se encuentra una asociación entre la edad de la madre y la presencia de anomalías congénitas. En el 87,2 % de los casos fueron con edad gestacional de término. Las anomalías más frecuentes fueron: displasia de cadera, criptorquidia, malformaciones cardiovasculares, pie equino e hidrocefalia. Conclusiones: Se encuentra una incidencia de anomalías congénitas en la población indígena de los Embera-Chamí de Riosucio, Caldas, mayor que para el promedio de la población general en Colombia.

Hyperglycemia differentially affects proliferation, apoptosis, and BNIP3 and p53 mRNA expression of human umbilical cord Wharton's jelly cells from non-diabetic and diabetic pregnancies

Diabetes in pregnancy constitutes an unfavorable environment for embryonic and fetal development, where the child has a higher risk of perinatal morbidity and mortality, with high incidence of congenital malformations and predisposition to long-term metabolic diseases that increase with a hypercaloric diet. To analyze whether hyperglycemia differentially affects proliferation, apoptosis, and mRNA expression in cells from children of normoglycemic pregnancies (NGPs) and diabetes mellitus pregnancies (DMPs), we used umbilical cord Wharton jelly cells as a research model. Proliferation assays were performed to analyze growth and determine the doubling time, and the rate of apoptosis was determined by flow cytometry-annexin-V assays. AMPK, BNIP3, HIF1α, and p53 mRNA gene expression was assessed by semi-quantitative RT-PCR. We found that hyperglycemia decreased proliferation in a statistically significant manner in NGP cells treated with 40 mM D-glucose and in DMP cells treated with 30 and 40 mM D-glucose. Apoptosis increased in hyperglycemic conditions in NGP and DMP cells. mRNA expression of BNIP3 and p53 was significantly increased in cells from DMPs but not in cells from NGPs. We found evidence that maternal irregular metabolic conditions, like diabetes with hyperglycemia in culture, affect biological properties of fetal cells. These observations could be a constituent of fetal programming.

Clinical report of 8 patients with 49,XXXXY syndrome: Delineation of the facial gestalt and depiction of the clinical spectrum

49,XXXXY syndrome is a rare sex chromosome aneuploidy syndrome. Cognitive impairment with expressive language deficits in combination with developmental and speech dyspraxia are cardinal symptoms. Testicular insufficiency becomes apparent during adolescence. Neurological, musculoskeletal, genital, orthodontic and immunological anomalies are common and a higher incidence of congenital malformations has been described. Here we show the evolving clinical and facial phenotype of eight boys and men with 49,XXXXY, demonstrating an increasingly perceptible distinct facial gestalt over time. In addition, almost all patients had muscular hypotonia, radioulnar synostosis, white matter anomalies, fifth-finger clinodactyly, recurrent respiratory infections in early childhood and teeth anomalies. IQ scores ranged between 40 and 70. Though many boys showed short stature at some point in early childhood, most outgrew it. As more long term data of boys and men with 49,XXXXY become available, parents of affected boys can be counseled more specifically as to the expected course and spectrum of this rare chromosomal disorder. Moreover, the multidisciplinary support can be optimized und unnecessary diagnostics avoided.

Malformações congênitas em regiões de monocultivo no estado de Minas Gerais, Brasil

Objective: to analyze the association between the use of agrochemicals and congenital malformations in municipalities with greater exposure, as well as to evaluate the nature of the correlation between the trend observed and the volume of agrochemicals considered as endocrine disruptors in the state of Minas Gerais, Brazil, between 1994 and 2014. Model Study: Cross-sectional study, exploratory, descriptive and quantitative character. Method: Rates of malformations for the periods 1994-2003 and 2004-2014 were calculated from the information on live births available at SINASC/Ministry of Health. Odds Ratio tested the association between types of malformations and variables for each variable separately. The significance was set at p&lt;0.05. Results: there was an increasing trend in the rates of congenital malformation in the state of Minas Gerais, especially at Triângulo Mineiro/Alto Paraíba and Vale do Mucuri/Jequitinhonha regions. It was found that the rates for congenital malformations were higher for the years of greatest exposure (2004-2014) and had a statistically significant association for all congenital malformations in the state of Minas Gerais. Conclusion: Maternal exposure to pesticides was related with higher incidence of congenital malformations.

Maternal nutrition and the risk of congenital malformations in the tea garden community of Assam, Northeast India

Problem consideredThere is a high prevalence of congenital malformations (CMs) in the tea garden community of Assam, Northeast India. The present cross-sectional study was carried out to assess if insufficiencies in maternal nutrition during the periconceptional period are associated with high incidence of CM in the said community. MethodOver a period of 2 years, 156 pregnant women with a mean age of 25.7 years (SD 4.7) were enrolled. During an interview, anthropometric and obstetric data pertaining to periconceptional use of iron and folic acid (IFA) were collected. Adequate iodine intake during pregnancy was determined by measuring urinary iodine (UI) levels in each trimester. ResultsMalformations were noted in 16 babies, giving an uncorrected incidence rate of 102.5/1000 births. Among the participants, 87 (55.8%) were underweight and 6 (3.8%) were overweight. Periconceptional IFA supplementation was self-reported by 31 (19.8%). The median urinary iodine concentrations (MUICs) in the 1st, 2nd and 3rd trimesters were 170μg/l (IQR 100μg/l), 275μg/l (IQR 166μg/l), and 265μg/l (IQR 160μg/l), respectively. An analysis of maternal nutrition indicated that IFA supplementation reduced the risk of birth defects. However, a pre-pregnancy BMI>23kg/m2 and a 1st trimester MUIC<150μg/l increased the odds of having an infant with CM. Maternal age <20 years and illiteracy also elevated the risk. ConclusionInadequacies in periconceptional maternal nutrition are associated with the high incidence of CM. Community members should also be sensitized against early pregnancy and educated to minimize the risk.

Congenital defects in the cities with high use of pesticides in the state of Mato Grosso, Brazil

Mato Grosso is the largest agricultural producer and the largest national consumer of pesticides in Brazil. Maternal exposure to pesticides in the periconceptional period has been associated with increased risk of congenital malformations. This article aims to analyze the association between the use of pesticides and congenital malformations in cities with highest exposure to pesticides in Mato Grosso. It was a case-control study conducted with 219 live births with congenital malformations and 862 live births. The average use of pesticides was estimated in the prior and subsequent trimester to the date of fertilization and throughout the periconceptional period per city, month and year of use. Subsequently, these measures were quartilized and transformed into indicator-type (dummy) variables, attributing an exposure level for each interquartile interval. Bivariate and multivariate logistic regression analysis was conducted. Significant associations were observed (p < 0.05) in the third (OR = 1.66, 95% CI 0.98 to 2.79) and fourth quartile (OR = 1.88, 95% CI 1.09 to 3.24) of the post-fertilization period and the fourth quartile (OR = 2.04, 95% CI 1.17 to 3.56) throughout the periconceptional period. Maternal exposure to pesticides was associated with higher incidence of congenital malformations.

Oxidized frying oil and its polar fraction fed to pregnant mice are teratogenic and alter mRNA expressions of vitamin A metabolism genes in the liver of dams and their fetuses

We previously observed a higher incidence of congenital malformations in the fetuses of dams fed an oxidized frying oil (OFO)-containing diet during pregnancy. In this study, we hypothesized that, during pregnancy, maternal ingestion of OFO, specifically the oxidized components (i.e. the polar fraction), modulates peroxisome proliferator-activated receptor (PPARα) or aryl hydrocarbon receptor (AhR) transactivity, altering the metabolism of retinoic acid (RA), a well-characterized morphogen, resulting in teratogenesis. Pregnant C57BL/6J mice were divided into four groups which, from d1 (conception) to d18, were fed a diet containing 10 g/100 g of fresh soybean oil (SO), OFO or the non-polar (NP) or polar (PO) fraction of OFO. Reporter assays testing the transactivity of PPARα and AhR showed that free fatty acids from OFO, specifically the PO fraction, up-regulated PPARα transactivity and down-regulated AhR transactivity. In vivo study showed that the PO fraction group had a significantly higher number of dead fetuses and resorptions per litter than the SO and NP fraction groups. The incidence of abnormalities in terms of gross morphology and skeletal ossification of the fetus was greatest in the PO fraction group, followed by the OFO group, both values being significantly higher than in the other two groups. Hepatic expression of genes encoding enzymes associated with RA synthesis and catabolism in dams and fetuses was differentially affected by PO fraction assault. We conclude that OFO-mediated teratogenesis is associated with disturbed RA metabolism in the dams and fetuses caused, at least in part, by modulation of PPARα and AhR transactivity by the oxidized components in OFO.

Developmental malformations in the area of the lumbosacral transitional vertebrae and sacrum: differences in gender and left/right distribution

The aim of this study was to determine the incidence of congenital malformations of the lumbosacral transitional vertebrae in the general population, and the differences in their gender and left/right distributions. The examined group comprised of all patients who underwent a pelvic X-ray during 2010 for any reason. The observed parameters included the following malformations: the presence of megatransversus at L5; sacralization of L5 or L6; a S1 lumbarization; the presence of six sacral vertebrae; or spina bifida at the level of L5, S1 or S2. In cases of megatransversus at L5, the lateral distribution was recorded. A total of 1,513 images were evaluated. Sex and lateral differences were evaluated using the Pearson's (χ (2)) test with a significance level of 5%. A total of 478 malformations were found in 417 patients, which constituted 27.6% of the entire group. Malformations occurred in 250 women (25.4% of all women) and 167 men (31.6% of all men) and the female to male ratio in affected individuals was 1.5:1. The predominance of the occurrence of malformations observed in men was statistically significant (p=0.009). The most frequently occurring malformations were the presence of six sacral vertebrae (179 patients) and megatransversus at L5 (150 patients). The study confirmed a high incidence of congenital malformations in the area of the lumbosacral transitional vertebrae and demonstrated a higher incidence in males. Unilaterally occurring megatransversus at L5 was significantly more common on the left side.

Cardiac diagnoses, procedures, and healthcare utilisation in inpatients with Ellis–van Creveld syndrome

Ellis-van Creveld syndrome is a rare condition associated with a very high incidence of congenital malformations of the heart. Prior reports have suggested increased morbidity and mortality following surgery for congenital malformations of the heart in patients with Ellis-van Creveld syndrome. The Pediatric Health Information System database, an administrative database containing data from 43 free-standing paediatric hospitals in North America, was queried to search for patients with the diagnostic code for Ellis-van Creveld syndrome between 2004 and 2011. Those patients who underwent cardiac procedures were compared with those who did not with respect to measures of healthcare utilisation. A total of 138 admissions occurred in 93 patients with Ellis-van Creveld syndrome during the study period. Of these, 74% had an underlying diagnosis of congenital malformations of the heart. Half of the patients in the sample underwent a cardiac surgical or interventional catheterisation procedure. Patients who underwent a cardiac procedure had a longer hospital length of stay, higher incidence of intensive care unit admission, and higher total and per day hospital charges than patients who did not undergo cardiac surgery during admission. In a large group of inpatients with Ellis-van Creveld syndrome, the prevalence of congenital malformations of the heart was similar to that reported in prior studies. Cardiac surgical and interventional procedures appear to drive a substantial portion of healthcare utilisation in these patients.

Cranial Malformations in Related White Lions (Panthera leo krugeri)

White lions (Panthera leo krugeri) have never been common in the wild, and at present, the greatest population is kept in zoos where they are bred for biological and biodiversity conservation. During the years 2003 to 2008 in a zoological garden in northern Italy, 19 white lions were born to the same parents, who were in turn paternally consanguineous. Out of the 19 lions, 4 (21%) were stillborn, 13 (69%) died within 1 month, and 1 (5%) was euthanatized after 6 months because of difficulty with prehension of food. Six lions (32%) showed malformations involving the head (jaw, tongue, throat, teeth, and cranial bones). One lion (5%) still alive at 30 months revealed an Arnold-Chiari malformation upon submission for neurological evaluation of postural and gait abnormalities. Paternal consanguinity of the parents, along with inbreeding among white lions in general, could account for the high incidence of congenital malformations of the head in this pride of white lions.

ART and major structural birth defects in the United States

Sir, We read with interest the study by Reefhuis et al. (2009) showing that assisted reproductive technology (ART) treatment is a risk for structural birth defects. The authors recognize that this risk may be over-stated because underlying subfertility may in itself be an important risk factor for such defects. In our meta-analysis of 19 studies (Rimm et al., 2004), where we found an overall risk of 1.29, we noted the failure of each of those 19 studies to use the most appropriate control group, namely infertile couples conceiving spontaneously. Responding to the concern we raised, Zhu et al. (2006) attempted to design an analysis with a control group made up of subfertile couples. They compared three groups of children: those born of fertile couples (Group A), those born of infertile couples who conceived spontaneously after 12 months (Group B) and those born of infertile couples who conceived after ART treatment (Group C). They found that when compared with Group A, singletons in Group B and in Group C both had a higher incidence of congenital malformations. The adjusted hazard ratios were 1.20 [95% confidence interval (CI): 1.07 –1.35] and 1.39, respectively (95% CI: 1.23– 1.57). When the singletons in Group C were compared with those in Group B, the adjusted hazard ratio was 1.17 (95% CI: 1.00– 1.36). Zhu et al. suggested that some of the determinants of infertility might share a common causal pathway with mechanisms that cause congenital malformations. We were surprised that the Reefhuis study presents no overall rate of malformations in women aged 35 and over. Apparently there is a very large difference in the age distribution of the ART group and the non-ART group as shown in Table 1 for those without major birth defects. Only 13% of the non-ART mothers were 35 and older, whereas 55% of the ART mothers were 35 or older. The authors failed to show the age of the ART and non-ART mothers with a major defect. When there is such a large difference in the age distribution between the two groups, adjustment for age is not a sensitive method of analysis. Stratifying by age is more sensitive because it takes interaction into account.

Male Predominance of Congenital Malformations in Infants of Women With Type 1 Diabetes

OBJECTIVETo investigate sex-related differences in maternal, perinatal, and neonatal outcome in type 1 diabetic pregnancies in the Netherlands.RESEARCH DESIGN AND METHODSThis was a nationwide prospective cohort-based study. Logistic regression analysis was used to identify sex-specific risk factors for adverse pregnancy outcome.RESULTSA total of 323 type 1 diabetic pregnancies were included; 314 were ongoing after 24 weeks of gestation. There were eight twin pregnancies and one triplet, resulting in 324 infants born after 24 weeks of gestation. Multiple logistic regression analysis showed that the occurrence of congenital malformations was independently associated with male newborns (OR 3.5 [95% CI 1.3–10.0]; P = 0.02).CONCLUSIONSThe higher incidence of congenital malformations in infants of women with type 1 diabetes appears to be restricted to male infants only.

Awareness about problems associated with consanguineous marriages: Survey among Israeli Arab adolescents

Purpose To evaluate the level of knowledge among adolescents about the issues associated with consanguinity, because consanguineous marriages are widely practiced among Arabs, and are associated with an increased incidence of congenital malformations. Methods We carried out a national survey among 2933 students aged 15–16 years within the Israeli Arab community. Variables considered were gender, religion, location of residence, parents’ level of education, number of siblings, whether their parents’ marriage was consanguineous, whether any family members had congenital malformations, and the respondents’ religious beliefs and traditions. Association among those variables and the level of knowledge that were statistically significant by univariate analysis were also assessed in a multivariate model. Results One-quarter of the students (24.5%) demonstrated a high level of knowledge, whereas 29.7% had a moderate level and 45.8% a low level. Overall, 81.5% knew that consanguinity was associated with a high incidence of congenital malformations, although only half of these (50.0%) knew what congenital malformations were and which were associated with consanguinity. The variables significantly associated with a low level of knowledge were gender, level of parents’ education, consanguinity between the students’ parents, and extreme religious attitudes. Conclusions Efforts to increase the knowledge of Israeli Arab adolescents about consanguinity should therefore be especially directed toward males with parents who have a lower level of education, with parents who are consanguineous, and who have extreme religious attitudes.

P12.19: Growth discordance in twin pregnancies at birth: determining factors?

To study factors determining severe intertwin growth discordance Obstetric and perinatal data of 494 consecutive twin pregnancies registered from 22 weeks of gestation were retrospectively retrieved from a computerized database. Pathological examination of the placenta was available in each case. Discordant fetal growth was defined as absent (ADG), moderate (MDG) or severe (SDG) when the intertwin weight difference at birth was respectively < 5%, 5–25% or > 25%. The impact of maternal age, fetal death, the presence of congenital malformations, total placental weight and placental and umbilical cord abnormalities was analyzed. SDG was present in 48/494 twin pregnancies (9.4%), but occurred significantly less frequently in dichorionic (36/429 or 8.4%) compared with monochorionic pregnancies (12/65 or 18.5%) (p: 0.02; RR: 0.45). SDG in dichorionic twin pregnancies was not significantly associated with maternal age, fetal death, an excess of congenital malformations, nor with placental or umbilical cord abnormalities. Total placental weight in the SDG twins (850 g ± 187) was not significantly lower than in MDG (893 ± 240) or ADG (906 g ± 216) (P = 0.428). Monochorionic pregnancies with SGD showed less frequently no congenital malformations in both fetuses (9/12) and had a significantly lower placenta weight (712 g ± 140) than normal or MGD ones (34/36; p: 0.07 and 880 g ± 214; p: 0.048). There were no other significant determining factors. Severe discordant birth weight in dichorionic pregnancies might reflect individual fetal growth potential or be induced by growth restriction related pathology. This will further be examined. In monochorionic pregnancies, the higher incidence of congenital malformations may contribute to SGD.