Higher Risk Of Congenital Malformations Research Articles

Maternal pre-pregnancy overweight or obesity and risk of birth defects in offspring: Population-based cohort study.

Maternal obesity, a health condition increasingly prevalent worldwide, has been suggested to be associated with a higher risk of birth defects in offspring, whereas evidence from population-based data from China was largely lacking. Additionally, the role of gestational diabetes in the association between maternal obesity and birth defects remains unclear. We aimed to investigate the association of maternal pre-pregnancy overweight or obesity with any and different types of birth defects in offspring and the interaction between pre-pregnancy overweight or obesity and gestational diabetes. We conducted a population-based cohort study including 257 107 singletons born between 2015 and 2021 in Longgang District, Shenzhen, China, using data from the Shenzhen Maternal and Child Health Management System. Poisson regression was conducted to estimate the associations of maternal pre-pregnancy overweight or obesity, as well as the interaction between pre-pregnancy overweight or obesity and gestational diabetes, with the risk of birth defects. Models were adjusted for maternal age at delivery, educational level, type of household registration, and gravidity. Maternal pre-pregnancy overweight was associated with a higher risk of any birth defect (risk ratio [RR] 1.21, 95% confidence interval [CI] 1.12 to 1.31) as well as of congenital malformations of the circulatory system (RR 1.26, 95% CI 1.12 to 1.41), eye/ear/face/neck (RR 1.42, 95% CI 1.04 to 1.94), and musculoskeletal system (RR 1.21, 95% CI 1.01 to 1.44). Maternal pre-pregnancy obesity was associated with a higher risk of any birth defect (RR 1.38, 95% CI 1.18 to 1.63) and congenital malformations of the circulatory system (RR 1.61, 95% CI 1.30 to 1.98). Infants born to overweight or obese mothers with gestational diabetes had a higher risk of congenital malformations of the circulatory system than infants born to overweight or obese mothers without gestational diabetes. Maternal pre-pregnancy overweight or obesity was associated with a higher risk of birth defects, particularly congenital malformations of the circulatory system, in offspring. Gestational diabetes interacts additively with pre-pregnancy overweight or obesity on modifying the risk of congenital malformations of the circulatory system. The importance of improving weight management and assessment of glucose and metabolic functions was emphasized among women planning for pregnancy who are overweight or obese.

Use of antipsychotics during pregnancy and their impact on congenital malformations and early neonatal adaptation.

Review of recent literature dealing with the effect of antipsychotic use during pregnancy on early postpartum adaptation of exposed infants and the development of congenital malformations. The use of antipsychotics during pregnancy does not appear to lead to significantly higher risk of congenital malformations but may pose a greater risk for the early adaptation of the newborn (especially the risk of preterm birth and intensive care unit admission). The study to date face methodological limitations - lack of information on exact doses of antipsychotics, lack of control groups of women with psychiatric problems but not taking antipsychotics and failure to control for confounding factors. The available data suggest the relative safety of antipsychotics during pregnancy, provided that potential risks are known, and the woman and her baby are carefully monitored.

Impact of consanguinity on spontaneous pregnancy loss and descendants’ health in north Morocco

PurposeThe present study aims to bring out the impact of consanguinity on spontaneous pregnancy loss (SPL) and on descendants’ health, among the population of north Morocco.Design/methodology/approachConvenience sampling was used for collecting data. A questionnaire was randomly administered to 385 couples represented by either the husband, the wife or both. The study lasted for three months, from January to March 2015.FindingsIn total, 238 valid questionnaires were analysed. The results showed that the consanguinity rate was 45.23% and that most consanguineous unions were between first cousins (91%). Data analysis revealed that SPL risk was similar in consanguineous and non-consanguineous couples (OR = 1.6; IC95% = 0.9–2.9). Also, no significant difference was observed in terms of SPL type (OR = 1.6; IC95% = 0.7–3.9) and frequency (p = 0.81). However, late SPL frequency was significantly lower in consanguineous couples (p < 0.001), whereas no significant difference was registered in terms of early SPL frequency (p = 0.73). On the other hand, consanguineous couples displayed a significantly higher risk of descendants’ health disorders in comparison with non-consanguineous ones. Moreover, the consanguineous couples had a significantly higher number of children with health disorders (p < 0.001). The risk analysis also showed that consanguineous couples displayed a significantly higher risk of congenital malformations (OR = 7.23; IC95% = 3.52–14.84) and multifactorial diseases (OR = 3.72; IC95% = 1.46–9.49), but no significant difference was observed in terms of behavioural disorders risk.Originality/valueThe population awareness regarding the negative effects of consanguinity should be raised through education programmes and premarital, prenatal and genetic counselling services.

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

<b>Introduction.</b> 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. <b>Aim.</b> 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. <b>Materials and methods.</b> 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. <b>Results and discussion.</b> 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. <b>Conclusions.</b> 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.

Assessment of indicators of reproductive health of the population of the Trans-Ural Republic of Bashkortostan in 2000–2020

BACKGROUND: The reproductive health of a population depends on many factors one of which is chemical pollution of the environment caused by both natural conditions and man-made impacts. The population living in geochemical provinces is often subject to pathological conditions caused by a lack, excess or imbalance of macro- and microelements. This study was carried out in the Republic of Bashkortostan in areas of natural and man-made anomalies with excessive content of heavy metals in the environment.
 AIM: To analyze the demographic profile and assess the reproductive health of the population of the Trans-Ural zone of the Republic of Bashkortostan.
 MATERIALS AND METHODS: A descriptive ecological study of the trend of reproductive health of the population of the Trans-Ural zone of the Republic of Bashkortostan was carried out using average population indicators. Statistical data presented in the open press by the Ministry of Health of the Republic of Bashkortostan for the 20002020 period were used. These data included demographic indicators, infant mortality, frequency of congenital malformations, and morbidity of children within the first year of life.
 RESULTS: In all the areas studied, there was a tendency for a decrease in the birth rate and an increase in the mortality rate. The highest average birth rate of 19.8 was recorded in the Burzyansky District and the lowest of 13.1 in the Zilairsky District, which was higher than the republican average of 12.4. During the study period, there was a significant decrease in infant mortality both in the republic and in the Trans-Urals regions. Average infant mortality rates relative to congenital malformations among newborns in the Sibay, Baymaksky, and Zianchurinsky Districts as well as the relative risk of blood diseases in children of the first year of life in most of the studied areas was higher than the average republican level.
 CONCLUSION: Reproductive health of the population of Sibay for the period 20002020 is exposed to a higher risk of congenital malformations and infant mortality than the average republican level. In the Baymaksky, Zianchurinsky, Uchalinsky and Khaibullinsky Districts, the risk of developing blood diseases in children within the first year of life was higher than the average republican level. The results further indicate the need to take measures to reduce risks and improve the safety of reproductive health of the population of the mining region.

Maternal and neonatal outcomes in pregnancies with type 2 diabetes in First Nation and other Manitoban people: a population-based study.

First Nation people living in Canada experience a high prevalence of type 2 diabetes in pregnancy. In this study, we aimed to describe maternal and neonatal outcomes in First Nation and all other females with type 2 diabetes living in Manitoba, Canada. This was a population-level retrospective cohort study using linked administrative data from Manitoba (2012-2017). We compared First Nation females with type 2 diabetes with all other Manitoban females with type 2 diabetes, using relative risks (RRs) and 95% confidence intervals (CIs). A total of 2181 females with type 2 diabetes were included, and 1218 (55.8%) were First Nation. First Nation females with type 2 diabetes were significantly more likely to experience stillbirth (RR 2.14, 95% CI 1.11-4.13) and perinatal death (RR 2.39, 95% CI 1.37-4.17) than all other Manitoban females with type 2 diabetes. Offspring of First Nation females with type 2 diabetes had a higher risk of most neonatal complications than offspring of all other Manitoban females with type 2 diabetes, including a higher risk of congenital malformations (RR 1.97, 95% CI 1.30-2.99), but First Nation people did not have a higher risk of most maternal complications. First Nation pregnant individuals living with type 2 diabetes experienced a higher risk for adverse pregnancy outcomes than all other Manitoban females with type 2 diabetes. Additional studies are needed to identify both high-risk and protective factors for pregnancy complications in First Nation people living with type 2 diabetes in pregnancy.

Maternal obesity: new placental paradigms unfolded.

The prevalence of maternal obesity is increasing at an alarming rate, and is providing a major challenge for obstetric practice. Adverse effects on maternal and fetal health are mediated by complex interactions between metabolic, inflammatory, and oxidative stress signaling in the placenta. Endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) are common downstream pathways of cell stress, and there is evidence that this conserved homeostatic response may be a key mediator in the pathogenesis of placental dysfunction. We summarize the current literature on the placental cellular and molecular changes that occur in obese women. A special focus is cast onto placental ER stress in obese pregnancy, which may provide a novel link for future investigation.

Twenty-year trends in the use of anti-seizure medication among pregnant women in the Netherlands

BackgroundAnti-seizure medications (ASMs) are used to treat conditions such as epilepsy and bipolar disorder. Some of these drugs are associated with an increased risk of congenital malformations and adverse developmental outcomes. ObjectivesTo examine trends in use of ASMs among pregnant women in the Netherlands according to medication safety profile. MethodsUsing population-based data from the PHARMO Perinatal Research Network, we assessed trends in use of ASMs among pregnant women in the Netherlands between 1999 and 2019, stratified by medication safety profile. Individual treatment patterns were also assessed. ResultsIn total, 671,709 pregnancies among 446,169 women were selected, of which 2405 (3.6 per 1000) were ASM-exposed. Over the study period, a significant increase was observed for use of known safest ASMs (0.7–18.0 per 10,000 pregnancies) as well as for those with uncertain risk (5.3–13.4 per 10,000 pregnancies). Use of ASMs with higher risk of congenital malformations decreased significantly (24.8–14.5 per 10,000 pregnancies), except for topiramate (0–6.7 per 10,000 pregnancies). Switches between ASM safety risk categories before and during pregnancy were uncommon; women rather discontinued treatment or switched within the same category. There was no clear change for the proportion using polytherapy during pregnancy (12% overall), however a non-significant trend toward inclusion of known safest ASMs was observed over time (1.9–3.6%). ConclusionsOver the last two decades, there has been an increase in use of known safest ASMs among pregnant women, together with a trend toward newer ASMs with uncertain risk. Only a small proportion of women switched to a safer alternative before or during pregnancy. Altogether, this highlights the need for an expansion of ASM risk knowledge and communication to healthcare providers and women of reproductive age to improve preconception counseling.

Análisis bioético del impacto de las Técnicas de Reproducción Asistida (TRA) en la salud de niños y madres

Las técnicas de reproducción asistida (TRA ) pueden estar asociadas a complicaciones obstétricas y perinatales, incluido un mayor riesgo de malformaciones congénitas y de patología adquirida. Es un deber de los profesionales sanitarios informar a quienes desean someterse a estas técnicas, sobre los riesgos para la salud de los hijos y las madres. A parte de los riesgos biológicos comentados, las TRA plantean también múltiples problemas bioéticos, que se han de abordar partiendo del valor fundamental de la vida humana.
 El objetivo principal de este estudio retrospectivo es el análisis bioético y biomédico del impacto de las TRA en la salud de los niños y sus madres, comparando el riesgo de patología entre los nacidos por TRA y por concepción natural.

Congenital heart disease and pregnancy

Annually, there > 30,000 infants are born with congenital heart defects; in different populations, the prevalence of congenital heart disease (CHD) varies from 2.4 to 14.15%. Women with CHD planning pregnancy are at increased risk of heart failure, arrhythmias, cerebrovascular disease, and embolism. In such patients, pregnancy course is complicated by intrauterine growth restriction, pre-eclampsia, and preterm birth. Their newborns generally have a low birth weight and high risk of congenital malformations including heart defects. European Society of Cardiology (ESC) developed risk assessment-based guidelines to optimise the management of pregnant women with CHD. This approach requires a cooperation of obstetrician-gynecologists, general practitioners, and cardiologists.

High mortality due to congenital malformations in children aged

BackgroundIn French Guiana, pregnant women may be exposed to infectious, environmental, and social risks leading to congenital malformation. The objective of the study was to study mortality rates from congenital malformations among infants < 1 year and to compare them with those in mainland France.MethodsWe used the CEPI DC (INSERM) database, which compiles annual data from death certificates in all French territories using the International Classification of Diseases. Annual deaths for French Guiana and mainland France between 2005 and 2015 were compiled. The age category studied was children less than 1 year and deaths from congenital malformations, deformations and chromosomal abnormalities were compiled. Crude risk ratios and 95% confidence intervals were calculated to quantify the excess risk of disease in French Guiana.ResultsIn French Guiana between 2005 and 2015 there were 666 deaths of children aged < 1 year, among which, 132 (19.8%) were due to congenital malformations and chromosomal anomalies. Overall the risk ratio of death from congenital malformations and chromosomal anomalies between French Guiana and mainland France was 2.7 (1.5–4.7), P < 0.001 for neurological congenital malformations it was 4.8 (1.2–19.7), P = 0.01 and for congenital malformations of the circulatory system it was 3.3 (1.5–6.9), P = 0.001.ConclusionsThe incidence of death from congenital malformations or chromosomal anomalies in French Guiana was significantly higher than in mainland France. Explanations for this may be infections, genetic causes, nutritional causes, and toxic causes that are prevalent. There is a need to identify factors that predispose children born in French Guiana to having a higher risk of congenital malformations and chromosomal anomalies.

Sexual and reproductive issues and inflammatory bowel disease: a neglected topic in men.

There has been considerable literature on sexual issues in women with inflammatory bowel disease (IBD), but relatively little attention has been paid to these aspects in men. To review the available literature and to provide the best management of sexual and reproductive issues in male patients with IBD. The scientific literature on sexual and reproductive issues in men with IBD was reviewed. Several factors, including surgical and medication treatments, disease activity, lifestyle, and psychological factors, may play a role in the development of infertility and sexual dysfunction and may negatively impact pregnancy outcomes. Proctocolectomy with ileal pouch-anal anastomosis increases the risk of erectile and ejaculatory dysfunction by up to 26%. A treatment with sildenafil can be effective. Sperm banking should be advised to young men with IBD before surgery. Both sulfasalazine and methotrexate may be responsible for reversible sexual dysfunction and infertility. Furthermore, sulfasalazine should be switched to mesalazine at least 4 months before conception because of a higher risk of congenital malformations in pregnancies fathered by men treated with this drug. Psychotropic drugs, frequently used in IBD, may cause sexual dysfunction up to 80%. Last but not the least, voluntary childlessness occurs frequently, mainly because of concerns about medication safety in pregnancy and fear of transmitting disease. Accurate counseling, and where necessary, psychological support can decrease any misperceptions and fears. Close collaboration between the gastroenterologist and the patient is recommended for the best management of these relevant, neglected aspects in men with IBD.

Adverse perinatal outcome in teenage pregnancies: an analysis of a 5-year period in Southeastern Hungary

Objective: To determine the risks of adverse perinatal outcomes of teenage mothers.Material and methods: A retrospective analysis was performed on teenage mothers (under 20 years of age) who delivered in the period of 2010–2014 at the Department of Obstetrics and Gynecology, University of Szeged (study group). All mothers who delivered in Hungary during the same period were studied as a control group. The following parameters were analyzed: demographic data of the mothers, maternal complications, perinatal outcome and congenital malformations of the newborns. The binominal test, Student’s t-test and Poisson’s regression were applied using STATA 9.0 (StataCorp, College Station, TX, USA) statistical software (p < .05 was considered to be statistically significant).Results: During this 5-year period, 12,845 births were recorded at the Department, of these 274 (2.1%) were teenage pregnancies with 275 newborns. The offsprings of teenage mothers had significantly lower mean birth weight (3110.2 ± 564.03 g versus 3247 g), higher rate of congenital malformations (8.0 versus 5.0%) and higher admission to neonatal intensive care unit (12.4 versus 8.0%) than the infants in the control group.Conclusions: Younger maternal age was significantly associated with lower mean birth weight, higher risk of congenital malformations, and increased admission rate to neonatal intensive care unit.

Catarata congénita en un paciente con aneuploidía cromosómica 47,XYY

Case reportThe case concerns a 16 year-old boy with a history of high myopia and unilateral congenital cataract, tall stature for age, facial dysmorphism, hypermobile metacarpal-phalangeal joints, as well as behavioural problems. The mother had a history of recurrent pregnancy loss. Chromosomal analysis of the peripheral blood lymphocytes reported 47,XYY. DiscussionPatients with sex chromosome aneuploidy 47,XYY have higher risk of congenital malformations, although ophthalmological anomalies are unusual. Evaluation of patients with tall stature and behavioural problems should include a chromosomal analysis in order to determine the aetiology.

Morbimortalidad hospitalaria en niños con síndrome de Down

IntroductionChildren with Down's syndrome (DS) have a higher risk of congenital malformations and acute diseases, with increased risk of hospital admissions compared with the general population. This study describes patterns of hospital admissions for children and adolescents with DS. Patients and methodsA retrospective study of hospital admissions of children with DS, younger than 15 years old, and cared for by the Paediatric Department of the Hospital Clínico Pontificia Universidad Católica de Chile, between 2008 and 2011. ResultsThere were 222 admissions of 161 patients with DS during the study period, of which 110 were girls. The median age was 8 months, and the median hospital stay was 6 days. Just over half (56.7%) of the hospital stays were in the Paediatric Critic Care Unit. Heart surgery was performed on 59.4%, and the principal congenital heart defect attended was atrioventricular canal. The principal diagnosis, other than heart surgery, was lower respiratory tract infection. In this series, 3 children died. ConclusionsChildren with DS are a relevant group for inpatient care, because their high incidence in Chile, their respiratory and cardiovascular risk, prolonged hospitalizations, high frequency of critical care days and mortality risk. This group has special and complex needs during their hospitalizations and it is necessary to create a multidisciplinary team with competences to take care the particular characteristics of this vulnerable group.

Assisted reproductive technology and risk of congenital malformations: a meta-analysis based on cohort studies.

To assess the association between assisted reproductive technology (ART) and risk of congenital malformations (CM) by conducting a meta-analysis of cohort studies. PubMed, Google Scholar, Cochrane Libraries and Chinese database were searched through August 2014 to identify studies that met pre-stated inclusion criteria. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Subgroup analysis was performed to explore potential heterogeneity moderators. Fifty-seven studies involving 119,874 infants conceived following ART and 1,212,320 infants conceived naturally were included in the analysis. The ART-conceived infants were associated with a higher risk of CM [relative risk (RR)=1.33; 95% confidence interval (CI) 1.24-1.43] when compared with those conceived naturally. When data were restricted to singleton births (RR=1.38; 95% CI 1.30-1.47), major CM (RR=1.47; 95% CI 1.29-1.68), matched/adjusted studies (RR=1.37; 95% CI 1.27-1.47) or high quality studies (RR=1.40; 95% CI 1.27-1.55), the increased risk of CM still existed in ART pregnancies. Additionally, an increased risk of CM was also found when the ART twin (RR=1.18; 95% CI 1.06-1.32) or multiple births (RR=1.16; 95% CI 1.05-1.27) were separately compared with spontaneously conceived twin or multiple births. Substantial heterogeneity was observed across studies (I (2)=68, 44, 39, and 33% for all infants, singletons, twins and multiples, respectively). Whether confounding factors were matched or adjusted, study quality and sample size as the first three of the most relevant heterogeneity moderators have been identified. No evidence of publication bias was observed (P>0.10). The ART-conceived infants have a higher risk of CM compared with those conceived naturally. However, these estimates have to be viewed with caution because of heterogeneity.

Perinatal outcomes among women with bipolar disorder: a population-based cohort study

To evaluate the risk of adverse perinatal outcomes among pregnant women previously hospitalized for bipolar disorder. We completed a population-based cohort study of women with a singleton delivery in Ontario, Canada (2003 to 2011). Women previously hospitalized for bipolar disorder (n = 1859) or major depressive disorder (n = 3724) were each compared to women without a documented mental illness (n = 432,358). Main study outcomes were preterm birth, severe small for gestational age <3rd percentile birthweight, and severe large for gestational age >97th percentile birthweight. Secondary outcomes included stillbirth, congenital malformations, neonatal morbidity and readmission to hospital <28 days. Odds ratios (ORs) were adjusted for maternal age, parity, prepregnancy obesity, substance use, and diabetes mellitus or hypertension before or during pregnancy. Bipolar disorder (adjusted OR [AOR], 1.95; 95% confidence interval [CI], 1.68-2.26) and major depressive disorder (AOR, 1.91; 95% CI, 1.72-2.13) were each associated with preterm birth. Bipolar disorder was associated with severe large for gestational age (AOR, 1.31; 95% CI, 1.03-1.67). Major depressive disorder was associated with severe small for gestational age (AOR, 1.22; 95% CI, 1.05-1.42). Both mood disorder groups had significantly higher risk of congenital malformations, neonatal morbidity, and neonatal hospital readmission. Although study covariates explained some of the increased risk, we could not address all potential explanatory factors. Women previously hospitalized for bipolar disorder are at increased risk of adverse perinatal outcomes compared with the general population. Their level of risk is comparable to women previously hospitalized for major depressive disorder. These risks must be considered in the management of pregnant women with a history of major mood disorders. Attention to potentially modifiable risk factors such as obesity, diabetes, and hypertension before and during pregnancy could reduce the risk for adverse perinatal outcomes.

Assisted reproductive techniques and the risk of anorectal malformations: a German case-control study.

BackgroundThe use of assisted reproductive techniques (ART) for treatment of infertility is increasing rapidly worldwide. However, various health effects have been reported including a higher risk of congenital malformations. Therefore, we assessed the risk of anorectal malformations (ARM) after in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).MethodsData of the German Network for Congenital Uro-REctal malformations (CURE-Net) were compared to nationwide data of the German IVF register and the Federal Statistical Office (DESTATIS). Odds ratios (95% confidence intervals) were determined to quantify associations using multivariable logistic regression accounting for potential confounding or interaction by plurality of births.ResultsIn total, 295 ARM patients born between 1997 and 2011 in Germany, who were recruited through participating pediatric surgeries from all over Germany and the German self-help organisation SoMA, were included. Controls were all German live-births (n = 10,069,986) born between 1997 and 2010. Overall, 30 cases (10%) and 129,982 controls (1%) were born after IVF or ICSI, which translates to an odds ratio (95% confidence interval) of 8.7 (5.9–12.6) between ART and ARM in bivariate analyses. Separate analyses showed a significantly increased risk for ARM after IVF (OR, 10.9; 95% CI, 6.2–19.0; P < 0.0001) as well as after ICSI (OR, 7.5; 95% CI, 4.6–12.2; P < 0.0001). Furthermore, separate analyses of patients with isolated ARM, ARM with associated anomalies and those with a VATER/VACTERL association showed strong associations with ART (ORs 4.9, 11.9 and 7.9, respectively). After stratification for plurality of birth, the corresponding odds ratios (95% confidence intervals) were 7.7 (4.6–12.7) for singletons and 4.9 (2.4–10.1) for multiple births.ConclusionsThere is a strongly increased risk for ARM among children born after ART. Elevations of risk were seen after both IVF and ICSI. Further, separate analyses of patients with isolated ARM, ARM with associated anomalies and those with a VATER/VACTERL association showed increased risks in each group. An increased risk of ARM was also seen among both singletons and multiple births.

Imatinib mesylate at therapeutic doses has no impact on folliculogenesis or spermatogenesis in a leukaemic mouse model

Imatinib should be avoided in women planning to become pregnant or during pregnancy, due to a higher risk of congenital malformations. However, it is not known whether imatinib affects future potential for fertility. Here we analysed ovaries and testes from adult mice receiving imatinib, focusing on testicular and ovarian functions. Seven male and 7 female mice were orally treated with 150mg/kg body weight/day imatinib for two months. No effects on folliculogenesis or spermatogenesis could be observed postmortem by histological examinations, suggesting that, at least in two mouse models of imatinib treatment this tyrosine kinase inhibitor does not reduce fertility.

Genetics and developmental pathology of twinning

Twin pregnancy is associated with a high risk of congenital malformations. This review covers the risk of such anomalies in both dizygotic and monozygotic twin pregnancies, and discusses current insights into the associations relating to zygosity, chorionicity and genetic factors. The pathological basis of specific malformations unique to the monochorionic twinning process, including conjoined twinning and twin reversed arterial perfusion (TRAP) sequence, is discussed in more detail, and factors contributing to the higher perinatal mortality rate in multiple pregnancies are addressed.