Birth Defects In Children Research Articles

A Reassessment of Birth Defects for Children of Participants of the Air Force Health Study

The Air Force Health Study (AFHS), also called the Ranch Hand Study, investigated the impact of exposure to dioxin the toxic contaminant in Agent Orange on health, survival, and reproductive outcomes of male Air Force Vietnam War veterans. It was concluded that available reproductive outcome data did not provide support for an adverse association with paternal dioxin exposure. A more extensive set of AFHS data was used to reassess this conclusion, restricting to the case of birth defects in children fathered after the start of the first Vietnam War tour. Analyses started by repeating published analyses, followed by assessing decisions made in those analyses, for example, of excluding participants with dioxin levels below the detectable limit, using a threshold of 10 parts per trillion for a high dioxin level, and not adjusting for multiple conceptions/children of the same participant. Using data for all participants with measured dioxin levels, both veterans who served in Operation Ranch Hand and other non-Ranch Hand veterans, and after accounting for correlation within children of the same participant, the occurrence for children fathered after the start of the first tour of a major defect, a non-major defect, and multiple defects depended significantly on participants having a high dioxin level. These conclusions were not changed by consideration of covariates. In contrast to prior published analyses, the more extensive AFHS data provided support for an adverse effect of paternal dioxin exposure on birth defects. However, the study had many limitations that could have affected the conclusions.

Birth defects after use of antithyroid drugs in early pregnancy: a Swedish nationwide study.

Antithyroid drugs (ATDs) may have teratogenic effects, but more evidence is needed on the risk and types of birth defects after the use of methimazole (MMI) and propylthiouracil (PTU). This study aimed to evaluate the association between the use of ATDs in early pregnancy and birth defects. Swedish nationwide register-based cohort study. The study included 684 340 children live-born in Sweden from 2006 to 2012. Exposure groups defined by maternal ATD use in early pregnancy were MMI (n = 162); PTU (n = 218); MMI and PTU (n = 66); ATD before or after, but not in pregnancy (n = 1551) and non-exposed (never ATD (n = 682 343)). Outcome was cumulative incidence of birth defects diagnosed before two years of age. The cumulative incidence of birth defects was not significantly different in children exposed to MMI (6.8%, P = 0.6) or PTU (6.4%, P = 0.4) vs non-exposed (8.0%). For subtypes of birth defects, MMI was associated with an increased incidence of septal heart defects (P = 0.02). PTU was associated with ear (P = 0.005) and obstructive urinary system malformations (P = 0.006). A case of choanal atresia was observed after exposure to both MMI and PTU. The incidence of birth defects in children born to mothers who received ATD before or after, but not in pregnancy, was 8.8% and not significantly different from non-exposed (P = 0.3), MMI exposed (P = 0.4) or PTU exposed (P = 0.2). MMI and PTU were associated with subtypes of birth defects previously reported, but the frequency of ATD exposure in early pregnancy was low and severe malformations described in the MMI embryopathy were rarely observed.

Etiology and clinical presentation of birth defects: population based study

Objective To assess causation and clinical presentation of major birth defects.Design Population based case cohort.Setting Cases of birth defects in children born 2005-09 to resident women, ascertained through Utah’s population...

Integrated analysis of DNA methylation and RNA‑sequencing data in Down syndrome.

Down syndrome (DS) is the most common birth defect in children. To investigate the mechanisms of DS, the present study analyzed the bisulfite‑sequencing (seq) data GSE42144, which was downloaded from the Gene Expression Omnibus. GSE42144 included DNA methylation data of three DS samples and three control samples, and RNA‑seq data of two DS samples and five control samples. The methylated sites in the bisulfite‑seq data were detected using Bismark and Bowtie2. The BiSeq tool was applied to determine differentially methylated regions and to identify adjacent genes. Using the Database for Annotation, Visualization and Integrated Discovery, the functions of the abnormal demethylated genes were predicted by functional enrichment analyses. Differentially expressed genes (DEGs) were then screened using a paired t‑test. Furthermore, the interactions of the proteins encoded by selected genes were determined using the Search Tool for the Retrieval of Interacting Genes, and a protein‑protein interaction (PPI) network was constructed using Cytoscape. A total of 74CpG regions showed significant differential DNA methylation between the DS and normal samples. There were five abnormal demethylated DNA regions in chromosome 21. In the DS samples, a total of 43 adjacent genes were identified with demethylation in their promoter regions and one adjacent gene was identified with upregulated methylation in its promoter regions. In addition, 584 upregulated genes were identified, including 24genes with transcriptional regulatory function. In particular, upregulated Runt‑related transcription factor1 (RUNX1) was located on chromosome 21. Functional enrichment analysis indicated that inhibitor of DNA binding4 (ID4) was involved in neuronal differentiation and transcriptional suppression. In the PPI network, genes may be involved in DS by interacting with others, including nuclear receptor subfamily4 groupA member2 (NR4A2)‑early growth response (EGR)2 and NR4A2‑EGR3. Therefore, RUNX1, NR4A2, EGR2, EGR3 and ID4 may be key genes associated with the pathogenesis of DS.

Birth defects in infants born to employees of a microelectronics and business machine manufacturing facility.

Concerns about solvent releases from a microelectronics/business machine manufacturing facility in upstate New York led to interest in the health of former workers, including this investigation of birth defects in children of male and female employees. Children born 1983 to 2001 to facility employees were enumerated and matched to New York State's Congenital Malformations Registry. Reported structural birth defects were compared with numbers expected from state rates (excluding New York City), generating standardized prevalence ratios (SPRs). Exposure assessors classified employees as ever/never potentially exposed at the facility to metals, chlorinated hydrocarbons, and other hydrocarbons during windows critical to organogenesis (female workers) or spermatogenesis (male workers). Among workers, adjusted prevalence ratios were generated to evaluate associations between potential exposures and specific birth defects. External comparisons for structural defects were at expectation for infants of male workers (SPR = 1.01; 95% confidence interval [CI], 0.77-1.29; n = 60) and lower for births to female workers (SPR = 0.84; 95% CI, 0.50-1.33; n = 18). Among full-term infants of male workers, ventricular septal defects (VSDs) were somewhat elevated compared with the general population (SPR = 1.58; 95% CI, 0.99-2.39; n = 22). Within the cohort, potential paternal metal exposure was associated with increased VSD risk (adjusted prevalence ratio = 2.70; 95% CI, = 1.09-6.67; n = 7). While overall SPRs were near expectation, paternal exposure to metals (primarily lead) appeared to be associated with increased VSD risk in infants. Take-home of occupational exposures, nonoccupational exposures, and chance could not be ruled out as causes. Case numbers for many defects were small, limiting assessment of the role of occupational exposures. Birth Defects Research (Part A) 106:696-707, 2016. © 2016 Wiley Periodicals, Inc.

Ondansetron Use in Pregnancy and Birth Defects: A Systematic Review.

To examine the risk of birth defects in children born to women who used ondansetron early in pregnancy for nausea and vomiting of pregnancy or hyperemesis gravidarum. PubMed, EMBASE, Cochrane, Scopus, Web of Science, Journals@Ovid Fulltext, ClinicalTrials.gov, and Google Scholar databases. Studies were included for review if they were written in English, included a comparison population of patients not exposed to ondansetron, and reported human data, original research, exposure to ondansetron during the first trimester, and structural birth defects as an outcome. A total of 423 records were identified. After accounting for duplicate records and including only relevant articles, a total of eight records met criteria for review. Data from the various studies were conflicting: whereas the three largest studies showed no increased risk of birth defects as a whole (36 malformations, 1,233 exposed compared with 141 malformations and 4,932 unexposed; 58/1,248 exposed compared with 31,357/895,770 unexposed; and 38/1,349 exposed compared with 43,620/1,500,085 unexposed; with odds ratios [ORs] of 1.12 (95% confidence interval [CI] 0.69-1.82), 1.3 [95% CI 1.0-1.7], and 0.95 [95% CI 0.72-1.26], respectively), two of these studies demonstrated a slightly increased risk of cardiac defects specifically (OR 2.0 [95% CI 1.3-3.1] and 1.62 [95% CI 1.04-2.14]), a finding that was not replicated in other studies. The most consistent association (if any) appears to be a small increase in the incidence of cardiac abnormalities, the bulk of which are septal defects. The overall risk of birth defects associated with ondansetron exposure appears to be low. There may be a small increase in the incidence of cardiac abnormalities in ondansetron-exposed neonates. Therefore, ondansetron use for nausea and vomiting of pregnancy should be reserved for those women whose symptoms have not been adequately controlled by other methods.

Prevalence of Extra-Cardiac Malformations with Congenital Heart Disease among Hospital Admitted Children- A Study in a Tertiary Level Hospital of Bangladesh

Introduction: Congenital anomalies are a major cause of stillbirths and infant mortality. In this post genomic era, congenital heart diseases (CHDs) are still the most common and lethal of all birth defects in children. Although most of the CHD occur as a sporadic event many of them have a well-defined genetic basis. This genetic basis is expressed in the form of concomitant occurrence of extra-cardiac malformations (ECM) which may occur alone or as a part of a syndrome.Objective: The present study was designed to find out the burden of CHDs in the hospital admitted children and to find out the prevalence of occurrence of clinically recognizable ECM associated with CHDs.Methods: This is a cross-sectional hospital based study. Total patients admitted during the study period were 5264. Of these 335 patients were found suffering from different types of congenital heart diseases. This gives the hospital admission rate for CHD, as 63.6 per 1000 admission (6.36%). Out of total 335 cases of CHD, 273 (81.5%) were acyanotic and 62 (18.5%) were cyanotic. Among the CHD patients 68 (20.3%) had a significant ECM. Out of the 68 patients with a significant ECM 53 (77.9%) had a clinically recognizable genetic syndrome, whereas 15 cases (22.1%) had a major ECM which was not a part of a syndrome.Conclusion: A high rate of hospital admission is found for CHDs in the pediatric setting, signifying the need for improvement of pediatric cardiology infrastructure in Bangladesh, which should help in providing better medical and surgical care for the patients with CHD. A significant proportion of patients with CHD have associated ECM, implicating a genetic background for the etiology of CHD. It also emphasizes the need for thorough evaluation of patient with CHD for ECM.Journal of Armed Forces Medical College Bangladesh Vol.10(2) 2014

SSRIs and venlafaxine show no major risk of cardiac birth defects

A population‐based cohort study that included births in five nations found no significant increase in the prevalence of cardiac birth defects in children born to mothers who took selective serotonin reuptake inhibitors (SSRIs) or venlafaxine during pregnancy. The study accounted for numerous potential confounding factors, including by using sibling‐controlled analyses to examine families in which one child was exposed to an antidepressant in utero and the other was not.

Maternal smoking during pregnancy and birth defects in children: a systematic review with meta-analysis.

This systematic review aimed to investigate the association between maternal smoking during pregnancy and birth defects in children. We performed an electronic search of observational studies in the databases ovid MEDLINE (1950 to April 2010), LILACS and SciELO. We included 188 studies with a total of 13,564,914 participants (192,655 cases). Significant positive associations were found between maternal smoking and birth defects in the following body systems: cardiovascular (OR: 1.11; 95%CI: 1.03-1.19), digestive (OR: 1.18; 95%CI: 1.07-1.30), musculoskeletal (OR: 1.27; 95%CI: 1.16-1.39) and face and neck (OR: 1.28; 95%CI: 1.19-1.37). The strength of association between maternal smoking and birth defects measured by the OR (95%CI) is significantly related to the amount of cigarettes smoked daily (χ2 = 12.1; df = 2; p = 0.002). In conclusion, maternal smoking during pregnancy is associated with congenital malformations in children and this association is dose-dependent.

Prenatal Phthalate Exposures and Anogenital Distance in Swedish Boys

Background: Phthalates are used as plasticizers in soft polyvinyl chloride (PVC) and in a large number of consumer products. Because of reported health risks, diisononyl phthalate (DiNP) has been introduced as a replacement for di(2-ethylhexyl) phthalate (DEHP) in soft PVC. This raises concerns because animal data suggest that DiNP may have antiandrogenic properties similar to those of DEHP. The anogenital distance (AGD)—the distance from the anus to the genitals—has been used to assess reproductive toxicity.Objective: The objective of this study was to examine the associations between prenatal phthalate exposure and AGD in Swedish infants.Methods: AGD was measured in 196 boys at 21 months of age, and first-trimester urine was analyzed for 10 phthalate metabolites of DEP (diethyl phthalate), DBP (dibutyl phthalate), DEHP, BBzP (benzylbutyl phthalate), as well as DiNP and creatinine. Data on covariates were collected by questionnaires.Results: The most significant associations were found between the shorter of two AGD measures (anoscrotal distance; AGDas) and DiNP metabolites and strongest for oh-MMeOP [mono-(4-methyl-7-hydroxyloctyl) phthalate] and oxo-MMeOP [mono-(2-ethyl-5-oxohexyl) phthalate]. However, the AGDas reduction was small (4%) in relation to more than an interquartile range increase in DiNP exposure.Conclusions: These findings call into question the safety of substituting DiNP for DEHP in soft PVC, particularly because a shorter male AGD has been shown to relate to male genital birth defects in children and impaired reproductive function in adult males and the fact that human levels of DiNP are increasing globally.Citation: Bornehag CG, Carlstedt F, Jönsson BA, Lindh CH, Jensen TK, Bodin A, Jonsson C, Janson S, Swan SH. 2015. Prenatal phthalate exposures and anogenital distance in Swedish boys. Environ Health Perspect 123:101–107; http://dx.doi.org/10.1289/ehp.1408163

Congenital Malformations, Chromosomal Abnormalities and Perinatal Results in IVF/ICSI Newborns Resulting from Very Poor Quality Embryos: A Case-Control Study

Aims: To explore whether the transfer of very poor quality (VPQ) embryos is associated with an increase in congenital malformations or perinatal problems. Methods: In this retrospective case-control study, 74 children conceived by in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) resulting exclusively from the transfer of VPQ embryos were compared with 1,507 children born after the transfer of top morphological quality (TQ) embryos over the same period of time in the same centers. Results: The prevalence of birth defects in children resulting from VPQ embryos was 1.35% (1/74), similar to the 1.72% (26/1,507) when only TQ embryos were transferred; the rate of chromosomal abnormalities detected was also similar (0.0 vs. 0.4%), as was perinatal mortality. After correcting for multiplicity (higher in the TQ group), the aforementioned parameters remained similar in the two groups. Conclusion: Congenital malformations and perinatal complications do not seem to be more common in children born after transfer of VPQ embryos in IVF/ICSI cycles. Given our preliminary data, which need to be confirmed in much larger studies, when only VPQ embryos are available for transfer in IVF/ICSI cycles, we do not believe that they should be discarded with the intention of avoiding birth defects or perinatal complications.

Physical and mental development of children after levonorgestrel emergency contraception exposure: a follow-up prospective cohort study.

Levonorgestrel (LNG), a dedicated emergency contraception (EC) product, has been available over-the-counter in China for more than 14 yr. Although LNG-EC is considered to have no effects on the developing fetus if the contraceptive fails and pregnancy occurs, there have been a few studies specifically examining this issue. The purpose of this study was to compare the physical and mental development of children born after LNG-EC failure with that of a cohort of children born to mothers with no history of exposure to LNG or any teratogenic substances. A group of 195 children who were exposed to LNG-EC during their mothers' conception cycle (study group) were matched to a group of 214 children without exposure to LNG (control group). The physical and mental development of the children were evaluated and compared over a 2-yr period. There were four congenital malformations in the study group and three in the control group (2.1% vs. 1.4%, respectively, P > 0.05). Over the 2-yr follow-up period, there were no statistically significant differences between the two groups with respect to children's weight, height, head circumference, and intelligence scores, and the values of all parameters of both groups were similar to those of the national standards. In summary, LNG-EC has no effect on the physical growth, mental development, or occurrence of birth defects in children born from pregnancies in which EC failed.

Extracardiac birth defects in children with congenital heart defects.

To assess the proportion and pattern of extracardiac birth defects in children with congenital heart defects referred to a tertiary care institute. Cross-sectional observational study from January 2010 to June 2011. Out of 560 children with congenital heart defects, 98 (17.5%) had extracardiac birth defects. Fifty-six had multiple congenital defects; 36 were syndromic cases and 6 had laterality defects. A total of 386 extracardiac birth defects (103 major and 283 minor) were documented, with craniofacial and skeletal birth defects being the commonest. Extracardiac birth defects are common in children with congenital heart defects.

Association between prenatal exposure to antiretroviral therapy and birth defects: an analysis of the French perinatal cohort study (ANRS CO1/CO11).

Antiretroviral therapy (ART) has major benefits during pregnancy, both for maternal health and to prevent mother-to-child transmission of HIV. Safety issues, including teratogenic risk, need to be evaluated. We estimated the prevalence of birth defects in children born to HIV-infected women receiving ART during pregnancy, and assessed the independent association of birth defects with each antiretroviral (ARV) drug used. The French Perinatal Cohort prospectively enrolls HIV-infected women delivering in 90 centers throughout France. Children are followed by pediatricians until 2 y of age according to national guidelines. We included 13,124 live births between 1994 and 2010, among which, 42% (n = 5,388) were exposed to ART in the first trimester of pregnancy. Birth defects were studied using both European Surveillance of Congenital Anomalies (EUROCAT) and Metropolitan Atlanta Congenital Defects Program (MACDP) classifications; associations with ART were evaluated using univariate and multivariate logistic regressions. Correction for multiple comparisons was not performed because the analyses were based on hypotheses emanating from previous findings in the literature and the robustness of the findings of the current study. The prevalence of birth defects was 4.4% (95% CI 4.0%-4.7%), according to the EUROCAT classification. In multivariate analysis adjusting for other ARV drugs, maternal age, geographical origin, intravenous drug use, and type of maternity center, a significant association was found between exposure to zidovudine in the first trimester and congenital heart defects: 2.3% (74/3,267), adjusted odds ratio (AOR) = 2.2 (95% CI 1.3-3.7), p = 0.003, absolute risk difference attributed to zidovudine +1.2% (95% CI +0.5; +1.9%). Didanosine and indinavir were associated with head and neck defects, respectively: 0.5%, AOR = 3.4 (95% CI 1.1-10.4), p = 0.04; 0.9%, AOR = 3.8 (95% CI 1.1-13.8), p = 0.04. We found a significant association between efavirenz and neurological defects (n = 4) using the MACDP classification: AOR = 3.0 (95% CI 1.1-8.5), p = 0.04, absolute risk +0.7% (95% CI +0.07%; +1.3%). But the association was not significant using the less inclusive EUROCAT classification: AOR = 2.1 (95% CI 0.7-5.9), p = 0.16. No association was found between birth defects and lopinavir or ritonavir with a power >85% for an odds ratio of 1.5, nor for nevirapine, tenofovir, stavudine, or abacavir with a power >70%. Limitations of the present study were the absence of data on termination of pregnancy, stillbirths, tobacco and alcohol intake, and concomitant medication. We found a specific association between in utero exposure to zidovudine and heart defects; the mechanisms need to be elucidated. The association between efavirenz and neurological defects must be interpreted with caution. For the other drugs not associated with birth defects, the results were reassuring. Finally, whatever the impact that some ARV drugs may have on birth defects, it is surpassed by the major role of ART in the successful prevention of mother-to-child transmission of HIV. Please see later in the article for the Editors' Summary.

Fetal growth restriction and birth defects with newer and older antiepileptic drugs during pregnancy

The primary aim of this study was to assess the risks of fetal growth restriction and birth defects in children exposed prenatally to newer and older antiepileptic drugs, using an unselected epilepsy cohort. Deliveries recorded in the compulsory Medical Birth Registry of Norway 1999-2011 formed the study population. All 2,600 children exposed to antiepileptic drugs during pregnancy were compared to all 771,412 unexposed children born to women without epilepsy. Children of untreated mothers with epilepsy served as an internal control group. The main outcomes were small for gestational age birth weight and head circumference, and major congenital malformations. Children exposed to antiepileptic drugs had a moderate risk of growth restriction. Infants exposed to topiramate had a considerable risk of microcephaly (11.4 vs. 2.4 %; OR 4.8; CI 2.5-9.3) and small for gestational age birth weight (24.4 vs. 8.9 %; OR 3.1; 95 % CI 1.9-5.3). Carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, gabapentin, and pregabalin had low malformation rates, whereas topiramate tended to have an elevated malformation rate. Valproate monotherapy was associated with a significant risk of birth defects (6.3 vs. 2.9 %; OR 2.5; CI 1.6-3.8), and specifically with septal heart defects and hypospadias. For mothers using valproate, the presence of major birth defect in one child was associated with a markedly increased risk for the siblings (42.9 vs. 6.7 %; OR 10.4; CI 2.3-46.7). Children of untreated mothers with epilepsy had malformation risk similar to the reference group. In conclusion, topiramate was associated with a substantial risk of fetal growth restriction, and possibly an increased malformation rate. Other newer-generation antiepileptic drugs had a low malformation rate. Valproate monotherapy had a significant malformation risk, especially in repeated pregnancies.

Birth Defects in Assisted Reproductive Technology and Spontaneously Conceived Children: A Meta-analysis

Objective To evaluate the risk of birth defects in children born following assisted reproductive technology (ART) and spontaneous conceptions. Methods This study carried out an updated systematic review to identify papers published by August 2013 with data relating to birth defects of children conceived using ART (IVF and/or ICSI) compared with those spontaneously conceived and also compared birth defects between subgroups of IVF and ICSI. Results Totally 76 studies were identified for review. The individual relative risk (RR) estimated for these studies ranged from 0.44 to 5.51, a significantly increased risk of birth defects was observed (RR=1.36, 95%CI=1.25–1.47) in ART compared with the spontaneously conceived group, which was also evident in the subgroup analysis. Among these studies, 16 studies simultaneously gave data of birth defects comparing IVF and ICSI children, which showed no difference in risk of combined effects (RR=0.90, 95%CI=0.80–1.02), but ICSI had a higher risk in subgroups of clinical research (RR=0.76, 95%CI=0.65–0.89) and crude RR value (RR=0.78, 95%CI=0.67–0.91). Conclusion Pooled results from all suitable published studies suggested that children born following ART were at increased risk of birth defects compared with spontaneous conceptions. There is no difference in birth defect risk between children conceived by IVF or ICSI using a summative analysis, however, ICSI had a significant higher risk in birth defect risk comparing with IVF when using subgroup analyses of sample size and RR value.

Alcohol, It’s Effect on Dental Structures and the Role of a Dentist

The first recognized and the most devastating effect of alcohol was the consequence of maternal ingestion of alcohol during pregnancy. Fetal Alcohol Syndrome (FAS) is a distinct condition associated with maternal alcoholism which causes serious birth defects in children due to disruption of normal embryonic development. Other problems that can occur are weak muscles around the mouth that make it difficult to consume food; unusual taste preferences for salty or spicy food at an inappropriate age; gross caries at a young age; prolonged and excessive drooling; weak buccinators muscles that prevent the proper placement of food for chewing. These are a few amongst the many problems which children diagnosed with FAS have to face thus increasing their predilection for caries and require special oral health care. Also, there are other direct and indirect effects of alcohol consumption on dental structures of which a few to be mentioned are dental erosion, attrition sometimes along with behavioral problems.

Low birth defects by deselecting abnormal spermatozoa before ICSI

Consistent evidence from meta-analysis has linked assisted conception by IVF, and particularly intracytoplasmic sperm injection (ICSI), with an increased risk of major birth defects. To compare the risk of major malformations of children born after standard ICSI and after intracytoplasmic injection of morphologically selected spermatozoa (IMSI), a prospective population-based study was conducted from 2005 to 2010. ICSI and IMSI were performed in only one assisted reproduction unit according to its classification of spermatozoa and using fresh semen. Medical data and follow up during 2 years of 1028 infants were collected. Major malformations were identified and classified by an external independent physician. The two groups were similar concerning the parents’ age, treatment, number of oocytes recovered, days of transfer, gestational age and birthweight. However, major malformations were significantly lower with IMSI (6/450, 1.33%) versus ICSI (22/578, 3.80%; adjusted odds ratio 0.35, 95% confidence interval 0.14–0.87, P=0.014), mainly affecting boys (adjusted odds ratio 2.84, 95% confidence interval 1.24–6.53, P=0.009). In conclusion, the significantly decreased risk of major birth defects associated with IMSI remained decreased after multivariate adjustment and highlights the beneficial effect of sperm selection before ICSI.The aim of this study was to compare the birth defects in children born after intracytoplasmic sperm injection (ICSI) and intracytoplasmic morphologically selected sperm injection (IMSI). We conducted a prospective population-based study from 2005 to 2010. Medical data and follow up at 2 years of age for 1028 infants were collected. We show that the major malformations were significantly lower in the IMSI group versus the ICSI group, and they mainly affected the boys. We found less abnormality when abnormal spermatozoa, according to the Cassuto Barak classification, were deselected at high magnification and not injected. In conclusion, the significantly decreased risk of major birth defects associated with IMSI remained decreased after multivariate adjustment and highlights the beneficial effect of spermatozoon selection before ICSI.

Assisted Reproductive Technology and Major Birth Defects in Western Australia

Assisted Reproductive Technology and Major Birth Defects in Western Australia

Oxidative stress and birth defects in infants of women with pregestational diabetes

Hyperglycemia characteristic of diabetes mellitus triggers pathological processes in fetal development of various structures such as the retina, peripheral nerves, renal glomerulus, and arterial and venous beds. Women with diabetes prior to conception have children with birth defects three to five times more frequently than women without diabetes. There is no specific pattern of birth defects, but the central nervous and cardiovascular systems are the most affected. Hyperglycemia leads to mitochrondrial superoxide radical production, which activates five metabolic pathways that mediate damage leading to diabetic embryopathy. Once oxidative stress is established, there is modification of gene expression controlling embryonic development in critical periods. Vitamin E application in animal models has greatly lowered occurrence of birth defects in embryonic and fetal stages, consistent with an etiologic role for oxidative stress in dysmorphogenesis. Effective metabolic control before and during pregnancy, achieved in Cuba by implementing programs for control of birth defects in children of diabetic pregnant women, has been found effective.