Risk Of Birth Defects Research Articles

P030 Quality improvement project on awareness in patients to stop teratogenic disease-modifying anti-rheumatic drugs (DMARDs) while planning pregnancy and need for highly effective contraception

Abstract Background/Aims The MHRA (Medicines and Healthcare Products Regulatory Agency) published guidelines in February 2018 on highly effective contraception (injectable/IUCD/partner vasectomy) for women of childbearing age consuming potentially teratogenic DMARDs (disease-modifying anti-rheumatic drugs) which might result in increased risk of birth defects. Objective: A quality improvement project was carried out in the rheumatology department at James Cook University Hospital, Middlesbrough to assess patient awareness of the potential teratogenicity of the DMARDS like methotrexate, leflunomide and mycophenolate mofetil and need for highly effective contraception to avoid foetal complications. Methods A spot audit was carried out from June to September 2019, through patient questionnaires to assess awareness in women of childbearing age (15- 45 years) about the potential teratogenic effects of these DMARDs and the need for highly effective contraception. Following this audit more tailored consent forms were introduced in February 2020 to increase awareness of potential teratogenicity at initiation of DMARDs with robust counselling. Subsequent to this we carried out quality improvement project to accumulate similar data between June and September 2021. Results Data were collected from 43 patients during the spot and 27 patients during the second cycle. 88% patients were on methotrexate, 9% on MMF, 2% on leflunomide and 2% on multiple DMARDS during the first audit compared to 66.6% on methotrexate, 16.6% on leflunomide and 6% on MMF during the second cycle. It was very positive to see 74% of patients reporting increased awareness about potential teratogenicity of the DMARDS gained through counselling compared to the 37% previously. 90% of the patients were aware to stop these DMARDs when planning pregnancy compared to the 88% previously. We achieved 100% awareness that the medication should be stopped in pregnancy compared to 90% previously. Rates of contraception use were comparable across cycles - 54% during the first cycle and 56.7% during the second. Of patients using contraception, 33.3% were using highly effective contraception the first cycle which improved to 37% during the second cycle. Nearly 44.4% patients were not on any contraception. Reasons why contraception was not used was not explored which was beyond remit of this project. Since this is a significant proportion there is certainly a need for further assessment and analysis. Conclusion Overall this quality improvement project has highlighted the need for robust counselling as well as structured and informative consent forms to improve the awareness of teratogenicity with certain DMARDs therapy in woman of childbearing age. In spite of increased awareness of the teratogenicity of these DMARD 44.4% patients were not on any form of contraception. There is definitely room for improvement in effectively disseminating information regarding highly effective form of contraception to prevent inadvertent exposure during pregnancy which may result in foetal birth defects. Disclosure F.A. Khan: None.

Evaluation of the Risk of Birth Defects Related to the Use of Assisted Reproductive Technology: An Updated Systematic Review.

Fertility problems constitute a serious medical, social, and demographic problem. With this review, we aim to critically appraise and evaluate the existing literature surrounding the risk of birth defects in offspring conceived using techniques based on assisted reproductive technology (ART). Based on searches of the literature in PubMed and ScienceDirect, we obtained a total of 2,003,275 works related to the topic. Ultimately, 11 original papers published in the last 10 years qualified for inclusion in the study. Based on five studies included in this analysis, it was shown that ART significantly increases the risk of congenital malformations in associated newborns. Due to the specifics of given studies, as well as potential confounding risk factors, this influence cannot be ignored. Therefore, considering the information contained in the articles included in this systematic review, it was determined that the risk of birth defects is not directly related to the use of ART itself but also depends on the age of partners, causes of infertility, comorbidities, and the number of fetuses during a pregnancy, as well as many other factors not covered in the literature. It is thus necessary to impress upon infertile couples who wish to have offspring that the use of ART is not risk-free but that the benefits outweigh the risks. Further education in this field, as well as social understanding, is also required.

Nutrient Transporter Gene Expression in the Early Conceptus-Implications From Two Mouse Models of Diabetic Pregnancy.

Maternal diabetes in early pregnancy increases the risk for birth defects in the offspring, particularly heart, and neural tube defects. While elevated glucose levels are characteristic for diabetic pregnancies, these are also accompanied by hyperlipidemia, indicating altered nutrient availability. We therefore investigated whether changes in the expression of nutrient transporters at the conception site or in the early post-implantation embryo could account for increased birth defect incidence at later developmental stages. Focusing on glucose and fatty acid transporters, we measured their expression by RT-PCR in the spontaneously diabetic non-obese mouse strain NOD, and in pregnant FVB/N mouse strain dams with Streptozotocin-induced diabetes. Sites of expression in the deciduum, extra-embryonic, and embryonic tissues were determined by RNAscope in situ hybridization. While maternal diabetes had no apparent effects on levels or cellular profiles of expression, we detected striking cell-type specificity of particular nutrient transporters. For examples, Slc2a2/Glut2 expression was restricted to the endodermal cells of the visceral yolk sac, while Slc2a1/Glut1 expression was limited to the mesodermal compartment; Slc27a4/Fatp4 and Slc27a3/Fatp3 also exhibited reciprocally exclusive expression in the endodermal and mesodermal compartments of the yolk sac, respectively. These findings not only highlight the significance of nutrient transporters in the intrauterine environment, but also raise important implications for the etiology of birth defects in diabetic pregnancies, and for strategies aimed at reducing birth defects risk by nutrient supplementation.

Pregnancy outcomes of women with multiple sclerosis treated with ocrelizumab in Canada: A descriptive analysis of real-world data

ObjectivesTo report and describe the real-world use of ocrelizumab in women with multiple sclerosis (MS) in Canada before and/or during pregnancy as well as their fetal outcomes. MethodsWe identified retrospective and prospective Canadian pregnancy exposure cases from the Roche Global Safety Database from November 5, 2008 until March 31, 2021, and linked these cases to information within the Canadian Roche Patient Support Program (COMPASS). The analysis only included spontaneous reports or those from a non-interventional program. Details of the pregnancy exposures, fetal outcomes, as well as relevant patient characteristics, were collected. ResultsA total of 107 cases of maternal exposures were retrieved, with 104 (97.2%) being prescribed ocrelizumab for relapsing-remitting MS (RRMS) and 105 (98.1%) being reported from the COMPASS program. Of these cases, 85 (79.4%) were prospective and 22 (20.6%) retrospective. Cases were pooled (n = 65), and unknown/lost to follow-up outcomes and ongoing pregnancies were excluded. All cases reporting an outcome were analyzed, including 47 (72.3%) live births (44.7% full term, 8.5% preterm, 46.8% unknown gestational age), 13 (20.0%) spontaneous abortions, 2 (3.1%) therapeutic abortions/elective terminations, and 3 (4.6%) ectopic pregnancies. One major congenital anomaly of the limb (polydactyly) was reported; however, multiple confounders were likely contributors. Of the total maternal exposures (n = 107), 50 cases (46.6%) were not exposed to ocrelizumab in utero, with 32 of these (64.0%) receiving their last ocrelizumab infusion >3 but ≤6 months prior to conception, 17 (34.0%) receiving it >6 months prior to conception and 1 case receiving it at an unknown time point not in utero. Among the 37 (34.6%) maternal exposure cases exposed in utero, 22 (59.5%) received their last ocrelizumab infusion ≤3 months prior to conception. ConclusionThe data presented, although not without limitations, continues to suggest no increased risk of congenital anomalies and are consistent with ocrelizumab global pregnancy safety data and epidemiological rates.

Genetic Diversity and Trends of Ancestral and New Inbreeding in Deutsch Drahthaar Assessed by Pedigree Data.

Simple SummaryDeutsch Drahthaar (DD) is the most popular hunting dog in Germany, fulfilling all aspects of hunting including searching for trails. This breed was newly created at the beginning of the 20th century from a large number existing versatile hunting dog breeds. The aim of the breed was, and still is, to achieve the best performance in all aspects of hunting. We analyzed pedigrees of DD using demographic measures to quantify genetic diversity such as probabilities of gene origin and degrees of ancestral and individual inbreeding. A large number of genetically diverse founder dogs should open up the opportunity of creating a breed with a high genetic diversity and a low increase of inbreeding per generation. On the other hand, intense use of top sires and dams from a limited number of breeding lines may accelerate breeding progress in hunting abilities but reduce genetic diversity. Monitoring genetic diversity should help to maintain a high diversity of breeding populations. Our analysis of pedigree data from 101,887 DD dogs revealed inbreeding measures (coefficient of inbreeding F = 0.042, individual rate of inbreeding ΔFi = 0.00551) and effective population size (Ne = 92) in the mean range compared to a wide range of other dog breeds. Ancestral inbreeding had a strong increasing trend, whereas trends in individual inbreeding and rate of individual inbreeding were slightly negative.Loss of genetic diversity and high inbreeding rates confer an increased risk of congenital anomalies and diseases and thus impacting dog breeding. In this study, we analyzed recent and ancestral inbreeding as well as other measures of genetic variability in the Deutsch Drahthaar (DD) dog population. Analyses included pedigree data from 101,887 animals and a reference population with 65,927 dogs born between 2000 and 2020. The mean equivalent complete generations was 8.6 with 69% known ancestors in generation 8. The mean realized effective population size was 92 with an increasing trend from 83 to 108 over birth years. The numbers of founders, effective founders and effective ancestors, as well as founder genomes, were 814, 66, 38 and 16.15, respectively. Thirteen ancestors explained 50% of the genetic diversity. The mean coefficient of inbreeding and individual rate of inbreeding (ΔFi) were 0.042 and 0.00551, respectively, with a slightly decreasing trend in ΔFi. Exposure of ancestors to identical-by-descent alleles explored through ancestral coefficients of inbreeding showed a strong increasing trend. Comparisons between new and ancestral inbreeding coefficients according to Kalinowski et al. showed an average relative contribution of 62% of new inbreeding to individual inbreeding. Comparisons among average coancestry within the parental population and average inbreeding in the reference population were not indicative of genetic substructures. In conclusion, the creation of the DD dog breed about 120 years ago resulted in a popular breed with considerable genetic diversity without substructuring into lines or subpopulations. The trend of new inbreeding was declining, while ancestral inbreeding through ancestors who were autozygous at least once in previous generations was increasing.

Preconception paternal metformin treatment: risk of major birth defects

Preconception paternal metformin treatment: risk of major birth defects

Female Off-Farm Employment and Fertility Timing in Rural China

BackgroundAdvanced maternal age is associated with fetal outcomes such as higher risks of birth defects and very low birth weight. Off-farm employment is an important factor in fertility transition in many developing countries. This study investigated the association between off-farm employment and fertility timing among Chinese rural women.MethodUsing data from the China Labor-force Dynamics Survey (CLDS), we employed the ordinary least squares and instrumental variable approaches to estimate the effect of female off-farm employment on fertility timing decisions as well as the differences in the effect across groups.ResultsThe results show that off-farm employment participation is significantly associated with a later age at first birth, and the effect is stronger for women participating in wage employment than in off-farm self-employment. The delayed effects on fertility timing are also more pronounced for less-educated women and low-income families, implying a heterogeneous effect in terms of women's socioeconomic status.ConclusionStudies of the relationship between women's off-farm employment and fertility timing in rural areas of developing countries remain limited. This study provides important insights on this topic, and it lends support to efforts to design effective policies and practices to facilitate female employment, childbearing, and health promotion.

National compliance with UK wide guidelines for usage of valproate in women of childbearing potential

Valproate (VPA) is an effective treatment for epilepsy and also used in bipolar disorder. However, VPA is associated with a significant risk of birth defects and developmental disorders if used during pregnancy. This has led to the introduction of measures to reduce the use of valproate in women of childbearing potential such as the ‘Prevent’ pregnancy prevention program (PPP) and the completion of an annual risk acknowledgement form (ARAF). The aim of the current audit was to assess compliance with the guidance.An audit tool was made available to neurologists registered with the Association of British Neurologists (ABN) and to epilepsy nurse specialists via the Epilepsy Nurses Association (ESNA) in the UK. Data were collected between November 2020 and March 2021.The main indication for valproate was generalised epilepsy (55.8%), followed by focal (22.5%). For most, there was documentation that the woman had been informed about the risks associated with taking valproate during pregnancy (93.1%) and the need to be on highly effective contraception or that this was not deemed appropriate (92.2%). A signed ARAF was available in the notes for 81.2% although only 66% were <12 months old.Although information had been made available for most women, there were still individuals where this was not documented. Further work is needed to facilitate identification of women taking valproate and implementation of a digital ARAF. For clinicians, the audit highlights a need to carefully counsel women about the teratogenic risks of continuing to take valproate versus the risk of deteriorating seizure control if the drug is withdrawn. This is particularly true of women with focal epilepsy, where there may be safer, equally effective, alternative anti-seizure medication (ASM). The aim should be to create a partnership of trust between the patient and clinician in order to arrive at the best clinical decision for that individual.

A mother’s health during pregnancy

A mother’s health and nutrition status both before and during pregnancy have an important and significant effect on its baby`s physical as well as mental health. Mothers health and dietary intake completely effects a baby`s birth weight, rate of postnatal growth and chances of survival. If a mother is maintaining a good nutritious status with a healthy life style throughout her pregnancy, it optimizes maternal health and reduces the risk of pregnancy complication, birth defects and chronic diseases in her children and later in adulthood. This paper describes a woman with proper dietary intake, good nutritious status, and proper life style will have a healthy pregnancy which automatically increases the chances of having healthy delivery of baby, with very low complications. The baby has a better chance of having healthy life ahead.

Congenital anomalies and maternal age: A systematic review and meta‐analysis of observational studies

Several studies have reported on the maternal age-associated risks of congenital anomalies. However, there is a paucity of studies with comprehensive review of anomalies. We aimed to quantify the risk of birth defects in children born to middle-aged mothers compared with that in children born to young or older mothers. We classified maternal ages into three groups: young (<20years old), middle (20-34years old) and older age (≥35years old). Observational studies that met our age criteria were eligible for inclusion. The articles searched using the Embase and MEDLINE databases were those published from 1989 to January 21, 2021. The Newcastle-Ottawa scale was used to assess the risk of bias. If heterogeneity exceeded 50%, the random effect method was used; otherwise, the fixed-effect method was used. Prospero registration number: CRD42021235229. We included 15 cohort, 14 case-control and 36 cross-sectional studies. The pooled unadjusted odds ratio (95% CI) of any congenital anomaly was 1.64 (1.40-1.92) and 1.05 (0.95-1.15) in the older and young age groups, respectively (very low quality of evidence). The pooled unadjusted odds ratio of chromosomal anomaly was 5.64 (5.13-6.20) and 0.69 (0.54-0.88) in the older and young age groups, respectively. The pooled unadjusted odds ratio of non-chromosomal anomaly was 1.09 (1.01-1.17) and 1.10 (1.01-1.21) in the older and young age groups, respectively (very low quality of evidence). The incidence of abdominal wall defects was increased in children of women in the young maternal age group. We identified that very low quality evidence suggests that women in the older maternal age group had increased odds of having children with congenital anomalies compared with those in the 20-34year age group. There was no increase in odds of children with congenital anomalies in women of <20 year age group except for abdominal defects compared with those in the 20-34year age group. The results stem from very low quality evidence with no adjustment of confounders.

Birth Outcomes in Women Who Have Taken Hydroxycholoroquine During Pregnancy: A Prospective Cohort Study.

Findings from previous small studies have been reassuring regarding the safety of treatment with hydroxychloroquine (HCQ) during pregnancy. In one recent study, it was demonstrated that the frequency of major birth defects was increased in women who had received HCQ at a dose of ≥400 mg/day during pregnancy. This study was undertaken to examine pregnancy outcomes among women following the use of HCQ. The study cohort comprised pregnant women who were prospectively enrolled in the MotherToBaby/Organization of Teratology Information Specialists Autoimmune Diseases in Pregnancy Study and were receiving treatment with HCQ. For the control groups, disease-matched women without HCQ exposure and healthy women were randomly selected from the same source, with subject matching using a 1:1 ratio. Data were collected through interviews, medical records, and dysmorphology examinations. Pregnancy outcome measures included the presence or absence of major and minor birth defects, rates of spontaneous abortion, rates of preterm delivery, and infant growth measures. Between 2004 and 2018, 837 pregnant women met the criteria for study inclusion, including 279 women exposed to HCQ during pregnancy and 279 women in each unexposed control group. Sixty pregnant women (7.2%) were lost to follow-up. Among the women with live births, major birth defects occurred as a pregnancy outcome in 20 (8.6%) of 232 women with HCQ exposure in the first trimester, compared to 19 (7.4%) of 256 disease-matched unexposed controls (odds ratio [OR] 1.18, 95% confidence interval [95% CI] 0.61-2.26) and 13 (5.4%) of 239 healthy controls (adjusted OR 0.76, 95% CI 0.28-2.05). Risks did not differ in women who were receiving an HCQ dose of ≥400 mg/day. No pattern of birth defects was identified. There were no differences in the rates of spontaneous abortion or preterm delivery between groups. Occurrence of infant growth deficiencies did not differ in the HCQ-exposed group compared to the disease-matched unexposed control group, except in the infant's head circumference at birth (adjusted OR 1.85, 95% CI 1.07-3.20). In this study, there was no evidence of an increased risk of structural birth defects or other adverse outcomes among women receiving HCQ during pregnancy, with the exception of infant head circumference at birth. For pregnant women being treated with HCQ, these findings are reassuring.

Comparative study on risk of birth defects in singleton ART birth under high levels of estrogen after fresh embryo transfer and frozen embryo transfer

Objective To investigate whether high estrogen (E2) levels caused by controlled ovarian hyperstimulation affect the birth defect rate in singleton assisted reproductive technology (ART) birth after conceived by fresh embryo transfer and frozen embryo transfer (FET). Methods This was a retrospective cohort study. A total of 581 women with singletons, as well as those who have become pregnant and have had an unwanted abortion under high E2 levels on trigger day were divided into three groups. Group A received FET and the E2 levels on trigger day were higher than 5000 pg/ml. Group B received fresh embryo transfer and the E2 levels were between 3000 and 5000 pg/ml. Group C received FET and the E2 levels were between 3000 and 5000 pg/ml. Results There were no significant differences in birth weight, delivery mode, preterm birth rate, and fetal sex between the three groups (p > .05). Birth defect rate in Group B was higher than that in Group A and C, and the rate between Group B and C had significant differences (p < .05). After adjusting for maternal age, BMI, and type of infertility, only a FET cycle is significantly associated with decreased birth defect rate. Conclusion Fresh embryo transfer under supraphysiological level of estrogen exposure may increase the birth defect rate of ART singletons. Even after prenatal screening and diagnosis, a part of birth defect could not be detected during pregnancy. When the estrogen levels on trigger day were no lower than 3000 pg/ml, FET should be advocated to reduce the occurrence of such risk.

Association of China\u2019s two-child policy with changes in number of births and birth defects rate, 2008\u20132017

BackgroundIn October 2015, China’s one-child policy was universally replaced by a so-called two-child policy. This study investigated the association between the enactment of the new policy and changes in the number of births, and health-related birth outcomes.MethodsWe used difference-in-difference model to analyse the birth record data in Pudong New Area, Shanghai.The design is descriptive before-and-after comparative study.ResultsThe data covered three policy periods: the one-child policy period (January 2008 to November 2014); the partial two-child policy period (December 2014 to June 2016); the universal two-child policy period (July 2016 to December 2017). There was an estimate of 7656 additional births during the 18 months of the implementation of the universal two-child policy. The trend of monthly percentage of births to mothers aged ≥35 increased by 0.24 percentage points (95% confidence interval 0.19 to 0.28, p < 0.001) during the same period. Being a baby boy, preterm birth, low birth weight, parents with lower educational attainment, and assisted delivery were associated with a higher risk of birth defects.ConclusionsThe universal two-child policy was associated with an increase in the number of births and maternal age. Preterm birth, low birth weight, and assisted delivery were associated with a higher risk of birth defects, which suggested that these infants needed additional attention in the future.

COVID-19 in pregnancy-what study designs can we use to assess the risk of congenital anomalies in relation to COVID-19 disease, treatment and vaccination?

BackgroundThe COVID‐19 pandemic has accelerated pregnancy outcome research, but little attention has been given specifically to the risk of congenital anomalies (CA) and first trimester exposures.ObjectivesWe reviewed the main data sources and study designs used internationally, particularly in Europe, for CA research, and their strengths and limitations for investigating COVID‐19 disease, medications and vaccines.PopulationWe classify research designs based on four data sources: a) spontaneous adverse event reporting, where study subjects are positive for both exposure and outcome, b) pregnancy exposure registries, where study subjects are positive for exposure, c) congenital anomaly registries, where study subjects are positive for outcome and d) population healthcare data where the entire population of births is included, irrespective of exposure and outcome.Study DesignEach data source allows different study designs, including case series, exposed pregnancy cohorts (with external comparator), ecological studies, case‐control studies and population cohort studies (with internal comparator).MethodsThe quality of data sources for CA studies is reviewed in relation to criteria including diagnostic accuracy of CA data, size of study population, inclusion of terminations of pregnancy for foetal anomaly, inclusion of first trimester COVID‐19‐related exposures and use of an internal comparator group. Multinational collaboration models are reviewed.ResultsPregnancy exposure registries have been the main design for COVID‐19 pregnancy studies, but lack detail regarding first trimester exposures relevant to CA, or a suitable comparator group. CA registries present opportunities for improving diagnostic accuracy in COVID‐19 research, especially when linked to other data sources. Availability of inpatient hospital medication use in population healthcare data is limited. More use of ongoing mother‐baby linkage systems would improve research efficiency. Multinational collaboration delivers statistical power.ConclusionsChallenges and opportunities exist to improve research on CA in relation to the COVID‐19 pandemic and future pandemics.

Year-end academic review of 2021: Advances in the field of birth defect prevention and control in China as of 2021

Year-end academic review of 2021: Advances in the field of birth defect prevention and control in China as of 2021

Umbilical Cord Entanglement.

Umbilical Cord Entanglement.

Healthy Balanced Diet during Pregnancy

Eating a nutritious diet during pregnancy is linked to good brain development a healthy birth weight and can reduce the risk of many birth defects. A balanced diet will also reduce the risks of anemia, as well as other unpleasant pregnancy symptoms such as fatigue and morning sickness. For this, the pregnant women should have knowledge of healthy balanced diet during pregnancy, so that she can decide that which food provide enough nutrients for the mother and the baby during pregnancy. For this, a study was done on pregnant women coming to the Tapovan Centers affiliated to Children's University. In the study 53 participants from different centers of Gujarat state provided information through online questionnaire system. In that 98.11 % pregnant women were attentive towards healthy balanced diet and 01.89% respondents were inattentive towards healthy balanced diet.

Pregnancy and neonatal outcomes after periconceptional exposure to isotretinoin in Koreans.

ObjectiveIsotretinoin should not be used during pregnancy because of the risk of birth defects. Most pregnant women exposed to isotretinoin choose voluntary pregnancy termination due to concerns about birth defects. However, birth outcome data supporting the termination of pregnancy are lacking. This study aimed to evaluate pregnancy and neonatal outcomes after periconception exposure to isotretinoin.MethodsThis was a prospective cohort study. We evaluated pregnancy and neonatal outcomes after exposure to isotretinoin in 151 pregnant women. Among 1,026 callers at the Korean Teratology Information Service from 2001 to 2017 exposed to isotretinoin during the periconception period, 151 pregnant women who received counseling on teratogenic risk after visiting the clinic were included.ResultsAmong the 151 participants who visited the clinic, only 42 were evaluated using ultrasonography until approximately 20 weeks of gestation. Ultimately, 23 patients were included in the study. The average gestation period during the last exposure to the drug was 2 weeks, and the average daily exposure dose was 12 mg. There were two cases of major birth defects in the exposure group. Spontaneous abortion rates were 17.7% and 8.7% in the exposure and non-exposure groups, respectively (P=0.035). There was no significant difference between the exposure and non-exposure groups in terms of pregnancy and neonatal outcomes.ConclusionThere was no significant difference in pregnancy and neonatal outcomes, including birth defects, between the exposure and non-exposure groups. Further studies with larger sample sizes are required to validate our findings.

Prescribed opioid analgesics in early pregnancy and the risk of congenital anomalies: a population-based cohort study.

Background:Recent data suggest an increased risk of congenital anomalies with prenatal exposure to opioid analgesics. We sought to further quantify the risk of anomalies after opioid analgesic exposure during the first trimester in a population-based cohort study.Methods:Using administrative health data from Ontario, we followed 599 579 gestational parent–infant pairs from singleton pregnancies without opioid use disorder. We identified opioid analgesics dispensed in the first trimester and congenital anomalies diagnosed during the first year of life. We estimated propensity score–adjusted risk ratios (RRs) between first trimester exposure (any opioid analgesic and specific agents) and congenital anomalies (any anomaly, organ system anomalies, major or minor anomalies and specific anomalies).Results:The prevalence of congenital anomalies was 2.8% in exposed infants and 2.0% in unexposed infants. Relative to unexposed infants, we observed elevated risks among those who were exposed for some anomaly groups, including gastrointestinal anomalies (any opioid analgesic: adjusted RR 1.46, 95% confidence interval [CI] 1.15–1.85; codeine: adjusted RR 1.53, 95% CI 1.12–2.09; tramadol: adjusted RR 2.69, 95% CI 1.34–5.38) and several specific anomalies, including ankyloglossia (any opioid: adjusted RR 1.88, 95% CI 1.30–2.72; codeine: adjusted RR 2.14, 95% CI 1.35–3.40). These findings persisted in sensitivity analyses.Interpretation:Although the absolute risk of congenital anomalies was low, our findings add to accumulating data that suggest a small increased risk of some organ system anomalies and specific anomalies with first trimester exposure to opioid analgesics. These findings further quantify the potential risks associated with prenatal exposure to opioid analgesics to inform treatment choices for pain in pregnancy.

Parental Perspective Regarding Consanguineous Marriages as the Cause for Speech and Language Disorders in Pakistan

Background: Consanguineous connections are portrayed as connections between close relatives. These relationships are generally preferred in the majority of Asian and African nations particularly in the Muslim nations. Nonetheless, it is clear that these sorts of marriages have higher risk of congenital anomalies and disorders in children. Objective: To determine the parental perspective regarding consanguineous marriages as the cause for speech and language disorders in children. Methodology: The cross-sectional study was conducted through different hospital and centers in Lahore, Pakistan (Mayo Hospital, Services hospital, Autism Resource center and The University of Lahore Teaching hospital). Questionnaire will be used and compromised of questions. Data was collected through standardized questionnaire after taking the consent and was distributed among the consanguineous parents who have children with speech and language disorders. Parents were asked to complete the questionnaire. The data was collected using the online questionnaire as well. Results score was recorded for every respondent. Results: The study showed that majority of the people thought that consanguinity cannot lead to speech and language disorders in children. Conclusion: According to my research, although there is higher frequency of speech and language disorders recorded among consanguineous marriages than non-consanguineous marriages but majority of the people had a trend and preference for cousin marriages. Keywords: Consanguinity, Cousin Marriage, parental attitude, speech problems, language disorders, perception, Pakistan