Risk Of Birth Defects Research Articles

Does polycystic ovarian syndrome increase the risk of congenital anomalies in intracytoplasmic sperm injection cycles?

Does polycystic ovarian syndrome increase the risk of congenital anomalies in intracytoplasmic sperm injection cycles?

Factors associated with increased odds of sensorineural hearing loss in infants exposed to the Zika virus during pregnancy.

The Zika virus (ZIKV) infection in pregnant women has been associated with an increased risk of birth defects. We aimed to estimate the prevalence of sensorineural hearing loss (SNHL) in infants exposed to the ZIKV during their gestation and evaluate the factors associated with its increased odds. A cross-sectional study was performed from July 2016 to June 2019 in a Western state of Mexico and data from 61 infants that presented with laboratory-positive (RT-qPCR) evidence of in utero exposure to ZIKV were analyzed. Brain stem auditory evoked potentials were used. Hearing loss was documented in 6 (9.8%) of infants. The prevalence of SNHL in children with microcephaly was 75.0%, as compared to 5.3% in those without anomalies (odds ratio, OR = 14.31, 95% CI = 2.54 - 19.12). Half of children with SNHL had no physical manifestations of gestational ZIKV exposure. Hearing loss was a frequent event in ZIKV-exposed children, particularly among those with microcephaly. Our results highlight the relevance of systematic hearing screening.

Effect of pre-pregnancy body mass index on neonatal outcomes in women undergoing autologous frozen-thawed embryo transfer

To investigate the associations between pre-pregnancy body mass index (BMI) and neonatal outcomes in women undergoing autologous frozen-thawed embryo transfer (FET). Retrospective cohort study. University-affiliated reproductive medical center. A total of 16,240 women with singleton deliveries achieved by autologous FET. None. Neonatal outcomes included preterm birth (PTB), low birth weight (LBW), small-for-gestational age (SGA), large-for-gestational age (LGA), fetal macrosomia, and birth defects. After adjusting for confounding factors, our study showed that in autologous FET cycles, the overweight women (23 kg/m2≤ BMI <27.5 kg/m2) were associated with increased rates of PTB (adjusted odds ratio [aOR], 1.226; 95% confidence interval [CI], 1.060-1.418), macrosomia (aOR, 1.692; 95% CI, 1.491-1.921), and LGA (aOR, 1.980; 95% CI, 1.715-2.286); and the obese women (BMI ≥27.5 kg/m2) were significantly associated with increased PTB (aOR, 1.503; 95% CI, 1.167-1.936), early PTB (aOR, 2.829; 95% CI, 1.679-4.765), very LBW (aOR, 3.087; 95% CI, 1.720-5.542), macrosomia (aOR, 2.325; 95% CI, 1.862-2.904), and LGA (aOR, 3.235; 95% CI, 2.561-4.085). The rate of SGA infants was higher in the underweight women (BMI <18.5 kg/m2) (aOR, 1.687; 95% CI, 1.375-2.071) than that in the normal-weight women (18.5 kg/m2≤ BMI ≤23 kg/m2). No significant difference was observed in the risk of birth defects between normal-weight cases and other BMI categories. Among women undergoing FET, pre-pregnancy BMI affected neonatal outcomes of singletons. BMI in Asian categories for overweight and obese showed significant increases in PTB, macrosomia, and LGA; early PTB and very LBW only increased in obese cases. In addition, underweight status was associated with increased risk of SGA. In contrast, there was no association between pre-pregnancy BMI and birth defects in FET cycles.

Association of Preconception Paternal Alcohol Consumption With Increased Fetal Birth Defect Risk

This cohort study investigates the association of paternal drinking before pregnancy with risk of fetal birth defect.

Associations between air pollution exposure and birth defects: a time series analysis.

Air pollution is a serious environmental problem in China. Birth defects are particularly vulnerable to outdoor air pollution. Our study was to evaluate the association between short-term exposure to air pollutants and the risk of birth defects. Daily data including the air pollutants, meteorological characteristics, and birth records were obtained in Hefei, China, during January 2013 to December 2016. The findings showed that PM2.5, PM10, SO2, NO2, and O3 exposures were positively correlated with the risk of birth defects. Maternal exposure to PM2.5 and SO2 during the 4th to 13th gestational weeks was observed to have a significant association with the risk of birth defects, with the maximum effect in the 7th or 8th week for PM2.5 and the maximum effect in the 7th week for SO2. The positively significant exposure windows were the 4th to 14th weeks for PM10, the 4th to 12th weeks for NO2, and the 26th to 35th weeks for O3, respectively. The strongest associations were observed in the 8th week for PM10, the 7th week for NO2, and in the 31st or 32nd week for O3. The findings of this study demonstrate that air pollutants increase the risk of birth defects among women during pregnancy in Hefei, China, which provide evidence for improving the health of pregnant women and neonates in developing countries, and uncovered potential opportunities to reduce or prevent birth defects by proactive measures during pregnancy.

Zika virus outbreak in Brazil-Lessons learned and perspectives for a safe and effective vaccine.

Zika virus (ZIKV) is an emerging pathogen of public health concern, associated with a dramatic burden in places where the virus caused outbreaks between 2015 and 2017. In the Americas, the ZIKV was first reported in Brazil and rapidly spread through the Americas. Since its first report, a number of studies have been published as we continue to learn, not only about modes of transmission, but also clinical manifestations, risk of congenital anomalies, including microcephaly and neurological malformations in fetuses born from mothers infected during pregnancy. Interventions to reduce the burden of ZIKV infection are restricted to mosquito control, and for Aedes spp mosquitoes the strategies implemented to that end proved to be unsuccessful so far. Hence the lessons we can learn following the ZIKV epidemics become of paramount importance in the development of drug treatments and in search for a vaccine.

New agent offers once-daily oral treatment option for overactive bladder

New agent offers once-daily oral treatment option for overactive bladder

The Incidence of Congenital Heart Defects in Offspring Among Women With Diabetes in Saudi Arabia.

Background: The risk of congenital anomalies is increased in infants of diabetic mothers (IDM). The most frequent cardiac anomalies in IDMs include ventricular septal defect, transposition of great arteries, and aortic stenosis.Objective: Estimating the incidence of infants with congenital heart defects (CHD) whose mothers have diabetes in Saudi Arabia at a tertiary hospital in the National Guard Health Affairs (NGHA) system.Materials and methods: This study was a retrospective cohort. The population was all births of type 1 and type 2 diabetic mothers and non-diabetic mothers (also mothers with gestational diabetes) in NGHA by following the exclusion criteria, which were mothers over 40 and below 20 years of age, and other risk factors such as drug-induced congenital disease. The data was from deliveries from January 1st 2018 to January 1st 2019. Data were collected by chart review using the Best-Care system at NGHA hospital. Statistical Package for the Social Sciences (SPSS) version 20 (IBM Corp., Armonk, NY, USA) was used for the statistical analysis.Results: A total of 1838 diabetic mothers and non-exposure, non-diabetic mothers, with the outcome of whether the infant had CHD, were included in this study. Most of the mothers (544, 30.11%) were aged 30-34 years old. About two-thirds of mothers, 1161 (63.24%), weren't diabetic, 500 (27.23%) had gestational diabetes, 132 (7.19%) were type 2 diabetes (T2DM), and 43 (2.34%) were type 1 diabetes (T1DM). Two hundred eighteen (11.82%) offspring had CHD, and the remaining 1625 (88.17%) did not. The most frequent echocardiographic abnormalities in infants of diabetic mothers were patent ductus arteriosus (PDA) (31.75%), patent foramen ovale (PFO) (31.75%), and atrial septal defect (ASD) (23.64%).Conclusion: The incidence of CHD among infants of included mothers in this cohort study was 11.82%. The most frequent echocardiographic abnormalities in the infants of diabetics were PDA and PFO. The incidence of CHD was higher among mothers who had T1DM followed by T2DM, and whose ages were between 30-34.

Antithyroid drug use during pregnancy and the risk of birth defects in offspring: systematic review and meta-analysis of observational studies with methodological considerations.

Maternal antithyroid drug (ATD) use during pregnancy has been associated with an increased risk of birth defects in offspring. Uncertainty remains on the size of this risk and how it compares to untreated hyperthyroidism due to methodological limitations of previous studies. Systematic review of MEDLINE and EMBASE identifying observational studies examining ATD use during pregnancy and risk of birth defects by 28 August 2020. Data were extracted on study characteristics, effect estimates and comparator groups. Adjusted effect estimates were pooled using a random-effects generic inverse variance method and absolute risk calculated. Seven cohort studies and 1 case-control study involving 6 212 322 pregnancies and 388 976 birth defects were identified reporting regression effect estimates. Compared to an unexposed population comparison, the association between ATD use during pregnancy and birth defects in offspring was: adjusted risk ratio (aRR) 1.16 95% confidence interval (CI) 1.08-1.25 for propylthiouracil (PTU); aRR 1.28 95%CI 1.06-1.54 for methimazole/carbimazole (MMI/CMZ); aRR 1.51, 95%CI 1.16-1.97 for both MMI/CMZ and PTU; and aRR 1.15 95%CI 1.02-1.29 for untreated hyperthyroidism. The excess risk of any and major birth defects per 1000, respectively, was: 10.2 and 1.3 for PTU; 17.8 and 2.3 for MMI/CMZ; 32.5 and 4.1 for both MMI/CMZ and PTU; and 9.6 and 1.2 for untreated hyperthyroidism. When appropriately analysed the risk of birth defects associated with ATD use in pregnancy is attenuated. Although still elevated, the risk of birth defects is smallest with PTU compared to MMI/CMZ and may be similar to that of untreated hyperthyroidism.

Patient compliance and satisfaction using web-based glucose monitoring for the management of pregnant women with pregestational diabetes

Background Optimal glycemic control is vital in decreasing the risk of congenital birth defects and perinatal complications in women with diabetes. Although frequent blood glucose (BG) monitoring is essential during pregnancy, studies have highlighted poor compliance and falsification of glucose readings. We designed this study to assess whether a web-based glucose monitor improves compliance, glycemic control, and patient satisfaction. Methods This was a prospective study of 30 women with pre-gestational diabetes. After 4 weeks of using paper logs, patients were given a web-based glucose monitor. The primary outcome of interest was the average number of BG readings prior to and during web-based implementation. Secondary outcomes included glycemic control and patient satisfaction as determined by a pre- and post-study survey. Results The number of BG readings after 2 months using the web-based meter was similar to baseline. Hemoglobin A1c (HbA1c) significantly improved and there was a trend toward improved overall glycemic values. Survey results demonstrated satisfaction with the new system, although 20% of patients felt uncomfortable with glucose values being available to providers in real time. Conclusions Compliance with BG monitoring was similar when comparing a web-based system with written logs. Since other studies have highlighted that some glucose data from written logs are falsified, actual compliance using the web-based monitor may be improved. This study demonstrates potential patient concerns using a web-based system. Further studies should explore patient reactions to providers having real-time access to online glycemic data given our survey results.

Original article: is the protective association between hyperemesis gravidarum and birth defects biased by pregnancy termination?

We assessed whether the protective association between hyperemesis gravidarum and birth defects could be due to selection bias from exclusion of pregnancy terminations. We designed a cohort study of 2,115,581 live births in Canada, 1990-2016. The main exposure measure was hyperemesis gravidarum. The main outcome measure included any birth defect at delivery. We estimated risk ratios (RR) and 95% confidence intervals (CI) for the association of hyperemesis gravidarum with birth defects in log-binomial regression models, and assessed the extent of selection bias through correction factors. Hyperemesis gravidarum was associated with 0.88 times the risk of birth defects in models not corrected for bias (95% CI 0.82-0.94). Correction for selection bias suggested that if screening for birth defects was associated with 1.33 times the chance of detecting birth defects and having a pregnancy termination, there would be no association with hyperemesis gravidarum. If ultrasound was associated with 2.00 times the chance of detecting birth defects and 1.50 times the risk of pregnancy termination, hyperemesis gravidarum would be associated with 1.27 times the risk of birth defects (95% CI 1.18-1.35). The protective association between hyperemesis gravidarum and birth defects in previous studies may be due to selection bias.

Prenatal exposure to criteria air pollutants and associations with congenital anomalies: A Lebanese national study

Maternal exposure to air pollution has been associated with a higher birth defect (BD) risk. Previous studies suffer from inaccurate exposure assessment methods, confounding individual-level variations, and classical analytical modelling. This study aimed to examine the association between maternal exposure to criteria air pollutants and BD risk. A total of 553 cases and 10,214 controls were identified from private and public databases. Two subgroups were then formed: one for a matched case-control design, and another for Feature Selection (FS) analysis. Exposure assessment was based on the mean air pollutant-specific levels in the mother’s residential area during the specific BD gestational time window of risk (GTWR) and other time intervals. Multivariate regression models outcomes consistently showed a significant protective effect for folic acid intake and highlighted parental consanguinity as a strong BD risk factor. After adjusting for these putative risk factors and other covariates, results show that maternal exposure to PM2.5 during the first trimester is significantly associated with a higher overall BD risk (OR:1.05, 95%CI:1.01–1.09), and with a higher risk of genitourinary defects (GUD) (OR:1.06, 95%CI:1.01–1.11) and neural tube defects (NTD) (OR:1.10, 95%CI:1.03–1.17) during specific GTWRs. Maternal exposure to NO2 during GTWR exhibited a significant protective effect for NTD (OR:0.94, 95%CI:0.90–0.99), while all other examined associations were not statistically significant. Additionally, maternal exposure to SO2 during GTWR showed a significant association with a higher GUD risk (OR:1.17, 95%CI:1.08–1.26). When limiting selection to designated monitor coverage radiuses, PM2.5 maintained significance with BD risk and showed a significant gene-environment interaction for GUD (p = 0.018), while NO2 protective effect expanded to other subtypes. On the other hand, FS analysis confirmed maternal exposure to PM2.5 and NO2 as important features for GUD, CHD, and NTD. Our findings, set the basis for building a novel BD risk prediction model.

The Impact of Down-Regulation on Obstetrics and Perinatal Outcomes in Singleton Pregnancies After In Vitro Fertilization.

Backgrounddown-regulation has been widely used in IVF treatment; however, it lacks reports on the impact of down-regulation on obstetrics and perinatal outcomes. The purpose of this study was to compare the obstetrics and perinatal outcomes among different down-regulation conditions.Methodsthis is a retrospective cohort study on 3578 patients achieving cumulative singleton clinical pregnancy after their first oocytes retrieval cycle. Patients were grouped according to the serum estradiol after down-regulation (E2D) into three groups: <30, 30-55, >55 pg/ml. The obstetrics and perinatal outcomes, and live-birth rate per clinical pregnancy were main outcome measures. In the subgroup analysis, patients were further divided according to the mode of transfer. ANOVA, chi-square test, multivariate logistic regression, and multivariate general linear model were performed for statistical analysis.Resultsthe patients with E2D <30, 30-55, >55 pg/ml had similar live-birth rates. The patients with E2D <30 pg/ml had a lower risk of hypertension disorders than those with E2D 30-55 pg/ml. No difference was found in the risks of placenta previa, placenta abruption, premature rupture of membrane, hemorrhage, gestational diabetes mellitus, or intrauterine growth restriction. The newborns in the group with E2D <30 pg/ml had a lower risk of PICU admission than those in the group with E2D >55 pg/ml. There was no difference in the risks of congenital anomalies or mortality among the three groups. No differences were found in the gestational week, percentages of preterm birth and very preterm birth, birth weight, percentages of low birth weight and very low birth weight, delivery mode, or sex of newborn. Subgroup analysis showed that E2D 30-55 pg/ml was associated with a higher risk of low birth weight in patients with one fresh transfer + frozen transfer(s).ConclusionDown-regulation has no effect on the live-birth rate per clinical pregnancy. Patients with E2D <30 pg/ml may have advantages regarding lower risks of both maternal hypertension and newborn PICU admission. E2D 30-55 pg/ml may be associated with low birth weight in patients with relatively low quality embryos.

Maternal Vitamin B12 Status and Risk of Cleft Lip and Cleft Palate Birth Defects in Tamil Nadu State, India.

The causal role of maternal nutrition in orofacial clefts is uncertain. We tested hypotheses that low maternal vitamin B12 and low folate status are each associated with an increased risk of isolated cleft lip with or without cleft palate (CL±P) in a case-control study in Tamil Nadu state, India. Case-mothers of CL±P children (n = 47) and control-mothers of unaffected children (n = 50) were recruited an average of 1.4 years after birth of the index child and plasma vitamin B12, methylmalonic acid (MMA), total homocysteine (tHcy), and folate were measured at that time. Logistic regression analyses estimated associations between nutrient biomarkers and case-control status. Odds ratios (ORs) contrasting biomarker levels showed associations between case-mothers and low versus high plasma vitamin B12 (OR = 2.48, 95% CI, 1.02-6.01) and high versus low plasma MMA, an indicator of poor B12 status (OR = 3.65 95% CI, 1.21-11.05). Case-control status was not consistently associated with folate or tHcy levels. Low vitamin B12 status, when defined by a combination of both plasma vitamin B12 and MMA levels, had an even stronger association with case-mothers (OR = 6.54, 95% CI, 1.33-32.09). Mothers of CL±P children in southern India were 6.5 times more likely to have poor vitamin B12 status, defined by multiple biomarkers, compared to control-mothers. Further studies in populations with diverse nutritional backgrounds are required to determine whether poor maternal vitamin B12 or folate levels or their interactions are causally related to CL±P.

Comparative analysis of perinatal outcomes and birth defects amongst adolescent and older Ugandan mothers: evidence from a hospital-based surveillance database

BackgroundUganda has one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes between adolescents (age 12–19 years) and mothers (age 20–34 years) in four urban hospitals.MethodsMaternal demographics, HIV status, and birth outcomes of all live births, stillbirths, and spontaneous abortions delivered from August 2015 to December 2018 were extracted from a hospital-based birth defects surveillance database. Differences in the distributions of maternal and infant characteristics by maternal age groups were tested with Pearson’s chi-square. Adjusted odds ratios (aORs) and 95% confidence intervals (CI) were calculated using logistic regression to compare the prevalence of adverse birth outcomes among adolescents to mothers 20–34 years.ResultsA total of 100,189 births were analyzed, with 11.1% among adolescent mothers and 89.0% among older mothers. Adolescent mothers had an increased risk of preterm delivery (aOR: 1.14; CI 1.06–1.23), low birth weight (aOR: 1.46; CI 1.34–1.59), and early neonatal deaths (aOR: 1.58; CI 1.23–2.02). Newborns of adolescent mothers had an increased risk of major external birth defects (aOR: 1.33; CI 1.02–1.76), specifically, gastroschisis (aOR: 3.20; CI 1.12–9.13) compared to mothers 20–34 years. The difference between the prevalence of gastroschisis among adolescent mothers (7.3 per 10,000 births; 95% CI 3.7–14.3) was statistically significant when compared to mothers 20–34 years (1.6 per 10,000 births; 95% CI 0.9–2.6).ConclusionsThis study found that adolescent mothers had an increased risk for several adverse birth outcomes compared to mothers 20–34 years, similar to findings in the region and globally. Interventions are needed to improve birth outcomes in this vulnerable population.

Reassessment of the risk of birth defects due to Zika virus in Guadeloupe, 2016.

BackgroundIn the French Territories in the Americas (FTA), the risk of birth defects possibly associated with Zika virus (ZIKV) infection was 7.0% (95%CI: 5.0 to 9.5) among foetuses/infants of 546 women with symptomatic RT-PCR confirmed ZIKV infection during pregnancy. Many of these defects were isolated measurement-based microcephaly (i.e. without any detected brain or clinical abnormalities) or mild neurological conditions. We wanted to estimate the proportion of such minor findings among live births of women who were pregnant in the same region during the outbreak period but who were not infected with ZIKV.MethodsIn Guadeloupe, pregnant women were recruited at the time of delivery and tested for ZIKV infection. The outcomes of live born infants of ZIKV non-infected women were compared to those of ZIKV-exposed live born infants in Guadeloupe, extracted from the FTA prospective cohort.ResultsOf 490 live born infants without exposure to ZIKV, 42 infants (8.6%, 95%CI: 6.2–11.4) had mild abnormalities that have been described as ‘potentially linked to ZIKV infection’; all but one of these was isolated measurement-based microcephaly. Among the 241 live born infants with ZIKV exposure, the proportion of such abnormalities, using the same definition, was similar (6.6%, 95%CI: 3.8–10.6).ConclusionsIsolated anthropometric abnormalities and mild neurological conditions were as prevalent among infants with and without in-utero ZIKV exposure. If such abnormalities had not been considered as ‘potentially linked to ZIKV’ in the original prospective cohort in Guadeloupe, the overall estimate of the risk of birth defects considered due to the virus would have been significantly lower, at approximately 1.6% (95% CI: 0.4–4.1).Trial registrationClinicalTrials.gov (NCT02916732)

Combination of HLA-DRB1 alleles as a factor causing risks of sporadic congenital heart defects and congenital malformations without chromosome diseases

Congenital heart defects are anomalies that are becoming more and more frequent every year. Their specific weight is the highest among all the defects and malformations in fetus. Besides, children with sporadic congenital heart defects and malformations are still born rather frequently. We made an assumption that congenital heart defects (CHD) and congenital malformations (CM) were formed due to inflammatory process decompensation within «mother – fetus» system occurring in case of a conflict as per HLA between a semi-allogenic fetus and its mother’s microenvironment. A risk of such a conflict might be associated with certain HLA combinations in parents’ genotypes. Our research goal was to reveal peculiarities of HLA-DRB1 alleles combinations in married couples who had children with sporadic CHD and CM without any chromosome diseases and to determine whether such peculiarities could cause risks of congenital anomalies. We determined frequency of 14 alleles in HLA-DRB1 gene in all people who took part in the research. Our research allowed establishing that parents whose children suffered from CHD more frequently had common HLA-DRB104, female HLA-DRB107 with male HLA-DRB113, HLA-DRB117 and female HLA-DRB113 with male HLA-DRB114. Children who suffered from CM more frequently had parents who were homologous as per HLA-DRB112, as well as with female HLA-DRB112 and male HLA-DRB101, HLA-DRB104, HLA-DRB113, and HLA-DRB115; this greater frequency was statistically significant. We also detected an authentic increase in frequency of HLA-DRB112 allele in children against their parents. Children with CM also had HLA-DRB112 allele statistically significantly more frequently than healthy children. Peculiarities related to HLA-DRB1 alleles combination are genetic predictors of CHD and CM occurrence; their determination will allow minimizing risks of such disorders due to early diagnostics and timely prevention.

Cочетание аллелей HLA-DRB1 как условие реализации риска формирования спорадических врожденных пороков сердца и врожденных пороков развития плода без хромосомных заболеваний

Congenital heart defects are anomalies that are becoming more and more frequent every year. Their specific weight is the highest among all the defects and malformations in fetus. Besides, children with sporadic congenital heart defects and malformations are still born rather frequently. We made an assumption that congenital heart defects (CHD) and congenital malformations (CM) were formed due to inflammatory process decompensation within «mother – fetus» system occurring in case of a conflict as per HLA between a semi-allogenic fetus and its mother’s microenvironment. A risk of such a conflict might be associated with certain HLA combinations in parents’ genotypes. Our research goal was to reveal peculiarities of HLA-DRB1 alleles combinations in married couples who had children with sporadic CHD and CM without any chromosome diseases and to determine whether such peculiarities could cause risks of congenital anomalies. We determined frequency of 14 alleles in HLA-DRB1 gene in all people who took part in the research. Our research allowed establishing that parents whose children suffered from CHD more frequently had common HLA-DRB104, female HLA-DRB107 with male HLA-DRB113, HLA-DRB117 and female HLA-DRB113 with male HLA-DRB114. Children who suffered from CM more frequently had parents who were homologous as per HLA-DRB112, as well as with female HLA-DRB112 and male HLA-DRB101, HLA-DRB104, HLA-DRB113, and HLA-DRB115; this greater frequency was statistically significant. We also detected an authentic increase in frequency of HLA-DRB112 allele in children against their parents. Children with CM also had HLA-DRB112 allele statistically significantly more frequently than healthy children. Peculiarities related to HLA-DRB1 alleles combination are genetic predictors of CHD and CM occurrence; their determination will allow minimizing risks of such disorders due to early diagnostics and timely prevention.

Congenital anomalies in breech presentation: A nationwide record linkage study.

Our study aimed to determine if congenital anomalies are associated with breech presentation at delivery. We conducted a nationwide, retrospective population-based record linkage study and analyzed all singleton births in Finland from 1996 to 2016 using the mandatory health register data collected by the Finnish Institute for Health and Welfare. We compared all major congenital anomalies detected during pregnancy, birth, or the first year of life according to the fetus's presentation at the time of delivery using X2 -square statistic and Student's t test. We adjusted the results for known risk factors for congenital anomalies to estimate adjusted odds ratios and 95% confidence intervals. Fetuses in breech presentation at delivery had an increased risk for congenital anomalies (6.5%) compared with fetuses in cephalic presentation (3.6%), P < .001. Breech presentation was associated with nearly all types of examined congenital anomalies. The strongest associations were observed with congenital deformities of the hip, the central nervous system, the respiratory system, and the musculoskeletal system. Our study supports the theory that breech presentation is, in many cases, a symptom of a fundamental problem in fetal morphogenesis or function. Neonates born in the breech presentation have a higher risk of congenital anomalies and should undergo a postnatal screening.

Abstract GS3-09: Chances of pregnancy after breast cancer, reproductive and disease outcomes: A systematic review and meta-analysis

Abstract Background: Pregnancy-related issues are a priority for young breast cancer (BC) patients. Increasing evidence has shown that pregnancy after prior BC diagnosis is feasible. Nevertheless, few BC survivors conceive following anticancer treatment completion and many physicians remain concerned about the potentially detrimental effects of pregnancy after BC in terms of fetal/obstetrical outcomes and maternal prognosis. This systematic review and meta-analysis aims at providing updated and solid evidence on these important issues. Methods: A systematic literature review up to January 31, 2020 with no language restriction was conducted to identify studies including patients with a pregnancy after prior BC diagnosis. Chances of pregnancy after BC, fetal and obstetrical outcomes, disease-free survival (DFS) and overall survival (OS) were assessed. Pooled relative risks (RRs), hazard ratios (HRs) or odds ratio (ORs) with 95% confidence intervals (CI) were calculated using the random effects models. The study is registered with the PROSPERO registration number CRD42020158324. Results: Overall, 39 studies were included. Out of the 8,265,713 young women included in these studies, 8,093,401 were from the general population, 57,739 had cancers other than BC, 114,573 had BC. Among the 114,573 BC patients, 7,505 had a pregnancy after BC diagnosis and 107,068 did not. Compared to women from the general population, BC patients had 60% reduced chances of having a pregnancy following anticancer treatment completion (RR 0.40, 95% CI 0.32-0.49). Among other cancer patients, only women with prior cervical cancer had lower pregnancy rates (RR 0.33, 95% CI 0.31-0.35) than BC patients. Compared to the general population, BC survivors had significantly increased risks of low birth weight (OR 1.50, 95% CI 1.31-1.73), small for gestational age (OR 1.16, 95% CI 1.01-1.33), preterm delivery (OR 1.45, 95% CI 1.11-1.88) and caesarean section (OR 1.14, 95% CI 1.04-1.25). No significant increased risk of congenital abnormalities (OR 1.63, 95% CI 0.89-2.98) or other pregnancy or delivery complications (spontaneous or induced abortion, gestosis, antepartum or postpartum hemorrhage) was observed. Prior chemotherapy exposure or short pregnancy interval (defined as &amp;lt;2 or &amp;lt;5 years after BC diagnosis) were not associated with additional increased risk of complications. Pregnancy after BC was not associated with a negative impact on patients’ outcomes. Compared to BC patients without subsequent pregnancy, those with pregnancy after BC had better OS (HR 0.56, 95% CI 0.46-0.67) and DFS (HR 0.73, 95% CI 0.56-0.94). Similar results were observed in the studies correcting for the potential “healthy mother effect” (OS: HR 0.52, 95% CI 0.42-0.65; DFS: HR 0.74, 95% CI 0.58-0.96). No detrimental prognostic effect of pregnancy after BC was observed in patients with hormone-receptor positive disease (DFS: HR 1.10, 95% CI 0.73-1.66), while better outcomes were observed for those with hormone-receptor negative disease (DFS: HR 0.72, 95% CI 0.55-0.95). The safety of pregnancy after BC was observed irrespective of BRCA status, nodal status, previous chemotherapy exposure, pregnancy interval and pregnancy outcomes. Conclusions: This large meta-analysis provides solid evidence on the safety of pregnancy after prior BC diagnosis. The increased risk of fetal and obstetrical complications (but not of congenital abnormalities) calls for ensuring a closer monitoring of these pregnancies. The significantly reduced chances of conceiving as compared to the general population and other cancer patients should raise further awareness on the need to improve the oncofertility counseling of young BC patients wishing to complete their family planning following anticancer treatment completion. Citation Format: Eva Blondeaux, Marta Perachino, Marco Bruzzone, Richard A. Anderson, Evandro De Azambuja, Philip D. Poorvu, Hee Jeong Kim, Cynthia Villarreal-Garza, Barbara Pistilli, Ines Vaz-Luis, Cristina Saura, Kathryn J. Ruddy, Maria Alice Franzoi, Chiara Sertoli, Marcello Ceppi, Hatem A. Azim, Jr., Frederic Amant, Isabelle Demeestere, Lucia Del Mastro, Ann H. Partridge, Olivia Pagani, Fedro A. Peccatori, Matteo Lambertini. Chances of pregnancy after breast cancer, reproductive and disease outcomes: A systematic review and meta-analysis [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS3-09.