Higher Risk Of Congenital Anomalies Research Articles

Ulipristal acetate and pregnancy outcome-an observational study.

Is the failure of the selective progesterone receptor modulator ulipristal acetate (UPA) as emergency contraception (EC; 30mg, single) or inadvertent exposure for myoma treatment (5mg/d) in pregnancy associated with a higher risk of birth defects, spontaneous abortion (SAB) or elective termination of pregnancy (ETOP)? We did not find an increased risk for birth defects, SABs or ETOPs after UPA exposure during implantation and early embryogenesis. Pregnancy outcome data after exposure to UPA are very limited. In cases of EC failure or unplanned pregnancy during myoma treatment, women need well-grounded risk assessment to minimize anxiety and prevent unjustified termination of pregnancy. Observational study of prospectively ascertained pregnancies from the German Embryotox institute with UPA exposure (EC, n= 95; myoma, n= 7). Four retrospectively reported pregnancy outcomes were evaluated separately. A total of 226 requests on ulipristal were directed to the German Embryotox institute during the study period 2010-2018. Outcomes of pregnancies exposed-(i) precycle, (ii) preconceptional or (iii) first trimester-were ascertained using standardized questionnaires. Descriptive statistics were applied. Failed EC with UPA resulted in 95 prospectively ascertained pregnancies, of which 56 had completed follow-up: 37 live births, 7 SABs and 12 ETOPs. There was no major birth defect. Just 34% of women had taken UPA during the fertile window. Seven prospectively enrolled pregnancies were treated for myoma and had known pregnancy outcomes: five healthy live births and two SABs. Among the four retrospectively reported pregnancies after EC, there was one child diagnosed with Beckwith-Wiedemann syndrome (BWS). Our limited sample size does not allow concluding safety of UPA use in pregnancy. We provide a preliminary basis for reassuring women who wish to carry their pregnancy to term after EC or myoma treatment with UPA. However, because of the report of a BWS after UPA exposure, a possible epigenetic effect could not be excluded and requires further evaluation. This work was performed with financial support from the German Federal Institute for Drugs and Medical Devices (BfArM). All authors declare that they have no conflicts of interest. Registered with the German Clinical Trial Register (DRKS00015155).

Metal mining and birth defects: a case-control study in Lubumbashi, Democratic Republic of the Congo

Widespread environmental contamination caused by mining of copper and cobalt has led to concerns about the possible association between birth defects and exposure to several toxic metals in southern Katanga, Democratic Republic of the Congo (DRC). We therefore aimed to assess the possible contribution of parental and antenatal exposure to trace metals to the occurrence of visible birth defects among neonates. We did a case-control study between March 1, 2013, and Feb 28, 2015, in Lubumbashi, DRC. We included newborns with visible birth defects (cases) and healthy neonates born in the same maternity ward (controls). Mothers were interviewed about potentially relevant exposures, including their partners' jobs. Various trace metals were measured by inductively coupled plasma mass spectrometry in maternal urine, maternal blood, umbilical cord blood, placental tissue, and surface dust at home. Multivariable logistic regression analyses were done to calculate adjusted odds ratios and their 95% CIs (CI). Our study included 138 neonates with visible birth defects (about 0·1% of the 133 662 births in Lubumbashi during the study period) and 108 control neonates. Potential confounders were similarly distributed between cases and controls. Vitamin consumption during pregnancy was associated with a lower risk of birth defects (adjusted odds ratio 0·2, 95% CI 0·1-0·5). Mothers having paid jobs outside the home (2·8, 1·2-6·9) and fathers having mining-related jobs (5·5, 1·2-25·0) were associated with a higher risk of birth defects. We found no associations for trace metal concentrations in biological samples, except for a doubling of manganese (Mn; 1·7, 1·1-2·7) and zinc (Zn; 1·6, 0·9-2·8) in cord blood. In a separate model including placentas, a doubling of Mn at the fetal side of the placenta was associated with an increased risk of birth defects (3·3, 1·2-8·0), as was a doubling of cord blood Zn (5·3, 1·6-16·6). To our knowledge, this is the first study of the effects of mining-related pollution on newborns in sub-Saharan Africa. Paternal occupational mining exposure was the factor most strongly associated with birth defects. Because neither Mn nor Zn are mined in Lubumbashi, the mechanism of the association between their increased prenatal concentrations and birth defects is unclear. Flemish Interuniversity Council-University Development Cooperation, The Coalition of the North-South movement in Flanders 11.11.11.

Preconception Paternal Smoking As a Risk Factor of Birth Defects in Offspring: Evidence from the Database of National Free Preconception Health Examination Project in China

Background: The association between paternal smoking and birth defects in offspring was indicated. However, there lacks prospective evidence to recommend father smoking quit before pregnancy for eliminating birth defects risk in his offspring. This study aimed to investigate the effect of preconception paternal smoking on birth defects in offspring in a prospective population based study. Methods: We carried out a prospective, population-based study utilizing preconception registry data from National Free Preconception Health Examination Project during 2010-12, and a matched case control study (1:1) with birth defects and normal pregnancy by maternal province, supplement of folic acid matched, and paternal alcohol consumption as well. Findings: A total of 566439 couples with complete preconception father smoking behavior were enrolled. Total paternal smoking rate before conception was 28.7% (162482), among whom 8.7% (49303) stopped smoking, 13.3% (75517) decreased and 6.6% (37662) continued in early pregnancy. Logistic regression models were used to examine the association between birth defects and smoking behavior. Paternal continued smoking group (P=0.000, OR=1.868, 95% CI: 1.361-2.564) and pre-conception paternal decreased smoking group in early pregnancy (P=0.007, OR=1.414, 95% CI: 1.100-1.816) were at higher risk of birth defects, while there was no difference with those father quitting smoking compared to paternal never smoking group (P=0.407). In addition, preconception paternal smoking behavior change was associated with birth defects in offspring in matched case control analysis, compared to those fetus whose father continued smoked, the fetus whose father quitted (P=0.003, OR=0.316, 95% CI: 0.149-0.669) or decreased smoking (P=0.000, OR=0.250, 95% CI: 0.129-0.485) were at lower risk of birth defects, especially for congenital heart diseases, limb abnormalities, digestive tract anomalies and neural tube defects. Interpretation: Preconception paternal smoking demonstrated to be associated with birth defects including congenital heart diseases, limb abnormalities and neural tube defects. Preconception paternal smoking cessation should be strengthened for eliminating related birth defects as part of pregnancy education program before pregnancy. Funding Statement: Database reported in this publication was supported by Chinese government, a national nonprofit project which benefits rural reproductive aged population. This study was supported by Chinese association of maternal and child health studies. Declaration of Interests: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Zhang SK reports National Free Preconception Health Examination Project (NFPHEP) supported by Chinese government, a national nonprofit project which benefits rural reproductive aged population. No other disclosures were reported. Ethics Approval Statement: The Institutional Review Board of Chinese Association of Maternal and Child Health Studies approved the project, and written informed consent was obtained from the participants (IRB201001).

The impact of obesity on pregnancy outcomes among women with psychiatric disorders: Results from a prospective pregnancy registry

ObjectiveObesity is associated with an increased risk of adverse pregnancy outcomes. As individuals with psychiatric disorders are at a higher risk of obesity than the general population, we aimed to examine the effect of obesity on neonatal and maternal outcomes in this population. MethodsPregnant women with psychiatric disorders were enrolled in the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications (NCT01246765) and followed prospectively until 6 months postpartum. Pre-pregnancy body mass index was used to categorize participants as normal-weight, overweight, and obese to assess comparative risk of adverse outcomes. ResultsWithin our sample of 584 participants (N = 252 normal-weight; N = 170 overweight; N = 162 obese), obesity was not significantly associated with higher risk for birth defects (OR: 3.19; 95% CI:0.79,12.95; p = 0.10; unadjusted due to the rarity of this outcome in the sample). After adjustment, women with obesity were at higher risk for gestational diabetes (p = 0.011; OR:3.23; 95% CI:1.30,7.98), as were women in the overweight BMI category (p = 0.003; OR:3.77; 95% CI:1.58,9.00). Among women with obesity, there was a tendency for a higher C-section rate (p = 0.07) compared to women in the normal-weight BMI category. Other outcomes were not significantly different among groups. ConclusionsPeripartum complications associated with obesity are common among women with psychiatric illness; thus, it is important to develop antenatal weight management interventions for this population.

Disturbed intracellular calcium homeostasis in neural tube defects in diabetic embryopathy

Pregnancies complicated by preexisting maternal diabetes mellitus are associated with a higher risk of birth defects in infants, known as diabetic embryopathy. The common defects seen in the central nervous system result from failure of neural tube closure. The formation of neural tube defects (NTDs) is associated with excessive programmed cell death (apoptosis) in the neuroepithelium under hyperglycemia-induced intracellular stress conditions. The early cellular response to hyperglycemia remains to be identified. We hypothesize that hyperglycemia may disturb intracellular calcium (Ca2+) homeostasis, which perturbs organelle function and apoptotic regulation, resulting in increased apoptosis and embryonic NTDs. In an animal model of diabetic embryopathy, we performed Ca2+ imaging and observed significant increases in intracellular Ca2+ ([Ca2+]i) in the embryonic neural epithelium. Blocking T-type Ca2+ channels with mibefradil, but not L-type with verapamil, significantly blunted the increases in [Ca2+]i, implicating an involvement of channel type-dependent Ca2+ influx in hyperglycemia-perturbed Ca2+ homeostasis. Treatment of diabetic pregnant mice with mibefradil during neurulation significantly reduced NTD rates in the embryos. This effect was associated with decreases in apoptosis, alleviation of endoplasmic reticulum stress, and increases of anti-apoptotic factors. Taken together, our data suggest an important role of Ca2+ influx in hyperglycemia-induced NTDs and of T-type Ca2+ channels as a potential target to prevent birth defects in diabetic pregnancies.

The health of children conceived by ART: 'the chicken or the egg?'

Worldwide, more than 7 million children have now been born after ART: these delivery rates are steadily rising and now comprise 2-6% of births in the European countries. To achieve higher pregnancy rates, the transfer of two or more embryos was previously the gold standard in ART. However, recently the practise has moved towards a single embryo transfer policy to avoid multiple births. The positive consequences of the declining multiple birth rates after ART are decreasing perinatal risks and overall improved health for the ART progeny. In this review we summarize the risks for short- and long-term health in ART singletons and discuss if the increased health risks are associated with intrinsic maternal or paternal factors related to subfertility or to the ART treatments per se. Although the risks are modest, singletons born after ART are more likely to have adverse perinatal outcomes compared to spontaneously conceived (SC) singletons dependent on the ART method. Fresh embryo transfer is associated with a higher risk of small for gestational age babies (SGA), low birthweight and preterm birth (PTB), while frozen embryo transfer is associated with large-for-gestational age babies and pre-eclampsia. ICSI may be associated with a higher risk of birth defects and transferral of the poor semen quality to male progeny, while oocyte donation is associated with increased risk of SGA and pre-eclampsia. Concerning long-term health risks, the current evidence is limited but suggests an increased risk of altered blood pressure and cardiovascular function in ART children. The data that are available for malignancies seem reassuring, while results on neurodevelopmental health are more equivocal with a possible association between ART and cerebral palsy. The laboratory techniques used in ART may also play a role, as different embryo culture media give rise to different birthweights and growth patterns in children, while culture to blastocyst stage is associated with PTB. In addition, children born after ART have altered epigenetic profiles, and these alterations may be one of the key areas to explore to improve our understanding of adverse child outcomes after ART. A major challenge for research into adverse perinatal outcomes is the difficulty in separating the contribution of infertility per se from the ART treatment (i.e. 'the chicken or the egg'?). Choosing and having access to the appropriate control groups for the ART children in order to eliminate the influence of subfertility per se (thereby exploring the pure association between ART and child outcomes) is in itself challenging. However, studies including children of subfertile couples or of couples treated with milder fertility treatments, such as IUI, as controls show that perinatal risks in these cohorts are lower than for ART children but still higher than for SC indicating that both subfertility and ART influence the future outcome. Sibling studies, where a mother gave birth to both an ART and a SC child, support this theory as ART singletons had slightly poorer outcomes. The conclusion we can reach from the well designed studies aimed at disentangling the influence on child health of parental and ART factors is that both the chicken and the egg matter.

Maternal obstructive sleep apnea and neonatal birth outcomes in a population based sample

ObjectiveEvaluate the association of OSA with birth outcomes including the risk of congenital anomalies and the need for a higher level of clinical care at delivery. MethodsPopulation-based study that linked newborn records with maternal records. Data from 95 perinatal centers across all geographic census divisions of the U.S. of women with a delivery diagnosis from 2010 to 2014 whose records could be linked to the corresponding newborn record. An International Classification of Diseases, ninth Revision (ICD-9) code for sleep apnea was used to identify exposure and outcome variables. Univariate and multivariate logistic regression analyses were performed with a model that included substance use, obesity, diabetes, maternal co-morbidities, and pregnancy complications. ResultsIn this study, 1,423,099 maternal records were linked to live newborn records. OSA was associated with a higher risk for congenital anomalies in offspring (aOR 1.26, 1.11 to 1.43), with the highest risk being that of musculoskeletal anomalies (aOR 1.89, 1.16 to 3.07) after adjusting for comorbidities and potential teratogens. Neonates born to mothers with OSA were more likely to be admitted to the intensive care unit (25.3% vs. 8.1%, p < 0.001), require resuscitation (aOR 2.76, 1.35 to 5.64) and have a longer hospital stay (aOR 2.25, 1.85 to 2.65). ConclusionsAlthough our study does not establish causation, it is the first to demonstrate a higher risk of congenital anomalies and resuscitation at birth in neonates of mothers with OSA, emphasizing the importance of identifying OSA in pregnant women and women of reproductive age.

Identifying latent sources of exposure to mercury in the mediterranean: the case of cyprus

Atazanavir and ritonavir are preferred protease inhibitors frequently used in combination antiretroviral therapy for prevention of HIV mother-to-child transmission. Although their use is associated with higher risk of congenital anomalies, factors affecting atazanavir and ritonavir placental transfer are not known. This study is the first attempt to evaluate whether the placental drug efflux ATP-binding cassette (ABC) transporters, p-glycoprotein (ABCB1), breast cancer resistance protein (ABCG2), and/or multidrug resistance-associated proteins 2 (ABCC2), affect placental pharmacokinetics of atazanavir or ritonavir. Transport experiments across MDCKII cells expressing respective human ABC carrier showed that atazanavir is a substrate of ABCB1 and dual perfusion studies in a rat placenta confirmed this finding. In conclusion, we suggest that placental ABCB1 might reduce ATV maternal-to-fetal transfer and therefore represent a site for pharmacokinetic drug-drug interactions of ATV. Further studies in human placenta models are necessary to provide additional data closer to clinical environment.

Interactions of protease inhibitors atazanavir and ritonavir with ABCB1, ABCG2, and ABCC2 transporters: Effect on transplacental disposition in rats

Atazanavir and ritonavir are preferred protease inhibitors frequently used in combination antiretroviral therapy for prevention of HIV mother-to-child transmission. Although their use is associated with higher risk of congenital anomalies, factors affecting atazanavir and ritonavir placental transfer are not known. This study is the first attempt to evaluate whether the placental drug efflux ATP-binding cassette (ABC) transporters, p-glycoprotein (ABCB1), breast cancer resistance protein (ABCG2), and/or multidrug resistance-associated proteins 2 (ABCC2), affect placental pharmacokinetics of atazanavir or ritonavir. Transport experiments across MDCKII cells expressing respective human ABC carrier showed that atazanavir is a substrate of ABCB1 and dual perfusion studies in a rat placenta confirmed this finding. In conclusion, we suggest that placental ABCB1 might reduce ATV maternal-to-fetal transfer and therefore represent a site for pharmacokinetic drug-drug interactions of ATV. Further studies in human placenta models are necessary to provide additional data closer to clinical environment.

Association of assisted reproductive technology and multiple pregnancies with the risks of birth defects and stillbirth: A retrospective cohort study

Assisted reproductive technology (ART) has been widely used among women with infertility. However, the association of ART with birth defects and stillbirth remains controversial and has rarely been reported in China. A retrospective cohort study of 112,043 pregnant women and 114,522 newborns from 2006 to 2016 was performed. Compared to spontaneously conceived infants, ART-conceived infants had a higher likelihood of any birth defect, with an adjusted odds ratio (OR) of 2.10 (95% confidence interval, 1.63–2.69). ART-conceived infants also had a significantly increased risk for subcategories of cardiovascular, musculoskeletal, urogenital, gastrointestinal, and respiratory defects. Most (62.25%) of the effect of ART on birth defects was a direct effect, whereas 37.75% of the effect of ART on birth defects was due to multiple pregnancies (i.e., an indirect effect). Compared with naturally conceived singletons, the combined effect of ART and twins on the risk of birth defects was lower than that of the sum of the individual effects of ART and twins on the risk of birth defects, with an adjusted OR of 0.54 (0.32–0.92). These findings clearly show that ART is associated with an increased risk of birth defects in China and may provide guidance to couples and obstetricians in selecting numbers of pregnancies and in identifying organs at a high risk of birth defects.

Women’s knowledge on activities associated with maternal hyperthermia during pregnancy. A cross-sectional study of the sample of Polish women

Abstract Introduction. Hyperthermia during the first trimester increases the risk of miscarriage and birth defects. A variety of activities predisposing to hyperthermia during pregnancy such as attending sauna, hot tubs or solarium may lead to irreversible abnormalities of the developing fetus. Aim. The aim of the study was to assess women‘s knowledge on the risks of maternal hyperthermia during each trimester of pregnancy. Material and methods. It was a cross-sectional study conducted by means of an anonymous questionnaire. The study group included 302 women aged 17-65 who were admitted to a tertiary referral hospital. The questionnaire was designed on the basis of the Committee Opinion formulated by the American College of Obstetricians and Gynecologists and was consisted of two sections: demographic data and respondents‘ opinions on activities associated with hyperthermia in pregnancy. Statistical analysis was conducted to estimate the association of age, level of education and obstetrical status. Results. The lowest percentage of given proper answers was observed in case of questions about early pregnancy. There was no association between respondents‘ level of education and choice of correct answers. Current pregnancy was associated with higher awareness of contraindicated using of hot tubs and steam rooms. Conclusions. Patients‘ education concerning hyperthermia in pregnancy should focus on information about high risk of birth defects caused by overheating in the early pregnancy and a variety of activities linked with temperature elevation.

Risk of childhood mortality in family members of men with poor semen quality.

What is the familial childhood mortality in first-degree (FDR) and second-degree relatives (SDR) of patients undergoing semen analysis (SA)? The relationship between infertility and congenital malformations (CM) in offspring is complex, with an increased risk of death due to CM in FDR, but not SDR, of men with lower semen parameters. Semen quality is an established predictor of men's somatic health. We can gain a better understanding of possible genetic or environmental determinants of the infertility phenotype by exploring familial aggregation of childhood mortality in relatives of men with poor semen quality. Retrospective cohort study from the Subfertility, Health and Assisted Reproduction study (cohort compiled 1996-2011) linked with patient/familial information from the Utah Population Database (UPDB). Index cases included a clinic-referred sample of 12 889 men who underwent SA and had adequate familial and follow-up data in the UPDB. Parameters of semen quality included: semen concentration, sperm count, motility, total motile count, sperm head morphology, sperm tail morphology and vitality. SA data were collected from two tertiary medical center andrology laboratories that have captured ~90% of all SA performed in Utah since 2004. Age- and sex-matched fertile controls were selected to create the comparison group for determining risk of childhood death (to age 20 years) in family members. A total of 79 750 siblings and 160 016 aunts/uncles were used to investigate the familial aggregation of childhood mortality. The main outcome was childhood mortality in FDR and SDR of men with SA and their matched controls. All-cause and cause-specific Cox proportional hazard models were used to test the association between semen quality and childhood mortality in family members. Cause-specific models were considered for cancer and CM. In the cohort of men with SA, there were 406 (1.0%) deaths in FDR and 772 (1.1%) deaths in SDR due to any cause. There was no significant difference in the risk of all-cause childhood mortality between the relatives of men with SA and the fertile control group [hazard ratio (HR)Female = 1.08, 95% CI = 0.88, 1.32; HRMale = 0.88, 95% CI = 0.75, 1.04]. We found no association between semen quality and risk for childhood cancer mortality in FDR or SDR (HRFDR = 0.98, 95% CI = 0.62, 1.54; HRSDR = 1.12, 95% CI = 0.83, 1.50). The FDR of men with SA and fertile controls were followed on average for 19.71 and 19.73 years, respectively. During this period of follow-up, FDR of men with SA had an unadjusted 40% relative risk of increased CM-related death. After stratifying by semen parameters and adjusting for birth year, we found FDR of men with worse semen quality, and notably azoospermic men (HR = 2.69, 95% CI = 1.24,5.84), were at higher risk of CM-related death. A large proportion of men with SA in the study had normal semen parameters. It is important to note that these men themselves may not be subfertile, but they were subfertile at the couple level (i.e. the female partner may be infertile). In addition, care is needed when interpreting our results, as we do not have semen measures on our sample of fertile men. Second, we were unable to include potential confounders such as medical comorbidities, smoking status, or environmental exposures. Third, men with SA were seen at the University of Utah or Intermountain Health Care clinics for a fertility evaluation thereby suggesting a more select population. Fourth, we chose to categorize morphology into equally distributed quartiles as a response to the fact that the World Health Organization threshold for normal motility changed multiple times during our study period. Lastly, we do not know the proportion of female partners with diagnosed infertility. We chose not to subcategorize each infertile male by infertile diagnosis because our goal was to understand how semen parameters influenced familial childhood mortality. We are not the first study to show a relationship between fertility and CMs. Children conceived through ART may be at higher risk of birth defects, however it is not known if the relationship is causal or if there is some underlying factor linking infertility and birth outcomes. This study provides further evidence that the increased risk of congenital birth defects may not be due to the ART, but rather genetic or environmental factors that link the two outcomes. We encourage further research in order to confirm a relationship between semen quality and increased risk for CM. This work was supported by the National Institutes of Health - National Institute of Aging [Grant numbers 1R21AG036938-01, 2R01 AG022095 and 1K12HD085852-01]. Authors have no competing interests to disclose. Not applicable.

Clinical application of whole‐genome low‐coverage next‐generation sequencing to detect and characterize balanced chromosomal translocations

Individuals carrying balanced translocations have a high risk of birth defects, recurrent spontaneous abortions and infertility. Thus, the detection and characterization of balanced translocations is important to reveal the genetic background of the carriers and to provide proper genetic counseling. Next-generation sequencing (NGS), which has great advantages over other methods such as karyotyping and fluorescence in situ hybridization (FISH), has been used to detect disease-associated breakpoints. Herein, to evaluate the application of this technology to detect balanced translocations in the clinic, we performed a parental study for prenatal cases with unbalanced translocations. Eight candidate families with potential balanced translocations were investigated using two strategies in parallel, low-coverage whole-genome sequencing (WGS) followed-up by Sanger sequencing and G-banding karyotype coupled with FISH. G-banding analysis revealed three balanced translocations, and FISH detected two cryptic submicroscopic balanced translocations. Consistently, WGS detected five balanced translocations and mapped all the breakpoints by Sanger sequencing. Analysis of the breakpoints revealed that six genes were disrupted in the four apparently healthy carriers. In summary, our result suggested low-coverage WGS can detect balanced translocations reliably and can map breakpoints precisely compared with conventional procedures. WGS may replace cytogenetic methods in the diagnosis of balanced translocation carriers in the clinic.

Congenital heart disease in twins: The contribution of type of conception and chorionicity

BackgroundIncreased incidence of congenital heart disease (CHD) has been reported in the offspring of monochorionic twin gestations. Assisted reproductive technology (ART), which is related to increased rates of twinning, has also been associated with higher risk of birth defects. We studied the incidence of CHD in a cohort of twins to clarify the contribution of type of conception and chorionicity. MethodsData concerning 874 live-born twins of which at least one was admitted in our Neonatal Unit during 1995–2012 were analysed. Forty-five % (N=197) of the gestations resulted from ART (in vitro fertilisation or intracytoplasmic sperm insertion). ResultsIn the ART group 32/389 (8.2%) had CHD compared to 21/485 (4.3%) infants conceived naturally (OR 1.90, 95%CI 1.08–3.34, p=0.024). Spontaneous-conception gestations had higher incidence of monochorionic placentation (47/245 versus 4/197, p<0.001), and included younger mothers (29.1±5.2 versus 33.9±5.5years, p<0.001) who had higher parity (median 2 [range 1–7] versus 1 Pinborg (2005), Blondel and Kaminski (2002), Knopman et al. (2014), Kyvik and Derom (2006) ; p<0.001). Multivariable logistic regression analysis showed that ART (OR 2.60, 95% CI 1.24–5.45) and monochorionicity (OR 3.49, 95% CI 1.57–7.77) were significant determinants of CHD, independently of maternal age, parity, and the gender of the offspring. ConclusionsWe confirmed that monochorionic twins have increased risk of CHD and we documented a higher incidence of CHD in ART twins independently of chorionicity. We suggest improvement of echocardiographic skills of health care professionals involved in prenatal screening and foetal cardiology referral of ART dichorionic twins with suspicious findings at screening, in addition to all monochorionic gestations.

Safety of Selective Serotonin Reuptake Inhibitors in Pregnancy: A Review of Current Evidence.

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressant medications worldwide. However, over the past decade, their use during pregnancy, a period of extreme vulnerability to the onset of depression, has become highly concerning to patients and their healthcare providers in terms of safety to the developing fetus. Exposure to SSRIs in pregnancy has been associated with miscarriage, premature delivery, neonatal complications, birth defects-specifically cardiac defects-and, more recently, neurodevelopmental disorders in childhood, specifically autism spectrum disorders. Studies addressing the effect of individual SSRIs indicate a small but higher risk for birth defects with maternal fluoxetine and paroxetine use. Though the excess in absolute risk is small, it may still be of concern to some patients. Meanwhile, antenatal depression itself is associated with adverse perinatal outcomes, and discontinuing antidepressant treatment during pregnancy is associated with a high risk of relapse of depression. Whether the observed adverse fetal effects are related to the mother's medication use or her underlying maternal illness remains difficult to determine. It is important that every pregnant woman being treated with an SSRI (or considering such treatment) carefully weighs the risks of treatment against the risk of untreated depression for both herself and her child. The importance of recognizing a higher risk for the development of adverse outcomes lies in the potential for surveillance and possibly a timely intervention. Therefore, we recommend that pregnant women exposed to any SSRI in early pregnancy be offered options for prenatal diagnosis through ultrasound examinations and fetal echocardiography to detect the presence of birth defects. Tapering off or switching to other therapy in early pregnancy, if appropriate for the individual, may also be considered on a case-by-case basis.

Neonatal and maternal outcome after blastocyst transfer: a population-based registry study

Previous studies have shown a higher risk of birth defects and preterm birth (PTB) in singletons born after blastocyst transfer as compared to singletons born after cleavage-stage transfer. Few studies have investigated the maternal outcomes. We sought to analyze the neonatal and maternal outcome after blastocyst transfer (day 5-6) compared to transfer of cleavage-stage embryos (day 2-3) and spontaneous conception. This was a population-based retrospective registry study including all singleton deliveries after blastocyst transfer in Sweden from 2002 through 2013. The in vitro fertilization register was cross-linked with the Swedish Medical Birth Register, the Register of Birth Defects, and the National Patient Register. Deliveries after blastocyst transfer were compared with deliveries after cleavage-stage transfer and deliveries after spontaneous conception. Outcome measures included birth defects, PTB, low birthweight, small for gestational age, large for gestational age, perinatal mortality, placenta previa, placental abruption, and preeclampsia. Crude and adjusted odds ratios (AOR) with 95% confidence interval (CI) were calculated. Adjustment was made for year of birth of child, maternal age, parity, smoking, body mass index, years of involuntary childlessness, and child's sex and, for cleavage stage, also for number of oocytes retrieved, number of embryos transferred, and fresh/frozen embryo transfer. There were 4819 singletons born after blastocyst transfer, 25,747 after cleavage-stage transfer, and 1,196,394 after spontaneous conception. Singletons born after blastocyst transfer had no increased risk of birth defects compared to singletons born after cleavage-stage transfer (AOR, 0.94; 95% CI, 0.79-1.13) or spontaneous conception (AOR, 1.09; 95% CI, 0.92-1.28). Perinatal mortality was higher in the blastocyst vs the cleavage-stage group (AOR, 1.61; 95% CI, 1.14-2.29). When comparing singletons born after blastocyst transfer to singletons born after spontaneous conception, a higher risk of PTB (<37 weeks) was seen (AOR, 1.17; 95% CI, 1.05-1.31). Singletons born after blastocyst transfer had a lower rate of low birthweight (AOR, 0.83; 95% CI, 0.71-0.97) as compared to cleavage-stage transfer. The rate of being small for gestational age was lower in singletons born after blastocyst transfer as compared to both cleavage-stage and spontaneous conception (AOR, 0.71; 95% CI, 0.56-0.88 and AOR, 0.70; 95% CI, 0.57-0.87, respectively). The risk of placenta previa and placental abruption was higher in pregnancies after blastocyst transfer as compared to pregnancies after cleavage-stage (AOR, 2.08; 95% CI, 1.70-2.55 and AOR, 1.62; 95% CI, 1.15-2.29, respectively) and spontaneous conception (AOR, 6.38; 95% CI, 5.31-7.66 and AOR, 2.31; 95% CI, 1.70-3.13, respectively). No increased risk of birth defects was found in singletons born after blastocyst transfer. Perinatal mortality and risk of placental complications were higher in the blastocyst group as compared to the cleavage-stage group, observations that need further investigations.

Anaesthesia practice and reproductive outcomes: Facts unveiled

Background and Aims: Anaesthetic practice is associated with a risk of chronic exposure to anaesthetic agents. With the advent of newer inhalational agents and changing anaesthetic practices, the risks for anaesthesiologists with regard to adverse reproductive outcomes is unknown. Hence, a nationwide online survey was conducted to study the anaesthetic practices prevalent in India and their association, if any, with poor reproductive outcomes. Methods: The online survey involved 9974 anaesthesiologists. A questionnaire soliciting information regarding anaesthetic practice techniques, reproductive outcomes and perinatal outcomes was designed. All the anaesthesiologists in the ISA National database were mailed a link to the above questionnaire. Results: Female anaesthesiologists and spouses of male anaesthesiologists had a higher incidence of first trimester spontaneous abortions than the general population. Female anaesthesiologists when compared with spouses of male anaesthesiologists faced more difficulty with conception (P = 0.015). Female anaesthesiologists who worked in the operating room (OR) in their first trimester of gestation had a higher incidence of spontaneous abortions than those who did not work in the OR (P = 0.05). Longer hours of general anaesthesia conducted in the first trimester of pregnancy was associated with a higher risk of birth defects in their progeny (P = 0.05). Conclusion: Spontaneous abortions and birth defects were higher in female anaesthesiologists who worked in the OR in the first trimester of gestation. Both female anaesthesiologists and spouses of male anaesthesiologists had a greater risk for a first trimester miscarriage than the general population.

Screening high-risk clusters for developing birth defects in mothers in Shanxi Province, China: application of latent class cluster analysis.

BackgroundFew studies on cluster-based synthetic effects of multiple risk factors for birth defects have been reported. The present study aimed to identify maternal exposure clusters, explore the association between clusters of risk factors and birth defects, and further screen women with high risk for birth defects among expectant mothers.MethodsData were drawn from a large-scale, retrospective epidemiological survey of birth defects from 2006 to 2008 in six counties of Shanxi Province, China, using a three-level stratified random cluster sampling technique. Overall risk factors were extracted using eight synthetic variables summed and examined as a total risk factor score: maternal delivery age, genetic factors, medical history, nutrition and folic acid deficiency, maternal illness in pregnancy, drug use in pregnancy, environmental risk factors in pregnancy, and unhealthy maternal lifestyle in pregnancy. Latent class cluster analysis was used to identify maternal exposure clusters based on these synthetic variables. Adjusted odds ratios (AOR) were used to explore associations between clusters and birth defects, after adjusting for confounding variables using logistic regression.ResultsThree latent maternal exposure clusters were identified: a high-risk (6.15 %), a moderate-risk (22.39 %), and a low-risk (71.46 %) cluster. The prevalence of birth defects was 14.08 %, 0.85 %, and 0.52 % for the high-, middle- and low-risk clusters respectively. After adjusting for maternal demographic variables, women in the high-risk cluster were nearly 31 times (AOR: 30.61, 95 % CI: [24.87, 37.67]) more likely to have an infant with birth defects than low-risk women.ConclusionsA high-risk group of mothers in an area with a high risk for birth defects were screened in our study. Targeted interventions should be conducted with women of reproductive age to improve neonatal birth outcomes in areas with a high risk of birth defects.

Insulin analogues in pregnancy and specific congenital anomalies: a literature review.

Insulin analogues are commonly used in pregnant women with diabetes. It is not known if the use of insulin analogues in pregnancy is associated with any higher risk of congenital anomalies in the offspring compared with use of human insulin. We performed a literature search for studies of pregnant women with pregestational diabetes using insulin analogues in the first trimester and information on congenital anomalies. The studies were analysed to compare the congenital anomaly rate among foetuses of mothers using insulin analogues with foetuses of mothers using human insulin. Of 29 studies, we included 1286 foetuses of mothers using short-acting insulin analogues with 1089 references of mothers using human insulin and 768 foetuses of mothers using long-acting insulin analogues with 685 references of mothers using long-acting human insulin (Neutral Protamine Hagedorn). The congenital anomaly rate was 4.84% and 4.29% among the foetuses of mothers using lispro and aspart. For glargine and detemir, the congenital anomaly rate was 2.86% and 3.47%, respectively. No studies on the use of insulin glulisine and degludec in pregnancy were found. There was no statistically significant difference in the congenital anomaly rate among foetuses exposed to insulin analogues (lispro, aspart, glargine or detemir) compared with those exposed to human insulin or Neutral Protamine Hagedorn insulin. The total prevalence of congenital anomalies was not increased for foetuses exposed to insulin analogues. The small samples in the included studies provided insufficient statistical power to identify a moderate increased risk of specific congenital anomalies.

Hépatites virales aiguës à Herpesviridae et grossesse : mise au point

Viral hepatitis are well defined during pregnancy, including hepatitis A, B, C, D or E. In contrast, viral hepatitis called non-alphabetic, like viruses Herpesviridae family hepatitis [cytomegalovirus (CMV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV) or herpes simplex virus (HSV)] are rarely described. The aim of this article is to make a focus on the care of these viral herpesviridae hepatitis during pregnancy. Herpes hepatitis is more common during pregnancy, with a neonatal risk at peripartum period. VZV infection can cause disease to the fetus, with possible vertical transmission, and induce congenital or neonatal varicella. While EBV infection during pregnancy seems benign, the CMV is a high risk of birth defects. The management of these patients therefore depends on the gestational age, but especially the type of virus involved. The diagnosis is therefore essential to adapt treatment and obstetrical care.