Congenital Malformation Risk According to Hemoglobin A1c Values in a Contemporary Cohort with Pregestational Diabetes

Objective The study aimed to evaluate the association between hemoglobin A1c values and likelihood of fetal anomalies in women with pregestational diabetes. Study Design Women with pregestational diabetes who delivered at a single institution that serves a nonreferred population from May 1, 2009 to December 31, 2018 were ascertained. Hemoglobin A1c values were obtained at the first prenatal visit. Women who delivered a singleton live- or stillborn infant with a major malformation as defined by European Surveillance of Congenital Anomalies criteria were identified. In infants with multiple system anomalies, each malformation was considered separately. Hemoglobin A1c values were analyzed categorically by using Mantel–Haenszel method and continuously with linear regression for trend for fetal anomalies. Results A total of 1,676 deliveries to women with pregestational diabetes were delivered at our institution, and hemoglobin A1c was assessed in 1,573 deliveries (94%). There were 129 deliveries of an infant with at least one major malformation, an overall anomaly rate of approximately 8%. Mean hemoglobin A1c concentration was significantly higher in pregnancies with anomalous infants, 9.3 ± 2.1% versus 8.0 ± 2.1%, and p <0.001. There was no difference in gestational age at the time hemoglobin A1c was obtained, 13 ± 8.3 versus 14 ± 8.7 weeks. Hemoglobin A1c was associated with increased probability of a congenital malformation. This reached 10% with a hemoglobin A1c concentration of 10%, and 20% with a hemoglobin A1c of 13%. Similar trends were seen when examining risk of anomalies by organ system with increasing hemoglobin A1c levels, with the greatest increase in probability for both cardiac and genitourinary anomalies. Conclusion In women with pregestational diabetes, hemoglobin A1c is strongly associated with fetal anomaly risk. Data from a contemporary cohort may facilitate counseling and also highlight the need for preconceptual care and glycemic optimization prior to entry to obstetric care. Key Points

First Trimester Hemoglobin A1 and Risk for Major Malformation and Spontaneous Abortion

This chapter summarizes a landmark study on the association of first trimester hemoglobin A1 values with risk for spontaneous abortions and major fetal malformations during pregnancy in women with pregestational diabetes. Is there a correlation between glycemic control during the first trimester and risk for spontaneous abortion and major malformations? Starting with this question, it describes the basics of the study, including study location, study population, amount of patients, study design, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case.

Morgagni-Larrey parasternal diaphragmatic hernia masquerading as pleural effusion: an interesting presentation with review of literature

Congenital diaphragmatic hernia (CDH) is a major malformation found in newborns and babies but rarely in adults. CDH is defined by the presence of a defect in the diaphragm, which permits the herniation of abdominal contents into the thorax. The diagnosis of CDH is based on clinical history, examinations and is confirmed by plain X-ray films and computed tomography scans. Here we report a case which was misdiagnosed at another centre as pleural effusion and managed by placement of intercostal tube drainage and later on diagnosed to be case of Morgnani-Larrey parasternal diaphragmatic hernia. Congenital diaphragmatic hernia (CDH) is a major malformation found in newborns and babies but rarely in adults. CDH is defined by the presence of a defect in the diaphragm, which permits the herniation of abdominal contents into the thorax. The diagnosis of CDH is based on clinical history, examinations and is confirmed by plain X-ray films and computed tomography scans. The purpose of reporting this case is to provide information on late-presenting CDH and to emphasize that a high index of suspicion is required for diagnosis and to avoid unwanted complications.

Associations between macrolide antibiotics prescribing during pregnancy and adverse child outcomes in the UK: population based cohort study

Objective To assess the association between macrolide antibiotics prescribing during pregnancy and major malformations, cerebral palsy, epilepsy, attention deficit hyperactivity disorder, and autism spectrum disorder in children. Design Population based cohort study. Setting The UK Clinical Practice Research Datalink. Participants The study cohort included 104 605 children born from 1990 to 2016 whose mothers were prescribed one macrolide monotherapy (erythromycin, clarithromycin, or azithromycin) or one penicillin monotherapy from the fourth gestational week to delivery. Two negative control cohorts consisted of 82 314 children whose mothers were prescribed macrolides or penicillins before conception, and 53 735 children who were siblings of the children in the study cohort. Main outcome measures Risks of any major malformations and system specific major malformations (nervous, cardiovascular, gastrointestinal, genital, and urinary) after macrolide or penicillin prescribing during the first trimester (four to 13 gestational weeks), second to third trimester (14 gestational weeks to birth), or any trimester of pregnancy. Additionally, risks of cerebral palsy, epilepsy, attention deficit hyperactivity disorder, and autism spectrum disorder. Results Major malformations were recorded in 186 of 8632 children (21.55 per 1000) whose mothers were prescribed macrolides and 1666 of 95 973 children (17.36 per 1000) whose mothers were prescribed penicillins during pregnancy. Macrolide prescribing during the first trimester was associated with an increased risk of any major malformation compared with penicillin (27.65 v 17.65 per 1000, adjusted risk ratio 1.55, 95% confidence interval 1.19 to 2.03) and specifically cardiovascular malformations (10.60 v 6.61 per 1000, 1.62, 1.05 to 2.51). Macrolide prescribing in any trimester was associated with an increased risk of genital malformations (4.75 v 3.07 per 1000, 1.58, 1.14 to 2.19, mainly hypospadias). Erythromycin in the first trimester was associated with an increased risk of any major malformation (27.39 v 17.65 per 1000, 1.50, 1.13 to 1.99). No statistically significant associations were found for other system specific malformations or for neurodevelopmental disorders. Findings were robust to sensitivity analyses. Conclusions Prescribing macrolide antibiotics during the first trimester of pregnancy was associated with an increased risk of any major malformation and specifically cardiovascular malformations compared with penicillin antibiotics. Macrolide prescribing in any trimester was associated with an increased risk of genital malformations. These findings show that macrolides should be used with caution during pregnancy and if feasible alternative antibiotics should be prescribed until further research is available. Trial registration ClinicalTrials.gov NCT03948620

O14 Paternal acitretin exposure and pregnancy risks

BackgroundIn the literature it is well known that acitretin is highly teratogen when used in pregnant women. Therefore, several restrictions to all fertile women prior, during and up to three years after ended treatment are recommended. However, as for paternal acitretin exposure data is very limited leading to worries and anxiety among couples planning or already pregnant.MethodsWe conducted a nationwide cohort study during the period between 1996–2016 investigating paternal acitretin exposure and the risk of spontaneous abortions and the association to major malformation. Data were obtained from the Medical Birth Registry and the National Hospital Registry. All fathers exposed to acitretin were identified by the Danish National Prescription Registry.ResultsWe identified in total 1.477.252 registered pregnancies with known father identity. Of these 244 pregnancies and 205 children were exposed to paternal acitretin treatment between one year prior to conception to the end of first trimester. The adjusted hazard risk (HR) of spontaneous abortion was 0.71 (95% CI: 0.43–1.17). When analysing exposure three months prior to conception and during first trimester only, the adjusted HR was 0.76 (95% CI:0.38–1.51) and 1.06 (95% CI:0.55–2.04), respectively. As for the association between major malformation and paternal acitretin exposure between one year prior to conception to the end of first trimester the adjusted odds ratio (OR) was 1.15 (95% CI: 0.57–2.34). When stratifying for the period of acitretin exposure the same insignificant trend was detected. In addition, both spontaneous abortions and major malformation were independent of dosage.ConclusionWe found no increased risk of spontaneous abortions or major malformation in pregnancies exposed to paternal acitretin one year before to three months after conception. This was persistent when sub-analysing exposure period and dosage. These data are an important contribute to the sparse evidence suggesting that paternal acitretin exposure during fertility is safe.Disclosure(s)Nothing to disclose

Robot-assisted thoracoscopic repair of a late-onset Bochdalek hernia: a case report

Bochdalek hernia (BH) is a major malformation that consists of a postero-lateral diaphragmatic defect through which abdominal contents can migrate into the thorax. It is most commonly a neonatal pathology associated with significant morbidity and mortality. Rarely, this type of congenital diaphragmatic hernia (CDH) presents later in life, some even in adulthood. Indications for surgery are not clear even though the majority of authors, being aware of the possible severe complications, recommend surgical correction in all cases. Many surgical approaches have been tried for this pathology, both open (laparotomic or thoracotomic) and minimally invasive (laparoscopic or thoracoscopic). We report a case of a late-onset BH corrected with a robot-assisted thoracoscopic procedure. The use of robotic technology for CDH has never been described to date.

Obstetric and neonatal outcome in women with epilepsy

Background: Epilepsy is the second most common neurological disorder complicating pregnancy next to migraine. Both mother and fetus stay at risk due to epilepsy and side effects of antiepileptic’s. This retrospective study was conducted to study fetal and maternal outcome in WWE.Methods: This study was conducted on 55 patients of epilepsy with pregnancy who attended antenatal clinic of our hospital from January 2016 to December 2016. Data was collected using antenatal registers in outdoor settings and medical case sheets in indoor patients and was analyzed statistically.Results: There were a total of 55 WWE in one year duration. Incidence of epilepsy being 0.4% in this study. 11 WWE were not on ante epileptic drug when conceived, while 34 WWE were on ante epileptic drugs when conceived, 8 WWE were newly diagnosed and 2 patients had both psychiatric disorders along with epilepsy. There were 3 IUDs, 4 major congenital malformation and 2 minor malformations. 2 major malformation occurred in patients taking both antipsychotic and ante epileptics since conception.Conclusions: There were a total of 55 WWE in one year duration. Incidence of epilepsy being 0.4% in this study. 11 WWE were not on ante epileptic drug when conceived, while 34 WWE were on ante epileptic drugs when conceived, 8 WWE were newly diagnosed and 2 patients had both psychiatric disorders along with epilepsy. There were 3 IUDs, 4 major congenital malformation and 2 minor malformations. 2 major malformation occurred in patients taking both antipsychotic and ante epileptics since conception.

Brain Malformations Do Not Predict Hypopituitarism in Young Children with Optic Nerve Hypoplasia

Background: Optic nerve hypoplasia (ONH), a leading cause of pediatric blindness, is associated with brain malformations and hypopituitarism in the constellation known as septo-optic dysplasia. Neuroimaging is used to anticipate hypopituitarism, but with unconfirmed reliability. We report prospective findings on the association of hypopituitarism with brain malformations. Methods: Children (<24 months) with ONH (n = 146; 87% bilateral) underwent baseline MRI and annual examinations and hormonal testing. Hypopituitarism status at age 5 years was classified. Results: A total of 74% had brain malformation(s). Hypopituitarism (69%) was not associated with brain malformations (p = 0.351); this persisted after adjusting for the laterality of ONH and the timing of MRI (padj = 0.869). No association was noted for absent septum pellucidum (38%; p = 0.073), corpus callosum abnormality (51%; p = 0.625), and major malformations (22%; p = 0.407). A malformation conferred a positive predictive value of 71% (95% CI: 62%, 80%), and a negative predictive value of 37% (95% CI: 22%, 54%). Overall, 10% (n = 15) of the cohort presented with a triad of absent septum pellucidum, corpus callosum abnormality, and other major malformation; only half (n = 8) of these had hypopituitarism. All 13 subjects with pituitary malformations manifested hypopituitarism, conferring predictive values of 100% (positive) and 34% (negative). Conclusions: Hypopituitarism and brain malformations are highly prevalent, but have unrelated associations with ONH. Brain MRI in infants and toddlers with ONH is an unreliable screen for hypopituitarism risk.

MicroSort® sperm sorting causes no increase in major malformation rate

The purpose of the present study was to evaluate the safety of MicroSort (MicroSort Division, GIVF, Fairfax, VA, USA) sperm sorting by monitoring major malformations in infants and fetuses conceived using sorted spermatozoa. Data were collected in a prospective protocol with monitoring that began from conception through birth until 1 year of life. Comprehensive ascertainment identified fetuses and stillbirths with malformations after 16 weeks gestation, pregnancies terminated for malformations and babies with major malformations. Outcomes in MicroSort pregnancies were compared with outcomes in published studies that used active and comprehensive ascertainment of malformations in the general population and in pregnancies established after assisted reproduction. Using comprehensive outcomes from all pregnancies, the rate of major malformations in MicroSort pregnancies conceived after IVF with or without intracytoplasmic sperm injection was 7.8%; this did not differ significantly from the rates reported in the three assisted reproductive technology control studies not associated with MicroSort (8.6%, 9.2% and 8.3%). Similarly, the rate of major malformations in MicroSort pregnancies initiated with intrauterine insemination was 6.0%, not significantly different from that reported in non-assisted reproductive technology pregnancies not associated with MicroSort (6.9%, 4.6% and 5.7%). Prospective record review of pregnancy outcomes and paediatric evaluation to 1 year indicate no association between MicroSort sperm sorting and major malformations.