Calvarial doughnut lesions with bone fragility in a French-Canadian family; case report and review of the literature.

Calvarial Doughnut Lesions with Bone Fragility (CDL) is an autosomal dominant genetic disease, characterized by low bone mineral density, multiple fractures starting in childhood, and sclerotic doughnut-shaped lesions in the cranial bones. Aubé and colleagues described in 1988 a French-Canadian family of 12 affected members who had a clinical diagnosis of doughnut lesions of the skull, with pathological fractures, osteopenia, "bone in bone" in the vertebral bodies and squaring of metatarsal and metacarpal bones. Herein we study new members of this family. Sequential genetic testing identified a nonsense variant c.148C>T, p. Arg50⁎ in SGMS2 previously reported in other families. SGMS2 encodes Sphingomyelin Synthase 2, which produces Sphingomyelin (SM), a major lipid component of the plasma membrane that plays a role in bone mineralization. The nonsense variant is associated with milder phenotype. The proband presents with bone in bone vertebral appearance that had been defined uniquely in the first cases described in the same family. The proband's son was identified to carry the same variant, which makes him the sixth generation with the diagnosis of CDL. We also report that the same pathogenic variant was identified in another previously described family, from France. These reports further confirm the genetic basis of CDL, the recurrence of the same variant (p.Arg50*) in individuals of the same ancestry, and the variable penetrance of some of the clinical findings.

Factors associated to early intrauterine fetal demise after laser for TTTS by preoperative fetal heart and Doppler ultrasound.

OBJECTIVE: To determine the prognostic value of fetal Doppler and echocardiographic parameters for intrauterine fetal demise (IUFD) within 24 hours and within 1 week after laser coagulation in monochorionic pregnancies complicated by twin-twin transfusion syndrome. METHOD: This retrospective study correlated the preoperative hemodynamic and echocardiography parameters to the outcome in fetuses with twin-twin transfusion syndrome undergoing laser therapy. RESULTS: One hundred and twelve laser coagulations were performed between February 2006 and June 2015. The total (single and double) IUFD rate was 27.7%. Further, 59% of IUFD occurred within 24 hours and 74.4% occurred within 1 week after laser. The following were associated to IUFD within 24 hours: the middle cerebral arterial pulsatility index in the donor, abnormal umbilical artery (UA) end diastolic flow, increased middle cerebral artery peak systolic velocity, and right ventricular myocardial performance index (RV-MPI) z-score in the recipient. For IUFD within 1 week were the pulsatility index in the donor UA and the recipient abnormalities in UA, ductus venosus, middle cerebral artery-peak systolic velocity, and RV-MPI z-score. CONCLUSION: Following laser was early IUFD that was associated with Doppler findings suggesting donor cerebroplacental redistribution, and recipient overload cardiomyopathy, such as abnormal ductus venosus and UA Dopplers as well as an increase of RV-MPI.

Association between Fetal Cerebral Ventriculomegaly and Platelet Alloimmunisation.

INTRODUCTION: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare condition that may lead to intracerebral haemorrhage (ICH) in the fetus or neonate. Platelet alloimmunisation causing FNAIT has been described in association with fetal cerebral ventriculomegaly (VM), presumably due to subclinical ICH. The objective of this study was to assess the association between fetal VM and platelet alloimmunisation. METHODS: This is a case series of pregnancies with fetal VM screened for platelet alloantibodies from 2003 to 2012. Cases of multiple pregnancies, structural anomalies, aneuploidies, or congenital infection were excluded. RESULTS: Of 45 pregnancies with fetal VM that were screened for platelet alloantibodies, 5 (11%) were positive. There was only one antenatal ICH, with confirmed fetal severe thrombocytopenia before termination of pregnancy. The other cases were treated with intravenous immunoglobulins without prior fetal blood sampling. No other case of neonatal thrombocytopenia was confirmed. CONCLUSIONS: The prevalence of platelet alloimmunisation was high in this series of fetal VM. Prospective large studies are needed to confirm the role of platelet alloimmunisation in fetal VM.

Oxidative conditions prevail in severe IUGR with vascular disease and Doppler anomalies.

OBJECTIVE: Intrauterine growth restriction (IUGR) and prenatal exposure to oxidative stress are thought to lead to increased risks of cardiovascular disease later in life. The objective of the present study was to document whether cord blood oxidative stress biomarkers vary with the severity of IUGR and of vascular disease in the twin pregnancy model in which both fetuses share the same maternal environment. METHODS: This prospective cohort study involved dichorionic twin pairs, with one co-twin with IUGR. Oxidative stress biomarkers were measured in venous cord blood samples from each neonate of 32 twin pairs, and compared, according to severity of IUGR (IUGR <5th percentile), Doppler anomalies of the umbilical artery and early onset IUGR (in the second trimester) of the growth restricted twin. RESULTS: Oxidized Low-Density Lipoproteins (oxLDL) and Malondialdehyde (MDA) concentrations were increased proportionally in cases of severe IUGR. OxLDL concentrations were also increased in cases of IUGR with Doppler anomaly. CONCLUSION: Our data indicate that severe IUGR, is related to a derangement in redox balance, illustrated by increased venous cord blood oxidative stress biomarkers concentrations. Severe IUGR and IUGR with abnormal Doppler can be translated into conditions with intense oxidative stress.

Impact of amniotic fluid "sludge" on the risk of preterm delivery.

OBJECTIVE: To evaluate the impact of amniotic fluid "sludge" (AFS) on the risk of preterm delivery and to describe the effect of antibiotic treatment in that situation. METHODS: Case-control study including singleton pregnancies with or without AFS, between 15-32 weeks of gestation. Factors associated with preterm delivery before 32 weeks, 34 weeks and 37 weeks were evaluated with univariate and multivariate logistic regression. Since all women with AFS in this study were treated with antibiotics, a historical comparison was performed with similar patients with AFS found before 2007 and not treated with antibiotics. RESULTS: AFS was observed in 90/1220 patients (7.4%). AFS was associated with shorter cervical length, greater body mass index, cervical cerclage and preterm birth before 28 weeks. However, after adjustment, AFS did not remain associated with preterm delivery before 32 or 34 weeks. The historical comparison suggested that azithromycin could significantly reduce the risk of preterm delivery before 34 weeks (odds ratio: 0.2; 95% CI: 0.04-0.92). CONCLUSIONS: AFS, treated with azithromycin, was associated with a higher risk of prematurity, but not independently after adjustment for cervical length and second trimester vaginal bleeding. Further studies need to evaluate the effect of antibiotics in pregnancies with AFS.

Angiographic embolization of a postpartum vulvovaginal hematoma in a patient with situs inversus totalis: an effective second-line treatment.

Situs inversus totalis is a rare congenital anomaly where asymmetrical positioning of internal organs may affect the surgical and radiological management of certain conditions. Vulvovaginal hematoma is a life-threatening complication of vaginal delivery whose primary treatment usually consists of incision and drainage of the hematoma and ligation of the responsible vessels, followed by wound packing. Failure of these measures to control the bleeding was previously considered as an indication for laparotomy to perform bilateral hypogastric artery ligation and, if needed, a hysterectomy. Relative to major abdominal surgery, selective percutaneous angiographic embolization offers considerable advantages and significant less morbidity. Indeed, angiographic embolization is routinely used as a measure to control refractory pelvic bleeding, though the literature and experience in women with situs inversus totalis are scarce. In this paper, we report a case of postpartum vulvovaginal hematoma in a patient with situs inversus, refractory to conventional treatment, where arteriographic embolization was successfully used to control the bleeding. The management of this obstetrical complication and the use of this minimally invasive technique are also reviewed. To the best of our knowledge, this is the first report in the literature describing the feasibility of this technique in a patient with situs inversus totalis.

[Obstetricians/gynaecologists and breastfeeding: practice, attitudes, training and knowledge]. / Obstétriciens-gynécologues et allaitement maternel : pratique, attitudes, formation et connaissances.

OBJECTIVE: Sole use of breastfeeding is recommended during the first six months of life. The treating physician's opinion influences whether or not the patient will opt for breastfeeding. We wanted to ascertain if obstetricians-gynaecologists and obstetrics and gynaecology residents from Quebec offered counselling on breastfeeding and to examine various aspects of their disposition towards such counselling. METHODS: A questionnaire evaluating five aspects of physicians' disposition towards breastfeeding was used: practice and confidence, attitudes, training, knowledge. We emailed obstetrics and gynaecology residents from Quebec and members of the Association des obstétriciens et gynécologues du Québec who had a valid email address to invite them to complete the questionnaire, which was offered on a secured website. RESULTS: Only 49% of obstetricians-gynaecologists and 35% of residents periodically offer counselling on breastfeeding. Furthermore, 56% and 35% respectively of both groups have confidence in their ability to meet the needs of breastfeeding patients, while 79% of the former and 93% of the latter believe that such counselling comes under their authority. On average, obstetricians-gynaecologists answered correctly 82% of the questions concerning theoretical knowledge. Only 16% of obstetricians-gynaecologists and 22% of residents believe they have received an "at least adequate" training on how to support breastfeeding women. CONCLUSION: Respondents have not adequately integrated breastfeeding counselling into their practice, in spite of the fact that they had adequate theoretical knowledge on the matter and that they were convinced that such a role was important and that it came under their authority. A more practical form of training could enhance their confidence level and encourage them to integrate such counselling into the obstetrical follow-up.

Oxidized low-density lipoproteins in cord blood from neonates with intra-uterine growth restriction.

OBJECTIVE: We verified whether oxidative stress indices (oxidized low-density lipoproteins and malondialdehyde) and inflammatory biomarkers (circulating C-reactive protein, interleukin-6, tumour necrosis factor-α, serum amyloid A and soluble intercellular vascular cell adhesion molecule) are increased in the umbilical vein of placental insufficiency induced intra-uterine growth restricted neonates. STUDY DESIGN: The prospective cohort study, involving 3 tertiary care centers, consists of 200 consecutively recruited pregnant women carrying twins. We chose the twin pregnancy model because both fetuses share the same maternal environment, thereby avoiding potential confounding factors when comparing oxidative stress and inflammation biomarkers. We analysed only twin pairs with one with intra-uterine growth restriction (N=38) defined as fetal growth<10th percentile with abnormal Doppler of the umbilical artery. Blood samples were taken at birth from the umbilical vein. Intra-pair comparisons on the biomarkers were performed using the Student paired t-test. RESULTS: We observed increased cord blood levels of oxidized low-density lipoproteins, (2.394 ± .412 vs 1.296 ± .204, p=.003) but not of malondialdehyde in growth restricted neonates when compared to their normal counterparts. Although indices of inflammation tended to be increased in cord blood from growth restricted newborns, the difference did not reach statistical significance. CONCLUSION: In the twin model, intra-uterine growth restriction is associated with low-density lipoprotein oxidation without apparent dysregulation of inflammation biomarkers. CONDENSATION: Increased oxidized low-density lipoproteins are observed in growth restricted twins compared to their co-twins with normal growth at birth.

Contingent use of fetal fibronectin testing and cervical length measurement in women with preterm labour.

OBJECTIVE: To evaluate the contingent use of fetal fibronectin (fFN) testing and cervical length (CL) measurement to predict preterm delivery, and to validate the use of phosphorylated IGFBP-1 as a predictor of preterm delivery. METHODS: We recruited 71 women with a clinical diagnosis of preterm labour between 24 and 34 weeks, and tested for the presence of fFN and IGFBP-1 in the cervicovaginal secretions of all women immediately before CL measurement. RESULTS: Among the 66 women with complete outcome, four were excluded from the final analysis as two had assessment for fFN but no CL measurement, and another two had CL measured but no screening for fFN. Among 62 women with complete results, the mean gestational age at recruitment was 29.4 +/- 2.5 weeks. Six women (9.6%) delivered within two weeks of assessment, and 14 (22.5%) delivered before 34 weeks. A positive fFN test resulted in a sensitivity of 83%, a specificity of 84%, a positive predictive value of 36%, and a negative predictive value of 98% for delivery within two weeks; for CL < 25 mm, these figures were 50%, 52%, 10%, and 91%, respectively, and for a positive IGFBP-1, they were 17%, 93%, 20%, and 91%, respectively. A policy of contingent use of fFN (in which the test was assumed to be positive if CL < or = 15 mm, and fFN was only measured if the CL was between 16 and 30 mm) gave sensitivity, specificity, positive and negative predictive values of 80%, 61%, 17%, and 97%, respectively for delivery within two weeks. Using this contingent use protocol, only one third of women needed fFN screening after CL measurement. CONCLUSION: In this study, IGFBP-1 screening did not predict preterm delivery and fFN screening provided the best predictive capacity. A policy of contingent use of testing for fFN after CL measurement, or contingent use of CL measurement after fFN screening (depending on available resources) is a promising approach to limit use of resources.

Singleton breech at term: two continents, two approaches.

Breech presentation is a complication in 3% to 4% of singleton pregnancies at term. On the strength of a large study published in the early 2000s, the American College of Obstetricians and Gynecologists (ACOG) recommended Caesarean section be routinely performed in such cases. However, French gynaecologists continue to perform vaginal breech deliveries. Through various observational studies, they have shown that their management approach, although different from the one used in North America, is safe. In 2006, the ACOG declared that vaginal delivery of a breech presentation may be acceptable under specific circumstances. In this analysis, we compare North American and French practices and present a protocol of care for the management of term breech presentation based on French recommendations.

An international trial of antioxidants in the prevention of preeclampsia (INTAPP).

OBJECTIVE: We sought to investigate whether prenatal vitamin C and E supplementation reduces the incidence of gestational hypertension (GH) and its adverse conditions among high- and low-risk women. STUDY DESIGN: In a multicenter randomized controlled trial, women were stratified by the risk status and assigned to daily treatment (1 g vitamin C and 400 IU vitamin E) or placebo. The primary outcome was GH and its adverse conditions. RESULTS: Of the 2647 women randomized, 2363 were included in the analysis. There was no difference in the risk of GH and its adverse conditions between groups (relative risk, 0.99; 95% confidence interval, 0.78-1.26). However, vitamins C and E increased the risk of fetal loss or perinatal death (nonprespecified) as well as preterm prelabor rupture of membranes. CONCLUSION: Vitamin C and E supplementation did not reduce the rate of preeclampsia or GH, but increased the risk of fetal loss or perinatal death and preterm prelabor rupture of membranes.

Postpartum pain relief: a randomized comparison of self-administered medication and standard administration.

OBJECTIVE: To compare pain relief in postpartum women receiving analgesia administered by nurses with the relief achieved by use of self-administered medication (SAM). METHOD: This randomized trial included women in spontaneous or induced labour or admitted for elective Caesarean section (CS). Women were stratified according to the mode of delivery. In the standard group, nurses administered the medications. In the SAM group, women kept the medications at the bedside and recorded each dose. The women were asked to record their pain level with a validated scale before and one hour after the administration of analgesia. A global pain score was calculated using the mean of these scores, and the satisfaction of patients and nurses with the process was recorded. RESULTS: We recruited 345 women for the study. Eleven women (3.15 %) were lost to follow-up. We analyzed data from 197 women in the vaginal delivery arm and 133 women in the CS arm. There was no difference between the global pain scores before and one hour after the administration of analgesia in each group, independent of the mode of delivery. Women who used SAM and had a vaginal delivery were significantly more likely to have used no medication (P = 0.02) or to have used acetaminophen (P = 0.008), and fewer of these women took naproxen (P = 0.05). No significant difference was seen in women who had CS. Narcotic use was similar in each group. Women who used SAM were more likely to indicate that they would choose this method again and recommend it to others. The level of satisfaction with SAM expressed by nurses did not change after the study. CONCLUSION: Postpartum pain relief was similar for women who had standard administration of medication by nurses and those who had SAM. More women using SAM used either no medication or acetaminophen only, and more women using SAM were highly satisfied with their method of pain relief. Use of self-administered medication should be considered for every postpartum unit.

Identifying barriers and facilitators towards implementing guidelines to reduce caesarean section rates in Quebec.

OBJECTIVE: To investigate obstetricians perceptions of clinical practice guidelines targeting management of labour and vaginal birth after previous caesarean birth, and to identify the barriers to, facilitators of and obstetricians solutions for implementing these guidelines in practice. METHODS: This qualitative study was conducted in three hospitals in Montreal that represent around 10% of births in Quebec. Data was collected from 10 focus groups, followed by six semi-structured interviews. Two researchers jointly analysed the verbatim transcripts according to A manual for the use of focus groups. FINDINGS: The identified barriers to and facilitators of the implementation of guidelines can be classified into four categories: 1) the hospital level, including management and hospital policies; 2) the departmental level, including local policies, leadership, organizational factors, economic incentive, and availability of equipment and staff; 3) the health professionals motivations and attitudes, including medico-legal concerns, skill levels, acceptance of guidelines and strategies used to implement recommendations; and 4) patients motivations. CONCLUSION: Identifying the barriers to and facilitators of the adoption of recommendations is an important way to guide the development of efficient strategies. The findings of this study suggest that the adoption of guidelines may be improved if local health professionals perceptions are considered to make recommendations more acceptable and useful. Our findings also support the assumption that obstetricians seek to implement best practices, but require evidence tools and support to assess their practices and enhance their performance. In addition, peer review activities championed by opinion leaders have been identified by obstetricians as the most suitable strategy to improve the use of the guidelines in their practices.

Vasa praevia after IVF: should there be guidelines? Report of two cases and literature review.

The paper gives an illustration and reminder of the risk of problems with placentation resulting from IVF and embryo transfer. Reported here is one neonatal death related to vasa praevia when the condition was not diagnosed antenatally and a neonatal survival when vasa praevia was detected antenatally. A search of the English literature was performed using PubMed for 'vasa praevia and in vitro fertilization'. There were four articles that directly addressed this relationship. Case reports of IVF-embryo transfer pregnancies with vasa praevia and also studies that look at the incidence of vasa praevia in such pregnancies are included in this report. Hence, since vasa praevia is thought to be caused by a disturbed orientation of the blastocyst at implantation, it is probably related to the IVF-embryo transfer procedure. Screening of all IVF-embryo transfer pregnancies with transvaginal sonography and colour Doppler to rule out vasa praevia is recommended in the second trimester.

Sublingual nitroglycerine as a tocolytic in external cephalic version: a comparative study.

OBJECTIVE: To study the effect of sublingual nitroglycerine as a tocolytic on the success rate of external cephalic version (ECV) in nulliparous and parous women. METHODS: A retrospective case-controlled study of all ECV cases from February 1996 to February 2000 in a single centre. The rates of successful ECV were compared between women who had their ECV before February 1998 (control group), those who had their ECV after February 1998 and received 0.8 mg sublingual nitroglycerine spray as a tocolytic agent, and those who had their ECV after February 1998 and received no tocolytic agents. Nulliparous and parous women were studied separately. Data were collected for parity, gestational age, maternal age, placental localization, and side effects. Chi-square and Kruskal-Wallis tests were performed for statistical comparison. RESULTS: Of 150 women who had their ECV after February 1998, 120 (80%) received sublingual nitroglycerine (group 1: cases using 0.8 mg sublingual nitroglycerine spray as a tocolytic agent) and were compared to the 30 patients who did not receive sublingual nitroglycerine or other tocolytics after February 1998 (group 2) and to 137 patients who had their ECV before February 1998 (control group). Of the women who received sublingual nitroglycerine, 5 (4%) had hypotension and 7 (6%) had headaches and/or nausea. The rate of successful ECV was 27% in group 1 versus 30% in group 2 (p = 0.86) versus 28% in the control group (p = 0.88) for nulliparous patients, and 67% versus 80% (p = 0.30) versus 51% (p = 0.09) respectively for parous women. However, the success rate was increased overall in parous women after the introduction of nitroglycerine as a tocolytic for ECV in February 1998 (71% vs. 51%, p = 0.02). CONCLUSION: Although the success rate of ECV has increased in recent years, the use of sublingual nitroglycerine as a tocolytic was not associated with this higher success rate. A randomized, controlled trial is needed.

Incidence of open neural tube defects in Nova Scotia after folic acid fortification.

BACKGROUND: With the goal of preventing open neural tube defects (NTDs), recommendations for folic acid supplementation before conception were introduced in Canada in 1994, and by November 1998 Canadian grain products were being fortified with folic acid. We wished to determine whether the annual incidence of open NTDs in Nova Scotia, including those in stillbirths and terminated pregnancies, changed after the introduction of either folic acid supplementation or fortification. METHODS: For the 10-year period from Jan. 1, 1991, to Dec. 31, 2000, we retrospectively extracted the total number of births in Nova Scotia and the number of live births and stillbirths with open NTDs from the Nova Scotia Atlee Perinatal Database as well as the number of terminated pregnancies affected by NTDs from the Fetal Anomaly Database. We determined the total annual incidence of all open NTDs, and of the subgroups spina bifida and anencephaly, per 1000 births in the province during the periods before (1991-1994) and after (1995-1998) folic acid supplementation initiatives were begun but before folic acid fortification of grain products was implemented, and during the periods before (1991-1997) and after (1998-2000) fortification. RESULTS: In the period after supplementation initiatives were begun but before fortification was implemented, the incidence of open NTDs did not change significantly: the mean annual rate was 2.55 per 1000 births during 1991-1994 and 2.61 per 1000 births during 1995-1997 (relative risk [RR] 1.02, 95% confidence interval [CI] 0.77-1.35). After the fortification was implemented the incidence of open NTDs decreased by more than 50%: the mean annual rate was 2.58 per 1000 births during 1991-1997 and 1.17 per 1000 births during 1998-2000 (relative risk 0.46, 95% CI 0.32-0.66). INTERPRETATION: The recommendations for folic acid supplementation alone did not appear to succeed in reducing the incidence of open NTDs in Nova Scotia, whereas the fortification of grain products with folic acid did result in a significant reduction in the incidence.

Does chorionicity or zygosity predict adverse perinatal outcomes in twins?

OBJECTIVE: The purpose of this study was to evaluate chorionicity and zygosity as risk factors for adverse perinatal outcomes in twins. STUDY DESIGN: A population-based, retrospective cohort study was conducted of all twin deliveries in Nova Scotia, Canada, from 1988 to 1997. Chorionicity was established by histologic examination. Zygosity was determined by chorionicity, sex, and infant blood group. Three groups were established: monochorionic/monozygotic twins, dichorionic/dizygotic twins, and dichorionic/majority monozygotic twins. RESULTS: Outcomes from 1008 twin pregnancies were analyzed. Monochorionic/monozygotic twins had lower mean birth weights compared with dichorionic/dizygotic twins. Rates of perinatal mortality of at least 1 twin were significantly higher among monochorionic/monozygotic twins relative to dichorionic/dizygotic twins (relative risk, 2.5; 95% CI, 1.1-2.5). Dichorionic/majority monozygotic twins had similar perinatal outcomes compared with dichorionic/dizygotic twins. CONCLUSION: Monochorionicity increases the risk of adverse perinatal outcome, whereas the effect of zygosity is less clear. Because chorionicity can be determined by prenatal ultrasound scanning, this information should be considered in the prenatal care of twin pregnancies.