No 373 - Insuffisance cervicale et cerclage cervical.

OBJECTIF: La présente directive clinique vise à fournir aux cliniciens un cadre à utiliser pour déterminer quelles femmes présentent un risque accru d'insuffisance cervicale et dans quelles situations le cerclage aurait une valeur potentielle. DONNéES PROBANTES: Nous avons examiné des études publiées récupérées au moyen de recherches dans PubMed, Medline, CINAHL et The Cochrane Library en 2018 à l'aide d'une terminologie (p. ex., uterine cervical incompetence) et de mots-clés (p. ex., cervical insufficiency, cerclage, Shirodkar cerclage, McDonald cerclage, abdominal, cervical length, mid-trimester pregnancy loss). Nous avons tenu compte des résultats provenant de revues systématiques, d'essais cliniques randomisés, d'essais cliniques contrôlés et d'études observationnelles. Aucune restriction de date ou de langue n'a été employée. Les recherches ont été refaites régulièrement, et les résultats ont été incorporés à la directive clinique jusqu'en juin 2018. Nous avons également tenu compte de la littérature grise (non publiée) trouvée sur les sites Web d'organismes d'évaluation des technologies de la santé et d'autres organismes liés aux technologies de la santé, dans des collections de directives cliniques et des registres d'essais cliniques, et obtenue auprès d'associations nationales et internationales de médecins spécialistes. VALEURS: La qualité des données probantes a été évaluée en fonction des critères décrits dans le rapport du Groupe d'étude canadien sur les soins de santé préventifs. RECOMMANDATIONS.

No. 373-Cervical Insufficiency and Cervical Cerclage.

OBJECTIVE: The purpose of this guideline is to provide a framework that clinicians can use to determine which women are at greatest risk of having cervical insufficiency and in which set of circumstances a cerclage is of potential value. EVIDENCE: Published literature was retrieved through searches of PubMed or Medline, CINAHL, and The Cochrane Library in 2018 using appropriate controlled vocabulary (e.g., uterine cervical incompetence) and key words (e.g., cervical insufficiency, cerclage, Shirodkar, cerclage, McDonald, cerclage, abdominal, cervical length, mid-trimester pregnancy loss). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to June 2018. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. VALUES: The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care.

Severe hemolytic disease of the fetus and newborn due to allo-anti-D in a patient with a partial DEL phenotype arising from the variant allele described as RHD*148+1T (RHD*01EL.31).

BACKGROUND: RhD DEL variants may show complete or partial expression of RhD epitopes. There have been only rare reports of anti-D causing hemolytic disease of the fetus and newborn (HDFN) in this context. We report a case of severe HDFN associated with a recently described DEL variant. CASE REPORT: A multiparous woman presented with an allo-anti-D and showed incongruent phenotyping and genotyping results on initial study. Further investigations identified the RHD mutation, defined as RHD*148+1T and named RHD*01EL.31, which had been previously associated with a DEL phenotype. Extended RhD phenotyping by adsorption-elution showed that there was reactivity with four of nine monoclonal anti-D antibodies, suggesting a partial DEL phenotype. The first child showed no clinical evidence of HDFN, although the cord direct antiglobulin test was positive. The second child developed fetal anemia treated with intrauterine transfusion, and neonatal hyperbilirubinemia requiring exchange transfusion. CONCLUSION: The RHD allele, RHD*148+1T, results in a partial Del phenotype, and the anti-D formed in pregnant women with this phenotype is capable of causing severe HDFN.

Fetal Outcomes of Prenatally Diagnosed Congenital Diaphragmatic Hernia: Nine Years of Clinical Experience in a Canadian Tertiary Hospital.

OBJECTIVE: To summarize the clinical outcome of congenital diaphragmatic hernia (CDH) identified on prenatal ultrasound. METHOD: We reviewed prenatally detected cases of CDH diagnosed between July 2000 and September 2009 at a single tertiary-care facility. RESULTS: Ninety-one cases were identified. Sixty-nine cases had complete medical records including karyotype. Of these, 40 were isolated defects and 29 cases had additional congenital or chromosome anomalies. An abnormal karyotype was present in 17.4% overall, affecting 2.5% of cases of isolated CDH (1/40) and 37.9% of cases of non-isolated CDH (11/29). The rate of termination of pregnancy in cases of isolated CDH diagnosed prior to 24 weeks was 33.3% (10/30), and in cases of non-isolated CDH it was 73.9% (17/23). The survival rate of the 44 liveborn infants was 66.7% (24/36) for those with isolated CDH and 37.5% (3/8) for those with non-isolated CDH. The decision to terminate the pregnancy was made in 73.9% of fetuses with prenatally diagnosed karyotype or additional anatomical abnormalities, in contrast to 37.5% of prenatally diagnosed isolated CDH. CONCLUSION: The outcomes of pregnancies that continue after identification of CDH are in keeping with previous reports, with an overall survival rate of 61.4%. The presence of additional anatomical anomalies was the only predictor of mortality among liveborn infants.

Insuffisance cervicale et cerclage cervical.

OBJECTIF: La présente directive clinique a pour but de fournir un cadre de référence que les cliniciens pourront utiliser pour identifier les femmes qui sont exposées aux plus grands risques de connaître une insuffisance cervicale, ainsi que pour déterminer les circonstances en présence desquelles la mise en place d'un cerclage pourrait s'avérer souhaitable. RéSULTATS: La littérature publiée a été récupérée par l'intermédiaire de recherches menées dans PubMed ou MEDLINE, CINAHL et The Cochrane Library en 2012 au moyen d'un vocabulaire contrôlé (p. ex. « uterine cervical incompetence ¼) et de mots clés appropriés (p. ex. « cervical insufficiency ¼, « cerclage ¼, « Shirodkar ¼, « cerclage ¼, « MacDonald ¼, « cerclage ¼, « abdominal ¼, « cervical length ¼, « mid-trimester pregnancy loss ¼). Les résultats ont été restreints aux analyses systématiques, aux essais comparatifs randomisés / essais cliniques comparatifs et aux études observationnelles. Aucune restriction n'a été appliquée en matière de date ou de langue. Les recherches ont été mises à jour de façon régulière et intégrées à la directive clinique jusqu'en janvier 2011. La littérature grise (non publiée) a été identifiée par l'intermédiaire de recherches menées dans les sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et auprès de sociétés de spécialité médicale nationales et internationales. VALEURS: La qualité des résultats est évaluée au moyen des critères décrits dans le rapport du Groupe d'étude canadien sur les soins de santé préventifs (Tableau). RECOMMANDATIONS.

Association between gestational age at birth, antenatal corticosteroids, and outcomes at 5 years: multiple courses of antenatal corticosteroids for preterm birth study at 5 years of age (MACS-5).

BACKGROUND: The Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study (MACS) showed no benefit in the reduction of major neonatal mortality/morbidity or neurodevelopment at 2 and 5 years of age. Using the data from the randomized controlled trial and its follow-up, the aim of this study was to evaluate the association between gestational ages at birth in children exposed to single versus multiple courses of antenatal corticosteroid (ACS) therapy in utero and outcomes at 5 years of age. METHOD: A total of 1719 children, with the breakdown into groupings of <30, 30-36, and ≥ 37 weeks gestation at birth, contributed to the primary outcome: death or survival with a disability in one of the following domains: neuromotor, neurosensory, and neurobehavioral/emotional disability and were included in this analysis. RESULTS: Gestational age at birth was strongly associated with the primary outcome, p < 0.001. Overall, the interaction between ACS groups and gestational age at birth was not significant, p = 0.064. Specifically, in the 2 preterm categories, there was no difference in the primary outcome between single vs. multiple ACS therapy. However, for infants born ≥37 weeks gestation, there was a statistically significant increase in the risk of the primary outcome in multiple ACS therapy, 48/213 (22.5%) compared to 38/249 (15.3%) in the single ACS therapy; OR = 1.69 [95% CI: 1.04, 2.77]; p = 0.037. CONCLUSION: Preterm birth (<37 weeks gestation) remained the primary factor contributing to an adverse outcome regardless of the number of courses of ACS therapy. Children born ≥ 37 weeks and exposed to multiple ACS therapy may have an increased risk of neurodevelopmental/neurosensory impairment by 5 years of age. To optimize outcomes for infants/children, efforts in reducing the incidence of preterm birth should remain the primary focus in perinatal research. TRIAL REGISTRATION: This study has been registered at (identifier NCT00187382).

Cervical insufficiency and cervical cerclage.

OBJECTIVE: The purpose of this guideline is to provide a framework that clinicians can use to determine which women are at greatest risk of having cervical insufficiency and in which set of circumstances a cerclage is of potential value. EVIDENCE: Published literature was retrieved through searches of PubMed or MEDLINE, CINAHL, and The Cochrane Library in 2012 using appropriate controlled vocabulary (e.g., uterine cervical incompetence) and key words (e.g., cervical insufficiency, cerclage, Shirodkar, cerclage, MacDonald, cerclage, abdominal, cervical length, mid-trimester pregnancy loss). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to January 2011. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. VALUES: The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table). Recommendations 1. Women who are pregnant or planning pregnancy should be evaluated for risk factors for cervical insufficiency. A thorough medical history at initial evaluation may alert clinicians to risk factors in a first or index pregnancy. (III-B) 2. Detailed evaluation of risk factors should be undertaken in women following a mid-trimester pregnancy loss or early premature delivery, or in cases where such complications have occurred in a preceding pregnancy. (III-B) 3. In women with a history of cervical insufficiency, urinalysis for culture and sensitivity and vaginal cultures for bacterial vaginosis should be taken at the first obstetric visit and any infections so found should be treated. (I-A) 4. Women with a history of three or more second-trimester pregnancy losses or extreme premature deliveries, in whom no specific cause other than potential cervical insufficiency is identified, should be offered elective cerclage at 12 to 14 weeks of gestation. (I-A) 5. In women with a classic history of cervical insufficiency in whom prior vaginal cervical cerclage has been unsuccessful, abdominal cerclage can be considered in the absence of additional mitigating factors. (II-3C) 6. Women who have undergone trachelectomy should have abdominal cerclage placement. (II-3C) 7. Emergency cerclage may be considered in women in whom the cervix has dilated to < 4 cm without contractions before 24 weeks of gestation. (II-3C) 8. Women in whom cerclage is not considered or justified, but whose history suggests a risk for cervical insufficiency (1 or 2 prior mid-trimester losses or extreme premature deliveries), should be offered serial cervical length assessment by ultrasound. (II-2B) 9. Cerclage should be considered in singleton pregnancies in women with a history of spontaneous preterm birth or possible cervical insufficiency if the cervical length is ≤ 25 mm before 24 weeks of gestation. (I-A) 10. There is no benefit to cerclage in a woman with an incidental finding of a short cervix by ultrasound examination but no prior risk factors for preterm birth. (II-1D) 11. Present data do not support the use of elective cerclage in multiple gestations even when there is a history of preterm birth; therefore, this should be avoided. (I-D) 12. The literature does not support the insertion of cerclage in multiple gestations on the basis of cervical length. (II-1D).

Objectif : La présente directive clinique a pour but de fournir un cadre de référence que les cliniciens pourront utiliser pour identifier les femmes qui sont exposées aux plus grands risques de connaître une insuffisance cervicale, ainsi que pour déterminer les circonstances en présence desquelles la mise en place d'un cerclage pourrait s'avérer souhaitable. Résultats : La littérature publiée a été récupérée par l'intermédiaire de recherches menées dans PubMed ou MEDLINE, CINAHL et The Cochrane Library en 2012 au moyen d'un vocabulaire contrôlé (p. ex. « uterine cervical incompetence ¼) et de mots clés appropriés (p. ex. « cervical insufficiency ¼, « cerclage ¼, « Shirodkar ¼, « cerclage ¼, « MacDonald ¼, « cerclage ¼, « abdominal ¼, « cervical length ¼, « mid-trimester pregnancy loss ¼). Les résultats ont été restreints aux analyses systématiques, aux essais comparatifs randomisés / essais cliniques comparatifs et aux études observationnelles. Aucune restriction n'a été appliquée en matière de date ou de langue. Les recherches ont été mises à jour de façon régulière et intégrées à la directive clinique jusqu'en janvier 2011. La littérature grise (non publiée) a été identifiée par l'intermédiaire de recherches menées dans les sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et auprès de sociétés de spécialité médicale nationales et internationales. Valeurs : La qualité des résultats est évaluée au moyen des critères décrits dans le rapport du Groupe d'étude canadien sur les soins de santé préventifs (Tableau). Recommandations 1. Les femmes qui sont enceintes ou qui planifient connaître une grossesse devraient faire l'objet d'une évaluation visant les facteurs de risque de l'insuffisance cervicale. L'exécution d'une anamnèse exhaustive au moment de l'évaluation initiale pourrait attirer l'attention des cliniciens sur des facteurs de risque s'étant manifestés au cours d'une première grossesse (ou grossesse probante). (III-B) 2. Les femmes qui connaissent une fausse couche au deuxième trimestre ou un accouchement prématuré précoce devraient par la suite faire l'objet d'une évaluation détaillée des facteurs de risque; une telle évaluation devrait également être menée chez les femmes qui ont connu ces complications dans le cadre d'une grossesse précédente. (III-B) 3. Chez les femmes qui présentent des antécédents d'insuffisance cervicale, une analyse d'urine (à des fins de mise en culture et pour la tenue d'une épreuve de sensibilité) et des mises en culture vaginales visant la vaginose bactérienne devraient être effectuées dans le cadre de la première consultation obstétricale, et toute infection ainsi mise au jour devrait être traitée. (I-A) 4. Les femmes qui ont déjà connu au moins trois fausses couches au deuxième trimestre ou accouchements extrêmement prématurés et chez qui aucune cause particulière autre qu'une insuffisance cervicale potentielle n'a été identifiée devraient se voir offrir un cerclage planifié (à 12 - 14 semaines de gestation). (I-A) 5. Dans le cas des femmes présentant des antécédents classiques d'insuffisance cervicale chez qui la mise en place précédente d'un cerclage vaginal a échoué, la mise en place d'un cerclage abdominal peut être envisagée en l'absence de facteurs atténuants additionnels. (II-3C) 6. Les femmes qui ont subi une trachélectomie devraient faire l'objet d'un cerclage abdominal. (II-3C) 7. La mise en place d'un cerclage d'urgence pourrait être envisagée chez les femmes dont le col présente une dilatation < 4 cm, sans contractions, à moins de 24 semaines de gestation. (II-3C) 8. Les femmes pour lesquelles la mise en place d'un cerclage n'est pas envisagée ou justifiée, mais dont les antécédents semblent indiquer un risque d'insuffisance cervicale (1 ou 2 fausses couches au deuxième trimestre ou accouchements extrêmement prématurés), devraient se voir offrir des évaluations échographiques en série de la longueur cervicale. (II-2B) 9. La mise en place d'un cerclage devrait être envisagée, en présence d'une longueur cervicale ≤ 25 mm avant 24 semaines de gestation, chez les femmes connaissant une grossesse monofœtale qui présentent une possible insuffisance cervicale ou des antécédents d'accouchement préterme spontané. (I-A) 10. Le cerclage ne s'avère d'aucune utilité dans le cas des femmes qui ont fait l'objet d'un examen échographique ayant révélé, de façon fortuite, la présence d'un col court et qui n'ont pas déjà présenté des facteurs de risque en ce qui concerne l'accouchement préterme ou l'insuffisance cervicale. (II-1D) 11. Les données actuelles ne soutiennent pas la mise en place planifiée d'un cerclage dans le cadre d'une grossesse multiple, même en présence d'antécédents d'accouchement préterme; ainsi, cette pratique devrait être évitée. (I-D) 12. Dans le cadre d'une grossesse multiple, la mise en place d'un cerclage en fonction de la longueur cervicale n'est pas soutenue par la littérature. (II-1D).

Prediction of pediatric outcome after prenatal diagnosis and expectant antenatal management of congenital cystic adenomatoid malformation.

OBJECTIVE: To determine whether the congenital cystic adenomatoid malformation (CCAM) volume ratio (CVR) is associated with fetal and postnatal outcome after prenatal diagnosis and antenatal expectant management in a provincial tertiary referral center that does not offer fetal surgery. METHODS: Retrospective cohort of 71 consecutive cases of prenatally diagnosed CCAM meeting study criteria (1996-2004). CVR was calculated on the initial ultrasound at the referral center, and associated with hydrops (Fisher's exact test) and a composite adverse postnatal outcome consisting of death, intubation for respiratory distress, extracorporeal membrane oxygenation, non-elective surgery for symptomatology, or respiratory infection requiring hospital admission (Mann-Whitney test). RESULTS: A CVR > 1.6 was significantly associated with hydrops (p = 0.003). In addition, the CVR was significantly associated with the composite adverse postnatal outcome (p = 0.004) at a mean age of follow-up of 41 months (range < 1-117 months). For CVR and postnatal outcome, the area-under-the-curve receiver operating characteristic was 0.81 (95% CI 0.69-0.93, p = 0.006), and choosing a CVR cut-off of < 0.56, the negative predictive value was 100% (95% CI 0.85-1.00). CONCLUSION: In a provincial referral center with antenatal expectant management of CCAM, the CVR was associated with hydrops and postnatal outcome, with a CVR < 0.56 predictive of good prognosis after birth.

In Utero diagnosis and management of a fetus with homozygous α-Thalassemia in the second trimester: a case report and literature review.

Alpha thalassemia with the absence of 4 α-globin genes leads to fetal hydrops and fetal death from anemia. Historically considered a lethal condition, optimal in utero management of homozygous α-thalassemia is unclear. A fetus of Filipino descent at 26 weeks gestation presented with ultrasound evidence of anemia. Cordocentesis confirmed anemia and homozygous α-thalassemia (--/--). Intrauterine transfusion corrected anemia but fetal growth restriction and oligohydramnios persisted. Intrauterine exchange transfusion improved hemoglobin parameters, fetal growth, and oligohydramnios. The late preterm infant was delivered with classic limb reduction defects. Hemoglobin Bart's is nonfunctional for oxygen transport, and intrauterine exchange transfusion may be effective first-line therapy and further investigation is warranted.

Maternal side-effects after multiple courses of antenatal corticosteroids (MACS): the three-month follow-up of women in the randomized controlled trial of MACS for preterm birth study.

OBJECTIVE: A single course of antenatal corticosteroids (ACS) is associated with a reduction in respiratory distress syndrome and neonatal death. Multiple Courses of Antenatal Corticosteroids Study (MACS), a study involving 1858 women, was a multicentre randomized placebo-controlled trial of multiple courses of ACS, given every 14 days until 33+6 weeks or birth, whichever came first. The primary outcome of the study, a composite of neonatal mortality and morbidity, was similar for the multiple ACS and placebo groups (12.9% vs. 12.5%), but infants exposed to multiple courses of ACS weighed less, were shorter, and had smaller head circumferences. Thus for women who remain at increased risk of preterm birth, multiple courses of ACS (every 14 days) are not recommended. Chronic use of corticosteroids is associated with numerous side effects including weight gain and depression. The aim of this postpartum assessment was to ascertain if multiple courses of ACS were associated with maternal side effects. METHODS: Three months postpartum, women who participated in MACS were asked to complete a structured questionnaire that asked about maternal side effects of corticosteroid use during MACS and included the Edinburgh Postnatal Depression Scale. Women were also asked to evaluate their study participation. RESULTS: Of the 1858 women randomized, 1712 (92.1%) completed the postpartum questionnaire. There were no significant differences in the risk of maternal side effects between the two groups. Large numbers of women met the criteria for postpartum depression (14.1% in the ACS vs. 16.0% in the placebo group). Most women (94.1%) responded that they would participate in the trial again. CONCLUSION: In pregnancy, corticosteroids are given to women for fetal lung maturation and for the treatment of various maternal diseases. In this international multicentre randomized controlled trial, multiple courses of ACS (every 14 days) were not associated with maternal side effects, and the majority of women responded that they would participate in such a study again.

Multiple courses of antenatal corticosteroids for preterm birth (MACS): a randomised controlled trial.

BACKGROUND: One course of antenatal corticosteroids reduces the risk of respiratory distress syndrome and neonatal death. Weekly doses given to women who remain undelivered after a single course may have benefits (less respiratory morbidity) or cause harm (reduced growth in utero). We aimed to find out whether multiple courses of antenatal corticosteroids would reduce neonatal morbidity and mortality without adversely affecting fetal growth. METHODS: 1858 women at 25-32 weeks' gestation who remained undelivered 14-21 days after an initial course of antenatal corticosteroids and continued to be at high risk of preterm birth were randomly assigned to multiple courses of antenatal corticosteroids (n=937) or placebo (n=921), every 14 days until week 33 or delivery, whichever came first. The primary outcome was a composite of perinatal or neonatal mortality, severe respiratory distress syndrome, intraventricular haemorrhage (grade III or IV), periventricular leucomalacia, bronchopulmonary dysplasia, or necrotising enterocolitis. Analysis was by intention to treat. All patients and caregivers were unaware of the treatment given. This trial is registered as number ISRCTN2654148. FINDINGS: Infants exposed to multiple courses of antenatal corticosteroids had similar morbidity and mortality to those exposed to placebo (150 [12.9%] vs 143 [12.5%]). Those receiving multiple doses of corticosteroids also weighed less at birth than those exposed to placebo (2216 g vs 2330 g, p=0.0026), were shorter (44.5 cm vs 45.4 cm, p<0.001), and had a smaller head circumference (31.1 cm vs 31.7 cm, p<0.001). INTERPRETATION: Multiple courses of antenatal corticosteroids, every 14 days, do not improve preterm-birth outcomes, and are associated with a decreased weight, length, and head circumference at birth. Therefore, this treatment schedule is not recommended. FUNDING: Canadian Institutes of Health Research.

The impact of prenatal diagnosis on neural tube defect (NTD) pregnancy versus birth incidence in British Columbia.

The birth incidence of neural tube defect (NTD) cases in British Columbia (B.C.), and elsewhere in North America, is reported to be declining. This decline is being attributed to folic acid (FA) supplementation and food fortification, but 2nd trimester prenatal screening of pregnancies for NTDs and other congenital anomalies has increased during this timeframe, as well. This descriptive, population-based study evaluates the impact of prenatal screening of NTD-affected pregnancies on (1) pregnancy outcome and (2) reporting of NTD births to the provincial Health Status Registry (B.C.H.S.R.); and it assesses (3) the use of periconceptional FA supplementation. NTD cases were ascertained from medical records of health centres providing care to families with NTD-affected pregnancies and newborns; and from NTD cases reported to the B.C.H.S.R. In 1997-1999, the B.C.H.S.R. published a NTD incidence of 0.77/1000. In this study, 151 NTD-affected pregnancies were identified, with an incidence of 1.16/1000. Partial Reporting of induced abortions in a NTD incidence 45.5% low than the actual incidence. Medical records were available for review on 144/151 pregnancies. Prenatal screening identified 86.1% (124/144) of NTD-affected pregnancies, with 72.6% (90/124) resulting in pregnancy termination, and 27.4% (34/124) continuing to term. Use of FA supplementation in the periconceptional period was recorded in 36.4% of pregnancies (39/107). Thus in B.C. the decline in the NTD incidence is due predominantly to pregnancy terminations following prenatal diagnosis, which reduces the NTD incidence by 60%, from 1.16/1000 to 0.47/1000. Continued efforts for primary and the option of secondary prevention of NTDs are recommended in order to improve newborn health in B.C. and elsewhere. These interventions need to be monitored, however, for optimal health care planning.

The evaluation of the fetal fibronectin test for prediction of preterm delivery in symptomatic patients.

OBJECTIVE: This study was conducted to evaluate the usefulness of testing for fetal fibronectin (fFN) to rule out the diagnosis of preterm labour in symptomatic patients in a Canadian setting. METHODS: This was a prospective, blinded clinical evaluation of fFN testing in women presenting with threatened preterm labour at between 24 and 34 weeks' gestation at two Canadian tertiary care centres. RESULTS: Of the 149 women tested, 32 had a positive fFN test. In the total patient population, 10.1% delivered within seven days of testing, and 18.2% delivered prior to 34 weeks. A negative fFN result was associated with a 97.4% likelihood of delivering more than seven days after testing and with a 91.4% chance of delivering after 34 weeks. CONCLUSION: The fFN test appears to provide useful information in the risk assessment of Canadian women presenting with symptoms compatible with preterm labour. A negative test has a high predictive value for delivering more than seven days after presentation.

Failure of methotrexate and internal iliac balloon catheterization to manage placenta percreta.

BACKGROUND: Placenta percreta is a rare but potentially lethal condition. Previously described conservative measures to avoid life-threatening hemorrhage and preserve fertility include use of methotrexate and uterine artery embolization. CASE: A woman with suspected placenta percreta diagnosed on ultrasound in the second trimester was delivered by classic, fundal cesarean at 30 weeks' gestation for bleeding and premature rupture of membranes. The placenta was left in situ, and she was treated with methotrexate. Postpartum bleeding 1 week later was managed by internal iliac balloon catheterization and manual transcervical removal of the placenta, which resulted in hysterectomy and required massive blood transfusion. CONCLUSION: Placenta percreta managed conservatively with methotrexate and internal iliac balloon catheterization resulted in serious morbidity.

Vesicouterine fistula in pregnancy: a case report.

BACKGROUND: Vesicouterine fistula is a rare complication of Caesarean delivery. This is the third known report of vesicouterine fistula diagnosed during pregnancy. CASE: Linda (pseudonym), a 28-year-old woman in her second pregnancy, having had a Caesarean delivery in her first pregnancy, was admitted to the delivery unit with possible preterm ruptured membranes at 23 weeks' gestation. She also complained of a fluid-filled sac bulging from her introitus during her admission assessment. Diagnosis of premature rupture of membranes was confirmed by a positive nitrazine paper test and appearance of ferning during microscopic evaluation of vaginal fluid. Cystoscopy, performed 3 days after admission, demonstrated ballooning of amnion into the bladder. At 24 weeks' gestation, the woman had a precipitous vaginal breech delivery. Two months later, the fistula was successfully repaired through a transabdominal route. CONCLUSION: Although uncommon in pregnancy, vesicouterine fistula should be considered in women who present with urinary incontinence or recurrent urinary tract infections after a lower transverse Caesarean section. Evaluation in pregnancy is usually limited to cystoscopy. Treatment is usually surgical and is often delayed until 2 to 3 months following delivery.

Multiple courses of antenatal corticosteroids for preterm birth study: outcomes in children at 5 years of age (MACS-5).

IMPORTANCE: A single course of antenatal corticosteroid therapy is recommended for pregnant women at risk of preterm birth between 24 and 33 weeks' gestational age. However, 50% of women remain pregnant 7 to 14 days later, leading to the question of whether additional courses should be given to women remaining at risk for preterm birth. The Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study (MACS) was an international randomized clinical trial that compared multiple courses of antenatal corticosteroids with a single course in women at risk of preterm birth. OBJECTIVE: To determine the effects of single vs multiple courses of antenatal corticosteroid therapy on death or neurodevelopmental disability (neuromotor, neurosensory, or neurocognitive/neurobehavioral function) at 5 years of age in children whose mothers participated in MACS. Our secondary aims were to determine the effect on height, weight, head circumference, blood pressure, intelligence, and specific cognitive (visual, spatial, and language) skills. DESIGN, SETTING, AND PARTICIPANTS: Cohort follow-up study of children seen between June 2006 and May 2012 at 55 centers. In total, 1724 women (2141 children) were eligible for the study, of whom 1728 children (80.7% of the 2141 eligible children) participated and 1719 children contributed to the primary outcome. INTERVENTION: Single and multiple courses of antenatal corticosteroid therapy. MAIN OUTCOMES AND MEASURES: The primary outcome was death or survival with a neurodevelopmental disability in 1 of the following domains: neuromotor (nonambulatory cerebral palsy), neurosensory (blindness, deafness, or need for visual/hearing aids), or neurocognitive/neurobehavioral function (abnormal attention, memory, or behavior). RESULTS: There was no significant difference between the groups in the risk of death or neurodevelopmental disability: 217 of 871 children (24.9%) in the multiple-courses group vs 210 of 848 children (24.8%) in the single-course group (odds ratio, 1.02 [95% CI, 0.81 to 1.29]; P = .84). CONCLUSIONS AND RELEVANCE: Multiple courses, compared with a single course, of antenatal corticosteroid therapy did not increase or decrease the risk of death or disability at 5 years of age. Because of a lack of strong conclusive evidence of short-term or long-term benefits, it remains our opinion that multiple courses not be recommended in women with ongoing risk of preterm birth. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00187382.

Effect of antenatal corticosteroids on fetal growth and gestational age at birth.

OBJECTIVE: To estimate the effect of multiple courses of antenatal corticosteroids on neonatal size, controlling for gestational age at birth and other confounders, and to determine whether there was a dose-response relationship between number of courses of antenatal corticosteroids and neonatal size. METHODS: This is a secondary analysis of the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study, a double-blind randomized controlled trial of single compared with multiple courses of antenatal corticosteroids in women at risk for preterm birth and in which fetuses administered multiple courses of antenatal corticosteroids weighed less, were shorter, and had smaller head circumferences at birth. All women (n=1,858) and children (n=2,304) enrolled in the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study were included in the current analysis. Multiple linear regression analyses were undertaken. RESULTS: Compared with placebo, neonates in the antenatal corticosteroids group were born earlier (estimated difference and confidence interval [CI]: -0.428 weeks, CI -0.10264 to -0.75336; P=.01). Controlling for gestational age at birth and confounding factors, multiple courses of antenatal corticosteroids were associated with a decrease in birth weight (-33.50 g, CI -66.27120 to -0.72880; P=.045), length (-0.339 cm, CI -0.6212 to -0.05676]; P=.019), and head circumference (-0.296 cm, -0.45672 to -0.13528; P<.001). For each additional course of antenatal corticosteroids, there was a trend toward an incremental decrease in birth weight, length, and head circumference. CONCLUSION: Fetuses exposed to multiple courses of antenatal corticosteroids were smaller at birth. The reduction in size was partially attributed to being born at an earlier gestational age but also was attributed to decreased fetal growth. Finally, a dose-response relationship exists between the number of corticosteroid courses and a decrease in fetal growth. The long-term effect of these findings is unknown. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00187382. LEVEL OF EVIDENCE: II.

Multiple courses of antenatal corticosteroids for preterm birth study: 2-year outcomes.

OBJECTIVE: The aim of this study was to determine the effects of repeated courses of prenatal corticosteroid therapy versus placebo on death or neurologic impairment among the children enrolled in the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study, at 18 to 24 months of age. METHODS: A total of 2305 infants were eligible for follow-up evaluation; 2104 infants (1069 in the prenatal corticosteroid therapy group and 1035 in the placebo group) were monitored. The primary outcome was death or neurologic impairment, defined as either cerebral palsy or cognitive delay, at 18 to 24 months of age. The secondary outcomes were measurements of growth (height, weight, and head circumference). RESULTS: Children exposed to multiple courses of prenatal corticosteroid therapy had similar rates of death or neurologic impairment, compared with children exposed to placebo (148 children [13.8%] vs 142 children [13.7%]; odds ratio: 1.001[95% confidence interval: 0.75-1.30]; P = .95). They had a mean weight of 11.94 kg, compared with 12.14 kg in the placebo group (P = .04), a mean height of 85.51 cm, compared with 85.46 cm (P = .87), and a mean head circumference of 48.18 cm, compared with 48.25 cm (P = .45). CONCLUSIONS: Multiple courses of prenatal corticosteroid therapy, given every 14 days, did not increase or decrease the risk of death or neurologic impairment at 18 to 24 months of age, compared with a single course of prenatal corticosteroid therapy. Continued follow-up monitoring of these children is necessary to assess neurobehavioral function, school performance, and possible susceptibility to disease.