Intravenous immunoglobulin in the management of severe early onset red blood cell alloimmunisation.

Our objective was to assess the effect of maternal intravenous immunoglobulin (IVIG) administration for severe red blood cell (RBC) alloimmunisation on fetal outcomes. This is a case-control study. Women with a history of severe early onset alloimmunisation resulting in fetal loss in a previous pregnancy and high anti-D or anti-K antibody titres received IVIG in a subsequent pregnancy. We assessed gestational age at first transfusion and fetal outcomes in the subsequent pregnancy and compared these with the outcomes in the previous pregnancy. The most responsible antibody was anti-D in 17 women and anti-K in two others, whilst seven had more than one antibody. In all, 19 women received IVIG in 22 pregnancies, two of which did not even need an intrauterine transfusion (IUT). For previous early losses despite transfusion, IVIG was associated with a relative increase in fetal haemoglobin between treated and untreated pregnancies of 36.5 g/L (95% confidence interval 19.8-53.2, p = 0.0013) and improved perinatal survival (eight of eight vs. none of six, p = 0.001). For previous losses at <20 weeks, it enabled first transfusion deferral in subsequent pregnancies to at least 19.9 weeks (mean 23.2 weeks). Overall, IVIG decreases the severity of haemolytic disease of the fetus and newborn and allows deferral of the first IUT to a safer gestation in severe early-onset RBC alloimmunisation and rarely may even avoid the need for IUT entirely.

Beckwith-Wiedemann syndrome in sibs discordant for IC2 methylation.

Genetically heterogeneous imprinting disorders include Beckwith-Wiedemann syndrome (BWS) and multiple maternal hypomethylation syndrome (MMHS). Using DNA sequencing, quantitative PCR, SNuPE, pyrosequencing, and hybridization to the Illumina GoldenGate Methylation Cancer Panel 1 array, we characterized the genomic DNA of two brothers with BWS who were discordant for loss of methylation at several differentially methylated regions (DMR), including imprinting center 2 (IC2) on chromosome band 11p15.5, which is often hypomethylated in BWS. In keeping with MMHS, the elder child had hypomethylation of SGCE and PLAGL1 as well as of IC2, whereas the younger brother demonstrated no loss of methylation at these DMRs. Although this discordance is consistent with the observation that 15-20% of individuals with BWS do not have detectable genetic or epigenetic alterations of 11p15.5, this is the first report of familial recurrence of BWS with discordance for chromosomal 11p15.5 alterations. We hypothesize that this apparent discordance arises either from mosaicism precluding identification of IC2 hypomethylation in blood or buccal mucosa DNA of the younger child, or from hypomethylation at a site not interrogated by our molecular studies.

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.

NAFTNet retrospective report on the treatment of anti-Ro/SSA mediated fetal heart block with dexamethasone.

BACKGROUND: Complete atrioventricular block (CAVB) is a complication of maternal antibody positivity and treatment of fetal disease is controversial in terms of efficacy and safety. We hypothesized that dexamethasone treatment for fetal anti-Ro/SSA antibody-mediated cardiac disease leads to better pregnancy outcomes than expectant management. METHODS: A retrospective multi-center cohort study of anti-Ro/SSA antibody positive pregnancies with fetal conduction disease reported by participating North American Fetal Therapy Network (NAFTNet) centers between January 2010 and December 2018. The primary outcomes included: fetal death, oligohydramnios, growth restriction, preterm delivery, and new maternal comorbidities. Secondary outcomes included: pacemaker prior to 28 days, transplantation, and neonatal death in maternal/fetal dyads treated with dexamethasone versus not. RESULTS: In 127 anti-Ro/SSA positive pregnancies, 98 were treated with dexamethasone and 29 were not. Of those treated, 61/96 (63.5%) met the primary outcome including 45/91 (49.4%) premature deliveries; 20 mothers developed comorbidities during treatment (fetal death 5, 10 growth restriction, 14 oligohydramnios, two new/worsening gestational diabetes). In the untreated group, 15/25 (60%) met the primary outcome including 11/22 (50%) premature deliveries and four mothers developing comorbidities during their pregnancy (fetal death 3, one growth restriction, one new onset maternal hypertension). Regarding secondary outcomes, 37/96 (43%) treated fetuses required a pacemaker or died by 28 days, while untreated 13/25 (52%) required pacemaker placement, died prior to 28 days or required listing for transplantation. Excluding terminations, survival without transplant was 17 (68%) in untreated and 85 (89%) in treated patients (p<.01). CONCLUSIONS: While the use of dexamethasone in anti-Ro/SSA positive pregnancies is associated with a high rate of poor pregnancy outcomes, there was an unexpected similarly high rate in untreated positive pregnancies. This suggests that the maternal disease itself is influencing pregnancy complications independent of dexamethasone. Our data, which show that treatment decreases neonatal morbidity and overall mortality without increasing overall pregnancy complications, warrant further study.

A quality improvement and educational initiative to reduce morbidity associated with massive postpartum hemorrhage.

OBJECTIVE: To determine the effect of a quality improvement and educational initiative on blood transfusion rates and patient morbidity from massive postpartum hemorrhage. METHODS: A retrospective chart review was performed of massive postpartum hemorrhage (mPPH) at an urban tertiary care center. Inclusion criteria are women with mPPH over 20 weeks gestational age. The primary outcome was the number of packed red blood cell (pRBC) transfusions required. Two time periods were compared-the control period (January 2006-December 2011), and the educational period (January 2012-December 2015) by calculating an incidence rate ratio using Poisson regression. RESULTS: Among 189 women with mPPH, 107 cases occurred during the control period and 82 during the educational period. In the educational period, there were 13% (95% confidence interval [CI] 2%-23%) fewer pRBC and 16% (95% CI 1%-29%) fewer fresh frozen plasma (FFP) units transfused compared with the control period. There was a decrease of 58 minutes (95% CI -106 to -9.52) of the median time from diagnosis of mPPH to transfusion of FFP. CONCLUSION: The quality improvement educational initiative decreased the number of pRBC and FFP transfusions required, and shortened the latency interval to transfusion of FFP.

Diagnosis and outcome of dextrocardia diagnosed in the fetus.

A retrospective review of 5,539 fetal echocardiograms over a 22-year period revealed 85 cases of dextrocardia. In primary dextrocardia (46 cases), the incidence of situs solitus, inversus, and ambiguous, was similar and associated with a high incidence of complex cardiac malformations in situs solitus and situs ambiguous. Secondary dextrocardia (39 cases) was due to intrathoracic displacement and, when caused by diaphragmatic hernia, was associated with cardiac malformations in 31% of cases. Even in complex cases, fetal echocardiography was highly accurate; therefore, specific counseling can be given to parents.

Is the nuchal index increased in fetuses with congenital structural heart defects?

OBJECTIVES: To determine if the Nuchal index (NIx) is increased in euploid fetuses with structural congenital heart defects (CHD). METHODS: Euploid fetuses with CHD between 18 and 24 weeks gestation were identified. The next fetus meeting the same criteria with a normal fetal echocardiogram were selected as a control. The NIx [(mean nuchal thickness /mean biparietal diameter) x 100] and cardiac axis (CA; degrees) were calculated for each fetus. Standard descriptive tests and two-tailed t test were used. RESULTS: The NIx in the abnormal (n = 20) and control (n = 20) groups were 9.10 (2.35) and 7.54 (p = 0.04) and CA was 55.8 degrees and 48.6 degrees (p = 0.02), respectively. CONCLUSIONS: The NIx and CA were significantly different in fetuses with CHD. A prospective study to confirm these findings and determine clinical utility is warranted.

Obstetric implications of the factor V leiden mutation: a review.

Factor V Leiden (FVL) is a newly discovered genetic mutation that impairs one of the body's naturally occurring anticoagulation systems. The result is resistance to activated protein C and a predisposition to thrombosis. FVL is the most common cause of primary and recurrent venous thromboembolism in the pregnant and nonpregnant state. The FVL gene is common in the general population and transmitted in an autosomal dominant fashion. When FVL is combined with the prothrombotic state of pregnancy, the result is an increased propensity to manifest a number of pregnancy complications. These include recurrent pregnancy loss and stillbirth, severe and early-onset preeclampsia, placental abruption and possibly, intrauterine growth restriction. It remains unknown whether thromboprophylaxis is effective in ameliorating these pregnancy complications. The current literature and management recommendations are highlighted in this article.

A randomized controlled trial comparing two protocols for the use of misoprostol in midtrimester pregnancy termination.

OBJECTIVE: Our purpose was to compare the efficacy of oral misoprostol with that of vaginal misoprostol for midtrimester termination of pregnancy. STUDY DESIGN: Women seen for midtrimester pregnancy termination were randomly assigned to receive either misoprostol orally in a dose of 200 microg every hour for 3 hours followed by 400 microg every 4 hours or vaginally in a dose of 400 microg every 4 hours. The protocol was followed for 24 hours, after which time further management was at the discretion of the attending physician. The primary outcome measure was the induction-to-delivery interval. Sample size was calculated a priori. Statistical analysis was performed with the t test for continuous variables and the chi(2) test for categorical variables. P <.05 was considered significant. RESULTS: One hundred fourteen women were randomized, with 49 receiving vaginal misoprostol and 65 receiving oral misoprostol. The two groups were comparable with respect to maternal age, parity, indication for pregnancy termination, gestational age, and maternal weight. The mean induction-to-delivery interval was significantly shorter for the vaginal group (19.6 +/- 17.5 hours vs 34.5 +/- 28.2 hours, P <.01). Length of stay was also shorter in the vaginal group (32.3 +/- 17.3 hours vs 50.9 +/- 27.9 hours, P <.01). Significantly more patients in the vaginal group were delivered within 24 hours (85.1% vs 39.5%, P <.01), and more patients in the oral group required changes in the method of induction when they were undelivered after 24 hours (38.2% vs 7%, P <.01). The only complication was an increase in febrile morbidity in the vaginal group (25% vs 6.7%, P =.046). This did not result in an increased use of antibiotics, and all the fevers resolved post partum without further complications. CONCLUSIONS: Vaginal administration of misoprostol resulted in a shorter induction-to-delivery interval. The shorter length of stay should result in improved patient care.