Postnatal Prophylaxis Research Articles

Targeted antenatal anti-D prophylaxis program for RhD-negative pregnant women - outcome of the first two years of a national program in Finland.

The aim of this study was to assess the accuracy of the non-invasive fetal RHD test at 24-26 weeks of gestation as part of the national antenatal screening program to target routine antenatal anti-D prophylaxis (RAADP) at 28-30 weeks at women carrying an RhD-positive fetus. A prospective cohort study involving all maternity care centers and delivery hospitals in Finland between February 2014 and January 2016. Fetal RHD genotyping using cell-free fetal DNA in maternal plasma was performed with real-time polymerase chain reaction in a centralized setting. The results were systematically compared with the serological newborn RhD typing. The main outcome measure was the accuracy of the fetal RHD assay; the secondary variable was compliance with the newly introduced RAADP program. Fetal RHD was screened from 10 814 women. For the detection of fetal RHD, sensitivity was 99.99% [95% confidence interval (CI) 99.92-99.99] and specificity 99.81% (95% CI 99.60-99.92). One false-negative and seven false-positive results were reported by the delivery hospitals in two years. The negative predictive value of the test was 99.97% (95% CI 99.81-99.99). At the end of the study period, over 98% of the RhD-negative women participated in the new screening program. The targeted RAAPD program was implemented effectively in the national maternity care program in Finland. An accurate fetal RHD screening test allows discontinuation of newborn testing without risking the postnatal prophylaxis program. In the future, the main area to investigate will be the clinical effect of RAADP on subsequent pregnancies.

Late vitamin K deficiency bleeding despite intramuscular prophylaxis at birth - is there a need for additional supplementation?

Introduction/Objective. Vitamin K deficiency is common in newborn infants and without prophylaxis there is a risk of vitamin K deficiency bleeding (VKDB). The most frequent prophylactic approach is an intramuscular (IM) injection of vitamin K1 immediately after birth. Its efficiency to prevent late VKDB has been recently questioned by several reports. Based on our experience, we discuss the need for additional vitamin K1 supplementation after its IM administration at birth. Methods. We present a retrospective review of 12 infants, 11 with confirmed and one with probable late VKDB despite IM prophylaxis at birth, who were treated in the two largest tertiary care pediatric hospitals in Serbia during the last 15 years. Results. All the patients were exclusively breastfed. In 11 patients, daily weight gain was normal or increased, and one patient had failure to gain weight. Six infants were previously healthy, three infants received antibiotics prior to bleeding, and in two diarrhea and cholestasis, respectively, existed previously. An intracranial bleeding was documented in nine infants, four of whom died. Conclusion. Low content of phytomenadione in human milk could occasionally be attributed to late VKDB despite postnatal IM injection of vitamin K1 in otherwise healthy, exclusively breastfed infants. This might be aggravated by transient disturbance of vitamin K turnover due to antibiotic use, acute diarrhea, or transient cholestasis. We suggest that an additional vitamin K1 supplementation after postnatal IM prophylaxis could be justified in exclusively breastfed infants.

Is antenatal RhIg completely safe?

The administration of antenatal and postnatal Rh immunoglobulin prophylaxis significantly prevents Rh D alloimmunization during pregnancy. A dose of 20 g anti-D IgG protects against 1 mL of D-positive red blood cells or 2 mL of whole blood. Rh D-negative women if unsensitized receive antenatal anti-D prophylaxis of 300 g at 28 weeks of pregnancy and postnatal prophylaxis if the baby is Rh D positive. Initial trials concluded that postpartum immunoprophylaxis decreased the incidence of Rh D immunization from 12–13% to 1–2% which was further shown to be reduced to 0.1% thanks to antenatal prophylaxis.1 Rh immunoglobulin (RhIg) administration is quite safe during pregnancy although RhIg can cross the placenta and cause hemolysis of the red cells of D-positive fetuses. Unfortunately data is sparse on this serious adverse event. Herein we present an unusual case of hemolytic disease of newborn (HDN) with positive Direct Coombs’ Test (DCT) due to antenatal RhIg prophylaxis in an Rh-negative mother.

Diagnóstico precoz de la infección por el virus de la inmunodeficiencia humana-1 en niños: programa de prevención de la transmisión maternoinfantil en Guinea Ecuatorial

BackgroundGreat efforts have been made in the last few years in order to implement the prevention of mother-to-child transmission (PMTCT) program in Equatorial Guinea (GQ). The aim of this study was to evaluate the rates of mother-to-child HIV transmission based on an HIV early infant diagnosis (EID) program. MethodsA prospective observational study was performed in the Regional Hospital of Bata and Primary Health Care Centre Maria Rafols, Bata, GQ. Epidemiological, clinical, and microbiological characteristics of HIV-1-infected mothers and their exposed infants were recorded. Dried blood spots (DBS) for HIV-1 EID were collected from November 2012 to December 2013. HIV-1 genome was detected using Siemens VERSANT HIV-1 RNA 1.0 kPCR assay. ResultsSixty nine pairs of women and infants were included. Sixty women (88.2%) had WHO clinical stage 1. Forty seven women (69.2%) were on antiretroviral treatment during pregnancy. Forty five infants (66.1%) received postnatal antiretroviral prophylaxis. Age at first DBS analysis was 2.4 months (IQR 1.2-4.9). One infant died before a HIV-1 diagnosis could be ruled out. Two infants were HIV-1 infected and started HAART before any symptoms were observed. The rate of HIV-1 transmission observed was 2.9% (95%CI 0.2-10.5). ConclusionsThe PMTCT rate was evaluated for the first time in GQ based on EID. EID is the key for early initiation of antiretroviral therapy and to reduce the mortality associated with HIV infection.

Prevalence of Rhesus D-negative blood type and the challenges of Rhesus D immunoprophylaxis among obstetric population in Ogbomoso, Southwestern Nigeria

Background: Rhesus incompatibility could pose a major problem in pregnancy, and it could be the cause of obstetric failure in a handful of women. Implementation of programs for antenatal and postnatal (Rhesus D) RhD immune globulin prophylaxis has led to a significant reduction in the frequency of maternal RhD alloimmunization and associated fetal and neonatal complications. Aims: To determine the prevalence of RhD negative among the pregnant population attending the antenatal clinic of a young tertiary health institution in Ogbomoso, a semi-urban town in southwestern Nigeria, and also the challenges faced by this sub-population of pregnant women. Materials and Methods: A retrospective review of the antenatal and labour records of obstetric patient attending Ladoke Akintola University of Technology Teaching Hospital (LTH), Ogbomoso, Nigeria. Variables were expressed as percentages. Result: Of the 596 booked patient who had their blood group systems determined, 563 women (94.5%) were RhD-positive, and 33(5.5%) women were RhD-negative. Almost 50% of the Rh-negative pregnant women were primipara. Twenty-three (69.7%) of the study population had a previous delivery or abortion, but only 9 (39.1%) of these had the Rhesus anti-D immunoglobulin following the delivery or the abortion. One of the RhD-negative women had been sensitized to the RhD positive antigen from the previous delivery at the time of booking the index pregnancy. Of the study population that delivered in our facility, only 11 (33.3%) received the anti-D immunoglobulin after the delivery, and financial inability to purchase the anti-D immunoglobulin was a major reason for refusing the immunoprophylaxis. Conclusion: Although the prevalence of RhD negative still remains low, and the rate of Rh-immunoprophylaxis remains quite low in our obstetric population, the risk of haemolytic disease of the newborn with its attendant perinatal morbidity and mortality is real in our community. The anti-D immunoglobulin should be made available and affordable.

Prevalence and Specificity of Red Blood Cell Alloantibodies in Patients from China During 1994-2013.

To analyze the data about red blood cell alloantibodies in patients from mainland China and to provide evidence for formulating a management guideline. The Chinese and English literatures about Chinese patients in mainland China published in periodicals were retrieved by CHKD, CNKI, CMJD and PubMed using the key words as unexpected antibody, irregular antibody, blood group antibody, hemolytic transfusion reaction (HTR), hemolytic disease of the newborn (HDN), hemolytic disease of the fetus and newborn (HDFN). A total of 5582 red blood cell alloantibodies were retrieved from 4800 patients. The average prevalence of alloantibody in 89 retrospective analysis reports was 0.34 %. Among all study patients, the 10 most common antibodies were anti-E (33.9%), anti-D (18.3%), anti-c (10.9%), anti-M (9.9%), anti-C (8.1%), anti-e (4.8%), anti-Le(a) (3.4%), anti-P1 (2.0%), anti-Mur (1.6%), and anti-Jk(a) (1.2%). Out of all 136 patients with HTR, the most frequentl alloantibodies were Rhesus antibodies (71.7%), and other antibodies included anti-Jk(b) (5.9%), anti-Le(a) (5.1%), anti-Jk(a) (3.7%), anti-M (1.5%), and anti-Mur (1.5%). A total of 644 alloantibodies contributing to HDFN come primarily from the Rhesus (93.1%) and MNS (6.0%) blood group systems. The postnatal Rh prophylaxis should become a routine procedure in mainland China. The use of blood matched for C, E, c, e, Jk(a) and Jk(b) should be recommended for Chinese patients with a history of multiple transfusions. Patients with MNS alloantibodies should be given sufficient attention, and Mur+ red blood cells should be included in antibody screening panels.

Delayed HIV detection among infants exposed to postnatal antiretroviral prophylaxis during breastfeeding

The objective of this study is to determine whether detection of HIV infection was delayed in infants exposed to antiretroviral prophylaxis to prevent HIV transmission during breastfeeding. The Breastfeeding, Antiretrovirals and Nutrition (BAN) study was a randomized trial of 2369 mother-infant pairs conducted from 2004 to 2010. In addition to an intrapartum regimen, all mother-infant pairs were randomly assigned to three antiretroviral intervention arms during 28 weeks of breastfeeding: no further antiretroviral prophylaxis (control arm); infant-daily nevirapine (nevirapine arm); and maternal zidovudine, lamivudine and either nevirapine, nelfinavir or lopinavir-ritonavir (maternal arm). After breastfeeding cessation counselling and stopping the antiretroviral interventions by 28 weeks, 28 infant HIV infections occurred. To determine whether these infections occurred during the breastfeeding and antiretroviral intervention phase but had delayed detection on the antiretroviral arms, we performed ultrasensitive (droplet digital PCR) HIV testing on infants with stored peripheral blood mononuclear cell (PBMC) specimens at 24 weeks (n = 9). Of the nine infants, all three on the infant nevirapine arm had detectable HIV DNA at 24 weeks, compared with two of four on the maternal antiretroviral arm and one of two on the control arm. For infants with detectable HIV at 24 weeks, the median delay in detection between the ultrasensitive and standard assays was 18.3 weeks for the nevirapine arm, 15.4 weeks for the maternal arm and 9.4 weeks for the control arm. The prolonged inability to detect HIV with standard assays in the context of postnatal antiretroviral prophylaxis suggests that early antiretrovirals may restrict HIV replication sufficiently to lead to missed diagnosis among infected infants. Therefore, repeat virologic testing is warranted beyond the WHO-recommended point of testing at 6 weeks after breastfeeding cessation.

PTU-111 A review of chronic hepatitis b virus infection in children in ireland

Introduction Although the majority of children with hepatitis B virus (HBV) infection remain asymptomatic, serious complications such as cirrhosis and hepatocellular carcinoma can occur in later life. Longterm follow up is important to identify these complications early. In Ireland, pregnant women are screened antenatally for HBV. Children born to HBV infected mothers are referred to the Rainbow Clinic. Method Data on all children with chronic HBV infection, attending the Rainbow Clinic from 2002 to 2014, were retrospectively reviewed using a standard data collection sheet. Chronic HBV infection is defined as HBsAg-positivity for greater than 6 months. Children with only one clinic visit or with HIV co-infection were excluded. Results 63 children with chronic HBV infection attended the Rainbow clinic between 2002 and 2014 (age range, 6 months-17 years).6 children were excluded (4 single clinic attendance; 2 HIV co-infection). 34 children (60%) were male. 13 children (23%) with chronic HBV were born in Ireland. The majority (44, 77%) were children immigrating to Ireland from overseas: Africa, 16; Central Asia, 14; Eastern Europe, 7; Unknown, 7. HBV was acquired vertically in 35 (61%) children and horizontally in 2. Parental HBV status was unknown in 22 children (15 adoptees).19 children had siblings with chronic HBV infection. 9 of 13 (69%) children born in Ireland received recommended prophylactic IVIG and HBV vaccine at birth. 4 (31%) received no prophylaxis. Birth details from children born outside of Ireland show suboptimal post natal prophylaxis in all: 13 of 16 received no prophylaxis and 3 received HBV vaccine alone. All 57 children had biochemistry performed twice a year. Abdominal ultrasound scans (USS) were performed in 49 children (86%).5 had abnormal USS (coarse echogenicity, 3; splenomegaly, 2). Liver biopsy was performed in 4 children with elevated ALT and high HBV VL. Biopsies showed fibrosis (3) or minimal inflammation (1). USS was normal in 3 of the 4 cases with abnormal biopsy. 3 children received antivirals (3TC) for fibrosis (2) and to reduce risk of transmission (1). Conclusion Immigration to Ireland accounts for the majority of paediatric HBV infection in this country. The majority of chronic HBV infection in children results from vertical transmission. Failure of postnatal prophylaxis remains a significant problem. Available evidence shows that 100% of foreign-born and 30% of Irish-born children with chronic HBV did not received recommended IVIG and vaccine prophylaxis. 4 children (7%) developed complications of chronic HBV. The need for improved diagnostic tools to identify children at risk of complicated HBV liver disease is again evidenced by failure of USS to identify those children with biopsy-proven abnormalities. Disclosure of interest None Declared.

Serious adverse events are uncommon with combination neonatal antiretroviral prophylaxis: a retrospective case review.

Six weeks of zidovudine (ZDV) is recommended for postnatal prophylaxis of HIV-exposed infants, but combination antiretrovirals are indicated if HIV transmission risk is increased. We investigated the frequency and severity of adverse events (AE) in infants receiving multiple drug prophylaxis compared to ZDV alone. In this retrospective review of 148 HIV-exposed uninfected infants born between 1997–2009, we determined clinical and laboratory AE that occurred between days of life 8–42. Thirty-six infants received combination prophylaxis; among those, a three-drug regimen containing ZDV, lamivudine, and nevirapine was most common (53%). Rates of laboratory AE grade ≥1 were as follows for the combination prophylaxis and ZDV alone groups, respectively: neutropenia 55% and 39%; anemia 50% and 39%; thrombocytopenia 0 and 3%; elevated aspartate aminotransferase 3% and 3%; elevated alanine aminotransferase 0 and 1%; hyperbilirubinemia 19% and 42%. Anemia occurred more frequently in infants who received three-drug prophylaxis compared to infants who received ZDV alone (63% vs. 39%, p = 0.04); all anemia AE were grade 1 or 2 in the three-drug prophylaxis group. Overall, 75% of infants on combination prophylaxis and 66% of infants on ZDV alone developed grade ≥1 AE (p = 0.32), and 17% of infants in either group developed grade ≥3 AE. Stavudine was substituted for ZDV in 23 infants due to anemia or neutropenia. After this antiretroviral change, 50% of evaluable infants demonstrated improvement in AE grade, and 25% had no change. In conclusion, low grade anemia, neutropenia, and hyperbilirubinemia occurred frequently regardless of the prophylactic regimen, but serious AE were uncommon. Although most AE were typical of ZDV toxicity, the combination of ZDV with lamivudine and nevirapine resulted in an increased frequency of low-grade anemia. Further studies are needed to identify prophylactic regimens with less toxicity for infants born to HIV-infected mothers.

Haemolytic disease of the fetus and newborn.

Haemolytic Disease of the Fetus and Newborn (HDFN) is caused by maternal alloimmunization against red blood cell antigens. In severe cases, HDFN may lead to fetal anaemia with a risk for fetal death and to severe forms of neonatal hyperbilirubinaemia with a risk for kernicterus. Most severe cases are caused by anti-D, despite the introduction of antental and postnatal anti-D immunoglobulin prophylaxis. In general, red blood cell antibody screening programmes are aimed to detect maternal alloimmunization early in pregnancy to facilitate the identification of high-risk cases to timely start antenatal and postnatal treatment. In this review, an overview of the clinical relevance of red cell alloantibodies in relation to occurrence of HDFN and recent views on prevention, screening and treatment options of HDFN are provided.

Effect of Prenatal and Postnatal Prophylaxis with Macrolide forUreaplasmaon the Development of Bronchopulmonary Dysplasia in Preterm Infants

Purpose: We aimed to evaluate the effects of two different macrolide prophylaxis protocols (prenatal and postnatal) for Ureaplasma on the development of broncho­ pulmonary dysplasia (BPD). Methods: We retrospectively reviewed the medical charts of 121 preterm infants whose birth weights were <1,250 g or gestational ages were <30 postmenstrual weeks. The demographic and clinical characteristics, including the presence of BPD, were compared between a prophylactic group, who received macrolide as prophylaxis prenatally and postnatally according to risk level, and a confirmed treatment group, who received macrolide prenatally and postnatally after detection of Ureaplasma infection. Results: Seventy­four (61.2%) of 121 preterm infants were included in the prenatal prophylaxis group. No significant differences in demographic characteristics were observed between the prenatal prophylaxis and prenatal confirmed treatment group. The detection rate of Ureaplasma and the frequency of postnatal therapeutic treatment with macrolide were lower in the prenatal prophylaxis group than in the prenatal confirmed treatment group (16.2% vs. 40.4%, P=0.003; 8.1% vs. 48.9%, P< 0.001, respectively). Although no significant differences in the incidence of mode rate to severe BPD, the rate of severe BPD was lower in the prenatal prophylaxis group than in prenatal confirmed treatment group (18.9% vs. 40.4%, P=0.010). No signifi­ cant differences in the incidences of BPD of any level of severity were observed between the postnatal prophylaxis and confirmed treatment groups. Conclusion: Administration of prenatal prophylaxis with macrolide decreased the detection rate of Ureaplasma after birth and was associated with the decrease in the incidence of severe BPD in preterm infants.

Diagnostic Accuracy of Routine Antenatal Determination of Fetal RHD Status Across Gestation

The RhD (RH1) antigen of the rhesus system is the most commonly implicated antigen for hemolytic disease of the fetus. Postnatal prophylaxis with anti-RhD immunoglobulin in RhD− women with an RhD+ child has been shown to reduce the risk of becoming alloimmunized. Subsequent introduction of routine antenatal prophylaxis with anti-RhD immunoglobulin in the third trimester for all RhD− women is now standard in many countries. Cell-free fetal DNA in maternal plasma can be tested for the presence or absence of the RHD gene, essentially screening for fetal Rh status. This prospective, multicenter cohort study was performed to determine the diagnostic accuracy of RHD genotyping in RhD− parturients and the optimal gestation for implementation into practice. From 2009 to 2012, consenting parturients had blood samples obtained at their initial appointment, at Down syndrome screening (11–21 weeks’ gestation), and at routine anomaly scanning (18–23 weeks’ gestation). At the third trimester visit (∼28 weeks), women were given the results of molecular testing, and an additional blood sample was obtained to confirm fetal RHD status. When this testing confirmed that the fetus was RHD−, women were allowed to opt out of receiving anti-RhD immunoglobulin. All women predicted to be carrying an RhD+ baby, or if the genotyping result was inconclusive, were offered anti-RhD immunoglobulin. All women who had a sensitizing event at less than 28 weeks were also offered anti-RhD immunoglobulin. RhD typing on cord blood samples was performed using routine serologic methods. Genotyping results were interpreted as RHD+, RHD−, or inconclusive. The final analysis included 2288 women and 4913 fetal genotype results with 4 analyses or less per parturient. Genotyping results were inconclusive for 393 samples (8.0%; 95% confidence interval, 7.3%–8.8%). Based on cord blood analyses, 2023 samples were from RhD− babies, of which 18 had been falsely predicted antenatally to be genotypically RHD+, and 85 were inconclusive; 2890 were RhD+, of which 308 were inconclusive on fetal RHD genotyping, and 19 were falsely predicted to be genotypically RHD−. The odds of correctly identifying RHD+ and RHD− fetuses increased significantly with gestational age, with low levels of false-negative results after 11 weeks’ gestation. At less than 11, 11 to 13, 14 to 17, 18 to 23, and more than 23 weeks, the sensitivities for detecting fetal RHD positivity were 96.85% (94.95%–98.05%), 99.83% (99.06%–99.97%), 99.67% (98.17%–99.94%), 99.82% (98.96%–99.97%), and 100% (99.59%–100%). At less than 11 weeks, 16 (1.9%) of 865 babies tested were falsely predicted to be RHD−. Massive throughput fetal RHD genotyping can be performed as soon as possible at 11 weeks or more. After 11 weeks, the incidence of false-negative results was considerably lower and did not decrease between 11 and 24 weeks, in agreement with evidence that concentrations of cell-free fetal DNA increase only minimally at 10 to 20 weeks’ gestation. The small number of false RHD− results after 11 weeks would lead to a small increase in the risk of alloimmunization. The tradeoffs between treating fewer women with antepartum immunoglobulin versus a few women becoming alloimmunized need to be considered carefully.

Delayed HIV detection among infants exposed to postnatal antiretroviral prophylaxis during breastfeeding

Delayed HIV detection among infants exposed to postnatal antiretroviral prophylaxis during breastfeeding

Anti-D Prophylaxis Reviewed in the Erea of Foetal RHD Genotyping

A few years ago, the prevention of anti-D immunization was currently based on systematic postnatal prophylaxis associated with targeted antenatal injection in high-risk situations of foeto-maternal haemorrhage. The failures of prevention are mainly due to the non-respect of established guidelines for RhIG prophylaxis, and to spontaneous undetected foetal-maternal haemorrhages without any obvious cause during the third trimester of pregnancy. In order to reduce the rate of residual post-pregnancy anti-D immunization, several countries decided to associate the classical prophylaxis to a routine antenatal anti-D prophylaxis (RAADP) during the 28th or 29th week of gestation. Since about ten years, the foetal RHD genotyping in maternal plasma enables us to limit the antenatal prophylaxis only to those D- women carrying a D+ foetus. This paper deals with: the advantages of an antenatal prevention in the light of non invasive foetal RHD genotyping, the rules rendering prevention protocols efficient whatever the algorithm applied, and the recommended immuno-haematology follow-up of women who have received RhIG.

Risk of maternal alloimmunization in Southern Pakistan – A study in a cohort of 1000 pregnant women

BackgroundHaemolytic disease of the fetus and the newborn [HDFN] is caused by incompatibility of maternal and fetal erythrocytes. Red blood cell alloimmunization is a well-known cause of HDFN. Due to heterogeneity of populations, the spectrum of alloimmunization varies around the world. This study aimed to determine the frequency of alloimmunization in pregnant women and to determine the risk of HDFN in our population. Study Design and MethodsThis was a descriptive study conducted at Aga Khan University Hospital Karachi. Blood type and red cell antibody screening was determined on every pregnant woman at her first antenatal visit. Red cell antibody identification was performed on positive screening results. ResultsA total of 1000 pregnant females including 633 (63.3%) multigravida were studied. Blood type B was predominant (n = 374 or 37.4%) and D negative was observed in 136 women (13.6%). No red cell antibody was detected in 982 females (98.2%). 20 red cell antibodies were detected in 18 women (1.8%). The incidence of non-anti-D was 16/1000 [1.6%] in all pregnant females. The non-anti-D alloantibodies included anti-M (n = 3; 15%), anti-Lewis(a) (n = 3; 15%), anti C ( n = 1; 5%), anti-E (n = 1; 5%), anti-e (n = 1; 5%), anti-Lewis(b) (n = 1; 5%) and nonspecific antibodies (n = 6; 30%). The incidence of anti-D was 4/136 or 2.9% in D negative blood type. After excluding prior sensitization due to blood transfusions, risk remained was 2.2%. Antibodies of clinical significance were identified in 9 (0.9%) females. ConclusionsIn our cohort, frequency of red cell alloimmunization during pregnancy was 1. 8% out of which 0.9% were clinically significant antibodies posing a risk for HDFN. Despite prenatal and post natal prophylaxis, risk of sensitization with D antigen in D negative women was high at 2.2%. We recommend that all pregnant women should be screened for irregular antibodies irrespective of the rhesus type.

RhD Immunization Despite Adequate Immunoprophylaxis: Role of Fc Gamma Receptor Gene Polymorphisms

▪Introduction: One of the most effective immunological interventions in clinical medicine is the prevention of hemolytic disease of the newborn by prophylactic Rh immune globulin (Rh-Ig) therapy. The administration of ante- and postnatal Rh-Ig has reduced the risk of RhD immunization in the Netherlands from 17% to a mere 0.31%, yet its mechanism of action is still unknown. To gain more insight into the possible working mechanism of the Rh-Ig prophylaxis we analyzed potential risk factors and genotyped all known IgG-Fc receptor (protein FcγR, gene FCGR) variants known to date, on a cohort of Dutch women who failed Rh-Ig prophylaxis and developed anti-D antibodies. Adequate Rh-Ig immunoprophylaxis was defined as an antenatal and postnatal prophylaxis of 1,000 IU (200 µg) in both current and previous pregnancies, according to the Dutch guidelines.Material and Methods: Between 1999 and 2013 we identified 274 women who produced anti-D antibodies. Through a structured questionnaire we collected information about Rh-Ig prophylaxis and additional clinical data for potential risk factors. In 122 cases, adequate Rh-Ig prophylaxis was given, and clinical risk factors for fetal maternal hemorrhage (FMH) could be collected. Their clinical circumstances were compared to a control group of 339 randomly selected pregnant women. The Rh-Ig therapy failure of 57 of those women could not be explained through our risk factor analysis. From these 57 cases, DNA was obtained, and used for the FcγR-specific multiplex ligation-dependent probe amplification (MLPA) assay, identifying both single nucleotide polymorphisms and copy number variations in the FCGR locus. The results were compared to a control group of 200 healthy donors.Results: A history of red blood cell transfusion (p=0.05) and caesarean section (p<0.0001) were identified to be independent risk factors for RhD immunization. All other described risk factors for FMH such as miscarriage, termination of pregnancy, or invasive diagnostic procedures, requiring an additional Rh-Ig dose according to the guidelines, were not found to increase the risk of immunoprophylaxis failure. RhD-immunization due to caesarian section or red blood cell transfusion accounted for 53% of our cohort, suggesting an alternative explanation for the production of Rh-Ig alloantibodies in the remaining 47% of the cases - despite adequate amount of prophylaxis given in current and previous pregnancies. We therefore postulate the existence of a genetic variation that puts women at increased risk for RhD immunization during pregnancy. To test this hypothesis we analyzed the genetic variation in the FCGR locus and found a significantly (p=0.02) increased prevalence of the FCGR2 -ORF, expressing a functional copy of the activating FcγRIIc, which is otherwise a pseudogene. Strikingly, the prevalence of the 2B.4-promotor haplotype of the FCGR2B gene, associated with a 1.5 fold increase of the inhibitory FcγRIIb, was strongly (p=0.0001) increased.Conclusion: Caesarian section and red blood cell transfusion are risk factors that increase RhD immunization during pregnancies, accounting for about half failed Rh-Ig prophylactic cases. Genetic variation in the FCGR-gene might be a possible explanation for increased immunization risk. In our cohort we encountered a significantly increased frequency of individuals expressing FcγRIIc, along with a polymorphism encoding for a higher expression of the inhibitory receptor FcγRIIb, suggesting these genes to influence immune responses to RBC in a manner previously unrecognized. DisclosuresNo relevant conflicts of interest to declare.

Prevention of vertical transmission of hepatitis B: an observational study.

For mothers with chronic hepatitis B virus (HBV) infection, the Centers for Disease Control and Prevention recommends immunoprophylaxis to decrease perinatal transmission. However, its effectiveness and risk factors for failure have not been well-studied in community practice. To investigate the effectiveness of a contemporary immunoprophylaxis protocol. Observational study. An HBV perinatal immunoprophylaxis program within Kaiser Permanente Northern California. 4446 infants born to 3253 HBV-positive mothers between 1997 and 2010. Adherence to immunoprophylaxis, follow-up testing rates, maternal risk factors for HBV transmission, and transmission rates. The infant infection rate was 0.75 per 100 births from 1997 to 2010 (Poisson 95% CI, 0.48 to 1.10). Rates per 100 births were 3.37 (CI, 2.08 to 5.14) for e antigen-positive mothers and 0.04 (CI, 0.001 to 0.24) for e antigen-negative mothers. Among mothers with viral load testing, the lowest level associated with transmission was 6.32×107 IU/mL. Infection rates per 100 births were 3.61 (CI, 0.75 to 10.56) among the 83 births to mothers with viral loads of 5×107 IU/mL or greater and 0 among the 831 births to mothers with viral loads less than 5×107 IU/mL, regardless of e antigen status. Testing for HBV immunity and infection was less complete in earlier years. Viral load testing was only consistently available starting in 2007. Prenatal HBV screening followed by postnatal prophylaxis is highly effective in preventing vertical transmission of HBV. A negative e antigen status or a viral load less than 5×107 IU/mL (90.9% of women tested) identifies women at extremely low risk for transmission after immunoprophylaxis who are unlikely to benefit from further interventions. Kaiser Permanente Community Benefit and National Institutes of Health.

Routine noninvasive prenatal screening for fetal RHD in plasma of RhD-negative pregnant women-2 years of screening experience from Denmark.

Prenatal and postnatal RhD prophylaxis reduces the risk of RhD immunization in pregnancies of RhD-negative women. Based on the result from prenatal screening for the fetal RHD gene, prenatal RhD prophylaxis in Denmark is targeted to RhD-negative women who carry an RhD-positive fetus. Here, we present a 2-year evaluation of a nationwide prenatal RHD screening. Blood samples were drawn from RhD-negative women in gestational week 25. DNA was extracted from maternal plasma and analyzed for the RHD gene. The prenatal RHD results were compared with the serological typing of newborns in 12,668 pregnancies. Early compliance was assessed for 690 pregnancies. The sensitivity for the detection of fetal RHD was 99.9% (95% CI: 99.7-99.9%). Unnecessary recommendation of prenatal RhD prophylaxis was avoided in 97.3% of the women carrying an RhD-negative fetus. Fetuses that were seropositive for RhD were not detected in 11 pregnancies (0.087%). The sample uptake percentage was 84.2%, and the compliance for prenatal anti-D administration was 93.2%. The high sensitivity, maintained over 2 years, underlines the reliability of routine prenatal fetal RHD screening in RhD-negative pregnant women, specifically at 25 weeks of gestation. The remaining challenges are logistical and are related to program compliance.

Noninvasive fetal RhD genotyping

Immunization against RhD is the major cause of hemolytic disease of the fetus and newborn (HDFN), which causes fetal or neonatal death. The introduction of postnatal immune prophylaxis in the 1960s drastically reduced immunization incidents in pregnant, D-negative women. In several countries, antenatal prophylaxis is combined with postnatal prophylaxis to further minimize the immunization risk. Due to lack of knowledge of the fetal RhD type, antenatal prophylaxis is given to all D-negative women. In the European population, approximately 40% of pregnant women carry a D-negative fetus and are thus at no risk of immunization. Noninvasive fetal RhD genotyping enables antenatal prophylaxis to be targeted to only those women carrying a D-positive fetus to avoid unnecessary treatment. Based on an analysis of cell-free fetal DNA from the plasma of pregnant women, this approach has recently undergone technical improvements and rapid clinical implementation. As a screening assay, the sensitivity is >99.3% from a gestational age of approximately 10-11 weeks. In addition, fetal RhD genotyping is widely used to assess the risk of HDFN in anti-D immunized women.

Suckling and non-nutritive sucking habit: what should we know?

Correct breast feeding can be considered a tool for the post-natal prophylaxis of craniofacial abnormalities, or at least a way of reducing their extent.Inadequate bottle feeding forces the tongue and cheek muscles to develop a compensating and atypical function, in order to obtain the milk. As a result, there can be an adaptation change of the dental and bone structures, leading to malocclusions.Finger-sucking is normal in the first two-three years of life. It gives the child a feeling of relaxation; that is why it is usually practiced before sleeping. The effects of non-nutritive sucking on the developing dentition are minor in the child under 3 years of age and are usually limited to changes in the incisor position. Some upper or lower incisors (depend on how the finger has been sucked) become spontaneously tipped toward the lips, and/or others are prevented from erupting. Normally children abandon this habit between 2 and 4 years of age. If it persists after this age, it will be the cause for some dental-maxillary anomalies: open-bite, narrow maxilla with upper protrusion, cross-bite; all these could be accompanied by retrognathic mandible.