Antenatal Prophylaxis Research Articles

Antibioprophylaxie maternelle et infection à bacille Gram négatif chez le nouveau-né

Prevention strategies by maternal antibiotic use have provided undeniable benefits for neonates regarding early neonatal group B streptococcal infections. But at a time where the evolution of resistance of Gram negative bacteria is of particular concern, it is our duty to reassess prevention strategies with a careful evaluation of their potential impact on Gram negative bacteria in the newborn. We conducted a literature review to define the state of the art of antenatal antibiotic prophylaxis and its bacteriological consequences on the newborn. Prevention strategies of early-onset neonatal group B streptococcal disease with selective intrapartum chemoprophylaxis should not be challenged, even at the cost of a small increase of the incidence of late-onset infections with resistant Gram negative bacteria. However, other indications seem more controversial and the type of antibiotics used is not always based on methodologically well-conducted studies. In these indications the prevention strategies should consider not only the immediate expected benefits, but also the long-term ecological impact by using whenever possible narrow-spectrum antibiotics.

Budesonide Therapy in Preterm Infants to Prevent Bronchopulmonary Dysplasia

Severe bronchopulmonary dysplasia (BPD) is common disease, especially for the tiniest infants with gestational age <27 weeks whose mothers did not receive adequate antenatal steroid prophylaxis. Systemic corticosteroids have been demonstrated to be effective in the prevention of BPD, but their adverse effects prevent routine use. The results of inhaled steroid therapy in intubated premature infants are disappointing. In a pilot study, infants in the treatment group who received early intratracheal instillation of budesonide by using surfactant as a vehicle required significantly less ventilator support during the first 2 weeks than infants in the control group. The combined outcome of deaths or BPD was significantly lower in the treatment group than in the control group. No clinically significant adverse effects from the treatment were observed during the study. The results are encouraging, and a large sample multicenter trial is warranted.

Coverage of the Prevention of Mother-to-Child Transmission Program in the Western Cape, South Africa Using Cord Blood Surveillance

The effectiveness of prevention of mother-to-child transmission of HIV (PMTCT) programs depends on the successful coverage of a series of interventions through pregnancy, intrapartum, and postpartum. Routine monitoring systems based on service data and limited to women on the PMTCT program may overestimate intervention coverage at multiple points along this cascade. Cord blood specimens with individually linked anonymous demographic and pregnancy data were collected from 3 delivery services in the Western Cape Province, South Africa, and screened for HIV. Seropositive specimens were tested for the presence of antiretrovirals. Comparisons were drawn between documented service data and cord blood findings for HIV seroprevalence and antenatal antiretroviral coverage. A total of 3034 specimens were tested for HIV, 507 (16.7%) of which were HIV seropositive. Of these, 470 (92.7%) were tested for the presence of antiretrovirals, of whom 58.1% had evidence of a standard of care maternal antiretroviral regimen and 73.6% some form of antenatal antiretroviral prophylaxis. Cord blood antiretroviral coverage was lower than that reported by service data. Incomplete antenatal HIV testing accounted for an estimated 46.2% of missed opportunities for transmission reduction. Even in this well-resourced setting, HIV screening and ensuring antenatal compliance with prescribed regimens were the most immediate priorities for reducing vertical transmission. Cord blood surveillance offers a unique opportunity to explore missed opportunities using methods not currently possible from routine antenatal and PMTCT program reporting.

Anti-D in Rh(D)-Negative Pregnant Women: Are At-Risk Pregnancies and Deliveries Receiving Appropriate Prophylaxis?

ObjectiveAlthough anti-D prophylaxis has greatly reduced the rate of Rh-immunization, there remain women who sensitize during or after pregnancy because of inadequate prophylaxis. The purpose of this study was to compare adherence to prophylaxis recommendations for antenatal and postnatal anti-D immunoglobulin administration. MethodsWe conducted a retrospective cohort study of all pregnancies recorded at the Royal Victoria Hospital between 2001 and 2006 to determine the rates of antenatal and postnatal prophylaxis in Rh(D)-negative women. We compared adherence to anti-D prophylaxis recommendations between our institution’s physician-dependent antenatal approach and the protocolbased postpartum approach. Logistic regression analysis was used to estimate the odds ratio and 95% confidence intervals of determinants of non-adherence to current recommendations for anti-D prophylaxis. ResultsAntenatal administration was analyzed in 1868 pregnancies in eligible Rh-negative women. Among these women, 85.7% received appropriate antenatal prophylaxis and 98.5% of eligible women received appropriate postnatal prophylaxis. Factors independently associated with non-adherence to antepartum prophylaxis included first visit in the third trimester (P < 0.001), transfer from an outside hospital (P = 0.03), and physician licensing before 1980 (P = 0.04). ConclusionUnlike hospital-based protocol-dependent systems, physician-dependent systems for antenatal anti-D prophylaxis remain subject to errors of omission. A more standardized system is needed to ensure effective antenatal prophylaxis.

Pharmacokinetics of 250 μg anti‐D IgG in the third trimester of pregnancy: An observational study

We present a pharmacokinetic study evaluating a single intramuscular dose of 250 μg anti-D immunoglobulin in the third trimester of pregnancy. The aim of the study was to determine the kinetic profile and duration of detectable levels of anti-D. Prospective observational study. Antenatal outpatient clinic. Healthy Rhesus D (RhD)-negative pregnant women with an RHD-positive fetus. Serial plasma anti-D quantitations following antenatal administration of anti-D immunoglobulin were performed using flow cytometry. Kinetic profiles for anti-D levels were generated from the concentration values at predetermined sampling time points. The half-lives were calculated by linear regression analysis. Main outcome measures. Time vs. concentration profile, half-life and anti-D concentration ≥1 ng/mL close to term. The maximal plasma concentration of anti-D was usually seen at 3-10 days postinjection, with a median value of 25 ng/mL. The half-life varied between individuals, with a median of 23 days. We found detectable levels of anti-D IgG within two weeks of parturition in 11 of 12 women. The preparation of anti-D immunoglobulin used in the present study, if administrated in pregnancy week 28-30, is associated with detectable levels of anti-D in most women at the time of delivery. Although the half-time is 23 days, it is uncertain whether all mothers have adequate anti-D concentrations at term. Alternative strategies may be evaluated in the future, with repeated administration of antenatal prophylaxis at term rather than conventional postpartum administration of anti-D.

Study of compliance with a new, targeted antenatal D immunization prevention programme in Denmark

A targeted routine antenatal anti-D prophylaxis programme was implemented in Denmark where anti-D immunoglobulin is given based on the result from noninvasive antenatal screening for fetal RHD. Our objective was to evaluate compliance with this new programme right after its initiation. We examined the treatment outcome of 239 D-negative pregnant women who gave birth at our hospital between June and September 2010. The majority of these women (90%) underwent antenatal RHD screening, 86% of the women who were recommended antenatal prophylaxis received anti-D, and 99% of the women who delivered RhD-positive infants received postnatal anti-D. These compliance results are acceptable as they were obtained only a few months after the initiation of the new prophylaxis regime. However, suggestions to further improve compliance are presented.

Impact of non-invasive fetal RhD genotyping on management costs of rhesus-D negative patients: results of a French pilot study

Fetal rhesus D (RhD) status determination using circulating cell-free fetal DNA from maternal plasma or serum is now recognized in Europe as a reliable and useful tool. A few countries are presently using this test in their management policy of rhesus D negative patients. The objective of this study is to evaluate the impact of this test on the costs of managing RhD-negative pregnant women, whether or not they are allo-immunized. A prospective follow-up of rhesus D negative women during their pregnancy was performed in three French obstetric departments. Non-invasive fetal RhD genotyping was performed in the first trimester and pregnancies were followed The costs of all procedures (biological tests and medication) associated with patient management in relation to their RhD-negative status were calculated according to different management options. A comprehensive follow-up, including medical and biological monitoring, was obtained for 99 of the 101 patients included in the study. Patients were separated into two groups: the "Adverse Event" group (AE, n=23) for which a potentially sensitizing event occurred and the "No Adverse Event" group (NAE, n=76). Fetal RhD status was accurately determined in all cases. The mean cost per patient was estimated at 237€ (range: 115-644) with differences observed depending on the group, notably 331€ (range: 236-644) for the AE group and 208€ (range: 115-366) for the NAE group. Various cost simulations were performed according to various policies of allo-immunization antenatal prophylaxis. Variations ranged from +36.2% to +105.3%. This study demonstrates that fetal RhD genotyping early during pregnancy is not an effective cost-reduction strategy whether or not antenatal prophylaxis is given. The economic issues could, however, be overcome by the fact that there is a major clinical benefit to offering the test systematically to all RhD-negative pregnant women while avoiding unnecessary testing and immunoglobulin injections.

First intention high-frequency oscillatory and conventional mechanical ventilation in premature infants without antenatal glucocorticoid prophylaxis*

Data comparing the effectiveness of high-frequency oscillatory ventilation and of conventional mechanical ventilation in the treatment of respiratory distress syndrome of very low birth weight infants are, to date, still matter of debate. We investigated the effects of first intention high-frequency oscillatory ventilation or conventional mechanical ventilation support on selected primary and secondary outcomes in very low birth weight infants complicated by respiratory distress syndrome in which antenatal glucocorticoid prophylaxis was not performed. Multicenter randomized control trial. Three tertiary centers of neonatal intensive care units from December 2004 to December 2007. Eighty-eight very low birth weight infants complicated by respiratory distress syndrome, without antenatal glucocorticoids, supported by first intention high-frequency oscillatory ventilation (n = 44) or conventional mechanical ventilation (n = 44). All newborns were monitored by standard monitoring procedure, including routine laboratory variables, neurologic patterns, and ultrasound imaging. Primary outcomes were: the length of ventilatory support, the need of reintubation, and the length of nasal continuous positive airway pressure support in the postextubation period. Secondary outcomes were: the length of stay in neonatal intensive care unit and in hospital, death before discharge, adverse short- and long-term pulmonary and neonatal outcomes, and the need for a second dose of surfactant and of postnatal glucocorticoid treatment. High-frequency oscillatory ventilation infants showed a significant lower duration (p < .001 for all) of ventilator dependency, lower need of reintubation and of duration of nasal continuous positive airway pressure support in the postextubation period. Among secondary outcomes in the high-frequency oscillatory ventilation infants, the need of a second dose of surfactant administration, and the length of stay in the neonatal intensive care unit and in hospital were significantly lower (p < .05 for all). We found that high-frequency oscillatory ventilation in very low birth weight infants without antenatal glucocorticoid prophylaxis reduced the need of ventilatory support, surfactant therapy, and reintubation, and shortened neonatal intensive care unit and hospital stay, thus reducing unit and hospital costs. These data would support the usefulness of first intention high-frequency oscillatory ventilation strategy in managing in a selected population, such as very low birth weight newborns complicated by severe respiratory distress syndrome not antenatally treated with glucocorticoids.

Report of the first nationally implemented clinical routine screening for fetal RHD in D− pregnant women to ascertain the requirement for antenatal RhD prophylaxis

A combination of antenatal and postnatal RhD prophylaxis is more effective in reducing D immunization in pregnancy than postnatal RhD prophylaxis alone. Based on the result from antenatal screening for the fetal RHD gene, antenatal RhD prophylaxis in Denmark is given only to those D- women who carry a D+ fetus. We present an evaluation of the first national clinical application of antenatal RHD screening. In each of the five Danish health care regions, blood samples were drawn from D- women in Gestational Week 25. DNA was extracted from the maternal plasma and analyzed for the presence of the RHD gene by real-time polymerase chain reaction targeting two RHD exons. Prediction of the fetal RhD type was compared with serologic typing of the newborn in 2312 pregnancies, which represented the first 6 months of routine analysis. For the detection of fetal RHD, the sensitivity was 99.9%. The accuracy was 96.5%. The recommendation for unnecessary antenatal RhD prophylaxis for women carrying a D- fetus was correctly avoided in 862 cases (37.3%), while 39 women (1.7%) were recommended for antenatal RhD prophylaxis unnecessarily. Two RHD+ fetuses (0.087%) were not detected, and antenatal RhIG was not given. These data represent the first demonstration of the reliability of routine antenatal fetal RHD screening in D-, pregnant women to ascertain the requirement for antenatal RhD prophylaxis. Our findings should encourage the implementation of such screening programs worldwide, to reduce the unnecessary use of RhIG.

SIGN guideline on venous thromboembolism

boembolism (House of Commons, 2005). Many of these deaths could have been prevented—despite the clear evidence supporting the benefits of prophylactic treatment to prevent thromboembolism, such treatment has only been used in about half of suitable patients and many healthcare professionals appear to be unaware of the risks (Hill and Treasure, 2010). The Scottish Intercollegiate Guidelines Network (SIGN) has published updated guidelines on the prevention and management of venous thromboembolism, based on new evidence published between 1998 and 2010, including evidence on new antithrombotic agents, diagnostic methods, and complications from treatment. This guidance was launched in December 2010 and it replaces the previous SIGN guideline 62 on the prophylaxis of venous thromboembolism (SIGN, 2002). In 2010, the National Institute for Health and Clinical Excellence (NICE) also published guidance on the prevention of venous thromboembolism for all patients admitted to hospital (NICE, 2010). As with SIGN, the NICE recommendations are based on systematic reviews of the best available evidence. However, the SIGN guidelines go further than the NICE recommendations, by providing guidance for all patients, discussing risk assessment, thromboprophylaxis in surgical and medical patients both in and out of hospital, antenatal and postnatal risk assessment and prophylaxis, travel-related thrombosis, and diagnosis and management of venous thromboembolism. SIGN has produced an implementation plan to accompany the guideline, to ensure that its recommendations are widely publicised and implemented. Some of the key issues raised in the guidance will be discussed here.

A new fetal RHD genotyping test: Costs and benefits of mass testing to target antenatal anti-D prophylaxis in England and Wales

BackgroundPostnatal and antenatal anti-D prophylaxis have dramatically reduced maternal sensitisations and cases of rhesus disease in babies born to women with RhD negative blood group. Recent scientific advances mean that non-invasive prenatal diagnosis (NIPD), based on the presence of cell-free fetal DNA in maternal plasma, could be used to target prophylaxis on "at risk" pregnancies where the fetus is RhD positive. This paper provides the first assessment of cost-effectiveness of NIPD-targeted prophylaxis compared to current policies.MethodsWe conducted an economic analysis of NIPD implementation in England and Wales. Two scenarios were considered. Scenario 1 assumed that NIPD will be only used to target antenatal prophylaxis with serology tests continuing to direct post-delivery prophylaxis. In Scenario 2, NIPD would also displace postnatal serology testing if an RhD negative fetus was identified. Costs were estimated from the provider's perspective for both scenarios together with a threshold royalty fee per test. Incremental costs were compared with clinical implications.ResultsThe basic cost of an NIPD in-house test is £16.25 per sample (excluding royalty fee). The two-dose antenatal prophylaxis policy recommended by NICE is estimated to cost the NHS £3.37 million each year. The estimated threshold royalty fee is £2.18 and £8.83 for Scenarios 1 and 2 respectively. At a £2.00 royalty fee, mass NIPD testing would produce no saving for Scenario 1 and £507,154 per annum for Scenario 2. Incremental cost-effectiveness analysis indicates that, at a test sensitivity of 99.7% and this royalty fee, NIPD testing in Scenario 2 will generate one additional sensitisation for every £9,190 saved. If a single-dose prophylaxis policy were implemented nationally, as recently recommended by NICE, Scenario 2 savings would fall.ConclusionsCurrently, NIPD testing to target anti-D prophylaxis is unlikely to be sufficiently cost-effective to warrant its large scale introduction in England and Wales. Only minor savings are calculated and, balanced against this, the predicted increase in maternal sensitisations may be unacceptably high. Reliability of NIPD assays still needs to be demonstrated rigorously in different ethnic minority populations. First trimester testing is unlikely to alter this picture significantly although other emerging technologies may.

Thromboembolieprophylaxe in Schwangerschaft und im Wochenbett: Highlights aus aktuellen Leitlinien

Venous thromboembolism (VTE) is one of the leading causes of maternal deaths worldwide. Mortality and morbidity of VTE are potentially preventable, since two-thirds of these women have identifiable risk factors and may benefit from appropriate thromboprophylaxis. Individual and careful assessment of the personal and family history as well as the assessment of pre-existing and new-onset/transient risk factors during pregnancy and after delivery are mandatory for an effective prevention of VTE. Current guidelines (American College of Chest Physicians 2008, AWMF-Guideline 003/001 2009 and the Royal College Guideline No. 37 2009) provide practical recommendations for risk stratification regarding low, intermediate and high risk conditions. At high risk are women with previous VTE or thrombophilia. Corresponding to risk stratification grade C recommendations have been made for VTE prophylaxis during pregnancy and the puerperium. Prophylaxis with low molecular weight heparin (LMWH) should begin as early in pregnancy as practical. In women with lower risk mobilisation, avoidance of dehydration and mechanical methods (e. g., graduated compressive stockings) are sufficient. After delivery women with intermediate risk should be given LMWH for 7 days, women at high risk for 6 weeks or as long as additional risk factors are present. All women who have additional risk factors and who have had an elective Caesarean section should receive prophylactic LMWH for 7 days as should also all women who have had a Caesarean section in labour or an emergency Caesarean section. At the onset of labour, in case of any vaginal bleeding, prior to induction of labour or 12 h before an elective Caesarean section, antenatal LMWH prophylaxis should be discontinued, LMWH prophylaxis can be continued for 4-6 h after vaginal and for 6-12 h after Caesarean delivery when the women do not have an increased risk of haemorrhage. Current guidelines recommend than LMWH are the agents of choice for antenatal thromboprophylaxis; in comparison to unfractionated heparin, LMWH are associated with a substantially lower risk of heparin-induced thrombocytopenia and osteoporosis. Both oral anticoagulants and heparin are safe when breast-feeding.

Evaluation of Two Real-Time Multiplex PCR Screening Assays Detecting Fetal RHD in Plasma from RhD Negative Women to Ascertain the Requirement for Antenatal RhD Prophylaxis

Objective: To evaluate two different multiplex real-time PCR assays detecting fetal RHD for screening of RhD negative women in relation to antenatal RhD prophylaxis. Methods: We designed a duplex assay for the detection of RHD exon 7 and 10 and a triplex assay for the detection of RHD exon 7, 10 and 5. We used the same fluorescent dye for the exon 7 and 10 probes to increase sensitivity; exon 5 was VIC labeled. We evaluated possible inhibition of DNA amplification with dilution experiments. We then tested the two multiplex assays with DNA extracted from 97 plasma samples from 38 RhD negative women in gestational weeks 6–37. Results: Dilution experiments revealed no inhibition of amplification in the multiplex assays. For plasma samples, the duplex assay was significantly more sensitive than the triplex assay (p < 0.0001). For the duplex assay (exon 7/10), accuracy was 99.0%. For the triplex assay (exon 7/10), accuracy was 94.2%. Detection of exon 5 was less reliable. Conclusion: The duplex assay using exon 7/10 was the most reliable for prenatal prediction of fetal RhD type as a candidate assay for screening of RhD negative women in relation to antenatal RhD prophylaxis. The triplex assay needs further optimization.

Antenatal Rh prophylaxis is unnecessary for “Asia type” DEL women

Background Generally Rh-negative patients need to be transfused with Rh-negative red blood cells. For pregnant women carrying Rh-positive fetus, the antenatal anti-D detection and Rh immunoglobulin prophylaxis are required worldwide. In East Asia, a RhD variant, termed “Asia type” DEL, was found in approximately 30% of apparent Rh-negative individuals. The antigenic and molecular properties of the DEL were previously defined. Few data discuss whether DEL could be immunized by D antigen clinically although DEL was reported arousing alloimmunization to true Rh-negative patients. Study design and methods To determine whether the DEL variant can be immunized to the D antigen, we retrospectively evaluated 104 Rh-negative pregnancies with allo-anti-D antibodies, and we also tracked 199 consecutive apparent Rh-negative pregnant women, with a history of gestations or parturitions but not subject to anti-D gamma-globulin prophylaxis, for evidence of allo-anti-D. The DEL variant was first excluded by ccee phenotypes and then identified through PCR analysis or sequencing. Results In the retrospective study, we expected to find 30 DEL variants, yet none of the anti-D alloimmunized women were DEL-positive. And in the second group, none of 44 DEL-positive women versus 38 of 155 (24.5%) true Rh-negative women (those excluding DEL) formed allo-anti-D. Conclusion The data indicate that the “Asia type” DEL variant does not appear at risk of alloimmunization to the D antigen. It strongly suggests that the antenatal Rh immune globulin prophylaxis is unnecessary for DEL women. Furthermore, it implicates that the “Asia type” DEL may be deemed Rh-positive safely for clinical transfusion therapy.

Preterm Newborns are Provided with Triggering Receptor Expressed on Myeloid Cells-1

Triggering receptor expressed on myeloid cells-1 (TREM-1) and soluble fraction (sTREM-1) are useful markers of infection in adults. Neonates, especially preterm infants, are exposed to high risk of sepsis due to the immature immune system and few data are available regarding TREM-1, mainly focused on the soluble form. We therefore decided to investigate the baseline assessment of TREM-1, membrane and soluble receptors, in preterm newborns without clinical or microbiological evidence of infection, in order to precociously measure the possible changes due to sepsis and compare them to the obtained reference values. Fifty-nine newborns were enrolled in the study. Median and Interquartile range of TREM-1 were: in monocytes 96 percent with 71 Mean Fluorescence Intensity (50-94); in PMNs: 80 percent (68-87); soluble TREM-1: 29.1 pg/ml (14.55-103.93). Monocyte expression and soluble TREM-1 concentrations appeared comparable to healthy adults, while not all PMNs expressed this receptor, possibly due to their immaturity. Birth weight negatively correlated with sTREM-1, while there were no statistical significances with gestational age, maternal age, gender, mode of delivery, patent ductus arteriosus, intrauterine growth restriction, premature rupture of membranes and TREM-1 or sTREM-1. We also reported a statistical relationship between monocyte TREM-1 and surfactant administration and between sTREM-1 and antenatal steroid prophylaxis. Even if untrained, the neonatal immune system of preterm newborns is equipped with TREM-1 system, but further studies are needed to evaluate the functionality in newborns.

To review practice in the management of rhesus D-negative women during pregnancy

The Department of Health has recommended that ‘Routine Antenatal Anti-D Prophylaxis’ (RAADP) should be offered to all non-sensitised Rhesus D (RhD)-negative pregnant women at 28 and 34 weeks of gestation.1...

Non-invasive fetal RHD genotyping in the first trimester of pregnancy

Hemolytic disease of the fetus and newborn (HDN) is caused primarily by feto-maternal RhD incompatibility. Although all RhD negative pregnant women undergo routine antenatal RhD prophylaxis at 28 weeks of gestation, and following delivery if the newborn is RhD positive, HDN has not been eradicated. Here, we investigated fetal Rhesus D (RHD) genotype in maternal plasma during the first trimester of pregnancy in our area. Plasma samples were obtained from 111 RhD negative pregnant women, between 9 and 13 weeks of gestation. DNA from maternal plasma containing cell-free fetal DNA (cffDNA) was analyzed by quantitative PCR (qPCR) to detect RHD exons 5 and 7. A beta-globin (HBB) sequence was quantified to estimate total DNA concentration. qPCR results were compared with newborn RhD determined in cord blood serum. The influence of several gestational parameters on DNA concentration was also analyzed. The specificity and sensitivity of the assay was 93% and 100%, respectively, with 97% diagnostic accuracy. Cell-free DNA concentrations during the first trimester of pregnancy were not affected by the gestational parameters studied (free-beta fraction of human chorionic gonadotropin and pregnancy-associated plasma protein A concentrations, fetal sex, materno-fetal ABO blood group incompatibility, maternal weight and gestational age). Non-invasive fetal RHD genotyping during the first trimester of pregnancy can be determined with a high specificity, thus representing a valuable tool for improving the management of RhD negative pregnant women. As a high percentage of pregnant women participate in the routine first trimester combined screening program for aneuploidies, the fetal RHD study could be of immediate implementation, since the same blood collection could be used.

Prophylaxis for venous thromboembolic disease in pregnancy and the early postnatal period.

Venous thromboembolic disease (TED), although rare, is a major cause of maternal mortality and morbidity, hence methods of prophylaxis are often used for women at risk. This may include women delivered by caesarean section, those with a personal or family history of TED and women with inherited or acquired thrombophilias (conditions that predispose people to thrombosis). Many methods of prophylaxis carry a risk of side effects, and as the risk of TED is low, it is possible that the benefits of thromboprophylaxis may be outweighed by harm. Current guidelines for clinical practice are based on expert opinion only, rather than high quality evidence from randomised trials. To determine the effects of thromboprophylaxis in women who are pregnant or have recently delivered and are at increased risk of TED on the incidence of venous TED and side effects of treatment. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (May 2009). Randomised trials comparing one method of thromboprophylaxis with placebo or no treatment, and randomised trials comparing two (or more) methods of thromboprophylaxis. Two review authors extracted data independently and resolved any discrepancies by discussion. Sixteen trials met the inclusion criteria but only 13 trials, involving 1774 women, examining a range of methods of thromboprophylaxis, contributed data for the outcomes of interest. Four of them compared methods of antenatal prophylaxis: low molecular weight heparin (LMWH) versus unfractionated heparin (UFH) (two studies), and heparin versus no treatment (two studies). Eight studies assessed postnatal prophylaxis after caesarean section; one compared hydroxyethyl starch with unfractionated heparin; four compared heparin with placebo; and the other three compared UFH with LMWH. One study examined prophylaxis in the postnatal period.The small number of statistically significant findings in this review are largely derived from trials which are not of high methodological quality. It was not possible to assess the effects of any of these interventions on most outcomes, and especially on rare outcomes such as death, TED and osteoporosis, because of small sample sizes and the small number of trials making the same comparisons.There was some evidence of side effects associated with thromboprophylaxis. There is insufficient evidence on which to base recommendations for thromboprophylaxis during pregnancy and the early postnatal period. Large scale randomised trials of currently-used interventions should be conducted.

Risk Factors for RhD Immunisation Despite Antenatal and Postnatal Anti-D Prophylaxis

Despite routine antenatal and postnatal administration of anti-D immunoglobulin (Ig) during pregnancy and delivery in a previous pregnancy, 0.1% to 0.3% of women are found to have Rhesus D (RhD) antibodies in their next pregnancy. The primary aim of this case-control study was to identify causative risk factors for rhesus D (RhD) immunization in the next pregnancy among women who had received adequate antenatal and postnatal anti-D prophylaxis in the previous pregnancy. A second aim was to evaluate the preventive effect of additional administration of anti-D Ig in such women with risk factors. Data obtained from the nationwide Dutch antenatal anti- D-prophylaxis program identified 42 new cases of RhD-immunized parae-1, detected with first-trimester screening, despite documented evidence of adequate antenatal and postnatal prophylaxis during the previous pregnancy. The controls were 339 parae-1 without red cell antibodies. Data on risk factors and other information was provided by the obstetric care worker and/or telephone interviews with the women. The primary study outcome measures were risk factors for RhD immunization. Multivariate analysis showed that statistically significant independent risk factors for RhD immunization were postmaturity (≥42 weeks of completed gestation) (odds ratio [OR], 3.07; 95% confidence interval [CI], 1.02-9.02), nonspontaneous delivery (assisted vaginal delivery or cesarean section) (OR, 2.23; 95% CI, 1.04-4.74), and age (OR, 0.89/yr; 95% CI, 0.80-0.98). Pregnancy-related red blood cell transfusion was almost significant; the OR was 3.51, with a 95% CI of 0.97 to 12.7. A condition related to increased feto-maternal hemorrhage and/or insufficient levels of anti-D Ig was observed in at least half of the failures of anti-D Ig prophylaxis. These findings provide direct evidence of causative risk factors for RhD immunization in the next pregnancy of women who had received adequate antenatal and postnatal anti-D prophylaxis in their previous pregnancy. The data show that RhD immunization may be further reduced by routine administration of extra anti-D Ig in these women.

A window into a public program for prevention of mother to child transmission of HIV: Evidence from a prospective clinical trial

OBJECTIVES: To evaluate efficacy of the antenatal, intra-partum and post-natal antiretroviral components of a public service Prevention of Mother to Child (MTCT) program in infants. DESIGN: Analysis of prospectively collected screening data of demographic and MTCT-related interventions and HIV-infection status of infants identified through HIV-specific DNA polymerase chain reaction. SETTING: Tygerberg Children's Hospital, Western Cape Province, South Africa. SUBJECTS: HIV-infected women and their infants identified through participation in a public service MTCT program were referred for possible participation in a prospective study of isoniazid prophylaxis. INTERVENTIONS: Key components of the Program include voluntary counselling and testing, zidovudine to the mother from between 28 and 34 weeks gestation and to the newborn infant for the first week, single dose nevirapine to the mother in labour and the newborn shortly after birth and free formula for 6 months. MAIN OUTCOME MEASURES: Number and percentage of HIV-infected infants and extent of exposure to antenatal, intrapartum and post-natal antiretrovirals. RESULTS: Of 656 infants with a median age of 12.6 weeks, screened between April 1(st) 2005 through May 2006, 39 were HIV-infected giving a transmission rate of 5.9% (95% CI: 4.4% - 8.0%). Antenatal prophylaxis was significantly associated with reduced transmission (OR: 0.43 (95% CI: 0.21 - 0.94)) as opposed to intrapartum and postpartum components (p=0.85 and p=0.84, respectively). In multivariable analysis the antenatal component remained significant (OR=0.40 (95% CI 0.19 - 0.90)). CONCLUSIONS: The antenatal phase is the most important antiretroviral component of the MTCT program, allowing most opportunity for intervention.