The experience and effectiveness of the Nova Scotia Rh program, 1964-84.

A program to reduce the incidence of erythroblastosis fetalis was started in Nova Scotia in 1964. Up to the end of 1984, 120 fetuses received 247 intrauterine transfusions. The survival rate was 45.6% in the first 10 years of the program and 66.7% in the next 11 years. For fetuses at or over 26 weeks'' gestation the figures were 51.5% and 73.7% respectively. Postpartum prevention was started in 1968, with administration of Rh immune globulin (RhIG) to Rh-negative unimmunized women within 72 hours after the birth of an Rh-positive infant. Antepartum prevention, started in 1979, consisted of administration of RhIG at 28 weeks'' gestation to Rh-negative unimmunized women. The effectiveness of the prevention program was evaluated by enumerating the known cases of Rh(D) alloimmunization in the province from 1982 to 1984: 55 cases were identified, a rate of 1.5 per 1000 births instead of the expected rate of about 10 per 1000.     

The effect of delivery on regression of abnormal cervical cytologic findings

The purpose of this study was to determine whether abnormal antepartum cervical cytologic findings result in differing postpartum regression rates. Between 1993 and 2000, 107 pregnant women with antepartum abnormal cervical cytologic findings were identified. Papanicolaou smear data were separated into three groups by use of the CIN classification system. Postpartum regression rates of antepartum Papanicolaou smears were analyzed six months after delivery. Normalization of Papanicolaou smears in the postpartum period were observed in 50 of 107 women (46.7%). Regression of cervical cytologic findings was noted in 61 of 107 women (57%). Respectively, persistence of Papanicolaou smear was noted in 43 of 107 patients (40%). Only 3 of 107 (3%) antepartum findings progressed after delivery. Desquamation of the cervical epithelium or enhancement of a localized reparative immunologic response after vaginal delivery could play an important role in the spontaneous regression of cervical dysplasia in the postpartum period.     

Maternal and neonatal outcome in pregnancies with no risk factors.

Between November 1979 and April 1984, 790 consecutive pregnant women who considered themselves as having a "normal" pregnancy were followed in private practice from 9 weeks'' gestation until 6 weeks post partum. The women had no pre-existing disease or problem classified as a risk to the pregnancy at the time of their first visit, had a singleton pregnancy and gave birth at Notre-Dame Hospital, Montreal. Maternal complications occurred during the course of pregnancy in 181 women (23%). Complications were mostly related to obstetric conditions (10%), such as preterm labour, intrauterine growth retardation (IUGR) and antepartum hemorrhage, or to medical conditions (12%), the most prevalent of which was hypertension (77% of medical conditions). Neonatal complications occurred in 183 infants (23%). The corrected perinatal death rate was 2.5 per 1000. Prematurity, IUGR and dysmaturity/postmaturity accounted for nearly half of the complications. Hyperbilirubinemia occurred in 7% of the cases. Among women without any maternal complications during pregnancy, the frequency rate of neonatal complications was 19%, compared with 23% among the entire group of 790 women. Our results suggest that the absence of maternal complications does not protect the infant from a neonatal complication. Further refinement is needed to identify markers of obstetric, medical and neonatal complications in pregnancies with no risk factors.     

Comparative pharmacokinetics of liquid and lyophilized formulations of IV RhIG immune globulin.

To compare the pharmacokinetics, safety, and tolerability of the liquid and lyophilized formulations of Rh(0)(D) immune globulin intravenous (human) (IV RhIG) administered intramuscularly (IM) and intravenously (IV). In 2 randomized, parallel arm, blinded, phase I studies, 142 healthy adult volunteers received a single dose of either the liquid or lyophilized formulation administered IM (300 microg in Study 1; 15 microg/kg in Study 2) or IV (50 microg/kg in Study 1). Pharmacokinetics (area under the curve [AUC}, C(max), t(1/2), T(max)) and safety data were assessed over 84 days. The 2 formulations had comparable pharmacokinetics following both IM and IV administration. The ratios (90% confidence intervals) for AUC and C(max) treatment means were, for most assessments, within the predefined FDA acceptance range of 80%-125%, demonstrating the bioequivalence of the liquid and lyophilized formulations. Both formulations were equally well tolerated. Study results demonstrate comparable safety and pharmacokinetic profiles of the liquid and lyophilized formulations of IV RhIG. These findings suggest that the liquid formulation will be therapeutically equivalent to the lyophilized formulation but in a more convenient ready-to-use dosage form that may also reduce preparation errors.     

Pregnancy-Associated Breast Cancer in Taiwanese Women: Potential Treatment Delay and Impact on Survival

This study investigated the clinicopathologic characteristics and survival of women diagnosed with pregnancy-associated breast cancer (PABC) in Taiwan. PABC is defined as breast cancer diagnosed during pregnancy or within 1 year after obstetric delivery. Our sample of PABC patients (N = 26) included all patients diagnosed at a major medical center in northern Taiwan from 1984 through 2009. Among these patients, 15 were diagnosed during pregnancy and 11 were diagnosed within 1 year after delivery. The comparison group included 104 patients within the same age range as the PABC patients and diagnosed with breast cancer not associated with pregnancy from 2004 through 2009 at the same hospital. Patients'' initiating treatment delayed, 5-year and 10-year overall survival were delineated by stratified Kaplan-Meier estimates. Patients'' characteristics were associated with initiating treatment delayed was evaluated with multivariate proportional hazards modeling. Antepartum PABC patients were younger and had longer time between diagnosis and treatment initiation than postpartum PABC patients. The predictor of treatment delayed was including birth parity, cancer stage, and pregnancy. The PABC group had larger tumors, more advanced cancer stage, and tumors with less progesterone receptor than the comparison group. The antepartum PABC patients had higher mortality than postpartum PABC and comparison groups within 5 years after diagnosis. Based on these results, we confirmed that pregnant women with breast cancer were more likely to delay treatment. Therefore, we recommend that breast cancer screening should be integrated into the prenatal and postnatal routine visits for early detection of the women''s breast problems.     

Epidemiology of venous thromboembolism (VTE) associated with pregnancy

This review is focused on the epidemiology of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), associated with pregnancy. Superficial vein thrombosis, a less hazardous and less studied type of thrombosis in pregnant women, is beyond the scope of this review. This study discusses the VTE incidence rate in women from developed countries for both antepartum and postpartum periods and for subpopulations of women affected by additional risk factors, such as thrombophilias, circulatory diseases, preeclampsia of varying degrees of severity, and Caesarean section. To minimize bias due to historical changes in medical and obstetric practices, lifestyle, diet, etc., this review is generally limited to relatively recent studies, i.e., those that cover the last 35 years. The absolute risk or incidence rate was used to ascertain risk of VTE associated with pregnancy. For the studies where the direct incidence rates of VTE were not reported, we calculated an estimate of the observed but not reported absolute incidence rates using the data presented in respective articles. Birth Defects Research (Part C) 105:167–184, 2015. © 2015 Wiley Periodicals, Inc.     

The Bristol third stage trial: active versus physiological management of third stage of labour.

OBJECTIVE--To compare the effects on fetal and maternal morbidity of routine active management of third stage of labour and expectant (physiological) management, in particular to determine whether active management reduced incidence of postpartum haemorrhage. DESIGN--Randomised trial of active versus physiological management. Women entered trial on admission to labour ward with allocation revealed just before vaginal delivery. Five months into trial high rate of postpartum haemorrhage in physiological group (16.5% v 3.8%) prompted modification of protocol to exclude more women and allow those allocated to physiological group who needed some active management to be switched to fully active management. Sample size of 3900 was planned, but even after protocol modification a planned interim analysis after first 1500 deliveries showed continuing high postpartum haemorrhage rate in physiological group and study was stopped. SETTING--Maternity hospital. PARTICIPANTS--Of 4709 women delivered from 1 January 1986 to 31 January 1987, 1695 were admitted to trial and allocated randomly to physiological (849) or active (846) management. Reasons for exclusion were: refusal, antepartum haemorrhage, cardiac disease, breech presentation, multiple pregnancy, intrauterine death, and, after May 1986, ritodrine given two hours before delivery, anticoagulant treatment, and any condition needing a particular management of third stage. INTERVENTIONS--All but six women allocated to active management actually received it, having prophylactic oxytocic, cord clamping before placental delivery, and cord traction; whereas just under half those allocated to physiological management achieved it. A fifth of physiological group received prophylactic oxytocic, two fifths underwent cord traction and just over half clamping of the cord before placental delivery. ENDPOINT--Reduction in incidence of postpartum haemorrhage from 7.5% under physiological management to 5.0% under active management. MEASUREMENTS AND MAIN RESULTS--Incidence of postpartum haemorrhage was 5.9% in active management group and 17.9% in physiological group (odds ratio 3.13; 95% confidence interval 2.3 to 4.2), a contrast reflected in other indices of blood loss. In physiological group third stage was longer (median 15 min v 5 min) and more women needed therapeutic oxytocics (29.7% v 6.4%). Apgar scores at one and five minutes and incidence of neonatal respiratory problems were not significantly different between groups. Babies in physiological group weighed mean of 85 g more than those in active group. When women allocated to and receiving active management (840) were compared with those who actually received physiological management (403) active management still produced lower rate of postpartum haemorrhage (odds ratio 2.4;95% CI1.6 to 3.7). CONCLUSIONS--Policy of active management practised in this trial reduces incidence of postpartum haemorrhage, shortens third stage, and results in reduced neonatal packed cell volume.     

Evaluation of rubella screening in pregnant women

BACKGROUND: The rationale for rubella vaccination in the general population and for screening for rubella in pregnant women is the prevention of congenital rubella syndrome. The objective of this study was to evaluate the effectiveness of the prenatal rubella screening program in Quebec. METHODS: A historical cross-sectional study was designed. Sixteen hospitals with obstetric services were randomly selected, 8 from among the 35 "large" hospitals in the province (500 or more live births/year) and 8 from among the 50 "small" hospitals (fewer than 500 live births/year). A total of 2551 women were randomly selected from all mothers of infants born between Apr. 1, 1993, and Mar. 31, 1994, by means of stratified 2-stage sampling. The proportions of women screened and vaccinated were ascertained from information obtained from the hospital chart, the physician''s office and the patient. RESULTS: The overall (adjusted) screening rate was 94.0%. The rates were significantly different between large and small hospitals (94.4% v. 89.6%). Five large hospitals and one small hospital had rates above 95.0%. The likelihood of not having been screened was statistically significantly higher for women who had been pregnant previously than for women pregnant for the first time (4.8% v. 1.4%; p < 0.001). Of the 200 women who were seronegative at the time of screening (8.4%), 79 had been vaccinated postpartum, had a positive serological result on subsequent testing or did not require vaccination, and 59 had not been vaccinated postpartum; for 62, subsequent vaccination status was unknown. INTERPRETATION: Continued improvement in screening practices is needed, especially in small hospitals. Because vaccination rates are unacceptably low, it is crucial that steps be taken to address this issue.     

Long term backache after childbirth: prospective search for causative factors.

OBJECTIVES--To assess in a prospective randomised study the association between motor block resulting from high and low dose epidural infusions of bupivacaine in labour and the incidence of long term backache after childbirth, and to compare the incidence of backache in women not receiving epidural analgesia. DESIGN--Women requesting epidural analgesia in labour between October 1991 and March 1994 were randomised to receive infusions of either bupivacaine alone or low dose bupivacaine with opioid. Data were collected during labour and the immediate postpartum period from these women and from women recruited at random over the same time from those who had laboured without epidural analgesia. A postal questionnaire about symptoms was sent three months after childbirth to all women. Further data were collected one year after childbirth from those who had reported new backache at three months. SETTING--St Thomas''s Hospital, London. SUBJECTS--599 women were recruited, of whom 450 (75%) replied to a follow up questionnaire. RESULTS--152 women (33.8% of responders) reported backache lasting three months after delivery and, of these, 33 (7.3%) had not previously suffered with backache. There were no significant differences between the treatment groups in the incidence of postnatal backache overall or of new backache or any symptoms after childbirth. Among all demographic, obstetric, and epidural variables examined the only factors significantly associated with backache after childbirth were backache before and during pregnancy. CONCLUSIONS--The incidence of new long term backache was not significantly increased in women who received epidural analgesia in labour. Motor block resulting from epidural local anaesthetic administration was not a significant factor in the development of backache.     

Study protocol: The Adherence and Intensification of Medications (AIM) study - a cluster randomized controlled effectiveness study

Background

Each year, worldwide about 530,000 women die from causes related to pregnancy and childbirth. Of the deaths 99% are in low and middle income countries. Obstetric haemorrhage is the leading cause of maternal mortality, most occurring in the postpartum period. Systemic antifibrinolytic agents are widely used in surgery to prevent clot breakdown (fibrinolysis) in order to reduce surgical blood loss. At present there is little reliable evidence from randomised trials on the effectiveness of tranexamic acid in the treatment of postpartum haemorrhage.

Methods

The Trial aims to determine the effect of early administration of tranexamic acid on mortality, hysterectomy and other morbidities (surgical interventions, blood transfusion, risk of non-fatal vascular events) in women with clinically diagnosed postpartum haemorrhage. The use of health services and safety, especially thromboembolic effect, on breastfed babies will also be assessed. The trial will be a large, pragmatic, randomised, double blind, placebo controlled trial among 15,000 women with a clinical diagnosis of postpartum haemorrhage. All legally adult women with clinically diagnosed postpartum haemorrhage following vaginal delivery of a baby or caesarean section will potentially be eligible. The fundamental eligibility criterion is the responsible clinician's 'uncertainty' as to whether or not to use an antifibrinolytic agent in a particular woman with postpartum haemorrhage. Treatment will entail a dose of tranexamic acid (1 gram by intravenous injection) or placebo (sodium chloride 0.9%) will be given as soon as possible after randomisation. A second dose may be given if after 30 minutes bleeding continues, or if it stops and restarts within 24 hours after the first dose. The main analyses will be on an 'intention to treat' basis, irrespective of whether the allocated treatment was received or not. Subgroup analyses for the primary outcome will be based on type of delivery; administration or not of prophylactic uterotonics; and on whether the clinical decision to consider trial entry was based primarily on estimated blood loss alone or on haemodynamic instability. A study with 15,000 women will have over 90% power to detect a 25% reduction from 4% to 3% in the primary endpoint of mortality or hysterectomy.

Trial registration

Current Controlled Trials: ISRCTN76912190 and Clinicaltrials.gov ID: NCT00872469     

Rh isoimmunization during pregnancy: antenatal prophylaxis.

Of 3533 Rh-negative women who began a pregnancy without detectable Rh antibodies, 62 (1.8%) demonstrated evidence of Rh isoimmunization during pregnancy or within 3 days after delivery. All denied transfusions as well as abortions or previous pregnancies not followed by the administration of Rh immune globulin. Rh isoimmunization during pregnancy or within 3 days after delivery, which will not be prevented by the administration of Rh immune globulin after delivery, is the most important cause of residual Rh isoimmunization. A clinical trial of antenatal administration of Rh immune globulin, initially at 34 weeks''s and subsequently at 28 and 34 weeks'' gestation, in 1357 Rh-negative pregnant women who were delivered of Rh-positive babies, was effective in preventing the development of Rh isoimmunization during pregnancy or within 3 days after delivery. Antenatal prophylaxis with Rh immune globulin will be necessary if the incidence of Rh isoimmunization is to be reduced to its lowest possible level. Antenatal prophylaxis at 28 weeks'' gestation is now an insured service in Manitoba.     

Effect of socioeconomic deprivation and health service utilisation on antepartum and intrapartum stillbirth: population cohort study from rural Ghana

BACKGROUND: No studies have examined the effect of socioeconomic deprivation on antepartum and intrapartum stillbirths in the poorest women in low income countries. METHODOLOGY/ PRINCIPAL FINDINGS: This study used data from a prospective population based surveillance system involving all women of childbearing age and their babies in rural Ghana. The primary objective was to evaluate associations between household wealth and risk of antepartum and intrapartum stillbirth. The secondary objective was to assess whether any differences in risk were mediated by utilisation of health services during pregnancy. Data were analysed using multivariable logistic regression. Random effect models adjusted for clustering of women who delivered more than one infant. There were 80267 babies delivered from 1 July 2003 to 30 September 2008: 77666 live births and 2601 stillbirths. Of the stillbirths 1367 (52.6%) were antepartum, 989 (38.0%) were intrapartum and 245 (9.4%) had no data on the timing of death. 94.8% of the babies born in the study (76129/80267) had complete data on all covariates and outcomes. 36 878 (48.4%) of babies were born to women in the two poorest quintiles and 3697 (4.9%) had no pregnancy care. There was no association between wealth and antepartum stillbirths. There was a marked 'dose response' of increasing risk of intrapartum stillbirth with increasing levels of socioeconomic deprivation (adjOR 1.09 [1.03-1.16] p value 0.002). Women in the poorest two quintiles had greater risk of intrapartum stillbirth (adjOR 1.19 [1.02-1.38] p value 0.023) compared to the richest women. Adjusting for heath service utilisation and other variables did not alter results. CONCLUSIONS/ SIGNIFICANCE: Poor women had a high risk of intrapartum stillbirth and this risk was not influenced by health service utilisation. Health system strengthening is required to meet the needs of poor women in our study population.     

Psychosocial and psychological interventions for prevention of postnatal depression: systematic review

Objective To assess the effects of psychosocial and psychological interventions compared with usual antepartum, intrapartum, or postpartum care on the risk of postnatal depression.Data sources Medline, Embase, CINAHL, Cochrane central register of controlled trials, Cochrane pregnancy and childbirth group trials register, Cochrane depression, anxiety, and neurosis trials register, secondary references and review articles, and experts in the field.Study selection All published and unpublished randomised controlled trials of preventive psychosocial or psychological interventions in which the primary or secondary aim was a reduction in the risk of postnatal depression. All trials recruited pregnant women or new mothers less than six weeks postpartum. Eligible studies were abstracted, assessed for methodological quality, and pooled with relative risk for categorical data and weighted mean difference for continuous data.Results Fifteen trials with 7697 women were included. Although there was no overall statistically significant effect on the prevention of postnatal depression in the meta-analysis of all types of interventions (15 trials, n = 7697; relative risk 0.81, 95% confidence interval 0.65 to 1.02), these results suggest a potential reduction in postnatal depression. The only intervention to have a clear preventive effect was intensive postpartum support provided by a health professional (0.68, 0.55 to 0.84). Identifying women “at risk” assisted in the prevention of postnatal depression (0.67, 0.51 to 0.89). Interventions with only a postnatal component were more beneficial (0.76, 0.58 to 0.98) than interventions that incorporated an antenatal component. In addition, individually based interventions were more effective (0.76, 0.59 to 1.00) than group based interventions (1.03, 0.65 to 1.63).Conclusions Diverse psychosocial or psychological interventions do not significantly reduce the number of women who develop postnatal depression. The most promising intervention is the provision of intensive, professionally based postpartum support.     

Changes in the management of labour: 1. Length and management of the second stage.

An analysis of 18,940 deliveries between 1981 and 1984 in a large British obstetric unit showed marked changes in the management of the second stage of labour. These changes included an increase in the length of the second stage (especially among primiparous women), a rise in the rate of spontaneous delivery and a large decline in the rate of episiotomy. There was no change in neonatal outcome or in the rate of maternal postpartum complications. These findings may have resulted from a more conservative approach to the management of the second stage. They may also reflect a better understanding among obstetric professionals of what constitutes a normal second stage and therefore better decisions about when to act and when to wait.     

Prevention of Rh(D) alloimmunization: a cost-benefit analysis.

The Rh Programme of Nova Scotia was established in 1964 for the prevention and treatment of Rh(D) alloimmunization. The program''s effectiveness in preventing the condition has been established previously. Because of increasing budget restraint in health care we decided to examine the cost-effectiveness of the program by comparing the cost of prevention (office administration fees, program staff salaries and the price of Rh immune globulin) with the cost of health care services required in addition to standard obstetric procedures and neonatal care in 80 cases of Rh(D) alloimmunization treated from 1982 to 1986. Neonatal intensive care accounted for 80.1% of the additional health care expenses; an extra 512 hospital days for such care constituted 65.7% of the total treatment expense. The cost per case prevented ($1495) was 2.7 times less than the cost per case treated ($3986).     

The Incidence of First Venous Thromboembolism in and around Pregnancy Using Linked Primary and Secondary Care Data: A Population Based Cohort Study from England and Comparative Meta-Analysis

Background

Recent linkage between primary and secondary care data has provided valuable information for studying heath outcomes that may initially present in different health care settings. The aim of this study was therefore, twofold: to use linked primary and secondary care data to determine an optimum definition for estimating the incidence of first VTE in and around pregnancy; and secondly to conduct a systematic literature review of studies on perinatal VTE incidence with the purpose of comparing our estimates.

Methods

We used primary care data from the Clinical Practice Research Datalink (CPRD), which incorporates linkages to secondary care contained within Hospital Episode Statistics (HES) between 1997 and 2010 to estimate the incidence rate of VTE in the antepartum and postpartum period. We systematically searched the literature on the incidence of VTE during antepartum and postpartum periods and performed a meta-analysis to provide comparison.

Findings

Using combined CPRD and HES data and a restrictive VTE definition, the absolute rate during the antepartum period and first six weeks postpartum (early postpartum) were 99 (95%CI 85–116) and 468 (95%CI 391–561) per 100,000 person-years respectively. These were comparable to the pooled estimates from our meta-analysis (using studies after 2005) during the antepartum period (118/100,000 person-years) and early postpartum (424/100,000 person-years). When we used only secondary care data to identify VTE events, incidence was lower during the early postpartum period (308/100,000 person-years), whereas relying only on primary care data lead to lower incidence during the time around delivery, but higher rates during the postpartum period (558/100,000 person-years).

Conclusion

Using combined CPRD and HES data gives estimates of the risk of VTE in and around pregnancy that are comparable to the existing literature. It also provides more accurate estimation of the date of VTE diagnosis which will allow risk stratification during specific pregnancy and postpartum periods.     

Outcome of planned home births in an inner city practice.

OBJECTIVE--To assess the outcome of pregnancy for women booking for home births in an inner London practice between 1977 and 1989. DESIGN--Retrospective review of practice obstetric records. SETTING--A general practice in London. SUBJECTS--285 women registered with the practice or referred by neighbouring general practitioners or local community midwives. MAIN OUTCOME MEASURES--Place of birth and number of cases transferred to specialist care before, during, and after labour. RESULTS--Of 285 women who booked for home births, eight left the practice area before the onset of labour, giving a study population of 277 women. Six had spontaneous abortions, 26 were transferred to specialist care during pregnancy, another 26 were transferred during labour, and four were transferred in the postpartum period. 215 women (77.6%, 95% confidence interval 72.7 to 82.5) had normal births at home without needing specialist help. Transfer to specialist care during pregnancy was not significantly related to parity, but nulliparous women were significantly more likely to require transfer during labour (p = 0.00002). Postnatal complications requiring specialist attention were uncommon among mothers delivered at home (four cases) and rare among their babies (three cases). CONCLUSIONS--Birth at home is practical and safe for a self selected population of multiparous women, but nulliparous women are more likely to require transfer to hospital during labour because of delay in labour. Close cooperation between the general practitioner and both community midwives and hospital obstetricians is important in minimising the risks of trial of labour at home.