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1.  Does the risk of cerebral palsy increase or decrease with increasing gestational age? 
Background
It is generally accepted that the risk of cerebral palsy decreases with increasing gestational age of live born infants. However, recent studies have shown that cerebral palsy often has prenatal antecedents including congenital malformations, vascular insults and maternal infection. Cerebral palsy is therefore better viewed as occurring among fetuses, rather than among infants. We explored the epidemiologic implications of this change in perspective.
Methods
We used recently published data from Shiga Prefecture, Japan and from North-East England to examine the pattern of gestational age-specific rates of cerebral palsy under these alternative perspectives. We first calculated gestational age-specific rates of cerebral palsy as per convention, by dividing the number of cases of cerebral palsy identified among live births within any gestational age category by the number of live births in that gestational age category. Under the alternative formulation, we calculated gestational age-specific rates of cerebral palsy by dividing the number of cases of cerebral palsy identified among live births within any gestational age category by the number of fetuses who were at risk of being born at that gestation and being afflicted with cerebral palsy.
Results
Under the conventional formulation, cerebral palsy rates decreased with increasing gestational age from 63.9 per 1,000 live births at <28 weeks gestation to 0.9 per 1,000 live births at 37 or more weeks gestation. When fetuses were viewed as potential candidates for cerebral palsy, cerebral palsy rates increased with increasing gestational age from 0.08 per 1,000 fetuses at risk at <28 weeks gestation to 0.9 per 1,000 fetuses at risk at 37 or more weeks gestation.
Conclusions
The fetuses-at-risk approach is the appropriate epidemiologic formulation for calculating the gestational age-specific rate of cerebral palsy from a causal perspective. It shows that the risk of cerebral palsy increases as gestational duration increases. This compelling view of cerebral palsy risk may help refocus research aimed at understanding and preventing cerebral palsy.
doi:10.1186/1471-2393-3-8
PMCID: PMC317470  PMID: 14693037
2.  Ectopic pregnancy rates with day 3 versus day 5 embryo transfer: a retrospective analysis 
Background
Blastocyst transfer may theoretically decrease the incidence of ectopic pregnancy following IVF-ET in view of the decreased uterine contractility reported on day 5. The purpose of our study is to specifically compare the tubal pregnancy rates between day 3 and day 5 transfers.
Methods
A retrospective analysis of all clinical pregnancies conceived in our IVF program since 1998 was performed. The ectopic pregnancy rates were compared for day 3 and day 5 transfers.
Results
There were 623 clinical pregnancies resulting from day 3 transfers of which 22 were ectopic (3.5%). In day 5 transfers, there were 13 ectopic pregnancies out of 333 clinical pregnancies (3.9%). The difference between these rates is not statistically significant (P = 0.8).
Conclusions
Our data suggests that the ectopic pregnancy rate is not reduced following blastocyst transfer compared to day 3 transfer. While there may be several benefits to extended culture in IVF, the decision to offer blastocyst transfer should be made independently from the issue of ectopic pregnancy risk.
doi:10.1186/1471-2393-3-7
PMCID: PMC270025  PMID: 14604439
Blastocyst; Ectopic pregnancy; Embryo transfer; IVF
3.  Critical pathways for the management of preeclampsia and severe preeclampsia in institutionalised health care settings 
Background
Preeclampsia is a complex disease in which several providers should interact continuously and in a coordinated manner to provide proper health care. However, standardizing criteria to treat patients with preeclampsia is problematical and severe flaws have been observed in the management of the disease. This paper describes a set of critical pathways (CPs) designed to provide uniform criteria for clinical decision-making at different levels of care of pregnant patients with preeclampsia or severe preeclampsia.
Methods
Clinicians and researchers from different countries participated in the construction of the CPs. The CPs were developed using the following steps: a) Definition of the conceptual framework; b) Identification of potential users: primary care physicians and maternal and child health nurses in ambulatory settings; ob/gyn and intensive care physicians in secondary and tertiary care levels. c) Structural development.
Results
The CPs address the following care processes: 1. Screening for preeclampsia, risk assessment and classification according to the level of risk. 2. Management of preeclampsia at primary care clinics. 3. Evaluation and management of preeclampsia at secondary and tertiary care hospitals: 4. Criteria for clinical decision-making between conservative management and expedited delivery of patients with severe preeclampsia.
Conclusion
Since preeclampsia continues to be one of the primary causes of maternal deaths and morbidity worldwide, the expected impact of these CPs is the contribution to improving health care quality in both developed and developing countries. The CPs are designed to be applied in a complex health care system, where different physicians and health providers at different levels of care should interact continuously and in a coordinated manner to provide care to all preeclamptic women. Although the CPs were developed using evidence-based criteria, they could require careful evaluation and remodelling according to each system's demands. Additionally, the CPs need to be tested in large-scale, multi-level studies in order to thoroughly examine and evaluate their efficacy and effectiveness.
doi:10.1186/1471-2393-3-6
PMCID: PMC270024  PMID: 14525621
4.  ABFAB. Attachment to the breast and family attitudes to breastfeeding. The effect of breastfeeding education in the middle of pregnancy on the initiation and duration of breastfeeding: a randomised controlled trial [ISRCTN21556494] 
Background
It has proven difficult to reach World Health Organization (WHO) recommendations that infants be exclusively breastfed from birth to six months of age [1,2], yet there is limited knowledge about interventions that are effective in increasing breastfeeding initiation and duration. Particularly lacking is evidence about how to maintain breastfeeding rates in countries which already have a high initiation of breastfeeding. This study aims to determine whether mid-pregnancy breastfeeding education, with a focus on either attitudes to breastfeeding or on technical aspects of breastfeeding, has an effect on rates of breastfeeding initiation and duration. Secondary aims of the study are to: explore what factors might affect the duration of breastfeeding and evaluate the interventions from the participant and childbirth facilitator perspectives.
Methods/Design
A randomised controlled trial (RCT) design will be used. Women having their first baby, and planning to give birth as public patients at the Royal Women's Hospital (RWH), Melbourne, will be approached at 18–20 weeks of pregnancy and invited to participate in the study. Participants will be randomly allocated to a control group or one of two group interventions: a previously designed and trialled tool to teach practical aspects of breastfeeding or an exploration of family attitudes to breastfeeding. The latter was developed and piloted by the investigators in conjunction with the group facilitators, prior to trial commencement. The interventions are planned to take place at 20–25 weeks. Data will be collected by questionnaire at recruitment, at interview in hospital after the birth and by telephone interview six months later. Medical/obstetric outcomes will be obtained from the medical record. The sample size (972) was calculated to identify an increase in breastfeeding initiation from 75 to 85% and an increase from 40 to 50% in breastfeeding at six months.
doi:10.1186/1471-2393-3-5
PMCID: PMC201032  PMID: 12946279
5.  Monochorionic-triamniotic triplet pregnancy after intracytoplasmic sperm injection, assisted hatching, and two-embryo transfer: first reported case following IVF 
Background
We present a case of monochorionic-triamniotic pregnancy that developed after embryo transfer following in vitro fertilization (IVF).
Methods
After controlled ovarian hyperstimulation and transvaginal retrieval of 22 metaphase II oocytes, fertilization was accomplished with intracytoplasmic sperm injection (ICSI). Assisted embryo hatching was performed, and two embryos were transferred in utero. One non-transferred blastocyst was cryopreserved.
Results
Fourteen days post-transfer, serum hCG level was 423 mIU/ml and subsequent transvaginal ultrasound revealed a single intrauterine gestational sac with three separate amnion compartments. Three distinct foci of cardiac motion were detected and the diagnosis was revised to monochorionic-triamniotic triplet pregnancy. Antenatal management included cerclage placement at 19 weeks gestation and hospital admission at 28 weeks gestation due to mild preeclampsia. Three viable female infants were delivered via cesarean at 30 5/7 weeks gestation.
Conclusions
The incidence of triplet delivery in humans is approximately 1:6400, and such pregnancies are classified as high-risk for reasons described in this report. We also outline an obstetric management strategy designed to optimize outcomes. The roles of IVF, ICSI, assisted embryo hatching and associated laboratory culture conditions on the subsequent development of monozygotic/monochorionic pregnancy remain controversial. As demonstrated here, even when two-embryo transfer is employed after IVF the statistical probability of monozygotic multiple gestation cannot be reduced to zero. We encourage discussion of this possibility during informed consent for the advanced reproductive technologies.
doi:10.1186/1471-2393-3-4
PMCID: PMC184457  PMID: 12906712
triplet pregnancy / IVF / monochorionic / cerclage / outcome
6.  A parsimonious explanation for intersecting perinatal mortality curves: understanding the effect of plurality and of parity 
Background
Birth weight- and gestational age-specific perinatal mortality curves intersect when compared across categories of maternal smoking, plurality, race and other factors. No simple explanation exists for this paradoxical observation.
Methods
We used data on all live births, stillbirths and infant deaths in Canada (1991–1997) to compare perinatal mortality rates among singleton and twin births, and among singleton births to nulliparous and parous women. Birth weight- and gestational age-specific perinatal mortality rates were first calculated by dividing the number of perinatal deaths at any given birth weight or gestational age by the number of total births at that birth weight or gestational age (conventional calculation). Gestational age-specific perinatal mortality rates were also calculated using the number of fetuses at risk of perinatal death at any given gestational age.
Results
Conventional perinatal mortality rates among twin births were lower than those among singletons at lower birth weights and earlier gestation ages, while the reverse was true at higher birth weights and later gestational ages. When perinatal mortality rates were based on fetuses at risk, however, twin births had consistently higher mortality rates than singletons at all gestational ages. A similar pattern emerged in contrasts of gestational age-specific perinatal mortality among singleton births to nulliparous and parous women. Increases in gestational age-specific rates of growth-restriction with advancing gestational age presaged rising rates of gestational age-specific perinatal mortality in both contrasts.
Conclusions
The proper conceptualization of perinatal risk eliminates the mortality crossover paradox and provides new insights into perinatal health issues.
doi:10.1186/1471-2393-3-3
PMCID: PMC166132  PMID: 12780942
7.  Characterization of mixed lymphocyte reaction blocking antibodies (MLR-Bf) in human pregnancy 
Background
It is known that during normal pregnancy and after immunotherapy blocking antibodies are developed, these antibodies inhibit mixed lymphocyte reaction and are also anti-mitogenic in nature. Mixed lymphocyte reaction blocking antibodies are specific to the husband's lymphocytes. In the present study an attempt has been made to characterize the mixed lymphocyte reaction blocking antibodies in normal pregnancy and in women with recurrent spontaneous abortion after immunotherapy.
Methods
Serum was obtained from women of different gestational windows of pregnancy (Ist, IInd, IIIrd trimesters and post delivery period of normal pregnancy), recurrent spontaneous aborters from pre and post immunization. Healthy (male and females) controls were screened for the presence of mixed lymphocyte reaction blocking antibodies. The standard mixed lymphocyte reaction technique was used to evaluate the inhibitory effect of serum in the mixed lymphocyte reaction. Each serum was tested for cytotoxic antibodies. Immunoglobulin G and its isotypes were isolated according to the standard protocol.
Results
In the present study we have observed that there was significant inhibition of proliferation response when immunoglobulin G from different trimesters of pregnancy were added to one way mixed lymphocyte reaction or to phytohemagglutinin activated lymphocyte proliferation assay. Similar pattern was seen when immunoglobulin G isolated from adequately immunized women with recurrent spontaneous abortion was used. It was further confirmed that amongst all the isotypes of immunoglobulin G, only immunoglobulin G-3 was found to be positive for the inhibitory effect.
Conclusions
Present study indicates that mixed lymphocyte reaction blocking antibodies are immunoglobulin G-3 in nature. It is developed during pregnancy and also after immunotherapy in women with recurrent spontaneous abortion who subsequently have the successful pregnancy.
doi:10.1186/1471-2393-3-2
PMCID: PMC150574  PMID: 12593676
8.  Prenatal diagnosis of Wolf-Hirschhorn syndrome (4p-) in association with congenital hypospadias and foot deformity 
Background
Wolf-Hirschhorn syndrome is caused by distal deletion of the short arm of chromosome 4 (4p-). We report a case in which intrauterine growth restriction, hypospadias and foot deformity were detected by prenatal ultrasound examination at 29 weeks of gestation.
Case Presentation
A 31-year-old gravida 2 partus 1 woman was referred at 29 weeks' gestation with suspicion of intrauterine growth restriction. Sonographic examination revealed deformity of the right lower limb and undescended testes with an irregular distal penis. A cordocentesis was performed and chromosome analysis revealed a 46,XY,del(4)(p14) karyotype.
Conclusion
The prenatal detection of intrauterine growth restriction, hypospadias and foot deformity should lead doctors to suspect the presence of Wolf-Hirschhorn syndrome.
doi:10.1186/1471-2393-3-1
PMCID: PMC149368  PMID: 12546710
Prenatal diagnosis; Wolf-Hirschhorn syndrome

Results 1-8 (8)