Low first-trimester PAPP-A in IVF (fresh and frozen-thawed) pregnancies, likely due to a biological cause.

PURPOSE: The purpose of this study is to confirm a difference in the first-trimester screen maternal biochemistry and false-positive rates (FPR) between pregnancies conceived spontaneously and those conceived via assisted reproductive technologies (ART). METHODS: Retrospective analysis of the complete population of women (17,889 pregnancies) who had undergone first-trimester screening between January 2004 and September 2009 at three private ultrasound clinics in Queensland, Australia was used in the study. The age, gestation, method of conception, ultrasound markers, biochemistry markers (PAPP-A, fß-hCG), and type of biochemical analyzer platform (Brahms Kryptor, Immulite 2000) data was collated. Univariate analysis of variance (ANOVA), Spearman's rank nonparametric correlation analysis, and Binary Logistic Regression analysis were used to analyze data. Spontaneous pregnancies were used as controls. Results were considered significant when the p value was less than 0.05. RESULTS: After exclusions, 16,363 singleton pregnancies, including 1543 conceived via ART, were analyzed. Results from the two biochemistry platforms, Brahms Kryptor and Immulite 2000 were significantly different (p < 0.001); thus, the data was divided for analysis purposes. PAPP-A was universally significantly lower in IVF pregnancies compared to spontaneously conceived pregnancies (p < 0.001). Using the Brahms Kryptor platform, ICSI was associated with significantly decreased PAPP-A (p < 0.046), and a significantly increased FPR (p = 0.012). CONCLUSIONS: Consistent with previous studies IVF pregnancies had significantly lower PAPP-A levels supporting the need to appropriately adjust the combined first-trimester screening (cFTS) risk algorithm for IVF conceptions. The Brahms Kryptor and Immulite 2000 platforms are significantly different; however, the universally lower PAPP-A findings support the hypothesis that the lower PAPP-A is due to a biological cause.

Prenatal administration of progesterone for preventing preterm birth.

BACKGROUND: Preterm birth is the major complication of pregnancy associated with perinatal mortality and morbidity and occurs in up to 6% to 10% of all births. Administration of progesterone for the prevention of preterm labour has been advocated. OBJECTIVES: To assess the benefits and harms of progesterone administration during pregnancy in the prevention of preterm birth. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Specialised Register of Controlled Trials (March 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2004), MEDLINE (1965 to January 2005), EMBASE (1988 to August 2004), and Current Contents (1997 to August 2004). SELECTION CRITERIA: All published and unpublished randomised controlled trials, in which progesterone was given by any route for preventing preterm birth. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Collaboration and the Cochrane Pregnancy and Childbirth Group were used. Evaluation of methodological quality and trial data extraction were undertaken independently by two authors. Results are presented using relative risk with 95% confidence intervals. MAIN RESULTS: For all women administered progesterone, there was a reduction in the risk of preterm birth less than 37 weeks (six studies, 988 participants, relative risk (RR) 0.65, 95% confidence interval (CI) 0.54 to 0.79) and preterm birth less than 34 weeks (one study, 142 participants, RR 0.15, 95% CI 0.04 to 0.64). Infants born to mothers administered progesterone were less likely to have birthweight less than 2500 grams (four studies, 763 infants, RR 0.63, 95% CI 0.49 to 0.81) or intraventricular haemorrhage (one study, 458 infants, RR 0.25, 95% CI 0.08 to 0.82). There was no difference in perinatal death between women administered progesterone and those administered placebo (five studies, 921 participants, RR 0.66, 95% CI 0.37 to 1.19). There were no other differences reported for maternal or neonatal outcomes. AUTHORS' CONCLUSIONS: Intramuscular progesterone is associated with a reduction in the risk of preterm birth less than 37 weeks' gestation, and infant birthweight less than 2500 grams. However, other important maternal and infant outcomes have been poorly reported to date, with most outcomes reported from a single trial only (Meis 2003). It is unclear if the prolongation of gestation translates into improved maternal and longer-term infant health outcomes. Similarly, information regarding the potential harms of progesterone therapy to prevent preterm birth is limited. Further information is required about the use of vaginal progesterone in the prevention of preterm birth.

Long term outcome of twin-twin transfusion syndrome.

AIMS: To compare the perinatal mortality and morbidity of infants with twin-twin transfusion syndrome (TTTS) with those of gestation matched twin controls and to assess the neurodevelopmental outcome of surviving twins with TTTS. METHODS: A cohort of 17 consecutive pregnancies with TTTS was enrolled over three years together with gestation matched twin pregnancies unaffected by TTTS. Serial amnioreduction for the TTTS pregnancies was performed as appropriate. Perinatal death and neonatal morbidities were recorded for both the TTTS cohort and controls. The TTTS survivors had neurodevelopmental follow up to at least 2 years of age. RESULTS: In 12 of the pregnancies, serial amniocenteses were performed, but, in five, the infants were born before intervention. The mean gestational age at delivery was 29.1 weeks (range 23-36). There were five intrauterine deaths in the TTTS cohort and six neonatal deaths (survival 68%). In the control group, there was one intrauterine death and five neonatal deaths (survival 82%). Infants in the TTTS group had a greater requirement for inotropes (p = 0.04) and a higher incidence of renal failure (p = 0.005). Periventricular leucomalacia and cerebral atrophy were seen in 17% of the TTTS group, but none of the controls (p = 0.03). The 23 surviving TTTS infants were all followed up, with 22% having significant neurological morbidity: cerebral palsy and global developmental delay. CONCLUSIONS: Twins with TTTS have high perinatal mortality and neonatal morbidity, and long term neurodevelopmental morbidity in survivors is high. Further investigation into the pathogenesis and management of TTTS is required.

Uterine artery waveform as a predictor of pregnancy outcome in women with underlying renal disease.

To investigate the use of uterine artery flow velocity waveforms in predicting gestational hypertension (GH), preeclampsia (PE) and intrauterine growth retardation (IUGR), Colour Doppler ultrasound of the uterine arteries was performed at 19-24 weeks gestation in 51 women with known renal disease. On four consecutive waveforms, peak systolic (A), end-diastolic (B) and early diastolic (C) velocities were measured. Resistance index (RI) was calculated as (A-B)/A, and the severity of the waveform notch expressed as the AC ratio (A/C). Gestational hypertension was defined as a blood pressure (BP) > or = 140/90 mmHg with an increase of at least 15 mmHg in diastolic BP. PE included women with gestational hypertension and proteinuria > 300 mg/24 h or a doubling of early gestation protein excretion. IUGR was defined as a birthweight less than the 10th percentile for gestation. RI and/or AC ratio in 14 women (27%) exceeded the 90th percentile for gestational age of our low risk control population. Of the women with an abnormal test, 11 (79%) developed complications, 8 (57%) developed GH or PE, 3 (21%) IUGR alone, 2 (14%) GH and IUGR, and in one women intrauterine fetal death of an IUGR infant occurred, and 3 (21%) had an uncomplicated pregnancy. Of the women with a normal test, 34 (92%) had an uncomplicated pregnancy, and only 3 (8%) developed GH or IUGR. In summary, uterine artery waveform indices at 19-24 weeks gestation may be useful for the prediction of pregnancy complications in woman with underlying renal disease.

Family history of pre-eclampsia as a predictor for pre-eclampsia in primigravidas.

OBJECTIVE: To assess the clinical utility of knowledge of a family history of pre-eclampsia as a predictor for the development of pre-eclampsia in primigravid women. METHODS: 368 primigravid women were prospectively recruited from the outpatients department of an obstetric teaching hospital. Details of any family history of pre-eclampsia were obtained from the women and their subsequent obstetric outcomes were observed. RESULTS: Of 368 primigravid women, 34 (9.2%) developed pre-eclampsia. Eighteen (4.9%) women of the total group stated that they had a mother (12), sister (five) or both (one) who had had pre-eclampsia. Of these 18 women, five (27.8%) developed pre-eclampsia. Of the women who had no family history, 29 (8.3%) developed pre-eclampsia (relative risk, RR = 3.4; 95% CI, 1.5-7.6; P = 0.018). Four (22.2%) of the women with a positive family history developed severe pre-eclampsia compared to 18 (5.1%) with a negative family history (RR = 4.3; 95% CI, 1.6-11.5; P = 0.017). CONCLUSIONS: In a primigravida, a family history of pre-eclampsia is associated with a fourfold increased risk of severe pre-eclampsia. This clinical history identifies a group who warrant close clinical surveillance during pregnancy and who may be suitable for trials of prophylactic interventions.

Screening for consumptive coagulopathy in preeclampsia.

OBJECTIVE: To identify a practical and cost-effective profile of tests to screen for consumptive coagulopathy in preeclampsia (PE). METHODS: Retrospective analysis of the results of measurements of platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), plasma fibrinogen and D-dimers in 100 patients presenting with PE uncomplicated by other disease or antepartum hemorrhage. Twenty-four patients had pregnancy-induced hypertension only, and 76 hypertension with proteinuria. RESULTS: The incidence of abnormal tests on presentation was raised D-dimers 34%, thrombocytopenia 14%, prolonged APTT 12%, prolonged PT 3%, and low fibrinogen 2%. Prolonged APTT without thrombocytopenia occurred in 8% of patients. In 19 patients with elevation of D-dimers alone, only one showed evidence of consumption of coagulation factors on subsequent testing. CONCLUSIONS: A combination of platelet count and APTT is probably a practical and cost-effective combination to screen for consumptive coagulopathy in PE.

Fetal endoscopic telesurgery using an Internet Protocol connection: clinical and technical challenges.

Until recently, fetoscopic laser surgery to seal the placental anastomoses that cause severe twin-to-twin transfusion syndrome has been available in only a few centres worldwide. The technique typically takes a long time to learn. We have used a dedicated Internet Protocol (IP) connection for tele-education to assist the introduction of fetoscopic laser surgery to Australia. During the implementation of the international telemedicine link, there were multiple clinical and technical problems, which were eventually overcome. The quality of images and of video-sequences was comparable to that supported by an ISDN connection. Pictures of live surgery performed by an expert in Florida, USA, were transmitted and viewed by a novice team in Brisbane, Australia. The Australian team has performed 19 fetoscopic laser operations to date. Preliminary results are comparable to those from centres that have performed over 100 procedures.

Randomized comparison of the quality of realtime fetal ultrasound images transmitted by ISDN and by IP videoconferencing.

We compared the quality of realtime fetal ultrasound images transmitted using ISDN and IP networks. Four experienced obstetric ultrasound specialists viewed standard recordings in a randomized trial and rated the appearance of 30 fetal anatomical landmarks, each on a seven-point scale. A total of 12 evaluations were performed for various combinations of bandwidths (128, 384 or 768 kbit/s) and networks (ISDN or IP). The intraobserver coefficient of variation was 2.9%, 5.0%, 12.7% and 14.7% for the four observers. The mean overall ratings by each of the four observers were 4.6, 4.8, 5.0 and 5.3, respectively (a rating of 4 indicated satisfactory visualization and 7 indicated as good as the original recording). Analysis of variance showed that there were no significant interobserver variations nor significant differences in the mean scores for the different types of videoconferencing machines used. The most significant variable affecting the mean score was the bandwidth used. For ISDN, the mean score was 3.7 at 128 kbit/s, which was significantly worse than the mean score of 4.9 at 384 kbit/s, which was in turn significantly worse than the mean score of 5.9 at 768 kbit/s. The mean score for transmission using IP was about 0.5 points lower than that using ISDN across all the different bandwidths, but the differences were not significant. It appears that IP transmission in a private (non-shared) network is an acceptable alternative to ISDN for fetal tele-ultrasound and one deserving further study.

Minimum requirements for remote realtime fetal tele-ultrasound consultation.

We studied the transmission bandwidth required for accurate diagnoses when performing realtime fetal tele-ultrasound consultations. The study was divided into three phases. In phase I, three experienced clinicians evaluated the quality of ultrasound images transmitted at various bandwidths (internally looped back within Brisbane) using eight commercially available codecs at random. The two codecs that performed best proceeded to phase 2, in which a realtime video-link of up to 2 Mbit/s was set up between Brisbane and Townsville (1,500 km apart). Testing with a standard video-tape was performed at seven different bandwidths selected at random, with four clinicians (who were blinded to the equipment and bandwidths used). The optimum line rates for transmission were determined, and testing was then performed using these line rates for fetuses with various anomalies (phase 3). The results showed significant differences in performance according to bandwidths used, but not according to observers. Bandwidths were grouped into three levels. At level I (256 kbit/s) the performance was significantly worse than at level II (384, 512 or 768 kbit/s), which was in turn worse than that at level III (1, 1.5 or 2 Mbit/s). However, within each level, performance at one bandwidth was not significantly different from that at the others. The most cost-effective transmission rates therefore appeared to be 384 kbit/s and 1 Mbit/s. Further testing with fetuses affected by various anomalies confirmed that the majority could be diagnosed using a 384 kbit/s link, with slight improvement in evaluation when the bandwidth was increased to 1 Mbit/s.

Linking community programs in environment to programs in population: towards sustainable communities that sustain sanctuaries.

PIP: This article briefly reviews several nongovernmental organization (NGO) programs that address environmental and population issues. A framework is constructed that identifies how linked programs are supposed to work. The potential for sustainable communities is explored. It is concluded that sanctuaries in developing countries will not survive unless population in surrounding communities is stabilized and the economic and ecological relationships between the community and the sanctuary ecosystem are sustainable. In developed countries resource needs must be identified in regional planning in order for environmental protection to occur. The author finds that NGOs can be instrumental in securing community participation in environmental protection. NGOs operating in Chiapas, Mexico, provide management assistance and public health and family planning awareness to displaced indigenous farmers and conservative professionals. Another NGO outside the Ranthambhore National Park in Rajasthan, India, works to promote alternative fuel and grazing sources among local farmers. Near Chautara, in Nepal, farmers are aided by NGOs in laying sanitary water pipes, which reduces the amount of women's time required for fetching water and increases the amount of time women can spend gardening or getting involved in environmental projects. NGO efforts that reduce women's time absorbed by domestic burdens help women fulfill family planning desires and allow for greater investment in the education of children. Environmental sustainability will be dependent on family planning and other population-related processes and on the awareness that public health is an environmental issue. Opposition to integrated environment and population programs stems from donor opposition, opposition to investment in low-density areas, and a priority on biodiversity issues over development of public health services near sanctuaries. This paper was presented at an international forum at the George Washington University before the 1994 Cairo conference.^ieng

A review of eclampsia in Melbourne: 1978-1992.

A retrospective review of all cases of eclampsia diagnosed at 3 obstetric teaching hospitals in Melbourne from January, 1978 to December, 1992 was undertaken. Ninety cases were identified; there were 5 maternal deaths and 17 perinatal deaths. Severe maternal morbidity such as pulmonary oedema, acute renal failure or HELLP syndrome was found in 26%. Significant maternal thrombocytopenia (< 100 x 10(9)/L) was found in 50% and 35% had abnormal maternal liver function tests. Forty six women received magnesium sulphate for treatment of eclampsia and of these 3 had further seizures compared to 4 of 18 who received phenytoin (odds ratio 0.24 (0.04-1.52) X2, p = 0.09). Eclampsia remains a significant complication of pregnancy with high maternal and perinatal mortality and morbidity. Results of this study show a trend that is in agreement with recent randomized controlled trials which demonstrate a reduced incidence of seizures and maternal and fetal complications with the use of magnesium sulphate. The results of these recent trials suggest that magnesium sulphate should be the drug of choice in the prevention and treatment of eclampsia.

Antepartum and postpartum complications of twin-twin transfusion.

Twin-twin transfusion is a condition that was previously associated with close to a 100% perinatal mortality. Recent reports suggest that a survival rate of about 60% can be achieved with serial amniocentesis and modern neonatal care. However, it is now apparent that the survivors of this condition have multisystem complications that can result in neonatal mortality and long-term morbidity. Fourteen cases of twin-twin transfusion were examined to determine the antenatal findings that may predict the postnatal outcomes of these infants. The overall survival was 61% (17 of 28). The mean gestation at diagnosis was 23.0 weeks (range 18-34 weeks) and the mean gestation at delivery was 29.0 weeks (range 23-37 weeks). The mean number of amniocenteses was 2.9 and the average total volume of amniotic fluid removed was 6,114 mL. Different patterns of complications were seen in the donor and recipient twins. Hypertrophic cardiomyopathy affected 9 of the recipient twins. Anuria/oliguria was found in 4 of the donor twins and none of the recipients. Periventricular leukomalacia was found in 8 twins and 7 also had mild ventriculomegaly; of the surviving 17 twins, 5 had either periventricular leukomalacia, mild ventriculomegaly or both. Amniotic fluid leakage and perforation of the intervening membrane subsequent to serial amniocentesis were seen in 5 cases. Severe intrauterine growth retardation and abnormal cardiotocographs were a common feature. These complications directly resulted in neonatal mortality and long-term morbidity in the survivors. Not all complications were detected antenatally and the severity was not able to be anticipated.

Human population in the biodiversity hotspots.

Biologists have identified 25 areas, called biodiversity hotspots, that are especially rich in endemic species and particularly threatened by human activities. The human population dynamics of these areas, however, are not well quantified. Here we report estimates of key demographic variables for each hotspot, and for three extensive tropical forest areas that are less immediately threatened. We estimate that in 1995 more than 1.1 billion people, nearly 20% of world population, were living within the hotspots, an area covering about 12% of Earth's terrestrial surface. We estimate that the population growth rate in the hotspots (1995-2000) is 1.8% yr(-1), substantially higher than the population growth rate of the world as a whole (1.3% yr(-1)) and above that of the developing countries (1.6% yr(-1)). These results suggest that substantial human-induced environmental changes are likely to continue in the hotspots and that demographic change remains an important factor in global biodiversity conservation. The results also underline the potential conservation significance of the continuing worldwide declines in human fertility and of policies and programs that influence human migration.

Factors influencing the prenatal detection of structural congenital heart diseases.

OBJECTIVE: To assess the factors influencing the prenatal detection rate of structural congenital heart diseases (CHDs). METHODS: A retrospective study was conducted at a major obstetric hospital in Australia between 1 January 1996 and 30 June 1999. The medical records of all fetuses and infants born with CHD, except those with isolated patent ductus arteriosus or secundum atrial septal defect, were reviewed. Only pregnancies that had prenatal ultrasound scan assessments for morphological surveys were included. The following factors that may influence the detection rate were assessed: complexity of the lesions; experience of the sonographers (performance in tertiary versus non-tertiary institutions); presence of other structural or chromosomal anomalies; and maternal body mass index (BMI). RESULTS: The incidence of structural CHD in this series, excluding cases referred from other hospitals, was 7.0 per 1000 (179/25 529). Of the 179 pregnancies with CHD, 151 had prenatal ultrasound scans and were included in the study. The overall detection rate for CHDs in this series was 40.4%. The detection rate for isolated septal defects was poor (13.7%). The detection rates were significantly higher for complex lesions (54%), for lesions with concomitant septal defects (66.7%), and for lesions with abnormal four-chamber views (62.9%). The detection rate was also higher if the scan was performed in the tertiary institution, and if there were other chromosomal or structural anomalies. Maternal BMI did not affect the detection rate in the current series. Stepwise logistic regression analysis showed that three independent variables affecting the detection rate were complexity of the cardiac lesion, experience of the operator, and the detection of chromosomal anomalies. CONCLUSION: A high detection rate for major CHDs can be achieved in a screening setting but there is still room for improvement in scanning skills in the four-chamber view and great-artery analysis in both tertiary and local centers.

Thrombolytic therapy for basilar artery thrombosis in the puerperium.

A case is presented of a woman in whom basilar artery thrombosis developed 14 days post partum. She was successfully treated with intraarterial urokinase. This case demonstrates that complete neurologic recovery can be achieved after recanalization of the basilar artery with thrombolytic therapy.

Fetal echocardiography: are we getting it right?

OBJECTIVE: To determine the diagnostic accuracy of prenatal fetal echocardiography. METHODS: The study was a retrospective chart review of 190 consecutive patients over a 3-year period from November 1998 to February 2002 of all women referred to the Maternal Fetal Medicine unit, Mater Mothers Hospital, for fetal echocardiography. The prenatal diagnosis was compared with the postnatal diagnosis made by postnatal echocardiography, surgical findings or post-mortem. The accuracy of prenatal diagnosis was described on a predetermined 4-point scale. RESULTS: Of the 89 patients, for whom complete diagnostic follow-up was available, there was complete agreement between the prenatal and postnatal diagnosis in 63 cases, minor discrepancies in 25 cases and major disagreement in 1 case. CONCLUSIONS: In experienced hands, fetal echocardiography is accurate and allows medical staff and patients information in order manage a pregnancy appropriately.

Pseudosinusoidal fetal heart rate pattern and fetal anaemia: case report and review.

The association of a pseudosinusoidal fetal heart rate pattern with fetal anaemia is reported. A system of classifying this cardiotocographic feature as minor, intermediate or major is discussed. The clinical correlates of each of these gradings and the differentiation from a true sinusoidal fetal heart rate pattern are presented.