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.

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.

Cardiac function in fetuses of poorly-controlled pre-gestational diabetic pregnancies--a pilot study.

OBJECTIVE: Cardiac impairment is frequently found in babies of diabetic mothers. It is still controversial whether this is due to poor glucose control. The aim of this study is to compare the cardiac function in fetuses of well- and poorly-controlled pre-gestational diabetic pregnancy in third trimester. METHODS: Women with type 1 pre-gestational diabetes were enrolled at 30-32 weeks. Cardiac size and interventricular septal wall thickness were measured by M-mode at end-diastolic phase. The right and left ventricular ejection fractions were calculated. At the mitral and tricuspid valves inflow, the ratio between early ventricular filling and active atrial filling (E/A) at both atrioventricular valves were measured by Doppler echocardiography. Peak velocities of ascending aorta and pulmonary artery were assessed. The angle of isonation was kept at <20 degrees. Women with poorly-controlled diabetes (HbA1c>6.5%) were compared with those with satisfactorily controlled diabetes (HbA1c < or = 6.5%). RESULTS: A total of 21 women with pre-gestational diabetes were recruited for this study. Eight women with well-controlled diabetes were compared with 9 women who had poorly-controlled diabetes. HbA1c in the poorly-controlled group was 7.3% and in the well-controlled group it was 5.4% (p<0.001). There was no difference between the two groups in cardiac size, interventricular septal wall thickness, ejection fraction, aorta and pulmonary artery peak flow velocities. The right atrioventricular E/A ratio was significantly lower among the poorly-controlled diabetic pregnancies (0.71 vs. 0.54; p<0.05). CONCLUSION: Fetuses of poorly-controlled diabetic mothers had a lower right atrioventricular E/A ratio. This may be due to metabolic acidosis, non-hypertrophic cardiac dysfunction or fetal polycythemia.

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.

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.

Routine ultrasound screening in diabetic pregnancies.

OBJECTIVES: To assess the detection rate of congenital fetal malformations and specific problems related to routine ultrasound screening in women with pre-existing diabetes. METHODS: A retrospective study was carried out to assess the performance of routine ultrasound screening in women with pre-existing diabetes (Types 1 and 2) within a tertiary institution. The incidence, type and risk factors for congenital fetal malformations were determined. The detection rate of fetal anomalies for diabetic women was compared with that for the low-risk population. Factors affecting these detection rates were evaluated. RESULTS: During the study period, 12 169 low-risk pregnant women and 130 women with pre-existing diabetes had routine ultrasound screening performed within the institution. A total of 10 major anomalies (7.7%) and three minor anomalies (2.3%) were present in the fetuses of the diabetic women. Central nervous system and cardiovascular system anomalies accounted for 60% of the major anomalies. Periconceptional hemoglobin A1c of more than 9% was associated with a high prevalence of major anomalies (143/1000). Women who had fetuses with major anomalies had a significantly higher incidence of obesity (78% vs. 37%; P < 0.05). Ultrasound examination of these diabetic pregnancies showed high incidences of suboptimal image quality (37%), incomplete examinations, and repeat examinations (17%). Compared to the 'low-risk' non-diabetic population from the same institution, the relative risk for a major congenital anomaly among the diabetic women was 5.9-fold higher (95% confidence interval, 2.9-11.9). The detection rate for major fetal anomalies was significantly lower for diabetic women (30% vs. 73%; P < 0.01), and the mean body mass index for the diabetic group was significantly higher (29 vs. 23 kg/m2; P < 0.001). CONCLUSION: The incidence of congenital anomalies is higher in diabetic pregnancies. Unfortunately, the detection rate for fetal anomalies by antenatal ultrasound scan was significantly worse than that for the low-risk population. This is likely to be related to the maternal body habitus and unsatisfactory examinations. Methods to overcome these difficulties are discussed.

Anticoagulation in pregnancy and the puerperium.

For the management of acute thrombotic events in pregnancy therapeutic doses of low molecular weight heparins (LMWH) may be used, unless the shorter half-life of intravenous unfractionated heparin (UH) and predictable reversibility by protamine are important. Treatment should be continued up until delivery and into the puerperium. Pregnant women who have had an acute thrombotic event should be delivered by a specialist team. In the case of recent thrombosis, delivery should be planned and the time during which anticoagulation therapy is ceased around the time of delivery should be minimised. Therapeutic doses of LMWH contraindicate the use of regional anaesthesia, and a switch to intravenous UH before delivery may allow greater flexibility in this regard. Prophylactic doses of LMWH can be used to reduce the risk of recurrent thromboembolic events in pregnancy. The regimen used will depend on the previous history, the family history and the presence of risk factors, including the genetic and acquired causes of thrombophilia. Women with mechanical heart valves are at high risk during pregnancy and require therapeutic anticoagulation throughout pregnancy under the direction of experienced specialists. Low-dose aspirin can reduce the risk of recurrent pre-eclampsia by about 15%, but the role of UH and LMWH in the prevention of recurrent miscarriage or obstetric complications associated with uteroplacental insufficiency is still uncertain.

Sonographic estimation of fetal weight in macrosomic fetuses: diabetic versus non-diabetic pregnancies.

The objective of this study is to compare the accuracy of sonographic estimation of fetal weight of macrosomic babies in diabetic vs non-diabetic pregnancies. All babies weighing 4,000 g or more at birth, and who had ultrasound scans performed within one week of delivery were included in this retrospective study Pregnancies with diabetes mellitus were compared to those without diabetes mellitus. The mean simple error (actual birthweight--estimated fetal weight); mean standardised absolute error (absolute value of simple error (g)/actual birthweight (kg)); and the percentage of estimated birthweight falling within 15% of the actual birthweight between the two groups were compared. There were 9,516 deliveries during the study period. Of this total 1,211 (12.7%) babies weighed 4,000 g or more. A total of 56 non-diabetic pregnancies and 19 diabetic pregnancies were compared. The average sonographic estimation of fetal weight in diabetic pregnancies was 8% less than the actual birthweight, compared to 0.2% in the non-diabetic group (p < 0.01). The estimated fetal weight was within 15% of the birthweight in 74% of the diabetic pregnancies, compared to 93% of the non-diabetic pregnancies (p < 0.05). In the diabetic group, 26.3 % of the birthweights were underestimated by more than 15 %, compared to 5.4% in the non-diabetic group (p < 0.05). In conclusion, the prediction accuracy of fetal weight estimation using standard formulae in macrosomic fetuses is significantly worse in diabetic pregnancies compared to non-diabetic pregnancies. When sonographic fetal weight estimation is used to influence the mode of delivery for diabetic women, a more conservative cut-off needs to be considered.

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.

Clinical value of real-time tertiary fetal ultrasound consultation by telemedicine: preliminary evaluation.

Congenital fetal abnormalities are major causes of perinatal mortality and morbidity. The performance of ultrasound in the diagnosis and assessment of fetal anomalies varies enormously between tertiary referral centers and general units. Telemedicine offers a chance for tertiary realtime ultrasound consultations using standard telephone lines for remote sites. Preliminary investigations by our group have shown that real-time transmission of fetal ultrasound images over long distances via telephone (integrated systems digital network [ISDN]) lines is technically feasible. A live link of up to 2 Mb/s was established between Mater Mothers Hospital in Brisbane and Kirwan Hospital for Women in Townsville, which are 1,500 km apart. The objective of the current study was to evaluate the clinical value of a tertiary teleultrasound consultation service. Patients requiring tertiary ultrasound consultations were recruited from North Queensland. Clinicians from the referral site established an initial diagnosis and management plan. Using standard ISDN lines, the real-time ultrasound images were transmitted to the maternal fetal medicine subspecialists in Brisbane. The ultrasound examination was completed under the direction of the subspecialist. The subspecialist explained the findings to the patient at the end of the session, and discussed the diagnosis and management plans with the clinicians involved. Any diagnosis and management variations were classified into minor and major upon agreement by the two teams of clinicians involved. The clinicians and patients in Townsville rated the value of the consultation, and the subspecialists rated the confidence of their diagnoses on five-point scales. Pregnancy outcomes were obtained and the data analyzed. Over a 3-month period, 24 teleultrasound consultations were carried out. The indications for referral were: assessment of growth restriction/fetal wellbeing in the third trimester (6); detailed assessment for high-risk patients (5); evaluation of markers for anomalies (5); isolated fetal anomalies (1); and complex fetal problems such as twin/twin transfusion, multiple anomalies, etc. (7). Overall, the consultations resulted in some modifications to the clinical diagnosis in 45.8% of the cases, and modifications to the management plan in 33.3% of the cases (about half of which were minor variations). The clinicians rated the teleconsultations highly (mean rating 4.7, SD 0.44). The patients also rated the consultations highly, and were comfortable that their privacy and confidentiality were maintained during the consultation. The subspecialists were confident in making their diagnoses by telemedicine (mean score for confidence 4.2, SD 0.43). All the pregnancies have now been completed, with all antenatal diagnoses confirmed to be correct postnatally. Tertiary real-time ultrasound consultation by telemedicine is not only technically feasible, it is welcomed by the clinicians and patients involved. It also contributes to diagnostic and management differences. Larger scale clinical trials are needed to evaluate the true benefits and costs involved. The social benefits in bridging the healthcare gap between the country and the city, and in enabling patients in remote areas to stay close to their family under times of stress is well recognized by all involved.

Management of essential thrombocythaemia during pregnancy.

Essential thrombocythaemia is a rare myeloproliferative disorder that often presents with haemorrhagic or thrombotic complications. It may be detected incidentally in an asymptomatic younger adult and there are only a few case reports of essential thrombocythaemia in pregnant women. The risks posed by essential thrombocythaemia during pregnancy and its optimal management are uncertain. To determine if there is increased incidence of obstetric complications seen in women who have essential thrombocythaemia, we collected a large case series from a number of tertiary obstetric units in Australia and New Zealand. There were 30 pregnancies in 12 women who had essential thrombocythaemia. There were 17 live births (57%), 7 stillbirths (23%), 5 miscarriages (17%) and 1 ectopic (3%). Five pregnancies were complicated by placental abruption. When the outcomes of those women who received treatment with aspirin or interferon were compared to those that did not receive any treatment, there was a trend towards a higher livebirth rate (79% v. 38%, p = 0.06). Seven women were treated with aspirin and 5 had successful outcomes with no fetal complications. Four women were treated with alpha-interferon which reduced their platelet counts and all had successful outcomes with no fetal complication. These findings suggest that there is a high incidence of miscarriage, stillbirth and abruption in women with essential thrombocythaemia. Their pregnancies should be carefully monitored. Treatment with low dose aspirin and/or the use of alpha-interferon may be associated with an improved pregnancy outcome.

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.

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.

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.