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Objective: To describe the epidemiology of rheumatic heart disease (RHD) in pregnancy in Australia and New Zealand (A&NZ).Design: Prospective population-based study.Setting: Hospital-based maternity units throughout A&NZ.Population: Pregnant women with RHD with a birth outcome of ≥20 weeks of gestation between January 2013 and December 2014.Methods: We identified eligible women using the Australasian Maternity Outcomes Surveillance System (AMOSS). De-identified antenatal, perinatal and postnatal data were collected and analysed.Main Outcome Measures: Prevalence of RHD in pregnancy. Perinatal morbidity and mortality.Results: There were 311 pregnancies associated with women with RHD (4.3/10 000 women giving birth, 95% CI 3.9-4.8). In Australia, 78% were Aboriginal or Torres Strait Islander (60.4/10 000, 95% CI 50.7-70.0), while in New Zealand 90% were Māori or Pasifika (27.2/10 000, 95% CI 22.0-32.3). One woman (0.3%) died and one in ten was admitted to coronary or intensive care units postpartum. There were 314 births with seven stillbirths (22.3/1000 births) and two neonatal deaths (6.5/1000 births). Sixty-six (21%) live-born babies were preterm and one in three was admitted to neonatal intensive care or special care units.Conclusion: Rheumatic heart disease in pregnancy persists in disadvantaged First Nations populations in A&NZ. It is associated with significant cardiac and perinatal morbidity. Preconception planning and counselling and RHD screening in at-risk pregnant women are essential for good maternal and baby outcomes.Tweetable Abstract: Rheumatic heart disease in pregnancy persists in First Nations people in Australia and New Zealand and is associated with major cardiac and perinatal morbidity. [ABSTRACT FROM AUTHOR]

Objective: Our purpose was to determine the transplacental transfer of thyrotropin-releasing hormone at the time of fetal blood sampling.Study Design: Four hundred micrograms of thyrotropin-releasing hormone was given intravenously to 13 pregnant women between 24 and 35 weeks' gestation and maternal-to-fetal transfer of thyrotropin-releasing hormone was determined at fetal blood sampling 1 to 93 minutes later. The fetal thyrotropic response to thyrotropin-releasing hormone was determined by measuring thyroid-stimulating hormone, thyroxine, and prolactin. For comparison, endogenous fetal and maternal levels of thyrotropin-releasing hormone, thyroid-stimulating hormone, thyroxine, and prolactin levels were determined in a further 20 patients undergoing fetal blood sampling between 19 and 35 weeks' gestation. The concentration of thyrotrophin-releasing hormone was measured by radioimmunoassay and thyroid-stimulating hormone, thyroxine, and prolactin by chemiluminescence assay.Results: Thyrotropin-releasing hormone was undetectable in the maternal circulation, whereas endogenous levels were detectable in the fetus from 19 weeks' gestation (median 150; range 50 to 276 pmol/L) and did not correlate with gestational age. After thyrotropin-releasing hormone injection as an intravenous bolus, peak levels in the mother were attained at 3 minutes (50,000 pmol/L). Maximal transplacental transfer of thyrotropin-releasing hormone occurred within 5 minutes of maternal administration but accounted in fetal blood for only 0.01% of initial dose administered (median 250; 30 to 550 pmol/L). Thyrotropin-releasing hormone-stimulated fetal peak thyroid-stimulating hormone levels occurred within 13 minutes and were higher than maternal values (p < 0.001). There was no change in fetal prolactin level with thyrotropin-releasing hormone therapy.Conclusion: Although maternally administered thyrotropin-releasing hormone crosses the placenta sparingly, it still elicits a thyroid-stimulating hormone but not a prolactin response in the human fetus. [ABSTRACT FROM AUTHOR]

The effects of natural and synthetic sex steroids on the proliferation of human decidual capillary endothelial cells in culture were investigated. Oestradiol at 5.0 ng/ml stimulated culture growth. Lower concentrations of oestradiol inhibited growth, while higher concentrations had no effect. Low concentrations of progesterone (5.0 and 10.0 ng/ml) had no effect on growth, while higher concentrations (20.0 and 40.0 ng/ml) inhibited growth. Combinations of oestradiol and progesterone usually reproduced the effects of progesterone alone. 3-Ketodesogestrel and levonorgestrel both inhibited endothelial cell growth, while medroxyprogesterone acetate had no effect. These findings suggest that (i) oestradiol and progesterone have direct effects on endothelial cells and are probably involved in the cyclical growth and regression of endometrial blood vessels in vivo, and (ii) the actions of certain progestogen-only contraceptives may have direct effects on endometrial blood vessels. [ABSTRACT FROM AUTHOR]

Asthma and gestational diabetes mellitus are prevalent during pregnancy and associated with adverse perinatal outcomes. The risk of gestational diabetes mellitus is increased with asthma, and more severe asthma; yet, the underlying mechanisms are unknown. This review examines existing literature to explore possible links.  Asthma and gestational diabetes mellitus are associated with obesity, excess gestational weight gain, altered adipokine levels and low vitamin D levels; yet, it's unclear if these underpin the gestational diabetes mellitus-asthma association. Active antenatal asthma management reportedly mitigates asthma-associated gestational diabetes mellitus risk. However, mechanistic studies are lacking.  Existing research suggests asthma management during pregnancy influences gestational diabetes mellitus risk; this may have important implications for future antenatal strategies to improve maternal-fetal outcomes by addressing both conditions. Addressing shared risk factors, as part of antenatal care, may also improve outcomes. Finally, mechanistic studies, to establish the underlying pathophysiology linking asthma and gestational diabetes mellitus, could uncover new treatment approaches to optimise maternal and child health outcomes., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: PGG reports personal fees from AstraZeneca, GlaxoSmithKline, Novartis and grants from AstraZeneca, GlaxoSmithKline, outside the submitted work., (© The Author(s) 2020.)

Objective: To describe the epidemiology of rheumatic heart disease (RHD) in pregnancy in Australia and New Zealand (A&NZ)., Design: Prospective population-based study., Setting: Hospital-based maternity units throughout A&NZ., Population: Pregnant women with RHD with a birth outcome of ≥20 weeks of gestation between January 2013 and December 2014., Methods: We identified eligible women using the Australasian Maternity Outcomes Surveillance System (AMOSS). De-identified antenatal, perinatal and postnatal data were collected and analysed., Main Outcome Measures: Prevalence of RHD in pregnancy. Perinatal morbidity and mortality., Results: There were 311 pregnancies associated with women with RHD (4.3/10 000 women giving birth, 95% CI 3.9-4.8). In Australia, 78% were Aboriginal or Torres Strait Islander (60.4/10 000, 95% CI 50.7-70.0), while in New Zealand 90% were Māori or Pasifika (27.2/10 000, 95% CI 22.0-32.3). One woman (0.3%) died and one in ten was admitted to coronary or intensive care units postpartum. There were 314 births with seven stillbirths (22.3/1000 births) and two neonatal deaths (6.5/1000 births). Sixty-six (21%) live-born babies were preterm and one in three was admitted to neonatal intensive care or special care units., Conclusion: Rheumatic heart disease in pregnancy persists in disadvantaged First Nations populations in A&NZ. It is associated with significant cardiac and perinatal morbidity. Preconception planning and counselling and RHD screening in at-risk pregnant women are essential for good maternal and baby outcomes., Tweetable Abstract: Rheumatic heart disease in pregnancy persists in First Nations people in Australia and New Zealand and is associated with major cardiac and perinatal morbidity., (© 2019 Royal College of Obstetricians and Gynaecologists.)

Objective: To assess maternal abdominal subcutaneous fat thickness (SFT) measured by ultrasound as an independent predictor of adverse pregnancy outcomes., Design: A prospective longitudinal cohort study performed on pregnancies delivered between 2012 and 2014., Setting: Sydney, Australia., Population: About 1510 pregnant women attending routine obstetric ultrasounds., Methods: Maternal SFT was measured on routine ultrasounds at 11-14 weeks' gestation (SFT1) and 18-22 weeks' gestation (SFT2). SFT measurements were assessed for estimating risks for obesity-related pregnancy outcomes using logistic regression modelling adjusted for maternal age, parity, smoking status and body mass index (BMI)., Main Outcome Measures: Hypertensive disease, gestational diabetes, caesarean section, low birthweight, preterm delivery, neonatal respiratory distress, Apgar scores, and admission to a neonatal intensive care unit., Results: SFT1 and SFT2 were measured on 1461 and 1363 women, respectively. Mean thickness (range) were 21.2 mm (6.9-73.9) for SFT1 and 20.3 mm (7.5-68.0) for SFT2. Complete outcome data were available for 1385 pregnancies. In all, 54% of the women were overweight/obese. The SFT measures decreased from early to mid-pregnancy in overweight/obese women. There was moderate correlation between BMI and SFT1 (R(2) = 0.56) and BMI and SFT2 (R(2) = 0.55). In a multivariate model, SFT1 and SFT2 were better predictors for adverse pregnancy outcomes than BMI., Conclusion: Maternal SFT is a significant independent predictor of adverse pregnancy outcomes. Incorporation of SFT into future models for adverse pregnancy outcome may prove valuable., (© 2015 Royal College of Obstetricians and Gynaecologists.)

This study examined the relationship of cigarette smoking and endothelial function in pregnant women by comparing smokers with nonsmokers. Endothelial function was assessed at 28-32 weeks of gestation by flow-mediated dilatation (FMD) using ultrasound of the brachial artery. The initial FMD was significantly different between the smoking group (n = 21) at 4.0 +/- 2.3, indicating endothelial dysfunction, and the nonsmoking group (n = 20) at 9.7 +/- 4.0 (P < 0.001). After smoking, this difference in the groups persisted. Babies who were growth restricted (<10th percentile) had mothers with a significantly lower FMD, that is endothelial dysfunction. This work demonstrates persistent endothelial dysfunction in smoking pregnant women.

In order to estimate the placental barrier to gas transfer, a novel carbon monoxide (CO) wash-in method was used to estimate the permeability-surface area (PS) product for the transfer of gas across the foetal circulation in the perfused human term placenta. The PS product for CO was 0.0096+/-0.006 ml/s/g or 0.012+/-0.007 ml/s/g using compartmental or Crone-Renkin analysis, respectively. Using this result and a published estimate of the placental capillary surface area, the permeability coefficient to CO across the foetal circulation was found to be approximately 4 x 10(-5)cm/s. This result is compatible with the hypothesis that the foetal circulation of the human placenta imposes a potentially significant barrier to gas transfer.

For many reasons, including the fear of fetal anomaly, the recognition of pregnancy being a normal physiological process and maternal choice, few drugs are prescribed and used during pregnancy. Nevertheless, there are certain common obstetric conditions that are associated with significant maternal and perinatal morbidity and mortality where drugs play an important and necessary part in treatment. These conditions include termination of pregnancy, threatened preterm labour, induction of labour and post-partum haemorrhage. This chapter deals with the role of drug therapy in these obstetric scenarios. A large amount of obstetric clinical trial research has been dedicated to the management of these conditions., (Copyright 2001 Harcourt Publishers Ltd.)

We describe a sporadic case of lethal prenatal onset infantile cortical hyperostosis (Caffey disease), which resulted in early postnatal death at 30 weeks gestation. The mother presented with antepartum haemorrhage and preterm labour. She was found to have polyhydramnios. The infant showed extensive symmetrical diaphyseal subperiosteal cortical thickening throughout the skeleton with short extremities. Hepatomegaly and lung hypoplasia were present. Currently, in the absence of a specific marker, diagnostic ultrasound offers the only prospect of prenatal diagnosis. This diagnosis should be considered in infants with short angulated long bones, where the diaphyses are irregular and echodense, and where there is no sign of fractures.

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.

We present the case of a twin pregnancy in which 1 fetus developed hydrops secondary to supraventricular tachycardia at 30 weeks' gestation. Transplacental flecainide administration successfully treated the condition without evidence of maternal or fetal side-effects. The case raises ethical and possibly legal issues that present when 1 fetus in a twin pregnancy develops a condition the management of which could cause complications to the other twin and/or the mother.

This prospective cross-sectional (10 women on each occasion) and longitudinal (20 women) study investigated activated protein C (APC) ratio in normal pregnancy. The APC ratio was measured at booking, 20, 30 and 36 weeks of gestation, and compared with a sample of normal nonpregnant women. No significant difference was found between APC ratios for pregnant women at any gestation and those of the nonpregnant population in either the longitudinal or cross-sectional studies. There was a significant decrease in APC ratios throughout pregnancy, but in all but one case values remained within the normal nonpregnant range. The APC ratio can therefore be used as a screening test for the factor V Leiden mutation during pregnancy.

Objective: Cord entanglement is a common complication of monoamniotic twins and it is associated with high perinatal mortality. Apart from preterm delivery, no treatment has previously been used to reduce the risks of this complication. We postulated that reducing amniotic fluid volume would stabilize fetal lie and reduce the risk of cord compression., Study Design: Cord entanglement was documented in three cases of monoamniotic twins in the midtrimester. Sulindac was administered to the mother. Amniotic fluid index, fetal urine output, and umbilical artery and ductus arteriosus Doppler waveforms were investigated before and during treatment by use of real-time and pulsed Doppler techniques., Results: Sulindac was associated with a dose-related reduction in amniotic fluid index and fetal urine production without alteration in fetal flow velocity waveforms. Fetal lie stabilized after commencement of treatment. All six twins were delivered with no complications., Conclusion: Medical amnioreduction with sulindac is a new management option in monoamniotic twins to reduce cord complications.

Rectal carcinoma is an uncommon malignancy in pregnancy. Described below is the case report of a patient with rectal carcinoma diagnosed in pregnancy. together with a review of the current literature. When rectal carcinoma is diagnosed at greater than 20 weeks' gestation the timing and mode of delivery became the major obstetric management decisions. The approaches to these problems are outlined in this report.

Serial Doppler ultrasonography in a severely growth-restricted fetus revealed progressive reduction in pulsatility index of the middle cerebral artery, consistent with brain-sparing effect. At 29 weeks, 1 week before fetal death, the pulsatility index in the middle cerebral artery returned to normal values and became reversed the day before fetal death. This report suggests that reverse flow in the middle cerebral artery is one of the terminal hemodynamic events preceding fetal death.

Obstetric physicians are physicians whose training and particular expertise lie in the care of the medical complications of pregnancy. We present an audit of the work of our bi-weekly obstetric medicine clinic at Queen Charlotte's Hospital, London, over a 10-month period from July 1994 to April 1995 inclusive, and discuss the need for obstetric physicians, with reference to individual medical conditions which complicate pregnancy.

The modified chick chorioallantoic membrane assay was used to measure the angiogenic activity of whole human endometrium, endometrial gland and endometrial stromal cell preparations. Specimens were studied from normal subjects and from those suffering from dysfunctional uterine bleeding. This was done in order to investigate possible sites of angiogenic factor synthesis in endometrium. Significant angiogenic activity was demonstrated in all three sites and was present in all phases of the cycle except for the late secretory phase specimens. In the late secretory phase, compared to the controls, there was no significant angiogenic activity in the whole endometrial, endometrial gland nor endometrial stromal cell preparations. There were no differences in angiogenic activities between the various phases studied apart from a significant decrease in angiogenic activity for the endometrial gland cell preparations between the midsecretory phase and the late secretory phase. This study suggests than human endometrium produces local angiogenic factors throughout the menstrual cycle and that these factors may decrease towards the end of the cycle. It has been suggested that dysfunctional uterine bleeding may be due to disturbances in local angiogenic factors produced in the endometrium. This study found no significant differences in angiogenic activities between normal endometrium and dysfunctional endometrium. This suggests that dysfunctional uterine bleeding may not be due to disturbances in local angiogenic factors.

Objective: To outline the maternal and perinatal features and outcome of patients referred to a tertiary referral obstetric hospital for management of their hypertension., Setting and Patients: 205 consecutive public patients admitted for assessment of hypertension (either full admission or day-stay) to King George V Hospital's Hypertension in Pregnancy Unit, between February 1993 and January 1994., Design: A prospective study in which patients were classified according to the Australasian Society for the Study of Hypertension in Pregnancy (ASSHP) Consensus Statement classification., Results: Of the 205 patients, 25% did not meet the criteria for pre-eclampsia or chronic hypertension, 33% had mild pre-eclampsia, 34% had severe pre-eclampsia and the remainder had chronic hypertension. The mean gestation at delivery for those with mild pre-eclampsia was 38.3 weeks and for severe pre-eclampsia 35.3 weeks. For the mild and severe groups respectively, the rate of elective delivery for raised blood pressure was 56% and 53%; for caesarean section, 17% and 61%; and for perinatal death, 2% and 4%. In the severe group, 49% had fetal problems and 25% required intravenous antihypertensives., Conclusions: The multisystem nature of pre-eclampsia makes comparison of management protocols difficult. Ongoing audit is needed of maternal and perinatal outcomes and features of disease in patients with hypertension in pregnancy under a universal classification. The ASSHP classification system successfully identifies patients who require more intensive management and intervention.

A reliable method of culturing human decidual capillary endothelial cells was developed. Endothelial growth cell supplement, heparin and newborn bovine serum were added to the culture medium to facilitate growth. Decidual capillary endothelial cell cultures showed similar growth curves to the more traditional human umbilical cord vein endothelial cell cultures. Culture growth was assessed by a new morphometric method of measuring cell culture area with the use of a computerised measuring tablet. This new method was compared with the more laborious method of counting individual cells and was found to be as reliable and more efficient.

Patients with placenta praevia in the third trimester are routinely confined to hospital for fear of major haemorrhage. Whilst this is arguably necessary for those who have had an episode of antepartum haemorrhage (APH), it is uncertain whether these same management principles are valid for those with placenta praevia without antepartum haemorrhage. A retrospective study was undertaken reviewing the case records of 69 consecutive patients diagnosed with placenta praevia in the third trimester of pregnancy. The outcome of 15 who had had no episodes of bleeding were compared with those who had at least 1 antepartum bleeding episode. Patients with placenta praevia without evidence of APH spent a significantly shorter amount of time in hospital and had a significantly lower rate of emergency delivery, with a neonatal outcome as good if not better than the APH group. We conclude that outpatient management in this cohort of patients may be a safe and cost-effective means of care, and warrants randomized prospective study.

The value of routine antenatal booking ultrasound as an adjunct to, or as an alternative to the 18 to 20 week ultrasound, is not known. A study into the possible benefits of routine antenatal booking ultrasound was undertaken. One year's experience, involving 1,372 scans is described. The main medical benefits include the establishment or correction of gestational age (41.7% of all pregnancies) and the identification of multiple pregnancies (0.7%), nonviable pregnancies (1.4%) and other pregnancies requiring specialist antenatal clinic referral (0.7%), resulting in a total of 44.5% of patients in whom some benefit was obtained.

Two in vitro methods for measuring human endometrial prostaglandin production were compared. Endometrial samples from eight patients were incubated over eight hours by a perifusion and a superfusion technique. The collected fractions were assayed by radioimmunoassay for PGE2 and PGF2 alpha. There was no significant difference between the perifusion and superfusion methods for the pattern and amount of PGE2 and PGF2 alpha production with time. Significantly higher production levels of PGE2 and PGF2 alpha were found in secretory phase endometria than in proliferative phase endometria. Histological examination of the tissue specimens by light and electron microscopy showed that both methods caused gross tissue damage after eight hours experimentation. The superfusion method produced more morphological damage than the perifusion method. However, no tissue damage could be detected after one hour of incubation with either method. Over an eight hour period neither the perifusion nor the superfusion technique appears to be a good indicator of in vivo endometrial prostaglandin production. Either technique used for only one to two hours may better reflect the in vivo situation.

Controversy still continues concerning the factors controlling endometrial prostaglandin concentrations measured under different circumstances. In this study an attempt was made to remove serial samples of normal human endometrium and standardise 4 different short incubation periods at room temperature before snap-freezing the tissue. No significant difference was found in the concentrations of PGE2 and PGF2 alpha, or PGE2/PGF2 alpha ratio, of the series of specimens with the shortest incubation (42.7 seconds) compared with the longest (93.1 secs). The most likely explanation for this is that trauma-induced prostaglandin production is such a rapid process that it is generally complete within less than 30 seconds at room temperature. As reported in previous studies, a significant correlation was found between PGE2 and PGF2 alpha concentrations in some specimens. Large and significant variations in concentration of prostaglandins were found between individuals which were partly accounted for by variations in stage of the menstrual cycle at the time of collection.

The chick chorioallantoic membrane assay has been used for many years as an in vivo assay of angiogenic activity. However it has been plagued with the problem of a high incidence of false positive angiogenic responses. In this study the conventional chick chorioallantoic membrane assay was compared with a modification of this technique in a series of batches using a total of 100 eggs. False positive reactions were recorded in 32 out of 50 (64%) using the conventional method and only 11 out of 50 (22%) with the modified method (chi 2 = 17.992; p less than 0.001).