The high prevalence and impact of rheumatic heart disease in pregnancy in First Nations populations in a high-income setting: a prospective cohort study.

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 Maori 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.

Maternal abdominal subcutaneous fat thickness as a predictor for adverse pregnancy outcome: a longitudinal cohort study.

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.

Smaller fetal thymuses in pre-eclampsia: a prospective cross-sectional study.

OBJECTIVE: To determine whether the thymus is smaller in fetuses of pre-eclamptic mothers than in those of normal controls. METHODS: This was a cross-sectional, prospective, comparative study of sonographically determined fetal thymus measurements in 39 pregnancies with pre-eclampsia and 70 healthy pregnancies. RESULTS: Both the diameter and the perimeter of the fetal thymus were smaller in pregnancies with pre-eclampsia than in healthy controls. The means of the thymus diameters were 28.6 ± 5.9 and 32.9 ± 4.5 mm and of thymus perimeters 80.9 ± 16.5 and 93.1 ± 16.6 mm for pre-eclamptic and healthy pregnancies, respectively (P < 0.001). General linear models showed that smaller fetal thymuses in pre-eclampsia were independent of gestational age, estimated fetal weight, small for gestational age status and antenatal steroid use. CONCLUSIONS: Pre-eclampsia is associated with smaller fetal thymuses.

Maternal asthma and gestational diabetes mellitus: Exploration of potential associations.

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.

The relationship between cigarette smoking, endothelial function and intrauterine growth restriction in human pregnancy.

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.

Carbon monoxide disposition and permeability-surface area product in the foetal circulation of the perfused term human placenta.

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.

Pharmacokinetics and pharmacodynamics of TRH during pregnancy.

OBJECTIVE: To determine the pharmacokinetics and pharmacodynamics of thyrotropin-releasing hormone (TRH) in pregnant women. METHODS: Twenty-four pregnant and eight nonpregnant women were given 400 micrograms TRH as either intravenous infusion or bolus. Serial venous samples were collected for TRH, TSH, thyroxine, and prolactin assay. RESULTS: When given as bolus, mean (+/- standard error of the mean) peak plasma concentration (50 +/- 5.2 and 73 +/- 5.1 ng/mL, P < .01), elimination half life (4.3 +/- 0.3 and 6.3 +/- 0.4 minutes, P < .001), and area under the curve (156.4 +/- 14.8 and 340.1 +/- 32.8 ng/mL/minute, P < .001) in pregnant subjects were reduced compared with controls, whereas plasma clearance (45.4 +/- 6.5 and 23.6 +/- 2.1 mL/kg/minute, P < .01) and volume of distribution (27.8 +/- 1.8 and 19.0 +/- 1.3% body weight, P < .01) were increased. When given by infusion, steady-state concentration (6.6 +/- 0.5 and 9.8 +/- 0.9 ng/mL, P < .01) and elimination half-life (4.6 +/- 0.5 and 6.3 +/- 0.3 minutes, P < .05) were lower in pregnant subjects than in controls. Thyrotropin-releasing hormone kinetics were independent of mode of administration. Although basal TSH and thyroid hormone concentrations were similar in patients and controls, the TSH response to TRH was blunted in pregnant subjects compared with controls (9.3 +/- 0.6 and 16.4 +/- 1.4 microIU/mL, P < .001). The basal (3187 +/- 488 and 147 +/- 16 mIU/L) and maximal prolactin response (6193 +/- 426 and 1316 +/- 106 mIU/L) were increased in pregnant subjects compared with controls (P < .001). CONCLUSION: The peak plasma concentration and elimination half-life of TRH are reduced during pregnancy because of the increased volume of distribution and rapid clearance. Mode of administration does not affect TRH pharmacokinetics, but the maternal pharmacodynamic response differs in patients receiving bolus compared with infusion.

Lethal prenatal onset infantile cortical hyperostosis (Caffey disease).

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.

Drugs in pregnancy. Drugs for obstetric conditions.

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.

Angiogenic activity in normal and dysfunctional uterine bleeding human endometrium; as measured by the chick chorioallantoic membrane assay.

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.

A new reliable method of culturing and measuring human decidual capillary endothelial cells.

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.

Do women with placenta praevia without antepartum haemorrhage require hospitalization?

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.

Rectal carcinoma in pregnancy.

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.

Antenatal lung maturation--should we all be using thyrotropin-releasing hormone?

Thyrotropin-releasing hormone (TRH) appears to be a promising antenatal therapy to help reduce neonatal lung disease. Clinical trials, however, show differing results. At present the optimum dosage, frequency and method of administration have not been established. TRH has been shown significantly to elevate blood pressure in patients with preeclampsia suggesting it should not be used in this group. Moreover concerns over its use in growth retarded fetuses and its long-term neonatal effects have not been addressed. Further trials are needed before routine clinical use can be recommended.

Umbilical vein to artery ratio in fetuses with single umbilical artery.

In fetuses with single umbilical artery (SUA) the entire blood flow to the placenta is transported through only one umbilical artery, resulting in a compensatory increase of the arterial diameter. In order to establish whether umbilical vessel size could be used as an additional ultrasonographic criterion for prenatal diagnosis of SUA, we measured umbilical vein and umbilical artery diameters in 55 fetuses with SUA and in 55 with a normal three-vessel cord matched for gestational age. In all but one fetus with SUA, the diameter of the umbilical artery was greater than 50% of that of the umbilical vein, resulting in an umbilical vein to umbilical artery ratio of < or = 2. In contrast, none of the fetuses with a three-vessel cord had a ratio of < or = 2. Increasing diameter of the umbilical artery with no modification of the diameter of the vein is a characteristic prenatal ultrasonographic feature of SUA, making this observation a useful technique for the detection of this vascular anomaly in utero.

Obstetric physicians: are they needed? The workload of a medical complications in pregnancy clinic.

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.

Reverse end-diastolic flow in the middle cerebral artery: an agonal pattern in the human fetus.

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.

Maternal-to-fetal transfer of thyrotropin-releasing hormone in vivo.

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.