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 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.

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.

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.

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.

Transplacental flecainide therapy for fetal supraventricular tachycardia in a twin pregnancy.

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.

Effects of antenatal thyrotropin-releasing hormone on fetal heart rate and breathing movements.

OBJECTIVE: To determine the effect of maternally administered thyrotropin-releasing hormone (TRH) on fetal heart rate (FHR) pattern and fetal breathing movements (FBM). METHODS: Prospective observational study of 75 pregnant women between 26 and 34 weeks' gestation in whom pharmacological fetal lung maturation was clinically indicated. Forty-minute recordings were made of FBM or FHR patterns before and after drug administration. Twenty-five received TRH 400 microg as an intravenous bolus, 25 TRH 400 microg in 50 ml 0.9% saline as an intravenous infusion, and 25 acted as controls. Recordings were processed digitally to calculate the change in FHR (n = 45) and FBM parameters (n = 30). The main outcome measures for FHR were number of accelerations and decelerations, baseline rate, overall and short-term variation and duration of high and low variability, while for FBM they were rate, breath-to-breath interval and incidence. Results between groups were compared by analysis of variance. RESULTS: There was no significant change in FHR, accelerations or variation in any of the groups. Similarly, there was no change in the incidence of FBM. TRH administered as a bolus produced a small statistically but not clinically significant increase in breathing rate (mean delta = 35 breaths/h, p = 0.004), which was not seen in the TRH infusion and control groups. CONCLUSIONS: Maternally administered TRH as used to enhance fetal lung maturation has no clinically significant direct effect on FHR or FBM patterns.

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.

Activated protein C resistance in normal pregnancy.

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.

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.

Medical amnioreduction with sulindac to reduce cord complications in monoamniotic twins.

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.