Infant adiposity following a randomised controlled trial of a behavioural intervention in obese pregnancy.

OBJECTIVES: Randomised controlled trials are required to address causality in the reported associations between maternal influences and offspring adiposity. The aim of this study was to determine whether an antenatal lifestyle intervention, associated with improvements in maternal diet and reduced gestational weight gain (GWG) in obese pregnant women leads to a reduction in infant adiposity and sustained improvements in maternal lifestyle behaviours at 6 months postpartum. SUBJECTS AND METHODS: We conducted a planned postnatal follow-up of a randomised controlled trial (UK Pregnancies Better Eating and Activity Trial (UPBEAT)) of a complex behavioural intervention targeting maternal diet (glycaemic load (GL) and saturated fat intake) and physical activity in 1555 obese pregnant women. The main outcome measure was infant adiposity, assessed by subscapular and triceps skinfold thicknesses. Maternal diet and physical activity, indices of the familial lifestyle environment, were assessed by questionnaire. RESULTS: A total of 698 (45.9%) infants (342 intervention and 356 standard antenatal care) were followed up at a mean age of 5.92 months. There was no difference in triceps skinfold thickness z-scores between the intervention vs standard care arms (difference -0.14 s.d., 95% confidence interval -0.38 to 0.10, P=0.246), but subscapular skinfold thickness z-score was 0.26 s.d. (-0.49 to -0.02; P=0.03) lower in the intervention arm. Maternal dietary GL (-35.34; -48.0 to -22.67; P<0.001) and saturated fat intake (-1.93% energy; -2.64 to -1.22; P<0.001) were reduced in the intervention arm at 6 months postpartum. Causal mediation analysis suggested that lower infant subscapular skinfold thickness was partially mediated by changes in antenatal maternal diet and GWG rather than postnatal diet. CONCLUSIONS: This study provides evidence from follow-up of a randomised controlled trial that a maternal behavioural intervention in obese pregnant women has the potential to reduce infant adiposity and to produce a sustained improvement in maternal diet at 6 months postpartum.

Social disparity and intrauterine death: from politics to policies.

Correlation between intrauterine demise (IUD) and social disparity, based on maternal post-code of residence, is assessed in this study in order to find out if there is any correlation between IUD and geographical area. A total of 190 IUD cases from September 2002 to August 2004 were collected retrospectively from the IUD register. The maternity computer health record programme (Terranova-Healthware) was used for the assessment of area of residence of the patient and GP, patient demography and pregnancy details. Data were then entered onto a MS Excel spreadsheet and analysed by a public health statistician and a consultant obstetrician using the IMD-Index of Multiple Deprivation and then on to a graph. The results of this study show that there was a strong correlation between the IMD and the distribution of IUDs. Disparities come at a personal, midwifery and obstetric price. Differential access may lead to disparities in quality.

Unified communication to reach vulnerable mothers.

The feasibility of using a mobile text to reach vulnerable patient groups was assessed in this study. A total of 121 pregnant or postnatal women were randomly asked to complete a questionnaire. The questionnaire was given to them in the antenatal clinic, postnatal ward, antenatal ward or in the day assessment unit at St Thomas' Hospital, London. The forms were collected and analysed using an Excel database. The results of this survey show that mobile technology is readily available for 97% of the obstetric population. In mothers from vulnerable groups and in mothers from deprived areas, 61% possessed 3rd generation mobile technology. The majority of mothers surveyed wanted their care supplemented by the use of their mobile phones.

Developing a community-based maternal obesity intervention: a qualitative study of service providers' views.

The aim of this study was to explore healthcare professionals' views on the development of multicomponent interventions for obese pregnant women. A cohort of 22 healthcare professionals was interviewed. The interview transcripts were analysed thematically. Three key themes were highlighted by the interviews: (1) the lack of existing services for obese pregnant women in south-east London; (2) the barriers and challenges that need to be overcome (e.g. ethnic and cultural) when considering the creation of a new service for obese women who are pregnant; (3) the possible components of a new intervention. The findings of this study will inform the design of a programme to combat maternal obesity.

Pregnancy outcomes in sickle cell disease: a retrospective cohort study from two tertiary centres in the UK.

The objective of this retrospective cohort study from two tertiary centres in the UK was to describe the pregnancy outcomes of women with sickle cell disease (SCD) who booked at these centres between 2004 and 2008, and to compare this with historical data. The study population comprised 122 singleton pregnancies in women with SCD: homozygous sickle cell disease 64, sickle cell haemoglobin C disease 45, sickle b plus thalassaemia 11, sickle cell haemoglobin E disease 1 and sickle cell delta disease 1 from 2004 to 2008 managed in the joint haematology/obstetric antenatal clinics in two tertiary teaching hospitals. The main outcome measures were the frequency of sickle cell crises and obstetric complications. Age and gestation at booking were 18-43 years (mean 29.7) and 9-36 weeks gestation (mean 17.3), respectively. Complications of SCD occurred in 25% of pregnancies. Fifty-four percent of women had induction of labour and 39% were delivered by emergency caesarean section. Thirty-three percent had a postpartum haemorrhage. Nineteen percent of women delivered before 37 completed weeks. Birth weight below 2500 g occurred in 20% of singleton pregnancies. Three neonates developed transient complications related to maternal opiate exposure postnatally. Three intrauterine deaths occurred at 24, 29 and 34 weeks. Two of these had congenital defects, and the other severe intrauterine growth restriction. No maternal deaths occurred. Successful pregnancy outcomes can be achieved in SCD. There has been an improvement in fetal and maternal morbidity and mortality compared with historical data. Pregnancy in women with SCD remains high risk. Early access to antenatal care and to expertise in SCD is essential. A matched control population from the same time period and prospective data collection is needed to address confounders such as ethnicity and deprivation.

Ovarian sickling as a proposed mechanism for premature ovarian failure necessitating ovum donation.

Iron overload in female patients with sickle cell disease (SCD) has been reported to result in gonadal dysfunction. To date there has been no report in the literature of ovarian sickling being a reason for gonadodysgenesis (premature ovarian failure [POF]) in women. This case report describes POF in a woman with SCD and suggests ovarian sickling as its cause. We propose that frequent episodes of intravascular sickling, vessel occlusion and infarction as well as tissue hypoxia associated with chronic anaemia could account for the ovarian dysgenesis and hence POF.

Maternal obesity: a review of interventions.

BACKGROUND: Obesity has become a serious global public health issue and has consequences for nearly all areas of medicine. Within obstetrics, obesity not only has direct implications for the health of a pregnancy but also impacts on the weight of the child in infancy and beyond. As such, maternal weight may influence the prevalence and severity of obesity in future generations. Pregnancy has been identified as a key time to target a weight control or weight loss strategy to help curb the rapidly growing obesity epidemic. In addition, if delivered sensitively, pregnancy may be a good time to target health behaviour changes by using the extra motivation women tend to have at this time to maximise the health of their child. AIM: This study reviews the current evidence for interventions to promote weight control or weight loss in women around the time of pregnancy. A comprehensive review of medical research--PubMed, Embase, Ovid Medline and the Cochrane Clinical Trials register--showed that despite numerous reports of the prevalence and complications of maternal obesity, few intervention strategies have been suggested. CONCLUSION: This study finds that there is a deficiency of appropriately designed interventions for maternal obesity and it concludes by highlighting areas for developing a more effective strategy.

Platelet count as a predictor of the severity of sickle cell disease during pregnancy.

Recent evidence implicates the immune system and the clotting mechanisms in the pathophysiology of sickle cell disease (SCD). This study investigates the association of steady state platelet count with the severity of SCD in pregnancy. A total of 40 SCD women who were asymptomatic early in pregnancy were studied retrospectively: 14 remained asymptomatic throughout pregnancy and 26 developed at least one SCD-related complication. The early pregnancy platelet count was compared between the two groups using t-test and its ability to predict SCD-related complications in pregnancy was investigated using Receiver-Operator Characteristics (ROC) curve. Compared with asymptomatic patients, women who developed SCD-related complications had significantly higher early-pregnancy platelet count [328x10(9)/l (95% CI: 268-389) vs 210x10(9)/l (146-275), p < 0.01]. The area under the ROC curve was 76.4% (95% CI 59.7-93.2). These indicate that the platelet count in early pregnancy is significantly higher in SCD patients who subsequently develop SCD-related complications and may be used for screening.

Birthweights in sickle cell trait pregnancies.

OBJECTIVES: Available evidence on the effect of sickle cell trait (SCT) on birthweight is conflicting, not gestational age specific, and does not account for maternal and infant factors. The objectives of this study are to determine the contemporary mean birthweight, mean customised birthweight centile, and to analyse the risk of small-for-gestational-age (SGA) and large-for-gestational-age (LGA) babies in SCT pregnancies. DESIGN: Large retrospective cohort study. SETTING: London hospital. POPULATION: Singleton pregnancies between 24 and 42 completed weeks delivered between 2000 and 2005 in parturient with body mass index between 18.0 and 35.0 kg/m(2). METHODS: All qualifying pregnancies were identified on Terra Nova Healthware. Birthweight centiles of these cases were computed with Gardosi customised bulk centile calculator using collected data on maternal height, weight, ethnicity and parity, and the infant's gender, gestational age and birthweight. Birthweight and birthweight centiles of SCT and pregnancies with no haemoglobinopathy (control) were compared. Statistical analysis was performed using Stata version 9.2. MAIN OUTCOME MEASURES: Birthweight and birthweight centiles. RESULTS: Five hundred and five SCT and 16 320 controls were analysed. The mean birthweight of SCT pregnancies was 3223 g, 57 g lower than controls (P = 0.024). However, its mean birthweight centile was 49.0% similar to that of controls' 47.5% (P = 0.320). There is an apparent risk of LGA babies in SCT pregnancies, but logistic regression analysis suggests that the odds are related to being an older non-white parturient and a male infant rather than SCT status. CONCLUSIONS: SCT is not a risk factor for SGA or LGA infants.

Sickle-cell trait and small-for-gestational age babies: Is there a link?

Sickle cell disease is the most common haemoglobinopathy in pregnancy that can result in small babies. Sickle cell trait's (SCT) influence is unclear with a few conflicting published studies which did not relate birth weight to gestation and maternal or fetal factors. To assess the incidence of small-for-gestation age (SGA) babies in SCT pregnancies we conducted a retrospective analysis of all SCT deliveries at St Thomas' Hospital, London between 2000 and 2005. The Gardosi bulk centile calculator was used to determine the customised birth weight centile accounting for maternal height, weight, parity, ethnicity, infant's birth weight, sex and gestational age. A total of 16.8% (79/471) SCT pregnancies analysed had SGA babies. When cases with identified pregnancy complications were excluded, the SGA rate remained higher than the anticipated 10%, at 14.8% (p

Selective arterial embolisation: a first line measure for obstetric haemorrhage?

Selective arterial embolisation is increasingly used to arrest intractable postpartum haemorrhage. We report a case of postpartum haemorrhage following a placenta praevia, which had a successful outcome with selective arterial embolisation as the first treatment option. This technique should be more widely available, and in many instances should be considered before and in lieu of any surgical intervention.

Characterization of human placental explants: morphological, biochemical and physiological studies using first and third trimester placenta.

The primary objective of this study was to characterize an in-vitro model of the human placenta using morphological, biochemical and physiological parameters. Placental villi were obtained from normal first trimester and term pregnancies. The villi were incubated with Dulbecco's modified Eagle's medium: Ham's F12 nutrient mixture in a shaking water bath at 37 degrees C for up to 310 min. The viability was determined by the production of beta human chorionic gonadotrophin (HCG) and lactic dehydrogenase (LDH) and the incorporation of [3H]thymidine, [3H]L-leucine and L-[U14C]arginine, while ultrastructure was assessed by transmission electron microscopy. In the first and third trimester group, the release into the medium of the intracellular enzyme LDH remained unaltered throughout the experiment. By contrast, beta-HCG concentrations increased linearly and concentrations were higher in the first trimester than term villi (354.5 +/- 37.8 versus 107 +/- 8.1 IU/g villi protein; P < 0.001). Electron microscopy confirmed preservation of tissue viability for up to 4 h of incubation. The incorporation of thymidine (12.2 +/- 2.9 versus 5.2 +/- 0.5 nmol/g villi protein; P < 0.05), leucine (9.4 +/- 2.1 versus 1.9 +/- 0.4 nmol/g villi protein; P < 0.02) and arginine (17 +/- 4.4 versus 4.2 +/- 0.5 nmol/g villi protein; P < 0.05) were markedly higher in early than in term placenta. Furthermore, placental uptake of L-leucine by the first (9.4 +/- 2.1 versus 17 + 4.4 mol/g villi protein; P < 0.001) and third trimester placental villi (1.9 +/- 0.4 versus 4.2 + 0.5 mol/g villi protein; P < 0.001) was less than that of L-arginine. This study describes a simple technique using placental explants to determine relative rates of uptake of substrate amino acids throughout gestation.

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.

Transfer and metabolism of thyrotropin releasing hormone across the perfused human term placenta.

The transport and uptake of TRH was investigated in the maternal-fetal-placental unit of perfused human term placenta. The degradation of TRH in biological fluid was first determined by incubating [125I]TRH with 100 microL 50% maternal or cord sera with or without pretreatment with 200 microM of p-hydroxymercuriphenyl sulfonic acid (p-HMSA), a proline dipeptidase inhibitor. Transplacental transfer of TRH was then studied by adding 10 microCi of [125I]- or [3H]TRH to the maternal circulation of dually perfused isolated lobule of human term placenta with or without 200 microM p-HMSA. Creatinine was used as an internal marker. The rate of degradation of TRH (P < 0.001) and inhibition by p-HMSA were significantly higher in maternal than cord sera (P < 0.05). In the maternal circulation, TRH concentration declined rapidly from 100% at time 0 to 33.5 +/- 1.2% at 120 min. The fetal concentration increased from undetectable levels to a maximum of 1.8 +/- 0.3% at 120 min with a low feto-maternal ratio (0.08 +/- 0.02). Perfusion in the presence of p-HMSA, however, did not significantly change fetal concentration, or the maternal and fetal concentration-time integral levels of TRH. Chromatography of maternal, fetal, and placental homogenates showed that TRH was metabolized by the placenta into small molecular weight fragments predominantly released in the maternal circulation. These results suggest that human placenta acts as an enzymatic barrier to the free passage of TRH.