Timothy Wheeler

Neonatal Bone Mass: Influence of Parental Birthweight, Maternal Smoking, Body Composition, and Activity During Pregnancy

Evidence is accumulating that intrauterine growth and development may influence an individuals risk of osteoporosis in later adult life. To examine maternal and paternal influences on intrauterine skeletal growth, we used dual‐energy X‐ray absorptiometry to measure the neonatal bone mineral content (BMC) and bone mineral density (BMD) of 145 infants born at term. Independently of the infants duration of gestation at birth, the birthweights of both parents and the height of the father were positively correlated with neonatal whole body BMC. Women who smoked during pregnancy had infants with a lower whole body BMC and BMD; overall, there was a 7.1‐g (11%) average difference between whole body BMC of infants whose mothers did and did not smoke during pregnancy (p = 0.005). Women with thinner triceps skinfold thicknesses (reflecting lower fat stores) and those who reported a faster walking pace and more frequent vigorous activity in late pregnancy also tended to have infants with a lower BMC and BMD (p values for BMC; 0.02, 0.03, and 0.05, respectively). Maternal thinness and faster walking pace but not maternal smoking or parental birthweight also were associated with lower bone mineral apparent density (BMAD). The influences on skeletal growth and mineralization were independent of placental weight, a marker of the placental capacity to deliver nutrients to the fetus. These observations point to a combination of genetic and intrauterine environmental influences on prenatal skeletal development and suggest that environmental modulation, even at this early stage of life, may reduce the risk of osteoporosis in adulthood.

Glycine rectifies vascular dysfunction induced by dietary protein imbalance during pregnancy

Protein restriction in rat pregnancy programmes the development of elevated systolic blood pressure and vascular dysfunction in the offspring. A recent study has shown that hypertension is reversed by maternal glycine supplementation. Whether this protective effect is exerted directly on the embryo and fetus, or indirectly via effects on the mother, is unknown although we have previously shown abnormalities in the maternal vasculature. We tested the hypothesis that dietary glycine repletion would reverse endothelial dysfunction in protein‐restricted pregnant rat dams using wire myography. Impaired acetylcholine‐ (P < 0.01) and isoprenaline‐induced (P < 0.05) vasodilatation in isolated mesenteric arteries (MA) from protein‐restricted pregnant dams was accompanied by reduced vascular nitric oxide (NO) release (P < 0.05). Dietary glycine supplementation reversed vascular dysfunction in MA (P < 0.05) and improved NO release thus potentially protecting the maternal circulation. The impaired NO release in the MA of low protein diet dams was not accompanied by reduced eNOS mRNA expression, suggesting that eNOS activity was altered. Protein restriction did not alter the vascular function of a conduit artery, the thoracic aorta. These results provide evidence that adequate provision of glycine, a conditionally essential amino acid in pregnancy, may play a role in the vascular adaptations to pregnancy, protecting the fetus from abnormal programming of the cardiovascular system.

Vasodilation to Vascular Endothelial Growth Factor in the Uterine Artery of the Pregnant Rat Is Blunted by Low Dietary Protein Intake

Pregnancy is associated with a substantial increase in uterine artery blood flow, which may in part result from dilation in response to vascular endothelial growth factor (VEGF). Uterine blood flow is reported to be reduced in globally diet-restricted pregnant rats. Both global and protein dietary restriction in pregnancy produce programmed effects in offspring. In this study we hypothesized that protein restriction in pregnancy impairs maternal uterine artery responses to VEGF. Vascular responses to VEGF were determined in isolated uterine arteries of pregnant (18 or 19 d of gestation) Wistar rats fed a diet containing either 18% or 9% casein throughout pregnancy. For comparison, responses to phenylephrine, potassium chloride, and acetylcholine were determined. In addition, the response of the mesenteric artery to VEGF was studied in the same animals. A significant reduction of the maximal relaxation to VEGF (p = 0.041) and in the overall response (p = 0.004) to VEGF was found in uterine arteries of the 9% compared with the 18% group, but responses to all other agonists were similar. The VEGF response was reduced by cyclooxygenase inhibition (indomethacin) in both groups. In the 18%, but not the 9%, group it was further reduced by nitric oxide synthase inhibition (Nω-nitro-l-arginine methyl ester). VEGF was shown to dilate the mesenteric artery but this effect was not significantly altered by the low-protein diet. These results show an attenuated uterine artery vasodilator response to VEGF produced by a low-protein diet in pregnancy, partly because of a reduction of the nitric oxide component of VEGF-mediated relaxation.

Antenatal cardiotocogram quality and interpretation using computers

To test the application in practice of computerized fetal heart rate (FHR) analysis in pregnancy.

Fetal heart rate and intrauterine growth

Objective— To assess whether fetal heart rate in early and late pregnancy relates to size at birth.

Increased Circulating Levels of Vascular Endothelial Growth Factor in Preeclampsia

Objective: To determine whether levels of vascular endothelial growth factor (VEGF) are raised in pregnancies complicated by preeclampsia.Methods: Samples of serum were collected from 10 patients with preeclampsia and 10 gestation-matched normotensive controls. Levels of VEGF were measured in samples using a radioimmunoassay with a polyclonal antibody capable of recognizing all VEGF isoforms.Results: Vascular endothelial growth factor was detectable in all samples assayed. The median serum concentration of VEGF in the preeclamptic subjects was 5.1 μg/L (interquartile range: 4.7-5.5 μg/L) and for the control group 3.9 μg/L (interquartile range: 3.4-4.1 μg/L). Serum VEGF levels were significantly higher (p < 0.001, Mann-Whitney U-test) in the preeclamptic subjects.Conclusion: The raised circulating levels of VEGF in preeclampsia and the known effects of this growth factor on endothelial cell function suggest that VEGF may be involved in the pathophysiology of this disease.

The influence of maternal haemoglobin and ferritin on mid‐pregnancy placental volume

Objective To investigate whether low maternal haemoglobin and ferritin levels are associated with increased placental volume by mid‐pregnancy.

An unusual mode of delivery

An 18 year old primigravida was referred to hospital for routine antenatal care. At booking, she weighed 52 kg, had a body mass index of 21 kg/cm and a haemoglobin of 10.7 g/L. No abnormalities were detected on routine fetal anomaly scanning at 20 weeks of gestation although, it was not possible to obtain satisfactory images of the fetal heart because of the position of the fetus, and one week later a repeat cardiac scan again proved unsatisfactory for the same reason At 27 weeks of gestation she was admitted from home to the antenatal ward complaining of epigastric and bilateral shoulder pain, vomiting and malaise. The only abnormal physical sign was epigastric tenderness. The uterus was reported to be of an appropriate size for the gestational age. She had a normocytic anaemia (haemoglobin concentration 8.6 g/L). Renal and liver function tests and serum amylase were normal. Obtaining a satisfactory cardiotocogram was dif®cult but the fetal heart rate pattern was reassuring. An ultrasound scan showed the fetus lying as an extended breech presentation with an abdominal circumference on the 30th centile. The placenta was reported to be anterior and on the left side of the uterus. The amniotic ̄uid index was normal. Ultrasound examination of the maternal liver, kidneys and bilary tract was also reported as normal although ̄uid to a depth of 1.7 cm was noted around the liver. The patients symptoms settled over two days and she was discharged home on oral haematinics. She was readmitted to the antenatal ward at 31 weeks of gestation with a two day history of vomiting and epigastric pain. She was clinically dehydrated and had epigastric tenderness. On abdominal palpation it was thought that the uterus was small for the gestational age. Cardiotocography was again dif®cult but the fetal heart pattern was normal. An ultrasound scan performed two days after admission revealed the fetus to be lying transversely across the upper abdomen with its head in the left upper quadrant. There was no amniotic ̄uid around the fetus. The placenta was thought to be attached over a large area to the anterior abdominal wall inferior to the umbilicus. The uterus was shown on transvaginal sonography to be deviated to the right within the pelvis, measuring 10.4 cm in length. These ®ndings were con®rmed by magnetic resonance imaging (MRI) (Fig. 1). The diagnosis of an abdominal pregnancy was made. The patient became increasingly distressed by her abdominal discomfort, and felt unable to continue with her pregnancy. She was given dexamethasone to aid fetal lung maturation, and preparations were made for delivery by laparotomy later that week. The day before delivery an ultrasound scan was performed allowing the exact location of the placenta to be marked on the abdominal wall. The area concerned effectively covered the whole abdomen inferior to the umbilicus. Delivery was undertaken under general anaesthesia with the assistance of a consultant vascular surgeon. The operative ®eld was prepared to allow access to both groins in case ligation of the inferior epigastric vessels became necessary. A right subcostal incision was made (Fig. 2) and the abdomen opened as if performing a cholecystectomy. A healthy female fetus weighing 1460 g was delivered in good condition by breech extraction from the upper abdomen. The umbilical cord was clamped, cut and ligated as close as possible to its placental insertion. The placenta was found to be attached to the back of the greater omentum, the lower edge of the omentum being tethered into the pelvis. The placenta was left undisturbed, and the abdomen closed. The patient made an uncomplicated post-operative recovery. Placental