Warwick Giles

Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: Associations with Neonatal Anthropometrics

OBJECTIVE—To examine associations of neonatal adiposity with maternal glucose levels and cord serum C-peptide in a multicenter multinational study, the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study, thereby assessing the Pederson hypothesis linking maternal glycemia and fetal hyperinsulinemia to neonatal adiposity. RESEARCH DESIGN AND METHODS—Eligible pregnant women underwent a standard 75-g oral glucose tolerance test between 24 and 32 weeks gestation (as close to 28 weeks as possible). Neonatal anthropometrics and cord serum C-peptide were measured. Associations of maternal glucose and cord serum C-peptide with neonatal adiposity (sum of skin folds >90th percentile or percent body fat >90th percentile) were assessed using multiple logistic regression analyses, with adjustment for potential confounders, including maternal age, parity, BMI, mean arterial pressure, height, gestational age at delivery, and the babys sex. RESULTS—Among 23,316 HAPO Study participants with glucose levels blinded to caregivers, cord serum C-peptide results were available for 19,885 babies and skin fold measurements for 19,389. For measures of neonatal adiposity, there were strong statistically significant gradients across increasing levels of maternal glucose and cord serum C-peptide, which persisted after adjustment for potential confounders. In fully adjusted continuous variable models, odds ratios ranged from 1.35 to 1.44 for the two measures of adiposity for fasting, 1-h, and 2-h plasma glucose higher by 1 SD. CONCLUSIONS—These findings confirm the link between maternal glucose and neonatal adiposity and suggest that the relationship is mediated by fetal insulin production and that the Pedersen hypothesis describes a basic biological relationship influencing fetal growth.

Flow velocity waveforms in the maternal uteroplacental and fetal umbilical placental circulations

A simple continuous-wave Doppler ultrasound system was used to record arterial flow velocity time waveforms from branches of the maternal uterine artery in the placental bed and the fetal umbilical arteries. The systolic-diastolic ratio of flow velocities was measured as an index of peripheral resistance. In normal pregnancy both circulations exhibit high diastolic flow velocities caused by low resistance. The study group consisted of 172 pregnancies with high fetal risk of which 53 resulted in delivery of a small-for-gestational age infant. The last study-to-delivery interval was less than 10 days. In the small-for-gestational age fetuses in whom both umbilical and uterine studies were normal there was good fetal outcome (19 cases). Neonatal morbidity occurred among those with abnormal umbilical studies with low diastolic flow velocities, indicating high resistance. Of these studies there were two subgroups. An abnormal uterine study (13 cases) indicated a primary maternal uteroplacental lesion and a normal study (21 cases) a primary fetal lesion. In cases of severe maternal hypertension, abnormal uterine artery waveforms were associated with abnormal umbilical artery waveforms.

Patterns of Plasma Corticotropin-Releasing Hormone, Progesterone, Estradiol, and Estriol Change and the Onset of Human Labor

CONTEXT Clinical prediction of preterm delivery is largely ineffective, and the mechanism mediating progesterone (P) withdrawal and estrogen activation at the onset of human labor is unclear. OBJECTIVES Our objectives were to determine associations of rates of change of circulating maternal CRH in midpregnancy with preterm delivery, CRH with estriol (E3) concentrations in late pregnancy, and predelivery changes in the ratios of E3, estradiol (E2), and P. DESIGN AND SETTING A cohort of 500 pregnant women was followed from first antenatal visits to delivery during the period 2000-2004 at John Hunter Hospital, New South Wales, Australia, a tertiary care obstetric hospital. PATIENTS Unselected subjects were recruited (including women with multiple gestations) and serial blood samples obtained. MAIN OUTCOME MEASURES CRH daily percentage change in term and preterm singletons at 26 wk, ratios E3/E2, P/E3, and P/E2 and the association between E3 and CRH concentrations in the last month of pregnancy (with spontaneous labor onset) were assessed. RESULTS CRH percentage daily change was significantly higher in preterm than term singletons at 26 wk (medians 3.09 and 2.73; P = 0.003). In late pregnancy, CRH and E3 concentrations were significantly positively associated (P = 0.003). E3/E2 increased, P/E3 decreased, and P/E2 was unchanged in the month before delivery (medians: E3/E2, 7.04 and 10.59, P < 0.001; P/E3, 1.55 and 0.98, P < 0.001; P/E2, 11.78 and 10.79, P = 0.07). CONCLUSIONS The very rapid rise of CRH in late pregnancy is associated with an E3 surge and critically altered P/E3 and E3/E2 ratios that create an estrogenic environment at the onset of labor. Our evidence provides a rationale for the use of CRH in predicting preterm birth and informs approaches to delaying labor using P supplementation.

Low-dose aspirin therapy improves fetal weight in umbilical placental insufficiency

A randomized, placebo-controlled, double-blind trial was carried out to evaluate the fetal benefits of low-dose aspirin (150 mg/day) as a treatment of placental insufficiency during the last trimester of pregnancy. Forty-six women referred for study because there was concern about fetal welfare were found to have an elevated umbilical artery wave form systolic/diastolic ratio. Mothers with severe hypertension were excluded because fetal condition would not necessarily be the dominant determinant of obstetric decision making. A distinction was made between a high systolic/diastolic ratio (greater than 95th but less than 99.95th percentile) and an extreme systolic/diastolic ratio (greater than 99.95th percentile). There were 34 patients in the high ratio group and 12 in the extreme group. Aspirin therapy was associated with an increase in birth weight (mean difference 526 gm [p less than 0.02]), head circumference (1.7 cm [p less than 0.025]), and placental weight (136 gm [p less than 0.02]) in those patients with a high initial umbilical artery systolic/diastolic ratio. For the 12 women with an extreme initial systolic/diastolic ratio, aspirin therapy did not result in a significantly different pregnancy outcome.

Umbilical artery velocity waveforms: normal reference values for A/B ratio and Pourcelot ratio

Summary. Normal reference values for the umbilical artery Pourcelot ratio and A/B ratio are reported. Thirty‐five normal patients were studied serially from 20 weeks to term. The A/B ratio centilcs were corrected for non‐normality of the underlying distribution by transforming from the Pourcelot ratio values. The correction needed was small during the last trimester, but larger for second trimester data. Of the 35 patients 24 were nulliparous and there was a slight tendency for the waveform indices to be higher in the nulliparae, but the numbers in this study were too small to be conclusive about the effect of parity.

Abnormal umbilical artery Doppler waveforms and cord blood corticotropin-releasing hormone.

Objective To determine whether placental secretion of corticotropin-releasing hormone into the fetal circulation is increased in pregnancies complicated by umbilical-placental vascular insufficiency. Methods Twenty women with abnormal Doppler umbilical artery flow velocity waveforms and six women with uncomplicated term pregnancies and normal umbilical artery flow velocity waveforms had cord blood concentrations of corticotropin-releasing hormone, ACTH, cortisol, and β-hCG estimated. Results The mean cord blood corticotropin-releasing hormone concentration was significantly higher in pregnancies with abnormal umbilical artery flow velocity waveforms than in normal pregnancies (108 ± 27 versus 24 ± 8 pg/mL, P = .019). Elevated cord blood corticotropin-releasing hormone levels were seen in the abnormal group regardless of the presence or absence of preeclampsia or fetal growth restriction. There were no significant differences in cord blood cortisol, ACTH, or β-hCG concentrations. Conclusion The concentration of corticotropin-releasing hormone in the fetal circulation is significantly increased in pregnancies complicated by abnormal umbilical artery flow velocity waveforms. This may represent a stress-responsive compensatory mechanism in the human placenta.

Dietary balance during pregnancy is associated with fetal adiposity and fat distribution

BACKGROUND The prenatal environment can induce permanent changes in offspring phenotype. Thinness at birth is associated with adult risk of cardiometabolic disease. OBJECTIVE The objective was to investigate the association between maternal nutrition during pregnancy and intrauterine development of fetal body composition. DESIGN We used prospective data from 179 Australian women with singleton pregnancies from the Women and Their Childrens Health Study. A validated food-frequency questionnaire was used at 18-24 wk and 36-40 wk of gestation to quantify maternal diet during the previous 3 mo of pregnancy. Fetal body-composition measurements were ascertained from abdominal and midthigh sites by ultrasound performed at 19, 25, 30, and 36 wk. The subcutaneous fat area at each site was calculated by subtracting the lean/visceral area from the total area. RESULTS In linear mixed-model regressions, maternal intakes of protein (b = -0.13; P = 0.04) and starch (b = 0.10; P = 0.02) and the protein:carbohydrate ratio (b = -3.61; P = 0.02) were associated with the percentage of abdominal fat, whereas SFA (b = 0.27; P = 0.04) and PUFA (b = -0.48; P = 0.03) were associated with the percentage of midthigh fat. Response surfaces for fetal adiposity were maximized at different macronutrient intakes. Abdominal fat was highest with low protein intakes (<16% of energy), and midthigh fat was highest at intermediate protein (18-21% of energy), high fat (>40% of energy), and low carbohydrate (<40% of energy) intakes. CONCLUSION Fetal body composition may be modifiable via nutritional intervention in the mother and thus may play an important role in influencing the offsprings risk of future disease.

Fetal volume blood flow and umbilical artery flow velocity waveform analysis: a comparison

Summary. The estimation of fetal umbilical vein and aortic volume blood flow was compared with umbilical artery flow velocity‐time waveform analysis in 42 pregnancies. The volume blood flow measurements were made with a combined linear array B‐mode and pulsed Doppler ultrasound system. The umbilical artery flow velocity‐time waveform analysis was made with either pulsed or continuous wave 2 MHzDoppler ultrasound and the systolic/diastolic (A/B) ratio was used as an index of flow resistance. There was no difference when continuous wave was compared to pulsed Doppler ultrasound as a method of recording flow velocity waveforms. Analysis of the umbilical artery flow velocity‐time waveform was more sensitive (100%‐50%) than the measurement of umbilical vein volume blood flow (ml/kg/min) in the detection of the small‐for‐gestational age (SGA) fetus. The predictive value of a positive test was higher (71%‐45%) while specificity was similar (88%‐81%). Descending aortic volume flow was reduced in only one SGA fetus. The increase in umbilical placental downstream resistance (high systolic/ diastolic ratio) was associated with a reduction in the percentage of fetal aortic blood flow directed to the umbilical placental circulation.

Regional block versus general anaesthesia for caesarean section and neonatal outcomes: a population-based study

BackgroundAnaesthesia guidelines recommend regional anaesthesia for most caesarean sections due to the risk of failed intubation and aspiration with general anaesthesia. However, general anaesthesia is considered to be safe for the foetus, based on limited evidence, and is still used for caesarean sections.MethodsCohorts of caesarean sections by indication (that is, planned repeat caesarean section, failure to progress, foetal distress) were selected from the period 1998 to 2004 (N = 50,806). Deliveries performed under general anaesthesia were compared with those performed under spinal or epidural, for the outcomes of neonatal intubation and 5-minute Apgar (Apgar5) <7.ResultsThe risk of adverse outcomes was increased for caesarean sections under general anaesthesia for all three indications and across all levels of hospital. The relative risks were largest for low-risk planned repeat caesarean deliveries: resuscitation with intubation relative risk was 12.8 (95% confidence interval 7.6, 21.7), and Apgar5 <7 relative risk was 13.4 (95% confidence interval 9.2, 19.4). The largest absolute increase in risk was for unplanned caesareans due to foetal distress: there were five extra intubations per 100 deliveries and six extra Apgar5 <7 per 100 deliveries.ConclusionThe infants most affected by general anaesthesia were those already compromised in utero, as evidenced by foetal distress. The increased rate of adverse neonatal outcomes should be weighed up when general anaesthesia is under consideration.

The Doppler Assessment in multiple pregnancy randomised controlled trial of ultrasound biometry versus umbilical artery Doppler ultrasound and biometry in twin pregnancy

Objective To assess the addition value of umbilical artery Doppler ultrasound added to standard ultrasound biometry measurements in the management of twin pregnancies.