Intrauterine volume, fetal abdominal area and biparietal diameter measurements with ultrasound in the prediction of small-for-dates babies in a high-risk obstetric population.

Summary. . The value of fetal biparietal diameter and abdominal area, total intrauterine, intra-amniotic and placental volume measurements for predicting small-for-dates babies in a high-risk obstetric population was investigated in 130 women. A parallel planimetric area method was used to measure volume. The commonest risk factors were suspected intrauterine growth-retardation, hypertensive complications and previous poor obstetric history. The prevalence of birthweight at and below the 10th or 3rd centiles was 30 and 16% respectively. Fetal abdominal area and total intrauterine volume measurements had the highest and comparable sensitivity, specificity and positive predictive value in the detection of infants with birthweights of 10th and 3rd centiles. While these measurements are of use in consolidating the clinical diagnosis of small-for-dates fetuses (growth retardation), high false positive rates (10% and 16–17% for birthweights 10th centile, and 3rd centile respectively) make further discriminatory tests necessary for part of the population.     

Intrauterine volume, fetal abdominal area and biparietal diameter measurements with ultrasound in the prediction of small-for-dates babies in a high-risk obstetric population

The value of fetal biparietal diameter and abdominal area, total intrauterine, intra-amniotic and placental volume measurements for predicting small-for-dates babies in a high-risk obstetric population was investigated in 130 women. A parallel planimetric area method was used to measure volume. The commonest risk factors were suspected intrauterine growth-retardation, hypertensive complications and previous poor obstetric history. The prevalence of birthweight at and below the 10th or 3rd centiles was 30 and 16% respectively. Fetal abdominal area and total intrauterine volume measurements had the highest and comparable sensitivity, specificity and positive predictive value in the detection of infants with birthweights of less than or equal to 10th and less than or equal to 3rd centiles. While these measurements are of use in consolidating the clinical diagnosis of small-for-dates fetuses (growth retardation), high false positive rates (10% and 16-17% for birthweights less than or equal to 10th centile, and less than or equal to 3rd centile respectively) make further discriminatory tests necessary for part of the population.     

Total intra-uterine volume and symphysis fundus height. Is there a relation?

The concordance between measurements of total intra-uterine volume (parallel planimetric area method) and symphysis fundus height and the efficacy of these measurements in predicting birthweight by centile range was prospectively investigated in a blind study of 81 measurement sets in 74 women in the third trimester of pregnancy. Gestational length was determined by early ultrasound scans in all cases. Reference curves were from separate populations. Correlation between the measurements was significant, both at 32 weeks (p = 0.015) and 36 weeks (p less than 0.001), but only 21% of the variation in intra-uterine volume at 32 weeks and 63% at 36 weeks' gestation was attributable to changes in fundal height. Intra-uterine volume was therefore not accurately reflected by fundal height. Fundal height and intra-uterine volume were in the same centile range in 34% of cases. Maternal height and weight did not correlate with intrauterine volume, but there were significant relations with fundal height, particularly at 36 weeks. Birthweight correlated better with volume (r = 0.665) than with fundal height (r = 0.461) at 32 weeks, while at 36 weeks there was little difference (r = 0.691 and 0.794). In 54% of volume and 47% of symphysis fundus measurements there was agreement with the same centile range of birthweight. Predictive capacity of volume measurements appeared better for the lower birthweight ranges.     

Evaluation of Fundal Height Measurement in Antenatal Care

The value of symphysis-fundus measurement (fundal height) as a screening procedure for fetal growth was assessed. The reproducibility of measurements between staff of differing antenatal experience was +/- 2 cm in 95% of cases. Fundal height was correlated with ultrasound measurement of biparietal diameter and abdominal area, and coefficients of 0.84 and 0.74 respectively were obtained; 73.1% of babies weighing below the 10th percentile for gestation were detected by one measurement of 3 cm or more below the mean for gestation.     

Growth retardation in preterm infants

This paper combines earlier results on the relation between birthweight and gestational age, and the relation between fetal weight and ultrasound measurements of the fetal biparietal diameter (BPD) and mean abdominal diameter (AD) to investigate whether preterm infants (viewed as a group) are smaller than unborn fetuses of the same gestational age. The birthweight distribution for each sex at 223 and 258 days gestation was derived from the birthweight-for-gestational age charts based on 3888 newborn infants. The sex-specific intrauterine weight distribution was estimated from ultrasound measurement of the fetal BPD and AD performed on randomly selected fetuses of gestational age 223 and 258 days. The birthweights were lower than the intrauterine weights, especially early in pregnancy and for female infants. Thus, the 10th birthweight centile for girls at day 223 corresponds to the 4th centile of the 'true' intrauterine weight, and the 'true' intrauterine 10th centile corresponds to the 25th centile birthweight at day 223.     

Growth of total intrauterine, intra-amniotic and placental volume in normal singleton pregnancy measured by ultrasound

Summary. The growth of total intrauterine, intra-amniotic and placental volume during the latter half of pregnancy was studied longitudinally with ultrasound in 115 healthy women with normal singleton pregnancies. A parallel planimetric area method was used. The range and distribution of normal values between 20 and 40 weeks was determined for a main study group of 103 primiparous women with which values from 12 parous women were compared. Total intrauterine volume increased from a median of 1006 ml to 4420 ml, intra-amniotic volume from 716 ml to 3406 ml and placental volume, calculated as the difference between total intrauterine and intra-amniotic volume, increased from 259 ml to 801 ml. Variation between individuals was wide at all stages of pregnancy. No significant difference was found between primiparous and parous women. Between successive 5-week periods from 20 to 40 weeks there was evidence that women tended to maintain their initial volume ranking. During the 30–35 week period, rate of growth of total intrauterine and intra-amniotic volume was somewhat faster than the near constant mean rate at other times, while the rate of growth of placental volume decreased after 30 weeks towards term.     

Fetal anterior abdominal wall thickness in diabetic pregnancy

OBJECTIVE: The purpose of this study was to investigate whether third trimester fetal anterior abdominal wall (AAW) thickness in diabetic pregnancy reflects glycaemic control and predicts macrosomia. STUDY DESIGN: Prospective cohort study in a tertiary level maternity unit. One hundred and twenty-five diabetic mothers (71 pre-gestational and 54 gestational diabetics on insulin) underwent routine serial third trimester ultrasound examination with the additional measurement of AAW thickness. Pregnancy outcome was obtained. RESULTS: 335 fetal AAW measurements were recorded in diabetic pregnancy from 30 to 38 weeks gestation. Third trimester AAW was significantly higher in macrosomic babies (5.4+/-1.4mm vs. 4.7+/-1.4mm, p<0.05). ROC derived cut off for AAW in the prediction of macrosomia was 3.5mm at 30 weeks, 4.5mm at 33 weeks and 5.5mm at 36 weeks gestation. Using either a raised AAW measurement or an AC>90th centile, the prediction of birth weight greater than the 90th centile was better (88%) than with AC alone (70%). This improvement in sensitivity held even at earlier gestations in the third trimester. CONCLUSION: Measurement of AAW in diabetic pregnancy may have a role in the prediction of macrosomia.     

Growth of total intrauterine, intra-amniotic and placental volume in normal singleton pregnancy measured by ultrasound

The growth of total intrauterine, intra-amniotic and placental volume during the latter half of pregnancy was studied longitudinally with ultrasound in 115 healthy women with normal singleton pregnancies. A parallel planimetric area method was used. The range and distribution of normal values between 20 and 40 weeks was determined for a main study group of 103 primiparous women with which values from 12 parous women were compared. Total intrauterine volume increased from a median of 1006 ml to 4420 ml, intra-amniotic volume from 716 ml to 3406 ml and placental volume, calculated as the difference between total intrauterine and intra-amniotic volume, increased from 259 ml to 801 ml. Variation between individuals was wide at all stages of pregnancy. No significant difference was found between primiparous and parous women. Between successive 5-week periods from 20 to 40 weeks there was evidence that women tended to maintain their initial volume ranking. During the 30-35 week period, rate of growth of total intrauterine and intra-amniotic volume was somewhat faster than the near constant mean rate at other times, while the rate of growth of placental volume decreased after 30 weeks towards term.     

Growth retardation in preterm infants

Summary. This paper combines earlier results on the relation between birthweight and gestational age, and the relation between fetal weight and ultrasound measurements of the fetal biparietal diameter (BPD) and mean abdominal diameter (AD) to investigate whether preterm infants (viewed as a group) are smaller than unborn fetuses of the same gestational age. The birthweight distribution for each sex at 223 and 258 days gestation was derived from the birthweight-for-gestational age charts based on 3888 newborn infants. The sex-specific intrauterine weight distribution was estimated from ultrasound measurement of the fetal BPD and AD performed on randomly selected fetuses of gestational age 223 and 258 days. The birthweights were lower than the intrauterine weights, especially early in pregnancy and for female infants. Thus, the 10th birthweight centile for girls at day 223 corresponds to the 4th centile of the'true' intrauterine weight, and the'true' intrauterine 10th centile corresponds to the 25th centile birthweight at day 223.     

Association between first trimester maternal serum pregnancy associated plasma protein-A and adverse pregnancy outcome

AIMS: To investigate whether low pregnancy associated plasma protein-A (PAPP-A) levels in the first trimester of pregnancy are associated with subsequent intrauterine fetal growth restriction, stillbirth and preterm delivery. METHODS: A retrospective review of pregnancy outcomes was undertaken in women who had PAPP-A carried out in the first trimester of pregnancy at the time of nuchal translucency scan. Pregnancy outcomes were assessed by the review of medical records, and postal questionnaires. Delivery details were collected, including livebirth, neonatal birthweight and gestational age at delivery. The chi2 test was used to investigate the association between low first trimester serum PAPP-A levels and adverse fetal outcomes. Unpaired t-test was used for continuous variables. Sensitivities and specificities were then calculated. RESULTS: A total of 894 women who had blood collected for PAPP-A were identified, and data was obtained for 827 deliveries. Each had a normal karyotype. There were six intrauterine deaths, 13 babies with birthweights below the 3rd centile, 55 babies weighing below the 10th centile, and 96 women who delivered prematurely. Four of six intrauterine deaths had low PAPP-A levels (<0.5 multiples of the median), with a relative risk of 13.75. Low PAPP-A levels were associated with fetal weight below the 10th centile (P = 0.01) but not the 3rd centile. There was no statistically significant association between low maternal serum PAPP-A levels and preterm delivery. CONCLUSION: At 11-13 weeks' gestation, low maternal serum PAPP-A levels are associated with fetal death in utero and birthweight below the 10th centile. First trimester PAPP-A may be a useful tool for identifying pregnancies at risk of adverse fetal outcomes.     

Combining 2nd-trimester maternal serum homocysteine levels and uterine artery Doppler for prediction of preeclampsia and isolated intrauterine growth restriction

AIM: To evaluate the efficacy of a combined 2nd-trimester maternal serum homocysteine and uterine artery Doppler screening at 20 weeks of gestation for complications of pregnancy: preeclampsia, isolated intrauterine growth restriction (IUGR), placental abruption, and stillbirths. METHODS: Consecutive singleton pregnancies without previous risk factors who had homocysteine measured as part of a serum-screening program for trisomy 21 had uterine artery Doppler performed. Sensitivity, specificity, positive and negative predictive values, odds ratio, and positive and negative likelihood ratios for the subsequent development of preeclampsia, isolated IUGR, placental abruption, stillbirth, and preterm delivery were calculated for the following methods (1) homocysteine cut-off level 6.3 micromol/l (95th centile); (2) on Doppler ultrasound bilateral notches with a mean resistance index (RI) >0.55 (50th centile), all unilateral notches with a mean RI >0.65 (80th centile), and absence of notches with a mean RI >0.7 (95th centile), and (3) Doppler ultrasound notch evaluation (bilateral, unilateral, absence as in method 2) combined with the homocysteine cut-off level of 6.3 micromol/l. RESULTS: By using a logistic regression model, methods 1 and 2 predicted preeclampsia (p < 0.001), isolated IUGR (p < 0.01), and "any complication" (p < 0.01). The sensitivity for prediction of preeclampsia using the combined method (3) was 61.3% for a false-positive rate of 2%, better than that for isolated IUGR (54%) below the 5th centile and "any complication" (56%). CONCLUSION: This prospective study confirms the potential of a combined method of elevated homocysteine and uterine artery Doppler screening for preeclampsia, isolated IUGR, and any obstetric complication.     

Elsevier Trophoblast Research Award Lecture: Searching for an early pregnancy 3-D morphometric ultrasound marker to predict fetal growth restriction

Fetal growth restriction (FGR) is a major cause of perinatal morbidity and mortality, even in term babies. An effective screening test to identify pregnancies at risk of FGR, leading to increased antenatal surveillance with timely delivery, could decrease perinatal mortality and morbidity. Placental volume, measured with commercially available packages and a novel, semi-automated technique, has been shown to predict small for gestational age babies. Placental morphology measured in 2-D in the second trimester and ex-vivo post delivery, correlates with FGR. This has also been investigated using 2-D estimates of diameter and site of cord insertion obtained using the Virtual Organ Computer-aided AnaLysis (VOCAL) software. Data is presented describing a pilot study of a novel 3-D method for defining compactness of placental shape. We prospectively recruited women with a singleton pregnancy and BMI of <35. A 3-D ultrasound scan was performed between 11 and 13 + 6 weeks' gestation. The placental volume, total placental surface area and the area of the utero–placental interface were calculated using our validated technique. From these we generated dimensionless indices including sphericity (ψ), standardised placental volume (sPlaV) and standardised functional area (sFA) using Buckingham π theorem. The marker for FGR used was small for gestational age, defined as <10th customised birth weight centile (cSGA). Regression analysis examined which of the morphometric indices were independent predictors of cSGA. Data were collected for 143 women, 20 had cSGA babies. Only sPlaV and sFA were significantly correlated to birth weight (p < 0.001). Regression demonstrated all dimensionless indices were inter-dependent co-factors. ROC curves showed no advantage for using sFA over the simpler sPlaV. The generated placental indices are not independent of placental volume this early in gestation. It is hoped that another placental ultrasound marker based on vascularity can improve the prediction of FGR offered by a model based on placental volume.     

Placental protein measurements in complicated pregnancies. I. Intrauterine growth retardation

Maternal serum levels of human placental lactogen (hPL), schwangerschaftsprotein 1 (SP1) and pregnancy-associated plasma protein A (PAPP-A) were measured serially throughout pregnancy in 753 women who had a normal pregnancy when recruited during the second trimester. Thirty-three women were delivered of an infant with low birth-weight and with phenotypic features of intrauterine growth retardation (IUGR). The predictive value of an abnormal (less than 10th centile) hPL result (PVpos) in the identification of IUGR was between 28 and 32%, the sensitivity (36-54%) being greatest at 35 weeks gestation. The predictive value of a normal result (PVneg) was 87-96% at various stages of pregnancy, also greatest at 35 weeks gestation. For SP1, the sensitivity and predictive values were also greatest at 35 weeks gestation (PVpos, 20%; sensitivity, 32%; PVneg, 95%), but for PAPP-A these values were considerably less at all gestations. The trends in levels of hPL, SP1 and PAPP-A observed in individual patients with IUGR were not apparently related to any clinically recognizable feature of the pregnancy or the degree of fetal compromise, irrespective of whether the levels were within or outside the 80% confidence limits of the normal range or whether the levels fell from within the normal range. These data suggest that maternal hPL measurements are superior in the identification of IUGR in samples obtained at 30-35 weeks gestation.     

Placental protein measurements in complicated pregnancies. I. Intrauterine growth retardation

Summary. Maternal serum levels of human placental lactogen (hPL), schwangerschaftsprotein l (SP1) and pregnancy-associated plasma protein A (PAPP-A) were measured serially throughout pregnancy in 753 women who had a normal pregnancy when recruited during the second trimester. Thirty-three women were delivered of an infant with low birth-weight and with phenotypic features of intrauterine growth retardation (IUGR). The predictive value of an abnormal (< 10th centile) hPL result (PVpos) in the identification of IUGR was between 28 and 32%, the sensitivity (36–54%) being greatest at 35 weeks gestation. The predictive value of a normal result (PVneg) was 87–96% at various stages of pregnancy, also greatest at 35 weeks gestation. For SP1, the sensitivity and predictive values were also greatest at 35 weeks gestation (PVpos, 20%; sensitivity, 32%; PVneg, 95%), but for PAPP-A these values were considerably less at all gestations. The trends in levels of hPL, SP1 and PAPP-A observed in individual patients with IUGR were not apparently related to any clinically recognizable feature of the pregnancy or the degree of fetal compromise, irrespective of whether the levels were within or outside the 80% confidence limits of the normal range or whether the levels fell from within the normal range. These data suggest that maternal hPL measurements are superior in the identification of IUGR in samples obtained at 30–35 weeks gestation.     

What investigation is appropriate following maternal perception of reduced fetal movements?

It has been proposed that maternal perception of reduced fetal movements may be indicative of placental insufficiency, and that women who present with reduced fetal movements should be investigated for evidence of placental insufficiency. A retrospective case notes-based analysis of patients presenting with reduced fetal movements was undertaken. There were 92 live-born infants, the mean gestation at delivery was 39(+4) weeks. The median birth weight was 3,140 g. A total of 29.1% of infants had a birth weight of less than the 10th centile. A total of 35 women underwent ultrasound assessment of fetal growth and liquor volume. Measurement of symphyseal fundal height (SFH) had a greater specificity than a single ultrasound assessment in the prediction of IUGR at delivery. To reduce unnecessary intervention, SFH measurement may be used as a screening tool for those who merit ultrasound assessment of growth and umbilical artery Doppler.     

The hidden mortality of monochorionic twin pregnancies

In an ultrasound screening study at 10 to 14 weeks of gestation for measurement of fetal nuchal translucency thickness there were 102 monochorionic and 365 dichorionic twin pregnancies. In the monochorionic compared with the dichorionic pregnancies there was a higher rate of fetal loss before 24 weeks of gestation (12.2% versus 1.8%), perinatal mortality (2.8% versus 1.6%), prevalence of delivery before 32 weeks (9.2% versus 5.5%), and prevalence of birthweight below the 5th centile in both twins (7.5% versus 1.7%). However, the proportion of pregnancies with a birthweight discordancy of more than 25% was similar in the two groups (11.3% versus 12.1%).     

Doppler investigation of uteroplacental blood flow resistance in the second trimester: a screening study for pre-eclampsia and intrauterine growth retardation

OBJECTIVE--To assess the screening properties of a mid-trimester uteroplacental Doppler scan in a normal unselected population. DESIGN--A cross-sectional study measuring an averaged resistance index (AVRI) from four sites (left and right uterine and arcuate arteries) with continuous wave Doppler ultrasound. SETTING--Routine booking ultrasound, King's College Hospital, London. SUBJECTS--977 women at 16-24 weeks gestation. MAIN OUTCOME MEASURES--Intrauterine death, birthweight, pregnancy-induced hypertension (PIH), antepartum haemorrhage. RESULTS--There was a 96.5% follow-up. Pregnancies with high AVRI values had a higher prevalence of proteinuric hypertension, placental abruption, small-for-gestational-age babies, and fetal loss. When AVRI was greater than 95th centile, the overall risk of pregnancy complications was 67%, and the risk of a severe complication was 25%. However, the sensitivity of the test for these complications was only 13% and 21% respectively. The risk for an individual woman with a high AVRI of developing a complication was increased by up to 9.8 times. CONCLUSION--Although Doppler screening does detect a unifying defect leading to perinatal death, pre-eclampsia, growth retardation and placental abruption, the predictive values do not yet justify its introduction as a routine test.     

The validity of screening for small-for-gestational-age and low-weight-for-length infants by Doppler ultrasound

A prospective blind study assessed the efficacy of Doppler examination of the umbilical arteries (pulsatility index) as a screening procedure for predicting small-for-gestational-age and low-weight-for-length (low ponderal index) infants. Birthweight below the 2.3rd and 10th centile and ponderal index below the 3rd and 10th centile were chosen as 'cut-off' levels. Of pregnant women from our university hospital population, 400 were examined at 28 and 34 weeks gestation. The sensitivity of the test was low, ranging from 16.9 to 41.7% for the different indices. The predictive value of a negative screening test also was unsatisfactory, ranging from 79.6% to 97.9%. It is concluded that a single umbilical artery Doppler examination at 28 or 34 weeks does not satisfy the need in obstetrics for a simple and accurate technique to screen for small-for-gestational-age and low-weight-for-length infants in an unselected obstetric population.     

Maternal blood levels of human placental lactogen in the prediction of fetal growth retardation: choosing a cut-off point between normal and abnormal

Single estimations of serum human placental lactogen (hPL) were made in 527 unselected women between 36 and 40 weeks gestation. The association between decreased serum levels of hPL and intrauterine growth retardation was confirmed. The effect of changing the cut-off point between normality and abnormality on the sensitivity, specificity and predictive value was determined. When the 10th centile of hPL values was used, 29% of all growth-retarded fetuses were identified and 91% of all 'normal' fetuses were excluded. The 15th and 25th centiles yielded improved sensitivities of 37 and 50% respectively, but specificity was reduced. It is suggested that the 10th centile provides a good compromise between sensitivity on the one hand and specificity and predictive value on the other.     

Maternal blood levels of human placental lactogen in the prediction of fetal growth retardation: choosing a cut-off point between normal and abnormal

Summary. Single estimations of serum human placental lactogen (hPL) were made in 527 unselected women between 36 and 40 weeks gestation. The association between decreased serum levels of hPL and intrauterine growth retardation was confirmed. The effect of changing the cut-off point between normality and abnormality on the sensitivity, specificity and predictive value was determined. When the 10th centile of hPL values was used, 29% of all growth-retarded fetuses were identified ard 91% of all 'normal' fetuses were excluded. The 15th and 25th centiles yielded improved sensitivities of 37 and 50% respectively, but specificity was reduced. It is suggested that the 10th centile provides a good compromise between sensitivity on the one hand and specificity and predictive value on the other.