Predictors of ratio of placental weight to fetal weight in multiethnic community

Introduction

Barker and colleagues have reported that the risk of essential hypertension in adult life falls with increasing birth weight and rises with increasing placental weight and that the people at highest risk are those with a high placental weight relative to birth weight—that is, a high placental ratio.1 The group has stressed the likely dominant influence of maternal nutrition, and in particular maternal iron deficiency anaemia, on intrauterine growth.2 Using data from the Oxford record linkage system, they described a specific association between low maternal haemoglobin combined with a fall in mean cell volume during pregnancy and a raised placental ratio.3

The maternal factors that lead to discordance between birth and placental weight are, however, poorly understood. The importance of maternal nutrition as a determinant of placental ratio is disputed.4 The data from the Oxford record linkage system showed a strong positive association between maternal body mass index and placental ratio, an association which has received relatively little attention.3 Obesity and hypertension are linked in pregnancy as in the non-pregnant state.5 Though preeclampsia is known to be associated with increased placental ratio,6 the relation between more common manifestations of hypertension in pregnancy, such as gestational hypertension, and placental ratio is unclear.

We studied maternal factors that influence the ratio of placental weight to birth weight (placental ratio) in women recruited for a study of early markers for pre-eclampsia. The women were from a multiethnic inner city community with a relatively high proportion of patients of Asian (mainly first generation from northern India, Pakistan, and Bangladesh) and Afro-Caribbean ethnic origin. There is evidence of poor maternal nutrition in pregnant Asian women relative to European women.7 8 If nutrition is an important determinant of placental ratio the placental ratio would be expected to be higher in this group.

The aim of this study was to identify maternal factors which influence placental ratio in this population, with particular reference to the role of maternal ethnic origin, obesity, and hypertension and haematological indices of maternal iron deficiency anaemia.

Subjects and methods

We studied a group of 692 healthy nulliparous pregnant women referred for antenatal care to Dudley Road Hospital, Birmingham, before the 31st week of gestation. The median gestational age at referral was 16 weeks (interquartile range 13-18 weeks), and 85% of the women were referred at or before the 20th completed week of pregnancy. These women were recruited for a prospective study of early markers for pre-eclampsia.9 10 Women with diabetes and twin births were excluded. Of the 692 women, 367 were European, 213 Asian, 99 Afro-Caribbean, and 13 of other or undocumented ethnic origin. This represents the usual ethnic distribution of nulliparous women referred to the hospital. Iron supplements were prescribed at the booking antenatal visit for women with a haemoglobin concentration below 11.0 g/l.

Proteinuric pre-eclampsia and gestational hypertension were defined according to current internationally agreed criteria.11 Data on birth weight and placental weight (untrimmed) and gestational age at birth (estimated from last menstrual period and ultrasound scan at first visit) were obtained from labour ward records. Additional data from the antenatal record included maternal ethnic origin, age, height, blood pressure at first antenatal visit, smoking status, and haemoglobin concentration, packed cell volume, and mean cell volume at first visit. Complete data from the antenatal and labour ward records were available for 80% of pregnancies. Third trimester blood samples (additional to those obtained routinely) were obtained for measurement of full blood count and serum ferritin from 407 and 318 women respectively. The availability of these data depended on whether women were asked and agreed to provide third trimester samples for research purposes. The women from whom third trimester samples were obtained were representative of the total study population with regard to ethnic origin, age, gestational age at booking, smoking status, and birth weight. Blood counts were determined on a Technicon H1 auto-analyser (Bayer, Basingstoke) and ferritin was measured by a quantitative immunoradiometric determination (Becton Dickinson, Oxford).12 Maternal body mass index was calculated as weight at the first visit divided by the square of height (kg/m²).

Factors influencing placental ratio, birth weight, and placental weight were studied in multiple regression analysis. Gestational hypertension and pre-eclampsia were fitted as separate indicator variables in regression analysis. Stepwise regression with the maximum F statistic criteria was used to identify significant predictors (at the 5% level) of placental ratio, birth weight, and placental weight.13 The distribution of serum ferritin was markedly skewed, and these data were log transformed before analysis.

Results

Table I shows the baseline characteristics and pregnancy outcome variables, including placental ratio, for the three ethnic groups. There were significant differences between the groups in age, height, body mass index, smoking prevalence, haemoglobin concentration, packed cell volume, mean cell volume, systolic blood pressure, and incidence of gestational hypertension. Gestational age at birth was similar in the three groups. Placental ratio was also similar in the three ethnic groups, but birth weight and placental weight were lower in Asian than in European and Afro-Caribbean women (table I). Gestational age at delivery was inversely associated with placental ratio (r=-0.34, P<0.001). A positive linear association between body mass index and placental ratio was observed (r=0.1, P=0.01). Mean (SD) placental ratio was not significantly higher in smokers (n=146) than in non-smokers n=536) (20.4% (3.9%) v 19.8% (3.9%); 95% confidence interval for difference - 1.3% to 0.1%).

Lower gestational age at birth and higher maternal body mass index were the only significant independent predictors of placental ratio in the multiple regression analysis (table II). Gestational age at delivery and body mass index were also both positively associated with placental weight and birth weight. Additional predictors of placental weight and birth weight are shown in table II. These findings were unaltered by exclusion of women booking after 20 weeks of gestation.

Of the 692 nulliparous women, 55 (8%) developed gestational hypertension and 12 (1.7%) pre-eclampsia. Placental ratio tended to be higher in women who developed gestational hypertension (20.4% (SD 4.5%)) and pre-eclampsia (22.3% (7.3%)) compared with those who remained normotensive (19.8% (3.8%)), though this trend, which largely reflects gestational age at delivery, was not significant.

Of 638 women with first antenatal haemoglobin data whose ethnic origin was documented, 33 (16%) of the Asian women had haemoglobin concentrations below 110 g/l, regarded as a cut off point for anaemia in pregnancy, compared with 43 (10%) of the combined European and Afro-Caribbean group (95% confidence interval for difference 0.6% to 11%, P=0.03). Placental ratio was not significantly associated with first antenatal visit haemoglobin concentration or mean cell volume (r=-0.02 and r=-0.02). Among 643 women with data available, placental ratio did not differ between the 79 women with a haemoglobin concentration below 110 g/l and the 564 women with a concentration of 110 g/l or above (19.8% (3.9%) v 19.8% (3.4%)). Mean cell volume increased by a mean (SD) of 3.3 (4.9) fl between the first antenatal visit and the third trimester (range -14 to 20 fl). Among 396 women with data available, no significant difference in placental ratio was observed between the 90 women whose mean cell volume fell between the first visit and third trimester measurements and the 306 whose mean cell volume was unchanged or increased (19.3% (3.0%) v 19.7% (3.6%); 95% confidence interval for difference -1.1% to 0.4%). Similarly, no significant associations were observed between placental weight or birth weight and change in mean cell volume between the first and second antenatal visit.

Third trimester serum ferritin concentrations were higher in women whose mean cell volume was unchanged or increased between the first and second antenatal visit (geometric mean (range) 13.9 (12.3-15.8) μg/l) than in women whose mean cell volume fell (8.9 (6.6-12.1) μg/l; P=0.009). However, no significant association between placental ratio and serum ferritin was observed (r=0.02). The univariate analysis showed weak inverse associations between birth weight and serum ferritin (r=-0.12, P=0.04) and between placental weight and serum ferritin (r=-0.12, P=0.04). When ethnic origin and gestational age at birth were adjusted for these associations were no longer significant. Of the 318 women for whom ferritin data were available, 113 had concentrations below the normal range (10 μg/l). Placental ratio was not significantly higher in these women than in those with normal ferritin concentrations (20.0% (3.5%) v 19.4% (3.7); -1.4% to 0.3%).

Discussion

In this study the ratio of placental weight to fetal weight, which has been linked to hypertension in adult life, was increased in the offspring of obese women. Placental ratio was similar in European, Asian, and Afro-Caribbean women despite the evidence of poor nutrition among pregnant Asian women in Birmingham.7 8 Placental ratio was not significantly associated with first visit haemoglobin concentration, mean cell volume, change in mean cell volume between the first antenatal visit and the third trimester, or third trimester serum ferritin concentration.

These findings do not support the hypothesis that a raised placental ratio is a marker for poor maternal nutrition. Edwards et al have argued that maternal nutrition (excepting extreme malnutrition) has little importance in fetal and placental growth, instead suggesting that raised placental ratios reflect increased fetal exposure to maternal glucocorticoids.4 14 Their work, taken with our results, suggests that maternal obesity rather than poor nutrition may be an important determinant of placental ratio through effects on maternal glucocorticoid concentrations. The link between raised placental ratio at birth and the subsequent development of essential hypertension may therefore be confounded by maternal obesity.