A total of 105
476 cases were entered during the two year collection period. Of these, 13
258 were excluded because of congenital anomaly or multiple pregnancy, which left 92
218 normally formed singleton pregnancies leading to 91
829 live births and 389 stillbirths. This represented a stillbirth rate of 4.2/1000 births and compares with nationally reported stillbirth rates of normally formed singletons of 3.9-4.1/1000 over the same period.26
The analysis included 841 (0.9%) repeat pregnancies during the two year period of the 92
218 mothers in the cohort.
Table 1 lists the variables, grouped according to maternal and fetal characteristics, social factors, medical history, and complications during pregnancy. Analysis was for complete cases only. The stillbirth rate is presented for subgroups, together with relative risks and 95% confidence intervals in relation to the respective reference values.
Table 1 Univariate analysis of risk factors associated with stillbirths compared with live births
For maternal characteristics, stillbirth rates were increased in first as well as third and subsequent pregnancies compared with second pregnancies, and in mothers of African, African-Caribbean, and South Asian ethnic origin compared with their European counterparts. First generation migrants had an overall higher risk of stillbirth. Maternal age indicated a slight increase in younger (<25) and older (≥35) mothers, suggesting a U-shaped distribution, but this trend did not reach significance.
Social factors with significant associations included deprivation and unemployment of the mother or her partner. Pregnancies in which the parents were blood relations were not at significantly increased risk. Obesity (body mass index ≥30), active as well as passive smoking, lack of antenatal folic acid, and booking after 13 weeks were all associated with an increased risk of stillbirth. A history of mental health problems, diabetes, and stillbirth increased the risk. In the current pregnancy, pre-eclampsia and antepartum haemorrhage were strongly associated, whereas gestational diabetes was not.
The strongest factor was fetal growth restriction, with a relative risk of 4.0 (95% confidence interval 2.8 to 5.7) when fetal growth restriction was detected antenatally, doubling to 8.0 (6.5 to 9.9) when it was not detected. The overall stillbirth rate (per 1000 births) was 4.2, which was a composite of a rate of 2.4 (185/76
356) in pregnancies without fetal growth restriction and 16.7 (195/11
697) in pregnancies with fetal growth restriction (table 1). Of pregnancies with fetal growth restriction, the stillbirth rate for cases detected antenatally was 9.7 (35/3601), whereas the rate increased to 19.8 (160/8096) when cases were not detected (fig 1).
Fig 1 Stillbirth rates in relation to fetal growth restriction and whether it was detected antenatally
Because of the strong interaction between smoking and fetal growth restriction, stillbirth rates for pregnancies with maternal smoking are also presented for subgroups of fetal growth restriction (table 2). The overall stillbirth rate (per 1000 births) was higher in mothers who smoked (5.8 v 3.8), but this was only the case for pregnancies with fetal growth restriction (13.0), whereas the risk of stillbirth in pregnancies without fetal growth restriction (3.7) was similar to that where the mother did not smoke (3.8). The highest risk of stillbirth was in pregnancies with fetal growth restriction where the mother did not smoke. Antenatal detection of fetal growth restriction during the study period was 31% overall (table 1) and higher in pregnancies where the mother smoked (1451/4012, 36.2%) than where she did not (1480/5280, 28.0%).
Table 2 Smoking and fetal growth restriction (birth weight <10th gestation related optimal weight centile)
Fig 2 shows cumulative frequency graphs for pregnancies with and without fetal growth restriction for stillbirths and live births. For both outcomes, pregnancies with fetal growth restriction tended to be delivered earlier. The median gestational age for stillbirths with fetal growth restriction was 32 weeks and three days compared with 36 weeks and six days for stillbirths without fetal growth restriction.
Fig 2 Stillbirths and live births with and without fetal growth restriction: cumulative percentage graph of gestational age at delivery
Table 3 lists the results of the Poisson regression model, which included all significant factors shown in the univariate analysis. Overall, 25
021 births, including 103 stillbirths, were excluded because of incomplete data. This represented a rate of 4.1/1000 births, which was similar to the overall rate of stillbirth (4.2/1000, table 1). Sensitivity analyses of the excluded factors (P>0.05 in univariate analysis), of clustering of births within maternity units (see supplementary appendices 1 and 2), and of repeat pregnancies by the same mother (results not shown) indicated only minor differences in confidence intervals and resulted in no changes in relative risks.
Table 3 Multivariable analysis of significant (P<0.1) risk factors in table 1
First, third, and higher order pregnancies were significantly associated with stillbirth as were pregnancies in African, African-Caribbean, and Indian mothers and first generation migrants from Pakistan. Obesity (body mass index >30), pre-existing diabetes, history of mental health problems, and antepartum haemorrhage in the index pregnancy were associated with an increased risk of stillbirth.
Interactions between all variables were tested and were found to be non-significant, with the exception of a strong interaction between smoking and fetal growth restriction. Therefore the results are presented separately for smokers with pregnancies that did or did not have fetal growth restriction. Active smoking was associated with an increased risk of stillbirth (adjusted relative risk 2.5, 95% confidence interval 1.7 to 3.6), but the association became substantially stronger (5.7, 3.6 to 8.9) for pregnancies where the fetus was also growth restricted. There was no association between passive smoking and stillbirth unless fetal growth restriction was also present, in which case the relative risk was even higher than with active smoking (10.0, 6.6 to 15.8). The risk of stillbirth was increased for all pregnancies with fetal growth restriction, but was highest when the mother did not smoke (7.8, 5.6 to 10.9).
Table 3 also lists the population attributable risk derived from prevalence and relative risk of each significant factor. The model was able to attribute risk factors to 80.6% of the stillbirths in this cohort. The highest population attributable risks were associated with fetal growth restriction, primiparity, and antepartum haemorrhage.
In pregnancies with fetal growth restriction, the adjusted risk of stillbirth was 3.4 (2.2 to 5.2) if fetal growth restriction was detected antenatally. The risk increased to 6.5 (4.9 to 8.4) if fetal growth restriction was not detected, and 32% of the stillbirths could be attributed to this group. Pregnancies with fetal growth restriction detected antenatally were delivered on average 10 days earlier than those not detected antenatally (table 4).
Table 4 Gestational age at delivery and risk of stillbirths in pregnancies with fetal growth restriction*, with and without antenatal detection
Just over half of the stillbirths (203/389, 52%) occurred after 34 weeks of gestation. Table 5 presents the significant pathological factors of the model, adjusted for maternal characteristics, for stillbirths before and after 34 weeks of gestation. For stillbirths between 24 and 33 weeks of gestation, the only significant factor was fetal growth restriction (adjusted relative risk 4.0, 2.9 to 5.6), which accounted for just under half of the stillbirths (population attributable risk 49.5%). At the same time, pre-eclampsia emerged as a significant protective factor. From 34 weeks of gestation, fetal growth restriction again represented the strongest risk, and was highest in pregnancies where the mother did not smoke.
Table 5 Fetal growth restriction and other pathological factors before and after 34 weeks of gestation