Maternal serum activin A levels in association with intrauterine fetal growth restriction

Objective To assess maternal serum activin A as a potential marker of fetal growth restriction.
Design A cohort study.
Setting A maternal–fetal medicine unit, university teaching hospital.
Population Fifty-seven women with a small fetus (less than 10th centile for gestation) referred for assessment of fetal size by ultrasound biometry.
Methods At the time of presentation for fetal biometry, maternal blood was collected for activin A measurement. The case records of each woman were independently reviewed after delivery and the pregnancy grouped into one of three groups: constitutionally small fetus, intrauterine growth restricted (IUGR) fetus or IUGR fetus and maternal pre-eclampsia (IUGR–pre-eclampsia). Activin A levels in the three groups were compared.
Main outcome measures Maternal serum activin A levels.
Results Sixteen of the 57 pregnancies were classified as constitutionally small, 17 as IUGR and 24 as IUGR–pre-eclampsia. Expressed as multiples of a normal median (MoMs), the median (95% CI) activin A level in the constitutionally small pregnancies was 1.12 (0.72–1.39) MoMs significantly lower than the level in both the IUGR pregnancies, 3.00 (1.84–4.11) MoMs, and the IUGR–pre-eclampsia pregnancies, 7.96 (5.73–10.62) MoMs (   P = 0.002 and 0.0001 for IUGR vs constitutionally small and IUGR–pre-eclampsia vs constitutionally small, respectively  ).
Conclusions Maternal serum activin A may be useful in the assessment of the small for gestational age fetus.     

Levels of C-reactive protein in pregnant women who subsequently develop pre-eclampsia

Objective To investigate whether a maternal inflammatory response precedes the development of pre-eclampsia.
Design Cross-sectional study.
Setting Antenatal clinic in an inner city teaching hospital.
Population Two groups of women were examined at 23–25 weeks of gestation. The first group (45 women) had normal uterine artery Doppler waveforms and subsequently had a normal pregnancy outcome. The second group (45 women) had Doppler evidence of impaired placental perfusion and 21 (47%) of them had normal outcome, 14 (31%) developed intrauterine growth restriction and 10 (22%) developed pre-eclampsia, with or without intrauterine growth restriction.
Methods C-reactive protein, an acute-phase reactant, was measured in maternal serum using a highly sensitive method with a detection limit of 0.05mg/L.
Main Outcome Measures Development of pre-eclampsia, as defined by the International Society for the Study of Hypertension in Pregnancy. Intrauterine growth restriction was defined as birthweight <5th centile for gestation and sex of the neonate.
Results The serum C-reactive protein concentration in women who subsequently developed pre-eclampsia (median 1.56, range 0.55–3.12mg/L) or delivered a baby with birthweight <5th centile (median 0.74, range 0.64–1.58mg/L) was not significantly different from that in women with uncomplicated pregnancies (median 1.28, range 0.75–2.08mg/L;   P = 0.95  and   P = 0.62  , respectively).
Conclusion These findings suggest that the onset of clinical signs of pre-eclampsia may not be preceded by a maternal inflammatory response, as assessed by measurement of C-reactive protein.     

Safety of birth centre care: perinatal mortality over a 10-year period

Objective   To study perinatal mortality in women booked for birth centre care during pregnancy.
Design   Retrospective cohort study.
Setting   In-hospital birth centre and standard maternity care in Stockholm.
Population   Two thousand and five hundred and thirty-four women (3256 pregnancies) admitted to an in-hospital birth centre over 10 years (1989–2000) and 126,818 women (180,380 pregnancies) who gave birth in standard care during the same period and who met the same medical inclusion criteria as in the birth centre. Multiple pregnancies were excluded.
Methods   Data were collected from the Swedish Medical Birth Register. Information on all cases of perinatal death in the birth centre group was retrieved from the medical records.
Main outcome measure   Perinatal mortality.
Results   No statistically significant difference in the overall perinatal mortality rate was observed between the birth centre group and the standard care group (odds ratio [OR] 1.5, 95% CI 0.9–2.4), but infants of primiparas were at greater risk (OR 2.2, 95% CI 1.3–3.9). Infants of multiparas tended to be at lower risk, but this difference was not statistically significant (OR 0.7, 95% CI 0.3–1.9). These figures were adjusted for maternal age and gestation in multiple regression analyses.
Conclusion   Birth centre care may be less safe for infants of first-time mothers.     

Antenatal glucocorticoid administration increases corticotrophin-releasing hormone in maternal plasma

Objective This study was designed to determine whether maternal corticotrophin-releasing hormone (CRH) concentrations are altered after maternal betamethasone administration for fetal lung maturity in women with threatened pretenn labour and whether these effects are dependent on gestational age.
Methods Our study included 49 women with threatened preterm labour who received prenatal betamethasone for fetal lung maturity between 24 and 31 weeks of gestational age and 11 women who did not. Maternal blood was taken before and after glucocorticoid administration or at 24 hours after initial sampling. Plasma CRH, adrenocorticotrophin (ACTH) and cortisol concentrations were determined by radioimmunoassays. The women were stratified into 24–25 weeks, 26–27 weeks, 28–29 weeks, and 30–31 weeks completed gestation.
Results At each gestational age, maternal cortisol concentrations decreased by approximately 85% after glucocorticoid administration. Overall mean cortisol values fell from 580.0 (SD, 351.8) to 89.7 (96.6) nmol/L ( n = 40,   P < 0.001  ). Overall mean ACTH values decreased from 9.9 (4.7) to 5.0 (3.4) pmol/L ( n = 43, P < 0*001), and the approximate 50% decrease was similar at each gestational age. In marked contrast, overall mean CRH values increased from 58.0 (37.0) to 87.8 (68.6) pmol/L ( n = 49,   P < 0.001  ) after betamethasone administration. There was no change in maternal cortisol, ACTH or CRH values over 24 hours in women who did not receive betamethasone.
Conclusions We conclude that maternal betamethasone administration increases maternal plasma CRH values between 24 and 31 completed weeks of gestation.     

S-relaxin as a predictor of preterm delivery in women with symptoms of preterm labour

Objective To evaluate whether serum relaxin (S-relaxin) can predict spontaneous delivery before 34 weeks of gestation in high risk pregnancies.
Design A prospective cohort study.
Setting Calculated sample size was reached over a two-year period, during which 9507 women gave birth. Of these, 157 healthy women were eligible for the study as they were admitted with symptoms of delivery before 34 weeks of gestation. Ninety-three women were included. Overall participation rate was 59%.
Population Healthy women with singleton pregnancies with symptoms of delivery before 34 weeks of gestation.
Methods S-relaxin was measured using a standard sandwich ELISA.
Main outcome measures End points were preterm delivery before 34 weeks of gestation and delivery within three days from initiation of symptoms. The best possible prediction of preterm delivery was established using logistic regression for risk factors individually associated with preterm delivery before 34 weeks of gestation. S-relaxin was dichotomised to obtain best possible fit and then entered into the model. The same analyses were done for delivery within three days.
Results Median S-relaxin levels varied significantly in the women with preterm prelabour rupture of membranes (PPROM) (316 pg/mL), contractions (222 pg/mL) or ripe cervices (203 pg/mL) (   P < 0.05  ). S-relaxin above the 80th centile (≥300 pg/mL) was associated with an increased risk of preterm delivery [crude  OR = 4.8; (95% CI: 1.9–12)  ]. Likelihood ratio of a positive test is 2.6 (1.5–4.9) and S-relaxin resulted in a post-test probability of preterm delivery of 0.72, compared with a pre-test probability of 0.49. S-relaxin contributed to the identification of delivery within three days [adj.  OR = 11 (95% CI: 1.8–64)  ].
Conclusion S-relaxin may be a useful predictor in women with symptoms of delivery before 34 weeks of gestation.     

Complications during pregnancy in women with epilepsy: population-based cohort study

Objective  To investigate whether women with epilepsy have an increased risk of complications during pregnancy and to explore the impact of antiepileptic drug (AED) use.
Design  Population-based cohort study.
Setting  Data from Medical Birth Registry of Norway based on all births in Norway 1999–2005.
Population  All births ( n  = 372 128) delivered in Norway, ensured through linkage with the National Population Registry run by Statistics Norway. All singleton births and the first child in multiple pregnancies were included, leaving 365 107 pregnancies for analyses.
Main outcome measures  Pre-eclampsia (mild and severe), gestational hypertension, eclampsia, vaginal bleeding (early and late) and preterm birth.
Results  We compared 2805 pregnancies in women with a current or past history of epilepsy (0.8%) and 362 302 pregnancies in women without a history of epilepsy. Women with epilepsy had an increased risk of mild pre-eclampsia, [odds ratio 1.3: 95% confidence interval (1.1–1.5)] and delivery before week 34 [1.2: (1.0–1.5)].
Antiepileptic drugs were used in 33.6% ( n  = 942) of the pregnant women with epilepsy. Compared to women without epilepsy, women with epilepsy and AED use had an increased risk of mild pre-eclampsia [1.8: (1.3–2.4)], gestational hypertension [1.5: (1.0–2.2)], vaginal bleeding late in pregnancy [1.9: (1.1–3.2)], and delivery before 34 weeks of gestation [1.5: (1.1–2.0)]. No significant increase in the risk of these complications was observed in women with epilepsy not using AED. These results remained unchanged after exclusion of multiple pregnancies.
Conclusion  Women with epilepsy have a low complication rate, but special attention should be paid to those using AED during pregnancy.     

Low dose acetylsalicylic acid in prevention of pregnancy-induced hypertension and intrauterine growth retardation in women with bilateral uterine artery notches

Objective To evaluate the efficacy of low-dose acetylsalicylic acid in the prevention of pregnancy-induced hypertension and intrauterine growth retardation in high-risk pregnancies as determined by transvaginal Doppler ultrasound study of the uterine arteries at 12 to 14 weeks of gestation.
Design Randomised, double blind and placebo-controlled trial.
Setting The Department of Obstetrics and Gynaecology, Tampere University Hospital, Finland.
Population One hundred and twenty pregnant women considered to be at high risk of pre-eclampsia or intrauterine growth retardation were screened by transvaginal Doppler ultrasound at 12 to 14 weeks of gestation.
Methods Ninety pregnant women with bilateral notches in the uterine arteries were randomised to receive acetylsalicyclic acid 0.5mg/kg/day (   n = 45  ) or placebo (   n = 45  ) from 12 to 14 weeks of gestation.
Main outcome measures Hypertensive disorders of pregnancy and intrauterine growth retardation.
Results Forty-three women on acetylsalicyclic acid and 43 on placebo were successfully followed up. The use of acetylsalicyclic acid was associated with a statistically significant reduction in the incidence of pregnancy-induced hypertension (  11.6% vs 37.2%, RR = 0.31, 95% CI 0.13–0.78  ) and pre-eclampsia (  4.7% vs 23.3%, RR = 0.2, 95% CI 0.05–0.86  ). The incidence of hypertension before 37 weeks of pregnancy was also significantly reduced (  2.3% vs 20.9%, RR = 0.22, 95% CI 0.05–0.97  ). The reduction in the incidence of intrauterine growth retardation (2.3% vs 7%) was not statistically significant. Acetylsalicyclic acid was not associated with excess risk of maternal or fetal bleeding.
Conclusion In women rated in Doppler velocimetry waveform analysis to be at high risk of pre-eclampsia, low-dose acetylsalicyclic acid reduces the incidence of pregnancy-induced hypertension and especially proteinuric pre-eclampsia.     

Ampicillin-metronidazole treatment in idiopathic preterm labour: a randomised controlled multicentre trial

Objective To determine whether treatment with ampicillin and metronidazole in women with threatened idiopathic preterm labour will prolong the gestation and reduce maternal and neonatal infectious morbidity.
Design Randomised controlled double-blind trial.
Setting Six obstetric departments in the Copenhagen area.
Population One hundred and twelve women with singleton pregnancies, with threatened idiopathic preterm labour and intact amniotic membranes at 26 to 34 weeks of gestation.
Methods Random allocation to eight days intravenous and oral treatment with ampicillin and metronidazole, or placebo.
Main outcome measures Number of days from admission to delivery, gestational age at delivery, rates of preterm delivery, low birthweight, maternal infections and neonatal infections.
Results Treatment with ampicillin and metronidazole was associated with a significant prolongation of pregnancy (admission to delivery 47.5 days versus 27 days,   P < 0.05  ), higher gestational age at delivery (37 weeks versus 34 weeks,   P < 0.05  ), decreased incidence of preterm birth (42% versus 65%,   P < 0.05  ), and lower rate of admission to neonatal intensive care unit (40% versus 63%,   P < 0.05  ), when compared with placebo treatment. Antibiotic treatment had no significant effects on infectious morbidity.
Conclusions Treatment with ampicillin and metronidazole in women with threatened idiopathic preterm labour significantly prolonged the gestation, but had no effects on maternal and neonatal infectious morbidity.     

Amniotic fluid interleukin-18 at mid-trimester genetic amniocentesis: relationship to intraamniotic microbial invasion and preterm delivery

Objective  To determine the value of amniotic fluid interleukin-18 (AF IL-18) in the diagnosis of microbial invasion of the amniotic cavity and prediction of preterm delivery (PTD).
Design  Analysis of the results of AF collected prospectively following genetic amniocentesis between February 2006 and September 2007.
Setting  A tertiary referral centre for fetal medicine.
Methods  Following amniocentesis, a sample of amniotic fluid was transferred to the laboratory for aerobic and anaerobic bacterial cultures, Ureaplasma urealyticum culture and IL-18 assays. All women who delivered preterm (<37 weeks of gestation) formed the study group. The control group consisted of the two subsequent women who also underwent amniocentesis during the same time period and delivered a normal neonate at term, matched for maternal age, parity and indication for amniocentesis.
Main outcome measures  The relationship between AF IL-18 levels and the risk of both microbial invasion of the amniotic cavity and PTD.
Results  Forty-eight women who delivered preterm (<37 weeks) were matched with 96 controls. The preterm delivery group had significantly higher concentrations of IL-18 (median = 609 pg/ml, interquartile range: 445.7–782.7) compared to controls (median = 322.1 pg/ml, interquartile range: 277.7–414.4), ( P  < 0.001). IL-18 level was also significantly higher ( P  < 0.001) in cases with positive amniotic fluid cultures (median = 697.7, interquartile range: 609.0–847.2) compared to those with negative ones (median = 330.9 pg/ml, interquartile range: 235.2–440.8).
Conclusions  Elevated mid-trimester concentrations of AF IL-18 can identify women at risk for intraamniotic infection and spontaneous PTD.     

Fetal macrosomia and pregnancy outcomes

Background:  Pregnancies with a macrosomic fetus comprise a subgroup of high-risk pregnancies. There is uncertainty in the clinical management and outcomes of such pregnancies.
Aim:  We sought to examine clinical management and maternal and fetal outcomes in pregnancies with macrosomic infants at Royal Brisbane and Women's Hospital (RBWH).
Methods:  Data from 276 macrosomic births (weighing ≥ 4500 g) and 294 controls (weighing 3250–3750 g) delivered during 2002–2004 at RBWH were collected from the hospital database. Univariate and logistic regression analyses were performed for maternal risk factors and maternal and neonatal outcomes that were associated with fetal macrosomia.
Results:  Macrosomia was more than two times likely in women with body mass index (BMI) of  > 30 kg/m² (odds ratio (OR) 2.41, 95% confidence interval (CI) 1.26–4.61) and in male infant sex (OR 2.05, 95% CI 1.35–3.12), and four times more likely in gestation of > 40 weeks (OR 3.93, 95% CI 1.99–7.74). Maternal smoking reduced the risk of fetal macrosomia (OR 0.27, 95% CI 0.14–0.51).
Macrosomia was associated with nearly two times higher risk of emergency caesarean section (OR 1.75, 95% CI 1.02–2.97) and maternal hospital stay of > 3 days (OR 1.66, 95% CI 1.11–2.50), and four times higher risk of shoulder dystocia (OR 4.08, 95% CI 1.62–10.29). Macrosomic infants were twice as likely to have resuscitation (OR 2.21, 95% CI 1.46–3.34) and intensive care nursery admission (OR 1.89, 95% CI 1.03–3.46).
Conclusion:  Macrosomia was associated with an increased risk of adverse maternal and neonatal health outcomes. Optimal management strategies of macrosomic pregnancies need evaluation.     

A longitudinal observational study of preference for elective caesarean section among nulliparous Hong Kong Chinese women

Objective  To establish whether women's preference for elective caesarean section (ELCS) changes as gestation advances.
Design  A prospective longitudinal observational study.
Setting  Two units providing obstetric care in Hong Kong, one public and one private.
Sample  Five hundred and one nulliparous Chinese pregnant women attending their routine fetal anomaly scan in either unit.
Methods  Consented subjects had two interviews using a structured questionnaire at 18–22 weeks and 35–37 weeks of gestation, respectively. Multivariate analysis was performed to identify determinants for preferring ELCS at the two gestational ages.
Main outcome measure  The preferences for the mode of delivery at the two gestational ages.
Results  The prevalence of maternal preference for ELCS in the study cohort was 17.2% (95% CI 13.9–20.5) and 12.7% (95% CI 9.6–15.8) at mid-trimester and at term, respectively. Significantly more women who preferred ELCS at mid-trimester changed to a trial of vaginal delivery (VD) at term than vice versa (42.0 versus 3.8%). The partner's preference for ELCS was a significant determinant for women preferring ELCS throughout the antenatal period. Among the women booked in the public sector, more women who preferred ELCS at term changed to deliver in private hospitals than those who preferred VD (46.2 versus 9.7%).
Conclusions  Many women changed from preferring ELCS to preferring VD as their pregnancy approached term. The partner's preference was a significant determinant for the women's choice. If a decrease in the proportion of women preferring ELCS is desired, the intervention programme should target the women and their partners who hold such a preference at 20 weeks.     

Serial Transvaginal Ultrasonography Following McDonald Cerclage and Repeat Suture Insertion

Summary: The aim of this study was to explore the hypothesis that serial transvaginal ultrasonography identifies early evidence of suture failure and that repeat cerclage delays delivery. We undertook a review of our policy of transvaginal ultrasonographic cervical surveillance after McDonald cerclage and of repeat suture insertion if persistent cervical effacement developed. Data from 26 pregnancies in 26 women are analyzed. The women had had a total of 57 mid-trimester miscarriages with a median of 2 (1–6) mid-trimester losses per woman. Twelve (46%) of the 26 women developed cervical changes at scan and underwent repeat cerclage. All 14 women who had a single suture inserted progressed to live births but 1 of the 13 women who had repeat cerclage had a mid-trimester miscarriage (p<0.05). The median gestation at delivery for the women who had repeat cerclage was 35 (22–39) weeks compared with 38 (36–40) weeks for those who had a single suture (p>0.05). The median interval from the detection of cervical changes at scan to delivery was 13 (4–19) weeks. Serial transvaginal ultrasonography after cervical cerclage identifies a group of women who are more likely to deliver preterm, and provides an opportunity for intervention (repeat cerclage) which appears to delay delivery by an average of 7 weeks.     

Serial Transvaginal Ultrasonography Following McDonald Cerclage and Repeat Suture Insertion

Summary: The aim of this study was to explore the hypothesis that serial transvaginal ultrasonography identifies early evidence of suture failure and that repeat cerclage delays delivery. We undertook a review of our policy of transvaginal ultrasonographic cervical surveillance after McDonald cerclage and of repeat suture insertion if persistent cervical effacement developed. Data from 26 pregnancies in 26 women are analyzed. The women had had a total of 57 mid-trimester miscarriages with a median of 2 (1–6) mid-trimester losses per woman. Twelve (46%) of the 26 women developed cervical changes at scan and underwent repeat cerclage. All 14 women who had a single suture inserted progressed to live births but 1 of the 13 women who had repeat cerclage had a mid-trimester miscarriage (p>0.05). The median gestation at delivery for the women who had repeat cerclage was 35 (22–39) weeks compared with 38 (36–40) weeks for those who had a single suture (p>0.05). The median interval from the detection of cervical changes at scan to delivery was 13 (4–19) weeks. Serial transvaginal ultrasonography after cervical cerclage identifies a group of women who are more likely to deliver preterm, and provides an opportunity for intervention (repeat cerclage) which appears to delay delivery by an average of 7 weeks.     

Twin deliveries and place of birth in NSW 2001–2005

Background:  Twin pregnancies have an elevated risk of adverse outcomes, particularly preterm twins.
Aims:  Describe the distribution of twin deliveries by hospital level, the associated perinatal and maternal morbidity, and determine predictors of perinatal morbidity and urgent transfer to a neonatal intensive care unit.
Methods:  Longitudinally linked New South Wales delivery and hospital records for the years 2001–2005 were used to identify perinatal and maternal morbidity/mortality in twin pregnancies. Regression analysis was used to examine predictive factors, including birth hospital volume.
Results:  At ≤ 32 weeks, 88.1% of twins were delivered in tertiary referral hospitals. By 34–35 weeks, only 39.7% of twins were delivered in tertiary units. Gestational age was the primary predictor of perinatal morbidity/mortality. Perinatal morbidity/mortality and maternal morbidity were lowest for deliveries at 38 weeks. There was no evidence that planned caesarean section at ≤ 38 weeks was protective against perinatal morbidity/mortality. There was an increased risk of perinatal morbidity/mortality (odds ratio (OR) = 2.22) for twins delivered at 33–35 weeks gestation at hospitals with < 500 deliveries per annum, and an increased risk of urgent neonatal transfer (OR = 2.06). Twin pairs for whom there was a ≥ 20% discordance in birthweight had an increased risk of morbidity/mortality at 36–38 weeks (OR = 1.79).
Conclusions:  Both infant and maternal morbidity increase from 39 weeks gestation. Delivery of twins before 36 weeks at smaller hospitals (< 500 deliveries per annum) should be avoided. A twin pregnancy where there is a ≥ 20% difference in estimated fetal weights should be considered for referral to a tertiary obstetric unit.     

Isolated oligohydramnios is not associated with adverse perinatal outcomes

Objective   To examine fetal growth and perinatal outcomes in pregnancies with isolated oligohydramnios.
Design   A cohort study.
Setting   Multiple clinics and hospitals.
Population   Low risk pregnant women.
Methods   We used data from the multicentre clinical trial of Routine Antenatal Diagnostic Imaging with UltraSound (RADIUS), in which 15,151 low risk pregnant women were randomly assigned to the ultrasound screening group or the control group. Women in the screening group underwent sonographic exams at 15–22 and 31–35 weeks of gestation. Both groups could have clinically indicated sonographic exams at any time.
Main outcome measures   We used changes of fetal weight z -score to assess whether fetal growth was compromised from the diagnosis of oligohydramnios until delivery, using a repeated-measures regression. We used a combined perinatal index as an indicator of adverse perinatal outcome, which consisted of severe perinatal morbidity and mortality.
Results   Oligohydramnios (amniotic fluid index ≤5 cm) was diagnosed in 1.5% (113/7617) of women with ultrasound screening compared with 0.8% (57/7534) among the controls. Approximately half of the oligohydramnios cases in the screening group were isolated with no clearly associated factors (e.g. premature rupture of the fetal membranes, congenital anomalies, diabetes, hypertension, postdate and intrauterine growth restriction). Fetal weight centiles in isolated oligohydramnios cases did not change significantly from diagnosis until delivery. Pregnancies with isolated oligohydramnios had perinatal outcomes similar to pregnancies with a normal amniotic fluid index.
Conclusion   Isolated oligohydramnios is not associated with impaired fetal growth or an increased risk of adverse perinatal outcomes.     

Cervicovaginal fibronectin and cervical length at 23 weeks of gestation: relative risk of early preterm delivery

Objectives To establish the prevalence of cervicovaginal fetal fibronectin positivity at 23 weeks of gestation in a routine population of singleton pregnancies and determine the relative risk of spontaneous delivery before 33 weeks in women with a fibronectin positive result.
Design Prospective clinical study.
Setting Inner city antenatal clinic.
Population Singleton pregnancies attending for routine antenatal care.
Methods Cervicovaginal fetal fibronectin and cervical length were measured at 23 weeks of gestation. The distribution of fibronectin positivity within subgroups according to maternal characteristics was calculated and the relative risk of spontaneous delivery before 33 weeks was estimated.
Main outcome measures Prevalence of a fibronectin positive result and its relation to cervical length measurement and spontaneous preterm delivery before 33 weeks.
Results Of 5146 women participating in the study, 182 (3.5%) had a fibronectin positive result and 76 (1.5%) had a cervical length of ≤ 15 mm. Fibronectin positive women were more likely to be Afro-Caribbean in origin, to have had a previous second trimester miscarriage and to have a short cervix. In the 5068 women who were managed expectantly, the significantly independent relative risk of spontaneous delivery at < 33 weeks was 46.2 (95% CI 18.8–113.6), for cervical length of ≤ 15 mm, 8.1 (95% CI 3.8–17.5) for a fibronectin positive result, and 4.4 (95% CI 2.2–9.1) for cigarette smoking.
Conclusion Fibronectin positivity at 23 weeks of gestation provides useful prediction of pregnancies at risk of spontaneous preterm delivery before 33 weeks, with a relative risk that is twice as high as cigarette smoking, but is a sixth of that of cervical length.     

Relationship between customised birthweight centiles and neonatal anthropometric features of growth restriction

Objective To determine the relationship between customised birthweight centiles (adjusted for maternal and fetal physiological variables) and neonatal anthropometric features of intrauterine growth restriction (IUGR).
Design Observational study.
Population Two-hundred and seventy women with low risk pregnancies participating in a cohort study of serial ultrasound biometry.
Methods Customised birthweight centiles were calculated following adjustment for maternal weight, height and ethnic origin, gestational age at delivery, birth order, and sex of the infant. Three separate neonatal anthropometric measures were used to define IUGR: subscapular or triceps skinfold thickness  <10th  centile; ponderal index  <25th  centile; and mid-arm circumference to occipito-frontal circumference ratio (MAC/OFC) <−1 standard deviation (SD). Relationship of the centiles to these outcomes was evaluated using likelihood ratios (LR) and kappa statistic. These approaches allowed us to examine the strength of the association: an LR of 5–10 would be expected to generate moderate changes in the pre-test probability of IUGR, whereas a kappa value of 0.2–0.4 would reflect fair agreement between customised birthweight centiles and neonatal anthropometric measures.
Results Customised birthweight centile of 10 or less had the following LR values for the various anthropometric criteria for IUGR: 5.1 (95% CI 3–8.5) for low skinfold thickness; 4.3 (95% CI 2.5–7.1) for low ponderal index; and 3.9 (95% CI 2–6.6) for low MAC/OFC ratio. The kappa values were: 0.4 (95% CI 0.26–0.51) for low skinfold thickness; 0.33 (95% CI 0.21–0.46) for low ponderal index; and 0.13 (95% CI 0–0.26) for low MAC/OFC ratio.
Conclusion In a low risk population, customised birthweight centiles can only be moderately useful in the identification of neonates with low skinfold thickness and low ponderal index.     

Reduced maternal serum concentrations of angiopoietin-2 in the first trimester precede intrauterine growth restriction associated with placental insufficiency

The aim of this study was to investigate whether maternal serum levels of angiopoietin-2 (Ang-2) and pregnancy-associated plasma protein A (PAPP-A) are associated with subsequent intrauterine growth restriction (IUGR). Ang-2 was measured in 29 nonpregnant and 44 pregnant women at 10–13 weeks of gestation. The median concentration of Ang-2 was 26.61 ng/ml in normal pregnant women compared with 1.71 ng/ml in nonpregnant controls ( P < 0.01). Women who subsequently developed severe IUGR had lower levels of Ang-2 compared with normal pregnant controls ( P < 0.01). PAPP-A levels were similar in all pregnant groups. These findings suggest that Ang-2 should be evaluated for its ability to predict pregnancies that later are affected by IUGR.     

World Health Organisation multicentre randomised trial of supplementation with vitamins C and E among pregnant women at high risk for pre-eclampsia in populations of low nutritional status from developing countries

Objective  To determine if vitamin C and E supplementation in high-risk pregnant women with low nutritional status reduces pre-eclampsia.
Design  Multicentred, randomised, controlled, double-blinded trial.
Setting  Antenatal care clinics and Hospitals in four countries.
Population  Pregnant women between 14 and 22 weeks' gestation.
Method  Randomised women received 1000 mg vitamin C and 400 iu of vitamin E or placebo daily until delivery.
Main outcome measures  Pre-eclampsia, low birthweight, small for gestational age and perinatal death.
Results  Six hundred and eighty-seven women were randomised to the vitamin group and 678 to the placebo group. Groups had similar gestational ages (18.1; SD 2.4 weeks), socio-economic, clinical and demographical characteristics and blood pressure at trial entry. Risk factors for eligibility were similar, except for multiple pregnancies: placebo group (14.7%), vitamins group (11.8%). Previous pre-eclampsia, or its complications, was the most common risk factor at entry (vitamins 41.6%, placebo 41.3%). Treatment compliance was 87% in the two groups and loss to follow-up was low (vitamins 2.0%, placebo 1.3%). Supplementation was not associated with a reduction of pre-eclampsia (RR: 1.0; 95% CI: 0.9–1.3), eclampsia (RR: 1.5; 95% CI: 0.3–8.9), gestational hypertension (RR: 1.2; 95% CI: 0.9–1.7), nor any other maternal outcome. Low birthweight (RR: 0.9; 95% CI: 0.8–1.1), small for gestational age (RR: 0.9; 95% CI: 0.8–1.1) and perinatal deaths (RR: 0.8; 95% CI: 0.6–1.2) were also unaffected.
Conclusion  Vitamins C and E at the doses used did not prevent pre-eclampsia in these high-risk women.     

Effect of routine screening for Down's syndrome on the significance of isolated fetal hydronephrosis

Objective To determine the risk of Down's syndrome in fetuses with isolated hydronephrosis at 18–23 weeks in an unselected general population after routine screening for Down's syndrome, using first trimester nuchal translucency measurement and second trimester maternal serum biochemistry.
Population All pregnant women undergoing a routine 18–23 week ultrasound scan, from a population who had been offered screening for Down's syndrome.
Setting A district general hospital serving a low risk obstetric population.
Methods Prospective study of all routine 18–23 weeks ultrasound scans. The prevalence of isolated hydronephrosis and Down's syndrome was determined and the relative risk for Down's syndrome was calculated for different ultrasound findings.
Results 10,971 women were scanned at 18–23 weeks during the study period. Down's syndrome was diagnosed in 14 of 20 cases before this stage using first trimester nuchal translucency measurement and second trimester maternal serum biochemistry. Isolated fetal hydronephrosis was diagnosed in 423 pregnancies (3.9%); none of these pregnancies were affected by Down's syndrome. The relative risk for Down's syndrome was 0.18 (95% CI 0.06–0.53) for women with a normal scan (   n = 9983  ). When multiple ultrasound markers were found (   n = 565  ), the relative risk for Down's syndrome was 2.00 (95% CI 0.18–22-10) and 9.00 (95% CI 1.14–71.30) for all other aneuploidies.
Conclusion The finding of isolated fetal hydronephrosis does not significantly increase the age-related risk for Down's syndrome. The presence of multiple ultrasound markers is associated with an increased risk of aneuploidies other than Down's syndlome. These findings are explained by the reduced prevalence of Down's syndrome as a result of prior screening and diagnosis of this condition.