E. Chan

Clinical risk prediction for pre-eclampsia in nulliparous women: development of model in international prospective cohort

Objectives To develop a predictive model for pre-eclampsia based on clinical risk factors for nulliparous women and to identify a subgroup at increased risk, in whom specialist referral might be indicated. Design Prospective multicentre cohort. Setting Five centres in Auckland, New Zealand; Adelaide, Australia; Manchester and London, United Kingdom; and Cork, Republic of Ireland. Participants 3572 “healthy” nulliparous women with a singleton pregnancy from a large international study; data on pregnancy outcome were available for 3529 (99%). Main outcome measure Pre-eclampsia defined as ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg, or both, on at least two occasions four hours apart after 20 weeks’ gestation but before the onset of labour, or postpartum, with either proteinuria or any multisystem complication. Preterm pre-eclampsia was defined as women with pre-eclampsia delivered before 37+0 weeks’ gestation. In the stepwise logistic regression the comparison group was women without pre-eclampsia. Results Of the 3529 women, 186 (5.3%) developed pre-eclampsia, including 47 (1.3%) with preterm pre-eclampsia. Clinical risk factors at 14-16 weeks’ gestation were age, mean arterial blood pressure, body mass index (BMI), family history of pre-eclampsia, family history of coronary heart disease, maternal birth weight, and vaginal bleeding for at least five days. Factors associated with reduced risk were a previous single miscarriage with the same partner, taking at least 12 months to conceive, high intake of fruit, cigarette smoking, and alcohol use in the first trimester. The area under the receiver operating characteristics curve (AUC), under internal validation, was 0.71. Addition of uterine artery Doppler indices did not improve performance (internal validation AUC 0.71). A framework for specialist referral was developed based on a probability of pre-eclampsia generated by the model of at least 15% or an abnormal uterine artery Doppler waveform in a subset of women with single risk factors. Nine per cent of nulliparous women would be referred for a specialist opinion, of whom 21% would develop pre-eclampsia. The relative risk for developing pre-eclampsia and preterm pre-eclampsia in women referred to a specialist compared with standard care was 5.5 and 12.2, respectively. Conclusions The ability to predict pre-eclampsia in healthy nulliparous women using clinical phenotype is modest and requires external validation in other populations. If validated, it could provide a personalised clinical risk profile for nulliparous women to which biomarkers could be added. Trial registration ACTRN12607000551493.

Risk factors for small-for-gestational-age infants by customised birthweight centiles: data from an international prospective cohort study

Please cite this paper as: McCowan L, Roberts C, Dekker G, Taylor R, Chan E, Kenny L, Baker P, Moss‐Morris R, Chappell L, North R on behalf of the SCOPE consortium. Risk factors for small‐for‐gestational‐age infants by customised birthweight centiles: data from an international prospective cohort study. BJOG 2010;117:1599–1607.

Risk factors for infants small for gestational age by customised birthweight centiles: data from an international prospective cohort study

Please cite this paper as: McCowan L, Roberts C, Dekker G, Taylor R, Chan E, Kenny L, Baker P, Moss‐Morris R, Chappell L, North R on behalf of the SCOPE consortium. Risk factors for small‐for‐gestational‐age infants by customised birthweight centiles: data from an international prospective cohort study. BJOG 2010;117:1599–1607.

Risk of First-Stage and Second-Stage Cesarean Delivery by Maternal Body Mass Index Among Nulliparous Women in Labor at Term

OBJECTIVE: To estimate in a cohort of nulliparous women in labor at term whether cesarean delivery rates are increased in first and second stages of labor in overweight and obese women and whether being overweight or obese is an independent risk factor for cesarean delivery. METHODS: Nulliparous women recruited to the prospective Screening for Pregnancy Endpoints study who went into labor after 37 weeks of gestation were categorized according to ethnicity-specific body mass index (BMI) criteria as normal, overweight, or obese. Normal BMI was the referent. Multivariable analysis, adjusting for known confounders for obesity and cesarean delivery, was performed to estimate if being overweight or obese was associated with an increased risk of cesarean in labor (all cesarean deliveries and in first stage of labor). RESULTS: Of 2,629 participants, 1,416 (54%) had normal BMIs, 773 (29%) were overweight, and 440 (17%) were obese. First-stage cesarean delivery was increased in overweight (n=149 [19%]) and obese (n=137 [31%]) women compared with normal-weight women (n=181 [13%; P<.001), whereas second-stage cesarean delivery was similar (normal BMI 76 [6.2%], overweight 45 [7.2%], obese 23 [7.6%], P=.87). Being overweight or obese was an independent risk factor for all cesarean deliveries in labor with adjusted odds ratio (OR) of 1.34 (95% confidence interval [CI] 1.07–1.67) and 2.51 (95% CI 1.94–3.25), respectively. Similarly, being overweight (adjusted OR 1.39; 95% CI 1.09–1.79) or obese (adjusted OR 2.89; 95% CI 2.19–3.80) was associated with increased cesarean delivery during the first stage. Risks of cesarean delivery were similar regardless of whether ethnicity-specific or World Health Organization (WHO) BMI criteria were used. CONCLUSION: Among nulliparous women in labor at term, being overweight or obese by either WHO or ethnicity-specific BMI criteria is an independent risk factor for cesarean delivery in the first stage but not the second stage of labor. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, www.anzctr.org.au, ACTRN12607000551493. LEVEL OF EVIDENCE: II

Patterns of Change in Uterine Artery Doppler Studies Between 20 and 24 Weeks of Gestation and Pregnancy Outcomes

OBJECTIVES: To describe changes in mean uterine artery resistance index and bilateral notches between 20 and 24 weeks of gestation in healthy nulliparous women and to relate these changes to pregnancy outcome. METHODS: A total of 2,189 nulliparous participants in the Screening for Pregnancy Endpoints study had pregnancy outcomes compared between four uterine artery Doppler groups: normal at 20 and 24 weeks of gestation (group 1), normal at 20 weeks and abnormal at 24 weeks (group 2), abnormal at 20 weeks and normal at 24 weeks (group 3), and abnormal at both 20 and 24 weeks (group 4). Abnormal uterine Doppler was defined as 1) mean resistance index greater than the 90th centile; 2) bilateral notches; and 3) a combination of 1, 2, or both. The main outcomes were preeclampsia and small for gestational age (SGA) neonates (less than the 10th customized centile). RESULTS: Preeclampsia developed in 116 (5.3%) women, and 223 (10.2%) delivered SGA neonates. With abnormal Doppler defined as mean resistance index greater than the 90th centile, the rate of SGA increased across Doppler groups: group 1, 156 (8.4%); group 2, 13 (11%); group 3, 25 (19.5%); and group 4, 29 (35.4%) (P<.001). The rate of SGA was higher in group 3 compared with group 1. Preeclampsia differed among groups 1 (85 [4.6%]), 2 (9 [7.6%], 3 (7 [5.5%]), and 4 (15 [18.3%]) (P<.001). CONCLUSION: Pregnancy outcomes in women with abnormal uterine artery Doppler results at either 20 or 24 weeks were intermediate between those with normal or abnormal results at both time points. If overall test performance could be enhanced by the addition of clinical data, biomarkers, or both, we would recommend that 20 weeks is the most appropriate gestation in the second trimester to perform uterine artery Doppler studies. LEVEL OF EVIDENCE: II

Transabdominal scanning of the cervix at the 20-week morphology scan: Comparison with transvaginal cervical measurements in a healthy nulliparous population

Background:  Healthy, nulliparous women at low risk for preterm birth would not usually undergo transvaginal scanning at the 20‐week morphology scan. The study aimed to determine whether transabdominal cervical measurement would be sufficient to exclude a short cervix in this population.

Changes in Doppler flow velocity waveforms and fetal size at 20 weeks gestation among cigarette smokers

Objectives  To compare umbilical and uterine artery Doppler waveforms and fetal size at 20 weeks between smokers and nonsmokers.

Paternal Contribution to Small for Gestational Age Babies: A Multicenter Prospective Study

Our aims were to investigate whether men who fathered small for gestational age (SGA) infants themselves had lower birthweight, were more likely to be obese, have central adiposity and elevated blood pressure in adult life compared with men who fathered non‐SGA infants. A total of 2,002 couples participating in the Screening for Pregnancy Endpoints (SCOPE) study were enrolled in early pregnancy and pregnancy outcome data collected prospectively. SGA was defined as birthweight <10th customized centile, obesity as BMI ≥30 kg/m2, central adiposity as waist circumference >102 cm. Logistic regression was used to compare rates of obesity, and central adiposity between men who fathered SGA infants compared with those with non‐SGA infants and the final model was adjusted for maternal and paternal confounders. The men who fathered an SGA infant (209 (10.4%)) themselves had lower mean birthweight (3,291 (530) g vs. 3,472 (584) g, P < 0.0001), were more likely to be obese (50 (24.8%) vs. 321 (18.3%), adjusted odds ratio (OR) 1.50, 95% confidence interval 1.05–2.16, adjusted for maternal and paternal factors) and to have central adiposity (52 (25.1%) vs. 341 (19.2%), adjusted OR 1.53, 95% confidence interval 1.06–2.20) compared with men who fathered a non‐SGA infant. Elevated paternal blood pressure was not associated with SGA. In conclusion, we report a novel relationship between paternal obesity/central adiposity and birth of an SGA infant, which appears to be independent of maternal factors associated with fetal growth restriction.

Antepartum haemorrhage of unknown origin and maternal cigarette smoking beyond the first trimester

Antepartum haemorrhage of unknown origin (APHUO) is associated with preterm birth and perinatal mortality.

Authors' Reply. Angiogenic factors combined with clinical risk factors to predict preterm pre-eclampsia in nulliparous women

Sir, The SCOPE consortium report (September 2013) on the plasma biomarkers placental growth factor, soluble fms-like tyrosine kinase-1 and endoglin early in pregnancy for predicting preterm pre-eclampsia is the climax of a huge piece of work. However, the SCOPE study registration site defined the planned primary outcome as pre-eclampsia ‘at any stage during pregnancy after recruitment until delivery or in the first 2 weeks after delivery’. It also defined a planned secondary outcome of ‘early onset pre-eclampsia’ defined as ‘pre-eclampsia resulting in delivery at <34 weeks’. Can the authors explain why the three tests’ predictions of neither of these were reported? Have they been reported elsewhere? Why was the tests’ prediction of a new outcome of ‘pre-eclampsia before 37 weeks’, which was not mentioned on the trial registry, reported instead?&