Customised Birthweight Centiles Research Articles

Stillbirths at Term: Case Control Study of Risk Factors, Growth Status and Placental Histology.

ObjectiveTo investigate the proportion of stillbirths at term associated with abnormal growth using customized birth weight percentiles and to compare histological placental findings both in underweight stillborn fetuses and in live births.MethodsA retrospective case-control study of 150 singleton term stillbirths. The livebirth control groups included 586 cases of low-risk pregnancies and 153 late fetal growth restriction fetuses. Stillbirths and livebirths from low-risk pregnancies were classified using customized standards for fetal weight at birth, as adequate for gestational age (AGA; 10-90th percentile), small (SGA; <10th percentile) or large for gestational age (LGA; >90th percentile). Placental characteristics in stillbirth were compared with those from livebirths using four categories: inflammation, disruptive, obstructive and adaptive lesions.ResultsThere was a higher rate of SGA (26% vs 6%, p<0.001) and LGA fetuses (10.6% vs 5.6%, p<0.05) in the stillbirth group. Among stillbirth fetuses, almost half of the SGA were very low birthweight (≤3°percentile) (12% vs 0.3%, p<0.001). The disruptive (7.3% vs 0.17%;p<0.001), obstructive (54.6% vs 7.5%;p<0.001) and adaptive (46.6% vs 35.8%;p<0.001) findings were significantly more common in than in livebirth-low risk. Placental characteristics of AGA and SGA stillbirth were compared with those of AGA and FGR livebirth. In stillbirths-SGA we found a higher number of disruptive (12.8% vs 0%; p<0.001), obstructive (58.9% vs 23.5%;p<0.001) and adaptive lesions (56.4% vs 49%; p 0.47) than in livebirth-FGR.ConclusionThe assessment of fetal weight with customized curves can identify fetuses which have not reached their genetically determined growth potential and are therefore at risk for adverse outcomes. Placental evaluation in stillbirths can reveal chronic histological signs that might be useful to clinical assessment, especially in underweight fetuses.

Enoxaparin for the prevention of preeclampsia and intrauterine growth restriction in women with a prior history - an open-label randomised trial (the EPPI trial): study protocol.

BackgroundPreeclampsia and intrauterine fetal growth restriction (IUGR) are two of the most common causes of maternal and perinatal morbidity and mortality. Current methods of predicting those at most risk of these conditions remain relatively poor, and in clinical practice past obstetric history remains the most commonly used tool. Aspirin and, in women at risk of preeclampsia only, calcium have been demonstrated to have a modest effect on risk reduction. Several observational studies and randomised trials suggest that low molecular weight heparin (LMWH) therapy may confer some benefit.Methods/designThis is a multicentre open label randomised controlled trial to determine the effect of the LMWH, enoxaparin, on the prevention of recurrence of preeclampsia and/or IUGR in women at high risk due to their past obstetric history in addition to standard high risk care for all participants.Inclusion criteria: A singleton pregnancy >6+0 and <16+0 weeks gestation with most recent prior pregnancy with duration >12 weeks having; (1) preeclampsia delivered <36+0 weeks, (2) Small for gestational age (SGA) infant <10th customised birthweight centile delivered <36+0 weeks or, (3) SGA infant ≤3rd customised birthweight centile delivered at any gestation. Randomisation is stratified for maternal thrombophilia status and women are randomly assigned to ‘standard high risk care’ or ‘standard high risk care’ plus enoxaparin 40 mg from recruitment until 36+0 weeks or delivery, whichever occurs sooner. Standard high risk care includes the use of aspirin 100 mg daily and calcium 1000–1500 mg daily (unless only had previous SGA with no preeclampsia).The primary outcome is preeclampsia and/or SGA <5th customised birthweight centile. Analysis will be by intention to treat.DiscussionThe EPPI trial has more focussed and clinically relevant inclusion criteria than other randomised trials with a more restricted composite primary outcome. The inclusion of standard use of aspirin (and calcium) for all participants will help to ensure that any differences observed in outcome are likely to be related to enoxaparin use. These data will make a significant contribution to future meta-analyses and systematic reviews on the use of LMWH for the prevention of placental mediated conditions.Trial registration ACTRN12609000699268 Australian New Zealand Clinical Trials Registry. Date registered 13/Aug/2009 (prospective registration).

Human placental growth hormone is increased in maternal serum at 20 weeks of gestation in pregnancies with large-for-gestational-age babies

To investigate the relationship between maternal serum concentrations of placental growth hormone (GH-V), insulin-like growth factor (IGF)-1 and 2, IGF binding proteins (IGFBP)-1 and 3 and birth weight in appropriate-for-gestational-age (AGA), large-for-gestational-age (LGA) and small-for-gestational-age (SGA) cases in a nested case-control study. Maternal serum samples were selected from the Screening for Pregnancy Endpoints (SCOPE) biobank in Auckland, New Zealand. Serum hormone concentrations were determined by ELISA. We found that maternal serum GH-V concentrations at 20 weeks of gestation in LGA pregnancies were significantly higher than in AGA and SGA pregnancies. Maternal GH-V concentrations were positively correlated to birth weights and customized birth weight centiles, while IGFBP-1 concentrations were inversely related to birth weights and customized birth weight centiles. Our findings suggest that maternal serum GH-V and IGFBP-1 concentrations at 20 weeks' gestation are associated with fetal growth.

Birth Weights in Sickle Cell Disease Pregnancies: A Cohort Study

Pregnancy in women with Sickle Cell Disease (SCD) has been linked with an increased incidence of adverse foetal outcomes when compared to women without haemoglobinopathies (HbAA). There’s a paucity of data into foetal outcomes for infants born to women with SCD. Customised growth charts have been demonstrated to be better than population-based growth charts at identifying unhealthy small babies. We analysed the mean birth weight and customised birth weight centiles of infants born to mothers with SCD versus mothers with HbAA genotype, to quantify the risk of having a smaller baby. Birth weight and birth weight centiles were analysed for 88 women with SCD (50 HbSS; 38 HbSC) and 176 controls (HbAA). Statistically significant differences were seen in the mean birth weight (P value = 0.004) and the mean birth weight centiles (P value = 0.016). We conclude that SCD is a risk factor for having a smaller baby.

Born Large for Gestational Age: Bigger Is Not Always Better

Born Large for Gestational Age: Bigger Is Not Always Better

Self-reported sleep in late pregnancy in relation to birth size and fetal distress: the E Moe, Māmā prospective cohort study

ObjectivesTo explore associations between features of sleep during pregnancy and adverse outcomes for the infant.SettingE Moe, Māmā is a cohort study in Aotearoa/New Zealand that investigates self-reported sleep and maternal...

Effect of a behavioural intervention in obese pregnant women (the UPBEAT study): a multicentre, randomised controlled trial

Behavioural interventions might improve clinical outcomes in pregnant women who are obese. We aimed to investigate whether a complex intervention addressing diet and physical activity could reduce the incidence of gestational diabetes and large-for-gestational-age infants. The UK Pregnancies Better Eating and Activity Trial (UPBEAT) is a randomised controlled trial done at antenatal clinics in eight hospitals in multi-ethnic, inner-city locations in the UK. We recruited pregnant women (15-18 weeks plus 6 days of gestation) older than 16 years who were obese (BMI ≥30 kg/m(2)). We randomly assigned participants to either a behavioural intervention or standard antenatal care with an internet-based, computer-generated, randomisation procedure, minimising by age, ethnic origin, centre, BMI, and parity. The intervention was delivered once a week through eight health trainer-led sessions. Primary outcomes were gestational diabetes (diagnosed with an oral glucose tolerance test and by criteria from the International Association of Diabetes in Pregnancy Study Groups) and large-for-gestational-age infants (≥90th customised birthweight centile). Analysis was by intention to treat. This trial is registered with Current Controlled Trials, ISCRTN89971375. Recruitment and pregnancy outcomes are complete but childhood follow-up is ongoing. Between March 31, 2009, and June 2, 2014, we assessed 8820 women for eligibility and recruited 1555, with a mean BMI of 36·3 kg/m(2) (SD 4·8). 772 were randomly assigned to standard antenatal care and 783 were allocated the behavioural intervention, of which 651 and 629 women, respectively, completed an oral glucose tolerance test. Gestational diabetes was reported in 172 (26%) women in the standard care group compared with 160 (25%) in the intervention group (risk ratio 0·96, 95% CI 0·79-1·16; p=0·68). 61 (8%) of 751 babies in the standard care group were large for gestational age compared with 71 (9%) of 761 in the intervention group (1·15, 0·83-1·59; p=0·40). Thus, the primary outcomes did not differ between groups, despite improvements in some maternal secondary outcomes in the intervention group, including reduced dietary glycaemic load, gestational weight gain, and maternal sum-of-skinfold thicknesses, and increased physical activity. Adverse events included neonatal death (two in the standard care group and three in the intervention group) and fetal death in utero (ten in the standard care group and six in the intervention group). No maternal deaths were reported. Incidence of miscarriage (2% in the standard care group vs 2% in the intervention group), major obstetric haemorrhage (1% vs 3%), and small-for-gestational-age infants (≤5th customised birthweight centile; 6% vs 5%) did not differ between groups. A behavioural intervention addressing diet and physical activity in women with obesity during pregnancy is not adequate to prevent gestational diabetes, or to reduce the incidence of large-for-gestational-age infants. National Institute for Health Research, Guys and St Thomas' Charity, Chief Scientist Office Scotland, Tommy's Charity.

Insulin family polymorphisms in pregnancies complicated by small for gestational age infants.

Being born small for gestational age (SGA) increases the risk for adverse perinatal outcomes and later life vascular and metabolic disorders. The insulin family plays a vital role in intrauterine growth. We investigated the association of functional SNPs in insulin (INS), insulin receptor (INSR) and insulin receptor substrate 2 (IRS2) with small for gestational age (SGA) pregnancies, uterine and umbilical artery Doppler and plasma insulin level. We conducted a nested case-control study of 1401 nulliparous Caucasian women, their partners and babies (216 SGA and 1185 uncomplicated). SGA was defined as a birthweight less than the 10th customized birthweight percentile adjusted for maternal height, weight, parity, ethnicity, gestational age at delivery and infant sex. Uterine and umbilical artery Doppler was performed at 20 ± 1 week gestation. The SNPs in the parent infant trios were genotyped using Sequenom MassARRAY. Plasma insulin was measured by double antibody RIA in 188 healthy non-pregnant adults to assess correlations between SNP genotypes and circulating insulin. Paternal [odds ratio (OR) (95% CI) = 2.2 (1.3-3.9), P = 0.005] and infant [OR (95% CI) = 3.3 (1.7-6.2), P = 0.0001] INSR rs2059806 AA genotype was associated with SGA. Infant INSR rs2059806 A allele was associated with abnormal umbilical artery Doppler [OR (95% CI) = 1.3(1.0-1.7), P = 0.04]. INSR rs2059806 AA homozygous individuals had lower plasma insulin compared with heterozygotes (P = 0.03) and GG homozygotes (P = 0.03). The INSR rs2059806 SNP previously associated with adult vascular and metabolic diseases is also associated with SGA pregnancies. This polymorphism may associate with the risk of vascular and metabolic disorders across the life course.

Pregnancy outcome in patients with systemic vasculitis: a single-centre matched case-control study.

To study the outcome of pregnancy in patients with systemic vasculitis (SV) compared with age-, BMI- and ethnicity-matched healthy pregnant controls. Fifty-one pregnancies in 29 SV patients were retrospectively studied. There were nine patients with granulomatosis with polyangiitis (GPA), three with eosinophilic GPA, seven with Takayasu's arteritis, two with ANCA-positive vasculitis with renal involvement, two with Behçet's disease, three with urticarial vasculitis, one with primary cerebral vasculitis, one with relapsing polychondritis and one with IgA vasculitis. BVAS and the vasculitis damage index were evaluated retrospectively. Sixty-two healthy women with 156 pregnancies matched in a 2:1 ratio for age, BMI and ethnicity formed the control group. Median gestational age at delivery was lower in the SV group: 36 weeks and 2 days (34-42) vs controls 40 (37-42) weeks (P < 0.03). Median birth weight in the SV group was 3.0 kg (2.0-5.2), whereas that of the controls was 3.5 (2.28-4.32) kg (P = 0.004). The median customized birth weight centile was 38.6 in the SV group and 37.2 in the control group. In the SV group, 9 patients had 13 miscarriages, 3 had pre-eclampsia, and 2 had an intrauterine death. In the control group, 20 patients had 27 miscarriages, 1 had pre-eclamptic toxaemia, and 1 had an antepartum haemorrhage. Eight patients with SV flared during pregnancy and 11 flared after delivery. Patients with SV had a lower median gestational age, but customized birth weights were similar to those of healthy women. Women with SV may flare during pregnancy and the post-partum period and may experience significant pregnancy morbidity.

Relation between birth weight and weight and height at the age of 2 in children born preterm.

The aim of the study was to evaluate associations between fetal growth and weight at 2 years in infants born preterm using a customized approach for birth weight. This is a secondary analysis of a multicenter trial that included a 2-year follow-up of children born prematurely. Customized birth weight percentiles were calculated using the Gardosi model for a U.S. population, and the relation between customized percentile and weight and height at 2 years (adjusted for gender using z-score) was determined using regression analysis and by comparing z-scores for children with birth weight <10th versus ≥10th percentile. Weight z-score at 2 years was significantly lower in the <10th than in the ≥10th percentile group (median [interquartile range, IQR]: -0.66 [-1.58, -0.01] vs. -0.23 [-1.05, 0.55]; p < 0.001), and remained after adjusting for maternal education (p < 0.001). A similar relationship was noted for height z-score between groups (median [IQR]: -0.56 [-1.29, 0.19] vs. -0.24 [-0.99, 0.37]; p < 0.001). Positive relationships between customized birth weight percentile and weight and height at 2 years were noted (p < 0.001 for both), but were not strong (R (2) = 0.04 and 0.02, respectively). Customized birth weight percentile is a minor determinant of weight at 2 years among children born preterm.

Influence of birthweight on perinatal outcome in fetuses with antenatal diagnosis of congenital heart disease.

The incidence of congenital heart disease (CHD) accounts for the largest proportion of infant mortality attributable to birth defects. Associations have previously been reported between CHD and low birthweight. Low birthweight is independently associated with adverse outcome and has characteristically been calculated using population-based charts. This aim of this study was to determine the incidence of small for gestational age (SGA) in fetuses with CHD utilizing customized birthweight centiles and to determine the effect of SGA on adverse outcome. A retrospective cohort study was performed between 2006 and 2011. All singleton fetuses with CHD, with no associated karyotype or structural extra-cardiac abnormalities, who delivered at St Thomas's Hospital, London, were included. Population and customized birthweight centiles were calculated and perinatal outcome data were recorded. A total of 17% of fetuses with CHD had a birthweight centile <10th when population centiles were used, and 25% when customized birthweight centiles were applied. There was no correlation between SGA and increased adverse perinatal outcome. A high proportion of fetuses with CHD are classified as SGA when both population and customized birthweight centiles are used. SGA does not correlate with adverse outcome in the perinatal period. The cardiac defect therefore appears to be the main determinant of outcome and not the size of the baby at delivery.

Hepatic hemodynamics and fetal growth: a relationship of interest for further research.

BackgroundIt is well known that hepatic hemodynamics is an important physiologic mechanism in the regulation of cardiac output (CO). It has been reported that maternal cardiac output relates to neonatal weight at birth.AimsIn this study, we assessed the correlation between maternal hepatic vein Doppler flow parameters, cardiac output and neonatal birth weight.MethodsHealthy women with uncomplicated second or third trimester pregnancy attending the outpatient antenatal clinic of Ziekenhuis Oost-Limburg in Genk (Belgium), had a standardized combined electrocardiogram-Doppler ultrasound with Impedance Cardiography, for measurement of Hepatic Vein Impedance Index (HVI = [maximum velocity – minimum velocity]/maximum velocity), venous pulse transit time (VPTT = time interval between corresponding ECG and Doppler wave characteristics) and cardiac output (heart rate x stroke volume). After delivery, a population-specific birth weight chart, established from a cohort of 27000 neonates born in the index hospital, was used to define customized birth weight percentiles (BW%). Correlations between HVI, VPTT, CO and BW% were calculated using Spearman's ρ, linear regression analysis and R2 goodness of fit in SPSS 22.0.ResultsA total of 73 women were included. There was a negative correlation between HVI and VPTT (ρ = −0.719, p<0.001). Both HVI and VPTT correlated with CO (ρ = −0.403, p<0.001 and ρ = 0.332, p<0.004 resp.) and with BW% (ρ = −0.341, p<0.003 and ρ = 0.296, p<0.011 resp.)ConclusionOur data illustrate that the known contribution of hepatic hemodynamics in the regulation of cardiac output is also true for women with uncomplicated pregnancies. Our study is the first to illustrate a potential link between maternal hepatic hemodynamics and neonatal birth weight. Whether this link is purely associative or whether hepatic vascular physiology has a direct impact on fetal growth is to be evaluated in more extensive clinical and experimental research.

The metabolic profile of intrahepatic cholestasis of pregnancy is associated with impaired glucose tolerance, dyslipidemia, and increased fetal growth.

Quantification of changes in glucose and lipid concentrations in women with intrahepatic cholestasis of pregnancy (ICP) and uncomplicated pregnancy and study of their influence on fetal growth. A prospective study comparing metabolic outcomes in cholestastic and uncomplicated singleton pregnancies was undertaken at two university hospitals in the U.K. and U.S. from 2011-2014. A total of 26 women with ICP and 27 control pregnancies with no prior history of gestational diabetes mellitus were recruited from outpatient antenatal services and followed until delivery. Alterations in glucose, incretins, cholesterol, and triglycerides were studied using a continuous glucose monitoring (CGM) system and/or a standard glucose tolerance test (GTT) in conjunction with GLP-1 and a fasting lipid profile. Fetal growth was quantified using adjusted birth centiles. Maternal blood glucose concentrations were significantly increased in ICP during ambulatory CGM (P < 0.005) and following a GTT (P < 0.005). ICP is characterized by increased fasting triglycerides (P < 0.005) and reduced HDL cholesterol (P < 0.005), similar to changes observed in metabolic syndrome. The offspring of mothers with ICP had significantly larger customized birth weight centiles, adjusted for ethnicity, sex, and gestational age (P < 0.005). ICP is associated with impaired glucose tolerance, dyslipidemia, and increased fetal growth. These findings may have implications regarding the future health of affected offspring.

Effectiveness of folic acid supplementation in pregnancy on reducing the risk of small-for-gestational age neonates: a population study, systematic review and meta-analysis.

To assess the effect of timing of folic acid (FA) supplementation during pregnancy on the risk of the neonate being small for gestational age (SGA). A population database study and a systematic review with meta-analysis including the results of this population study. A UK regional database was used for the population study and an electronic literature search (from inception until August 2013) for the systematic review. Singleton live births with no known congenital anomalies; 111,736 in population study and 188,796 in systematic review. The main outcome was SGA based on customised birthweight centile. Associations are presented as odds ratios (OR) and adjusted odds ratios (aOR), adjusted for maternal and pregnancy-related characteristics. Of 108,525 pregnancies with information about FA supplementation, 92,133 (84.9%) had taken FA during pregnancy. Time of commencement of supplementation was recorded in 39,416 pregnancies, of which FA was commenced before conception in 10,036, (25.5%) cases. Preconception commencement of FA supplementation was associated with reduced risk of SGA <10th centile (aOR 0.80, 95% CI 0.71-0.90, P < 0.01) and SGA <5th centile (aOR 0.78, 95% CI 0.66-0.91, P < 0.01). This result was reproduced when the data were pooled with other studies in the systematic review, showing a significant reduction in SGA (<5th centile) births with preconception commencement of FA (aOR 0.75, 95% CI 0.61-0.92, P < 0.006). In contrast, postconception folate had no significant effect on SGA rates. Supplementation with FA significantly reduces the risk of SGA at birth but only if commenced preconceptually independent of other risk factors. This systematic review was prospectively registered with PROSPERO number CRD42013004895.

PFM.31 Retrospective review of in-utero fetal death cases in Leicester. Could the use of customised birth centiles and risk stratification improved the detection of in utero growth restriction?

Fetal growth restriction (FGR) affects around 5% of pregnancies. Failing to detect and manage pregnancies with FGR increases the risk of stillbirth. There are two main challenges to detecting these...

8.3 Placental growth factor (PLGF) and ultrasound parameters for predicting the small for gestational age infant (SGA) in suspected small for gestational age: pelican FGR study

The SGA infant is at increased risk of short and long-term health complications. Identifying the SGA fetus remains challenging. Placental insufficiency contributes to pathogenesis and it has been proposed that...

PFM.27 Birth Weights in Sickle Cell Disease Pregnancies: a Cohort Study

ObjectivesThere is a paucity of data into foetal outcomes for infants born to women with Sickle Cell Disease (SCD). Customised growth charts have been demonstrated to be better at identifying...

PFM.71 Decreased fetal movements: risk of fetal growth restriction and stillbirth

ObjectiveWe wanted to quantify the association between decreased fetal movements (DFM), fetal growth restriction (FGR) and stillbirth in a maternity population which routinely receives reminders throughout pregnancy about the significance...

Use of Customized Birth Weight Percentiles for the Prediction of Shoulder Dystocia

INTRODUCTION: To investigate the use of customized birth weight percentiles as a predictor for shoulder dystocia. METHODS: Over a 3-year period, shoulder dystocia occurred among 99 of 11,493 deliveries, for an incidence of 0.9%. To conduct a case–control study, 386 deliveries with no shoulder dystocia were randomly selected. Customized birth weight percentile was determined for each woman using Gestation Related Optimal Weight software, which accounts for maternal height, weight, ethnicity, parity, gestational age, and neonate sex. The relationship between customized birth weight percentile and shoulder dystocia was examined using logistic regression and receiver operating characteristic (ROC) curve analysis. RESULTS: The area under the ROC curve for customized birth weight percentile was 0.84 (95% confidence interval [CI] 0.80–0.88), indicating moderate performance of customized birth weight percentile as a risk discriminator. The 70th percentile had the highest sensitivity (79%) and specificity (76%) for prediction of shoulder dystocia (positive likelihood ratio 3.3, negative likelihood ratio 3.6). The area under the ROC curve for birth weight) alone was also 0.84 (95% CI 0.79–0.88). The average birth weight was 3,983 g (standard deviation 516) for those in the case group and 3,320 (standard deviation 435) for those in the control group (P<.001). Most cases of shoulder dystocia (85%) occurred at a birth weight of less than 4,500 g and only three (0.03%) would have been offered prophylactic cesarean delivery based on American College of Obstetricians and Gynecologists recommendations. CONCLUSIONS: Customized birth weight percentile is not an accurate predictor of shoulder dystocia and performs no better than birth weight alone. Continued efforts to identify patients at high risk for shoulder dystocia are needed among those with weights lower than that used to offer prophylactic cesarean delivery by American College of Obstetricians and Gynecologists recommendations.

A complex intervention to improve pregnancy outcome in obese women; the UPBEAT randomised controlled trial.

BackgroundDespite the widespread recognition that obesity in pregnant women is associated with adverse outcomes for mother and child, there is no intervention proven to reduce the risk of these complications. The primary aim of this randomised controlled trial is to assess in obese pregnant women, whether a complex behavioural intervention, based on changing diet (to foods with a lower glycemic index) and physical activity, will reduce the risk of gestational diabetes (GDM) and delivery of a large for gestational age (LGA) infant. A secondary aim is to determine whether the intervention lowers the long term risk of obesity in the offspring.Methods/DesignMulticentre randomised controlled trial comparing a behavioural intervention designed to improve glycemic control with standard antenatal care in obese pregnant women.Inclusion criteria; women with a BMI ≥30 kg/m2 and a singleton pregnancy between 15+0 weeks and 18+6 weeks’ gestation. Exclusion criteria; pre-defined, pre-existing diseases and multiple pregnancy. Randomisation is on-line by a computer generated programme and is minimised by BMI category, maternal age, ethnicity, parity and centre. Intervention; this is delivered by a health trainer over 8 sessions. Based on control theory, with elements of social cognitive theory, the intervention is designed to improve maternal glycemic control. Women randomised to the control arm receive standard antenatal care until delivery according to local guidelines. All women have a 75 g oral glucose tolerance test at 27+0- 28+6 weeks’ gestation.Primary outcome; Maternal: diagnosis of GDM, according to the International Association of Diabetes in Pregnancy Study Group (IADPSG) criteria. Neonatal; infant LGA defined as >90th customised birth weight centile.Sample size; 1546 women to provide 80% power to detect a 25% reduction in the incidence of GDM and a 30% reduction in infants large for gestational age.DiscussionAll aspects of this protocol have been evaluated in a pilot randomised controlled trial, with subsequent optimisation of the intervention. The findings of this trial will inform whether lifestyle mediated improvement of glycemic control in obese pregnant women can minimise the risk of pregnancy complications.Trial registrationCurrent controlled trials; ISRCTN89971375.