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1.  Maternal positioning to correct occipito-posterior fetal position in labour: a randomised controlled trial 
Background
The occipito-posterior (OP) fetal head position during the first stage of labour occurs in 10-34% of cephalic presentations. Most will spontaneous rotate in anterior position before delivery, but 5-8% of all births will persist in OP position for the third stage of labour. Previous observations have shown that this can lead to an increase of complications, such as an abnormally long labour, maternal and fetal exhaustion, instrumental delivery, severe perineal tears, and emergency caesarean section. Usual care in the case of diagnosis of OP position is an expectant management. However, maternal postural techniques have been reported to promote the anterior position of the fetal head for delivery. A Cochrane review reported that these maternal positions are well accepted by women and reduce back pain. However, the low sample size of included studies did not allow concluding on their efficacy on delivery outcomes, particularly those related to persistent OP position. Our objective is to evaluate the efficacy of maternal position in the management of OP position during the first stage of labour.
Methods/design
A randomised clinical trial is ongoing in the maternity unit of the Geneva University Hospitals, Geneva, Switzerland. The unit is the largest in Switzerland with 4,000 births/year. The trial will involve 438 women with a fetus in OP position, confirmed by sonography, during the first stage of the labour. The main outcome measure is the position of the fetal head, diagnosed by ultrasound one hour after randomisation.
Discussion
It is important to evaluate the efficacy of maternal position to correct fetal OP position during the first stage of the labour. Although these positions seem to be well accepted by women and appear easy to implement in the delivery room, the sample size of the last randomised clinical trial published in 2005 to evaluate this intervention had insufficient power to demonstrate clear evidence of effectiveness. If the technique demonstrates efficacy, it would reduce the physical and psychological consequences of complications at birth related to persistent OP position.
Trial registration
ClinicalTrials.gov, http://www.clinicaltrials.gov: (no. NCT01291355).
doi:10.1186/1471-2393-14-83
PMCID: PMC3942064  PMID: 24564746
Fetal head position; Occipito-posterior; Maternal position; Randomised controlled trial; Second stage of labour
2.  A randomised clinical trial on cardiotocography plus fetal blood sampling versus cardiotocography plus ST-analysis of the fetal electrocardiogram (STAN®) for intrapartum monitoring 
Background
Cardiotocography (CTG) is worldwide the method for fetal surveillance during labour. However, CTG alone shows many false positive test results and without fetal blood sampling (FBS), it results in an increase in operative deliveries without improvement of fetal outcome. FBS requires additional expertise, is invasive and has often to be repeated during labour. Two clinical trials have shown that a combination of CTG and ST-analysis of the fetal electrocardiogram (ECG) reduces the rates of metabolic acidosis and instrumental delivery. However, in both trials FBS was still performed in the ST-analysis arm, and it is therefore still unknown if the observed results were indeed due to the ST-analysis or to the use of FBS in combination with ST-analysis.
Methods/Design
We aim to evaluate the effectiveness of non-invasive monitoring (CTG + ST-analysis) as compared to normal care (CTG + FBS), in a multicentre randomised clinical trial setting. Secondary aims are: 1) to judge whether ST-analysis of fetal electrocardiogram can significantly decrease frequency of performance of FBS or even replace it; 2) perform a cost analysis to establish the economic impact of the two treatment options.
Women in labour with a gestational age ≥ 36 weeks and an indication for CTG-monitoring can be included in the trial.
Eligible women will be randomised for fetal surveillance with CTG and, if necessary, FBS or CTG combined with ST-analysis of the fetal ECG.
The primary outcome of the study is the incidence of serious metabolic acidosis (defined as pH < 7.05 and Bdecf > 12 mmol/L in the umbilical cord artery). Secondary outcome measures are: instrumental delivery, neonatal outcome (Apgar score, admission to a neonatal ward), incidence of performance of FBS in both arms and cost-effectiveness of both monitoring strategies across hospitals.
The analysis will follow the intention to treat principle. The incidence of metabolic acidosis will be compared across both groups. Assuming a reduction of metabolic acidosis from 3.5% to 2.1 %, using a two-sided test with an alpha of 0.05 and a power of 0.80, in favour of CTG plus ST-analysis, about 5100 women have to be randomised. Furthermore, the cost-effectiveness of CTG and ST-analysis as compared to CTG and FBS will be studied.
Discussion
This study will provide data about the use of intrapartum ST-analysis with a strict protocol for performance of FBS to limit its incidence. We aim to clarify to what extent intrapartum ST-analysis can be used without the performance of FBS and in which cases FBS is still needed.
Trial Registration Number
ISRCTN95732366
doi:10.1186/1471-2393-7-13
PMCID: PMC1976105  PMID: 17655764
3.  Intrapartum Ultrasound Assessment of Fetal Head Position, Tip The Scale: Natural or Instrumental Delivery? 
Objectives: The main objective of this study was to observe the behavior of the fetal head position during labor, when starting from occiput anterior or posterior position and also to determine their importance in labor management (if the starting fetal head position can be a strong argument in favour of vaginal or cesarean delivery). Methods:187 patients in labor were included in this study, with gestational age over 37 weeks and estimated fetal weight over 2500 g, singleton pregnancy, cephalic presentation, empty urinary bladder. For these patients the ultrasound assessed parameters were: fetal head position at the beginning of labour and fetal head rotation during labour. Results: 89,18 percent of the patients starting from OTP (occiput transverse or posterior position) had a vaginal birth after an anterior rotation of the fetal head, and only 10,82 % presented persitent occiput posterior requiring cesarean section for delivery. Furthermore, considering only initial occiput posterior position, we observed an increased rate for cesarean section delivery (22,72%) by persistence of this position during labour. None of the patients starting with an anterior fetal head position rotated posteriorly. Conclusions: vaginal delivery in occiput anterior position was the most common result in both OTP and OP fetal head initial position. The main reason for cesarean delivery was persistent OP position. Patients with occiput posterior position were subsequent only to an initial posterior/transverse position.
doi:10.12865/CHSJ.40.01.03
PMCID: PMC4006330  PMID: 24791200
Intrapartum ultrasound; occiput posterior; cesarean section; persistent OP
4.  Fetal demise and associated factors following umbilical cord prolapse in Mulago hospital, Uganda: a retrospective study 
Reproductive Health  2014;11:12.
Background
Umbilical cord prolapse is an obstetric complication associated with high perinatal morbidity and mortality. A few interventions may improve fetal outcome. In developed countries these have advanced to giving intrauterine fetal resuscitation. Conditions in low resource settings do not allow for some of these advanced techniques. Putting the mother in knee chest position and immediate delivery may be the only options possible.
We set out to determine the incidence of fetal demise and associated factors following umbilical cord prolapsed (UCP) in Mulago Hospital, Uganda.
Methods
In a retrospective study conducted in Mulago hospital, Uganda, file records of mothers who delivered between 1st January 2000 to 31st December 2009 and had pregnancies complicated by umbilical cord prolapse with live fetus were selected. We collected information on referral status, cord position, cervical dilatation, fetal heart state at the time of diagnosis of UCP, diagnosis to delivery interval, use of knee chest position, mode of delivery, birth weight and fetal outcome.
We computed incidence of fetal demise following UCP and determined factors associated with fetal demise in pregnancies complicated by UCP.
Results
Of 438 cases with prolapsed cord, 101(23%) lost their babies within 24 hours after birth or were delivered dead. This gave annual cumulative incidence of fetal death following UCP of 23/1000 live UCP cases delivered /year.
The major factors associated with fetal outcome in pregnancies complicated by UCP included; diagnosis to delivery interval <30 min, RR 0.79 (CI 0.74-0.85), mode of delivery, RR 1.14 (CI 1.02-1.28), knee chest position, RR 0.81 (CI 0.70-0.95).
Conclusions
The annual cumulative incidence of fetal death in our study was 23/1000 live UCP cases delivery per year for the period of 10 years studied. Cesarean section reduced perinatal mortality by a factor of 2. Diagnosis to delivery interval <30 minutes and putting mother in knee chest position were protective against fetal death.
doi:10.1186/1742-4755-11-12
PMCID: PMC3911795  PMID: 24485199
Fetal demise; Umbilical cord prolapse; Uganda
5.  Oxytocin infusion during second stage of labour in primiparous women using epidural analgesia: a randomised double blind placebo controlled trial. 
BMJ : British Medical Journal  1989;299(6713):1423-1426.
OBJECTIVE--To determine whether the high rate of forceps delivery associated with the use of epidural analgesia could be reduced through giving an intravenous infusion of oxytocin during the second stage of labour. DESIGN--A randomised, double blind, placebo controlled trial. SETTING--Delivery suites in three hospitals. SUBJECTS--226 Primiparous women with adequate epidural analgesia in whom full dilatation of the cervix had been achieved without prior stimulation with oxytocin. INTERVENTION--An infusion of oxytocin or placebo starting at the diagnosis of full cervical dilatation at an initial dose rate of 2 mU/min increasing to a maximum of 16 mU/min. MAIN OUTCOME MEASURES--The outcome of labour was assessed in terms of the duration of the second stage, mode of delivery, fetal condition at birth, postpartum blood loss, and the incidence of perineal trauma. RESULTS--Treatment with oxytocin was associated with a shorter second stage (p = 0.01), a reduction in the number of non-rotational forceps deliveries (p = 0.03), and less perineal trauma (p = 0.03) but was not associated with any reduction in the number of rotational forceps deliveries performed for malposition of the occiput. No adverse effects on fetal condition at birth or in the early puerperium were seen in association with the use of oxytocin. CONCLUSIONS--The use of an oxytocin infusion may reduce the high rate of operative delivery associated with epidural analgesia provided that the fetal occiput is in an anterior position at the onset of the second stage of labour but within the dose range studied does not seem to correct malposition of the fetal occiput.
PMCID: PMC1838287  PMID: 2514824
6.  Ultrasound for fetal assessment in early pregnancy 
Background
Diagnostic ultrasound is a sophisticated electronic technology, which utilises pulses of high frequency sound to produce an image. Diagnostic ultrasound examination may be employed in a variety of specific circumstances during pregnancy such as after clinical complications, or where there are concerns about fetal growth. Because adverse outcomes may also occur in pregnancies without clear risk factors, assumptions have been made that routine ultrasound in all pregnancies will prove beneficial by enabling earlier detection and improved management of pregnancy complications. Routine screening may be planned for early pregnancy, late gestation, or both. The focus of this review is routine early pregnancy ultrasound.
Objectives
To assess whether routine early pregnancy ultrasound for fetal assessment (i.e. its use as a screening technique) influences the diagnosis of fetal malformations, multiple pregnancies, the rate of clinical interventions, and the incidence of adverse fetal outcome when compared with the selective use of early pregnancy ultrasound (for specific indications).
Search methods
We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (September 2009).
Selection criteria
Published, unpublished, and ongoing randomised controlled trials that compared outcomes in women who experienced routine versus selective early pregnancy ultrasound (i.e. less than 24 weeks’ gestation). We have included quasi-randomised trials.
Data collection and analysis
Two review authors independently extracted data for each included study. We used the Review Manager software to enter and analyse data.
Main results
Routine/revealed ultrasound versus selective ultrasound/concealed: 11 trials including 37505 women. Ultrasound for fetal assessment in early pregnancy reduces the failure to detect multiple pregnancy by 24 weeks’ gestation (risk ratio (RR) 0.07, 95% confidence interval (CI) 0.03 to 0.17). Routine scan is associated with a reduction in inductions of labour for ‘post term’ pregnancy (RR 0.59, 95% CI 0.42 to 0.83). Routine scans do not seem to be associated with reductions in adverse outcomes for babies or in health service use by mothers and babies. Long-term follow up of children exposed to scan in utero does not indicate that scans have a detrimental effect on children’s physical or cognitive development.
Authors’ conclusions
Early ultrasound improves the early detection of multiple pregnancies and improved gestational dating may result in fewer inductions for post maturity. Caution needs to be exercised in interpreting the results of aspects of this review in view of the fact that there is considerable variability in both the timing and the number of scans women received.
doi:10.1002/14651858.CD007058.pub2
PMCID: PMC4084925  PMID: 20393955
Congenital Abnormalities [ultrasonography]; Fetal Monitoring [methods]; Gestational Age; Perinatal Mortality; Pregnancy Trimester, First; Pregnancy Trimester, Second; Pregnancy, Multiple; Ultrasonography, Prenatal [methods]; Female; Humans; Pregnancy
7.  Post-neonatal Mortality, Morbidity, and Developmental Outcome after Ultrasound-Dated Preterm Birth in Rural Malawi: A Community-Based Cohort Study 
PLoS Medicine  2011;8(11):e1001121.
Using data collected as a follow-up to a randomized trial, Melissa Gladstone and colleagues show that during the first two years of life, infants born preterm in southern Malawi are disadvantaged in terms of mortality, growth, and development.
Background
Preterm birth is considered to be associated with an estimated 27% of neonatal deaths, the majority in resource-poor countries where rates of prematurity are high. There is no information on medium term outcomes after accurately determined preterm birth in such settings.
Methods and Findings
This community-based stratified cohort study conducted between May–December 2006 in Southern Malawi followed up 840 post-neonatal infants born to mothers who had received antenatal antibiotic prophylaxis/placebo in an attempt to reduce rates of preterm birth (APPLe trial ISRCTN84023116). Gestational age at delivery was based on ultrasound measurement of fetal bi-parietal diameter in early-mid pregnancy. 247 infants born before 37 wk gestation and 593 term infants were assessed at 12, 18, or 24 months. We assessed survival (death), morbidity (reported by carer, admissions, out-patient attendance), growth (weight and height), and development (Ten Question Questionnaire [TQQ] and Malawi Developmental Assessment Tool [MDAT]). Preterm infants were at significantly greater risk of death (hazard ratio 1.79, 95% CI 1.09–2.95). Surviving preterm infants were more likely to be underweight (weight-for-age z score; p<0.001) or wasted (weight-for-length z score; p<0.01) with no effect of gestational age at delivery. Preterm infants more often screened positively for disability on the Ten Question Questionnaire (p = 0.002). They also had higher rates of developmental delay on the MDAT at 18 months (p = 0.009), with gestational age at delivery (p = 0.01) increasing this likelihood. Morbidity—visits to a health centre (93%) and admissions to hospital (22%)—was similar for both groups.
Conclusions
During the first 2 years of life, infants who are born preterm in resource poor countries, continue to be at a disadvantage in terms of mortality, growth, and development. In addition to interventions in the immediate neonatal period, a refocus on early childhood is needed to improve outcomes for infants born preterm in low-income settings.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Being born at term in Africa is not necessarily straightforward. In Malawi, 33 of every 1,000 infants born die in the first 28 days after birth; the lifetime risk for a mother dying during or shortly after pregnancy is one in 36. The comparable figures for the United Kingdom are three infants dying per 1,000 births and a lifetime risk of maternal death of one in 4,700. But for a baby, being born preterm is even more risky and the gap between low- and high-income countries widens still further. According to a World Health Organization report in 2010, a baby born at 32 weeks of gestation (weighing around 2,000 g) in Africa has little chance of survival, while the chances of survival for a baby born at 32 weeks in North America or Europe are similar to one born at term. There are very few data on the longer term outcomes of babies born preterm in Africa and there are multiple challenges involved in gathering such information. As prenatal ultrasound is not routinely available, gestational age is often uncertain. There may be little routine follow-up of preterm babies as is commonplace in high-income countries. Data are needed from recent years that take into account both improvements in perinatal care and adverse factors such as a rising number of infants becoming HIV positive around the time of birth.
Why Was This Study Done?
We could improve outcomes for babies born preterm in sub-Saharan Africa if we understood more about what happens to them after birth. We cannot assume that the progress of these babies will be the same as those born preterm in a high-income country, as the latter group will have received different care, both before and after birth. If we can document the problems that these preterm babies face in a low-income setting, we can consider why they happen and what treatments can be realistically tested in this setting. It is also helpful to establish baseline data so that changes over time can be recorded.
The aim of this study was to document four specific outcomes up to the age of two years, on which there were few data previously from rural sub-Saharan Africa: how many babies survived, visits to a health center and admissions to the hospital, growth, and developmental delay.
What Did the Researchers Do and Find?
The researchers examined a group of babies that had been born to mothers who had taken part in a randomized controlled trial of an antibiotic to prevent preterm birth. The trial had previously shown that the antibiotic (azithromycin) had no effect on how many babies were born preterm or on other measures of the infants' wellbeing, and so the researchers followed up babies from both arms of the trial to look at longer term outcomes. From the original group of 2,297 women who took part in the trial, they compared 247 infants born preterm against 593 term infants randomly chosen as controls, assessed at 12, 18, or 24 months. The majority of the preterm babies who survived past a month of age (all but ten) were born after 32 weeks of gestation. Compared to the babies born at term, the infants born preterm were nearly twice as likely to die subsequently in the next two years, were more likely to be underweight (a third were moderately underweight), and to have higher rates of developmental delay. The commonest causes of death were gastroenteritis, respiratory problems, and malaria. Visits to a health center and admissions to hospital were similar in both groups.
What Do these Findings Mean?
This study documents longer term outcomes of babies born preterm in sub-Saharan Africa in detail for the first time. The strengths of the study include prenatal ultrasound dating and correct adjustment of follow-up age (which takes into account being born before term). Because the researchers defined morbidity using routine health center attendances and self-report of illnesses by parents, this outcome does not seem to have been as useful as the others in differentiating between the preterm and term babies. Better means of measuring morbidity are needed in this setting.
In the developed world, there is considerable investment being made to improve care during pregnancy and in the neonatal period. This investment in care may help by predicting which mothers are more likely to give birth early and preventing preterm birth through drug or other treatments. It is to be hoped that some of the benefit will be transferable to low-income countries. A baby born at 26 weeks' gestation and admitted to a neonatal unit in the United Kingdom has a 67% chance of survival; preterm babies born in sub-Saharan Africa face a starkly contrasting future.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001121.
UNICEF presents useful statistics on mother and child outcomes
The World Health Organization has attempted to analyse preterm birth rates worldwide, including mapping the regional distribution and has also produced practical guides on strategies such as Kangaroo Mother Care, which can be used for the care of preterm infants in low resource settings
Healthy Newborn Network has good information on initiatives taking place to improve neonatal outcomes in low income settings
The March of Dimes, a nonprofit organization for pregnancy and baby health, provides information on research being conducted into preterm birth
Tommy's is a nonprofit organization that funds research and provides information on the risks and causes of premature birth
doi:10.1371/journal.pmed.1001121
PMCID: PMC3210771  PMID: 22087079
8.  Comparison of midwife-led and consultant-led care of healthy women at low risk of childbirth complications in the Republic of Ireland: a randomised trial 
Background
No midwifery-led units existed in Ireland before 2004. The aim of this study was to compare midwife-led (MLU) versus consultant-led (CLU) care for healthy, pregnant women without risk factors for labour and delivery.
Methods
An unblinded, pragmatic randomised trial was designed, funded by the Health Service Executive (Dublin North-East). Following ethical approval, all women booking prior to 24 weeks of pregnancy at two maternity hospitals with 1,300-3,200 births annually in Ireland were assessed for trial eligibility.1,653 consenting women were centrally randomised on a 2:1 ratio to MLU or CLU care, (1101:552). 'Intention-to-treat' analysis was used to compare 9 key neonatal and maternal outcomes.
Results
No statistically significant difference was found between MLU and CLU in the seven key outcomes: caesarean birth (163 [14.8%] vs 84 [15.2%]; relative risk (RR) 0.97 [95% CI 0.76 to 1.24]), induction (248 [22.5%] vs 138 [25.0%]; RR 0.90 [0.75 to 1.08]), episiotomy (126 [11.4%] vs 68 [12.3%]; RR 0.93 [0.70 to 1.23]), instrumental birth (139 [12.6%] vs 79 [14.3%]; RR 0.88 [0.68 to 1.14]), Apgar scores < 8 (10 [0.9%] vs 9 [1.6%]; RR 0.56 [0.23 to 1.36]), postpartum haemorrhage (144 [13.1%] vs 75 [13.6%]; RR 0.96 [0.74 to 1.25]); breastfeeding initiation (616 [55.9%] vs 317 [57.4%]; RR 0.97 [0.89 to 1.06]). MLU women were significantly less likely to have continuous electronic fetal monitoring (397 [36.1%] vs 313 [56.7%]; RR 0.64 [0.57 to 0.71]), or augmentation of labour (436 [39.6%] vs 314 [56.9%]; RR 0.50 [0.40 to 0.61]).
Conclusions
Midwife-led care, as practised in this study, is as safe as consultant-led care and is associated with less intervention during labour and delivery.
Trial registration number
ISRCTN: ISRCTN14973283
doi:10.1186/1471-2393-11-85
PMCID: PMC3226589  PMID: 22035427
9.  A randomised clinical trial of intrapartum fetal monitoring with computer analysis and alerts versus previously available monitoring 
Background
Intrapartum fetal hypoxia remains an important cause of death and permanent handicap and in a significant proportion of cases there is evidence of suboptimal care related to fetal surveillance. Cardiotocographic (CTG) monitoring remains the basis of intrapartum surveillance, but its interpretation by healthcare professionals lacks reproducibility and the technology has not been shown to improve clinically important outcomes. The addition of fetal electrocardiogram analysis has increased the potential to avoid adverse outcomes, but CTG interpretation remains its main weakness. A program for computerised analysis of intrapartum fetal signals, incorporating real-time alerts for healthcare professionals, has recently been developed. There is a need to determine whether this technology can result in better perinatal outcomes.
Methods/design
This is a multicentre randomised clinical trial. Inclusion criteria are: women aged ≥ 16 years, able to provide written informed consent, singleton pregnancies ≥ 36 weeks, cephalic presentation, no known major fetal malformations, in labour but excluding active second stage, planned for continuous CTG monitoring, and no known contra-indication for vaginal delivery. Eligible women will be randomised using a computer-generated randomisation sequence to one of the two arms: continuous computer analysis of fetal monitoring signals with real-time alerts (intervention arm) or continuous CTG monitoring as previously performed (control arm). Electrocardiographic monitoring and fetal scalp blood sampling will be available in both arms. The primary outcome measure is the incidence of fetal metabolic acidosis (umbilical artery pH < 7.05, BDecf > 12 mmol/L). Secondary outcome measures are: caesarean section and instrumental vaginal delivery rates, use of fetal blood sampling, 5-minute Apgar score < 7, neonatal intensive care unit admission, moderate and severe neonatal encephalopathy with a marker of hypoxia, perinatal death, rate of internal monitoring, tracing quality, and signal loss. Analysis will follow an intention to treat principle. Incidences of primary and secondary outcomes will be compared between groups. Assuming a reduction in metabolic acidosis from 2.8% to 1.8%, using a two-sided test with alpha = 0.05, power = 0.80, and 10% loss to follow-up, 8133 women need to be randomised.
Discussion
This study will provide evidence of the impact of intrapartum monitoring with computer analysis and real-time alerts on the incidence of adverse perinatal outcomes, intrapartum interventions and signal quality. (Current controlled trials ISRCTN42314164)
doi:10.1186/1471-2393-10-71
PMCID: PMC2987886  PMID: 21029466
10.  Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia between 34 and 37 weeks' gestation (HYPITAT-II): a multicentre, open-label randomised controlled trial 
Background
Gestational hypertension (GH) and pre-eclampsia (PE) can result in severe complications such as eclampsia, placental abruption, syndrome of Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) and ultimately even neonatal or maternal death. We recently showed that in women with GH or mild PE at term induction of labour reduces both high risk situations for mothers as well as the caesarean section rate. In view of this knowledge, one can raise the question whether women with severe hypertension, pre-eclampsia or deterioration chronic hypertension between 34 and 37 weeks of gestation should be delivered or monitored expectantly. Induction of labour might prevent maternal complications. However, induction of labour in late pre-term pregnancy might increase neonatal morbidity and mortality compared with delivery at term.
Methods/Design
Pregnant women with severe gestational hypertension, mild pre-eclampsia or deteriorating chronic hypertension at a gestational age between 34+0 and 36+6 weeks will be asked to participate in a multi-centre randomised controlled trial. Women will be randomised to either induction of labour or expectant monitoring. In the expectant monitoring arm, women will be induced only when the maternal or fetal condition detoriates or at 37+0 weeks of gestation. The primary outcome measure is a composite endpoint of maternal mortality, severe maternal complications (eclampsia, HELLP syndrome, pulmonary oedema and thromboembolic disease) and progression to severe pre-eclampsia. Secondary outcomes measures are respiratory distress syndrome (RDS), neonatal morbidity and mortality, caesarean section and vaginal instrumental delivery rates, maternal quality of life and costs. Analysis will be intention to treat. The power calculation is based on an expectant reduction of the maternal composite endpoint from 5% to 1% for an expected increase in neonatal RDS from 1% at 37 weeks to 10% at 34 weeks. This implies that 680 women have to be randomised.
Discussion
This trial will provide insight as to whether in women with hypertensive disorders late pre-term, induction of labour is an effective treatment to prevent severe maternal complications without compromising the neonatal morbidity.
Trial Registration
NTR1792 Clinical trial registration: http://www.trialregister.nl
doi:10.1186/1471-2393-11-50
PMCID: PMC3161905  PMID: 21736705
11.  Treatment of fetal anemia in Rh isoimmunized pregnancies with intrauterine fetal blood transfusion 
Introduction
Despite the availability of prophylactic rhesus immune globulin, hemolytic disease of the newborn and fetal death (hydrops fetalis) due to rhesus alloimmunization, is still a major contributor to perinatal morbidity and mortality in India. Pregnancy outcome after fetal therapy with ultrasound guided intrauterine transfusion (IUT) for fetal anemia was studied.
Methods
A prospective cohort study of 99 Rh isoimmunized pregnancies, Indirect Coomb’s test Positive (ICT > 1:16) was conducted from July 2002 to June 2007. Intensive fetal monitoring by sériai ultrasound and middle cerebral artery peak systolic velocity using Color Doppler was performed to detect fetal anemia. When necessary, invasive testing with cordocentesis for Hb, PCV was per-formed if pregnancy was less than 32–34 weeks gestation. If PCV was <30, or there was fetal hydrops, Ultrasound guided intrauterine transfusion was carried out by the intravascular (IVT) or the intraperitoneal (IPT) routes. Primary outcome variables were fetal survival in relation to gestational age and procedure related factors.
Result
Of 99 pregnancies, 43 cases (25 — hydropic, 18-nonhydropic fetuses) required 135 intrauterine blood transfusions. The rest 56 pregnancies were managed conservatively and did not need IUT. IUTs were performed when indicated starting from 16 weeks (IPT) and 21 weeks (IVT) of gestation by the intraperitoneal / intravascular routes respectively. Pre-transfusion Hb ranged from 3g% to 8g%. The amount of blood transfused varied from 10 ml to > 110 ml depending on the period of gestation and degree of fetal anemia. The number of transfusions per pregnancy was 1–7, at intervals of 1–4 weeks, till delivery at 28 to 36 weeks of gestation. Survival of hydropic babies (88%) was almost similar to those without hydrops (83.3%) Prognosis was slightly better in Rh isoimmunized pregnancies not requiring IUT (94%) compared to fetuses receiving transfusions (85.6%)
Conclusion
Intrauterine fetal blood transfusion was found to be the only life saving therapy, and very effective in the management of preterm Rh isoimmunized pregnancies. Results are comparable with the best centers in the world, hence early referral to specialized centers with expertise of specialized intensive fetal monitoring for early diagnosis of fetal anemia, and of intrauterine fetal blood transfusion are important for optimal perinatal outcome.
doi:10.1007/s13224-010-0019-y
PMCID: PMC3372062
Rh isoimmunsation; Intrauterine transfusion; fetus
12.  Risk Factors of Dystocia in Nulliparous Women 
Background: Detection of women at risk for dystocia will allow physicians to make preparations and treatment decisions that can minimize maternal and neonatal morbidity. We aimed to determine the risk factors for dystocia in nulliparous women.
Methods: This case series enrolled 447 nulliparous women who presented with a single pregnancy in the vertex presentation and gestational age of 38-42 weeks. Maternal anthropometric measurements were obtained upon admission. We defined dystocia as a cesarean section or vacuum delivery for abnormal progression of labor as evidenced by the presence of effective uterine contractions, cervical dilation of less than 1 cm/h in the active phase for 2 h, duration of the second stage beyond 2 h, or fetal head descent less than 1 cm/h. Data were analyzed by SPSS software version 11.5. Kruskal-Wallis, logistic regression, chi-square, Student’s t test and the Mann-Whitney tests were used as appropriated.
Results: The state anxiety score (OR=10.58, CI: 1.97-56.0), posterior head position (OR=9.53, CI: 4.68-19.36), fetal head swelling in the second stage of labor (OR=6.85, CI: 2.60-18.01), transverse diagonal of Michaelis sacral ≤9.6 cm (OR=6.19, CI: 2.49-15.40), and height to fundal ratio <4.7 (OR=2.68, CI: 1.09-10.60) were significant risk factors for dystocia.
Conclusion: Critical care during labor and delivery in women who have a height to fundal height ratio of <4.7 or transverse diagonal of Michaelis sacral ≤9.6 cm, an anxiety score greater than moderate, and posterior head position or fetal head swelling during the second phase could play an effective and important role in preventing dystocia.
PMCID: PMC4027004  PMID: 24850982
Dystocia; Risk factor; Iran
13.  Interventions for helping to turn term breech babies to head first presentation when using external cephalic version 
Background
Breech presentation is associated with increased complications. Turning a breech baby to head first presentation using external cephalic version (ECV) attempts to reduce the chances of breech presentation at birth, and reduce the adverse effects of breech vaginal birth or caesarean section. Tocolytic drugs and other methods have been used in an attempt to facilitate ECV.
Objectives
To assess interventions such as tocolysis, fetal acoustic stimulation, regional analgesia, transabdominal amnioinfusion or systemic opioids on ECV for a breech baby at term.
Search methods
We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (30 September 2011) and the reference lists of identified studies.
Selection criteria
Randomised and quasi-randomised trials comparing the above interventions with no intervention or other methods to facilitate ECV at term.
Data collection and analysis
We assessed eligibility and trial quality. Two review authors independently assessed for inclusion all potential studies identified as a result of the search strategy and independently extracted the data using a designed data extraction form.
Main results
We included 25 studies, providing data on 2548 women. We used the random-effects model for pooling data due to clinical heterogeneity in the included studies in the various comparisons. The overall quality of the evidence was reasonable, but a number of assessments had insufficient data to provide an answer with any degree of assurance.
Tocolytic drugs, in particular betastimulants, were effective in increasing cephalic presentations in labour (average risk ratio (RR) 1.38, 95% confidence interval (CI) 1.03 to 1.85, eight studies, 993 women) and in reducing the number of caesarean sections (average RR 0.82, 95% CI 0.71 to 0.94, eight studies, 1177 women). No differences were identified in fetal bradycardias (average RR 0.95, 95% CI 0.48 to 1.89, three studies, 467 women) although the review is underpowered for assessing this outcome. We identified no difference in success, cephalic presentation in labour and caesarean sections between nulliparous and multiparous women. There were insufficient data comparing different groups of tocolytic drugs. Sensitivity analyses by study quality agreed with the overall findings.
Regional analgesia in combination with a tocolytic was more effective than the tocolytic alone in terms of increasing successful versions (assessed by the rate of failed ECVs, average RR 0.67, 95% CI 0.51 to 0.89, six studies, 550 women) but there was no difference identified in cephalic presentation in labour (average RR 1.63, 95% CI 0.75 to 3.53, three studies, 279 women) nor in caesarean sections (average RR 0.74, 95% CI 0.40 to 1.37, three studies, 279 women) or fetal bradycardia (average RR 1.48, 95% CI 0.62 to 3.57, two studies, 210 women).
There were insufficient data on the use of vibroacoustic stimulation, amnioinfusion or systemic opioids.
Authors’ conclusions
Betastimulants, to facilitate ECV, increased cephalic presentation in labour and birth, and reduced the caesarean section rate in both nulliparous and multiparous women, but there were insufficient data on adverse effects. Calcium channel blockers and nitric acid donors had insufficient data to provide good evidence. At present we recommend betamimetics for facilitating ECV.
There is scope for further research. The possible benefits of tocolysis to reduce the force required for successful version and the possible risks of maternal cardiovascular side effects, need to be addressed further. Further trials are needed to compare the effectiveness of routine versus selective use of tocolysis, the role of regional analgesia, fetal acoustic stimulation, amnioinfusion and the effect of intravenous or oral hydration prior to ECV.
Although randomised trials of nitroglycerine are small, the results are sufficiently negative to discourage further trials.
doi:10.1002/14651858.CD000184.pub3
PMCID: PMC4171393  PMID: 22258940
Analgesia, Obstetrical [methods]; Breech Presentation [* prevention & control]; Calcium Channel Blockers [therapeutic use]; Delivery, Obstetric; Nitroglycerin [therapeutic use]; Randomized Controlled Trials as Topic; Tocolysis [* methods]; Tocolytic Agents [therapeutic use]; Version, Fetal [* methods]; Vibration [therapeutic use]; Female; Humans; Pregnancy
14.  The APPLe Study: A Randomized, Community-Based, Placebo-Controlled Trial of Azithromycin for the Prevention of Preterm Birth, with Meta-Analysis 
PLoS Medicine  2009;6(12):e1000191.
In a randomized trial in Malawi of azithromycin versus placebo in over 2,000 pregnant women, Jim Neilson and colleagues show no benefit of azithromycin for a number of outcomes including preterm birth and prenatal death.
Background
Premature birth is the major cause of perinatal mortality and morbidity in both high- and low-income countries. The causes of preterm labour are multiple but infection is important. We have previously described an unusually high incidence of preterm birth (20%) in an ultrasound-dated, rural, pregnant population in Southern Malawi with high burdens of infective morbidity. We have now studied the impact of routine prophylaxis with azithromycin as directly observed, single-dose therapy at two gestational windows to try to decrease the incidence of preterm birth.
Methods and Findings
We randomized 2,297 pregnant women attending three rural and one peri-urban health centres in Southern Malawi to a placebo-controlled trial of oral azithromycin (1 g) given at 16–24 and 28–32 wk gestation. Gestational age was determined by ultrasound before 24 wk. Women and their infants were followed up until 6 wk post delivery. The primary outcome was incidence of preterm delivery, defined as <37 wk. Secondary outcomes were mean gestational age at delivery, perinatal mortality, birthweight, maternal malaria, and anaemia. Analysis was by intention to treat. There were no significant differences in outcome between the azithromycin group (n = 1,096) and the placebo group (n = 1,087) in respect of preterm birth (16.8% versus 17.4%), odds ratio (OR) 0.96, 95% confidence interval (0.76–1.21); mean gestational age at delivery (38.5 versus 38.4 weeks), mean difference 0.16 (−0.08 to 0.40); mean birthweight (3.03 versus 2.99 kg), mean difference 0.04 (−0.005 to 0.08); perinatal deaths (4.3% versus 5.0%), OR 0.85 (0.53–1.38); or maternal malarial parasitaemia (11.5% versus 10.1%), OR 1.11 (0.84–1.49) and anaemia (44.1% versus 41.3%) at 28–32 weeks, OR 1.07 (0.88–1.30). Meta-analysis of the primary outcome results with seven other studies of routine antibiotic prophylaxis in pregnancy (>6,200 pregnancies) shows no effect on preterm birth (relative risk 1.02, 95% confidence interval 0.86–1.22).
Conclusions
This study provides no support for the use of antibiotics as routine prophylaxis to prevent preterm birth in high risk populations; prevention of preterm birth requires alternative strategies.
Trial registration
Current Controlled Trials ISRCTN84023116
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Most pregnancies last about 40 weeks. Labor that occurs before 37 weeks of gestation (the period during which a baby develops in its mother) is defined as a preterm birth. In industrialized countries, 5%–10% of all births are preterm. Figures for preterm births are harder to obtain for low-income countries because of uncertainties about gestational dates but, in both rich and poor countries, preterm birth is a major cause of infant death and illness around the time of birth. Babies who are born prematurely also often have long-term health problems and disabilities. There are many reasons why some babies are born prematurely. Structural problems such as a weak cervix (the neck of the womb, which dilates during labor to allow the baby to leave the mother's body) can result in a premature delivery, as can pregnancy-induced diabetes, blood-clotting disorders, bacterial infections in the vagina or the womb, and malaria. However, it is impossible to predict which mothers will spontaneously deliver early.
Why Was This Study Done?
At present there is no effective way to prevent premature births. Because infection is often associated with preterm labor and can occur early in pregnancy but remain undetected, one way to reduce the incidence of preterm births may be to give pregnant women antibiotics even when they have no obvious infection (prophylactic antibiotics). In this study, the researchers test this hypothesis by giving the antibiotic azithromycin to pregnant women living in Southern Malawi in a randomized, placebo-controlled trial. One baby in five is born before 37 weeks gestation in Southern Malawi and the women living in this part of sub-Saharan Africa have a high burden of infection. Azithromycin is a safe antibiotic that can treat many of the bacterial infections that have been implicated in preterm birth. It also has some antimalarial activity. In a randomized, placebo-controlled trial, participants are randomly assigned to receive a drug or identical-looking “dummy” tablets (placebo).
What Did the Researchers Do and Find?
The researchers enrolled more than 2,000 pregnant women into the APPLe study (Azithromycin for the Prevention of Preterm Labor) and determined the gestational age of their unborn babies using ultrasound. Half of the women were given an oral dose of azithromycin at 16–24 weeks and at 28–32 weeks gestation. The remaining women were given a placebo at similar times. The mothers and their babies were followed up until 6 weeks after delivery. There was no significant difference in the primary outcome of the study—the incidence of delivery before 37 weeks gestation—between the two groups of women. Secondary outcomes—including mean gestational age at delivery, mean birth weight, and still births and infant deaths within a week of birth—were also similar in the two groups of women. Finally, the researchers did a meta-analysis (a statistical technique that combines the results of several studies) of their study and seven published studies of routine antibiotic prophylaxis in pregnancy, which indicated that the prophylactic use of antibiotics did not alter the risk of preterm birth.
What Do These Findings Mean?
These findings provide no support for the use of antibiotics as prophylaxis to prevent preterm birth. The women included in this study had an unusually high incidence of preterm delivery and a high burden of infection so these findings may not be generalizable. The results of the meta-analysis, however, also provide no support for prophylactic antibiotics. Given that observational data have associated infection with preterm labor, why are the results of the APPLe trial and the meta-analysis negative? One possibility is that different antibiotics or dosing regimens might be more effective. Another possibility is that infection might be a secondary consequence of some other condition that causes preterm birth rather than the primary cause of early delivery. Whatever the reason for the lack of effect of prophylactic antibiotics, the researchers recommend that pregnant women should not be given antibiotics prophylactically to prevent preterm birth particularly since, in a recent study, the babies of women given antibiotics to halt ongoing preterm labor had an increased risk of developmental problems.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000191.
The March of Dimes, a nonprofit organization for pregnancy and baby health, provides information on preterm birth (in English and Spanish)
The Nemours Foundation, another nonprofit organization for child health, also provides information on premature babies (in English and Spanish)
Tommy's is a nonprofit organization that funds research and provides information on the causes and prevention of miscarriage, premature birth, and stillbirth
The US Centers for Disease Control and Prevention provides information on maternal and infant health (in English and Spanish)
The US National Women's Health Information Center has detailed information about pregnancy (in English and Spanish)
MedlinePlus provides links to other information on premature babies (in English and Spanish)
doi:10.1371/journal.pmed.1000191
PMCID: PMC2776277  PMID: 19956761
15.  Obstetric risk indicators for labour dystocia in nulliparous women: A multi-centre cohort study 
Background
In nulliparous women dystocia is the most common obstetric problem and its etiology is largely unknown. The frequency of augmentation and cesarean delivery related to dystocia is high although it is not clear if a slow progress justifies the interventions. Studies of risk factors for dystocia often do not provide diagnostic criteria for the diagnosis. The aim of the present study was to identify obstetric and clinical risk indicators of dystocia defined by strict and explicit criteria.
Methods
A multi-centre population based cohort study with prospectively collected data from 2810 nulliparous women in term spontaneous labour with a singleton infant in cephalic presentation. Data were collected by self-administered questionnaires and clinical data-records. Logistic regression analyses were used to estimate adjusted Odds Ratios (OR) and 95% confidence intervals (CI) are given.
Results
The following characteristics, present at admission to hospital, were associated with dystocia during labour (OR, 95% CI): dilatation of cervix < 4 cm (1.63, 1.38–1.92), tense cervix (1.31, 1.04–1.65), thick lower segment (1.32, 1.09–1.61), fetal head above the inter-spinal diameter (2.29, 1.80–2.92) and poor fetal head-to-cervix contact (1.83, 1.31–2.56). The use of epidural analgesia (5.65, 4.33–7.38) was also associated with dystocia.
Conclusion
Vaginal examinations at admission provide useful information on risk indicators for dystocia. The strongest risk indicator was use of epidural analgesia and if part of that is causal, it is of concern.
doi:10.1186/1471-2393-8-45
PMCID: PMC2569907  PMID: 18837972
16.  Fetal and umbilical Doppler ultrasound in high-risk pregnancies 
Background
Abnormal blood flow patterns in fetal circulation detected by Doppler ultrasound may indicate poor fetal prognosis. It is also possible false positive Doppler ultrasound findings could encourage inappropriate early delivery.
Objectives
The objective of this review was to assess the effects of Doppler ultrasound used to assess fetal well-being in high-risk pregnancies on obstetric care and fetal outcomes.
Search methods
We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (September 2009) and the reference lists of identified studies.
Selection criteria
Randomised and quasi-randomised controlled trials of Doppler ultrasound for the investigation of umbilical and fetal vessels waveforms in high-risk pregnancies compared to no Doppler ultrasound.
Data collection and analysis
Two authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. Data entry was checked.
Main results
Eighteen completed studies involving just over 10,000 women were included. The trials were generally of unclear quality with some evidence of possible publication bias. The use of Doppler ultrasound in high-risk pregnancy was associated a reduction in perinatal deaths (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.52 to 0.98, 16 studies, 10,225 babies, 1.2% versus 1.7 %, numbers needed to treat = 203; 95%CI 103 to 4352). There were also fewer inductions of labour (average RR 0.89, 95% CI 0.80 to 0.99, 10 studies, 5633 women, random effects) and fewer caesarean sections (RR 0.90, 95% CI 0.84 to 0.97, 14 studies, 7918 women). No difference was found in operative vaginal births (RR 0.95, 95% CI 0.80 to 1.14, four studies, 2813 women) nor in Apgar scores less than seven at five minutes (RR 0.92, 95% CI 0.69 to 1.24, seven studies, 6321 babies).
Authors’ conclusions
Current evidence suggests that the use of Doppler ultrasound in high-risk pregnancies reduced the risk of perinatal deaths and resulted in less obstetric interventions. The quality of the current evidence was not of high quality, therefore, the results should be interpreted with some caution. Studies of high quality with follow-up studies on neurological development are needed.
doi:10.1002/14651858.CD007529.pub2
PMCID: PMC4167858  PMID: 20091637
*Pregnancy, High-Risk; *Ultrasonography, Prenatal; Cesarean Section [utilization]; Fetal Monitoring [*methods]; Labor, Induced [utilization]; Perinatal Mortality; Randomized Controlled Trials as Topic; Umbilical Cord [blood supply; *ultrasonography]; Female; Humans; Pregnancy
17.  Prenatal diagnosis of fetal unilateral lung agenesis complicated with cardiac malposition 
Background
Fetal unilateral lung agenesis, complicated with cardiac shifting, is a rare anomaly, the diagnosis of which remains a challenge for many sonographers in routine screening programs. The present study describes a systematic approach for the diagnosis of fetal unilateral lung agenesis and cardiac malpositions in routine prenatal screening.
Methods
A total of 18 cases of fetal unilateral lung agenesis complicated with cardiac malposition were reviewed. A systematic method was proposed to identify the fetal left side and right side according to the fetal head position and posture by acquiring a long axis and transverse view of the fetus. Fetal unilateral lung agenesis was diagnosed by evaluation of the ipsilateral pulmonary artery. The diagnosis was confirmed by postnatal echocardiography, digital radiology, and computed tomography after birth or by autopsy findings.
Results
The left-sided fetal heart with the cardiac apex rotating to the left and posterior were confirmed in all 7 left lung agenesis cases, while the rightward shifting of the fetal heart together with the cardiac axis deviating to the right were confirmed in all 11 cases of right lung agenesis. The disappearance of the ipsilateral pulmonary artery was confirmed in all 18 cases of unilateral lung agenesis. Cardiac anomalies were present in a total of 7 of the18 cases of lung agenesis with 4 of 7 in cases of left lung agenesis and 3 of 11 in cases of right agenesis.
Conclusions
The systematic approach introduced in the current report is helpful in the diagnosis of fetal unilateral lung agenesis complicated with cardiac malposition. The information provided by this study may be helpful to better understand unilateral lung agenesis anatomically and to facilitate its potential examination.
doi:10.1186/1471-2393-13-79
PMCID: PMC3617058  PMID: 23530545
Fetus; Lung agenesis; Cardiac malposition; Fetal echocardiography
18.  Fetal Growth and Risk of Stillbirth: A Population-Based Case–Control Study 
PLoS Medicine  2014;11(4):e1001633.
Radek Bukowski and colleagues conducted a case control study in 59 US hospitals to determine the relationship between fetal growth and stillbirth, and find that both restrictive and excessive growth could play a role.
Please see later in the article for the Editors' Summary
Background
Stillbirth is strongly related to impaired fetal growth. However, the relationship between fetal growth and stillbirth is difficult to determine because of uncertainty in the timing of death and confounding characteristics affecting normal fetal growth.
Methods and Findings
We conducted a population-based case–control study of all stillbirths and a representative sample of live births in 59 hospitals in five geographic areas in the US. Fetal growth abnormalities were categorized as small for gestational age (SGA) (<10th percentile) or large for gestational age (LGA) (>90th percentile) at death (stillbirth) or delivery (live birth) using population, ultrasound, and individualized norms. Gestational age at death was determined using an algorithm that considered the time-of-death interval, postmortem examination, and reliability of the gestational age estimate. Data were weighted to account for the sampling design and differential participation rates in various subgroups. Among 527 singleton stillbirths and 1,821 singleton live births studied, stillbirth was associated with SGA based on population, ultrasound, and individualized norms (odds ratio [OR] [95% CI]: 3.0 [2.2 to 4.0]; 4.7 [3.7 to 5.9]; 4.6 [3.6 to 5.9], respectively). LGA was also associated with increased risk of stillbirth using ultrasound and individualized norms (OR [95% CI]: 3.5 [2.4 to 5.0]; 2.3 [1.7 to 3.1], respectively), but not population norms (OR [95% CI]: 0.6 [0.4 to 1.0]). The associations were stronger with more severe SGA and LGA (<5th and >95th percentile). Analyses adjusted for stillbirth risk factors, subset analyses excluding potential confounders, and analyses in preterm and term pregnancies showed similar patterns of association. In this study 70% of cases and 63% of controls agreed to participate. Analysis weights accounted for differences between consenting and non-consenting women. Some of the characteristics used for individualized fetal growth estimates were missing and were replaced with reference values. However, a sensitivity analysis using individualized norms based on the subset of stillbirths and live births with non-missing variables showed similar findings.
Conclusions
Stillbirth is associated with both growth restriction and excessive fetal growth. These findings suggest that, contrary to current practices and recommendations, stillbirth prevention strategies should focus on both severe SGA and severe LGA pregnancies.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Pregnancy is usually a happy time, when the parents-to-be anticipate the arrival of a new baby. But, sadly, about 20% of pregnancies end in miscarriage—the early loss of a fetus (developing baby) that is unable to survive independently. Other pregnancies end in stillbirth—fetal death after 20 weeks of pregnancy (in the US; after 24 weeks in the UK). Stillbirths, like miscarriages, are common. In the US, for example, one in every 160 pregnancies ends in stillbirth. How women discover that their unborn baby has died varies. Some women simply know something is wrong and go to hospital to have their fears confirmed. Others find out when a routine check-up detects no fetal heartbeat. Most women give birth naturally after their baby has died, but if the mother's health is at risk, labor may be induced. Common causes of stillbirth include birth defects and infections. Risk factors for stillbirth include being overweight and smoking during pregnancy.
Why Was This Study Done?
Stillbirths are often associated with having a “small for gestational age” (SGA) fetus. Gestation is the period during which a baby develops in its mother's womb. Gestational age is estimated from the date of the woman's last menstrual period and/or from ultrasound scans. An SGA fetus is lighter than expected for its age based on observed distributions (norms) of fetal weights for gestational age. Although stillbirth is clearly associated with impaired fetal growth, the exact relationship between fetal growth and stillbirth remains unclear for two reasons. First, studies investigating this relationship have used gestational age at delivery rather than gestational age at death as an estimate of fetal age, which overestimates the gestational age of stillbirths and leads to errors in estimates of the proportions of SGA and “large for gestational age” (LGA) stillbirths. Second, many characteristics that affect normal fetal growth are also associated with the risk of stillbirth, and this has not been allowed for in previous studies. In this population-based case–control study, the researchers investigate the fetal growth abnormalities associated with stillbirth using a new approach to estimate gestational age and accounting for the effect of characteristics that affect both fetal growth and stillbirth. A population-based case–control study compares the characteristics of patients with a condition in a population with those of unaffected people in the same population.
What Did the Researchers Do and Find?
The researchers investigated all the stillbirths and a sample of live births that occurred over 2.5 years at 59 hospitals in five US regions. They used a formula developed by the Stillbirth Collaborative Research Network to calculate the gestational age at death of the stillbirths. They categorized fetuses as SGA if they had a weight for gestational age within the bottom 10% (below the 10th percentile) of the population and as LGA if they had a weight for gestational age above the 90th percentile at death (stillbirth) or delivery (live birth) using population, ultrasound, and individualized norms of fetal weight for gestational age. Population norms incorporate weights for gestational age from normal pregnancies and from pregnancies complicated by growth abnormalities, whereas the other two norms include weights for gestational age from normal pregnancies only. Having an SGA fetus was associated with a 3- to 4-fold increased risk of stillbirth compared to having a fetus with “appropriate” weight for gestational age based on all three norms. LGA was associated with an increased risk of stillbirth based on the ultrasound and individualized norms but not the population norms. Being more severely SGA or LGA (below the 5th percentile or above the 95th percentile) was associated with an increased risk of stillbirth.
What Do These Findings Mean?
These findings indicate that, when the time of death is accounted for and norms for weight for gestational age only from uncomplicated pregnancies are used, stillbirth is associated with both restricted and excessive fetal growth. Overall, abnormal fetal growth was identified in 25% of stillbirths using population norms and in about 50% of stillbirths using ultrasound or individualized norms. Although the accuracy of these findings is likely to be affected by aspects of the study design, these findings suggest that, contrary to current practices, strategies designed to prevent stillbirth should focus on identifying both severely SGA and severely LGA fetuses and should use norms for the calculation of weight for gestational age based on normal pregnancies only. Such an approach has the potential to identify almost half of the pregnancies likely to result in stillbirth.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001633.
The March of Dimes, a nonprofit organization for pregnancy and baby health, provides information on stillbirth
Tommy's, a UK nonprofit organization that funds research into stillbirth, premature birth, and miscarriage and provides information for parents-to-be, also provides information on stillbirth (including personal stories)
The UK National Health Service Choices website provides information about stillbirth (including a video about dealing with grief after a stillbirth)
MedlinePlus provides links to other resources about stillbirth (in English and Spanish)
Information about the Stillbirth Collaborative Research Network is available
doi:10.1371/journal.pmed.1001633
PMCID: PMC3995658  PMID: 24755550
19.  Health implications resulting from the timing of elective cesarean delivery 
Background
The literature is nearly unanimous in recommending elective cesarean delivery at 39 weeks of gestation because of the lower rates of neonatal respiratory complications compared to 38 weeks. However, elective cesarean delivery at 39 weeks or more may have maternal and other fetal consequences compared to delivery at 38 weeks, which are not always addressed in these studies.
Discussion
Between 38 and 39 weeks of gestation, approximately 10% - 14% of women go into spontaneous labor; meaning that a considerable number of women scheduled for an elective cesarean delivery at 39 weeks will deliver earlier in an unscheduled, frequently emergency, cesarean delivery. The incidence of maternal morbidity and mortality is higher among women undergoing non-elective cesarean deliveries than among those undergoing elective ones. Complications may be greater among women after numerous repeat cesarean deliveries and among older women. Other than reducing the frequency of non-elective cesarean deliveries, bringing forward the timing of elective cesarean delivery to 38 weeks, may occasionally prevent intrauterine fetal demise which has been shown to increase with increasing gestational age and to avoid other fetal consequences related to the emergency delivery. All these considerations need to be weighed against the medical and the economic impact of the increase in neonatal morbidity resulting from births at 38 weeks compared to 39 weeks.
Summary
Until prospective randomized trials are conducted, we are unlikely to be able to precisely answer all risk:benefit questions as to the best timing of scheduled elective cesarean delivery. Older women, and women with numerous prior cesarean deliveries, are of particular concern. It is reasonable to inform the pregnant women of the risk of each of the above options and to respect her autonomy and decision-making.
doi:10.1186/1477-7827-8-68
PMCID: PMC2902487  PMID: 20565934
20.  Randomised controlled trial of intrapartum fetal heart rate monitoring. 
BMJ : British Medical Journal  1994;308(6927):497-500.
OBJECTIVE--To compare effectiveness of different methods of monitoring intrapartum fetal heart rate. DESIGN--Prospective randomised controlled trial. SETTING--Referral maternity hospital, Harare, Zimbabwe. SUBJECTS--1255 women who were 37 weeks or more pregnant with singleton cephalic presentation and normal fetal heart rate before entry into study. INTERVENTIONS--Intermittent monitoring of fetal heart rate by electronic monitoring, Doppler ultrasound, use of Pinard stethoscope by a research midwife, or routine use of Pinard stethoscope by attending midwife. MAIN OUTCOME MEASURES--Abnormal fetal heart rate patterns, need for operative delivery for fetal distress, neonatal mortality, Apgar scores, admission to neonatal unit, neonatal seizures, and hypoxic ischaemic encephalopathy. RESULTS--Abnormalities in fetal heart rate were detected in 54% (172/318) of the electronic monitoring group, 32% (100/312) of the ultrasonography group, 15% (47/310) of the Pinard stethoscope group, and 9% (28/315) of the routine monitoring group. Caesarean sections were performed for 28% (89%), 24% (76), 10% (32), and 15% (46) of the four groups respectively. Neonatal outcome was best in the ultrasonography group: hypoxic ischaemic encephalopathy occurred in two, one, seven, and 10 cases in the four groups respectively; neonatal seizures occurred only in the last two groups (six and nine cases respectively); and deaths occurred in eight, two, five, and nine cases respectively. CONCLUSIONS--Abnormalities in fetal heart rate were more reliably detected by Doppler ultrasonography than with Pinard stethoscope, and its use resulted in good perinatal outcome. The use of relatively cheap ultrasound monitors should be further evaluated and promoted in obstetric units caring for high risk pregnancies in developing countries with scarce resources.
PMCID: PMC2542781  PMID: 8136665
21.  Induction of labour versus expectant monitoring in women with pregnancy induced hypertension or mild preeclampsia at term: the HYPITAT trial 
Background
Hypertensive disorders, i.e. pregnancy induced hypertension and preeclampsia, complicate 10 to15% of all pregnancies at term and are a major cause of maternal and perinatal morbidity and mortality. The only causal treatment is delivery. In case of preterm pregnancies conservative management is advocated if the risks for mother and child remain acceptable. In contrast, there is no consensus on how to manage mild hypertensive disease in pregnancies at term. Induction of labour might prevent maternal and neonatal complications at the expense of increased instrumental vaginal delivery rates and caesarean section rates.
Methods/Design
Women with a pregnancy complicated by pregnancy induced hypertension or mild preeclampsia at a gestational age between 36+0 and 41+0 weeks will be asked to participate in a multi-centre randomised controlled trial. Women will be randomised to either induction of labour or expectant management for spontaneous delivery. The primary outcome of this study is severe maternal morbidity, which can be complicated by maternal mortality in rare cases. Secondary outcome measures are neonatal mortality and morbidity, caesarean and vaginal instrumental delivery rates, maternal quality of life and costs. Analysis will be by intention to treat. In total, 720 pregnant women have to be randomised to show a reduction in severe maternal complications of hypertensive disease from 12 to 6%.
Discussion
This trial will provide evidence as to whether or not induction of labour in women with pregnancy induced hypertension or mild preeclampsia (nearly) at term is an effective treatment to prevent severe maternal complications.
Trial Registration
The protocol is registered in the clinical trial register number ISRCTN08132825.
doi:10.1186/1471-2393-7-14
PMCID: PMC1950708  PMID: 17662114
22.  Perinatal Survival of a Fetus with Intestinal Volvulus and Intussusception: A Case Report and Review of the Literature 
AJP Reports  2013;3(2):107-112.
Fetal intestinal volvulus is a rare life-threatening condition. Late diagnosis of volvulus contributes to high rate of morbidity and mortality. It has variable degrees of presentation and survival. Intrauterine volvulus may be complicated by intestinal atresia due to ischemic necrosis. To our knowledge, there are three reported cases of term fetal demise. We report a case of fetal intestinal volvulus with perinatal survival of the largest term infant described with this complication to date. The volvulus was associated with type 3A jejunal atresia and intestinal pathology was noted on prenatal ultrasound. The infant was born via urgent cesarean delivery at 376/7 weeks of gestation and underwent emergent exploratory laparotomy with resection of small bowel and primary end-to-end anastomosis. Intrauterine intestinal volvulus may be suspected on prenatal ultrasound but only definitively diagnosed postnatally. Signs of fetal distress and volvulus are rarely associated with reports of survival in the term fetus. We review reported cases of prenatally suspected volvulus in infants documented to survive past the neonatal period. As fetal volvulus and most intestinal atresias/stenoses manifest during the third trimester, we recommend that the limited fetal anatomical survey during growth ultrasounds at 32 to 36 weeks routinely include an assessment of the fetal bowel.
doi:10.1055/s-0033-1349367
PMCID: PMC3799706  PMID: 24147247
fetal intestinal volvulus; perinatal mortality; intussusception; intrauterine volvulus
23.  Planned Vaginal Birth or Elective Repeat Caesarean: Patient Preference Restricted Cohort with Nested Randomised Trial 
PLoS Medicine  2012;9(3):e1001192.
A study conducted in Australia provides new data on the outcomes for mother and baby associated with either planned vaginal birth, or elective repeat caesarean section following a previous caesarean section.
Background
Uncertainty exists about benefits and harms of a planned vaginal birth after caesarean (VBAC) compared with elective repeat caesarean (ERC). We conducted a prospective restricted cohort study consisting of a patient preference cohort study, and a small nested randomised trial to compare benefits and risks of a planned ERC with planned VBAC.
Methods and findings
2,345 women with one prior caesarean, eligible for VBAC at term, were recruited from 14 Australian maternity hospitals. Women were assigned by patient preference (n = 2,323) or randomisation (n = 22) to planned VBAC (1,225 patient preference, 12 randomised) or planned ERC (1,098 patient preference, ten randomised). The primary outcome was risk of fetal death or death of liveborn infant before discharge or serious infant outcome. Data were analysed for the 2,345 women (100%) and infants enrolled.
The risk of fetal death or liveborn infant death prior to discharge or serious infant outcome was significantly lower for infants born in the planned ERC group compared with infants in the planned VBAC group (0.9% versus 2.4%; relative risk [RR] 0.39; 95% CI 0.19–0.80; number needed to treat to benefit 66; 95% CI 40–200). Fewer women in the planned ERC group compared with women in the planned VBAC had a major haemorrhage (blood loss ≥1,500 ml and/or blood transfusion), (0.8% [9/1,108] versus 2.3% [29/1,237]; RR 0.37; 95% CI 0.17–0.80).
Conclusions
Among women with one prior caesarean, planned ERC compared with planned VBAC was associated with a lower risk of fetal and infant death or serious infant outcome. The risk of major maternal haemorrhage was reduced with no increase in maternal or perinatal complications to time of hospital discharge. Women, clinicians, and policy makers can use this information to develop health advice and make decisions about care for women who have had a previous caesarean.
Trial registration
Current Controlled Trials ISRCTN53974531
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Rates of caesarean section are rising around the world, particularly in high- and middle-income countries, where most women have a choice of how their baby is delivered. Historically, the obstetrician in charge of the woman's care made the decision on whether to perform an elective (planned) caesarean section based on medical criteria. For women who have had a previous caesarean section, typically, their options for mode of childbirth are either a trial of vaginal birth or an elective repeat caesarean section. The proportion of women attempting a vaginal birth after a previous caesarean section has been declining in many countries partly due to the variable chance of achieving a successful vaginal birth (reported between 56% and 80%) and partly because of negative reports of the risk of complications, both to the mother and the baby, of a having a vaginal delivery following a caesarean section. Consequently, the rates of repeat caesarean section have risen sharply, for example, currently 83% in Australia and almost 90% in the US.
Why Was This Study Done?
Both elective repeat caesarean section and subsequent vaginal delivery after a previous caesarean section have clinical risks and benefits. Most obviously, having a surgical procedure puts the woman having the repeat caesarean section at risk of surgical complications, especially if performed under a general anesthetic, and her baby may be at risk of respiratory complications. However, subsequent vaginal delivery following a previous caesarean section may put the mother at risk of bleeding severely enough to need a blood transfusion (more than 1,500 ml blood loss) and she may also be at increased risk of rupturing her uterus; and her baby may have an increased risk of dying or of becoming brain damaged due to lack of oxygen.
However, to date there have been no randomized controlled trials of elective repeat caesarean section versus vaginal delivery following a previous caesarean section to compare the health outcomes of mother and baby and a recent systematic review could draw no conclusions. So the researchers conducted this prospective cohort study based on patient preference (with a few women agreeing to be randomized to mode of delivery), to compare the health outcomes for mother and baby for elective repeat caesarean section versus vaginal delivery in women following a previous caesarean section.
What Did the Researchers Do and Find?
Between 2002 and 2007, the researchers recruited 2,345 suitable women (that is, women who had one previous caesarean section, were currently 37 weeks pregnant with a single baby, and who were clinically able to have a vaginal delivery) from 14 maternity hospitals throughout Australia. A few women (22) agreed to be randomized to either mode of delivery but most women chose her preferred option. Then, depending on the woman's preferences for mode of birth, participating obstetricians either scheduled a date for an elective caesarean section (1,098 women) or assessed on-going suitability for the woman to have a planned vaginal delivery (1,225 women). However only 535 (43.2%) women who chose to have a vaginal birth were able to deliver this way because of failure to progress in labor or fetal distress: 334 of these women (27.0%) had to have an elective caesarean section and 368 women had to have an emergency caesarean section.
Although no women died, women who had a planned caesarean section experienced less severe bleeding than women who delivered vaginally. There were no infant deaths in those born by elective caesarean section but two unexplained stillbirths in the planned vaginal delivery group. There was also a reduced risk of nonfatal serious outcome before discharge from hospital for infants delivered by in the elective caesarean section. The researchers calculated that one infant death or near death would be prevented for every 66 elective caesarean sections performed in women who had a previous caesarean section.
What Do These Findings Mean?
These findings show that in women who had delivered by a previous caesarean section delivering their next baby by planned caesarean section was associated with less infant death and better health outcomes for the mother before she was discharged from the hospital compared to women who had a subsequent vaginal delivery. This information can be used by women, clinicians, and policy makers in helping to make decisions about the mode of subsequent deliveries and best care for women who have had a previous caesarean section.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001192.
This study is linked to a PLoS Medicine Research Article by Fitzpatrick and colleagues and a PLoS Medicine Perspective by Catherine Spong
The American Congress of Obstetricians and Gynecologists has information sheets for patients on caesarean sections and on vaginal birth after caesarean delivery
Childbirth Connection, a US-based not-for-profit organization, provides information about caesarean sections and about vaginal birth after caesarean
The National Childbirth Trust, a UK charity, provides information for parents on all aspects of pregnancy and birth, including caesarean sections and vaginal birth after caesarean delivery
The UK charity Healthtalkonline has personal stories from women making decisions about birth after a caesarean section
doi:10.1371/journal.pmed.1001192
PMCID: PMC3302845  PMID: 22427749
24.  Characterization of the fetal blood transcriptome and proteome in maternal anti-fetal rejection: evidence of a distinct and novel type of human fetal systemic inflammatory response 
Background
The human fetus is able to mount a systemic inflammatory response when exposed to microorganisms. This stereotypic response has been termed the “fetal inflammatory response syndrome” (FIRS), defined as an elevation of fetal plasma interleukin-6 (IL-6). FIRS is frequently observed in patients who delivered preterm associated with intra-amniotic infection (IAI), acute inflammatory lesions in the placenta, and a high rate of neonatal morbidity. Recently, a novel form of fetal systemic inflammation, characterized by an elevation of fetal plasma CXCL10, has been identified in patients with placental lesions suggestive of “maternal anti-fetal rejection”. These lesions include chronic chorioamnionitis, plasma cell deciduitis and villitis of unknown etiology (VUE). In addition, a seropositivity for HLA panel-reactive antibodies (PRA) in maternal sera can also be used as an index of suspicious for “maternal anti-fetal rejection”. The purpose of this study was to determine: 1) the frequency of pathologic evidence of “maternal anti-fetal rejection” in term and spontaneous preterm births; 2) the fetal serum concentration of CXCL10 in patients with and without evidence of maternal anti-fetal rejection; and 3) the fetal blood transcriptome and proteome in pregnancy with evidence of fetal inflammatory response associated with maternal anti-fetal rejection.
Methods
Maternal and fetal sera were obtained from normal term birth (N=150) and spontaneous preterm births (N=150). Fetal inflammatory response associated with maternal anti-fetal rejection was diagnosed when the patients met two or more of the following criteria: 1) presence of chronic placental inflammation; 2) ≥80% of maternal HLA class I panel-reactive antibody (PRA) seropositivity; and 3) fetal serum CXCL10 concentration > 75th percentile of normal. Maternal HLA PRA was analyzed by flow cytometry. The concentration of fetal CXCL10 and IL-6 were determined by ELISA. Transcriptome analysis was undertaken after extraction of total RNA from white blood cells with a whole-genome DASL assay. Proteomic analysis of fetal serum was conducted by two-dimensional difference gel electrophoresis. Differential gene expression was considered significant when there was a p<0.01 and a fold-change >1.5.
Results
1) The frequency of placental lesions consistent with maternal anti-fetal rejection was higher in patients with preterm delivery than in those with term delivery (56% vs. 32%; P<0.001); 2) patients with spontaneous preterm births had a higher rate of maternal HLA PRA class I positivity than those who delivered at term (50% vs. 32%; P=0.002); 3) fetuses who were born to mothers with positive maternal HLA PRA results had a higher median serum CXCL10 concentration than in those with negative HLA PRA results (P<0.001); 4) the median serum CXCL10 concentration (but not IL-6) was higher in fetuses with placental lesions associated with maternal anti-fetal rejection than in those without such lesions (P<0.001); 5) a whole-genome DASL assay of fetal blood RNA demonstrated differential expression of 128 genes between fetuses with and without fetal inflammatory response associated with maternal anti-fetal rejection; and 6) comparison of the fetal serum proteome demonstrated 20 proteins whose abundance differed between fetuses with and without fetal inflammatory response associated with maternal anti-fetal rejection.
Conclusions
We describe systemic inflammatory response in the fetus born to mothers with evidence of maternal anti-fetal rejection. Using high-dimensional biology techniques, the transcriptome and proteome of this novel type of fetal inflammatory response demonstrated the distinct profile from FIRS type I (which is associated with acute infection). This information is crucial to gain a mechanistic understanding of the syndrome as well as to identify biomarkers for this condition.
doi:10.1111/aji.12142
PMCID: PMC3939790  PMID: 23905683
anti-HLA panel-reactive antibody; apolipoprotein C-III; CD34; CXCL10; chronic placental inflammation; pregnancy; proteome; transcriptome
25.  Cervical assessment by ultrasound for preventing preterm delivery 
Background
Measurement of cervical length (CL) by transvaginal ultrasound (TVU) is predictive of preterm birth (PTB). It is unclear if this screening test is effective for prevention of PTB.
Objectives
To assess the effectiveness of antenatal management based on TVU CL screening for preventing PTB.
Search methods
We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (September 2008), MEDLINE (1966 to September 2008), and reviewed the reference list of all articles. We updated the search of the Cochrane Pregnancy and Childbirth Group’s Trials Register on 27 January 2012 and added the results to the awaiting classification section.
Selection criteria
Published and unpublished randomized controlled trials including pregnant women between the gestational ages of 14 to 32 weeks screened with TVU CL for risk of PTB. This review focuses exclusively on studies based on knowledge versus no knowledge of TVU CL results.
Data collection and analysis
All potential studies identified as in the search were assessed for inclusion by three independent review authors. We also analyzed studies for quality measures and extracted data.
Main results
Of 12 trials identified, five were eligible for inclusion (n = 507). Three included singleton gestations with preterm labor (PTL); one included singleton gestations with preterm prelabour rupture of membranes (PPROM); and one included twin gestations without or with PTL.
In the three trials of singleton gestations with PTL, 290 women were randomized; 147 to knowledge and 143 to no knowledge of TVU CL. Knowledge of TVU CL results was associated with a non-significant decrease in PTB at less than 37 weeks (22.3% versus 34.7%, respectively; risk ratio 0.59, 95% confidence interval (CI) 0.26 to 1.32). Delivery occurred at a later gestational age in the knowledge versus no knowlege groups (mean difference 0.64 weeks (CI 0.03 to 1.25)). All other outcomes for which there were available data (PTB at less than 34 or 28 weeks; birthweight less than 2500 grams; perinatal death; maternal hospitalization; tocolysis; and steroids for fetal lung maturity) were similar in the two groups.
The trial of singleton gestations with PPROM (n = 92) evaluated as its primary outcome safety of TVU CL in this population, and not its effect on management. The incidence of maternal and neonatal infections was similar in the TVU CL and no TVU CL groups.
In the trial of twin gestations with or without PTL (n = 125), PTB at less than 36, 34, or 30 weeks, gestational age at delivery, and other perinatal and maternal outcomes were similar in the TVU CL and the no TVU CL groups. Life table analysis revealed significantly less preterm birth at less than 35 weeks in the TVU CL group compared to the no TVU CL group (P = 0.02).
Authors’ conclusions
Currently there is insufficient evidence to recommend routine screening of asymptomatic or symptomatic pregnant women with TVU CL. Since there is a non-significant association between knowledge of TVU CL results and a lower incidence of PTB at less than 37 weeks in symptomatic women, we encourage further research. Future studies should look at specific populations separately (eg singleton versus twins; symptoms of PTL or no such symptoms), report on all pertinent maternal and perinatal outcomes, and include cost-effectiveness analyses. Most importantly, future studies should include a clear protocol for management of women based on TVU CL results, so that it can be easily evaluated and replicated.
[Note: The two citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]
doi:10.1002/14651858.CD007235.pub2
PMCID: PMC4239539  PMID: 19588421
Cervical Length Measurement [*methods]; Cervix Uteri [*ultrasonography]; Pregnancy, Multiple; Premature Birth [*prevention & control; ultrasonography]; Randomized Controlled Trials as Topic; Twins; Female; Humans; Pregnancy

Results 1-25 (620175)