Implementation of fetal clinical exome sequencing: Comparing prospective and retrospective cohorts.

PURPOSE: We compared the diagnostic yield of fetal clinical exome sequencing (fCES) in prospective and retrospective cohorts of pregnancies presenting with anomalies detected using ultrasound. We evaluated factors that led to a higher diagnostic efficiency, such as phenotypic category, clinical characterization, and variant analysis strategy. METHODS: fCES was performed for 303 fetuses (183 ongoing and 120 ended pregnancies, in which chromosomal abnormalities had been excluded) using a trio/duo-based approach and a multistep variant analysis strategy. RESULTS: fCES identified the underlying genetic cause in 13% (24/183) of prospective and 29% (35/120) of retrospective cases. In both cohorts, recessive heterozygous compound genotypes were not rare, and trio and simplex variant analysis strategies were complementary to achieve the highest possible diagnostic rate. Limited prenatal phenotypic information led to interpretation challenges. In 2 prospective cases, in-depth analysis allowed expansion of the spectrum of prenatal presentations for genetic syndromes associated with the SLC17A5 and CHAMP1 genes. CONCLUSION: fCES is diagnostically efficient in fetuses presenting with cerebral, skeletal, urinary, or multiple anomalies. The comparison between the 2 cohorts highlights the importance of providing detailed phenotypic information for better interpretation and prenatal reporting of genetic variants.

Exercise for pregnant women with pre-existing diabetes for improving maternal and fetal outcomes.

BACKGROUND: Pregnancies with pre-existing diabetes are high risk, with increased risk of poorer fetal, neonatal, and maternal outcomes. Identifying interventions to improving health outcomes for women with diabetes and their infants is a priority, as rates of diabetes continue to increase.Exercise has been shown to have benefits for non-pregnant individuals with pre-existing type 2 diabetes, such as improving glycaemic control, and reducing visceral adipose tissue and plasma triglycerides. For pregnant women with pre-existing diabetes, the effects of exercise interventions on the mother and her baby are unknown.An earlier Cochrane review on 'Exercise for pregnant women with diabetes' considered both pre-existing diabetes and gestational diabetes. That Cochrane review has now been split into two new reviews (following new protocols) - one on gestational diabetes and one on pre-existing diabetes (this review). OBJECTIVES: To evaluate the effects of exercise interventions for improving maternal and fetal outcomes in women with pre-existing diabetes. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP) on 27 June 2017, and reference lists of retrieved studies. SELECTION CRITERIA: We had planned to include published or unpublished randomised controlled trials (RCT) or cluster-randomised trials, in full text or abstract format that compared any type of exercise programme, added to standard care, targeted at women with known pre-gestational diabetes (type 1 or type 2 diabetes), at any stage of pregnancy, compared with 1) standard care alone or 2) standard care plus another exercise intervention. Quasi-randomised and cross-over trials were excluded. Conference abstracts were handled in the same way as full-text publications.Women with gestational diabetes mellitus were excluded, as they were covered in a separate Cochrane review. DATA COLLECTION AND ANALYSIS: We had planned that two review authors would independently assess all the potential studies we identified as a result of the search strategy. For eligible studies, two review authors would have independently extracted the data using an agreed form. We had planned to resolve discrepancies through discussion, or by consulting a third person. We also had planned to assess the evidence using the GRADE approach. MAIN RESULTS: We did not identify any randomised controlled trials. AUTHORS' CONCLUSIONS: There was no evidence from RCTs that evaluated the effects of exercise interventions for improving maternal and fetal outcomes in women with pre-existing diabetes.Good quality, large randomised controlled trials are urgently needed to identify exercise interventions that are safe, and improve health outcomes for women with pre-existing diabetes and their babies. Future studies in this area could utilise the standardised outcomes in this review, in order to improve consistency between trials in this area, and aid future meta-analysis.

Exercise for pregnant women with gestational diabetes for improving maternal and fetal outcomes.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with both short- and long-term complications for the mother and her baby. Exercise interventions may be useful in helping with glycaemic control and improve maternal and infant outcomes.The original review on Exercise for diabetic pregnant women has been split into two new review titles reflecting the role of exercise for pregnant women with gestational diabetes and for pregnant women with pre-existing diabetes. Exercise for pregnant women with gestational diabetes for improving maternal and fetal outcomes (this review) Exercise for pregnant women with pre-existing diabetes for improving maternal and fetal outcomes OBJECTIVES: To evaluate the effects of exercise interventions for improving maternal and fetal outcomes in women with GDM. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (27 August 2016), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (18th August 2016), and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing an exercise intervention with standard care or another intervention in pregnant women diagnosed with gestational diabetes. Quasi-randomised and cross-over studies, and studies including women with pre-existing type 1 or type 2 diabetes were not eligible for inclusion. DATA COLLECTION AND ANALYSIS: All selection of studies, assessment of trial quality and data extraction was conducted independently by two review authors. Data were checked for accuracy. MAIN RESULTS: We included 11 randomised trials, involving 638 women. The overall risk of bias was judged to be unclear due to lack of methodological detail in the included studies.For the mother, there was no clear evidence of a difference between women in the exercise group and those in the control group for the risk of pre-eclampsia as the measure of hypertensive disorders of pregnancy (risk ratio (RR) 0.31, 95% confidence interval (CI) 0.01 to 7.09; two RCTs, 48 women; low-quality evidence), birth by caesarean section (RR 0.86, 95% CI 0.63 to 1.16; five RCTs, 316 women; I2 = 0%; moderate-quality evidence), the risk of induction of labour (RR 1.38, 95% CI 0.71 to 2.68; one RCT, 40 women; low-quality evidence) or maternal body mass index at follow-up (postnatal weight retention or return to pre-pregnancy weight) (mean difference (MD) 0.11 kg/m2, 95% CI -1.04 to 1.26; three RCTs, 254 women; I2 = 0%; high-quality evidence). Development of type 2 diabetes, perineal trauma/tearing and postnatal depression were not reported as outcomes in the included studies.For the infant/child/adult, a single small (n = 19) trial reported no perinatal mortality (stillbirth and neonatal mortality) events in either the exercise intervention or control group (low-quality evidence). There was no clear evidence of a difference between groups for a mortality and morbidity composite (variously defined by trials, e.g. perinatal or infant death, shoulder dystocia, bone fracture or nerve palsy) (RR 0.56, 95% CI 0.12 to 2.61; two RCTs, 169 infants; I2 = 0%; moderate-quality evidence) or neonatal hypoglycaemia (RR 2.00, 95% CI 0.20 to 20.04; one RCT, 34 infants; low-quality evidence). None of the included trials pre-specified large-for-gestational age, adiposity (neonatal/infant, childhood or adulthood), diabetes (childhood or adulthood) or neurosensory disability (neonatal/infant) as trial outcomes.Other maternal outcomes of interest: exercise interventions were associated with both reduced fasting blood glucose concentrations (average standardised mean difference (SMD) -0.59, 95% CI -1.07 to -0.11; four RCTs, 363 women; I2 = 73%; T2 = 0.19) and a reduced postprandial blood glucose concentration compared with control interventions (average SMD -0.85, 95% CI -1.15 to -0.55; three RCTs, 344 women; I2 = 34%; T2 = 0.03). AUTHORS' CONCLUSIONS: Short- and long-term outcomes of interest for this review were poorly reported. Current evidence is confounded by the large variety of exercise interventions. There was insufficient high-quality evidence to be able to determine any differences between exercise and control groups for our outcomes of interest. For the woman, both fasting and postprandial blood glucose concentrations were reduced compared with the control groups. There are currently insufficient data for us to determine if there are also benefits for the infant. The quality of the evidence in this review ranged from high to low quality and the main reason for downgrading was for risk of bias and imprecision (wide CIs, low event rates and small sample size). Development of type 2 diabetes, perineal trauma/tearing, postnatal depression, large-for-gestational age, adiposity (neonate/infant, childhood or adulthood), diabetes (childhood or adulthood) or neurosensory disability (neonate/infant) were not reported as outcomes in the included studies.Further research is required comparing different types of exercise interventions with control groups or with another exercise intervention that reports on both the short- and long-term outcomes (for both the mother and infant/child) as listed in this review.

Induction of labour versus expectant management for large-for-date fetuses: a randomised controlled trial.

BACKGROUND: Macrosomic fetuses are at increased risk of shoulder dystocia. We aimed to compare induction of labour with expectant management for large-for-date fetuses for prevention of shoulder dystocia and other neonatal and maternal morbidity associated with macrosomia. METHODS: We did this pragmatic, randomised controlled trial between Oct 1, 2002, and Jan 1, 2009, in 19 tertiary-care centres in France, Switzerland, and Belgium. Women with singleton fetuses whose estimated weight exceeded the 95th percentile, were randomly assigned (1:1), via computer-generated permuted-block randomisation (block size of four to eight) to receive induction of labour within 3 days between 37(+0) weeks and 38(+6) weeks of gestation, or expectant management. Randomisation was stratified by centre. Participants and caregivers were not masked to group assignment. Our primary outcome was a composite of clinically significant shoulder dystocia, fracture of the clavicle, brachial plexus injury, intracranial haemorrhage, or death. We did analyses by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00190320. FINDINGS: We randomly assigned 409 women to the induction group and 413 women to the expectant management group, of whom 407 women and 411 women, respectively, were included in the final analysis. Mean birthweight was 3831 g (SD 324) in the induction group and 4118 g (392) in the expectant group. Induction of labour significantly reduced the risk of shoulder dystocia or associated morbidity (n=8) compared with expectant management (n=25; relative risk [RR] 0·32, 95% CI 0·15-0·71; p=0·004). We recorded no brachial plexus injuries, intracranial haemorrhages, or perinatal deaths. The likelihood of spontaneous vaginal delivery was higher in women in the induction group than in those in the expectant management group (RR 1·14, 95% CI 1·01-1·29). Caesarean delivery and neonatal morbidity did not differ significantly between the groups. INTERPRETATION: Induction of labour for suspected large-for-date fetuses is associated with a reduced risk of shoulder dystocia and associated morbidity compared with expectant management. Induction of labour does not increase the risk of caesarean delivery and improves the likelihood of spontaneous vaginal delivery. These benefits should be balanced with the effects of early-term induction of labour. FUNDING: Assistance Publique-Hôpitaux de Paris and the University of Geneva.

Repeat digital cervical assessment in pregnancy for identifying women at risk of preterm labour.

BACKGROUND: Repeat digital cervical assessment (RDCA - examination of the cervix with a finger) has been promoted as a routine intervention in the antenatal clinic as a screening test for the risk of preterm birth (that is, birth occurring before 37 weeks of gestation). OBJECTIVES: To assess the effect of repeat digital cervical assessment during pregnancy for the risk of preterm birth and other adverse effects for mother and baby. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (September 2009) and CENTRAL (The Cochrane Library 2009, Issue 3). SELECTION CRITERIA: All known randomized clinical trials comparing repeat digital cervical assessment with internal examination limited to clinical indication or no internal examination. We have not included studies where repeat cervical assessment is only a component of complex interventions targeted at decreasing preterm birth. DATA COLLECTION AND ANALYSIS: We evaluated relevant studies for meeting the inclusion criteria and methodological quality without considering their results. Three review authors extracted the data. For all data analyses, we entered data based on the principle of intention to treat. We calculated odds ratios and 95% confidence intervals for dichotomous data. MAIN RESULTS: We included two trials that enrolled a total of 7163 women. Preterm birth before 37 weeks, was reported in both trials. The odds ratio for birth before 37 weeks was 1.05 (95% confidence interval 0.85 to 1.31; two trials, 6070 women). One trial (involving 5836 women) found no significant difference between the two treatment arms for the following outcomes: preterm birth before 34 weeks; preterm, prelabour rupture of membranes; hospital admission before 37 weeks; caesarean section; use of tocolytic drugs; low birthweight; very low birthweight, stillbirth, neonatal death, neonatal intensive care admissions; use of health services. The other prespecified outcomes were not evaluated in the included studies. We did not conduct the planned subgroup analyses due to insufficient data. AUTHORS' CONCLUSIONS: We found no evidence to support the use of RDCA in pregnancy to reduce the prevalence of preterm birth. We have found insufficient evidence to assess adverse effects of the intervention.

Spontaneous delivery or manual removal of the placenta during caesarean section: a randomised controlled trial.

OBJECTIVE: To compare blood loss with spontaneous delivery and manual removal of the placenta during caesarean section. DESIGN: A randomised controlled trial. SETTING: Four university hospitals between September 1999 and June 2002. POPULATION: A total of 472 women delivering by caesarean section at term were randomised to spontaneous placental delivery (n= 235) or manual removal (n= 237). METHODS: The allocation was made by opening the next available of a series of sealed opaque envelopes and derived from a computer-generated list of numbers. MAIN OUTCOME MEASURES: Significant blood loss, defined as either a drop in haemoglobin of greater than 2.5 g/dL, or the need for blood transfusion. RESULTS: The mean interval between delivery of the newborn and the placenta was longer in the spontaneous delivery group (3.4 vs 1.9 minutes), but the mean duration of the operation was similar. Significant blood loss occurred in 30 women (13%) in the spontaneous delivery group and 49 women (21%) in the manual removal one (RR 0.62; 95% CI 0.41-0.94). Post-operative fever affected 6 and 5 cases, respectively, and antibiotics were used in 14 and 12 cases, respectively. CONCLUSIONS: Allowing spontaneous delivery of the placenta reduces significant blood loss without increasing operating time.