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Objective: To assess the natural history and contemporary outcomes in pregnancies complicated by previable preterm premature rupture of membranes (PROM).Methods: Retrospective study of all women with a singleton or twin pregnancy admitted to a single tertiary referral center who experienced preterm PROM between 20 and 23 6/7 weeks of gestation during 2004-2014 and underwent expectant management. Women electing termination of pregnancy and pregnancies complicated by major fetal anomalies were excluded. Severe neonatal morbidity was defined as a composite of bronchopulmonary dysplasia, severe neurologic injury, or severe retinopathy of prematurity. Long-term follow-up to a corrected age of 18-21 months was available for the majority of surviving neonates.Results: Of the 140 neonates born to women with previable preterm PROM during the study period, 104 were eligible for the study. Overall 51 (49.0%, 95% confidence interval [CI] 39.4-58.6%) newborns survived to discharge, of whom 24 (47.1%, 95% CI 33.4-60.8%) experienced severe neonatal morbidity. The overall rate of long-term morbidity among surviving neonates was 23.3% (95% CI 11.7-34.9%) and was significantly higher among neonates who previously experienced severe neonatal morbidity compared with those who did not (39.1% compared with 10.0%, P=.04). The only two factors that were significantly associated with overall survival and survival without severe neonatal morbidity were gestational age at preterm PROM of 22 weeks or greater (adjusted odds ratio [OR] 12.2, 95% CI 3.3-44.8 and adjusted OR 4.8, 95% CI 1.2-19.3, respectively) and a latency period of greater than 7 days (adjusted OR 10.1, 95% CI 3.2-31.6, and adjusted OR 6.7, 95% CI 2.2-21.0, respectively). Expectant management was associated with maternal risks including placental abruption (17.3%, 95% CI 10.0-24.6%) and sepsis (4.8%, 95% CI 0.7-8.9%).Conclusion: Expectant management in pregnancies complicated by previable preterm PROM between 20 and 23 6/7 weeks of gestation is associated with an overall neonatal survival rate of 49.0%, high risk of short- and long-term severe morbidity among survivors, and carries considerable maternal risks. [ABSTRACT FROM AUTHOR]

Background: Women with type 1 diabetes strive for optimal glycemic control before and during pregnancy to avoid adverse obstetric and perinatal outcomes. For most women, optimal glycemic control is challenging to achieve and maintain. The aim of this study is to determine whether the use of real-time continuous glucose monitoring (RT-CGM) will improve glycemic control in women with type 1 diabetes who are pregnant or planning pregnancy.Methods/design: A multi-center, open label, randomized, controlled trial of women with type 1 diabetes who are either planning pregnancy with an HbA1c of 7.0 % to ≤10.0 % (53 to ≤ 86 mmol/mol) or are in early pregnancy (<13 weeks 6 days) with an HbA1c of 6.5 % to ≤10.0 % (48 to ≤ 86 mmol/mol). Participants will be randomized to either RT-CGM alongside conventional intermittent home glucose monitoring (HGM), or HGM alone. Eligible women will wear a CGM which does not display the glucose result for 6 days during the run-in phase. To be eligible for randomization, a minimum of 4 HGM measurements per day and a minimum of 96 hours total with 24 hours overnight (11 pm-7 am) of CGM glucose values are required. Those meeting these criteria are randomized to RT- CGM or HGM. A total of 324 women will be recruited (110 planning pregnancy, 214 pregnant). This takes into account 15 and 20 % attrition rates for the planning pregnancy and pregnant cohorts and will detect a clinically relevant 0.5 % difference between groups at 90 % power with 5 % significance. Randomization will stratify for type of insulin treatment (pump or multiple daily injections) and baseline HbA1c. Analyses will be performed according to intention to treat. The primary outcome is the change in glycemic control as measured by HbA1c from baseline to 24 weeks or conception in women planning pregnancy, and from baseline to 34 weeks gestation during pregnancy. Secondary outcomes include maternal hypoglycemia, CGM time in, above and below target (3.5-7.8 mmol/l), glucose variability measures, maternal and neonatal outcomes.Discussion: This will be the first international multicenter randomized controlled trial to evaluate the impact of RT- CGM before and during pregnancy in women with type 1 diabetes.Trial Registration: ClinicalTrials.gov Identifier: NCT01788527 Registration Date: December 19, 2012. [ABSTRACT FROM AUTHOR]

Background: Offspring of women with type 1 diabetes are at increased risk of fetal growth patterns which are associated with perinatal morbidity. Our aim was to compare rates of large- and small-for-gestational age (LGA; SGA) defined according to different criteria, using data from the Continuous Glucose Monitoring in Type 1 Diabetes Pregnancy Trial (CONCEPTT).Methods: This was a pre-specified analysis of CONCEPTT involving 225 pregnant women and liveborn infants from 31 international centres ( ClinicalTrials.gov NCT01788527; registered 11/2/2013). Infants were weighed immediately at birth and GROW, INTERGROWTH and WHO centiles were calculated. Relative risk ratios, sensitivity and specificity were used to assess the different growth standards with respect to perinatal outcomes, including neonatal hypoglycaemia, hyperbilirubinaemia, respiratory distress, neonatal intensive care unit (NICU) admission and a composite neonatal outcome.Results: Accelerated fetal growth was common, with mean birthweight percentiles of 82.1, 85.7 and 63.9 and LGA rates of 62, 67 and 30% using GROW, INTERGROWTH and WHO standards respectively. Corresponding rates of SGA were 2.2, 1.3 and 8.9% respectively. LGA defined according to GROW centiles showed stronger associations with preterm delivery, neonatal hypoglycaemia, hyperbilirubinaemia and NICU admission. Infants born > 97.7th centile were at highest risk of complications. SGA defined according to INTERGROWTH centiles showed slightly stronger associations with perinatal outcomes.Conclusions: GROW and INTERGROWTH standards performed similarly and identified similar numbers of neonates with LGA and SGA. GROW-defined LGA and INTERGROWTH-defined SGA had slightly stronger associations with neonatal complications. WHO standards underestimated size in preterm infants and are less applicable for use in type 1 diabetes.Trial Registration: This trial is registered with ClinicalTrials.gov . number NCT01788527 . Trial registered 11/2/2013. [ABSTRACT FROM AUTHOR]

An abstract of the article "Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study: 2-Year Outcomes," by Elizabeth V. Asztalos and colleagues is presented.

Objective: To test the hypothesis that the risk of neonatal morbidity among late-preterm twins is similar to that of late-preterm singletons.Methods: We conducted a retrospective cohort study of all women with twin or singleton pregnancy who gave birth during the late-preterm period in a single tertiary center between 2008 and 2015. Neonatal outcomes of low-risk, late-preterm twins were compared with those of low-risk, late-preterm singletons. The primary outcome was the same primary composite respiratory morbidity variable that was used in the randomized controlled trial of Gyamfi-Bannerman et al on the administration of antenatal corticosteroids during the late-preterm period.Results: A total of 922 singleton and 721 twin late-preterm neonates met the inclusion criteria. The rates of composite respiratory morbidity and severe composite respiratory morbidity were similar for twins and singletons (8.3% compared with 7.4%, P=.5 and 6.8% compared with 6.0%, P=.5, respectively), but were lower than the rates of the same composite respiratory morbidity variable in the randomized controlled study described previously. The odds for respiratory morbidity were similar for twins and singletons for both composite respiratory morbidity (adjusted odds ratio [OR] 0.73, 95% CI 0.48-1.12) and severe composite respiratory morbidity (adjusted OR 0.79, 95% CI 0.50-1.24).Conclusion: The risk of respiratory morbidity among late-preterm twins is similar to that of late-preterm singletons. Still, the low absolute rates of the composite respiratory morbidity in our population suggest that administration of antenatal corticosteroids may be mostly justified among neonates born closer to 34 weeks of gestation. [ABSTRACT FROM AUTHOR]

Background: The incidence of type 2 diabetes in pregnancy is rising and rates of serious adverse maternal and fetal outcomes remain high. Metformin is a biguanide that is used as first-line treatment for non-pregnant patients with type 2 diabetes. We hypothesize that metformin use in pregnancy, as an adjunct to insulin, will decrease adverse outcomes by reducing maternal hyperglycemia, maternal insulin doses, maternal weight gain and gestational hypertension/pre-eclampsia. In addition, since metformin crosses the placenta, metformin treatment of the fetus may have a direct beneficial effect on neonatal outcomes. Our aim is to compare the effectiveness of the addition of metformin to insulin, to standard care (insulin plus placebo) in women with type 2 diabetes in pregnancy.Methods: The MiTy trial is a multi-centre randomized trial currently enrolling pregnant women with type 2 diabetes, who are on insulin, between the ages of 18-45, with a gestational age of 6 weeks 0 days to 22 weeks 6 days. In this randomized, double-masked, parallel placebo-controlled trial, after giving informed consent, women are randomized to receive either metformin 1,000 mg twice daily or placebo twice daily. A web-based block randomization system is used to assign women to metformin or placebo in a 1:1 ratio, stratified for site and body mass index. The primary outcome is a composite neonatal outcome of pregnancy loss, preterm birth, birth injury, moderate/severe respiratory distress, neonatal hypoglycemia, or neonatal intensive care unit admission longer than 24 h. Secondary outcomes are large for gestational age, cord blood gas pH < 7.0, congenital anomalies, hyperbilirubinemia, sepsis, hyperinsulinemia, shoulder dystocia, fetal fat mass, as well as maternal outcomes: maternal weight gain, maternal insulin doses, maternal glycemic control, maternal hypoglycemia, gestational hypertension, preeclampsia, cesarean section, number of hospitalizations during pregnancy, and duration of hospital stays. The trial aims to enroll 500 participants.Discussion: The results of this trial will inform endocrinologists, obstetricians, family doctors, and other healthcare professionals caring for women with type 2 diabetes in pregnancy, as to the benefits of adding metformin to insulin in this high risk population.Trial Registration: ClinicalTrials.gov Identifier: no. NCT01353391 . Registered February 6, 2009. [ABSTRACT FROM AUTHOR]

Purpose: To compare pregnancy outcomes in women with pPROM and a cervical cerclage in whom the cerclage was removed within 24 h and those in whom the cerclage was retained in situ.Methods: A two-center retrospective cohort study of women with a singleton gestation with pPROM at < 340/7 weeks of gestation in the presence of cervical cerclage (January 1, 2012-July 30, 2016). Maternal and perinatal outcomes were compared between women in whom cerclage was removed within 24 h from pPROM and those in whom cerclage was retained until the onset of delivery. The primary outcome was time from pPROM to delivery.Results: Seventy women met inclusion criteria. Cerclage was left in situ in 47 (67.1%) and removed in 23 (32.9%) women. Women in the cerclage retention group had a higher pPROM-to-delivery interval (7.0 ± 7.2 vs. 6.0 ± 10.9 days, p = 0.03), and were more likely to have a latency period > 48 h (87.2% vs. 65.2%, p = 0.03; aOR 3.9, 95% CI 3.1-4.9) or > 7 days (29.8% vs. 8.7%, p = 0.04; aOR 7.0, 95% CI 2.5-19.6) compared with women in whom cerclage was removed. Furthermore, chorioamnionitis rate was lower in the cerclage retention group compared to cerclage removal group (aOR 0.7, 95% CI 0.5-1.0). There were no differences between the groups in early neonatal sepsis, severe brain injury, or composite neonatal outcome.Conclusion: In women with pPROM and cervical cerclage, retention of cerclage may be associated with a longer latency period, and a lower chorioamnionitis rate, without an associated increase in the risk of neonatal infectious morbidity. Presentation information: The abstract of this study was presented as a poster at the 38th SMFM (Society of Maternal and Fetal Medicine) annual meeting, February 2018, Dallas, Texas, USA. [ABSTRACT FROM AUTHOR]

Background: The Twin Birth Study, a multicenter randomized controlled trial, found no differences in neonatal outcomes in women with twins randomized to planned cesarean or vaginal delivery. Nevertheless, women who present in spontaneous labor might expect a better outcome following a trial of vaginal delivery than undergoing cesarean delivery. In this secondary analysis, we aimed to compare neonatal outcomes of women who presented in spontaneous labor in the two arms of the Twin Birth Study. Methods: Women in whom the first twin was in the cephalic presentation were randomized between 32 + 0 and 38 + 6 weeks to planned vaginal delivery or cesarean. The primary outcome was a composite of fetal or neonatal death or serious neonatal morbidity. Results: Of the 2804 women included in the Twin Birth Study, 823 women in the planned vaginal delivery arm and 612 in the planned cesarean arm presented in spontaneous labor. Although the odds ratio favored planned vaginal delivery, there was no statistically significant difference in the rate of primary outcome between the vaginal delivery and cesarean arms (1.8% vs 2.7%, respectively; P = 0.16; OR 1.49; 95% CI, 0.87‐2.55). Similarly, the rates of the individual components of the primary outcome and of maternal adverse outcome were similar between the two arms. Conclusion: In women with twins who present in spontaneous labor between 32 + 0 and 38 + 6 weeks' gestation, where the first twin is cephalic, a policy of planned vaginal delivery or cesarean is not associated with significant differences in neonatal or maternal outcomes. [ABSTRACT FROM AUTHOR]

Background: Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes.Methods: In this multicentre, open-label, randomised controlled trial, we recruited women aged 18-40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527.Findings: Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference -0·19%; 95% CI -0·34 to -0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy).Interpretation: Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use.Funding: Juvenile Diabetes Research Foundation, Canadian Clinical Trials Network, and National Institute for Health Research. [ABSTRACT FROM AUTHOR]

It has been conclusively established that folic acid supplementation prior to and during early pregnancy (up to 12 weeks of gestation) can prevent neural tube defects (NTDs). We hypothesized that folate effects may extend from neuro-structural defects to alterations in neuro-behavioural and emotional skills including autism spectrum disorders (ASDs) and other developmental disorders. The objective of this review was to comprehensively evaluate evidence on the impact of folic acid on neurodevelopment other than NTDs. We conducted an online search of relevant literature compiled by the National Library of Medicine from Medline and EMBASE (searched on Dec 31, 2014: and ). We first created 3 files (search restricted to English literature) using the following key words: 1) folate or folic acid (171322 papers identified by this search); 2) maternal or pregnancy or pregnant or gestation or gestational or prenatal or antenatal or periconception or periconceptional (1349219 papers identified by this search); and 3) autism or autism spectrum disorders or developmental delay or development or neurodevelopment or mental or cognitive or language or personal-social or gross motor or fine motor or behaviour or intellectual or intelligence or Bayley Scale (8268145 papers identified by this search). We then merged the 3 files and reviewed the papers that addressed these three issues simultaneously. A total of 22 original papers that examined the association between folic acid supplementation in human pregnancy and neurodevelopment/autism were identified after the screening, with 15 studies showing a beneficial effect of folic acid supplementation on neurodevelopment/autism, 6 studies showed no statistically significant difference, while one study showed a harmful effect in > 5 mg folic acid supplementation/day during pregnancy. Folic acid supplementation in pregnancy may have beneficial effects on the neurodevelopment of children beyond its proven effect on NTDs. [ABSTRACT FROM AUTHOR]

Objective: To compare women's views about blood pressure (BP) control in CHIPS (Control of Hypertension In Pregnancy Study) (NCT01192412).Design: Quantitative and qualitative analysis of questionnaire responses.Setting: International randomised trial (94 sites, 15 countries).Population/sample: 911 (92.9%) women randomised to 'tight' (target diastolic blood pressure, 85mmHg) or 'less tight' (target diastolic blood pressure, 100mmHg) who completed questionnaires.Methods: A questionnaire was administered at ∼6-12 weeks postpartum regarding post-discharge morbidity and views about trial participation. Questionnaires were administered by the site co-ordinator, and contact was made by phone, home or clinic visit; rarely, data was collected from medical records. Quantitative analyses were Chi-square or Fisher's exact test for categorical variables, mixed effects multinomial logistic regression to adjust for confounders, and p<0.001 for statistical significance. NVivo software was used for thematic analysis of women's views.Main Outcome Measures: Satisfaction, measured as willingness to have the same treatment in another pregnancy or recommend that treatment to a friend.Results: Among the 533 women in 'tight' (N=265) vs. 'less tight' (N=268) control who provided comments for qualitative analysis, women in 'tight' (vs. 'less tight') control made fewer positive comments about the amount of medication taken (5 vs. 28 women, respectively) and intensity of BP monitoring (7 vs. 17, respectively). However, this did not translate into less willingness to either have the same treatment in another pregnancy (434, 95.8% vs. 423, 92.4%, respectively; p=0.14) or recommend that treatment to a friend (435, 96.0% and 428, 93.4%, respectively; p=0.17). Importantly, although satisfaction remained high among women with an adverse outcome, those in 'tight' control who suffered an adverse outcome (vs. those who did not) were not consistently less satisfied, whereas this was not the case among women in 'less tight' control among whom satisfaction was consistently lower for the CHIPS primary outcome (p<0.001), severe hypertension (p≤0.01), and pre-eclampsia (p<0.001).Conclusions: Women in 'tight' (vs. 'less tight') control were equally satisfied with their care, and more so in the face of adverse perinatal or maternal outcomes. [ABSTRACT FROM AUTHOR]

Introduction: For women with chronic or gestational hypertension in CHIPS (Control of Hypertension In Pregnancy Study, NCT01192412), we aimed to examine whether clinical predictors collected at randomization could predict adverse outcomes.Material and Methods: This was a planned, secondary analysis of data from the 987 women in the CHIPS Trial. Logistic regression was used to examine the impact of 19 candidate predictors on the probability of adverse perinatal (pregnancy loss or high level neonatal care for >48 h, or birthweight <10th percentile) or maternal outcomes (severe hypertension, preeclampsia, or delivery at <34 or <37 weeks). A model containing all candidate predictors was used to start the stepwise regression process based on goodness of fit as measured by the Akaike information criterion. For face validity, these variables were forced into the model: treatment group ("less tight" or "tight" control), antihypertensive type at randomization, and blood pressure within 1 week before randomization. Continuous variables were represented continuously or dichotomized based on the smaller p-value in univariate analyses. An area-under-the-receiver-operating-curve (AUC ROC) of ≥0.70 was taken to reflect a potentially useful model.Results: Point estimates for AUC ROC were <0.70 for all but severe hypertension (0.70, 95% CI 0.67-0.74) and delivery at <34 weeks (0.71, 95% CI 0.66-0.75). Therefore, no model warranted further assessment of performance.Conclusions: CHIPS data suggest that when women with chronic hypertension develop an elevated blood pressure in pregnancy, or formerly normotensive women develop new gestational hypertension, maternal and current pregnancy clinical characteristics cannot predict adverse outcomes in the index pregnancy. [ABSTRACT FROM AUTHOR]

Aims: While preterm infants are known to be at risk of intracranial haemorrhages, advances in ultrasound imaging of preterm babies have facilitated recognition of presence of haemorrhages in the posterior fossa, which include cerebellar and Cisterna Magna haemorrhages. There are limited data on the profile and predisposing risk factors. The objective was to identify antenatal, intrapartum and post-natal risk factors for and to define the clinical spectrum. The study was designed as a retrospective case-control study in the setting of a tertiary level neonatal intensive care unit. Preterm babies ≤30 weeks gestation age admitted between January 2005 and December 2006, with an ultrasound diagnosis of posterior fossa haemorrhage and an equal number of controls matched for gestation age, gender and month of birth with normal cranial scans were selected. Systematic chart and radiographic review was done. All cranial ultrasounds in both groups were reviewed. Results: Eighteen babies had documented posterior fossa haemorrhage (13 cerebellar, 5 isolated Cisterna Magna, 10 both), the median time of detection being 2.5 days. Eleven babies had either no or grade I/II supratentorial bleeds, while half of all cerebellar bleeds were bilateral. All haemorrhages were visualised from mastoid view and none from anterior fontanel. On univariate analysis, multiple gestations, lack of antenatal steroids, foetal heart rate abnormalities, need for volume expanders and cardiotrophins and sepsis were associated with a higher risk for having posterior fossa bleeds. Conclusions: Posterior fossa haemorrhages in preterm babies are being increasingly recognised. Antenatal, intrapartum and post-natal factors may predispose towards haemorrhages in the cerebellum or Cisterna Magna. [ABSTRACT FROM AUTHOR]