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Background: Preterm premature rupture of membranes complicates approximately 3% of pregnancies. Currently, in the absence of chorioamnionitis or placental abruption, expectant management, including antenatal steroids for lung maturation and prophylactic antibiotic treatment, is recommended. The benefits of individualized management have not been adequately explored.Objective: This study aimed to compare the impact of 2 different management strategies of preterm premature rupture of membranes in 2 tertiary obstetrical centers on latency of >7 days, latency to birth, chorioamnionitis, funisitis, and short-term adverse maternal and neonatal outcomes.Study Design: This was a multicenter retrospective study of women with singleton pregnancies with preterm premature rupture of membranes from 23 0/7 to 33 6/7 weeks of gestation between 2014 and 2018 and undelivered within 24 hours after hospital admission managed at Sunnybrook Health Sciences Center, Toronto, Canada (standard management group), and BCNatal (Hospital Clínic of Barcelona and Hospital Sant Joan de Déu Barcelona), Barcelona, Spain (individualized management group), following local protocols. The standard management group received similar management for all patients, which included a standard antibiotic regimen and routine maternal and fetal surveillance, whereas the individualized management group received personalized management on the basis of amniocentesis at hospital admission (if possible), to rule out microbial invasion of the amniotic cavity and targeted treatment. The exclusion criteria were cervical dilatation >2 cm, active labor, contraindications to expectant management (acute chorioamnionitis, placental abruption, or abnormal fetal tracing), and major fetal anomalies. The primary outcome was latency of >7 days, and the secondary outcomes included latency to birth, chorioamnionitis, and short-term adverse maternal and neonatal outcomes. Statistical comparisons between groups were conducted with propensity score weighting.Results: A total of 513 pregnancies with preterm premature rupture of membranes were included in this study: 324 patients received standard management, and 189 patients received individualized management, wherein amniocentesis was performed in 112 cases (59.3%). After propensity score weighting, patients receiving individualized management had a higher latency of >7 days (76.0% vs 41.6%; P<.001) and latency to birth (18.1±14.7 vs 9.7±9.7 days; P<.001). Although a higher rate of clinical chorioamnionitis was suspected in the individualized management group than the standard group (34.5% vs 22.0%; P<.01), there was no difference between the groups in terms of histologic chorioamnionitis (67.2% vs 73.4%; P=.16), funisitis (57.6% vs 58.1%; P=.92), or composite infectious maternal outcomes (9.1% vs 7.9%; P=.64). Prolonged latency in the individualized management group was associated with a significant reduction of preterm birth at <32 weeks of gestation (72.1% vs 90.5%; P<.001), neonatal intensive care unit admission (75.6% vs 83.0%; P=.046), and neonatal respiratory support at 28 days of life (16.1% vs 26.1%; P<.01) compared with that in the standard management group. Moreover, prolonged latency was not associated with neonatal severe morbidity at discharge (survival without severe morbidity, 80.4% vs 73.5%; P=.09).Conclusion: Individualized management of preterm premature rupture of membranes may prolong pregnancy and reduce preterm birth at <32 weeks of gestation, the need for neonatal support, and neonatal intensive care unit admissions, without an increase in histologic chorioamnionitis, funisitis, neonatal infection-related morbidity, and short-term adverse maternal and neonatal outcomes. [ABSTRACT FROM AUTHOR]

Objective To compare oxygen saturations as displayed to caregivers on offset pulse oximeters in the 2 groups of the Canadian Oxygen Trial. Study design In 5 double-blind randomized trials of oxygen saturation targeting, displayed saturations between 88% and 92% were offset by 3% above or below the true values but returned to true values below 84% and above 96%. During the transition, displayed values remained static at 96% in the lower and at 84% in the higher target group during a 3% change in true saturations. In contrast, displayed values changed rapidly from 88% to 84% in the lower and from 92% to 96% in the higher target group during a 1% change in true saturations. We plotted the distributions of median displayed saturations on days with >12 hours of supplemental oxygen in 1075 Canadian Oxygen Trial participants to reconstruct what caregivers observed at the bedside. Results The oximeter masking algorithm was associated with an increase in both stability and instability of displayed saturations that occurred during the transition between offset and true displayed values at opposite ends of the 2 target ranges. Caregivers maintained saturations at lower displayed values in the higher than in the lower target group. This differential management reduced the separation between the median true saturations in the 2 groups by approximately 3.5%. Conclusions The design of the oximeter masking algorithm may have contributed to the smaller-than-expected separation between true saturations in the 2 study groups of recent saturation targeting trials in extremely preterm infants. [ABSTRACT FROM AUTHOR]

Objective: To determine whether extremely low birth weight infants (ELBW) transfused at lower hemoglobin thresholds versus higher thresholds have different rates of survival or morbidity at discharge. Study design: Infants weighing <1000 g birth weight were randomly assigned within 48 hours of birth to a transfusion algorithm of either low or high hemoglobin transfusion thresholds. The composite primary outcome was death before home discharge or survival with any of either severe retinopathy, bronchopulmonary dysplasia, or brain injury on cranial ultrasound. Morbidity outcomes were assessed, blinded to allocation. Results: Four hundred fifty-one infants were randomly assigned to low (n = 223) or high (n = 228) hemoglobin thresholds. Groups were similar, with mean birth weight of 770 g and gestational age of 26 weeks. Fewer infants received one or more transfusions in the low threshold group (89% low versus 95% high, P = .037). Rates of the primary outcome were 74.0% in the low threshold group and 69.7% in the high (P = .25; risk difference, 2.7%; 95% CI –3.7% to 9.2%). There were no statistically significant differences between groups in any secondary outcome. Conclusions: In extremely low birth weight infants, maintaining a higher hemoglobin level results in more infants receiving transfusions but confers little evidence of benefit. [Copyright &y& Elsevier]

Background: The current literature regarding the recommended mode of delivery of monochorionic-diamniotic twins is limited to small numbers, retrospective studies, and comparisons of outcomes of monochorionic-diamniotic twin pregnancies with those of dichorionic-diamniotic twin pregnancies instead of outcomes of trial of labor vs elective cesarean delivery of monochorionic-diamniotic twins.Objective: This study aimed to compare perinatal and maternal outcomes of planned cesarean delivery and planned vaginal delivery of monochorionic-diamniotic twins using the Twin Birth Study data.Study Design: This study is a secondary analysis of the Twin Birth Study. Women were randomized from 32 weeks and 0 days gestation to 38 weeks and 6 days gestation to planned cesarean delivery or planned vaginal delivery. Twin A in the cephalic presentation and estimated weight of each twin between 1500 and 4000 grams were the inclusion criteria. Pregnancies complicated by fetal reduction after 13 weeks of gestation, lethal fetal anomaly, or contraindication to vaginal delivery were excluded. Elective delivery was planned between 37 weeks and 5 to 7 days of gestation and 38 weeks and 6 to 7 days of gestation. Perinatal and maternal outcomes of monochorionic-diamniotic twin pregnancies were compared between those randomized for planned cesarean delivery and those randomized for planned vaginal delivery. In addition, outcomes of monochorionic-diamniotic twin pregnancies were compared with those of dichorionic-diamniotic twin pregnancies.Results: Out of the 1393 women in each arm, 346 (24.9%) women in the planned cesarean delivery arm and 324 (23.3%) women in the planned vaginal delivery arm had monochorionic-diamniotic twin pregnancies and were eligible for the first analysis. The rate of cesarean delivery was 39.2% in the planned vaginal delivery arm and was 91.3% in the planned cesarean delivery arm. There was no significant difference in gestational age at delivery between the groups (34.4±1.8 weeks vs 34.5±1.8 weeks; P=.78). No difference was found in maternal outcomes. As for perinatal outcomes, the rate of the primary adverse neonatal composite outcomes in twins A or twins B was similar in both the planned vaginal delivery and the planned cesarean delivery arms (twins A, 1.2% vs 1.2% [P=.92]; twins B, 1.2% vs 3.2% [P=.09]). Within the planned cesarean delivery arm, the rate of primary adverse neonatal composite outcome was higher in twins B than twins A (3.2% vs 1.2%; P=.03). There was no difference in the primary adverse neonatal composite outcome between twins A in the monochorionic-diamniotic group and the dichorionic-diamniotic group (1.2% vs 1.3%; P=.89) or between twins B in similar groups (2.3% vs 2.7%; P=.47).Conclusion: In monochorionic-diamniotic twin pregnancy between 32 weeks and 0 to 7 days of gestation and 38 weeks and 6 to 7 days of gestation, with twin A in a cephalic presentation, planned cesarean delivery did not decrease or increase the risk of fetal or neonatal death or serious neonatal morbidity, as compared with planned vaginal delivery. [ABSTRACT FROM AUTHOR]

Objective: The reported incidence of combined twin delivery (vaginal delivery of twin A followed by cesarean delivery for twin B) ranges between 5% and 10%. These estimates are based mostly on small studies or retrospective data. We aimed to evaluate to incidence and risk factors for and outcomes of combined twin deliveries, using a subanalysis of the Twin Birth Study, a randomized, controlled, prospective study.Study Design: The Twin Birth Study included women with twin gestation between 32+0 and 38+6 weeks, with the first twin in vertex presentation at randomization. Women were randomized to planned cesarean delivery or planned vaginal delivery. For the purpose of this subanalysis, we included women who had a vaginal delivery of twin A. Women who had a combined delivery (cesarean delivery for twin B) were compared with women who had a vaginal delivery of both twins. Our primary objective was to identify risk factors for combined twin deliveries. Our secondary objective was to assess the rate of fetal/neonatal death or serious neonatal morbidity in combined deliveries.Results: Of the 2786 women included in the original study, 842 women delivered twin A by a vaginal delivery and were included in the current analysis, of whom 59 (7%) had a combined delivery. Women in the combined delivery group had a lower rate of nulliparity (22.0% vs 34.7%, P = 0.047) and higher rates of noncephalic presentation of twin B at delivery (61.0% vs 27.3%, P < 0.001) and spontaneous version from presentation at randomization of twin B (72.9% vs 44.3%, P < 0.0001). In a multivariable model, the only risk factor significantly associated with a combined delivery was transverse/oblique lie of twin B following delivery of twin A (adjusted odds ratio, 47.7; 95% confidence interval, 15.4-124.5). Twins B in the combined delivery group had a higher rate of fetal/neonatal death or serious neonatal morbidity (13.6% vs 2.3%, P < 0.001), 5-minute Apgar score <7, neonatal intensive care unit admission, abnormal level of consciousness, and assisted ventilation.Conclusion: Transverse/oblique lie of twin B following vaginal delivery of twin A is a risk factor for combined delivery. Combined delivery is associated with higher risk of adverse neonatal outcomes of twin B. These data may be used to better counsel women with twin gestation who consider a trial of labor. [ABSTRACT FROM AUTHOR]

Background: The Twin Birth Study randomized women with uncomplicated pregnancies, between 32(0/7)-38(6/7) weeks' gestation where the first twin was in cephalic presentation, to a policy of either a planned cesarean or planned vaginal delivery. The primary analysis showed that planned cesarean delivery did not increase or decrease the risk of fetal/neonatal death or serious neonatal morbidity as compared with planned vaginal delivery.Objective: This study presents the secondary outcome of death or neurodevelopmental delay at 2 years of age.Study Design: A total of 4603 children from the initial cohort of 5565 fetuses/infants (83%) contributed to the outcome of death or neurodevelopmental delay. Surviving children were screened using the Ages and Stages Questionnaire with abnormal scores validated by a clinical neurodevelopmental assessment. The effect of planned cesarean vs planned vaginal delivery on death or neurodevelopmental delay was quantified using a logistic model to control for stratification variables and using generalized estimating equations to account for the nonindependence of twin births.Results: Baseline maternal, pregnancy, and infant characteristics were similar. Mean age at assessment was 26 months. There was no significant difference in the outcome of death or neurodevelopmental delay: 5.99% in the planned cesarean vs 5.83% in the planned vaginal delivery group (odds ratio, 1.04; 95% confidence interval, 0.77-1.41; P = .79).Conclusion: A policy of planned cesarean delivery provides no benefit to children at 2 years of age compared with a policy of planned vaginal delivery in uncomplicated twin pregnancies between 32(0/7)-38(6/7)weeks' gestation where the first twin is in cephalic presentation. [ABSTRACT FROM AUTHOR]

Objective: To evaluate bronchopulmonary dysplasia (BPD), serious brain injury, and severe retinopathy of prematurity (ROP) as predictors of poor long-term outcome in very low birth weight infants.Study Design: We examined the associations between counts of the 3 morbidities and long-term outcomes in 1514 of 1791 (85%) infants with birth weights of 500-1250 g who were enrolled in the Caffeine for Apnea of Prematurity trial from October 1999, to October 2004, had complete morbidity data, and were alive at 36 weeks postmenstrual age (PMA). BPD was defined as use of supplemental oxygen at 36 weeks PMA. Serious brain injury on cranial ultrasound included grade 3 and 4 hemorrhage, cystic periventricular leucomalacia, porencephalic cysts, or ventriculomegaly of any cause. Poor long-term outcome was death after 36 weeks PMA or survival to 5 years with 1 or more of the following disabilities: motor impairment, cognitive impairment, behavior problems, poor general health, deafness, and blindness.Results: BPD, serious brain injury, and severe ROP occurred in 43%, 13%, and 6% of the infants, respectively. Each of the 3 morbidities was similarly and independently correlated with poor 5-year outcome. Rates of death or disability (95% CI) in children with none, any 1, any 2, and all 3 morbidities were 11.2% (9.0%-13.7%), 22.9% (19.6%-26.5%), 43.9% (35.5%-52.6%), and 61.5% (40.6%-79.8%), respectively.Conclusions: In very low birth weight infants who survive to 36 weeks PMA, a count of BPD, serious brain injury, and severe ROP predicts the risk of a late death or survival with disability at 5 years. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the benefits of caffeine vary in three subgroups of 2006 participants in the Caffeine for Apnea of Prematurity (CAP) trial. Study design: Post-hoc subgroup analyses were performed on the basis of: (1) indication for commencement of study drug: treat apnea, prevent apnea, or facilitate extubation; (2) positive pressure ventilation (PPV) at randomization: endotracheal tube (ETT), noninvasive ventilation, or none; and (3) timing of commencement of study drug: early or late (≤3 versus >3 days). Outcomes assessed were those showing treatment effects in the original analyses. We investigated the consistency of caffeine effects by using regression models that incorporated treatment/subgroup factor interactions. Results: There was little evidence of a differential treatment effect of caffeine in subgroups defined by the clinical indication for starting study drug. The size and direction of the caffeine effect on death or disability differed depending on PPV at randomization (P = .03). Odds ratios (95% CI) were: no support, 1.32 (0.81-2.14); noninvasive support, 0.73 (0.52-1.03); and ETT, 0.73 (0.57-0.94). Adjustment for baseline factors strengthened this effect (P = .02). Starting caffeine early resulted in larger reductions in days of respiratory support. Postmenstrual age at time of discontinuing PPV was shorter with earlier treatment (P = .01). Mean differences (95% CI) were: early, 1.35 weeks (0.90-1.81); and late 0.55 weeks (–0.11-0.99). Adjustment for baseline factors weakened this effect (P = .03). Conclusions: There is evidence of variable beneficial effects of caffeine. Infants receiving respiratory support appeared to derive more neurodevelopmental benefits from caffeine than infants not receiving support. Earlier initiation of caffeine may be associated with a greater reduction in time on ventilation. [Copyright &y& Elsevier]

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]

Abstract: Background: To date, there are over 40 infant pain measures. Despite this plethora of measures, only 8 have included preterm infants and only 2 have included Extremely Low Gestational Age (ELGA; infants <28 weeks GA) in their development. Without reliable, valid and clinically useful indicators for procedural pain in ELGA infants, clinicians have no means to interpret the responses from an immature infant who may respond differently from infants of older GA. Objective: To examine the physiological, behavioural and biochemical responses to painful and non-painful procedures in ELGA infants and the influence of GA and sex. Design/methods: A prospective crossover design with 50 ELGA infants from one Canadian tertiary level NICU was conducted. Infants were assessed in random order during standardized painful (heel lance) and non-painful (diaper change) procedures. Physiological (heart rate, oxygen saturation) and behavioural (facial and body movement) indicators were continuously collected during 4 phases of the procedures. Biochemical (salivary cortisol) indicators were collected immediately before and 20 min following the procedures. Results: Four facial actions (brow bulge, eye squeeze, nasolabial furrow, vertical mouth stretch) increased immediately following the heel lance. There were no specific changes in physiological, body movement or cortisol indicators following the heel lance. ELGA infants demonstrated greater body movements during the diaper change, which may reflect immature motor coordination. No differences in pain responses were found for infants born between 23-25 6/7 weeks GA and those between 26-28 weeks GA. Similarly, no gender differences were found. Conclusions: Changes in 4 facial actions were the most sensitive indicators of pain in ELGA infants. This finding is consistent with existing measures where facial actions are the most prominent pain indicators. Specific body movements such as those included in NIDCAP, may provide more information about pain in ELGA infants. Movements such as hand-on-face, finger splaying, fisting, arching or yawning need to be examined in future research. [Copyright &y& Elsevier]

Childhood exposure to phthalates, a class of chemicals with known reproductive and developmental effects, has been hypothesized to increase the risk of obesity, but this association is not well understood in preschool children. We examined the association between urinary concentrations of phthalate metabolites and concurrently measured body mass index (BMI) and skinfolds among children between the ages of two and five years. We collected anthropometric measures and biomonitoring data on approximately 200 children enrolled in the Maternal-Infant Research on Environmental Chemicals Child Development Plus study. We measured 22 phthalate metabolites in children's urine and used the 19 metabolites detected in at least 40% of samples. Our primary outcome was BMI z-scores calculated using the World Health Organization growth standards. Skinfold z-scores were secondary outcomes. We used multivariable linear regression to evaluate the association between tertiles of phthalate concentrations and each anthropometric measure. We also used weighted quantile sum regression to identify priority exposures of concern. Our analytic sample included 189 singleton-born children with complete anthropometric data. Children with concentrations of the parent compound di-n-butyl phthalate (∑DnBP) in the third tertile had 0.475 (95% CI: 0.068, 0.883) higher BMI z-scores than those in the lower tertile. ∑DnBP was identified as a priority exposure in the weighted quantile sum regression BMI model. In this population of Canadian preschool aged children, we identified DnBP as a potential chemical of concern in regard to childhood obesity. Future research with serial phthalate measurements and anthropometric measurements in young children will help confirm these findings. [ABSTRACT FROM AUTHOR]

• Prenatal PBDE exposure can interfere with children's neurodevelopment. • PBDE blood concentrations in Canada are less than half those in the U.S.A. • We measured PBDEs in maternal blood and assessed IQ for 592 3-year-old children. • Prenatal PBDE exposure was related to lower IQ scores, but only among boys. • It suggests sex-specific neurotoxicity at the low PDBE levels in Canada. Prenatal exposure to polybrominated diphenyl ethers (PBDEs) has been associated with adverse neurodevelopmental outcomes in children, but evidence remains mixed regarding sex differences in this association. To examine the prospective association between prenatal PBDE exposure and cognitive ability in young children, as well as potential sex differences. The study was conducted in a multi-site Canadian pregnancy cohort recruited in 2008–11. PBDEs were measured in maternal plasma samples collected early in pregnancy. Cognitive ability was assessed using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) in children at age 3 years (mean = 3.4). Multiple linear regression was used to analyze the association between maternal PBDE plasma concentrations (lipid-standardized and log10-transformed) and Verbal, Performance, and Full Scale IQ scores on the whole sample and stratified by sex, adjusting for confounders. The sample was composed of 592 children (291 boys and 301 girls). A tenfold increase in maternal blood PBDE concentration (sum of BDE-47, −99, −100, and −153) was associated with lower Full Scale scores in boys (−3.4 points; 95% CI: −7.0, 0.1), after adjusting for confounders. BDE-47 was the congener with the highest concentrations in maternal blood and a tenfold increase in exposure was associated with significantly lower Full Scale IQ scores in boys (−4.4 points; 95% CI: −7.9, −0.9), after adjusting for confounders. Verbal and Performance IQ scores were similarly associated with PBDE exposure. Maternal blood PBDE concentrations were not associated with IQ scores in girls. Prenatal exposure to background levels of PBDEs, especially BDE-47, was associated with lower IQ scores in boys, but not in girls. Our results support that exposure to PBDEs during early development may be sex-dependent and detrimental to a child's neurodevelopmental trajectory. [ABSTRACT FROM AUTHOR]