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Background: Immediately after birth, the oxygen saturation is between 30 and 50%, which then increases to 85–95% within the first 10 min. Over the last 10 years, recommendations regarding the ideal level of the initial fraction of inspired oxygen (FiO2) for resuscitation in preterm infants have changed from 1.0, to room air to low levels of oxygen (< 0.3), up to moderate concentrations (0.3–0.65). This leaves clinicians in a challenging position, and a large multi-center international trial of sufficient sample size that is powered to look at safety outcomes such as mortality and adverse neurodevelopmental outcomes is required to provide the necessary evidence to guide clinical practice with confidence. Methods: An international cluster, cross-over randomized trial of initial FiO2 of 0.3 or 0.6 during neonatal resuscitation in preterm infants at birth to increase survival free of major neurodevelopmental outcomes at 18 and 24 months corrected age will be conducted. Preterm infants born between 230/7 and 286/7 weeks' gestation will be eligible. Each participating hospital will be randomized to either an initial FiO2 concentration of either 0.3 or 0.6 to recruit for up to 12 months' and then crossed over to the other concentration for up to 12 months. The intervention will be initial FiO2 of 0.6, and the comparator will be initial FiO2 of 0.3 during respiratory support in the delivery room. The sample size will be 1200 preterm infants. This will yield 80% power, assuming a type 1 error of 5% to detect a 25% reduction in relative risk of the primary outcome from 35 to 26.5%. The primary outcome will be a composite of all-cause mortality or the presence of a major neurodevelopmental outcome between 18 and 24 months corrected age. Secondary outcomes will include the components of the primary outcome (death, cerebral palsy, major developmental delay involving cognition, speech, visual, or hearing impairment) in addition to neonatal morbidities (severe brain injury, bronchopulmonary dysplasia; and severe retinopathy of prematurity). Discussion: The use of supplementary oxygen may be crucial but also potentially detrimental to preterm infants at birth. The HiLo trial is powered for the primary outcome and will address gaps in the evidence due to its pragmatic and inclusive design, targeting all extremely preterm infants. Should 60% initial oxygen concertation increase survival free of major neurodevelopmental outcomes at 18–24 months corrected age, without severe adverse effects, this readily available intervention could be introduced immediately into clinical practice. Trial registration: The trial was registered on January 31, 2019, at ClinicalTrials.gov with the Identifier: NCT03825835. [ABSTRACT FROM AUTHOR]

An editorial examines the efficacy and safety of administering late preterm corticosteroids based on insights from the Antenatal Late Preterm Steroids (ALPS) trial and subsequent follow-up studies. It discusses the trade-offs between benefits and risks associated with corticosteroid exposure during the late preterm period and presents findings regarding neurodevelopmental outcomes in children exposed to these medications.

Objective  A single course of synthetic antenatal corticosteroids is standard care for women considered to be at risk for preterm birth before 34 weeks of gestation. While the intended target is the fetal lung, the fetal brain contains remarkably high levels of glucocorticoid receptors in structures critical in the regulation of behavior and endocrine function. Negative programming signals may occur which can lead to permanent maladaptive changes and predispose the infant/child to an increased risk in physical, mental, and developmental disorders. Methods  Framed around these areas of concerns for physical, mental, and developmental disorders, this narrative review drew on studies (animal and clinical), evaluating the long-term effects of antenatal corticosteroids to present the case that a more targeted approach to the use of antenatal corticosteroids for the betterment of the fetus urgently needed. Results  Studies raised concerns about the potential negative long-term consequences, especially for the exposed fetus who was born beyond the period of the greatest benefit from antenatal corticosteroids. The long-term consequences are more subtle in nature and usually manifest later in life, often beyond the scope of most clinical trials. Conclusion  Continued research is needed to identify sufficient safety data, both short term and long term. Caution in the use of antenatal corticosteroids should be exercised while additional work is undertaken to optimize dosing strategies and better identify women at risk of preterm birth prior to administration of antenatal corticosteroids. Key Points A single-course ACS is a remarkable therapy with substantial benefits. There is a potential of long-term neurodevelopmental consequences in the ACS-exposed fetus. There is a need to improve dosing strategies and identification of appropriate at risk women. [ABSTRACT FROM AUTHOR]

Background: Capnocytophaga is an anaerobic gram-negative bacillus part of oral flora in humans, cats, and dogs. It usually causes periodontal infection but may exhibit systemic manifestations, particularly in immunocompromised individuals. In rare cases, it may cause chorioamnionitis leading to preterm birth and early-onset neonatal sepsis. Case Presentation: We present a rare case of early-onset sepsis due to Capnocytophaga in an extremely preterm newborn presenting severe respiratory distress, lethargy, and leukopenia at birth. This was treated with Cefotaxime for 14 days. Conclusion: Our case report highlights the importance of considering unusual pathogens such as Capnocytophaga as a cause for intra-amniotic infections leading to preterm birth and early-onset neonatal infection. [ABSTRACT FROM AUTHOR]

Objective This study aims to examine the association between the absence of neonatal comorbidities, as well as the presence of indicators of clinical progress with good neurodevelopmental (ND) outcomes, at 18 months corrected age in a national cohort of preterm infants of < 29 weeks' gestation. Design Study subjects included preterm infants (< 29 weeks' gestation) born in 2010 and 2011. Univariate analyses were conducted and regression estimates were calculated forvariableswhereoddsof a good ND outcome, composite scores ≥ 100 in three domains (cognitive, language, and motor) in the Bayley Scales of Infant and Toddler Development, 3rd ed. (Bayley-III), were estimated. Results In total, 2,069 infants were included in the analyses. For all three domains evaluated on the Bayley-III, cognition, language, motor, respectively, the absence of three major morbidities was associated with a score ≥ 100: bronchopulmonary dysplasia, necrotizing enterocolitis, and severe neurological injury. Less time spent on positive pressure support and on total parenteral nutrition administration were associated with a positive motor outcome and showed a positive trend for both cognition and language scores. Conclusion The absence of neonatal comorbidities was associated with good ND outcome. Less time spent on positive pressure support and parenteral nutrition may also contribute to a good ND outcome. [ABSTRACT FROM AUTHOR]

Objective This study aims to explore the association between primary caregiver education and cognitive and language composite scores of the Bayley Scales of Infant and Toddler Development, 3rd ed. (Bayley-III) in preterm infants at 18 to 21 months corrected age. Design An observational study was performed on preterm infants born before 29 weeks' gestation between 2010 and 2011. Primary caregivers were categorized by their highest education level and cognitive and language composite scores of the Bayley-III were compared among infants between these groups with adjustment for perinatal and neonatal factors. Results In total, 1,525 infants/caregivers were included in the multivariate analysis. Compared with those with less than a high school education, infants with primary caregivers who received partial college/specialized training displayed higher cognitive (adjusted difference [AD]: 4.6, 95% confidence interval [CI]: 1.8-7.4) and language scores (AD: 4.0, 95% CI: 0.8-7.1); infants with primary caregivers with university graduate education or above also demonstrated higher cognitive (AD: 6.4, 95% CI: 2.6-10.1) and language scores (AD: 9.9, 95% CI: 5.7-14.1). Conclusion Higher levels of education of the primary caregiver were associated with increased cognitive and language composite scores at 18 to 21 months corrected age in preterm infants. [ABSTRACT FROM AUTHOR]

Background: This secondary analysis for the Twin Birth Study, an international, multicenter trial, aimed to compare the cesarean section rates and safety between methods of induction of labor in twin pregnancies.Methods: Women with twin pregnancies where the first twin was in a cephalic presentation and who presented for labor induction, were non-randomly assigned to receive prostaglandin or amniotomy and/or oxytocin. Main outcome measures were the rates of unplanned cesarean section and neonatal and maternal mortality or serious morbidity.Results: 153 (41.5%) were induced by prostaglandin (prostaglandin group) and 215 (58.5%) were induced by amniotomy and/or oxytocin alone (no prostaglandin group). Induction using prostaglandin was more common in countries with a low perinatal mortality rate <10/1000 (45.7 versus 32.5%, p = 0.02). Cesarean section rates were similar in the two groups: 62/153 (40.5%) in the prostaglandin group and 87/215 (40.5%) in the no prostaglandin group (odds ratio 1, 95% CI 0.65-1.5). Nulliparity, late maternal age, non-cephalic presentation of twin B and high country's perinatal mortality rate were found to be independently associated with the induction to end with an unplanned cesarean section. There were no significant differences between groups with respect to maternal or neonatal adverse outcomes.Conclusions: The need for cervical ripening by prostaglandin had no effect on the incidence of cesarean delivery or an abnormal outcome. There is a significant risk of unplanned cesarean section independent of chosen induction method.Trial Registration: This trial was registered at the International Standard Randomized Controlled Trial Register (identifier ISRCTN74420086 ; December 9, 2003) and retrospectively registered at the www.clinicaltrials.gov (identifier NCT 00187369 ; September 12, 2005). [ABSTRACT FROM AUTHOR]

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: The Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study (MACS) showed no benefit in the reduction of major neonatal mortality/morbidity or neurodevelopment at 2 and 5 years of age. Using the data from the randomized controlled trial and its follow-up, the aim of this study was to evaluate the association between gestational ages at birth in children exposed to single versus multiple courses of antenatal corticosteroid (ACS) therapy in utero and outcomes at 5 years of age. Method: A total of 1719 children, with the breakdown into groupings of <30, 30-36, and ≥ 37 weeks gestation at birth, contributed to the primary outcome: death or survival with a disability in one of the following domains: neuromotor, neurosensory, and neurobehavioral/emotional disability and were included in this analysis. Results: Gestational age at birth was strongly associated with the primary outcome, p < 0.001. Overall, the interaction between ACS groups and gestational age at birth was not significant, p = 0.064. Specifically, in the 2 preterm categories, there was no difference in the primary outcome between single vs. multiple ACS therapy. However, for infants born ≥37 weeks gestation, there was a statistically significant increase in the risk of the primary outcome in multiple ACS therapy, 48/213 (22.5%) compared to 38/249 (15.3%) in the single ACS therapy; OR = 1.69 [95% CI: 1.04, 2.77]; p = 0.037. Conclusion: Preterm birth (<37 weeks gestation) remained the primary factor contributing to an adverse outcome regardless of the number of courses of ACS therapy. Children born ≥ 37 weeks and exposed to multiple ACS therapy may have an increased risk of neurodevelopmental/neurosensory impairment by 5 years of age. To optimize outcomes for infants/children, efforts in reducing the incidence of preterm birth should remain the primary focus in perinatal research. [ABSTRACT FROM AUTHOR]

Preterm birth remains a major health issue worldwide. Since the 1990s, women at risk for preterm birth received a single course of exogenous antenatal corticosteroids (ACSs) to facilitate fetal lung maturity. More recently, repeated or multiple courses of ACS have been supported to provide continued fetal maturity support for women with continued risk of preterm birth. However, exogenous ACS reduces birth weight which, in turn, is associated with adverse adult outcomes such as coronary heart disease, stroke, hypertension, and type 2 diabetes. The long-term effects of ACS exposure on HPA axis activity and neurological function are well documented in animal studies, and it appears that ACS, regardless of dose exposure, is capable of affecting fetal HPA axis development causing permanent changes in the HPA axis that persists through life and is manifested by chronic illness and behavioral changes. The challenge in human studies is to demonstrate whether an intervention such as ACS administration in pregnancy contributes to developmental programming and how this is manifested in later life. [ABSTRACT FROM AUTHOR]

Background: The use of mother's own breast milk during initial hospitalization has a positive impact not only in reducing potential serious neonatal morbidities but also contribute to improvements in neurodevelopmental outcomes. Mothers of very preterm infants struggle to maintain a supply of breast milk during their infants' prolonged hospitalization. Galactogogues are medications that induce lactation by exerting its effects through oxytocin or prolactin enhancement. Domperidone is a potent dopamine D2 receptor antagonist which stimulates the release of prolactin. Small trials have established its ability in enhancing breast milk production. EMPOWER was designed to determine the safety and efficacy of domperidone in mothers experiencing an inadequate milk supply. Methods/design: EMPOWER is a multicenter, double masked, randomized controlled phase-II trial to evaluate the safety and effectiveness of domperidone in those mothers identified as having difficulty in breast milk production. Eligible mothers will be randomized to one of two allocated groups: Group A: domperidone 10 mg orally three times daily for 28 days; and Group B: identical placebo 10 mg orally three times daily for 14 days followed by domperidone 10 mg orally three times daily for 14 days. The primary outcome will be determined at the completion of the first 2-week period; the second 2-week period will facilitate answering the secondary questions regarding timing and duration of treatment. To detect an estimated 30% change between the two groups (from 40% to 28%, corresponding to an odds ratio of 0.6), a total sample size of 488 mothers would be required at 80%power and alpha = 0.05. To account for a 15% dropout, this number is increased to 560 (280 per group). The duration of the trial is expected to be 36-40 months. Discussion: The use of a galactogogue often becomes the measure of choice for mothers in the presence of insufficient breast milk production, particularly when the other techniques are unsuccessful. EMPOWER is designed to provide valuable information in guiding the practices for this high-risk group of infants and mothers. The results of this trial will also inform both mothers and clinicians about the choices available to increase and maintain sufficient breast milk. [ABSTRACT FROM AUTHOR]

Context: Despite more than 2 decades of outcomes research after very preterm birth, clinicians remain uncertain about the extent to which neonatal morbidities predict poor long-term outcomes of extremely low-birth-weight (ELBW) infants. Objective: To determine the individual and combined prognostic effects of bronchopulmonary dysplasia (BPD), ultrasonographic signs of brain injury, and severe retinopathy of prematurity (ROP) on 18-month outcomes of ELBW infants. Design: Inception cohort assembled for the Trial of Indomethacin Prophylaxis in Preterms (TIPP). Setting and Participants: A total of 910 infants with birth weights of 500 to 999 g who were admitted to 1 of 32 neonatal intensive care units in Canada, the United States, Australia, New Zealand, and Hong Kong between 1996 and 1998 and who survived to a postmenstrual age of 36 weeks. Main Outcome Measures: Combined end point of death or survival to 18 months with 1 or more of cerebral palsy, cognitive delay, severe hearing loss, and bilateral blindness. Results: Each of the neonatal morbidities was similarly and independently correlated with a poor 18-month outcome. Odds ratios were 2.4 (95% confidence interval [CI], 1.8-3.2) for BPD, 3.7 (95% CI, 2.6-5.3) for brain injury, and 3.1 (95% CI, 1.9-5.0) for severe ROP. In children who were free of BPD, brain injury, and severe ROP the rate of poor long-term outcomes was 18% (95% CI, 14%-22%). Corresponding rates with any 1, any 2, and all 3 neonatal morbidities were 42% (95% CI, 37%-47%), 62% (95% CI, 53%-70%), and 88% (64%-99%), respectively. Conclusion: In ELBW infants who survive to a postmenstrual age of 36 weeks, a simple count of 3 common neonatal morbidities strongly predicts the risk of later death or neurosensory impairment. [ABSTRACT FROM AUTHOR]

Objective: In the MiTy (Metformin in Women With Type 2 Diabetes in Pregnancy) randomized trial of metformin versus placebo added to insulin, we found numerous benefits with metformin but identified an increased proportion of infants who were small for gestational age (SGA). We aimed to determine the predictors of SGA in order to individualize care.Research Design and Methods: Using logistic regression, we assessed baseline maternal characteristics as predictors of SGA. We compared maternal/neonatal outcomes in SGA metformin and placebo groups using the t, χ2, or Fisher exact test, as appropriate.Results: Among the 502 mothers, 460 infants were eligible for this study. There were 30 infants with SGA in the metformin group (12.9%) and 15 in the placebo group (6.6%) (P = 0.026). Among SGA infants, those in the metformin group were delivered significantly later than those in the placebo group (37.2 vs. 35.3 weeks; P = 0.038). In adjusted analyses, presence of a comorbidity (chronic hypertension and/or nephropathy) (odds ratio [OR] 3.05; 95% CI 1.58-5.81) and metformin use (OR 2.26; 95% CI 1.19-4.74) were predictive of SGA. The absolute risk of SGA was much higher in women receiving metformin with comorbidity compared with women receiving metformin without comorbidity (25.0% vs. 9.8%).Conclusions: In this study, we observed a high percentage of SGA births among women with type 2 diabetes and chronic hypertension and/or nephropathy who were treated with metformin. Therefore, with the aim of reducing SGA, it is reasonable to be cautious in our use of metformin in those with type 2 diabetes and chronic hypertension or nephropathy in pregnancy. [ABSTRACT FROM AUTHOR]

Multiple courses versus a single course of antenatal corticosteroids (ACS) have been associated with mild respiratory benefits but also adverse outcomes like smaller head circumference and birth weight. Long-term effects warrant study. We systematically reviewed long-term outcomes (≥1 year) in both preterm and term birth after exposure to preterm multiple courses (including a rescue dose or course) versus a single course. We searched seven databases from January 2000 to October 2021. We included follow-up studies of randomized controlled trials (RCTs) and cohort studies with births occurring in/after the year 2000, given advances in perinatal care. Two reviewers assessed titles/abstracts, articles, quality, and outcomes including psychological disorders, neurodevelopment, and anthropometry. Six follow-up studies of three RCTs and two cohort studies (over 2,860 children total) met inclusion criteria. Among children born preterm, randomization to multiple courses versus a single course of ACS was not associated with adjusted beneficial or adverse neurodevelopmental/psychological or other outcomes, but data are scant after a rescue dose (120 and 139 children, respectively, low certainty) and nonexistent after a rescue course. For children born at term (i.e., 27% of the multiple courses of ACS 5-year follow-up study of 1,728 preterm/term born children), preterm randomization to multiple courses (at least one additional course) versus a single course was significantly associated with elevated odds of neurosensory impairment (adjusted odds ratio = 3.70, 95% confidence interval: 1.57–8.75; 212 and 247 children, respectively, moderate certainty). In this systematic review of long-term outcomes after multiple courses versus a single course of ACS, there were no significant benefits or risks regarding neurodevelopment in children born preterm but little data after one rescue dose and none after a rescue course. However, multiple courses (i.e., at least one additional course) should be considered cautiously: after term birth, there are no long-term benefits but neurosensory harms. Key Points We systematically reviewed the long-term impact of multiple versus a single course of ACS. Long-term follow-up data were scant after a rescue dose and absent after one rescue course of ACS. In children born preterm, multiple courses of ACS were not associated with long-term benefits/harms. In children born at term, multiple courses of ACS were associated with neurosensory impairment. Preterm administration of multiple courses of ACS should be considered cautiously. [ABSTRACT FROM AUTHOR]

Background: With an increasing demand for mother's own milk to be viewed as a primary source of nutritional support in the care of very small and preterm infants, mothers of preterm infants may be at risk of expressing suboptimal amounts of milk. The use of a galactogogue is often considered when these mothers are still having challenges in breast milk production. Methods: For this analysis, the study participants were the 90 mothers who participated in the EMPOWER trial and, at the time of randomization, were stratified by days post-delivery, 8–14 days and 15–21 days. The primary outcome measure was the proportion of mothers in each of the days post-delivery groups who achieved a 50% increase in breast milk volume on day 14 of the study treatment period. Results: There was no significant difference in the proportion of mothers in the 8–14 days group (75.0%) who achieved a 50% increase in breast milk volume on day 14 of the study treatment period. compared to those in the 15–21 days group (60.9%), OR 1.93 (95% CI 0.78, 4.76; p = 0.15). Because comorbidities and exposure to antenatal corticosteroids between the groups of mothers were viewed as potential confounders, a logistic regression was performed after controlling for these two variables with the adjusted OR being 1.84 (0.73, 4.64; p = 0.19). Conclusions: This secondary analysis was able to demonstrate that mothers of very preterm infants, < 30 weeks gestation at birth, were able to respond to the study treatment in a similar fashion regardless of timing of entry and exposure to domperidone. In the presence of a suboptimal breast milk production by the end of the first week postpartum, below 250 ml/kg/d based on infant birth weight, a 14 day treatment of domperidone could be considered to augment breast milk production. Trial registration: EMPOWER has been registered at http://www.clinicaltrials.gov (identifier NCT 01512225) on January 10, 2012. [ABSTRACT FROM AUTHOR]

Background: The pan-Canadian Maternal-Infant Research on Environmental Chemicals (MIREC) study was established to determine whether maternal environmental chemical exposures were associated with adverse pregnancy outcomes in 2001 pregnant women. Objectives: The MIREC-Child Development (CD PLUS) study followed this cohort with the goal of assessing the potential effects of prenatal exposures on anthropometry and neurodevelopment in early childhood. Population: MIREC families with children between the ages of 15 months and 5 years who had agreed to be contacted for future research (n = 1459) were invited to participate in MIREC-CD PLUS which combines data collected from an online Maternal Self-Administered Questionnaire with biomonitoring and neurodevelopment data collected from two in-person visits. Preliminary Results: Between April 2013 and March 2015, 803 children participated in the Biomonitoring visit where we collected anthropometric measures, blood, and urine from the children. The Behavioural Assessment System for Children-2, Behaviour Rating Inventory of Executive Function, MacArthur-Bates Communicative Development Inventories and the Communication subscale of the Adaptive Behaviour Scale from the Bayley Scales of Infant and Toddler Development-III are available on close to 900 children. There were 610 singleton children who completed in-person visits for neurodevelopment assessments including the Social Responsiveness Scale, Wechsler Preschool Primary Scale of Intelligence-III and NEuroPSYchological assessments (NEPSY). Currently, we are following the cohort into early adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). Conclusions: Data collection for the MIREC-CD PLUS study is complete and analysis of the data continues. We are now extending the follow-up of the cohort into adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). MIREC-CD PLUS is limited by loss to follow-up and the fact that mothers are predominately of higher socioeconomic status and 'White' ethnicity, which limits our generalizability. However, the depth of biomonitoring and clinical measures in MIREC provides a platform to examine associations of prenatal, infancy and childhood exposures with child growth and development. [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]

The article reflects on the need to restrict use of antenatal corticosteroids (ACS) to avoid causing harm. It mentions administration of ACS to pregnant women with a pre-viable gestation and women at the late preterm gestation. It also highlights efforts to identifying at-risk pregnancies as it relates to their risk for preterm delivery.

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: Clinicians favour low oxygen concentrations when resuscitating preterm infants immediately after birth despite inconclusive evidence to support this practice. Prospective meta‐analysis (PMA) is a novel approach where studies are identified as eligible for inclusion in the meta‐analysis before their results are known. Aims: To explore whether high (60%) or low (30%) oxygen is associated with greater efficacy and safety for the initial resuscitation (immediately after birth) of preterm infants born at <29 weeks' gestation. Methods: We will conduct a prospective meta‐analysis (PMA) with individual participant data (IPD). We will perform a systematic search to identify ongoing RCTs including infants <29 weeks' gestation randomised to high (60%) or low (30%) oxygen for initial resuscitation after birth. IPD will be sought for all infants randomised for the purpose of meta‐analysis. We will employ a one‐stage random‐effects approach to IPD meta‐analysis. Potential heterogeneity and the differential effect of high or low oxygen will be explored through subgroup and interaction analyses. The primary outcome of this study is all‐cause mortality prior to hospital discharge. There will be a follow‐up analysis of neurodevelopmental outcomes once available. Results/Conclusion: The results of neonatal outcomes at hospital discharge are expected by 2025, and neurodevelopmental outcomes by 2027. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed at determining the proportion of women who receive antenatal corticosteroids (ACS) within the optimal time window before birth based on the indication for ACS, and to explore in more detail indications that are associated with suboptimal timing. Methods: A retrospective cohort study of all women who received ACS in a single tertiary center between 2014 and 2017. The primary outcome was an ACS-to-birth interval ≤ 7 days. Secondary outcomes were ACS-to-birth interval of ≤ 14 days, and the proportion women who received ACS but ultimately gave birth at term (≥ 370/7 weeks). The study outcomes were stratified by the clinical indication for ACS. Results: A total of 1261 women met the study criteria, of whom 401 (31.8%) and 569 (45.1%) received ACS within ≤ 7 days and ≤ 14 days before birth, respectively, and 203 (16.1%) ultimately gave birth at term. The proportion of women who received ACS within 7 days before birth was highest for women with preeclampsia (50.4%), and was lowest for women with an incidental finding of a short cervix (8.4%). In the subgroup of women with an incidental finding of a short cervix, the likelihood of optimal timing was not related to the magnitude of cervical shortening, history of preterm birth, multifetal gestation, presence of cervical funneling, or the presence of cervical cerclage. Conclusion: Over two-thirds of infants who are exposed to ACS do not get the maximal benefit from this intervention. The current study identified clinical indications for ACS that are associated with suboptimal timing of ACS where more research is needed to develop quantitative, indication-specific prediction models to guide the timing of ACS. [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]

Objective: To estimate the likelihood and identify predictors of spontaneous fetal version during the third trimester in twins using data from a multicenter randomized controlled trial on mode of delivery in twin pregnancies.Methods: Women with twin pregnancies after 32 weeks of gestation in which twin A was vertex were randomized to planned cesarean or planned vaginal delivery. In the current study we analyzed the likelihood of a spontaneous version of any of the twins between ultrasound assessment at the time of randomization and delivery.Results: A total of 2,603 women were analyzed. Twin A tended to persist in the vertex presentation after 32 weeks of gestation with a spontaneous version rate to nonvertex presentation of 3.0% (95% confidence interval [CI] 2.3-3.7%). Twin B was less stable and underwent spontaneous version in 24.8% (95% CI 23.1-26.5%) of cases; the rate remained higher than 20% even after 34 weeks of gestation. On multivariable analysis, twin A was more likely to undergo version when twin B was smaller (adjusted odds ratio [OR] 2.0, 95% CI 1.04-3.3), when twin B was breech (adjusted OR 3.7, 95% CI 2.2-6.4) or transverse (adjusted OR 2.9, 95% CI 1.6-5.5), and when the interval to delivery exceeded 4 weeks (adjusted OR 2.5, 95% CI 1.3-5.0). Twin B was more likely to undergo version when it was in the breech presentation (adjusted OR 1.7, 95% CI 1.4-2.1) or transverse lie (adjusted OR 3.1, 95% CI 2.5-3.9) compared with vertex presentation, when it was smaller (adjusted OR 1.7, 95% CI 1.1-2.0), when the interval to delivery exceeded 4 weeks (adjusted OR 1.7, 95% CI 1.3-2.4), and in multiparous women (adjusted OR 1.3, 95% CI 1.04-1.5).Conclusion: The likelihood of spontaneous version of twin A after 32 weeks of gestation is low when twin A is in the vertex presentation but is much higher for twin B, even late during the third trimester.Clinical Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00187369.Level Of Evidence: II. [ABSTRACT FROM AUTHOR]

Objective To evaluate the association of intrapartum magnesium sulfate for fetal neuroprotection (MgSO4-FN) with the delivery room resuscitation and neonatal outcomes of preterm infants in an era of minimisation of invasive mechanical ventilation. Design Retrospective cohort study. Setting Neonatal intensive care units in the Canadian Neonatal Network. Patients and intervention Preterm infants (230 to 316 weeks gestational age) born in 2011 or 2012. Resuscitation requirements and neonatal outcomes were compared between infants exposed and unexposed to intrapartum MgSO4-FN. Main outcome measures The primary outcome was a composite outcome of 'intensive resuscitation', defined as the need for intubation and ventilation or chest compressions or epinephrine administration in the delivery room. Secondary outcomes included mortality and major neonatal morbidities. Results Of 6015 eligible infants, 1387 (23.1%) were exposed to intrapartum MgSO4-FN. Significantly fewer MgSO4-FN infants (41.0% vs 44.6%, p=0.02) required intensive resuscitation. However, after adjustment for confounders, this difference was no longer significant (adjusted OR (AOR) 0.88; 95% CI 0.66 to 1.17). Infants exposed to MgSO4-FN had decreased odds of death (AOR 0.61; 95% CI 0.40 to 0.94), but there was no difference in neonatal morbidities compared with the unexposed infants. Conclusions Intrapartum MgSO4 for fetal neuroprotection was not associated with an increased need for intensive delivery room resuscitation in this cohort of preterm infants. [ABSTRACT FROM AUTHOR]

Importance: The goal of oxygen therapy is to deliver sufficient oxygen to the tissues while minimizing oxygen toxicity and oxidative stress. It remains uncertain what values of arterial oxygen saturations achieve this balance in preterm infants.Objective: To compare the effects of targeting lower or higher arterial oxygen saturations on the rate of death or disability in extremely preterm infants.Design, Setting, and Participants: Randomized, double-blind trial in 25 hospitals in Canada, the United States, Argentina, Finland, Germany, and Israel in which 1201 infants with gestational ages of 23 weeks 0 days through 27 weeks 6 days were enrolled within 24 hours after birth between December 2006 and August 2010. Follow-up assessments began in October 2008 and ended in August 2012.Interventions: Study participants were monitored until postmenstrual ages of 36 to 40 weeks with pulse oximeters that displayed saturations of either 3% above or below the true values. Caregivers adjusted the concentration of oxygen to achieve saturations between 88% and 92%, which produced 2 treatment groups with true target saturations of 85% to 89% (n = 602) or 91% to 95% (n = 599). Alarms were triggered when displayed saturations decreased to 86% or increased to 94%.Main Outcomes and Measures: The primary outcome was a composite of death, gross motor disability, cognitive or language delay, severe hearing loss, or bilateral blindness at a corrected age of 18 months. Secondary outcomes included retinopathy of prematurity and brain injury.Results: Of the 578 infants with adequate data for the primary outcome who were assigned to the lower target range, 298 (51.6%) died or survived with disability compared with 283 of the 569 infants (49.7%) assigned to the higher target range (odds ratio adjusted for center, 1.08; 95% CI, 0.85 to 1.37; P = .52). The rates of death were 16.6% for those in the 85% to 89% group and 15.3% for those in the 91% to 95% group (adjusted odds ratio, 1.11; 95% CI, 0.80 to 1.54; P = .54). Targeting lower saturations reduced the postmenstrual age at last use of oxygen therapy (adjusted mean difference, -0.8 weeks; 95% CI, -1.5 to -0.1; P = .03) but did not alter any other outcomes.Conclusion and Relevance: In extremely preterm infants, targeting oxygen saturations of 85% to 89% compared with 91% to 95% had no significant effect on the rate of death or disability at 18 months. These results may help determine the optimal target oxygen saturation.Trial Registrations: ISRCTN Identifier: 62491227; ClinicalTrials.gov Identifier: NCT00637169. [ABSTRACT FROM AUTHOR]

The article describes a study whose aim was to compare the effects of targeting lower or higher arterial oxygen saturations on the rate of death or disability in extremely preterm infants and states that as part of the study 1201 infants were included from randomized, double-blind trial in 25 hospitals in Canada, the U.S., Argentina, Finland, Germany and Israel. As mentioned, study participants were monitored until postmenstrual ages of 36 to 40 weeks with pulse oximeters that displayed saturations of either 3% above or below the true values. Also the result of the study revealed that in extremely preterm infants, targeting oxygen saturations of 85%-89% compared with 91%-95% had no significant effect on the rate of death or disability at 18 months.

Several Canadian professional organizations recently recommended that the growth of preterm infants be monitored using the World Health Organization Growth Standards (WHO-GS) after hospital discharge. The WHO-GS are a prescriptive set of growth charts that describe how term infants should grow under ideal environmental conditions. Whether preterm infants following this pattern of growth have better outcomes than infants that do not has yet to be evaluated. Our aim was to determine whether the pattern of growth of very low birth weight (VLBW) infants during the first 2 years, assessed using the WHO-GS or the traditional Centers for Disease Control and Prevention reference growth charts (CDC-RGC), is associated with neurodevelopment. Pattern of weight, length, and head circumference gain of appropriate-for-gestation VLBW preterm infants ( n = 289) from birth to 18-24 months corrected age was classified, using the WHO-GS and CDC-RGC, as sustained (change in Z-score ≤1 SD), decelerated (decline >1 SD), or accelerated (incline >1 SD). Development was assessed using the Bayley Scales of Infant and Toddler Development (BSID)-III at 18-24 months corrected age. Using the WHO-GS, children with a decelerated pattern of weight gain had lower cognitive (10 points), language (6 points), and motor (4 points) scores than infants with sustained weight gain ( p < 0.05), even after adjustment for morbidities. No association was found using the CDC-RGC. In conclusion, a decelerated pattern of weight gain, determined with the WHO-GS, but not the CDC-GRC, is associated with poorer neurodevelopment scores on the BSID-III than a pattern of sustained growth. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVE. Extremely low birth weight infants frequently receive red cell transfusions. We sought to determine whether a restrictive versus liberal hemoglobin transfusion threshold results in differences in death or adverse neurodevelopmental outcomes of extremely low birth weight infants. PATIENTS AND METHODS. Extremely low birth weight infants previously enrolled in the Preterm Infants in Need of Transfusion Trial, a randomized, controlled trial of low versus high hemoglobin transfusion thresholds, were followed up at 18 to 21 months' corrected age. Erythrocyte transfusion was determined by an algorithm of low (restrictive) or high (liberal) hemoglobin transfusion thresholds, differing by 10 to 20 g/L and maintained until first hospital discharge. The primary composite outcome was death or the presence of cerebral palsy, cognitive delay, or severe visual or hearing impairment. RESULTS. Of 451 enrolled infants, the primary outcome was available in 430. There was no statistically significant difference in the primary outcome, found in 94 (45%) of 208 in the restrictive group and 82 (38%) of 213 in the liberal group. There were no statistically significant differences in preplanned secondary outcomes. However, the difference in cognitive delay (Mental Development Index score < 70) approached statistical significance. A posthoc analysis with cognitive delay redefined (Mental Development Index score < 85) showed a significant difference favoring the liberal threshold group. CONCLUSIONS. Maintaining the hemoglobin of extremely low birth weight infants at these restrictive rather than liberal transfusion thresholds did not result in a statistically significant difference in combined death or severe adverse neurodevelopmental outcome. [ABSTRACT FROM AUTHOR]

Background: The General Movements Assessment is a non-invasive and cost-effective tool with demonstrated reliability for identifying infants at risk for cerebral palsy. Early detection of cerebral palsy allows for the implementation of early intervention and is associated with better functional outcomes. No review to date has summarized the utility of the General Movements Assessment to predict cerebral palsy in term and late-preterm infants diagnosed with neonatal encephalopathy. Methods: We conducted a scoping review involving infants born greater than or equal to 34 weeks gestational age to identify all available evidence and delineate research gaps. We extracted data on sensitivity, specificity, and positive and negative predictive values and described the strengths and limitations of the results. We searched five databases (MEDLINE, Embase, PsychINFO, Scopus, and CINAHL) and the General Movements Trust website. Two reviewers conducted all screening and data extraction independently. The articles were categorized according to key findings, and a critical appraisal was performed. Results: Only three studies, a cohort and two case series, met all of the inclusion criteria. The total number of participants was 118. None of the final eligible studies included late-preterm neonates. All three studies reported on sensitivity, specificity, and positive predictive and negative predictive values. An abnormal General Movement Assessment at 3–5 months has a high specificity (84.6–98%) for cerebral palsy with a similarly high negative predictive value (84.6–98%) when it was normal. Absent fidgety movements, in particular, are highly specific (96%) for moderate to severe cerebral palsy and carry a high negative predictive value (98%) when normal. In the time period between term and 4–5 months post-term, any cramped synchronized movements had results of 100% sensitivity and variable results for specificity, positive predictive value, and negative predictive value. Conclusions: A normal General Movements Assessment at 3 months in a term high-risk infant is likely associated with a low risk for moderate/severe cerebral palsy. The finding of cramped synchronized General Movements is a strong predictor for the diagnosis of cerebral palsy by 2 years of age in the term population with neonatal encephalopathy. The deficit of high-quality research limits the applicability, and so the General Movements Assessment should not be used in isolation when assessing this population. Systematic review registration: Title registration with Joanna Briggs Institute. URL: http://joannabriggswebdev.org/research/registered_titles.aspx. [ABSTRACT FROM AUTHOR]

This article discusses a study which investigated whether infants with severe retinopathy who were diagnosed and treated under modern protocols retain on increased risk of nonvisual disabilities compared with those without severe retinopathy. Researchers revealed that motor impairment, cognitive impairment and severe hearing loss were more common in children with severe retinopathy. The association between severe retinopathy of prematurity and nonvisual disabilities at age 5 years are explored.

Aim: To compare composite outcomes of neonatal mortality or morbidity using a split-week gestational age (GA) model to completed weeks GA maturity at 23-26 weeks gestation.Methods: This was a retrospective cohort study of infants born at 23-26 weeks GA. Outcomes using a split-week GA model defined as early (X, 0-3) and late (X, 4-6) with X being 23-26 weeks GA were compared to outcomes using completed weeks GA, with a similar comparison between the late split of the preceding week (X, 4-6) and early split of the subsequent week (X + 1, 0-3).Results: A total of 1345 infants were included in the study. Statistically significant differences were noted in outcomes between the early and late split of the gestational week at 24 (early vs late, 85.6% vs 73.0%), 25 (69.6% vs 56.6%) and 26 weeks (55.9% vs 37.4%), but not at 23 weeks GA (95.2% vs 94.5%). No statistically significant differences were noted between the late vs early part of the subsequent week (23, 4-6) vs (24, 0-3), and (24, 4-6) vs (25, 0-3) GA.Conclusion: Neonatal outcome estimates using a split week model differs from that based on the use of completed weeks of gestational maturity. [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: Prediction of long-term neurodevelopmental outcomes remains an elusive goal for neonatology. Clinical and socioeconomic markers have not proven to be adequately reliable. The limitation in prognostication includes those term and late-preterm infants born with neonatal encephalopathy. The General Movements Assessment tool by Prechtl has demonstrated reliability for identifying infants at risk for neuromotor impairment. This tool is non-invasive and cost-effective. The purpose of this study is to identify the published literature on how this tool applies to the prediction of cerebral palsy in term and late-preterm infants diagnosed with neonatal encephalopathy and so detect the research gaps. Methods: We will conduct a systematic scoping review for data on sensitivity, specificity, positive, and negative predictive value and describe the strengths and limitations of the results. This review will consider studies that included infants more than or equal to 34 + 0 weeks gestational age, diagnosed with neonatal encephalopathy, with a General Movements Assessment done between birth to six months of life and an assessment for cerebral palsy by at least 2 years of age. Experimental and quasi-experimental study designs including randomized controlled trials, non-randomized controlled trials, before and after studies, interrupted time-series studies and systematic reviews will be considered. Case reports, case series, case control, and cross-sectional studies will be included. Text, opinion papers, and animal studies will not be considered for inclusion in this scoping review as this is a highly specific and medical topic. Studies in the English language only will be considered. Studies published from at least 1970 will be included as this is around the time when the General Movements Assessment was first introduced in neonatology as a potential predictor of neuromotor outcomes. We will search five databases (MEDLINE, Embase, PsychINFO, Scopus, and CINAHL). Two reviewers will conduct all screening and data extraction independently. The articles will be categorized according to key findings and a critical appraisal performed. Discussion: The results of this review will guide future research to improve early identification and timely intervention in infants with neonatal encephalopathy at risk of neuromotor impairment. Systematic review registration: Title registration with Joanna Briggs Institute https://joannabriggs.org/ebp/systematic_review_register. [ABSTRACT FROM AUTHOR]

Prenatal and childhood mercury (Hg) exposures have been associated with negative impacts on child neurodevelopment. It is unclear if associations persist at the low Hg exposures typical in Western countries. To examine associations between prenatal/childhood blood Hg concentrations and child IQ in Canadian male and female children while considering the potential modifying role of prenatal fish consumption. We analyzed data from the Maternal-Infant Research on Environmental Chemicals study. Hg was measured in first trimester (n = 527), cord (n = 430), and child (at 3–4 years of age, n = 355) blood and examined sex-stratified associations between blood Hg and children's Full Scale IQ (FSIQ), Verbal IQ (VIQ), Performance IQ (PIQ), and General Language Composite (GLC) scores (assessed with WPPSI-III). Prenatal Hg analyses were further stratified by prenatal fish consumption (low: 0–2, moderate: 3–7, or high: ≥8 times/month). Higher cord blood Hg concentrations were associated with lower PIQ (ß = −3.27; 95%CI: 6.44, −0.09) in male children with the lowest prenatal fish consumption. Progressively stronger positive associations were observed with PIQ in male children for moderate (ß = 1.08; 95%CI: 0.10, 2.26) and high (ß = 3.07; 95%CI: 1.95, 4.19) prenatal fish consumption. Cord blood Hg concentrations were positively associated with female children's FSIQ (ß = 1.29; 95% CI: 0.77, 1.81) and PIQ (ß = 2.01; 95% CI: 1.19, 2.83); however, when stratified only in the highest fish consumption subgroup. Among female children, higher child blood Hg concentrations were associated with an approximately 1-point increase in FSIQ, VIQ, and GLC. Prenatal exposure to low levels of Hg was associated with lower PIQ scores in male children with low prenatal fish intake. Positive associations between cord and child blood Hg concentrations and IQ were primarily observed in female children and may be due to beneficial effects of prenatal fish intake. • Examined associations between prenatal and child blood mercury (Hg) with child IQ. • Cord blood Hg with low fish intake was associated with lower performance IQ in males. • Cord blood Hg with high fish intake was associated with higher IQ in females. • Each doubling of child blood Hg associated with 1-point increase in IQ in females. • Results highlight the beneficial effects of fish intake during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Infants born preterm compared with infants born at term are at an increased risk of dying and of serious morbidities in early life, and those who survive have higher rates of neurological impairments. It remains unclear whether exposure to repeat courses of prenatal corticosteroids can reduce these risks. This individual participant data (IPD) meta-analysis (MA) assessed whether repeat prenatal corticosteroid treatment given to women at ongoing risk of preterm birth in order to benefit their infants is modified by participant or treatment factors.Methods and Findings: Trials were eligible for inclusion if they randomised women considered at risk of preterm birth who had already received an initial, single course of prenatal corticosteroid seven or more days previously and in which corticosteroids were compared with either placebo or no placebo. The primary outcomes for the infants were serious outcome, use of respiratory support, and birth weight z-scores; for the children, they were death or any neurosensory disability; and for the women, maternal sepsis. Studies were identified using the Cochrane Pregnancy and Childbirth search strategy. Date of last search was 20 January 2015. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. IPD were analysed using a one-stage approach. Eleven trials, conducted between 2002 and 2010, were identified as eligible, with five trials being from the United States, two from Canada, and one each from Australia and New Zealand, Finland, India, and the United Kingdom. All 11 trials were included, with 4,857 women and 5,915 infants contributing data. The mean gestational age at trial entry for the trials was between 27.4 weeks and 30.2 weeks. There was no significant difference in the proportion of infants with a serious outcome (relative risk [RR] 0.92, 95% confidence interval [CI] 0.82 to 1.04, 5,893 infants, 11 trials, p = 0.33 for heterogeneity). There was a reduction in the use of respiratory support in infants exposed to repeat prenatal corticosteroids compared with infants not exposed (RR 0.91, 95% CI 0.85 to 0.97, 5,791 infants, 10 trials, p = 0.64 for heterogeneity). The number needed to treat (NNT) to benefit was 21 (95% CI 14 to 41) women/fetus to prevent one infant from needing respiratory support. Birth weight z-scores were lower in the repeat corticosteroid group (mean difference -0.12, 95%CI -0.18 to -0.06, 5,902 infants, 11 trials, p = 0.80 for heterogeneity). No statistically significant differences were seen for any of the primary outcomes for the child (death or any neurosensory disability) or for the woman (maternal sepsis). The treatment effect varied little by reason the woman was considered to be at risk of preterm birth, the number of fetuses in utero, the gestational age when first trial treatment course was given, or the time prior to birth that the last dose was given. Infants exposed to between 2-5 courses of repeat corticosteroids showed a reduction in both serious outcome and the use of respiratory support compared with infants exposed to only a single repeat course. However, increasing numbers of repeat courses of corticosteroids were associated with larger reductions in birth z-scores for weight, length, and head circumference. Not all trials could provide data for all of the prespecified subgroups, so this limited the power to detect differences because event rates are low for some important maternal, infant, and childhood outcomes.Conclusions: In this study, we found that repeat prenatal corticosteroids given to women at ongoing risk of preterm birth after an initial course reduced the likelihood of their infant needing respiratory support after birth and led to neonatal benefits. Body size measures at birth were lower in infants exposed to repeat prenatal corticosteroids. Our findings suggest that to provide clinical benefit with the least effect on growth, the number of repeat treatment courses should be limited to a maximum of three and the total dose to between 24 mg and 48 mg. [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]

Importance: There are potential benefits and harms of hyperoxemia and hypoxemia for extremely preterm infants receiving more vs less supplemental oxygen.Objective: To compare the effects of different target ranges for oxygen saturation as measured by pulse oximetry (Spo2) on death or major morbidity.Design, Setting, and Participants: Prospectively planned meta-analysis of individual participant data from 5 randomized clinical trials (conducted from 2005-2014) enrolling infants born before 28 weeks' gestation.Exposures: Spo2 target range that was lower (85%-89%) vs higher (91%-95%).Main Outcomes and Measures: The primary outcome was a composite of death or major disability (bilateral blindness, deafness, cerebral palsy diagnosed as ≥2 level on the Gross Motor Function Classification System, or Bayley-III cognitive or language score <85) at a corrected age of 18 to 24 months. There were 16 secondary outcomes including the components of the primary outcome and other major morbidities.Results: A total of 4965 infants were randomized (2480 to the lower Spo2 target range and 2485 to the higher Spo2 range) and had a median gestational age of 26 weeks (interquartile range, 25-27 weeks) and a mean birth weight of 832 g (SD, 190 g). The primary outcome occurred in 1191 of 2228 infants (53.5%) in the lower Spo2 target group and 1150 of 2229 infants (51.6%) in the higher Spo2 target group (risk difference, 1.7% [95% CI, -1.3% to 4.6%]; relative risk [RR], 1.04 [95% CI, 0.98 to 1.09], P = .21). Of the 16 secondary outcomes, 11 were null, 2 significantly favored the lower Spo2 target group, and 3 significantly favored the higher Spo2 target group. Death occurred in 484 of 2433 infants (19.9%) in the lower Spo2 target group and 418 of 2440 infants (17.1%) in the higher Spo2 target group (risk difference, 2.8% [95% CI, 0.6% to 5.0%]; RR, 1.17 [95% CI, 1.04 to 1.31], P = .01). Treatment for retinopathy of prematurity was administered to 220 of 2020 infants (10.9%) in the lower Spo2 target group and 308 of 2065 infants (14.9%) in the higher Spo2 target group (risk difference, -4.0% [95% CI, -6.1% to -2.0%]; RR, 0.74 [95% CI, 0.63 to 0.86], P < .001). Severe necrotizing enterocolitis occurred in 227 of 2464 infants (9.2%) in the lower Spo2 target group and 170 of 2465 infants (6.9%) in the higher Spo2 target group (risk difference, 2.3% [95% CI, 0.8% to 3.8%]; RR, 1.33 [95% CI, 1.10 to 1.61], P = .003).Conclusions and Relevance: In this prospectively planned meta-analysis of individual participant data from extremely preterm infants, there was no significant difference between a lower Spo2 target range compared with a higher Spo2 target range on the primary composite outcome of death or major disability at a corrected age of 18 to 24 months. The lower Spo2 target range was associated with a higher risk of death and necrotizing enterocolitis, but a lower risk of retinopathy of prematurity treatment. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: Caffeine is effective in the treatment of apnea of prematurity. Although caffeine therapy has a benefit on gross motor skills in school-aged children, effects on neurobehavioral outcomes are not fully understood. We aimed to investigate effects of neonatal caffeine therapy in very low birth weight (500 -1250 g) infants on neurobehavioral outcomes in 11-year-old participants of the Caffeine for Apnea of Prematurity trial. METHODS: Thirteen academic hospitals in Canada, Australia, Great Britain, and Sweden participated in this part of the 11-year follow-up of the double-blind, randomized, placebo-controlled trial. Measures of general intelligence, attention, executive function, visuomotor integration and perception, and behavior were obtained in up to 870 children. The effects of caffeine therapy were assessed by using regression models. RESULTS: Neurobehavioral outcomes were generally similar for both the caffeine and placebo group. The caffeine group performed better than the placebo group in fine motor coordination (mean difference [MD] = 2.9; 95% confidence interval [CI]: 0.7 to 5.1; P = .01), visuomotor integration (MD = 1.8; 95% CI: 0.0 to 3.7; P < .05), visual perception (MD = 2.0; 95% CI: 0.3 to 3.8; P = .02), and visuospatial organization (MD = 1.2; 95% CI: 0.4 to 2.0; P = .003). CONCLUSIONS: Neonatal caffeine therapy for apnea of prematurity improved visuomotor, visuoperceptual, and visuospatial abilities at age 11 years. General intelligence, attention, and behavior were not adversely affected by caffeine, which highlights the long-term safety of caffeine therapy for apnea of prematurity in very low birth weight neonates. [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]

Background. Neonatal invasive candidiasis (IC) presenting in the first week of life is less common and less well described than later-onset IC. Risk factors, clinical features, and disease outcomes have not been studied in early-onset disease (EOD, ⩽7 days) or compared to late-onset disease (LOD, >7 days). Methods. All extremely low birth weight (ELBW, <1000 g) cases with IC and controls from a multicenter study of neonatal candidiasis enrolled from 2001 to 2003 were included in this study. Factors associated with occurrence and outcome of EOD in ELBW infants were determined. Results. Forty-five ELBW infants and their 84 matched controls were included. Fourteen (31%) ELBW infants had EOD. Birth weight <750 g, gestation <25 weeks, chorioamnionitis, and vaginal delivery were all strongly associated with EOD. Infection with Candida albicans, disseminated disease, pneumonia, and cardiovascular disease were significantly more common in EOD than in LOD. The EOD case fatality rate (71%) was higher than in LOD (32%) or controls (15%) (P = .0001). The rate of neurodevelopmental impairment and mortality combined was similar in EOD (86%) and LOD (72%), but higher than in controls (32%; P = .007). Conclusions. ELBW infants with EOD have a very poor prognosis compared to those with LOD. The role of perinatal transmission in EOD is supported by its association with chorioamnionitis, vaginal delivery, and pneumonia. Dissemination and cardiovascular involvement are common, and affected infants often die. Empiric treatment should be considered for ELBW infants delivered vaginally who have pneumonia and whose mothers have chorioamnionitis or an intrauterine foreign body. [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]

Importance: For many very low-birth-weight (VLBW) infants, there is insufficient mother's milk, and a supplement of pasteurized donor human milk or preterm formula is required. Awareness of the benefits of mother's milk has led to an increase in use of donor milk, despite limited data evaluating its efficacy.Objective: To determine if nutrient-enriched donor milk compared with formula, as a supplement to mother's milk, reduces neonatal morbidity, supports growth, and improves neurodevelopment in VLBW infants.Design, Setting, and Participants: In this pragmatic, double-blind, randomized trial, VLBW infants were recruited from 4 neonatal units in Ontario, Canada, within 96 hours of birth between October 2010 and December 2012. Follow-up was completed in July 2015.Interventions: Infants were fed either donor milk or formula for 90 days or to discharge when mother's milk was unavailable.Main Outcomes and Measures: The primary outcome was the cognitive composite score on the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) at 18 months' corrected age (standardized mean, 100 [SD, 15]; minimal clinically important difference, 5 points). Secondary outcomes included Bayley-III language and motor composite scores, growth, and a dichotomous mortality and morbidity index.Results: Of 840 eligible infants, 363 (43.2%) were randomized (181 to donor milk and 182 to preterm formula); of survivors, 299 (92%) had neurodevelopment assessed. Mean birth weight and gestational age of infants was 996 (SD, 272) g and 27.7 (2.6) weeks, respectively, and 195 (53.7%) were male. No statistically significant differences in mean Bayley-III cognitive composite score (adjusted scores, 92.9 in donor milk group vs 94.5 in formula group; fully adjusted mean difference, -2.0 [95% CI, -5.8 to 1.8]), language composite score (adjusted scores, 87.3 in donor milk group vs 90.3 in formula group; fully adjusted mean difference, -3.1 [95% CI, -7.5 to 1.3]), or motor composite score (adjusted scores, 91.8 in donor milk group vs 94.0 in formula group; fully adjusted mean difference, -3.7 [95% CI, -7.4 to 0.09]) were observed between groups. There was no statistically significant difference in infants positive for the mortality and morbidity index (43% in donor milk group, 40% in formula group) or changes in growth z scores.Conclusions and Relevance: Among VLBW infants, use of supplemental donor milk compared with formula did not improve neurodevelopment at 18 months' corrected age. If donor milk is used in settings with high provision of mother's milk, this outcome should not be considered a treatment goal.Trial Registration: isrctn.org Identifier: ISRCTN35317141. [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]

IMPORTANCE Extremely preterm infants may experience intermittent hypoxemia or bradycardia for many weeks after birth. The prognosis of these events is uncertain. OBJECTIVE To determine the association between intermittent hypoxemia or bradycardia and late death or disability. DESIGN, SETTING, AND PARTICIPANTS Post hoc analysis of data from the inception cohort assembled for the Canadian Oxygen Trial in 25 hospitals in Canada, the United States, Argentina, Finland, Germany, and Israel, including 1019 infants with gestational ages of 23 weeks 0 days through 27 weeks 6 days who were born between December 2006 and August 2010 and survived to a postmenstrual age of 36 weeks. Follow-up assessments occurred between October 2008 and August 2012. EXPOSURES Episodes of hypoxemia (pulse oximeter oxygen saturation <80%) or bradycardia (pulse rate <80/min) for 10 seconds or longer. Values were sampled every 10 seconds within 24 hours after birth until at least 36 weeks’ postmenstrual age. MAIN OUTCOMES AND MEASURES The primary outcome was a composite of death after 36 weeks’ postmenstrual age, motor impairment, cognitive or language delay, severe hearing loss, or bilateral blindness at 18 months’ corrected age. Secondary outcomes were motor impairment, cognitive or language delay, and severe retinopathy of prematurity. RESULTS Downloaded saturation and pulse rate data were available for a median of 68.3 days (interquartile range, 56.8-86.0 days). Mean percentages of recorded time with hypoxemia for the least and most affected 10% of infants were 0.4% and 13.5%, respectively. Corresponding values for bradycardia were 0.1% and 0.3%. The primary outcome was ascertained for 972 infants and present in 414 (42.6%). Hypoxemic episodes were associated with an estimated increased risk of late death or disability at 18 months of 56.5% in the highest decile of hypoxemic exposure vs 36.9% in the lowest decile (modeled relative risk, 1.53; 95% CI, 1.21-1.94). This association was significant only for prolonged hypoxemic episodes lasting at least 1 minute (relative risk, 1.66; 95% CI, 1.35-2.05 vs for shorter episodes, relative risk, 1.01; 95% CI, 0.77-1.32). Relative risks for all secondary outcomes were similarly increased after prolonged hypoxemia. Bradycardia did not alter the prognostic value of hypoxemia. CONCLUSIONS AND RELEVANCE Among extremely preterm infants who survived to 36 weeks’ postmenstrual age, prolonged hypoxemic episodes during the first 2 to 3 months after birth were associated with adverse 18-month outcomes. If confirmed in future studies, further research on the prevention of such episodes is needed. [ABSTRACT FROM AUTHOR]