Long-Term Outcomes of Multiple versus a Single Course of Antenatal Steroids: A Systematic Review.

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..

Cohort profile update: The Canadian Maternal-Infant Research on Environmental Chemicals Child Development study (MIREC-CD PLUS).

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.

Prenatal and concurrent blood mercury concentrations and associations with IQ in canadian preschool children.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

PROspective Meta-analysis Of Trials of Initial Oxygen in preterm Newborns (PROMOTION): Protocol for a systematic review and prospective meta-analysis with individual participant data on initial oxygen concentration for resuscitation of preterm infants.

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.

The Impact of Infant Sex on Multiple Courses versus a Single Course of Antenatal Corticosteroids: A Secondary Analysis of a Randomized Controlled Trial.

OBJECTIVE: Animal literature has suggested that the impact of antenatal corticosteroids (ACS) may vary by infant sex. Our objective was to assess the impact of infant sex on the use of multiple courses versus a single course of ACS and perinatal outcomes. STUDY DESIGN: We conducted a secondary analysis of the Multiple Courses of Antenatal Corticosteroids for Preterm Birth trial, which randomly allocated pregnant people to multiple courses versus a single course of ACS. Our primary outcome was a composite of perinatal mortality or clinically significant neonatal morbidity (including neonatal death, stillbirth, severe respiratory distress syndrome, intraventricular hemorrhage [grade III or IV], cystic periventricular leukomalacia, and necrotizing enterocolitis [stage II or III]). Secondary outcomes included individual components of the primary outcome as well as anthropometric measures. Baseline characteristics were compared between participants who received multiple courses versus a single course of ACS. An interaction between exposure to ACS and infant sex was assessed for significance and multivariable regression analyses were conducted with adjustment for predefined covariates, when feasible. RESULTS: Data on 2,300 infants were analyzed. The interaction term between treatment status (multiple courses vs. a single course of ACS) and infant sex was not significant for the primary outcome (p = 0.86), nor for any of the secondary outcomes (p > 0.05). CONCLUSION: Infant sex did not modify the association between exposure to ACS and perinatal outcomes including perinatal mortality or neonatal morbidity or anthropometric outcomes. However, animal literature indicates that sex-specific differences after exposure to ACS may emerge over time and thus investigating long-term sex-specific outcomes warrants further attention. KEY POINTS: · We explored the impact of infant sex on perinatal outcomes after multiple versus a single course of ACS.. · Infant sex was not a significant effect modifier of ACS exposure and perinatal outcomes.. · Animal literature indicates that sex-specific differences after ACS exposure may emerge over time.. · Further investigation of long-term sex-specific outcomes is warranted..

Individualized treatment of preterm premature rupture of membranes to prolong the latency period, reduce the rate of preterm birth, and improve neonatal outcomes.

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.

A Growing Dilemma: Antenatal Corticosteroids and Long-Term Consequences.

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..

Timing of antenatal corticosteroids in relation to clinical indication.

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.

Which growth standards should be used to identify large- and small-for-gestational age infants of mothers with type 1 diabetes? A pre-specified analysis of the CONCEPTT trial.

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.

Mycoplasma hominis meningitis in an extremely preterm newborn: a case report.

BACKGROUND: Mycoplasma Hominis is a micro-organism which is a part of the human genitourinary tract flora. Neonates are susceptible to acquire this pathogen either in utero or through vertical transmission. In rare cases, it may cause central nervous system infections with severe morbidity and mortality in preterm and term neonates. CASE PRESENTATION: We present a case of Mycoplasma Hominis meningitis in an extremely preterm neonate who presented with lethargy, tachycardia and seizures on day 7 of life. There was no history of maternal systemic or genitourinary infection during pregnancy and at the time of delivery. Empirical antibiotic therapy for neonatal meningitis was commenced after sending blood and cerebrospinal fluid cultures. Cerebrospinal fluid analysis showed pleocytosis with neutrophilic predominance, but no bacteria was identified on gram staining. Blood culture yielded no growth of any bacterial pathogen. However, growth of Mycoplasma Hominis was suspected in cerebrospinal fluid culture which was confirmed by 16S ribosomal ribonucleic acid (RNA) polymerase chain reaction analysis. Subsequently, antibiotics were changed to Moxifloxacin and Doxycycline which were given for a total duration of 6 weeks. Multiple cerebrospinal fluid cultures were performed during this treatment. No growth of any pathogen was identified on any of these cerebrospinal fluid cultures. CONCLUSIONS: We report a rare case of Mycoplasma Hominis meningitis in an extremely preterm neonate which was successfully treated with a combination therapy of Moxifloxacin and Doxycycline. It is important to consider the possibility of Mycoplasma Hominis meningitis in neonates who present with clinical signs and pleocytosis in cerebrospinal fluid but negative gram staining and no growth on conventional culture media.

Two-Thirds of Preterm Parents Would Participate in a Randomized Controlled Trial Comparing Double Doses of Steroids to a Single Dose and Placebo.

Animal research strongly suggests that a single dose of antenatal corticosteroids (ACS) is as effective as a double dose to mature preterm lungs; however, a human randomized controlled trial (RCT) is urgently needed. From August to November 2020, we conducted an online survey of Canadian parents of preterm infants. Survey respondents watched a parent-to-parent video introducing an RCT to study whether the standard double dose of ACS is non-inferior to a single dose (and matching placebo). Approximately two-thirds of respondents reported they were either likely or very likely to participate in the RCT, indicating high parental interest in and support for such a trial.

Delivery of monochorionic twins: lessons learned from the Twin Birth Study.

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.

Lactoferrin infant feeding trial_Canada (LIFT_Canada): protocol for a randomized trial of adding lactoferrin to feeds of very-low-birth-weight preterm infants.

BACKGROUND: In Canada alone, almost 3000 VLBW infants are born and treated annually with almost 1200 going onto death or survival with severe brain injury, chronic lung disorders, aggressive retinopathy of prematurity, late-onset sepsis, or significant necrotizing enterocolitis. Lactoferrin is an antimicrobial, antioxidant, anti-inflammatory iron-carrying, bifidogenic glycoprotein found in all vertebrates and in mammalian milk, leukocytes and exocrine secretions. Lactoferrin aids in creating an environment for growth of beneficial bacteria in the gut, thus reducing colonization with pathogenic bacteria. It is hypothesized that oral bovine lactoferrin (bLF), through its antimicrobial, antioxidant and anti-inflammatory properties, will reduce the rate of mortality or major morbidity in very low birth weight preterm infants. METHOD: Lactoferrin Infant Feeding Trial_Canada (LIFT_Canada) is a multi-centre, double-masked, randomized controlled trial with the aim to enroll 500 infants whose data will be combined with the data of the 1542 infants enrolled from Lactoferrin Infant Feeding Trial_Australia/New Zealand (LIFT_ANZ) in a pooled intention-to-treat analysis. Eligible infants will be randomized and allocated to one of two treatment groups: 1) a daily dose of 200 mg/kg bLF in breast/donor human milk or formula milk until 34 weeks corrected gestation or for a minimum of 2 weeks, whichever is longer, or until discharge home or transfer, if earlier; 2) no bLF with daily feeds. The primary outcome will be determined at 36 weeks corrected gestation for the presence of neonatal morbidity and at discharge for survival and treated retinopathy of prematurity. The duration of the trial is expected to be 36 months. DISCUSSION: Currently, there continues to be no clear answer related to the benefit of bLF in reducing mortality or any or all of the significant neonatal morbidities in very low birth weight infants. LIFT_Canada is designed with the hope that the pooled results from Australia, New Zealand, and Canada may help to clarify the situation. TRIAL REGISTRATION: Clinical Trials.Gov, Identifier: NCT03367013, Registered December 8, 2017.

Split-week gestational age model provides valuable information on outcomes in extremely preterm infants.

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.

Removal vs. retention of cervical cerclage in pregnancies complicated by preterm premature rupture of membranes: a retrospective study.

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.

Effects of repeat prenatal corticosteroids given to women at risk of preterm birth: An individual participant data meta-analysis.

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.

The worst of both worlds-combined deliveries in twin gestations: a subanalysis of the Twin Birth Study, a randomized, controlled, prospective study.

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.

Blood metal levels and early childhood anthropometric measures in a cohort of Canadian children.

Fetal exposure to some toxic metals has been associated with reduced fetal growth, but the impact of contemporary, low-level metals on anthropometric measures in childhood is not well understood. Our primary objective was to quantify associations between childhood levels of toxic metals and concurrently measured body mass index (BMI) in a population of Canadian preschool-aged children. We collected biomonitoring data and anthropometric measures on 480 children between the ages of two and five years in the Maternal-Infant Research on Environmental Chemicals (MIREC) Child Development Plus study. Concentrations of four toxic metals (lead, arsenic, cadmium, and mercury) were measured in whole blood collected from pregnant women and their children. Blood levels of key essential elements were also measured in children. Children's weight, height, and BMI z-scores were calculated using the World Health Organization growth standards. We used a series of linear regression models, adjusted for potential parental confounders, concurrently measured metals and elements, and prenatal blood metal levels, to evaluate associations between tertiles of each toxic metal and anthropometric measures. We tested for effect modification by sex. Of the 480 children, 449 (94%) were singleton births and had complete biomonitoring and anthropometric data. The majority of children had detectable concentrations of metals. In the adjusted models, girls with blood lead concentrations in the highest tertile (>0.82 µg/dL) had, on average, 0.26 (95% Cl: -0.55, 0.03) lower BMI z-scores than those in the referent category. In contrast, boys with lead levels in the highest tertile had, on average, 0.14 higher BMI z-scores (95% Cl: -0.14, 0.41) (p-value heterogeneity = 0.04). In this population of Canadian preschool-aged children with low-level blood lead concentrations, we observed effect modification by sex in the association between Pb and BMI but no statistically significant associations in the sex-specific strata. Child blood levels of As, Cd, and Hg were not associated with childhood BMI, weight, or height in boys or girls.

Planned cesarean or vaginal delivery for women in spontaneous labor with a twin pregnancy: A secondary analysis of the Twin Birth Study.

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.