Planned Cesarean or planned vaginal delivery for twins: secondary analysis of randomized controlled trial.

OBJECTIVE: To evaluate whether there is a differential benefit of planned Cesarean delivery (CD) over planned vaginal delivery (VD) in women with a twin pregnancy and the first twin in cephalic presentation, depending on prespecified baseline maternal and pregnancy characteristics, and/or gestational age (GA) at delivery. METHODS: This was a secondary analysis of the Twin Birth Study, which included 2804 women with a twin pregnancy and the first twin (Twin A) in cephalic presentation between 32 + 0 and 38 + 6 weeks' gestation at 106 centers in 25 countries. Women were assigned randomly to either planned CD or planned VD. The main outcome measure was composite adverse perinatal outcome, defined as the occurrence of perinatal mortality or serious neonatal morbidity in at least one twin. The baseline maternal and pregnancy characteristics (markers) considered were maternal age, parity, history of CD, use of antenatal corticosteroids, estimated fetal weight (EFW) of Twin A, EFW of Twin B, > 25% difference in EFW between the twins, presentation of Twin B, chorionicity on ultrasound, method of conception, complications of pregnancy, ruptured membranes at randomization and GA at randomization. Separate logistic regression models were developed for each marker in order to model composite adverse perinatal outcome as a function of the specific marker, planned delivery mode and the interaction between these two terms. In addition, multivariable logistic regression analysis with backward variable elimination was performed separately in each arm of the trial. The association between planned mode of delivery and composite adverse perinatal outcome, according to GA at delivery, was assessed using logistic regression analysis. RESULTS: Of the 2804 women initially randomized, 1391 were included in each study arm. None of the studied baseline markers was associated with a differential benefit of planned CD over planned VD in the rate of composite adverse perinatal outcome. GA at delivery was associated differentially with composite adverse perinatal outcome in the treatment arms (P for interaction < 0.001). Among pregnancies delivered at 32 + 0 to 36 + 6 weeks, there was a trend towards a lower rate of composite adverse perinatal outcome in those in the planned-VD group compared with those in planned-CD group (29 (2.2%) vs 48 (3.6%) cases; odds ratio (OR) 0.62 (95% CI, 0.37-1.03)). In pregnancies delivered at or after 37 + 0 weeks, planned VD was associated with a significantly higher rate of composite adverse perinatal outcome, as compared with planned CD (23 (1.5%) vs 10 (0.7%) cases; OR, 2.25 (95% CI, 1.06-4.77)). CONCLUSION: The perinatal outcome of twin pregnancies with the first twin in cephalic presentation may differ depending on GA at delivery and planned mode of delivery. At 32-37 weeks, planned VD seems to be favorable, while, from around 37 weeks onwards, planned CD might be safer. The absolute risks of adverse perinatal outcomes at term are low and must be weighed against the increased maternal risks associated with planned CD. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Benefit of antenatal corticosteroids by year of birth among preterm infants in Canada during 2003-2017: a population-based cohort study.

OBJECTIVE: To evaluate the changes in the associations of antenatal corticosteroids (ACS) with neonatal mortality and severe neurological injury over time (2003-17). DESIGN: National, population-representative, retrospective cohort study. SETTING: Level III neonatal intensive care units participating in the Canadian Neonatal Network. POPULATION: All infants born at 230/7 -336/7 weeks of gestation (n = 43 456). METHODS: We estimated the associations between exposure to ACS and neonatal outcomes by year of birth. Year of birth was considered both continuously and categorically as three consecutive epochs. MAIN OUTCOME MEASURE: Neonatal mortality and severe neurological injury. RESULTS: The absolute rates of neonatal mortality and severe neurological injury decreased during the study period in both the ACS and No ACS groups. For infants born at 230/7 -306/7 weeks of gestation, ACS was associated with similar reductions in neonatal mortality across the three epochs (9.0% versus 18.1%, adjusted relative risk [aRR] 0.54, 95% CI 0.47-0.61 in 2003-09; 7.6% versus 19.6%, aRR 0.51, 95% CI 0.44-0.59 in 2010-13; and 7.3% versus 14.5%, aRR 0.56, 95% CI 0.46-0.68 in 2014-17) and in severe neurological injury (13.2% versus 25.8%, aRR 0.57, 95% CI 0.50-0.64 in 2003-09; 7.4% versus 17.4%, aRR 0.53, 95% CI 0.43-0.66 in 2010-14; and 7.2% versus 14.8%, aRR 0.59, 95% CI 0.48-0.74 in 2014-17). CONCLUSION: Despite the ongoing improvements in neonatal care of preterm infants, as reflected by the gradual decrease in the absolute rates of neonatal mortality and severe neurological injury, the association of ACS treatment with neonatal mortality and severe neurological injury among extremely preterm infants born at 23-30 weeks of gestation has remained stable throughout the study period of 15 years. TWEETABLE ABSTRACT: Despite the gradual decrease in the rates of neonatal mortality and severe neurological injury, antenatal corticosteroids remain an important intervention in the current era of neonatal care.

The impact of pre-eclampsia definitions on the identification of adverse outcome risk in hypertensive pregnancy - analyses from the CHIPS trial (Control of Hypertension in Pregnancy Study).

OBJECTIVE: To examine the association between pre-eclampsia definition and pregnancy outcome. DESIGN: Secondary analysis of Control of Hypertension in Pregnancy Study (CHIPS) trial data. SETTING: International multicentre randomised controlled trial (RCT). POPULATION: In all, 987 women with non-severe non-proteinuric pregnancy hypertension. METHODS: We evaluated the association between pre-eclampsia definitions and adverse pregnancy outcomes, stratified by hypertension type and blood pressure control. MAIN OUTCOME MEASURES: Main CHIPS trial outcomes: primary (perinatal loss or high-level neonatal care for >48 hours), secondary (serious maternal complications), birthweight <10th centile, severe maternal hypertension, delivery at <34 or <37 weeks, and maternal hospitalisation before birth. RESULTS: Of 979/987 women with informative data, 280 (28.6%) progressed to pre-eclampsia defined restrictively by new proteinuria, and 471 (48.1%) to pre-eclampsia defined broadly as proteinuria or one/more maternal symptoms, signs or abnormal laboratory tests. The broad (versus restrictive) definition had significantly higher sensitivities (range 62-79% versus 36-50%), lower specificities (range 53-65% versus 72-82%), and similar or higher diagnostic odds ratios and 'true-positive' to 'false-positive' ratios. Stratified analyses showed similar results. Addition of available fetoplacental manifestations (stillbirth or birthweight <10th centile) to the broad pre-eclampsia definition improved sensitivity (74-87%). CONCLUSIONS: A broad (versus restrictive) pre-eclampsia definition better identifies women who develop adverse pregnancy outcomes. These findings should be replicated in a prospective study within routine healthcare to ensure that the anticipated increase in surveillance and intervention in a larger number of women with pre-eclampsia is associated with improved outcomes, reasonable costs and congruence with women's values. TWEETABLE ABSTRACT: A broad (versus restrictive) pre-eclampsia definition better identifies the risk of adverse pregnancy outcomes.

Cesarean delivery or induction of labor in pre-labor twin gestations: a secondary analysis of the twin birth study.

BACKGROUND: In the Twin Birth Study, women at 320/7-386/7 weeks of gestation, in whom the first twin was in cephalic presentation, were randomized to planned vaginal delivery or cesarean section. The study found no significant differences in neonatal or maternal outcomes in the two planned mode of delivery groups. We aimed to compare neonatal and maternal outcomes of twin gestations without spontaneous onset of labor, who underwent induction of labor or pre-labor cesarean section as the intervention of induction may affect outcomes. METHODS: In this secondary analysis of the Twin Birth Study we compared those who had an induction of labor with those who had a pre-labor cesarean section. The primary outcome was a composite of fetal or neonatal death or serious neonatal morbidity. Secondary outcome was a composite of maternal morbidity and mortality. TRIAL REGISTRATION: NCT00187369. RESULTS: Of the 2804 women included in the Twin Birth Study, a total of 1347 (48%) women required a delivery before a spontaneous onset of labor occurred: 568 (42%) in the planned vaginal delivery arm and 779 (58%) in the planned cesarean arm. Induction of labor was attempted in 409 (30%), and 938 (70%) had a pre-labor cesarean section. The rate of intrapartum cesarean section in the induction of labor group was 41.3%. The rate of the primary outcome was comparable between the pre-labor cesarean section group and induction of labor group (1.65% vs. 1.97%; p = 0.61; OR 0.83; 95% CI 0.43-1.62). The maternal composite outcome was found to be lower with pre-labor cesarean section compared to induction of labor (7.25% vs. 11.25%; p = 0.01; OR 0.61; 95% CI 0.41-0.91). CONCLUSION: In women with twin gestation between 320/7-386/7 weeks of gestation, induction of labor and pre-labor cesarean section have similar neonatal outcomes. Pre-labor cesarean section is associated with favorable maternal outcomes which differs from the overall Twin Birth Study results. These data may be used to better counsel women with twin gestation who are faced with the decision of interventional delivery.

Amniotic fluid volume at presentation with early preterm prelabor rupture of membranes and association with severe neonatal respiratory morbidity.

OBJECTIVE: Amniotic fluid volume (AFV) plays an important role in early fetal lung development, and oligohydramnios in early pregnancy is associated with pulmonary hypoplasia. The aim of this study was to evaluate the association between AFV at the time of presentation with early preterm prelabor rupture of membranes (PPROM) and severe neonatal respiratory morbidity and other adverse pregnancy outcomes. METHODS: This was a retrospective study of all women with a singleton pregnancy, admitted to a single tertiary referral center between 2004 and 2014, for expectant management of PPROM at 20 + 0 to 28 + 6 weeks' gestation. The primary exposure was AFV at presentation, classified according to sonographic maximum vertical pocket (MVP) as: normal AFV (> 2 cm), oligohydramnios (≤ 2 cm and > 1 cm) or severe oligohydramnios (≤ 1 cm). The primary outcome was a composite variable of severe respiratory morbidity, defined as either of the following: (1) need for respiratory support in the form of mechanical ventilation using an endotracheal tube for ≥ 72 h and need for surfactant; or (2) bronchopulmonary dysplasia, defined as requirement for oxygen at postmenstrual age of 36 weeks or at the time of transfer to a Level-II facility. Adjusted odds ratios (aOR) and 95% CI for the primary and secondary outcomes were calculated for each AFV-at-presentation group (using normal AFV as the reference), adjusting for gestational age (GA) at PPROM, latency period, birth weight, mode of delivery and chorioamnionitis. RESULTS: In total, 580 women were included, of whom 304 (52.4%) had normal AFV, 161 (27.8%) had oligohydramnios and 115 (19.8%) had severe oligohydramnios at presentation. The rates of severe respiratory morbidity were 16.1%, 26.7% and 45.2%, respectively. Compared with normal AFV at presentation, oligohydramnios (aOR, 3.27; 95% CI, 1.84-5.84) and severe oligohydramnios (aOR, 4.11; 95% CI, 2.26-7.56) at presentation were associated independently with severe respiratory morbidity. Other variables that were associated independently with the primary outcome were GA at PPROM (aOR, 0.54; 95% CI, 0.43-0.69), latency period (aOR, 0.94; 95% CI, 0.91-0.98) and Cesarean delivery (aOR, 2.01; 95% CI, 1.21-3.32). CONCLUSIONS: In women with early PPROM, AFV at presentation, as assessed by the MVP on ultrasound examination, is associated independently with severe neonatal respiratory morbidity. This information may be taken into consideration when counseling women with early PPROM regarding neonatal outcome and management options. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Urinary stress incontinence and other maternal outcomes 2 years after caesarean or vaginal birth for twin pregnancy: a multicentre randomised trial.

OBJECTIVE: Does planned caesarean compared with planned vaginal birth lower the risk of problematic urinary stress, faecal, or flatal incontinence? DESIGN: Women between 320/7 and 386/7 weeks of gestation with a twin pregnancy were randomised to planned caesarean or planned vaginal birth. SETTING: The trial took place at 106 centres in 25 countries. POPULATION: A total of 2305 of the 2804 women enrolled in the study completed questionnaires at 2 years (82.2% follow-up): 1155 in the planned caesarean group and 1150 in the planned vaginal birth group. METHODS: A structured self-administered questionnaire completed at 2 years postpartum. MAIN OUTCOME MEASURES: The primary maternal outcome of the Twin Birth Study was problematic urinary stress, or fecal, or flatal incontinence at 2 years RESULTS: Women in the planned caesarean group had lower problematic urinary stress incontinence rates compared with women in the planned vaginal birth group [93/1147 (8.11%) versus 140/1143 (12.25%); odds ratio, 0.63; 95% confidence interval, 0.47-0.83; P = 0.001]. Among those with problematic urinary stress incontinence, quality of life (measured using the Incontinence Impact Questionnaire, IIQ-7) was not different for planned caesarean versus planned vaginal birth groups [mean (SD): 18.4 (21.0) versus 19.1 (21.5); P = 0.82]. There were no differences in problematic faecal or flatal incontinence, or in other maternal outcomes. CONCLUSIONS: Among women with a twin pregnancy and no prior history of urinary stress incontinence, a management strategy of planned caesarean compared with planned vaginal birth reduces the risk of problematic urinary stress incontinence at 2 years postpartum. Our findings show that the prevalence but not the severity of urinary stress incontinence was associated with mode of birth. FUNDING: Canadian Institutes of Health Research (CIHR) (grant no. MCT-63164). TWEETABLE ABSTRACT: For women with twins, planned caesarean compared with planned vaginal birth is associated with decreased prevalence but not severity of urinary stress incontinence at 2 years.

Cognitive, motor, behavioural and academic performances of children born preterm: a meta-analysis and systematic review involving 64 061 children.

BACKGROUND: Preterm birth may leave the brain vulnerable to dysfunction. Knowledge of future neurodevelopmental delay in children born with various degrees of prematurity is needed to inform practice and policy. OBJECTIVE: To quantify the long-term cognitive, motor, behavioural and academic performance of children born with different degrees of prematurity compared with term-born children. SEARCH STRATEGY: PubMed and Embase were searched from January 1980 to December 2016 without language restrictions. SELECTION CRITERIA: Observational studies that reported neurodevelopmental outcomes from 2 years of age in children born preterm compared with a term-born cohort. DATA COLLECTION AND ANALYSIS: We pooled individual estimates of standardised mean differences (SMD) and odds ratios (OR) with 95% confidence intervals using a random effects model. MAIN RESULTS: We included 74 studies (64 061 children). Preterm children had lower cognitive scores for FSIQ (SMD: -0.70; 95% CI: -0.73 to -0.66), PIQ (SMD: -0.67; 95% CI: -0.73 to -0.60) and VIQ (SMD: -0.53; 95% CI: -0.60 to -0.47). Lower scores for preterm children in motor skills, behaviour, reading, mathematics and spelling were observed at primary school age, and this persisted to secondary school age, except for mathematics. Gestational age at birth accounted for 38-48% of the observed IQ variance. ADHD was diagnosed twice as often in preterm children (OR: 1.6; 95% CI: 1.3-1.8), with a differential effect observed according to the severity of prematurity (I2 = 49.4%, P = 0.03). CONCLUSIONS: Prematurity of any degree affects the cognitive performance of children born preterm. The poor neurodevelopment persists at various ages of follow up. Parents, educators, healthcare professionals and policy makers need to take into account the additional academic, emotional and behavioural needs of these children. TWEETABLE ABSTRACT: Adverse effect of preterm birth on a child's neurodevelopment persists up to adulthood.

Control of Hypertension In Pregnancy Study randomised controlled trial-are the results dependent on the choice of labetalol or methyldopa?

OBJECTIVE: To determine whether the difference in outcomes between 'less tight' (target diastolic blood pressure [dBP] of 100 mmHg) versus 'tight' control (target dBP of 85 mmHg) in the CHIPS Trial (ISRCTN 71416914, http://pre-empt.cfri.ca/;CHIPS) depended on the choice of labetalol or methyldopa, the two most commonly used antihypertensive agents in CHIPS. DESIGN: Secondary analysis of CHIPS Trial data. SETTING: International multicentre randomised controlled trial (94 sites, 15 countries). POPULATION OR SAMPLE: A total of 987 women with non-severe non-proteinuric pregnancy hypertension. METHODS: Logistic regression was used for comparisons of 'less tight' versus 'tight' control among women treated with labetalol (but not methydopa) versus methyldopa (but not labetalol). Analyses were adjusted for the influence of baseline factors, including use of any antihypertensive therapy at randomisation. MAIN OUTCOME MEASURES: Main CHIPS Trial outcomes: primary (perinatal loss or high-level neonatal care for > 48 hours), secondary (serious maternal complications), birthweight < 10th centile, severe maternal hypertension, pre-eclampsia, and delivery at < 34 or < 37 weeks. RESULTS: Of 987 women in CHIPS, antihypertensive therapy was taken by 566 women at randomisation (labetalol 111 ['less tight'] versus 127 ['tight'] or methyldopa 126 ['less tight'] versus 117 ['tight']) and 815 women after randomisation (labetalol 186 ['less tight'] versus 247 ['tight'] and methyldopa by 98 ['less tight'] versus 126 ['tight']). Following adjustment, odds ratios for outcomes in 'less tight' versus 'tight' control were similar between antihypertensive groups according to 'at randomisation' and 'after randomisation' therapy. CONCLUSION: Outcomes for 'less tight' versus 'tight' control were not dependent on use of methyldopa or labetalol. TWEETABLE ABSTRACT: In the CHIPS Trial, maternal and infant outcomes were not dependent on use of labetalol or methyldopa.

Do labetalol and methyldopa have different effects on pregnancy outcome? Analysis of data from the Control of Hypertension In Pregnancy Study (CHIPS) trial.

OBJECTIVE: To compare pregnancy outcomes, accounting for allocated group, between methyldopa-treated and labetalol-treated women in the CHIPS Trial (ISRCTN 71416914) of 'less tight' versus 'tight' control of pregnancy hypertension. DESIGN: Secondary analysis of CHIPS Trial cohort. SETTING: International randomised controlled trial (94 sites, 15 countries). POPULATION OR SAMPLE: Of 987 CHIPS recruits, 481/566 (85.0%) women treated with antihypertensive therapy at randomisation. Of 981 (99.4%) women followed to delivery, 656/745 (88.1%) treated postrandomisation. METHODS: Logistic regression to compare outcomes among women who took methyldopa or labetalol, adjusted for the influence of baseline factors. MAIN OUTCOME MEASURES: CHIPS primary (perinatal loss or high level neonatal care for >48 hours) and secondary (serious maternal complications) outcomes, birthweight <10th centile, severe maternal hypertension, pre-eclampsia and delivery at <34 or <37 weeks. RESULTS: Methyldopa and labetalol were used commonly at randomisation (243/987, 24.6% and 238/987, 24.6%, respectively) and post-randomisation (224/981, 22.8% and 433/981, 44.1%, respectively). Following adjusted analyses, methyldopa (versus labetalol) at randomisation was associated with fewer babies with birthweight <10th centile [adjusted odds ratio (aOR) 0.48; 95% CI 0.20-0.87]. Methyldopa (versus labetalol) postrandomisation was associated with fewer CHIPS primary outcomes (aOR 0.64; 95% CI 0.40-1.00), birthweight <10th centile (aOR 0.54; 95% CI 0.32-0.92), severe hypertension (aOR 0.51; 95% CI 0.31-0.83), pre-eclampsia (aOR 0.55; 95% CI 0.36-0.85), and delivery at <34 weeks (aOR 0.53; 95% CI 0.29-0.96) or <37 weeks (aOR 0.55; 95% CI 0.35-0.85). CONCLUSION: These nonrandomised comparisons are subject to residual confounding, but women treated with methyldopa (versus labetalol), particularly those with pre-existing hypertension, may have had better outcomes. TWEETABLE ABSTRACT: There was no evidence that women treated with methyldopa versus labetalol had worse outcomes.

Maternal outcomes at 3 months after planned caesarean section versus planned vaginal birth for twin pregnancies in the Twin Birth Study: a randomised controlled trial.

OBJECTIVE: To compare outcomes at 3 months post partum for women randomised to give birth by planned caesarean section (CS) or by planned vaginal birth (VB) in the Twin Birth Study (TBS). DESIGN: We invited women in the TBS to complete a 3-month follow-up questionnaire. SETTING: Two thousand and eight hundred and four women from 25 countries. POPULATION: Two thousand and five hundred and seventy women (92% response rate). METHODS: Women randomised between 13 December 2003 and 4 April 2011 in the TBS completed a questionnaire and outcomes were compared using an intention-to-treat approach. MAIN OUTCOME AND MEASURES: Breastfeeding, quality of life, depression, fatigue and urinary incontinence. RESULTS: We found no clinically important differences between groups in any outcome. In the planned CS versus planned VB groups, breastfeeding at any time after birth was reported by 84.4% versus 86.4% (P = 0.13); the mean physical and mental Short Form (36) Health Survey (SF-36) quality of life scores were 51.8 versus 51.6 (P = 0.65) and 46.7 versus 46.0 (P = 0.09), respectively; the mean Multidimensional Assessment of Fatigue score was 20.3 versus 20.8 (P = 0.14); the frequency of probable depression on the Edinburgh Postnatal Depression Scale was 14.0% versus 14.8% (P = 0.57); the rate of problematic urinary incontinence was 5.5% versus 6.4% (P = 0.31); and the mean Incontinence Impact Questionnaire-7 score was 20.5 versus 20.4 (P = 0.99). Partner relationships, including painful intercourse, were similar between the groups. CONCLUSION: For women with twin pregnancies randomised to planned CS compared with planned VB, outcomes at 3 months post partum did not differ. The mode of birth was not associated with problematic urinary incontinence or urinary incontinence that affected the quality of life. Contrary to previous studies, breastfeeding at 3 months was not increased with planned VB. TWEETABLE ABSTRACT: Planned mode of birth for twins doesn't affect maternal depression, wellbeing, incontinence or breastfeeding.

Assembly of photosynthetic apparatus in Rhodobacter sphaeroides as revealed by functional assessments at different growth phases and in synchronized and greening cells.

The development of photosynthetic membranes of intact cells of Rhodobacter sphaeroides was tracked by light-induced absorption spectroscopy and induction and relaxation of the bacteriochlorophyll fluorescence. Changes in membrane structure were induced by three methods: synchronization of cell growth, adjustment of different growth phases and transfer from aerobic to anaerobic conditions (greening) of the bacteria. While the production of the bacteriochlorophyll and carotenoid pigments and the activation of light harvesting and reaction center complexes showed cell-cycle independent and continuous increase with characteristic lag phases, the accumulation of phospholipids and membrane potential (electrochromism) exhibited stepwise increase controlled by cell division. Cells in the stationary phase of growth demonstrated closer packing and tighter energetic coupling of the photosynthetic units (PSU) than in their early logarithmic stage. The greening resulted in rapid (within 0-4 h) induction of BChl synthesis accompanied with a dominating role for the peripheral light harvesting system (up to LH2/LH1 ~2.5), significantly increased rate (~7·10(4) s(-1)) and yield (F v/F max ~0.7) of photochemistry and modest (~2.5-fold) decrease of the rate of electron transfer (~1.5·10(4) s(-1)). The results are discussed in frame of a model of sequential assembly of the PSU with emphasis on crowding the LH2 complexes resulting in an increase of the connectivity and yield of light capture on the one hand and increase of hindrance to diffusion of mobile redox agents on the other hand.

Long-term child follow-up after large obstetric randomised controlled trials for the evaluation of perinatal interventions: a systematic review of the literature.

BACKGROUND: Although the hope is that many perinatal interventions are performed with an ultimate aim to improve the long-term health and development of the child, long-term outcome is rarely used as a primary end-point in perinatal randomised controlled trials (RCTs). OBJECTIVE: To evaluate how often and with which tools long-term follow-up is performed after large obstetric RCTs. SEARCH STRATEGY: We searched the Cochrane Library for Cochrane reviews published by the Cochrane Pregnancy and Childbirth Group for reviews on interventions that aimed to improve neonatal outcome. Selection criteria Reviews on perinatal interventions that were not performed to improve the condition of the neonate were excluded. We limited our review to RCTs with more than 350 participating women. For each included study, we checked in Web of Science as to whether the researchers had reported on follow-up in subsequent publications. DATA COLLECTION AND ANALYSIS: Relevant information was extracted from these RCTs by two reviewers using a predefined data collection sheet. All information was analysed using SPSS 17.0 (SPSS Inc., Chicago, IL, USA). MAIN RESULTS: We studied 212 reviews including 1837 RCTs on perinatal interventions, 249 (14%) of which included 350 participants. Only 40 of 249 RCTs (16%) followed the children after discharge from the hospital to evaluate the effect of a specific perinatal intervention. The number of RCTs with long-term follow-up remained stable, with 10 of 67 RCTs (15%) reporting follow-up before 1990, 17 of 115 (15%) between 1990 and 2000, and 13 of 67 (19%) after 2000 (P = 0.68). CONCLUSIONS: Only a small minority of large perinatal RCTs report the long-term follow-up of the child. Future obstetric RCTs should consider performing long-term follow-up at the start of the trial.

Cytokine levels in neonatal necrotizing enterocolitis and long-term growth and neurodevelopment.

OBJECTIVE: To investigate if circulating cytokines are related to growth and neurodevelopmental outcome following necrotizing enterocolitis (NEC). STUDY DESIGN: Pro-inflammatory cytokine levels were measured prospectively in 40 neonates and compared with neurodevelopmental outcome. Cytokine levels were measured at the onset of feeding intolerance (Group II, n = 17) or NEC (Group III, n = 10) and at weeks 2-3 in control infants (Group I, n = 13). Neurodevelopmental outcome was assessed at the age of 24-28 months. Data were analysed using descriptive statistics, non-parametric tests and Student t-test. RESULTS: Median birth weights (range) in groups I, II and III were 1120 (525-1564) g, 1068 (650-1937) g and 1145 (670-2833) g, and median gestational ages (range) were 28 (24-35) weeks 28 (24-35) weeks and 28 (25-37) weeks respectively. NEC occurred in 10 infants. Serum IL-6 (interleukin-6) was elevated in group III, (p = 0.03). Significant developmental delay was found in 12% of the infants in Group II and 20% of the infants in Group III, but no infant in group I. Five infants in group III with NEC (50%), had head ultrasound abnormalities. At 1 year of age, growth, weight and head circumference were significantly different in Group III, however, at two years of age, only height was significantly different, p < 0.02. Although there was wide variation, neonatal cytokine levels tended to be greater in the infants later found to have abnormal cognitive and psychomotor outcomes. CONCLUSION: This study suggests that increased serum levels of pro-inflammatory cytokines may play a role in the poor growth and neurodevelopment associated with this high-risk population.

Cytomegalovirus transmission to extremely low-birthweight infants through breast milk.

AIM: To determine the incidence, timing and clinical significance of acquired postnatal cytomegalovirus (CMV) in extremely low-birthweight (ELBW) infants. METHODS: Prospective, longitudinal surveillance study. ELBW infants were recruited in the first week of life. Maternal blood was tested for CMV-specific IgG antibodies. Weekly urine samples were obtained from infants for CMV culture and rapid antigen testing. Data were collected regarding clinical course and breast milk intake. RESULTS: Of 181 eligible infants, 119 infants, born to 101 mothers, were enrolled. Eighty of the 101 mothers had their serum checked for CMV status. Seventy percent of those tested were seropositive for CMV. Of the 65 infants born to seropositive mothers, 94% received breast milk during their hospital stay. Complete urine collection was obtained in 92 infants. CMV was cultured from the urine of only four infants, all of whom were born to seropositive mothers. Only one of these four infants was symptomatic. The range at which CMV was first detected was between 48 and 72 postnatal days of age. CONCLUSIONS: Despite a very high CMV seropositivity rate in mothers of ELBW infants, and the previously reported high rate of CMV excretion into breast milk, the incidence of postnatal CMV transmission was extremely low in our study.

The management and outcome of higher order multifetal pregnancies: obstetric, neonatal and follow-up data.

The objective of this study was to describe current obstetric, neonatal, and long-term neurodevelopmental outcomes of higher order multifetal gestations (> or = 3 fetuses) in the 1990s. We also intended to identify a target gestational age at which neonatal and neurodevelopmental morbidities are low. Records from all multifetal pregnancies (> or = 3 viable fetuses > or = 20 weeks gestation) delivered at the two perinatal centers in Toronto, Ontario, Canada during the study period (January 1, 1990-December 31, 1996) were reviewed. Data were collected on obstetric, neonatal, and long-term neurodevelopmental outcomes. Follow up data were gathered regarding the presence of a severe deficit in four categories (vision, hearing, cognition, and motor skills). Statistical analysis was performed to determine a gestational age at which a significant decrease in deficit occurred. During the study period 165 multifetal pregnancies were delivered. This resulted in 511 fetuses, of which 496 were live births. Of these 496 infants, 453 survived to discharge. Follow up data were obtained on 332 (73.3 per cent) infants. Infant survival increased with gestational age, and was approximately 90 per cent or greater at 26 weeks or more. Of all infants followed, the proportion of those without deficit increased with increasing gestational age, such that the percent without deficit was 96.9 at 31 weeks or greater. Of all infants followed, 301 (90.7 per cent) had no deficit. Statistical analysis revealed a significant difference in long-term neurodevelopmental outcome between infants born before and after 28 weeks gestation. The incidence of a major deficit was 44.1 per cent for those born earlier than and 5.4 per cent for those born later than this gestational age (p = 0.001). In our cohort, survival figures were high. Even in lower gestational groupings, survival was high, but not without serious concerns about severe morbidity. This information is useful when counseling parents of higher order multifetal pregnancies.

Neonatal brain injury.

Complacency about long-term outcomes in newborns is being eroded rapidly with new information. We have examined developments in the area from an explicitly clinical approach, focusing on etiology, diagnostic modalities, and therapies. We attempt to discuss relevance from the preterm and the term perspective. Emerging evidence implicating chorioamnionitis as a significant contributor to neonatal brain injury is discussed. Therapeutic modalities such as magnetic resonance imaging and electrophysiological monitoring offer some potentially new tools for the clinician. An exploding series of basic advances suggest several potentially new strands of therapy. We discuss two that deserve further clinical exploration, namely anti-inflammatory strategies and thread hormone supplementation. In the arena of therapy, however, the paucity of large trials from which to guide therapies is a predominant theme, leaving a large reservoir of uncertainty for the clinician.

Evaluating 2 year outcome in twins < or = 30 weeks gestation at birth: a regional perinatal unit's experience.

With improved technology in assisted reproductive medicine, there has been an absolute increase in the numbers of twin pregnancies with an associated increase in perinatal mortality and morbidity. This increase in perinatal mortality and morbidity is largely due to a higher incidence of delivering preterm as compared to singletons. Twin pregnancies have their unique complications that include abnormal placental communication and discordant growth which are associated with perinatal mortality and morbidity. The objectives of this study were two-fold: i) to determine if the morbidity/mortality outcome at 18-24 months corrected age seen in a cohort of twins born between 24-30 weeks gestation was significantly different as compared to singleton preterm infants of the same gestation; and ii) to determine and evaluate any differences between monochorionic (MC) and dichorionic (DC) twins. Twins 24-30 weeks gestation at birth born between 01/01/97-30/06/99 were identified and prospectively followed to 18-24 months corrected age (c.a.). They were matched with a singleton infant of the same gender and within 1 week of the same gestation. Obstetrical, neonatal and neurodevelopmental data were gathered and analyzed. The primary outcome was death or the presence of a severe neurodevelopmental deficit at 18-24 months corrected age. Of the 56 sets of twins identified, 52 sets were followed prospectively with 101 infants available for matching. In this cohort, twin pregnancies had a lower incidence of pregnancy-induced hypertension and premature rupture of membranes than singletons (p < 0.05). The two groups were comparable in neonatal characteristics. The incidence of death or severe disability was 29.7% in twins vs. 22.8% in singletons (p = 0.337, Fisher's exact test). The major area of defect was in the cognitive category for both groups, 9.9% vs. 7.9% respectively. MC twins made up 35.6%; DC twins 64.4%. Twin to twin transfusion syndrome (TTTS) occurred in 6.9%. Discordant growth occurred more frequently in MC pregnancies (p = 0.016). MC twins tended to be more premature, lower in birth weight, and experience neonatal morbidity in the form of patent ductus arteriosus and sepsis (p < 0.05) as compared to DC twins. However, the primary outcome of death or severe neurodevelopmental deficit at 18-24 months c.a. was not significantly different between the two groups, 38.9% (MC) vs. 24.6% (DC), (p = 0.173, Fisher's exact test). Neurodevelopmental morbidity or mortality in twins with TTTS was 42%. Mortality and severe neurodevelopmental morbidity were not signif cantly higher in twins as compared to singletons in this cohort. However, the trend is slightly higher in twins, which may have clinical significance. Though not statistically significant, the incidence of 38.9% in adverse outcome wth MC twins may be clinically significant. With the number of twins steadily increasing, further monitor ng is required to determine future directions in intervention and research. Early recognition of monochorionicity remains essential to optimize care and neurodevelopment for these infants.

Hypothyroxinemia of prematurity and infant neurodevelopment: a pilot study.

To assess whether hypothyroxinemia has specific effects on neurodevelopment in premature infants, thyroid hormone levels were determined at 2 weeks of life and 40 weeks postconceptional age (PCA), and infants were evaluated at 3 months corrected age using the Bayley Scales of Infant Development and Early Infancy Temperament Questionnaire. Additional attention scales were derived from the factor analysis of relevant Bayley items. Fifteen infants born between 30 and 35 weeks and 21 full-term infants were studied. Results indicated no group differences on the Bayley or derived attention scales, whereas the temperament questionnaire revealed lower sensory thresholds and greater reactivity in the preterm group. The preterm group had normal thyroxine (T4) levels at 2 weeks of age, which declined by 40 weeks PCA for both free T4 (p < .01 for reference value and p < .0001 for gestational age-adjusted value) and total T4 (p < .05 for age-adjusted value). Correlations revealed that higher 40-week PCA free T4 levels were associated with better attentiveness ratings (p < .01 for reference and p < .0001 for gestational-age values) and sustained attention (p < .05) and higher 40-week total T4 with better motor skills (p < .05 for gestational-age value). These findings signify that a mild degree of hypothyroxinemia is evident in preterm infants without neurological risk and predicts subsequently poorer cognitive and motor abilities.

Favourable neurological outcomes following delivery room cardiopulmonary resuscitation of infants < or = 750 g at birth.

OBJECTIVE: To study short- and long-term outcomes of infants < or = 750 g birthweight who received cardiopulmonary resuscitation (CPR) in the delivery room. METHODOLOGY: A retrospective analysis of all inborn live births < or = 750 g birthweight from 1990 to 1996. Cardiopulmonary resuscitation was defined as positive pressure ventilation via an endotracheal tube and chest compressions. Univeriate analysis were conducted comparing patients according to the use of CPR or positive pressure ventilation alone. RESULTS: Cardiopulmonary resuscitation was administered to 16 infants: four received chest compressions only and 12 also received adrenaline. Cardiopulmonary resuscitation recipients had significantly lower Apgar scores at both 1 and 5 min, and had delayed onset of spontaneous respiration (P < 0.01). Seven patients died, and eight of nine survivors were free of major neurodevelopmental abnormalities at follow up. All CPR recipients with a 5 min Apgar score of < or = 5 and delayed onset of spontaneous respiration beyond 5 min had poor outcomes. CONCLUSION: Contrary to the majority of published evidence, delivery room CPR in our extremely small infants was not associated with a high risk of severe neurodevelopmental disability.