Survival without severe neonatal morbidity after antenatal betamethasone dose reduction: a post hoc analysis of a randomized non-inferiority trial.

BACKGROUND: Antenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, its optimal dose remains unknown. A 50% dose reduction was proposed to decrease the potential dose-related long-term neurodevelopmental side effects, including psychological development, sleep, and emotional disorders. Because noninferiority of the half dose in terms of the need for exogenous surfactant was not shown in the primary analysis, its impact on survival without major neonatal morbidity needs to be investigated. OBJECTIVE: This study aimed to investigate the impact of antenatal betamethasone dose reduction on survival of very preterm infants without severe neonatal morbidity, a factor known to have a strong correlation with long-term outcomes. STUDY DESIGN: We performed a post hoc secondary analysis of a randomized, multicenter, double-blind, placebo-controlled, noninferiority trial, testing half (11.4 mg once; n=1620) vs full (11.4 mg twice, 24 hours apart; n=1624) antenatal betamethasone doses in women at risk of preterm delivery. To measure survival without severe neonatal morbidity at hospital discharge among neonates born before 32 weeks of gestation, we used the definition of the French national prospective study on preterm children, EPIPAGE 2, comprising 1 of the following morbidities: grade 3 to 4 intraventricular hemorrhage, cystic periventricular leukomalacia, necrotizing enterocolitis stage ≥2, retinopathy of prematurity requiring anti-vascular endothelial growth factor therapy or laser, and moderate-to-severe bronchopulmonary dysplasia. RESULTS: After exclusion of women who withdrew consent or had pregnancy termination and of participants lost to follow-up (8 in the half-dose and 10 in the full-dose group), the rate of survival without severe neonatal morbidity among neonates born before 32 weeks of gestation was 300 of 451 (66.5%) and 304 of 462 (65.8%) in the half-dose and full-dose group, respectively (risk difference, +0.7%; 95% confidence interval, -5.6 to +7.1). There were no significant between-group differences in the cumulative number of neonatal morbidities. Results were similar when using 2 other internationally recognized definitions of severe neonatal morbidity and when considering the overall population recruited in the trial. CONCLUSION: In the BETADOSE trial, severe morbidity at discharge of newborns delivered before 32 weeks of gestation was found to be similar among those exposed to 11.4-mg and 22.8-mg antenatal betamethasone. Additional studies are needed to confirm these findings.

Extrauterine Growth Restriction: Need for an Accurate Definition.

Neonates show considerable variation in growth that can be recognized through serial measurements of basic variables such as weight, length, and head circumference. If possible, measurement of subcutaneous and total body fat mass can also be useful. These biometric measurements at birth may be influenced by demographics, maternal and paternal anthropometrics, maternal metabolism, preconceptional nutritional status, and placental health. Subsequent growth may depend on optimal feeding, total caloric intake, total metabolic activity, genetic makeup, postnatal morbidities, medications, and environmental conditions. For premature infants, these factors become even more important; poor in utero growth can be an important reason for spontaneous or induced preterm delivery. Later, many infants who have had intrauterine growth restriction (IUGR) and are born small for gestational age (SGA) continue to show suboptimal growth below the 10th percentile, a condition that has been defined as extrauterine growth restriction (EUGR) or postnatal growth restriction (PNGR). More importantly, a subset of these growth-restricted infants may also be at high risk of abnormal neurodevelopmental outcomes. There is a need for well-defined criteria to recognize EUGR/PNGR, so that correctional steps can be instituted in a timely fashion.

Impact on neonatal morbidities after a change in policy to administer antenatal corticosteroids to mothers at risk for late preterm delivery.

OBJECTIVES: Antenatal corticosteroids (ACS) administered to mothers at risk for preterm delivery before 34 weeks has been standard care to improve neonatal outcomes. After introducing a new obstetric policy based on updated recommendations advising the administration of ACS to pregnant women at risk for late preterm (LPT) delivery (34-36 6/7 weeks), we set out to determine the short-term clinical impact on those LPT neonates. METHODS: Retrospective chart review of LPT neonates delivered at NYU Langone Medical Center both one year before and after the policy went into place. We excluded subjects born to mothers with pre-gestational diabetes, multiple gestations, and those with congenital/genetic abnormalities. We also excluded subjects whose mothers already received ACS previously in pregnancy. Subjects were divided into pre-policy and post-policy groups. Neonatal and maternal data were compared for both groups. RESULTS: 388 subjects; 180 in the pre-policy and 208 in the post-policy group. This policy change resulted in a significant increase in ACS administration to mothers who delivered LPT neonates (67.3 vs. 20.6%, p<0.001). In turn, there was a significant reduction in LPT neonatal intensive care unit (NICU) admissions (44.2 vs. 54.4%, p=0.04) and need for respiratory support (27.9 vs. 42.8%, p<0.01). However, we also found an increased incidence of hypoglycemia (49.5 vs. 28.3%, p<0.001). CONCLUSIONS: This LPT ACS policy appears effective in reducing the need for LPT NICU level care overall. However, clinicians must be attentive to monitor for adverse effects like hypoglycemia, and there remains a need for better understanding of potential long-term impacts.

Effect of arachidonic and docosahexaenoic acid supplementation on respiratory outcomes and neonatal morbidities in preterm infants.

BACKGROUND & AIMS: Studies have suggested that supplementation with docosahexaenoic acid (DHA) to preterm infants might be associated with an increased risk of bronchopulmonary dysplasia (BPD). Our aim was to investigate the effect of enteral supplementation with arachidonic acid (ARA) and DHA on short-term respiratory outcomes and neonatal morbidities in very preterm infants. METHODS: This is a secondary analysis of data from the ImNuT (Immature, Nutrition Therapy) study, a randomized double blind clinical trial. Infants with gestational age less than 29 weeks were randomized to receive a daily enteral supplement with ARA 100 mg/kg and DHA 50 mg/kg (intervention) or medium chain triglycerides (MCT) oil (control), from second day of life to 36 weeks postmenstrual age. Study outcomes included duration of respiratory support, incidence of BPD and other major morbidities associated with preterm birth. RESULTS: 120 infants with mean (SD) gestational age 26.4 (1.7) weeks were randomized and allocated to either the intervention or control group. Supplementation with ARA and DHA led to a significant reduction in number of days with respiratory support (mean (95% CI) 63.4 (56.6-71.3) vs 80.6 (72.4-88.8); p = 0.03) and a lower oxygen demand (FiO2) (mean (95% CI) 0.26 (0.25-0.28) vs 0.29 (0.27-0.30); p = 0.03) compared to control treatment. There were no clinically important differences in incidence of BPD and other major morbidities between the treatment groups. CONCLUSIONS: Supplementation with ARA and DHA to preterm infants was safe and might have a beneficial effect on respiratory outcomes. CLINICAL TRIAL REGISTRATION: The trial has been registered in www. CLINICALTRIALS: gov, ID: NCT03555019.

Neonatal Morbidities and Feeding Tolerance Outcomes in Very Preterm Infants, before and after Introduction of Probiotic Supplementation.

While probiotics are reported to reduce the risks of neonatal morbidities, less is known about probiotics and feeding tolerance. With this retrospective cohort study, we investigate whether introduction of probiotic supplementation as the standard of care was associated with fewer neonatal morbidities and improved feeding tolerance in very preterm infants. Using the Swedish Neonatal Quality Register, 345 live-born very preterm infants (28-31 weeks' gestation), from January 2019-August 2021, in NICUs in Stockholm, Sweden, either received probiotic supplementation (Bifidobacterium infantis, Bifidobacterium lactis, Streptococcusthermophilus) (139) or no supplementation (206); they were compared regarding a primary composite outcome of death, sepsis, and/or necrotising enterocolitis and secondary outcomes: time to full enteral feeding and antibiotics use. Probiotics seemed associated with a reduced risk of the composite outcome (4.3% versus 9.2%, p = 0.08). In the subgroup of 320 infants without the primary outcome, probiotics were associated with shorter time to full enteral feeding (6.6 days versus 7.2 days) and less use of antibiotics (5.2 days versus 6.1 days). Our findings suggest that probiotics improve feeding tolerance and further support that very preterm infants may benefit from probiotic supplementation.

Changes Overtime in Perinatal Management and Outcomes of Extremely Preterm Infants in One Tertiary Care Romanian Center.

Background and Objectives: Extremely preterm infants were at increased risk of mortality and morbidity. The purpose of this study was to: (1) examine changes over time in perinatal management, mortality, and major neonatal morbidities among infants born at 250-286 weeks' gestational age and cared for at one Romanian tertiary care unit and (2) compare the differences with available international data. Material and Methods: This study consisted of infants born at 250-286 weeks in one tertiary neonatal academic center in Romania during two 4-year periods (2007-2010 and 2015-2018). Major morbidities were defined as any of the following: severe intraventricular hemorrhage (IVH), severe retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), and bronchopulmonary dysplasia (BPD). Adjusted logistic regression models examined the association between the mortality and morbidity outcome and the study period. Results: The two cohorts differed with respect to antenatal antibiotics and rates of cesarean birth but had similar exposure to antenatal steroids and newborn referral to the tertiary care center. In logistic regression analyses, infants in the newer compared to the older cohort had a lower incidence of death (OR: 0.19; 95% CI: 0.11-0.35), a lower incidence of IVH (OR: 0.26; 95% CI: 0.15-0.46), and increased incidence of NEC (OR: 19.37; 95% CI: 2.41-155.11). Conclusions: Changes over time included higher use of antenatal antibiotics and cesarean delivery and no change in antenatal steroids administration. Overall mortality was lower in the newer cohort, especially for infants 250-266 weeks' gestation, NEC was higher while BPD and ROP were not different.

Neonatal morbidities and postnatal growth failure in very low birth weight, very preterm infants.

AIM: To assess postnatal growth in infants with and without major neonatal morbidities. METHODS: This study is based on analysis of data collected by the Israel Neonatal Network on VLBW infants (≤1500 g) born in Israel from 2009 to 2018. Postnatal growth was assessed in two 5 years epochs: 2009-2013 (n = 4583) and 2014-2018 (n = 4558). Outcome was considered as severe, mild and no postnatal growth failure (PNGF). Morbidities included respiratory distress syndrome, bronchopulmonary dysplasia, necrotising enterocolitis, patent ductus arteriosus and grades 3-4 intraventricular haemorrhage. Multinomial logistic regression analyses with the generalised estimating equation approach were applied. RESULTS: The study population composed 9141 infants. Of them, 2089 had at least one major morbidity and 7052 infants had none. In infants with no morbidities, 2.1% had severe PNGF, 23.7% mild PNGF and 74.2% had no PNGF, as compared to 13.6%, 43.9% and 42.5%, respectively, in infants with any major neonatal morbidity (p < 0.0001). CONCLUSION: Despite enormous advances in neonatal care, postnatal growth remains a challenge in VLBW infants, particularly in infants with major neonatal morbidities. Along with efforts to decrease morbidity, a more personalised plan and follow-up may be required in infants with major morbidities, given their high risk for diminished growth and potentially, adverse neurodevelopmental outcomes.

Contribution of portable obstetric ultrasound service innovation in averting maternal and neonatal morbidities and mortalities at semi-urban health centers of Ethiopia: a retrospective facility-based study.

BACKGROUND: The maternal and neonatal mortalities in Ethiopia are high. To achieve the Sustainable Development Goals, innovations in ultrasound scanning and surveillance activities have been implemented at health centers for over 2 years. This study aims to estimate the contribution of obstetric ultrasound services on averted maternal and neonatal morbidities and mortalities in Ethiopia. METHODS: A retrospective facility-based cross-sectional study design was conducted in 25 selected health centers. Data were extracted from prenatal ultrasound registers. SPSS version 25 was used for analysis. To claim statistically significant relationship among sartorial variables, a chi-square test was analyzed and P < 0.05 was the cut-off point. RESULTS: Over the 2 years, 12,975 pregnant women were scanned and 52.8% of them were residing in rural areas. Abnormal ultrasound was reported in 12.7% and 98.4% of them were referred for confirmation of diagnosis and treatment. The ultrasound service has contributed to the prevention of 1,970 maternal and 19.05 neonatal morbidities and mortalities per 100,000 and 1,000 live births respectively. The averted morbidities and mortalities showed a statistically significant difference among women residing in rural and semi-urban areas, X,2 df (10) = 24.07, P = 0. 007 and X,2 df (5) = 20.87. P = 0.00, 1 respectively. CONCLUSION: After availing the appropriate ultrasound machines with essential supplies and capacitating mid-level providers, significant number of high-risk pregnant women were identified on time and managed or referred to health facilities with safe delivery services. Therefore, scaling-up limited obstetric ultrasound services in similar setups will contribute to achieving the Sustainable Development Goals by 2030. It is recommended to enhance community awareness for improved utilization of ultrasound services by pregnant women before the 24th week of gestational age.

National cohort of infants born before 24 gestational weeks showed increased survival rates but no improvement in neonatal morbidity.

AIM: To describe survival and neonatal morbidities in infants born before 24 weeks of gestation during a 12-year period. METHODS: Data were retrieved from national registries and validated in medical files of infants born before 24 weeks of gestation 2007-2018 in Sweden. Temporal changes were evaluated. RESULTS: In 2007-2018, 282 live births were recorded at 22 weeks and 460 at 23 weeks of gestation. Survival to discharge from hospital of infants born alive at 22 and 23 weeks increased from 20% to 38% (p = 0.006) and from 45% to 67% (p < 0.001) respectively. Caesarean section increased from 12% to 22% (p = 0.038) for infants born at 22 weeks. Neonatal morbidity rates in infants alive at 40 weeks of postmenstrual age (n = 399) were unchanged except for an increase in necrotising enterocolitis from 0 to 33% (p = 0.017) in infants born at 22 weeks of gestation. Bronchopulmonary dysplasia was more common in boys than girls, 90% versus 82% (p = 0.044). The number of infants surviving to 40 weeks doubled over time. CONCLUSION: Increased survival of infants born before 24 weeks of gestation resulted in increasing numbers of very immature infants with severe neonatal morbidities likely to have a negative impact on long-term outcome.

Gestational Age-Related Associations between Early-Life Feeding Trajectories and Growth Outcomes at Term Equivalent Age in Very Preterm Infants.

Establishing the different feeding trajectories based on daily enteral feeding data in preterm infants at different gestational ages (GAs), may help to identify the risks and extrauterine growth restriction (EUGR) outcomes associated with the adverse feeding pattern. In a single center, we retrospectively included 625 infants born at 23-30 weeks of gestation who survived to term-equivalent age (TEA) from 2009 to 2020. The infants were designated into three GA groups: 23-26, 27-28, and 29-30 weeks. The daily enteral feeding amounts in the first 56 postnatal days were analyzed to determine the feeding trajectories. The primary outcomes were EUGR in body weight and head circumference calculated, respectively, by the changes between birth and TEA. Clustering analysis identified two feeding trajectories, namely the improving and adverse patterns in each GA group. The adverse feeding pattern that occurred in 49%, 20%, and 17% of GA 23-26, 27-28, and 29-30 weeks, respectively, was differentiated from the improving feeding pattern as early as day 7 in infants at GA 23-26 and 27-28 weeks, in contrast to day 21 in infants at GA 29-30 weeks. The adverse feeding patterns were associated with sepsis, respiratory, and gastrointestinal morbidities at GA 23-26 weeks; sepsis, hemodynamic and gastrointestinal morbidities at GA 27-28 weeks; and preeclampsia, respiratory, and gastrointestinal morbidities at GA 29-30 weeks. Using the improving feeding group as a reference, the adverse feeding group showed significantly higher adjusted odds ratios of EUGR in body weight and head circumference in infants at GA 23-26 and 27-28 weeks. Identifying the early-life adverse feeding trajectories may help recognize the related EUGR outcomes of preterm infants in a GA-related manner.

Docosahexaenoic acid and bronchopulmonary dysplasia in preterm infants: a systematic review and meta-analysis.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a common and serious complication of extremely preterm birth. Given the anti-inflammatory properties, docosahexaenoic acid (DHA) supplementation has been proposed as a strategy for the management of BPD. This study aimed to investigate the effects of DHA supplementation on BPD based on a systematic review. METHODS: A comprehensive literature search was conducted using ClinicalTrials.Gov, CINAHL, Cochrane Library, EMBASE, MEDLINE, PubMed, and the WHO ICTRP from their respective dates of inception to June 2017. The studies included were randomized controlled trials (RCTs) that enrolled preterm infants <33 weeks of gestational age. Trials were included if DHA supplementation was compared with a control. RESULTS: Four RCTs from five reports (1,966 neonates) met our inclusion criteria. The meta-analysis of these studies showed that DHA supplementation did not decrease the risk of BPD at 36 weeks of postmenstrual age among preterm infants (low certainty of evidence). DHA supplementation did not significantly reduce the risk of other neonatal morbidities including death (low certainty of evidence), BPD at 28 days of life (moderate certainty of evidence), necrotizing enterocolitis (low certainty of evidence), intraventricular hemorrhage, severe retinopathy of prematurity, or sepsis. CONCLUSION: DHA supplementation may not exert significant clinical benefits in the treatment of BPD and other neonatal morbidities.

The possible association between neonatal morbidities and amniotic fluid pH and electrolyte levels in infants of preeclamptic mothers.

BACKGROUND: Preeclampsia is a pregnancy-specific syndrome associated with increased perinatal mortality characterized by hypertension and proteinuria. An increasing number of studies have been published on the effect of preeclampsia on neonatal morbidities. However, there is no study regarding the possible effect of preeclampsia on amniotic fluid pH and electrolytes. The aim of this study was to determine the possible role of amniotic fluid pH and electrolytes for the prediction of and/or association with preeclampsia and neonatal morbidities. METHODS: This was a prospective, case-control study. During cesarean section (C/S), 1 ml of amniotic fluid was aspirated before incision of membranes. Amniotic fluid pH and electrolytes were analyzed by blood gas machine and biochemistry laboratory concurrently. Maternal and neonatal demographic features and clinical outcomes, presence of respiratory morbidities were all recorded. RESULTS: Amniotic fluid pH, sodium and gestational age were found to be independent risk factors for preeclampsia. Subgroup analysis revealed that in early onset preeclampsia group mechanical ventilation duration, duration of 02 therapy, sepsis and intrauterine growth retardation (IUGR) were higher than infants in control group born before 32 gestational weeks. Also, in the early onset preeclampsia group pH and potassium were higher compared with the control group. CONCLUSIONS: To the best of our knowledge, this is the first study that reported the value of amniotic fluid electrolyte analysis for the prediction of preeclampsia and neonatal morbidities in term and preterm infants. However, more studies including a larger number of infants are required to confirm the role of amniotic fluid analysis to predict preeclampsia and/or neonatal morbidities.

A Randomized Controlled Trial Comparing Two Doses of Caffeine for Apnoea in Prematurity.

Caffeine is the most commonly used methyl xanthine for the prevention of apnoea in prematurity, but the ideal dose was uncertain, until now. This study compared two doses of caffeine for the prevention of apnoea in prematurity. A clinical trial was conducted on 78 preterm infants ≤32 weeks in Neonatal Intensive Care Unit. They were randomly allocated to receive the intervention (loading 40 mg/kg/day and maintenance of 20 mg/kg/day) or the control (loading 20 mg/kg/day and maintenance of 10 mg/kg/day) dose of caffeine. The primary outcome of the study was the frequency and total days of apnoea per duration of treatment for both groups. The frequency of apnoea ranged from zero to fourteen in the intervention group and zero to twelve in the control group. There was no statistically significant difference between the groups, with a p-value of 0.839. The number of days of apnoea was also similar between both groups, with a p-value of 0.928. There was also no significant difference in adverse events between both regimens. This study did not support the use of higher doses of caffeine as a prevention for apnoea in prematurity.

Antenatal corticosteroid therapy is associated with a lower risk of cystic periventricular leukomalacia.

AIM: To evaluate the association of antenatal corticosteroids (ACS) therapy on the risk for cystic periventricular leukomalacia (c-PVL) in very low birth weight (VLBW), very preterm infants, whilst accounting for the occurrence of major neonatal morbidities; sepsis, necrotising enterocolitis, intraventricular haemorrhage and bronchopulmonary dysplasia. METHODS: Population-based observational cohort study applying data collected by the Israel national VLBW infant database from 1995-2016. RESULTS: Cystic PVL was diagnosed in 692 (6.8%) of the 10,170 study infants. Among 7522 infants exposed to ACS, the rate of c-PVL was 5.4%, compared to 10.7% among those not exposed (p < 0.0001). ACS was associated with significantly lower odds for c-PVL (Odds Ratio [OR] 0.69, 95% confidence interval [CI] 0.57-0.84). In subgroup analyses, excluding infants with one or more morbidities the rates of c-PVL ranged from 2.7% to 5.4% among infants exposed to ACS compared to 5.6% to 10.7% in those not exposed (all p < 0.0001). ACS was associated with significantly lower OR's for c-PVL in all subgroups, ranging from 0.52 (95% CI 0.40-0.66) to 0.62 (95% CI 0.50-0.77). CONCLUSION: Infants exposed to ACS had a significantly lower risk of c-PVL. Subgroup analyses excluding infants with major neonatal comorbidities showed a consistent reduction of 40%-50% in the risk for c-PVL following ACS therapy.

Antecedents and outcomes of hypothermia at admission to the neonatal intensive care unit.

Objective: To evaluate the association between morbidities preceding and following neonatal intensive care unit (NICU) admission with hypothermia.Study design: NICU admission temperatures for 1271 infants admitted to the NICU at Tufts Medical Center (TMC) between 2012 and 2015 were compared to all Vermont Oxford Network (VON) centers in 2014. We analyzed demographic data, prevalence of hypothermia, and associations with prenatal and neonatal morbidities.Result: Prevalence of hypothermia at TMC was 19% compared to 25% in the VON. We found a significant association between hypothermia and maternal race, birth weight, gestational age, antenatal steroids, chorioamnionitis, mode of delivery, and Apgar scores.Conclusion: Continued emphasis should be placed on avoiding neonatal hypothermia during the first hours of postnatal life.

Type of Re-Hospitalization and Association with Neonatal Morbidities in Infants of Very Low Birth Weight.

BACKGROUND: Preterm infants are at high risk for long-term morbidities and an increased rate of re-hospitalization. OBJECTIVE: The aim of this study was to evaluate the type of re-hospitalization of very low birth weight (VLBW) infants, from infancy through adolescence, and to assess the association of neonatal morbidities with specific types of re-hospitalization. STUDY DESIGN: The study cohort comprised 6,385 VLBW infants who were registered with the Maccabi Healthcare Services (MHS) from their birth hospitalization. Data were collected for up to 18 years (median 10.7 years) following neonatal intensive care unit discharge. Hospitalization types were determined from the MHS coding. Neonatal morbidities included necrotizing enterocolitis (NEC), grades 3-4 intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), bronchopulmonary dysplasia (BPD), and retinopathy of prematurity (ROP). Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) were calculated using the Cox proportional hazards model. RESULTS: Overall, 3,956 infants were re-hospitalized at least once and a total of 11,595 hospitalization types were identified. NEC, IVH, PVL, and BPD were associated with significantly higher aHRs for general pediatric (aHR 1.28-1.55), general surgical (aHR 1.18-1.46), and pediatric intensive care unit (aHR 1.57-2.04) hospitalizations. IVH and PVL were associated with significantly higher aHRs for orthopedic (aHR 2.12 and 4.88, respectively) and ophthalmology (1.76 and 4.02, respectively) hospitalizations. IVH was associated with a 14.2-fold higher aHR for neurosurgical admissions, and ROP with a 1.62-fold higher aHR for ophthalmology hospitalizations. CONCLUSION: Among VLBW infants, specific patterns of re-hospitalization types associated with major neonatal morbidities were identified as particularly high risks for orthopedic and ophthalmology hospitalizations in infants with IVH and PVL, and for intensive care admissions in infants with NEC and BPD.

Elective Deliveries and Neonatal Outcomes in Full-Term Pregnancies.

Cesarean and induced delivery rates have risen substantially in recent decades and currently account for over one-third and one-fourth of US births, respectively. Initiatives to encourage delaying deliveries until a gestational age of 39 weeks appear to have slowed the increases but have not led to declines. The rates are at historic highs and the consequences of these interventions when not medically necessary have not been systematically explored at the population level. In this study, we used population-level data on births in New Jersey (1997-2011) to document trends in elective deliveries (induced vaginal delivery, cesarean delivery with no labor trial, and cesarean delivery after induction) and estimate logistic and linear regression models of associations between delivery method and neonatal morbidities and cost-related outcomes in low-risk pregnancies. We found that elective deliveries more than doubled during the observation period and were associated with neonatal morbidities and cost-related outcomes even at gestational ages of 39 and 40 weeks. Findings suggest that delaying beyond 39 weeks and avoiding delivery interventions when not medically necessary would improve infant health and reduce health-care costs.

Relative contributions of prenatal complications, perinatal characteristics, neonatal morbidities and socio-economic conditions of preterm infants on the occurrence of developmental disorders up to 7 years of age.

BACKGROUND: To investigate the relative contributions of prenatal complications, perinatal characteristics, neonatal morbidities and socio-economic conditions on the occurrence of motor, sensory, cognitive, language and psychological disorders in a large longitudinal preterm infant population during the first 7 years after birth. METHODS: The study population comprised 4122 infants born at <35 weeks of gestation who were followed for an average of 74.0 months after birth. Developmental disorders, including motor, sensory, cognitive, language and psychological, were assessed at each follow-up visit from 18 months to 7 years of age. The investigated determinants included prenatal complications (prolonged rupture of membranes >24 hours, intrauterine growth restriction, preterm labour and maternal hypertension), perinatal characteristics (gender, multiple pregnancies, gestational age, birth weight, APGAR score and intubation or ventilation in the delivery room), neonatal complications (low weight gain during hospitalization, respiratory assistance, severe neurological anomalies, nosocomial infections) and socio-economic characteristics (socio-economic level, parental separation, urbanicity). Based on hazard ratios determined using a propensity score matching approach, population-attributable fractions (PAF) were calculated for each of the four types of determinants and for each developmental disorder. RESULTS: The percentages of motor, sensory, cognitive, language and psychological disorders were 17.0, 13.4, 29.1, 25.9 and 26.1%, respectively. The PAF for the perinatal characteristics were the highest and they were similar for the different developmental disorders considered (around 60%). For the neonatal and socio-economic determinants, the PAF varied according to the disorder, with contributions of up to 17% for motor and 27% for language disorders, respectively. Finally, prenatal complications had the lowest contributions (between 6 and 13%). CONCLUSIONS: This study illustrates the heterogeneity of risk factors on the risk of developmental disorder in preterm infants. These results suggest the importance of considering both medical and psycho-social follow-ups of preterm infants and their families.

Impact of major neonatal morbidities on adolescents born at 23-25 weeks of gestation.

AIM: More infants born extremely preterm (EPT) are surviving, but major neonatal morbidities are consistently high. This study examined the impact of bronchopulmonary dysplasia (BPD), brain injuries and severe retinopathy of prematurity (ROP) on adolescents who were born EPT. METHODS: We focused on EPT infants born at 23-25 weeks at the Swedish university hospitals in Uppsala and Umeå from January 1992 to December 1998. The poor outcome data covered 140 of 142 who survived to 36 weeks, and the chronic conditions data reported by parents covered 132 of 134 still alive at 10-15 years. RESULTS: Of the 140 survivors at 36 weeks, 29 (21%) had poor outcomes: eight of 140 (6%) died, and 21 of 132 (16%) adolescent survivors had severe neurodevelopmental disabilities (NDD). BPD, severe ROP and/or brain injuries correlated independently with poor outcome. Of those adolescents who were free from BPD, brain injury and severe ROP, 6% had a severe NDD. The corresponding rates with any one, any two or all three neonatal morbidities were 21, 33 and 67%, respectively. BPD and brain injuries were associated with high rates of chronic conditions at 10-15 years of age resulting in functional limitations. CONCLUSION: In adolescent EPT survivors, BPD and brain injuries were associated with high rates of chronic conditions and special healthcare needs.

Antenatal corticosteroids: an assessment of anticipated benefits and potential risks.

Antenatal corticosteroids are standard of care for pregnancies at risk of preterm delivery between 24-34 weeks' gestational age. Recent trials demonstrate modest benefits from antenatal corticosteroids for late preterm and elective cesarean deliveries, and antenatal corticosteroids for periviable deliveries should be considered with family discussion. However, many women with threatened preterm deliveries receive antenatal corticosteroids but do not deliver until >34 weeks or at term. The net effect is that a substantial fraction of the delivery population will be exposed to antenatal corticosteroids. There are gaps in accurate assessments of benefits of antenatal corticosteroids because the randomized controlled trials were performed prior to about 1990 in pregnancies generally >28 weeks. The care practices for the mother and infant survival were different than today. The randomized controlled trial data also do not strongly support the optimal interval from antenatal corticosteroid treatment to delivery of 1-7 days. Epidemiology-based studies using large cohorts with >85% of at-risk pregnancies treated with antenatal corticosteroids probably overestimate the benefits of antenatal corticosteroids. Although most of the prematurity-associated mortality is in low-resource environments, the efficacy and safety of antenatal corticosteroids in those environments remain to be evaluated. The short-term benefits of antenatal corticosteroids for high-risk pregnancies in high-resource environments certainly justify antenatal corticosteroids as few risks have been identified over many years. However, cardiovascular and metabolic abnormalities have been identified in large animal models and cohorts of children exposed to antenatal corticosteroids that are consistent with fetal programming for adult diseases. These late effects of antenatal corticosteroids suggest caution for the expanded use of antenatal corticosteroids beyond at-risk pregnancies at 24-34 weeks. A way forward is to develop noninvasive fetal assessments to identify pregnancies across a wider gestational age that could benefit from antenatal corticosteroids.