Evaluating WHO-Recommended Interventions for Preterm Birth: A Mathematical Model of the Potential Reduction of Preterm Mortality in Sub-Saharan Africa.

BACKGROUND: Preterm birth, a leading cause of neonatal mortality, has the highest burden in low-income countries. In 2015, the World Health Organization (WHO) published recommendations for interventions to improve preterm outcomes. Our analysis uses the Maternal and Neonatal Directed Assessment of Technology (MANDATE) model to evaluate the potential effects that WHO-recommended interventions could have had on preterm mortality in sub-Saharan Africa in 2015. METHODS: We modeled preterm birth subconditions causing mortality (respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, sepsis, birth asphyxia, and low birth weight). For each subcondition, models were populated with estimates of WHO-recommended intervention prevalence, case fatality, coverage, and efficacy. Various scenarios modeled improved coverage of single and combined interventions compared with baseline. RESULTS: In 2015, approximately 500,000 neonatal deaths due to preterm birth occurred in sub-Saharan Africa. Single interventions with the greatest impact on preterm mortality included oxygen/continuous positive airway pressure (44,000 lives saved), cord care (38,500 lives saved), and breastfeeding (30,200 lives saved). Combined with improved diagnosis/transfer to a hospital, the impact of interventions showed greater reductions in mortality (oxygen/continuous positive airway pressure, 134,100 lives saved; antibiotics, 28,600 lives saved). Combined interventions had the greatest impact. Together, hospital delivery with comprehensive care for respiratory distress syndrome saved 190,600 lives, and comprehensive thermal care, breastfeeding, and prevention/treatment for sepsis saved 94,400 lives. CONCLUSION: In 2015, WHO-recommended interventions could have saved the lives of nearly 300,000 infants born preterm in sub-Saharan Africa. Combined interventions are necessary to maximize impact. Mathematical models such as MANDATE can estimate effects on health outcomes to allow health officials to prioritize implementation strategies.

Melatonin as a master regulator of cell death and inflammation: molecular mechanisms and clinical implications for newborn care.

Melatonin, more commonly known as the sleep hormone, is mainly secreted by the pineal gland in dark conditions and regulates the circadian rhythm of the organism. Its intrinsic properties, including high cell permeability, the ability to easily cross both the blood-brain and placenta barriers, and its role as an endogenous reservoir of free radical scavengers (with indirect extra activities), confer it beneficial uses as an adjuvant in the biomedical field. Melatonin can exert its effects by acting through specific cellular receptors on the plasma membrane, similar to other hormones, or through receptor-independent mechanisms that involve complex molecular cross talk with other players. There is increasing evidence regarding the extraordinary beneficial effects of melatonin, also via exogenous administration. Here, we summarize molecular pathways in which melatonin is considered a master regulator, with attention to cell death and inflammation mechanisms from basic, translational and clinical points of view in the context of newborn care.

Nifedipine maintenance tocolysis and perinatal outcome: an individual participant data meta-analysis.

BACKGROUND: Preterm birth is the leading cause of neonatal mortality and morbidity in developed countries. Whether continued tocolysis after 48 hours of rescue tocolysis improves neonatal outcome is unproven. OBJECTIVES: To evaluate the effectiveness of maintenance tocolytic therapy with oral nifedipine on the reduction of adverse neonatal outcomes and the prolongation of pregnancy by performing an individual patient data meta-analysis (IPDMA). SEARCH STRATEGY: We searched PubMed, Embase, and Cochrane databases for randomised controlled trials of maintenance tocolysis therapy with nifedipine in preterm labour. SELECTION CRITERIA: We selected trials including pregnant women between 24 and 36(6/7)  weeks of gestation (gestational age, GA) with imminent preterm labour who had not delivered after 48 hours of initial tocolysis, and compared maintenance nifedipine tocolysis with placebo/no treatment. DATA COLLECTION AND ANALYSIS: The primary outcome was perinatal mortality. Secondary outcome measures were intraventricular haemorrhage (IVH), necrotising enterocolitis (NEC), infant respiratory distress syndrome (IRDS), prolongation of pregnancy, GA at delivery, birthweight, neonatal intensive care unit admission, and number of days on ventilation support. Pre-specified subgroup analyses were performed. MAIN RESULTS: Six randomised controlled trials were included in this IPDMA, encompassing data from 787 patients (n = 390 for nifedipine; n = 397 for placebo/no treatment). There was no difference between the groups for the incidence of perinatal death (risk ratio, RR 1.36; 95% confidence interval, 95% CI 0.35-5.33), intraventricular haemorrhage (IVH) ≥ grade II (RR 0.65; 95% CI 0.16-2.67), necrotising enterocolitis (NEC) (RR 1.15; 95% CI 0.50-2.65), infant respiratory distress syndrome (IRDS) (RR 0.98; 95% CI 0.51-1.85), and prolongation of pregnancy (hazard ratio, HR 0.74; 95% CI 0.55-1.01). CONCLUSION: Maintenance tocolysis is not associated with improved perinatal outcome and is therefore not recommended for routine practice. TWEETABLE ABSTRACT: Nifedipine maintenance tocolysis is not associated with improved perinatal outcome or pregnancy prolongation.

Risk factors and neonatal/infant mortality risk of small-for-gestational-age and preterm birth in rural Nepal.

OBJECTIVE: Our study seeks to elucidate risk factors for and mortality consequences of small-for-gestational-age (SGA) and preterm birth in rural Nepal. In contrast with previous literature, we distinguish the epidemiology of SGA and preterm birth from each other. METHODS: We analyzed data from a maternal micronutrient supplementation trial in rural Nepal (n = 4130). We estimated adjusted risk ratios (aRR) for risk factors of SGA and preterm birth, and aRRs for the associations between SGA/preterm birth and neonatal/infant mortality. We used mutually exclusive categories of term-appropriate-for-gestational-age (AGA), term-SGA, preterm-AGA, and preterm-SGA (with term-AGA as reference) in our analyses. RESULTS: Stunted (<145 cm) and wasted (<18.5 kg/m(2)) women both had increased risk of having term-SGA (aRR 1.36, 95% CI: 1.14-1.61, aRR 1.22, 95% CI: 1.09-1.36 respectively) and preterm-SGA (aRR 2.48, 95% CI: 1.29-4.74, aRR 1.99, 95% CI: 1.33-2.97 respectively), but not preterm-AGA births. Similar results were found for low maternal weight gain per gestational week. Those born preterm-SGA generally experienced the highest neonatal and infant mortality risk, although term-SGA and preterm-AGA newborns also had statistically significantly high mortality risks compared to term-AGA babies. CONCLUSIONS: SGA and preterm birth have distinct risk factors and mortality patterns. Maternal chronic and acute malnutrition appear to be associated with SGA outcomes. Because of high SGA prevalence in South Asia and the increased neonatal and infant mortality risk associated with SGA, there is an urgent need to intervene with effective interventions.

Late prematurity in twins: a Polish multicenter study.

The study aimed at investigating the impact of late prematurity (LPT) on neonatal outcome in twins and neonatal morbidity and mortality within LPT with regard to the completed weeks of gestation. The study was conducted in six tertiary obstetric departments from different provinces of Poland (Warsaw, Lublin, Poznan, Wroclaw, Bytom). It included 465 twin deliveries in the above centers in 2012. A comparative analysis of maternal factors, the course of pregnancy and delivery and neonatal outcome between LPT (34 + 0-36 + 6 weeks of gestation) and term groups (completed 37 weeks) was performed. The neonatal outcome included short-term morbidities. The analysis of neonatal complication rates according to completed gestational weeks was carried out. Out of 465 twin deliveries 213 (44.8%) were LPT and 156 (33.55%) were term. There were no neonatal deaths among LPT and term twins. One-third of LPT newborns suffered from respiratory disorders or required antibiotics, 40% had jaundice requiring phototherapy, and 30% were admitted to NICU. The analysis of neonatal morbidity with regard to each gestational week at delivery showed that most analyzed complications occurred less frequently with the advancing gestational age, especially respiratory disorders and NICU admissions. The only two factors with significant influence on neonatal morbidity rate were neonatal birth weight (OR = 0.43, 95% CI = 0.2-0.9, p = .02) and gestational age at delivery (OR = 0.62, 95% CI = 0.5-0.8, p < .01). LPT have a higher risk of neonatal morbidity than term twins. Gestational age and neonatal birth weight seem to play a crucial role in neonatal outcome in twins.

Zinc supplementation reduces morbidity and mortality in very-low-birth-weight preterm neonates: a hospital-based randomized, placebo-controlled trial in an industrialized country.

BACKGROUND: Zinc plays a pivotal role in the pathogenesis of many diseases and in body growth. Preterm neonates have high zinc requirements. OBJECTIVE: The objective of the study was to investigate the efficacy of zinc supplementation in reducing morbidity and mortality in preterm neonates and to promote growth. DESIGN: This was a prospective, double-blind, randomized controlled study of very-low-birth-weight preterm neonates randomly allocated on the seventh day of life to receive (zinc group) or not receive (control group) oral zinc supplementation. Total prescribed zinc intake ranged from 9.7 to 10.7 mg/d in the zinc group and from 1.3 to 1.4 mg/d in the placebo control group. The main endpoint was the rate of neonates with ≥ 1 of the following morbidities: late-onset sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, periventricular leucomalacia, and retinopathy of prematurity. Secondary outcomes were mortality and body growth. RESULTS: We enrolled 97 neonates in the zinc group and 96 in the control group. Morbidities were significantly lower in the zinc group (26.8% compared with 41.7%; P = 0.030). The occurrence of necrotizing enterocolitis was significantly higher in the control group (6.3% compared with 0%; P = 0.014). Mortality risk was higher in the placebo control group (RR: 2.37; 95% CI: 1.08, 5.18; P = 0.006). Daily weight gain was similar in the zinc (18.2 ± 5.6 g · kg⁻¹ · d⁻¹) and control (17.0 ± 8.7 g · kg⁻¹ · d⁻¹) groups (P = 0.478). CONCLUSION: Oral zinc supplementation given at high doses reduces morbidities and mortality in preterm neonates. This trial was registered in the Australian New Zealand Clinical Trial Register as ACTRN12612000823875.

Vitamin A supplementation in extremely low-birth-weight infants: subgroup analysis in small-for-gestational-age infants.

OBJECTIVE: Preterm infants with intrauterine growth restriction are at increased risk of respiratory distress syndrome and bronchopulmonary dysplasia (BPD). A randomized clinical trial by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network demonstrated that vitamin A supplementation in extremely low-birth-weight (ELBW) preterm infants requiring early respiratory support decreased the risk of developing BPD. STUDY DESIGN: A subgroup analysis of small-for-gestational-age (SGA) infants from the original NICHD trial was performed to test the hypothesis that in infants requiring early respiratory support, vitamin A supplementation decreases the relative risk of BPD or death in premature SGA infants to a greater extent than in gestational age-equivalent vitamin A-treated appropriate-for-gestational-age (AGA) infants. RESULTS: Although vitamin A supplementation significantly increased serum retinol concentrations in AGA ELBW infants (median [5th percentile, 95th percentile]: 16.3 [-7.0, 68.8] versus 2.4 [-13.9, 55.1]; p < 0.001), no increases were noted in SGA ELBW infants. CONCLUSIONS: Given the limited power of this analysis due to a low number of SGA infants, these data did not provide evidence to support the hypothesis that vitamin A supplementation in preterm SGA infants requiring early respiratory support decreases the relative risk of BPD or death as compared with preterm AGA infants.

Prevalence and morbidity of late preterm infants: current status in a medical center of Northern Taiwan.

BACKGROUND: "Late preterm" defines infants born at 34(0/7) through 36(6/7) weeks' gestation, which comprise a majority of preterm births. These infants were treated clinically as "near-term" in the past, but recent studies have implied increased morbidities that differentiate late preterm and term infants. The purpose of this study was to examine the prevalence and clinical complications that could be associated with late preterm birth, as compared to term. METHODS: This was a retrospective cohort study that reviewed infants born in a medical center in Northern Taiwan during a 2-year period between 2008 and 2009. Maternal obstetrical factors, neonatal demographic distributions, and neonatal complications were compared between full-term and late preterm deliveries. RESULTS: During the study period, there were 7998 live births in the institute, including 6507 term and 1491 preterm infants. Of the latter, there were 914 (61.3%) born after 34 weeks' gestation. The Neonatal Intensive Care Unit (NICU) (including a special care nursery) admission rate was higher in late preterm infants when compared to term (36% vs. 2%), and was 74%, 43%, and 21% in infants born at 34, 35, and 36 weeks' gestation, respectively. Compared with term infants, late-preterm infants had longer hospital stay if admitted to NICU (including special care nursery) (17 days vs. 10 days), and they were associated with increased risk of neonatal morbidities, including respiratory distress syndrome (2.6% vs. 0.02%), respiratory distress of other etiologies (16% vs. 2%), culture-proven sepsis (0.7% vs. 0.2%), hypoglycemia (3% vs. 0.4%), temperature instability (0.4% vs. 0.05%), feeding difficulty (2% vs. 0.4%), and hyperbilirubinemia needing phototherapy (14% vs. 3%). Late-preterm infants also had higher hospital readmission rate (4.4% vs. 2.3%, p<0.001) and neonatal mortality rate (0.3% vs. 0.08%, p=0.03). CONCLUSION: Late-preterm infants have increased risk of neonatal morbidities associated with organ immaturity. The results of this study emphasize the importance of judicious obstetrical decision-making when considering late preterm delivery, and the need to set up anticipatory clinical guidelines for the care of late preterm infants.

Analysis of neonatal morbidity and mortality in late-preterm newborn infants.

OBJECTIVE: To compare mortality and the principal intercurrent clinical conditions suffered by late-preterm newborn infants born with gestational ages of 34 full weeks to 36 weeks and 6 days, and full term newborns. METHODS: This was a cross-sectional study of all preterm newborn infants born at a public hospital from August 2010 to August 2011. The study sample comprised late-preterm infants (cases) and a group of full term newborns (controls). Three controls were enrolled for each case. Maternal, gestational and neonatal variables were analyzed. Means and standard deviations were used to compare numerical variables between case and control groups using Student's t test and the Mann-Whitney test; Pearson's chi-square was used for categorical variables. Odds ratios and 95% confidence intervals were calculated to estimate risk. RESULTS: The study sample comprised 239 late-preterm infants and 698 full term newborns. Mothers aged over 35 years and/or with a history of previous premature deliveries had a higher proportion of late-preterm children. The following gestational variables were associated with late-preterm delivery: hypertension, infectious diseases, rupture of membranes more than 18 hours previously and multiple pregnancies. When compared with full term newborns, late-preterms were statistically more likely to be subject to hypothermia/hyperthermia, hypoglycemia, respiratory pathologies, resuscitation in the delivery room, phototherapy, supplementary feeding, mechanical ventilation, venous infusions, antibiotics and admission to the neonatal intensive care unit, resulting in a nine times greater neonatal mortality rate. Intercurrent conditions were inversely related to gestational age. CONCLUSION: Late-preterm newborn infants had a mortality rate nine times that of full term infants and were exposed to a greater risk of intercurrent conditions during the neonatal period. These intercurrent conditions were inversely related to gestational age.

Zinc supplementation during pregnancy protects against lipopolysaccharide-induced fetal growth restriction and demise through its anti-inflammatory effect.

LPS is associated with adverse developmental outcomes, including preterm delivery, fetal death, teratogenicity, and intrauterine growth restriction (IUGR). Previous reports showed that zinc protected against LPS-induced teratogenicity. In the current study, we investigated the effects of zinc supplementation during pregnancy on LPS-induced preterm delivery, fetal death and IUGR. All pregnant mice except controls were i.p. injected with LPS (75 µg/kg) daily from gestational day (GD) 15 to GD17. Some pregnant mice were administered zinc sulfate through drinking water (75 mg elemental Zn per liter) throughout the pregnancy. As expected, an i.p. injection with LPS daily from GD15 to GD17 resulted in 36.4% (4/11) of dams delivered before GD18. In dams that completed the pregnancy, 63.2% of fetuses were dead. Moreover, LPS significantly reduced fetal weight and crown-rump length. Of interest, zinc supplementation during pregnancy protected mice from LPS-induced preterm delivery and fetal death. In addition, zinc supplementation significantly alleviated LPS-induced IUGR and skeletal development retardation. Further experiments showed that zinc supplementation significantly attenuated LPS-induced expression of placental inflammatory cytokines and cyclooxygenase-2. Zinc supplementation also significantly attenuated LPS-induced activation of NF-κB and MAPK signaling in mononuclear sinusoidal trophoblast giant cells of the labyrinth zone. It inhibited LPS-induced placental AKT phosphorylation as well. In conclusion, zinc supplementation during pregnancy protects against LPS-induced fetal growth restriction and demise through its anti-inflammatory effect.

Análise da morbiletalidade neonatal em recém-nascidos pré-termo tardios / Analysis of neonatal morbidity and mortality in late-preterm newborn infants

OBJETIVO: Comparar as taxas de óbito e as principais intercorrências clínicas entre recém-nascidos pré-termo tardios nascidos com idade gestacional entre 34 semanas completas e 36 semanas e 6 dias e recém-nascidos a termo. MÉTODOS: Estudo transversal envolvendo todos os recém-nascidos pré-termo tardios nascidos entre agosto de 2010 e agosto de 2011. A população do estudo foi constituída pelos recém-nascidos pré-termo tardios (casos) e um grupo de recém-nascidos a termo (controles), sendo selecionados três controles para cada caso. Foram analisadas variáveis maternas, da gestação e neonatais. Na análise estatística, utilizaram-se médias, desvios padrão e testes t de Student e de Mann-Whitney para variáveis numéricas, o qui-quadrado de Pearson para variáveis categóricas e estimativa de risco pela odds ratio com intervalo de confiança de 95%. RESULTADOS: A população do estudo foi constituída por 239 recém-nascidos pré-termo tardios e 698 recém-nascidos a termo. As gestantes com mais de 35 anos e/ou história de prematuros prévios tiveram um número maior de pré-termo tardios. As variáveis da gestação relacionadas com o pré-termo tardio foram a hipertensão, doenças infecciosas, ruptura de membrana há mais de 18 horas e gravidez gemelar. Os recém-nascidos pré-termo, em comparação com os recém-nascidos a termo, apresentaram estatisticamente mais hipo/hipertermia, hipoglicemia, patologias respiratórias, necessidade de reanimação em sala de parto, necessidade de fototerapia, uso de complemento alimentar, necessidade de ventilação mecânica, infusão venosa, uso de antibiótico e internação em unidade de tratamento intensivo neonatal, sendo a sua taxa de óbito neonatal nove vezes maior. As intercorrências se mostraram inversamente relacionadas à idade gestacional. CONCLUSÃO: Os recém-nascidos pré-termo tardios apresentaram uma taxa de óbito nove vezes maior do que os recém-nascidos a termo e maior risco de intercorrências no período neonatal, sendo estas inversamente relacionadas com a idade gestacional.

OBJECTIVE: To compare mortality and the principal intercurrent clinical conditions suffered by late-preterm newborn infants born with gestational ages of 34 full weeks to 36 weeks and 6 days, and full term newborns. METHODS: This was a cross-sectional study of all preterm newborn infants born at a public hospital from August 2010 to August 2011. The study sample comprised late-preterm infants (cases) and a group of full term newborns (controls). Three controls were enrolled for each case. Maternal, gestational and neonatal variables were analyzed. Means and standard deviations were used to compare numerical variables between case and control groups using Student's t test and the Mann-Whitney test; Pearson's chi-square was used for categorical variables. Odds ratios and 95% confidence intervals were calculated to estimate risk. RESULTS: The study sample comprised 239 late-preterm infants and 698 full term newborns. Mothers aged over 35 years and/or with a history of previous premature deliveries had a higher proportion of late-preterm children. The following gestational variables were associated with late-preterm delivery: hypertension, infectious diseases, rupture of membranes more than 18 hours previously and multiple pregnancies. When compared with full term newborns, late-preterms were statistically more likely to be subject to hypothermia/hyperthermia, hypoglycemia, respiratory pathologies, resuscitation in the delivery room, phototherapy, supplementary feeding, mechanical ventilation, venous infusions, antibiotics and admission to the neonatal intensive care unit, resulting in a nine times greater neonatal mortality rate. Intercurrent conditions were inversely related to gestational age. CONCLUSIONS: Late-preterm newborn infants had a mortality rate nine times that of full term infants and were exposed to a greater risk of intercurrent conditions during the neonatal period. These intercurrent conditions were inversely related to gestational age.

Morbilidad neonatal de los prematuros tardíos en embarazos únicos: estudio de caso-control / Neonatal morbidity of late preterm: a case-control study

Objetivo: Comparar los riesgos de morbilidad neonatal entre los prematuros tardíos (PT) y neonatos de término. Método: Estudio de caso control. Se revisan fichas clínicas de partos durante el año 2007. Se excluyen neonatos con malformaciones congénitas mayores, alteración neuromuscular, embarazos múltiples y aneuploidias. Los casos corresponden a todo PT nacido durante el periodo estudiado y los controles a nacidos de término en el mismo periodo. Los resultados neonatales fueron obtenidos y los riesgos calculados usando pruebas de Chi cuadrado y exacto de Fisher. Resultados: Se identifican 1536 partos, con una tasa de PT de 7,1 por ciento (109 casos), 62 cumplieron con criterios de inclusión. El grupo control consistió en 124 partos de término. PT presentaron 2 veces más riesgo de cesárea (p=0,0094) que los de término. El riesgo de ser admitido en UCIN fue de 88 (p=0,000). Los riesgos de morbilidad neonatal fueron: SDR (OR 23; p=0,000), hipoglicemia (OR 6; p=0,014), hipocalcemia (OR 6; p=0,014), hiperbilirrubinemia (OR 28; p=0,000) y necesidad de fototerapia (OR 23; p=0,000). No hubo diferencias en la presentación de enterocolitis necrotizante (p=0,478) ni sepsis neonatal (p=0,615). La mortalidad neonatal fue significativamente superior en los PT (p=0,044). Conclusión: Los PT deben ser considerados de alto riesgo en el período neonatal. Nuestros resultados son importantes para tomar decisiones clinicas respecto al mejor momento de finalizar un embarazo con riesgo inminente de prematurez.

Objective: To compare neonatal morbidity risks between late preterm (LP) and term deliveries. Methods: Case control study. Medical records in 2007 were reviewed. Major congenital malformations, neuromuscular handicap, twin pregnancies and aneuploidies were excluded. The Study group corresponds to all LP births during that period and the control group to term deliveries in the same period. Neonatal outcomes were collected and different risks were calculated using Chi square test and Fisher exact tests. Results: 1536 deliveries with a LP rate of 7.1 percent (109 cases) were observed, 62 cases met inclusion criteria. The control group consisted in 124 single term deliveries. LP had 2 times more risk of cesarean section (p=0.0094) than term deliveries. The risk of NICU admission was 88 (p=0.000). Neonatal morbidity risks were: RDS (OR 23, p=0.000), hypoglycemia (OR 6, p=0.014), hypocalcaemia (OR 6, p=0.014), hyperbillirrubinemia (OR 28, p=0.000) and phototherapy (OR 23, p=0.000). There were no differences in necrotizing enterocolitis (p=0.478) and risk of neonatal sepsis (p=0.615). Neonatal mortality was significantly higher in LP babies (p=0.044). Conclusion: LP newborn must be considered as high risk in the neonatal period. These results are important in making clinical decisions about the better time to end pregnancy.

Neurodevelopmental outcomes of premature infants treated with l-arginine for prevention of necrotising enterocolitis.

AIM: This study aimed to compare the long-term neurodevelopmental outcomes at 36 months adjusted age in preterm infants (birth weight < or = 1250 gm) who received supplementation with L-arginine during the first 28 days of life with controls. METHODS: Surviving infants enrolled in a randomised control study of L-arginine supplementation were prospectively followed longitudinally to determine their neurodevelopmental outcomes at 36 months of adjusted age. Neurologic examination and neurodevelopmental assessments were performed by examiners who were unaware of the original treatment assignments. RESULTS: A total of 132 children (95% of survivors) were evaluated at 36 months adjusted age. In the group given L-arginine, 5 of 61 (8.1%) had major neurodevelopmental disabilities, defined as the presence of one or more of cerebral palsy, cognitive delay (cognitive index <70), bilateral blindness or bilateral hearing loss requiring hearing aids as compared with 9 of 71 (12.6%) in the placebo group (relative risk, 0.64; 95 % confidence interval, 0.22-1.82; P= 0.40). CONCLUSIONS: There is no increase in neurodevelopmental disability in preterm infants who received L-arginine supplementation.

[At the limits of viability: Dutch referral policy for premature birth too reserved]. / Op de grens van levensvatbaarheid: Nederlands verwijsbeleid bij vroeggeboorte te terughoudend.

OBJECTIVE: Evaluation of policy and treatment of deliveries at the limits of viability in the Netherlands and resulting survival figures. DESIGN: Cohort study. METHOD: Within the framework of the European 'Models of organising access to intensive care for very preterm births in Europe' (MOSAIC) study, data was collected on all 512 births in 2003 (terminations excluded) following 22-31 weeks gestation in the catchment areas of the perinatal centres in Nijmegen and Utrecht, the Netherlands. RESULTS: Gynaecologists and neonatologists practised a reserved policy for the active treatment of pregnancies under 25 weeks (5/77; 6%); all infants died. At 25 weeks, an active obstetric policy was used in one quarter of pregnancies, but none of the infants survived. Even at 26 weeks pregnancy, the obstetric policy was reserved and the mortality relatively high (9/31; 29%). From the neonatal deaths, 86 out of 92 (93%) were preceded by a decision either not to start or to discontinue treatment. CONCLUSION: Dutch obstetricians and neonatologists practised a reserved policy at the limits of neonatal viability. There is more need for active antenatal transfer to perinatal centres for those at the lower limit of neonatal viability to enable well-balanced decisions to take place. The parents' wishes should always be taken into account.

Neonatal mortality and morbidity rates in late preterm births compared with births at term.

OBJECTIVE: To analyze neonatal mortality and morbidity rates at 34, 35, and 36 weeks of gestation compared with births at term over the past 18 years at our hospital and to estimate the magnitude of increased risk associated with late preterm births compared with births later in gestation. METHODS: We performed a retrospective cohort study of births at our hospital over the past 18 years. The study included all liveborn singleton infants between 34 and 40 weeks of gestation and without anomalies that were delivered to women who received prenatal care in our hospital system. Neonatal outcomes for late preterm births were compared with those for infants delivered at 39 weeks. RESULTS: Late preterm singleton live births constituted approximately 9% of all deliveries at our hospital and accounted for 76% of all preterm births. Late preterm neonatal mortality rates per 1,000 live births were 1.1, 1.5, and 0.5 at 34, 35, and 36 weeks, respectively, compared with 0.2 at 39 weeks (P<.001). Neonatal morbidity was significantly increased at 34, 35, and 36 weeks, including ventilator-treated respiratory distress, transient tachypnea, grades 1 or 2 intraventricular hemorrhage, sepsis work-ups, culture-proven sepsis, phototherapy for hyperbilirubinemia, and intubation in the delivery room. Approximately 80% of late preterm births were attributed to idiopathic preterm labor or ruptured membranes and 20% to obstetric complications. CONCLUSION: Late preterm births are common and associated with significantly increased neonatal mortality and morbidity compared with births at 39 weeks. Preterm labor was the most common cause (45%) for late preterm births. LEVEL OF EVIDENCE: II.

Causes of stillbirths and early neonatal deaths: data from 7993 pregnancies in six developing countries.

OBJECTIVE: To report stillbirth and early neonatal mortality and to quantify the relative importance of different primary obstetric causes of perinatal mortality in 171 perinatal deaths from 7993 pregnancies that ended after 28 weeks in nulliparous women. METHODS: A review of all stillbirths and early newborn deaths reported in the WHO calcium supplementation trial for the prevention of pre-eclampsia conducted at seven WHO collaborating centres in Argentina, Egypt, India, Peru, South Africa and Viet Nam. We used the Baird-Pattinson system to assign primary obstetric causes of death and classified causes of early neonatal death using the International classification of diseases and related health problems, Tenth revision (ICD-10). FINDINGS: Stillbirth rate was 12.5 per 1000 births and early neonatal mortality rate was 9.0 per 1000 live births. Spontaneous preterm delivery and hypertensive disorders were the most common obstetric events leading to perinatal deaths (28.7% and 23.6%, respectively). Prematurity was the main cause of early neonatal deaths (62%). CONCLUSIONS: Advancements in the care of premature infants and prevention of spontaneous preterm labour and hypertensive disorders of pregnancy could lead to a substantial decrease in perinatal mortality in hospital settings in developing countries.