An Algorithm for Predicting Neonatal Mortality in Threatened Very Preterm Birth.

OBJECTIVE: To develop a prediction model for neonatal mortality using information readily available in the antenatal period. METHODS: A multiple logistic regression model of a complete population-based geographically defined cohort of very preterm infants of 23+0 to 30+6 weeks' gestation was used to identify antenatal factors which were predictive of mortality in this population. Infants lt; 23 weeks and those with major anomalies were excluded. RESULTS: Between 1996 and 2012, 1240 live born infants lt; 31 weeks' gestation were born to women residing in Nova Scotia. Decreasing gestational age strongly predicted an increased mortality rate. Other factors significantly contributing to increased mortality included classification as small for gestational age, oligohydramnios, maternal psychiatric disorders, antenatal antibiotic therapy, and monochorionic twins. Reduced neonatal mortality was associated with antenatal use of antihypertensive agents and use of corticosteroids of any duration of therapy given at least 24 hours before delivery. An algorithm was developed to estimate the risk of mortality without the need for a calculator. CONCLUSION: Prediction of the probability of neonatal mortality is influenced by maternal and fetal factors. An algorithm to estimate the risk of mortality facilitates counselling and informs shared decision making regarding obstetric management.

Objectif : Élaborer un modèle prédictif en ce qui concerne la mortalité néonatale au moyen de renseignements faciles à obtenir au cours de la période prénatale. Méthodes : Nous avons eu recours au modèle de régression logistique multiple d'une cohorte exhaustive, populationnelle et définie géographiquement de nouveau-nés très prématurés (âge gestationnel : de 23+0 à 30+6 semaines) pour identifier les facteurs prénataux permettant de prédire la mortalité au sein de cette population. Les nouveau-nés dont l'âge gestationnel était inférieur à 23 semaines et ceux qui présentaient des anomalies majeures ont été exclus. Résultats : Entre 1996 et 2012, 1 240 enfants nés vivants à moins de 31 semaines de gestation ont été issus de femmes résidant en Nouvelle-Écosse. La baisse de l'âge gestationnel constituait un facteur solide permettant de prédire une hausse du taux de mortalité. Parmi les autres facteurs contribuant de façon significative à la hausse du taux de mortalité, on trouvait l'hypotrophie fœtale, l'oligohydramnios, les troubles psychiatriques maternels, l'antibiothérapie prénatale et les jumeaux monozygotes. La baisse du taux de mortalité néonatale était associée à l'utilisation prénatale d'antihypertenseurs et à l'utilisation de corticostéroïdes (peu importe la durée du traitement) administrés au moins 24 heures avant l'accouchement. Nous avons élaboré un algorithme pour estimer le risque de mortalité sans avoir recours à une calculatrice. Conclusion : La prévision de la probabilité de la mortalité néonatale est influencée par des facteurs maternels et fœtaux. Le fait de disposer d'un algorithme pour estimer le risque de mortalité facilite le counseling et éclaire le processus décisionnel partagé en ce qui concerne la prise en charge obstétricale.

Trends in the prevalence of cerebral palsy among very preterm infants (<31 weeks' gestational age).

BACKGROUND: The birth prevalence of cerebral palsy varies over time among very preterm infants, and the reasons are poorly understood. OBJECTIVE: To describe the variation in the prevalence of cerebral palsy among very preterm infants over time, and to relate these differences to other maternal or neonatal factors. METHODS: A population-based cohort of very preterm infants was evaluated over a 20-year period (1988 to 2007) divided into four equal epochs. RESULTS: The prevalence of cerebral palsy peaked in the third epoch (1998 to 2002) while mortality rate peaked in the second epoch (1993 to 1997). Maternal anemia, tocolytic use and neonatal need for home oxygen were highest in the third epoch. CONCLUSIONS: Lower mortality rates did not correlate well with the prevalence of cerebral palsy. Maternal risk factors, anemia and tocolytic use, and the newborn need for home oxygen were highest during the same epoch as the peak prevalence of cerebral palsy.

HISTORIQUE: La prévalence de paralysie cérébrale à la naissance varie au fil du temps chez les nourrissons très prématurés, et on en comprend mal les raisons. OBJECTIF: Décrire la variation de la prévalence de paralysie cérébrale chez les nourrissons très prématurés au fil du temps et les relier à d'autres facteurs relatifs à la mère ou à la période néonatale. MÉTHODOLOGIE: Les chercheurs ont évalué une cohorte de nourrissons très prématurés sur 20 ans (1988 à 2007), divisée en quatre périodes d'égale longueur. RÉSULTATS: La prévalence de paralysie cérébrale a atteint un pic pendant la troisième période (1998 à 2002), tandis que le pic du taux de mortalité est survenu pendant la deuxième période (1993 à 1997). L'anémie et l'utilisation de tocolytiques chez la mère, ainsi que l'assistance ventilatoire néonatale à domicile, étaient plus élevées pendant la troisième période. CONCLUSIONS: Les taux de mortalité plus faibles n'étaient pas bien corrélés avec la prévalence de paralysie cérébrale. Les facteurs de risque de la mère, c'est-à-dire l'anémie et l' utilisation de tocolytiques, de même que l'assistance ventilatoire du nouveau-né à domicile, étaient tous plus élevés pendant la période qui s'associait à la plus forte prévalence de paralysie cérébrale.

Hypothermia for neonatal hypoxic ischemic encephalopathy: an updated systematic review and meta-analysis.

OBJECTIVE: To establish the evidence of therapeutic hypothermia for newborns with hypoxic ischemic encephalopathy(HIE). DATA SOURCES: Cochrane Central Register of Controlled Trials, Oxford Database of Perinatal Trials, MEDLINE, EMBASE, and previous reviews. STUDY SELECTION: Randomized controlled trials that compared therapeutic hypothermia to normothermia for newborns with HIE. INTERVENTION: Therapeutic hypothermia. MAIN OUTCOME MEASURES: Death or major neurodevelopmental disability at 18 months. RESULTS: Seven trials including 1214 newborns were identified. Therapeutic hypothermia resulted in a reduction in the risk of death or major neurodevelopmental disability(risk ratio [RR], 0.76; 95% CI, 0.69-0.84) and increase in the rate of survival with normal neurological function (1.63; 1.36-1.95) at age 18 months. Hypothermia reduced the risk of death or major neurodevelopmental disability at age 18 months in newborns with moderate HIE (RR, 0.67; 95% CI, 0.56-0.81) and in newborns with severe HIE (0.83; 0.74-0.92). Both total body cooling and selective head cooling resulted in reduction in the risk of death or major neurodevelopmental disability(RR, 0.75; 95% CI, 0.66-0.85 and 0.77; 0.65-0.93,respectively). CONCLUSION: Hypothermia improves survival and neurodevelopment in newborns with moderate to severe HIE.Total body cooling and selective head cooling are effective methods in treating newborns with HIE. Clinicians should consider offering therapeutic hypothermia as part of routine clinical care to these newborns.

Prenatal corticosteroid prophylaxis for women delivering at late preterm gestation.

OBJECTIVE: We studied patterns of prenatal corticosteroid use, respiratory distress syndrome, and associated mortality rates to assess the congruence between knowledge and clinical practice related to such prophylaxis. METHODS: We used data on all live births in the United States (for the years 1989-1991, 1995-1997, and 2002-2004) and Nova Scotia, Canada (for the years 1988-2007). Gestational age-specific temporal trends in infant deaths resulting from respiratory distress syndrome were quantified in the United States, and gestational age-specific temporal trends in corticosteroid use and morbidity (respiratory distress syndrome and intraventricular hemorrhage) were quantified in Nova Scotia. RESULTS: In the United States, infant deaths associated with respiratory distress syndrome decreased by 48% (95% confidence interval: 46%-50%) from 1989-1991 to 1995-1997 and then decreased by another 18% (95% confidence interval: 15%-22%) by 2002-2004. The latter mortality reduction was evident at 28 to 32 weeks but not 33 to 36 weeks of gestation. Corticosteroid use at 28 to 32 weeks was high in Nova Scotia and increased from 30.7% in 1988-1989 to 50.0% in 1996-1997 and to 52.9% in 2006-2007, whereas rates of use at 33 to 36 weeks were much lower (eg, 6.7%, 17.0%, and 15.7% at 34 weeks in the 3 periods). Increased corticosteroid use at 33 and 34 weeks was estimated to reduce respiratory distress syndrome substantially. CONCLUSION: Addressing the knowledge-practice gap in corticosteroid use at 33 to 34 weeks should reduce infant morbidity and mortality rates.

Neurodevelopmental outcome of extremely low birth weight infants randomly assigned to restrictive or liberal hemoglobin thresholds for blood transfusion.

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

A randomized trial of aggressive versus conservative phototherapy for hyperbilirubinemia in infants weighing less than 1500 g: Short- and long-term outcomes.

OBJECTIVE: Treatment regimens for hyperbilirubinemia vary for very low birth weight infants. The present study seeks to determine whether the initiation of conservative phototherapy is as effective as aggressive phototherapy in reducing peak bilirubin levels without increasing adverse effects. STUDY DESIGN: The present randomized, controlled study included infants with birth weights between 500 g and 1500 g, stratified into two birth weight groups. In one group, aggressive phototherapy was commenced by 12 h of age, while in the other group, conservative phototherapy was commenced if serum bilirubin levels exceeded 150 mumol/L. The primary outcome variables were peak serum bilirubin levels and hours of phototherapy. Secondary outcomes were age at peak bilirubin levels, number of infants with rebound hyperbilirubinemia, and number of adverse short- and long-term outcomes. RESULTS: Of 174 eligible infants, 95 consented to participate -49 in the conservative arm and 46 in the aggressive arm. Ninety-two infants completed the study. There was no significant difference in peak bilirubin levels except in infants who weighed less than 1000 g -171.2+/-26 mumol/L (conservative) versus 139.2+/-46 mumol/L (aggressive); P<0.02. There was no difference in duration of phototherapy or rebound hyperbilirubinemia. There were no differences in short-term adverse outcomes. Of the 87 infants who survived until hospital discharge, 82 (94%) had some follow-up and 75 (86%) attended follow-up until 18 months corrected age. The incidence of cerebral palsy, abnormal mental developmental index at 18 months corrected age, or combined outcome of cerebral palsy and death did not significantly differ between the two groups. CONCLUSIONS: In infants weighing less than 1000 g, peak bilirubin levels were significantly higher using conservative phototherapy regimens and there was a tendency for poor neurodevelopmental outcome.

Increasing prevalence of cerebral palsy among very preterm infants: a population-based study.

OBJECTIVES: It is unclear whether declines in neonatal and infant mortality have led to changes in the occurrence of cerebral palsy. We conducted a study to examine and investigate recent temporal changes in the prevalence of cerebral palsy in a population-based cohort of very preterm infants who were 24 to 30 weeks of gestational age. METHODS: A population-based cohort of very preterm infants who were born between January 1, 1993, and December 31, 2002, was evaluated by the Perinatal Follow-up Program of Nova Scotia. Follow-up extended to age 2 years to ascertain the presence or absence of cerebral palsy and for overall survival. Infant survival and cerebral palsy rates were compared by year and also in two 5-year periods, 1993-1997 and 1998-2002. Logistic regression analyses were used to identify factors that potentially were responsible for temporal changes in cerebral palsy rates. RESULTS: A total of 672 liveborn very preterm infants were born to mothers who resided in Nova Scotia between 1993 and 2002. Infant mortality among very preterm infants decreased from 256 per 1000 live births in 1993 to 114 per 1000 live births in 2002, whereas the cerebral palsy rates increased from 44.4 per 1000 live births in 1993 to 100.0 per 1000 live births in 2002. Low gestational age, postnatal dexamethasone use, patent ductus arteriosus, severe hyaline membrane disease, resuscitation in the delivery room, and intraventricular hemorrhage were associated with higher rates of cerebral palsy, whereas antenatal corticosteroid use was associated with a lower rate. CONCLUSION: Cerebral palsy has increased substantially among very preterm infants in association with and possibly as a consequence of large declines in infant mortality.

A population-based study to determine the performance of the Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale to Predict the Mental Developmental Index at 18 Months on the Bayley Scales of Infant Development-II in very preterm infants.

OBJECTIVES: To determine optimal ages to perform the Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) and optimal "cutoff" score of the CAT/CLAMS to screen very preterm infants (<31 weeks) for severe cognitive-adaptive delay and to ascertain the sensitivity, specificity and likelihood ratios using optimal cutoff scores compared with the Mental Developmental Index (MDI) of the Bayley Scales of Infant Development II. METHODS: A population-based cohort of very preterm infants who were born to mothers who resided in Nova Scotia or Prince Edward Island were evaluated at 4, 8, 12, and 18 months' corrected gestational age, which included a CAT/CLAMS by a physician. At 18 months' corrected gestational age, each child was assessed using the Bayley Scales of Infant Development II, the "gold standard" for developmental delay in young infants. The results of each CAT/CLAMS was compared with the 18-month MDI to identify significant developmental delay (MDI <70). RESULTS: Optimal scores on the CAT/CLAMS to identify correctly MDI <70 were determined by using the kappa statistic for chance independent agreement. Sensitivities and specificities for optimal cutoff scores were as follows: 4-month score <109 (88% and 37%), 8-month score <98 (75% and 82%), 12-month score <81 (63% and 99%), and 18-month score <83 (88% and 98%). CONCLUSION: Sensitivity and specificity of the CAT/CLAMS are high in very preterm infants at identifying major developmental delay at 12 and 18 months. For follow-up programs without psychology services, the CAT/CLAMS at 12 and 18 months is a reasonable screening tool to determine which children need expedited psychology referral for cognitive delay.

Twin-twin transfusion syndrome: a population-based study.

OBJECTIVE: To study the incidence and mortality and morbidity rates of twin-twin transfusion syndrome in a complete population-based cohort in Nova Scotia. METHODS: A population-based cohort study of all monochorionic diamniotic twin pregnancies of 20 weeks of gestation or longer born to Nova Scotia (Canada) residents between 1988 and 2000 was examined. The effect of gestational age adjustment and birth weight discordancy of more than 20% on mortality and 1-year survival was studied. Other outcomes studied included birth depression, respiratory distress syndrome, chronic lung disease, interventricular hemorrhage, periventricular leukomalacia, acute renal failure, and congestive heart failure. RESULTS: Of 404 monochorionic-diamniotic twin pregnancies examined, 48 were identified with twin-twin transfusion syndrome. Total mortality rates per pregnancy were significantly greater in the twin-twin transfusion syndrome group than in the remainder of our monochorionic diamniotic population (P < .01). However, when adjusted for gestational age, mortality failed to achieve statistical significance. Similarly, no differences were noted for 1-year survival and other outcomes of liveborn infants after gestational age adjustment. Discordance in birth weight predicted a higher incidence of morbid outcomes per pregnancy, but this effect was lost after gestational age adjustment. CONCLUSION: Increased morbidity and mortality of twins with twin-twin transfusion syndrome is likely to be due to a higher incidence of preterm birth. Birth weight discordancy was not found to be an independent predictor of mortality after controlling for gestational age and twin-twin transfusion syndrome.

Does the risk of cerebral palsy increase or decrease with increasing gestational age?

BACKGROUND: It is generally accepted that the risk of cerebral palsy decreases with increasing gestational age of live born infants. However, recent studies have shown that cerebral palsy often has prenatal antecedents including congenital malformations, vascular insults and maternal infection. Cerebral palsy is therefore better viewed as occurring among fetuses, rather than among infants. We explored the epidemiologic implications of this change in perspective. METHODS: We used recently published data from Shiga Prefecture, Japan and from North-East England to examine the pattern of gestational age-specific rates of cerebral palsy under these alternative perspectives. We first calculated gestational age-specific rates of cerebral palsy as per convention, by dividing the number of cases of cerebral palsy identified among live births within any gestational age category by the number of live births in that gestational age category. Under the alternative formulation, we calculated gestational age-specific rates of cerebral palsy by dividing the number of cases of cerebral palsy identified among live births within any gestational age category by the number of fetuses who were at risk of being born at that gestation and being afflicted with cerebral palsy. RESULTS: Under the conventional formulation, cerebral palsy rates decreased with increasing gestational age from 63.9 per 1,000 live births at <28 weeks gestation to 0.9 per 1,000 live births at 37 or more weeks gestation. When fetuses were viewed as potential candidates for cerebral palsy, cerebral palsy rates increased with increasing gestational age from 0.08 per 1,000 fetuses at risk at <28 weeks gestation to 0.9 per 1,000 fetuses at risk at 37 or more weeks gestation. CONCLUSIONS: The fetuses-at-risk approach is the appropriate epidemiologic formulation for calculating the gestational age-specific rate of cerebral palsy from a causal perspective. It shows that the risk of cerebral palsy increases as gestational duration increases. This compelling view of cerebral palsy risk may help refocus research aimed at understanding and preventing cerebral palsy.