Five-year outcomes for extremely preterm babies with active perinatal management: A clinical prediction model.

OBJECTIVE: To develop and validate a clinical prediction model for outcomes at 5 years of age for children born extremely preterm and receiving active perinatal management. DESIGN: The EPIPAGE-2 national prospective cohort. SETTING: France, 2011. POPULATION: Live-born neonates between 24+0 and 26+6 weeks of gestation who received active perinatal management (i.e. birth in a tertiary-level hospital, with antenatal steroids and resuscitation at birth). METHODS: A prediction model using logistic modelling, including gestational age, small-for gestational-age (SGA) status and sex, was developed. Model performance was assessed through calibration and discrimination, with bootstrap internal validation. MAIN OUTCOME MEASURES: Survival without moderate or severe neurodevelopmental disability (NDD) at 5 years. RESULTS: Among the 557 neonates included, 401 (72%) survived to 5 years, of which 59% survived without NDD (95% CI 54% to 63%). Predicted rates of survival without NDD ranged from 45% (95% CI 33% to 57%), to 56% (95% CI 49% to 64%) to 64% (95% CI 57% to 70%) for neonates born at 24, 25 and 26 weeks of gestation, respectively. Predicted rates of survival without NDD were 47% (95% CI 18% to 76%) and 62% (95% CI 49% to 76%) for SGA and non-SGA children, respectively. The model showed good calibration (calibration slope 0.85, 95% CI 0.54 to 1.16; calibration-in-the-large -0.0123, 95% CI -0.25 to 0.23) and modest discrimination (C-index 0.59, 95% CI 0.53 to 0.65). CONCLUSIONS: A simple prediction model using three factors easily known antenatally may help doctors and families in their decision-making for extremely preterm neonates receiving active perinatal management.

The Trend in Costs of Tertiary-Level Neonatal Intensive Care for Neonates Born Preterm at 220/7-286/7 Weeks of Gestation from 2010 to 2019 in Canada.

OBJECTIVE: To describe the trend in costs over 10 years for tertiary-level neonatal care of infants born 220/7-286/7 weeks of gestation during an ongoing Canadian national quality improvement project. STUDY DESIGN: Clinical characteristics, outcomes, and third-party payor costs for the tertiary neonatal care of infants born 220/7-286/7 weeks of gestation between the years 2010 and 2019 were analyzed from the Canadian Neonatal Network database. Costs were estimated using resource use data from the Canadian Neonatal Network and cost inputs from hospitals, physician billing, and administrative databases in Ontario, Canada. Cost estimates were adjusted to 2017 Canadian dollars (CAD). A generalized linear mixed-effects model with gamma regression was used to estimate trends in costs. RESULTS: Between 2010 and 2019, the number of infants born <24 weeks of gestation increased from 4.4% to 7.7%. The average length of stay increased from 68 days to 75 days. Unadjusted average ± SD total costs per neonate were $120 717 ± $93 062 CAD in 2010 and $132 774 ± $93 161 CAD in 2019. After adjustment for year, center, and gestation, total costs and length of stay increased significantly, by $13 612 CAD (P < .01) and 8.1 days (P < .01) over 10 years, respectively; whereas costs accounting for LOS remained stable. CONCLUSIONS: The total costs and length of stay for infants 220/7-286/7 weeks of gestation have increased over the past decade in Canada during an ongoing national quality improvement initiative; however, there was an increase in the number and survival of neonates at the age of periviability.

Birth outcomes between 22 and 26 weeks' gestation in national population-based cohorts from Sweden, England and France.

AIM: We investigated the timing of survival differences and effects on morbidity for foetuses alive at maternal admission to hospital delivered at 22 to 26 weeks' gestational age (GA). METHODS: Data from the EXPRESS (Sweden, 2004-07), EPICure-2 (England, 2006) and EPIPAGE-2 (France, 2011) cohorts were harmonised. Survival, stratified by GA, was analysed to 112 days using Kaplan-Meier analyses and Cox regression adjusted for population and pregnancy characteristics; neonatal morbidities, survival to discharge and follow-up and outcomes at 2-3 years of age were compared. RESULTS: Among 769 EXPRESS, 2310 EPICure-2 and 1359 EPIPAGE-2 foetuses, 112-day survival was, respectively, 28.2%, 10.8% and 0.5% at 22-23 weeks' GA; 68.5%, 40.0% and 23.6% at 24 weeks; 80.5%, 64.8% and 56.9% at 25 weeks; and 86.6%, 77.1% and 74.4% at 26 weeks. Deaths were most marked in EPIPAGE-2 before 1 day at 22-23 and 24 weeks GA. At 25 weeks, survival varied before 28 days; differences at 26 weeks were minimal. Cox analyses were consistent with the Kaplan-Meier analyses. Variations in morbidities were not clearly associated with survival. CONCLUSION: Differences in survival and morbidity outcomes for extremely preterm births are evident despite adjustment for background characteristics. No clear relationship was identified between early mortality and later patterns of morbidity.

Maternal and perinatal outcomes of pregnancies delivered at 23 weeks' gestation.

OBJECTIVE: To evaluate the maternal and perinatal outcomes of pregnancies delivered at 23+0 to 23+6 weeks' gestation. METHODS: This prospective cohort study included women in the Canadian Perinatal Network who were admitted to one of 16 Canadian tertiary perinatal units between August 1, 2005, and March 31, 2011, and who delivered at 23+0 to 23+6 weeks' gestation. Women were included in the network if they were admitted with spontaneous preterm labour with contractions, a short cervix without contractions, prolapsing membranes with membranes at or beyond the external os or a dilated cervix, preterm premature rupture of membranes, intrauterine growth restriction, gestational hypertension, or antepartum hemorrhage. Maternal outcomes included Caesarean section, placental abruption, and serious complication. Perinatal outcomes were mortality and serious morbidity. RESULTS: A total of 248 women and 287 infants were included in the study. The rate of Caesarean section was 10.5% (26/248) and 40.3% of women (100/248) had a serious complication, the most common being chorioamnionitis (38.6%), followed by blood transfusion (4.5%). Of infants with known outcomes, perinatal mortality was 89.9% (223/248) (stillbirth 23.3% [67/287] and neonatal death 62.9% [156/248]). Of live born neonates with known outcomes (n = 181), 38.1% (69/181) were admitted to NICU. Of those admitted to NICU, neonatal death occurred in 63.8% (44/69). Among survivors at discharge, the rate of severe brain injury was 44.0% (11/25), of retinopathy of prematurity 58.3% (14/24), and of any serious neonatal morbidity 100% (25/25). Two subgroup analyses were performed: in one, antepartum stillbirths were excluded, and in the other only centres that indicated they offered fetal monitoring at 23 weeks' gestation were included and antepartum stillbirths were excluded. In each of these, perinatal outcomes similar to the overall group were found. CONCLUSION: Pregnant women delivering at 23 weeks' gestation are at risk of morbidity. Their infants have high rates of serious morbidity and mortality. Further research is needed to identify strategies and forms of management that not only increase perinatal survival but also reduce morbidities in these extremely low gestational age infants and reduce maternal morbidity.

Objectif : Évaluer les issues maternelles et périnatales des grossesses donnant lieu à un accouchement entre 23+0 et 23+6 semaines de gestation. Méthodes : Cette étude de cohorte prospective portait sur des femmes du Réseau périnatal canadien qui ont été admises à l'une des 16 unités périnatales tertiaires canadiennes participantes entre le 1er août 2005 et le 31 mars 2011, et qui ont accouché entre 23+0 et 23+6 semaines de gestation. Les femmes ont été admises dans le réseau si elles avaient été hospitalisées en raison d'un travail préterme spontané (s'accompagnant de contractions), d'un col court (sans contractions), d'un prolapsus des membranes (s'accompagnant d'une dilatation du col ou dans le cadre duquel les membranes se situaient au niveau de l'orifice externe ou faisaient saillie au-delà de ce dernier), d'une rupture prématurée des membranes préterme, d'un retard de croissance intra-utérin, d'une hypertension gestationnelle ou d'une hémorragie antepartum. Parmi les issues maternelles, on trouvait la césarienne, le décollement placentaire et la manifestation d'une complication grave. La morbidité grave et la mortalité constituaient les issues périnatales. Résultats : En tout, 248 femmes et 287 nouveau-nés ont été inclus dans l'étude. Le taux de césarienne était de 10,5 % (26/248) et 40,3 % des femmes (100/248) ont connu une complication grave (la plus courante étant la chorioamnionite [38,6 %], suivie de la transfusion sanguine [4,5 %]). Parmi les nouveau-nés pour lesquels les issues étaient connues, le taux de mortalité périnatale était de 89,9 % (223/248) (taux de mortinaissance : 23,3 % [67/287] et taux de décès néonatal : 62,9 % [156/248]). Une admission à l'UNSI a été requise pour 38,1 % (69/181) des enfants nés vivants pour lesquels les issues étaient connues (n = 181). Parmi ces enfants ayant dû être admis à l'UNSI, un décès néonatal a été constaté dans 63,8 % (44/69) des cas. Chez les survivants (au moment de l'obtention de leur congé de l'UNSI), le taux de lésion cérébrale grave était de 44,0 % (11/25), le taux de rétinopathie des prématurés était de 58,3 % (14/24) et le taux de quelque morbidité néonatale grave que ce soit était de 100 % (25/25). Deux analyses de sous-groupe ont été menées : dans le cadre de l'une d'entre elles, les mortinaissances pendant la période antepartum ont été exclues; dans le cadre de l'autre, seuls les centres ayant indiqué qu'ils offraient le monitorage fœtal à 23 semaines de gestation ont été inclus et les mortinaissances pendant la période antepartum ont également été exclues. Des issues périnatales semblables à celles du groupe général ont été constatées dans chacune de ces analyses. Conclusion : Les femmes enceintes qui accouchent à 23 semaines de gestation sont exposées à des risques de morbidité. Leurs nouveau-nés présentent des taux élevés de morbidité grave et de mortalité. La poursuite de la recherche s'avère requise pour permettre l'identification de stratégies et de formes de prise en charge qui entraînent non seulement une amélioration du taux de survie périnatale, mais également une baisse des taux de morbidité que connaissent ces nouveau-nés d'âge gestationnel extrêmement faible et les mères.

Preterm Delivery; Who Is at Risk?

Preterm birth (PTB) is the leading cause of perinatal morbidity and mortality. Adverse effects of preterm birth have a direct correlation with the degree of prematurity, in which infants who are born extremely preterm (24-28 weeks gestation) have the worst outcomes. We sought to determine prominent risk factors for extreme PTB and whether these factors varied between various sub-populations with known risk factors such as previous PTB and multiple gestations. A population-based retrospective cohort study was conducted. Risk factors were examined in cases of extreme PTB in the general population, as well as various sub-groups: singleton and multiple gestations, women with a previous PTB, and women with indicated or induced PTB. A total of 334,415 deliveries were included, of which 1155 (0.35%) were in the extreme PTB group. Placenta previa (OR = 5.8, 95%CI 4.14-8.34, p < 0.001), multiple gestations (OR = 7.7, 95% CI 6.58-9.04, p < 0.001), and placental abruption (OR = 20.6, 95%CI 17.00-24.96, p < 0.001) were the strongest risk factors for extreme PTB. In sub-populations (multiple gestations, women with previous PTB and indicated PTBs), risk factors included placental abruption and previa, lack of prenatal care, and recurrent pregnancy loss. Singleton extreme PTB risk factors included nulliparity, lack of prenatal care, and placental abruption. Placental abruption was the strongest risk factor for extreme preterm birth in all groups, and risk factors did not differ significantly between sub-populations.

Trends in obstetric management of extreme preterm birth at 23 to 27 weeks' gestation in a tertiary obstetric unit: A 10-year retrospective review.

OBJECTIVE: To evaluate maternal and perinatal outcomes in deliveries from 23 + 0 to 26 + 6 weeks gestation in a tertiary hospital. STUDY DESIGN: A 10-year retrospective analysis was performed which included all women who delivered between 23 + 0 and 26 + 6 weeks gestation in a tertiary obstetric unit from 01/01/2007 to 31/12/2017 inclusive. Data were collected from electronic patient records and individual chart reviews using predetermined variables. RESULTS: 340 women and 402 infants were included. 84 % (282/340) were singleton pregnancy and 17 % (59/340) had multiple pregnancies. 36.8 % (125/340) of women were delivered by Caesarean section, 11.2 % (14/125) had a classical caesarean section. The leading indications for delivery were preterm premature ruptured membranes (PPROM) 28.2 % (96/340), 8.5 % (29/340) severe pre-eclampsia (PET) and 5.6 % (19/340) were delivered for suspected placental abruption. Of all infants (N = 402), 18.9 % (76/402) were stillborn. 300 infants were admitted to the Neonatal Intensive Care Unit (NICU). The NICU survival to discharge rate was 83.7 % (251/300). The overall perinatal mortality rate (PNMR) was 328.4/1000 and a further late neonatal mortality of 47.3/1000 births. Notably, at the 23 week gestation NNDs are the major contributor to the PNMR and at later gestations stillbirths are the largest contributor. CONCLUSION: Pregnant women delivering at extreme preterm gestations are at risk of maternal morbidity. Their infants have high rates of serious morbidity and mortality, with all survivors in this cohort affected by neonatal morbidity. Informed decision-making by providers and parents requires evidence based information on perceived outcomes, ideally individualized to the mother and pregnancy in question. Information from this retrospective cohort study can be used to counsel women and their families on potential morbidity and mortality and to manage expectations.

Public Health Implications of Very Preterm Birth.

With advanced perinatal care and technology, survival among infants born very preterm (<32 weeks gestation) has improved dramatically over the last several decades. However, adverse medical and neurodevelopmental outcomes for those born very preterm remains high, particularly at the lowest gestational ages. Public health plays a critical role in providing data to assess population-based risks associated with very preterm birth, addressing disparities, and identifying opportunities for prevention, including improving the health of reproductive-age women, before, during, and after pregnancy.

Providing active antenatal care depends on the place of birth for extremely preterm births: the EPIPAGE 2 cohort study.

Survival rates of infants born before 25 weeks of gestation are low in France and have not improved over the past decade. Active perinatal care increases these infants' likelihood of survival. OBJECTIVE: Our aim was to identify factors associated with active antenatal care, which is the first step of proactive perinatal care in extremely preterm births. METHODS: The population included 1020 singleton births between 220/6 and 260/6 weeks of gestation enrolled in the Etude Epidémiologique sur les Petits Ages Gestationnels 2 study, a French national population-based cohort of very preterm infants born in 2011. The main outcome was 'active antenatal care' defined as the administration of either corticosteroids or magnesium sulfate or delivery by caesarean section for fetal rescue. A multivariable analysis was performed using a two-level multilevel model taking into account the maternity unit of delivery to estimate the adjusted ORs (aORs) of receiving active antenatal care associated with maternal, obstetric and place of birth characteristics. RESULTS: Among the population of extremely preterm births, 42% received active antenatal care. After standardisation for gestational age, regional rates of active antenatal care varied between 22% (95% CI 5% to 38%) and 61% (95% CI 44% to 78%). Despite adjustment for individual and organisational characteristics, active antenatal care varied significantly between maternity units (p=0.03). Rates of active antenatal care increased with gestational age with an aOR of 6.46 (95% CI 3.40 to 12.27) and 10.09 (95% CI 5.26 to 19.36) for infants born at 25 and 26 weeks' gestation compared with those born at 24 weeks. No other individual characteristic was associated with active antenatal care. CONCLUSION: Even after standardisation for gestational age, active antenatal care in France for extremely preterm births varies widely with place of birth. The dependence of life and death decisions on place of birth raises serious ethical questions.

Deficits in Approximate Number System Acuity and Mathematical Abilities in 6.5-Year-Old Children Born Extremely Preterm.

Preterm children are at increased risk for poor academic achievement, especially in math. In the present study, we examined whether preterm children differ from term-born children in their intuitive sense of number that relies on an unlearned, approximate number system (ANS) and whether there is a link between preterm children's ANS acuity and their math abilities. To this end, 6.5-year-old extremely preterm (i.e., <27 weeks gestation, n = 82) and term-born children (n = 89) completed a non-symbolic number comparison (ANS acuity) task and a standardized math test. We found that extremely preterm children had significantly lower ANS acuity than term-born children and that these differences could not be fully explained by differences in verbal IQ, perceptual reasoning skills, working memory, or attention. Differences in ANS acuity persisted even when demands on visuo-spatial skills and attention were reduced in the ANS task. Finally, we found that ANS acuity and math ability are linked in extremely preterm children, similar to previous results from term-born children. These results suggest that deficits in the ANS may be at least partly responsible for the deficits in math abilities often observed in extremely preterm children.

The overlap between miscarriage and extreme preterm birth in a limited-resource setting on the Thailand-Myanmar border: a population cohort study.

Background:  The WHO definition of stillbirth uses 28 weeks' gestation as the cut-point, but also defines extreme preterm birth as 24 to <28 weeks' gestation. This presents a problem with the gestational limit of miscarriage, and hence reporting of stillbirth, preterm birth and neonatal death. The objective of this study is to provide a synopsis of the outcome of a population cohort of pregnancies on the Thailand-Myanmar border between 24 to <28 weeks' gestation.  Methods: Records from the Shoklo Malaria Research Unit Antenatal Clinics were reviewed for pregnancy outcomes in the gestational window of 24 to <28 weeks, and each record, including ultrasounds reports, were reviewed to clarify the pregnancy outcome. Pregnancies where there was evidence of fetal demise prior to 24 weeks were classified as miscarriage; those viable at 24 weeks' gestation and born before 28 weeks were coded as births, and further subdivided into live- and stillbirth.  Results:  Between 1995 and 2015, in a cohort of 49,931 women, 0.6% (318) of outcomes occurred from 24 to <28 weeks' gestation, and 35.8% (114) were miscarriages, with confirmatory ultrasound of fetal demise in 45.4% (49/108). Of pregnancies not ending in miscarriage, 37.7% (77/204) were stillborn and of those born alive, neonatal mortality was 98.3% (115/117). One infant survived past the first year of life. Congenital abnormality rate was 12.0% (23/191). Ultrasound was associated with a greater proportion of pregnancy outcome being coded as birth.  Conclusion:  In this limited-resource setting, pregnancy outcome from 24 to <28 weeks' gestation included: 0.6% of all outcomes, of which one-third were miscarriages, one-third of births were stillborn and mortality of livebirths approached 100%. In the scale-up to preventable newborns deaths, at least initially, greater benefits will be obtained by focusing on the greater number of viable newborns with a gestation of 28 weeks or more.