Late Preterm Gestation Research Articles

Extrauterine support of pre-term lambs achieves similar transcriptomic profiling to late pre-term lamb brains

Our group has developed an extra-uterine environment for newborn development (EXTEND) using an ovine model, that aims to mimic the womb to improve short and long-term health outcomes associated with prematurity. This study’s objective was to determine the histologic and transcriptomic consequences of EXTEND on the brain. Histology and RNA-sequencing was conducted on brain tissue from three cohorts of lambs: control pre-term (106–107 days), control late pre-term (127 days), and EXTEND lambs who were born pre-term and supported on EXTEND until late pre-term age (125–128 days). Bioinformatic analysis determined differential gene expression among the three cohorts and across four different brain tissue sections: basal ganglia, cerebellum, hippocampus, and motor cortex. There were no clinically relevant histological differences between the control late pre-term and EXTEND ovine brain tissues. RNA-sequencing demonstrated that there was greater differential gene expression between the control pre-term lambs and EXTEND lambs than between the control late pre-term lambs and EXTEND lambs (Supplemental Figs. 1 and 2). Our study demonstrates that the use of EXTEND to support pre-term lambs until they reach late pre-term gestational age results in brain tissue gene expression that more closely resembles that of the lambs who reached late pre-term gestation within their maternal sheep’s womb than that of the lambs who were born prematurely.

Association of antenatal steroid administration with neonatal morbidities among late preterm multiple gestation infants.

There is limited evidence on the efficacy of antenatal steroids (ANS) among women with multiple gestations at risk of late preterm delivery. This retrospective study included multiple gestation, late preterm infants (340/7-366/7 weeks' gestational age), born between January 2013 and December 2022. The primary outcome was composite respiratory outcome, defined as the need for respiratory support by 72 hours of age. Logistic and linear regressions were performed to compare the primary and secondary outcomes with and without exposure to any ANS, adjusted for gestational age, sex of infant, histologic chorioamnionitis, and intrauterine growth restriction. The composite respiratory outcome was significantly lower in any ANS group compared to no ANS group (28.6% vs. 33.7%) [adjusted odds ratio 0.50, 95% CI, 0.33-0.75, p < 0.001]. In late preterm multiple gestation infants, any ANS exposure was associated with lower risk of composite respiratory outcome.

Infants Born at Late Preterm Gestation: Management During the Birth Hospitalization

To examine the admission practices, frequency of common clinical morbidities, and rates of medical intervention in infants born at 34-36 weeks gestational age (GA, late preterm). This retrospective, single institution, cohort study analyzed electronic health records of infants born late preterm from 2019 through 2021. Infants with anomalies necessitating neonatal intensive care unit admission were excluded. Analysis included descriptive and inferential statistics. The study included 1022 infants: 209 (21%) 34 weeks GA; 263 (26%) 35 weeks GA; and 550 (54%) 36 weeks GA. Sixty-three percent of infants at 35 weeks GA and 78% of infants of 36 weeks GA remained in well newborn care throughout the birth hospitalization; infants born at 34 weeks GA were ineligible for well newborn care. The need for respiratory support was 32%, 18% and 11% in infants of 34, 35, and 36 weeks GA, respectively. Supplemental tube feeds were administered in 55%, 24%, and 8% of infants of 34, 35, and 36 weeks GA, respectively. Most infants born at 34 weeks GA (91%) were placed in an incubator; this was less frequent in infants at 35 (37%) and 36 weeks (16%). Tachypnea, hypoglycemia, and hypothermia were noted in 40%, 61%, and 57% of infants, respectively. A subset of these infants (30% with tachypnea, 23% with hypoglycemia, 46% with hypothermia) required medical intervention for these abnormalities. This single center study provides an outlook on the care of infants born late preterm. Multi-center studies can contextualize these findings in order to develop clinical benchmarks and quality markers for this large population of infants.

851 Neonatal outcome in late preterm twin gestation: impact of antenatal corticosteroids before 34 weeks

851 Neonatal outcome in late preterm twin gestation: impact of antenatal corticosteroids before 34 weeks

Admission and respiratory outcomes of late preterm infants in the setting of high cesarean section deliveries: A single center retrospective analysis

Background Late preterm infants (LPIs) account for most preterm births and are at high risk of developing prematurity-related morbidities. Due to the increasing rate of cesarean section delivery, it is expected that more LPIs with respiratory complications will be admitted to neonatal intensive care units (NICU). Objectives To assess the rate of NICU admission and respiratory complications among LPIs and to compare their outcomes based on the mode of delivery. Patients and Methods The list of all LPIs who were admitted in the period 2015–2020 was reviewed. Data collected about demographic characteristics, delivery information, NICU admission, respiratory complications, respiratory support, length of stay, and readmission. Infants were classified according to their mode of delivery into: vaginal delivery group (VD) and cesarean section group (CS). Results Out of 2236 LPIs included, 321 (14%) were born at 34-week gestation, 1137 (51%) were males. 1243 (56%) were admitted to NICU. The CS group comprised 77% (1719) while the VD group 23% (517). Compared to the VD group, infants in the CS group had a higher rate of NICU admission (57.1% vs. 50.7%, P = 0.006), respiratory distress syndrome (RDS) (22% vs. 17%, P = 0.000), and transient tachypnea of newborn (TTN) (17% vs. 11%, P = 0.019). Also, more babies in the CS group received CPAP (36.2% vs. 24.6%, P = 0.000) and surfactant therapy (6.6% vs. 4.6%, P = 0.02). After logistic regression analysis, CS remains an independent factor for NICU admission (OR 1.3, 95% confidence intervals [CI] 1.1–1.6, P = 0.01), respiratory complications (OR 1.6, 95% CI 1.2–2.2, P = 0.001), CPAP requirement (OR 1.6, 95% CI 1.3–2, P = 0.000), and a longer length of stay &gt; 3 days (OR 1.5, 95% CI 1.2–1.8, P = 0.000). Conclusion The rate of CS delivery among late preterm gestation is very high and alarming. CS delivery of LPI increases the rate of NICU admission, respiratory complications, and the need for respiratory support.

Educational achievement to age 11 years in children born at late preterm and early term gestations

ObjectiveTo investigate the effects of being born late preterm (LPT, 34–36 weeks’ gestation) or early term (37–38 weeks) on children’s educational achievement between ages 5 and 11 years.DesignA series of...

Understanding what patients and physicians need to improve their decision-making about antenatal corticosteroids in late preterm gestation: a qualitative framework analysis.

It is unclear whether the benefits of administration of antenatal corticosteroids in late preterm gestation outweigh its harms. We sought to understand whether patients and physicians need increased support to decide whether to administer antenatal corticosteroids in late preterm gestation, and their informational needs and preferences for decision-making roles related to this intervention; we also wanted to know if creation of a decision-support tool would be useful. We conducted individual, semistructured interviews with pregnant people, obstetricians and pediatricians in Vancouver, Canada, in 2019. Using a qualitative framework analysis method, we coded, charted and interpreted interview transcripts into categories that formed an analytical framework. We included 20 pregnant participants, 10 obstetricians and 10 pediatricians. We organized codes into the following categories: informational needs to decide whether to administer antenatal corticosteroids; preferences for decision-making roles regarding this treatment; the need for support to make this treatment decision; and the preferred format and content of a decision-support tool. Pregnant participants wanted to be involved in decision-making about antenatal corticosteroids in late preterm gestation. They wanted information on the medication, respiratory distress, hypoglycemia, parent-neonate bonding and long-term neurodevelopment. There was variation in physician counselling practices, and in how patients and physicians perceived the balance of treatment harms and benefits. Responses suggested a decision-support tool may be useful. Participants desired clear descriptions of risk magnitude and uncertainty. Pregnant people and physicians would likely benefit from increased support to consider the harms and benefits of antenatal corticosteroids in late preterm gestation. Creation of a decision-support tool may be useful.

Predictive utility of the fetal cerebroplacental ratio for hypoxic ischaemic encephalopathy, severe neonatal morbidity and perinatal mortality in late-preterm and term infants.

The aim of this study was to evaluate the association of a low cerebroplacental ratio (CPR) with hypoxic ischaemic encephalopathy (HIE), severe neonatal morbidity (SNM) and perinatal mortality (PNM). This was a retrospective cohort study of late-preterm and term births at Mater Mothers' Hospital, Brisbane, between 2016 and 2020. Study outcomes were HIE, PNM and SNM (a composite of severe acidosis, Apgar score less than four at 5min, severe respiratory distress or need for significant cardiopulmonary resuscitation at birth). Univariate and multivariable logistic regressions were used to determine if a low CPR was associated with HIE, SNM or PNM. A total of 51 870 births met the inclusion criteria. Of these, 216 (0.42%) were complicated by HIE, 10 224 (19.7%) had SNM and 251 (0.48%) had PNM. Rates of low CPR (<10th and <5th centile) were significantly higher in the SNM cohort (20.1 and 13.2%, respectively) and PNM cohort (21.1 and 15.1%, respectively) compared to the overall cohort. A low CPR was associated with significantly increased adjusted odds for SNM but not for HIE or PNM. The area under the receiver operating characteristic curve for CPR <10th centile was greatest for SNM (0.768) and lowest for HIE (0.595). Predictive margins of a low CPR for HIE, SNM and PNM were significant only for SNM at late-preterm gestations. A low CPR is associated with increased odds of SNM in infants born >34 weeks' gestation but not for HIE or PNM.

Perinatal antecedents of moderate and severe neonatal hypoxic ischaemic encephalopathy: An Australian birth cohort study.

Neonatal hypoxic ischaemic encephalopathy (HIE) is the most common cause of encephalopathy in the neonatal period and carries a high risk of mortality and long-term morbidity. The aim of this study was to investigate key antecedents of moderate and severe HIE in a large contemporary birth cohort. A retrospective cohort study of births meeting criteria was conducted between 2016 and 2020 at the Mater Mothers' Hospital, Brisbane, Australia. This is a quaternary perinatal centre and Australia's largest maternity hospital. Univariate and multivariate Firth logistic regression were used to account for imbalanced frequency classes between non-HIE and HIE groups. Maternal variables and intrapartum factors were investigated for associations with neonatal moderate and severe HIE. Overall, 133 of 46 041 (0.29%) infants were diagnosed with HIE: 77 (0.17%) with mild HIE and 56 (0.12%) with moderate/severe HIE. Nulliparity, type 1 diabetes mellitus and maternal intensive care unit admission were associated with increased odds of moderate/severe HIE. Intrapartum risk factors included emergency caesarean birth, emergency caesarean for non-reassuring fetal status or failure to process, intrapartum haemorrhage and an intrapartum sentinel event (shoulder dystocia, cord prolapse, uterine rupture and placental abruption). Neonatal risk factors included male sex, late preterm gestation (35+0 -36+6 weeks), Apgar score less than four at 5min, severe respiratory distress requiring ventilatory support and severe acidosis at birth. This cohort study identified a series of potentially modifiable maternal and obstetric risk factors for HIE. Risk factors for HIE do not appear to have changed significantly with evolution in modern obstetric care.

Antenatal Corticosteroid Prophylaxis at Late Preterm Gestation: Clinical Guidelines Versus Clinical Practice

ObjectiveWe investigated how the Antenatal Late Preterm Steroids (ALPS) trial findings have been translated into clinical practice in Canada and the United States (U.S.). MethodsThe study included all live births in Nova Scotia, Canada, and the U.S. from 2007 to 2020. Antenatal corticosteroids (ACS) administration within specific categories of gestational age was assessed by calculating rates per 100 live births, and temporal changes were quantified using odds ratio (OR) and 95% confidence intervals (CI). Temporal trends in optimal and suboptimal ACS use were also assessed. ResultsIn Nova Scotia, the rate of any ACS administration increased significantly among women delivering at 350 to 366 weeks, from 15.2% in 2007–2016 to 19.6% in 2017–2020 (OR 1.36, 95% CI 1.14–1.62). Overall, the U.S. rates were lower than the rates in Nova Scotia. In the U.S., rates of any ACS administration increased significantly across all gestational age categories: among live births at 350 to 366 weeks gestation, any ACS use increased from 4.1% in 2007–2016 to 18.5% in 2017–2020 (OR 5.33, 95% CI 5.28–5.38). Among infants between 240 and 346 weeks gestation in Nova Scotia, 32% received optimally timed ACS, while 47% received ACS with suboptimal timing. Of the women who received ACS in 2020, 34% in Canada and 20% in the U.S. delivered at ≥37 weeks. ConclusionPublication of the ALPS trial resulted in increased ACS administration at late preterm gestation in Nova Scotia, Canada, and the U.S. However, a significant fraction of women receiving ACS prophylaxis delivered at term gestation.

Corticosteroids to safely reduce neonatal respiratory morbidity after late preterm and term planned caesarean section birth? A randomised placebo-controlled feasibility study

ObjectivesTo assess the feasibility of conducting a randomised placebo-controlled trial of corticosteroids prior to planned caesarean section from 35+0 to 39+6 weeks.DesignA triple-blind, placebo-controlled, parallel, trial randomised at the participant...

The Use of Antenatal Dexamethasone in Late Preterm and Term Pregnancies to Improve Neonatal Morbidity and Mortality: A Systematic Review and Meta-Analysis.

There are no acceptable worldwide recommendations regarding the use of dexamethasone in late-preterm newborns delivered either vaginally or via cesarean section and term gestation that are performed via cesarean section. The present study aims to compare the effectiveness of antenatal intramuscular dexamethasone versus placebo/no-treatment in reducing neonatal respiratory complications in high-risk for imminent preterm birth in late preterm pregnancies and term pregnancies undergoing elective cesarean section. The PubMed, Scopus, and Cochrane Library databases were searched to assess the effectiveness of dexamethasone during late preterm and term gestation. The last literature search was performed on March 20th, 2022. Randomized controlled trials compared antenatal dexamethasone administration with placebo or no treatment. The outcomes of interest were: the incidence of Respiratory Distress Syndrome; Transient Tachypnea of the Newborn, Neonatal Intensive Care Unit admissions; and the need for ventilatory support or mechanical ventilation.A standardized data form and three independent investigators performed the data extraction. Ten RCTs fulfilled our inclusion criteria. No statistically significant difference was found regarding all of the outcomes in the 34th-36th gestational week group. In the >37th gestational week group, a statistically significant difference was found regarding the incidence of RDS [RR (95% CI); p-value: 0.56 (0.36, 0.87); 0.01], TTN [RR (95% CI); p-value: 0.54 (0.42, 0.71); <0.00001], need for ventilatory support [RR (95% CI); p-value: 0.71 (0.52, 0.96); 0.03] and need for mechanical ventilation [RR (95% CI); p-value: 0.56 (0.33, 0.95); 0.03]. To conclude, the antenatal administration of dexamethasone can be considered to prevent neonatal complications and reduce perinatal morbidity in term pregnancies.

EBNEO commentary: Antenatal corticosteroids for late preterm gestation in low-resource countries.

EBNEO commentary: Antenatal corticosteroids for late preterm gestation in low-resource countries.

Peripartum Severe COVID-19 Pneumonia: Fetal and Neonatal Implications.

Peripartum Severe COVID-19 Pneumonia: Fetal and Neonatal Implications.

The impact of the Antenatal Late Preterm Steroids trial on the administration of antenatal corticosteroids

In 2016 the Antenatal Late Preterm Steroids study was published, demonstrating that antenatal corticosteroid therapy given to women at risk of late preterm delivery reduces respiratory morbidity in infants. However, the administration of antenatal corticosteroid therapy in late-preterm infants remains controversial. Late-preterm infants do not suffer from the same rates of morbidity as early-preterm infants, and the short-term benefits of antenatal corticosteroid therapy are less pronounced; consequently, the risk of possible harm is more difficult to balance. This study aimed to evaluate the association between the publication of the Antenatal Late Preterm Steroids study or the subsequent changes in guidelines and the rates of antenatal corticosteroid therapy administration in late-preterm infants in the United States. Data analyzed were publicly available US birth certificate data from January 1, 2016 to December 31, 2018. An interrupted time series design was used to analyze the association between publication of the Antenatal Late Preterm Steroids study and changes in monthly rates of antenatal corticosteroid administration in late preterm gestation (34+0 to 36+6 weeks). Births at 28+0 to 31+6 weeks' gestation were used as a control. Antenatal corticosteroid therapy administration in women with births at 32+0 to 34+6 weeks was explored to analyze whether the intervention influenced antenatal corticosteroid therapy administration in women in the subgroup approaching 34 weeks' gestation. Antenatal corticosteroid therapy administration in women with term births (>37 weeks' gestation) was analyzed to explore if the intervention influenced the number of term babies exposed to antenatal corticosteroid therapy. Our regression model allowed analysis of both step and slope changes. February 2016 was chosen as the intervention period. Our sample size was 18,031,950 total births. Of these, 1,056,047 were births at 34+0 to 36+6 weeks' gestation, 123,788 at 28+0 to 31+6 weeks, 153,708 at 32 to 33 weeks, and 16,602,699 were term births. There were 95,708 births at <28 weeks' gestation. There was a statistically significant increase in antenatal corticosteroid therapy administration rates in late preterm births following the online publication of the Antenatal Late Preterm Steroids study (adjusted incidence rate ratio, 1.48; 95% confidence interval, 1.36-1.61; P=.00). A significant increase in antenatal corticosteroid therapy administration rates was also seen in full-term births following the online publication of the Antenatal Late Preterm Steroids study. No significant changes were seen in antenatal corticosteroid administration rates in gestational age groups of 32+0 to 33+6 weeks or 28+0 to 31+6 weeks. Online publication of the Antenatal Late Preterm Steroids study was associated with an immediate and sustained increase in the rates of antenatal corticosteroid therapy administration in late preterm births across the United States, demonstrating a swift and successful implementation of the Antenatal Late Preterm Steroids study guidance into clinical practice. However, there is an unnecessary increase in full-term infants receiving antenatal corticosteroid therapy. Given that the long-term consequences of antenatal corticosteroid therapy are yet to be elucidated, efforts should be made to minimize the number of infants unnecessarily exposed to antenatal corticosteroid therapy.

Antenatal factors for neonatal seizures among late preterm births**

Objective The objective of this study was to evaluate for antenatal risk factors for neonatal seizures among late preterm births. Study design This was a case control study which included late preterm births without anomaly from the United States Natality database. Cases were infants with neonatal seizures, while the controls consisted of infants without neonatal seizures. Maternal and pregnancy characteristics were compared. Multivariable logistic regression was performed to investigate risk factors for neonatal seizures. Results Of the 943,580 late preterm births, 512 (0.05%) developed neonatal seizures. Significant risk factors associated with neonatal seizures among late preterm births included number of prenatal visits (adjusted odds ratio [aOR] 0.94, 95% CI [0.92–0.96]), smoking history (aOR 1.78, 95% CI [1.41–2.25]), chorioamnionitis (aOR 4.37, 95% CI [2.65–7.21]), non-Hispanic White race (aOR 1.41, 95% CI [1.13–1.76]), and cesarean birth (aOR 2.31, 95% CI [1.91–2.80]). Conclusion Number of prenatal visits, history of smoking, chorioamnionitis, non-Hispanic white race, and cesarean birth are risk factors for neonatal seizures at late preterm gestation.

Antenatal corticosteroid administration and attention-deficit/hyperactivity disorder in childhood: a regression discontinuity study.

Background:Antenatal corticosteroids reduce respiratory morbidity in preterm infants, but their use during late preterm gestation (34–36 weeks) is limited because their safety for longer-term child neurodevelopment is unclear. We sought to determine if fetuses with higher probability of exposure to antenatal corticosteroids had increased rates of prescriptions for attention-deficit/hyperactivity disorder (ADHD) medication in childhood, using a quasiexperimental design that better controls for confounding than existing observational studies.Methods:We identified 16 358 children whose birthing parents were admitted for delivery between 31 + 0 (31 weeks, 0 days) and 36 + 6 weeks’ gestation in 2000–2013, using a perinatal data registry from British Columbia, Canada, and linked their records with population-based child ADHD medication data (2000–2018). We used a regression discontinuity design to capitalize on the fact that pregnancies presenting for delivery immediately before and immediately after the clinical cut-off for antenatal corticosteroid administration of 34 + 0 weeks’ gestation have very different levels of exposure to corticosteroids, but are otherwise similar with respect to confounders.Results:Over a median follow-up period of 9 years, 892 (5.5%) children had 1 or more dispensations of ADHD medication. Children whose birthing parents were admitted for delivery just before the corticosteroid clinical cut-off of 34 + 0 weeks’ gestation did not appear to be more likely to be prescribed ADHD medication than those admitted just after the cut-off (rate ratio 1.1, 95% confidence interval [CI] 0.8 to 1.6; 1.3 excess cases per 100 children, 95% CI −2.5 to 5.7).Interpretation:We found little evidence that children with higher probability of exposure to antenatal corticosteroids have higher rates of ADHD prescriptions in childhood, supporting the safety of antenatal corticosteroids for this neurodevelopmental outcome.

Management of severe hyperbilirubinemia in the cholestatic neonate: a review and an approach.

A review of the literature demonstrates that severe total hyperbilirubinemia (total serum bilirubin≥20 mg/dL [340 µmol/L])in some cholestatic term (≥37 weeks) and late-preterm (≥340/7-366/7 weeks) gestation neonates poses a risk for bilirubin-induced brain damage. When the direct bilirubin fraction is <50% of the total serum bilirubin this risk is associated with the total serum bilirubin alone and treatment decisions should be based on the total serum bilirubin. On the other hand, there are limited data on the risk of bilirubin-induced brain damage in the neonate with severe total hyperbilirubinemia and a direct bilirubin fraction that is equal to or exceeds 50% of the total serum bilirubin. When this rare combination occurs, efforts to keep the indirect bilirubin fraction from reaching severe levels might, nevertheless, be prudent.

Association between cesarean section rate and maternal age in twin pregnancies

To evaluate the effect of maternal age to the cesarean section rate of twin pregnancies in late preterm and term gestation. A retrospective study was performed on twin pregnancies delivered at Seoul National University Bundang Hospital from June 2003 to December 2020. Preterm births before 34weeks of gestation were excluded, and only live births were analyzed. The patients were classified into four groups according to maternal age (<30, 30-34, 35-39, and≥40 years). The primary outcome was the rate of cesarean section. The median value of maternal body mass index, the rate of assisted reproductive technology, dichorionic twin pregnancy, preeclampsia, and gestational diabetes increased significantly according to the maternal age group (all p<0.05). Among a total of 2,075 twin pregnancies, the rates of cesarean section were 65, 74, 80, and 95% for groups with maternal age under 30, 30-34, 35-39, and≥40 years, respectively (p<0.001). The cesarean section rates after a trial of labor were 22, 22, 28, and 63%, respectively (p=0.032). Maternal old age was an independent risk factor for cesarean section after a trial of labor in both nulliparous and multiparous women after adjusting for confounding factors. The rate of cesarean section in twin pregnancies significantly increased as maternal age increased, even in multiparous women.

Evaluation of Risk Factors and Approach to Screening for Asymptomatic Neonatal Hypoglycemia

Introduction: Protocols to identify asymptomatic neonatal hypoglycemia (NH) rely on the presence of established risk factors (late preterm gestation, large or small for gestational age, and infant of a diabetic mother) for inclusion. We analyzed the performance of these risk factors in identifying hypoglycemia in modern practice, and additionally evaluated the optimal duration of screening blood glucose measurements. Methods: We analyzed a retrospective cohort of 830 infants with 1 or more known risk factor(s) for NH admitted to the mother-baby unit of a single tertiary-care center from May 2017 to April 2018. Manual chart review was performed for data extraction and confirmation of risk factor(s). Infants were excluded if glucose measurements were obtained for any reason other than screening for asymptomatic NH. Results: Of the 830 included infants, 31 (3.7%) ultimately received intravenous dextrose (IVD). Most screened infants (n = 510, 61.4%) did not develop hypoglycemia. None of the established risk factors showed strong association with hypoglycemia. Cesarean delivery was associated with hypoglycemia, although not strongly. All infants who received IVD for feeding-refractory hypoglycemia were identified by the first 2 measurements with nearly all (30/31, 97%) identified at the initial measurement. Conclusions: Currently accepted risk factors are limited in their ability to identify infants who subsequently develop hypoglycemia, and as a result, most screened infants do not develop hypoglycemia. The majority of infants in our cohort who did develop hypoglycemia achieved normoglycemia with feeding-based interventions and did not require IVD. Those that received IVD were more likely to develop hypoglycemia early and to a more severe degree. Together, our data suggest further refinement of protocol duration and risk factors utilized for screening as potential areas of screening protocol optimization.