Neonatal respiratory complications in twins at 36-38 weeks of gestation.

BACKGROUND: Twin pregnancies are associated with a high risk of perinatal mortality and morbidity. Late preterm or early term delivery is frequently performed to avoid unexpected fetal death in uncomplicated twin pregnancies. Nonetheless, delivery before full term is associated with neonatal respiratory complications. This study aimed to evaluate perinatal respiratory complications in twins delivered between 36 and 38 weeks of gestation. METHODS: A retrospective cohort study was conducted on twins delivered between 36 and 38 weeks of gestation from January 2008 to June 2020. The primary outcomes were the incidence of composite neonatal respiratory morbidity, which included respiratory distress syndrome, transient tachypnea of the newborn, meconium aspiration syndrome, mechanical ventilation or continuous positive airway pressure according to gestational age at delivery, and chorionicity. The relationship between gestational age at delivery and composite neonatal respiratory morbidity was evaluated using multivariate logistic regression analysis adjusted for potential confounders. RESULTS: This study included 1608 twins (614 monochorionic diamniotic twins, 994 dichorionic diamniotic twins). At 36, 37, and 38 weeks of gestation, the frequencies of composite neonatal respiratory morbidity were 19.4%, 10.7%, and 9.2% in dichorionic diamniotic twins and 13.6%, 8.7%, and 9.4% in monochorionic diamniotic twins, respectively. In dichorionic diamniotic twins, the composite neonatal respiratory morbidity rate was higher for twins delivered at 36 weeks of gestation than for those delivered at 37 weeks. No significant differences between monochorionic diamniotic twins were detected. CONCLUSIONS: In uncomplicated dichorionic diamniotic twin pregnancies, delivery should be considered after 37 weeks of gestation to reduce neonatal respiratory complications.

The World Health Organization Antenatal CorTicosteroids for Improving Outcomes in preterm Newborns (ACTION-III) Trial: study protocol for a multi-country, multi-centre, double-blind, three-arm, placebo-controlled, individually randomized trial of antenatal corticosteroids for women at high probability of late preterm birth in hospitals in low- resource countries.

BACKGROUND: Preterm birth complications are the leading cause of newborn and under-5 mortality. Over 85% of all preterm births occur in the late preterm period, i.e. between 34 and < 37 weeks of gestation. Antenatal corticosteroids (ACS) prevent mortality and respiratory morbidity when administered to women at high risk of an early preterm birth, i.e. < 34 weeks' gestation. However, the benefits and risks of ACS in the late preterm period are less clear; both guidelines and practices vary between settings. Emerging evidence suggests that the benefits of ACS may be achievable at lower doses than presently used. This trial aims to determine the efficacy and safety of two ACS regimens compared to placebo, when given to women with a high probability of late preterm birth, in hospitals in low-resource countries. METHODS: WHO ACTION III trial is a parallel-group, three-arm, individually randomized, double-blind, placebo-controlled trial of two ACS regimens: dexamethasone phosphate 4 × 6 mg q12h or betamethasone phosphate 4 × 2 mg q 12 h. The trial is being conducted across seven sites in five countries-Bangladesh, India, Kenya, Nigeria, and Pakistan. Eligible women are those with a gestational age between 34 weeks 0 days and 36 weeks 5 days, who have a high probability of preterm birth between 12 h and 7 days (up to 36 weeks 6 days gestation). The primary outcome is a composite of stillbirth or neonatal death within 72 h of birth or use of newborn respiratory support within 72 h of birth or prior to discharge from hospital, whichever is earlier. Secondary outcomes include safety and health utilization measures for both women and newborns. The sample size is 13,500 women. DISCUSSION: This trial will evaluate the benefits and possible harms of ACS when used in women likely to have a late preterm birth. It will also evaluate a lower-dose ACS regimen based on literature from pharmacokinetic studies. The results of this trial will provide robust critical evidence on the safe and appropriate use of ACS in the late preterm period internationally. TRIAL REGISTRATION: ISRCTN11434567 . Registered on 7 June 2021.

SIRT1 alleviates insulin resistance and respiratory distress in late preterm rats by activating QKI5-mediated PPARγ/PI3K/AKT pathway.

Neonatal respiratory distress syndrome (NRDS) is a common complication of gestational diabetes mellitus (GDM) and late preterm births. Research suggests that SIRT1 was involved in LPS-induced acute respiratory distress syndrome, but its mechanism remains to be further explored. Here, pregnant rats were intraperitoneally injected with 45 mg/Kg streptozotocin at day 0 of gestation to induce GDM and injected with LPS at day 17 of gestation to induce late preterm birth. Pioglitazone (a PPARγ agonist) was administered from day 17 to parturition in GDM group, and it was administered for 3 days before LPS injection in late preterm birth group. SRT1720 (a SIRT1 activator) was administered by oral gavage from day 0 to day 17 in both groups. Our data showed that activation of SIRT1 or PPARγ alleviated the abnormal blood glucose metabolism and lung tissue injury, downregulated expression of surfactant proteins (SP-B and SP-C), and decreased activation of the PI3K/AKT pathway induced by GDM and late preterm birth in neonatal rats. Moreover, an insulin resistance model was established by treating primary AT-II cells with insulin. Activation of SIRT1 reversed insulin-induced reduction in cell proliferation, glucose consumption, SP-B and SP-C expression, and the activity of the PI3K/AKT pathway and increase in cellular inflammation and apoptosis. Mechanistically, SIRT1 upregulated PPARγ expression via deacetylation of QKI5, an RNA binding protein that can stabilize its target mRNA molecules, and then activated the PI3K/AKT pathway. In conclusion, SIRT1 promotes the expression of PPARγ via upregulation of QKI5 and activates the PI3K/AKT pathway, thus mitigating NRDS caused by GDM and late preterm birth.

Prevalence of preterm birth in Scandinavian countries: a systematic review and meta-analysis.

OBJECTIVES: As welfare societies, Scandinavian countries share characteristics of equality related to healthcare access, gender, and social services. However, cultural and lifestyle variations create country-specific health differences. This meta-analysis assessed the prevalence of preterm birth (PTB) and its categories in Scandinavian countries. METHODS: A systematic search in key databases of literature published between 1990 and 2021 identified studies of the prevalence of PTB and its categories. Following the use of the Freeman-Tukey double arcsine transformation, a meta-analysis of weighted data was performed using the random-effects model and meta-prop method. RESULTS: We identified 109 observational studies that involved 86,420,188 live births. The overall pooled prevalence (PP) of PTB was 5.3% (PP = 5.3%, 95% confidence interval [CI] 5.1%, 5.5%). The highest prevalence was in Norway (PP = 6.2%, 95% CI 5.3%, 7.0%), followed by Sweden (PP = 5.3%, 95% CI 5.1%, 5.4%), Denmark (PP = 5.2%, 95% CI 4.9%, 5.3%), and Iceland (PP = 5.0%, 95% CI 4.4%, 5.7%). Finland had the lowest PTB rate (PP = 4.9%, 95% CI 4.7%, 5.1%). CONCLUSIONS: The overall PP of PTB was 5.3%, with small variations among countries (4.9%-6.2%). The highest and lowest PPs of PTB were in Norway and Finland, respectively.

Factors associated with low birthweight among late preterm singletons in Japan using pregnancy birth registry data.

Late preterm (LP, born between 34 0/7 and 36 6/7 weeks of gestation) infants may experience several adverse outcomes, similar to those experienced by low birthweight (LBW, birthweight <2500 g) infants. However, while LP infants are often born with LBW, the association between LP and LBW remains unknown. This study aimed to investigate LBW rate and independent risk factors for LBW in LP singleton neonates. We retrospectively analyzed data of LP singleton neonates, born between 2013 and 2017, from the Japan Society of Obstetrics and Gynecology Successive Pregnancy Birth Registry System. The exclusion criteria included stillbirths and infants with missing data. Logistic regression analyses were performed to investigate maternal and perinatal factors associated with LBW in LP singletons. LBW was observed in 62.5% (n = 35,113) of 56,160 LP singleton births. In the multiple logistic regression analysis, LBW in LP neonates was independently associated with modifiable maternal factors, including pre-pregnancy underweight, inadequate gestational weight gain, and smoking during pregnancy, as well as non-modifiable factors, including younger maternal age, nulliparity, hypertensive disorder of pregnancy, preeclampsia, cesarean section delivery, and female offspring. According to the Japanese pregnancy birth registry data, more than half of LP neonates were LBW. We previously discussed the issue of LBW regarding infants with different backgrounds, as there are many different causes of LBW. Several risk factors should be subdivided and considered for the risk of LP and LBW.

Reduction in preterm birth among COVID-19-vaccinated pregnant individuals in the United States.

BACKGROUND: Most studies investigating preterm birth and COVID-19 vaccination have suggested no difference in preterm birth rates between vaccinated and unvaccinated pregnant individuals; however, 1 recent study suggested a protective effect of COVID-19 vaccination on preterm birth rates in Australia. OBJECTIVE: This study aimed to determine whether a similar association and protective effect of COVID-19 vaccination on preterm birth would be found in our multistate, US cohort. STUDY DESIGN: A cohort study was conducted using the Vizient Clinical Database, which included data from 192 hospitals in 38 states. Pregnant individuals who delivered between January 2021 and April 2022 were included. Propensity score matching was used to match a "treated" group of pregnant individuals with any COVID-19 vaccination (incomplete or complete vaccination) to a group that had not received any COVID-19 vaccination (the "untreated" group). A complete vaccination series of ≥2 doses of the Moderna or Pfizer vaccines or at least 1 dose of the Johnson & Johnson vaccine was considered. An incomplete series was receipt of 1 dose of the Pfizer or Moderna vaccine. We examined the association between COVID-19 vaccination status and preterm birth at <28, <34, and <37 weeks of gestation. Multivariable logistic regression models were used to adjust for potential confounders, with adjusted odds ratios as the measure of treatment effect. RESULTS: Matching with replacement was performed for 5749 treated participants. After propensity score matching, there was no difference in maternal demographics of age, race, insurance status, parity, or comorbid conditions. Vaccinated individuals were 26% less likely to deliver at <37 weeks of gestation (adjusted odds ratio, 0.74; 95% confidence interval, 0.73-0.75; P<.001), 37% less likely to deliver at <34 weeks of gestation (adjusted odds ratio, 0.63; 95% confidence interval, 0.61-0.64; P<.001), and 43% less likely to deliver at <28 weeks of gestation (adjusted odds ratio, 0.57; 95% confidence interval, 0.55-0.60; P<0.001) than unvaccinated individuals. CONCLUSION: Vaccination against COVID-19 may be protective against preterm birth.

Different pathways for preterm birth between singleton and twin pregnancies: a population-based registry study of 481 176 nulliparous women.

OBJECTIVE: To explore the contribution of pregnancy-related complications on the prevalence of extremely, very and late preterm births in singleton and twin pregnancies. To study the risk of spontaneous preterm birth in twin pregnancies compared with singleton pregnancies. DESIGN: Population-based registry study. SETTING: Medical birth registry of Norway and Statistics Norway. POPULATION: Nulliparous women with singleton (n = 472 449) or twin (n = 8727) births during 1999-2018. METHODS: Prevalence rates of pregnancy-related complications for extremely, very and late preterm birth in twin and singleton pregnancies were calculated with 95% confidence intervals. Multivariable logistic regression was applied to assess odds ratios for preterm birth, adjusted for obstetric and socio-economic factors. MAIN OUTCOME MEASURES: Extremely preterm (<28+0  weeks of gestation), very preterm (28+0 -33+6  weeks of gestation) and late preterm (34+0 -36+6  weeks of geatation) birth. RESULTS: Preterm birth was significantly more prevalent in twin pregnancies than in singleton pregnancies in all categories: all preterm (54.7% vs 6.1%), extremely preterm (3.6% vs 0.4%), very preterm (18.2% vs 1.4%) and late preterm (33.0% vs 4.3%) births. Stillbirth, congenital malformation and pre-eclampsia were more prevalent in twin pregnancies than in singleton pregnancies, but the prevalence of complications differed in the three categories of preterm birth. Pre-eclampsia was more prevalent in singleton than in twin pregnancies ending in extremely and very preterm birth. The adjusted odds of spontaneous preterm live birth were between 19- and 54-fold greater in twin pregnancies than in singleton pregnancies. CONCLUSIONS: Singleton and twin pregnancies seem to have different pathways leading to extremely, very and late preterm birth.

Associations between Phthalate Exposure and Gestational Age at Delivery in a Diverse Pregnancy Cohort.

The association between prenatal phthalate exposure and late preterm birth (LPTB) is unclear. We examined singleton pregnancies (2006-2011) from a racially and socioeconomically diverse sample of women in the CANDLE cohort of the ECHO-PATHWAYS Consortium. Urine collected in the second and third trimester was analyzed for 14 phthalate metabolites. Multivariate logistic and linear regressions were performed for LPTB, defined as delivery 34-37 weeks, and gestational week, respectively. Models were controlled for socio-demographics, behavioral factors, clinical measurements, medical history, and phthalates in the other trimester. Effect modification by race and pregnancy stress, indicated by intimate partner violence (IPV), was investigated. We conducted a secondary analysis in women with spontaneous preterm labor. The rate of LPTB among 1408 women (61% Black, 32% White) was 6.7%. There was no evidence of decreased gestational age (GA) in association with any phthalate metabolite. Each two-fold increase in third trimester mono-benzyl phthalate (MBzP) was associated with 0.08 weeks longer gestational age (95% CI: 0.03, 0.12). When restricting to women with spontaneous labor, second trimester mono-n-butyl phthalate (MBP) was associated with 54% higher odds (95% CI: 2%, 132%) of LPTB. Associations were not modified by maternal race or IPV exposure. In conclusion, we observed mixed evidence concerning our hypothesis that prenatal phthalate exposure increases risk of LPTB, though secondary analyses suggest increased risk of spontaneous LPTB associated with MBP, which is consistent with a recent pooled analysis of 16 cohorts.

Motor Optimality Scores are significantly lower in a population of high-risk infants than in infants born moderate-late preterm.

BACKGROUND: The Motor Optimality Score-Revised (MOS-R) is a detailed scoring of the General Movement Assessment (GMA), measuring the spontaneous behaviors of infants. Infants born moderate-late preterm are not traditionally followed in high-risk clinics, but have increased risk of neurodevelopmental disability. AIMS: Compare MOS-R at 3 months corrected age (CA) in high-risk (HR; very preterm or abnormal neuroimaging) infants to infants born moderate-late preterm (MLP). STUDY DESIGN: In this prospective cohort study, parents of enrolled infants created video recordings using an app at 3 months CA. Videos were scored with the General Movement Assessment (GMA) and MOS-R. MOS-R scores were divided into "higher-risk" (≤19) and "lower-risk" (≥20). SUBJECTS: 181 infants born MLP or categorized as HR. RESULTS: Among enrolled infants, 68 (38 %) were in the MLP group, and 113 infants were in the HR group. The HR group had 3.8 increased odds of having an aberrant GMA score compared to the MLP group (p < 0.01, 95 % CI 1.38-10.52). The HR group had significantly lower MOS-R scores (mean 20) than the MLP group (mean 24; p < 0.001; 95%CI 3.3-7.3). The HR group had 11.2 increased odds of having a higher-risk MOS-R score (95%CI 2.5-47.6, p < 0.001) than MLP group. Infants were most likely to have a lower MOS-R score if they had any of the following: VP shunt placement, periventricular leukomalacia, or bronchopulmonary dysplasia. CONCLUSIONS: Aberrant GMA and higher-risk MOS-R scores were more common in infants at high-risk, reflecting history of brain lesions and younger gestational age at birth.

Impact of early term and late preterm birth on infants' neurodevelopment: evidence from a cohort study in Wuhan, China.

BACKGROUND: The incidences of early term and late preterm birth have increased worldwide during recent years. However, there is a lack of prospective study about the influence of early term and late preterm birth on infants' neurodevelopment, especially at the early stage. Therefore, we conducted this cohort study to investigate the impact of early term and late preterm birth on infants' neurodevelopment within 6 months. METHODS: This cohort study was conducted in Wuhan, China, between October 2012 and September 2013. A total of 4243 singleton infants born within 34-41 weeks of gestation at Wuhan Children's Hospital were included. The Gesell Developmental Scale (GDS) was utilized to evaluate the neurodevelopment of infants. RESULTS: Among the 4243 included participants, 155 (3.65%) were late preterm infants, 1288 (30.36%) were early term infants, and 2800 (65.99%) were full term infants. After adjusted for potential confounders, significant negative relationship was shown between late preterm birth and development quotient (DQ) in all domains of neurodevelopment: gross motor (ß = - 17.42, 95% CI: - 21.15 to - 13.69), fine motor (ß = - 23.61, 95% CI: - 28.52 to - 18.69), adaptability (ß = - 10.10, 95% CI: - 13.82 to - 6.38), language (ß = - 6.28, 95% CI: - 9.82 to - 2.74) and social behavior (ß = - 5.99, 95% CI: - 9.59 to - 2.39). There was a significant negative trend for early term birth in DQ of fine motor (ß = - 2.01, 95% CI: - 3.93 to - 0.09). Late preterm infants had a significantly elevated risk of neurodevelopmental delay in domains of gross motor (adjusted OR = 3.82, 95% CI: 2.67 to 5.46), fine motor (adjusted OR = 3.51, 95% CI: 2.47 to 5.01), and adaptability (adjusted OR = 1.60, 95% CI: 1.12 to 2.29), whereas early term birth was significantly associated with neurodevelopmental delay of fine motor (adjusted OR = 1.22, 95% CI: 1.05 to 1.42). CONCLUSIONS: This study suggested that late preterm birth mainly elevated the risk of neurodevelopmental delay of gross motor, fine motor, and adaptability, whereas early term birth was associated with the developmental delay of fine motor within 6 months. Further research is needed to determine the effectiveness and necessity of the interventions at the early stage for early term and late preterm infants who had suspected neurodevelopmental delay.

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.

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

BACKGROUND: 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. OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Indications for late preterm birth, and factors associated with short term maternal and neonatal outcomes at a tertiary care institution.

Background: The preterm birth rate is rising mainly because of the marked increase in late preterm deliveries. Objectives: To evaluate the indications for LPTB and the factors associated with the short term maternal and neonatal outcomes. Methods: This retrospective study was conducted at a tertiary health care institution. The study sample included 191 women who delivered between October 2019 to November 2020. Results: The majority (81%) were medically indicated LPTB, and mainly for maternal indications (77%). The most common maternal indication for LPTB was for hypertensive disease of pregnancy (HDP) (82.5%). There was a significant increase in the high care/ ICU admission for maternal indication of LPTB, maternal age < 20 years, and patients with HDP. There was 1 maternal death and 1 neonatal death. 48% of the neonates were admitted to NICU and 53% had neonatal complications. Neonates born by caesarean delivery were more likely to have respiratory complications and be admitted to NICU. Conclusion: These maternal/ neonatal factors should be used to identify patients at risk of adverse maternal and neonatal outcomes.

Risk of preterm birth in relation to history of preterm birth: a population-based registry study of 213 335 women in Norway.

OBJECTIVE: To assess the association between preterm first birth and preterm second birth according to gestational age and to determine the role of placental disorder in recurrent preterm birth. DESIGN: Population-based registry study. SETTING: Medical Birth Registry of Norway and Statistics Norway. POPULATION: Women (n = 213 335) who gave birth to their first and second singleton child during 1999-2014 (total n = 426 670 births). METHODS: Multivariate logistic regression analyses, adjusted for placental disorders, maternal, obstetric and socio-economic factors. MAIN OUTCOME MEASURES: Extremely preterm (<28+0 weeks), very preterm (28+0 -33+6 weeks) and late preterm (34+0 -36+6 weeks) second birth. RESULTS: Preterm birth (<37 weeks) rates were 5.6% for first births and 3.7% for second births. Extremely preterm second births (0.2%) occurred most frequently among women with an extremely preterm first birth (aOR 12.90, 95% CI 7.47-22.29). Very preterm second births (0.7%) occurred most frequently after an extremely preterm birth (aOR 12.98, 95% CI 9.59-17.58). Late preterm second births (2.8%) occurred most frequently after a previous very preterm birth (aOR 6.86, 95% CI 6.11-7.70). Placental disorders contributed 30-40% of recurrent extremely and very preterm births and 10-20% of recurrent late preterm birth. CONCLUSION: A previous preterm first birth was a major risk factor for a preterm second birth. The contribution of placental disorders was more pronounced for recurrent extremely and very preterm birth than for recurrent late preterm birth. Among women with any category of preterm first birth, more than one in six also had a preterm second birth (17.4%). TWEETABLE ABSTRACT: Preterm first birth is a major risk factor for subsequent preterm birth, regardless of maternal, obstetric or fetal risk factors.

Incidence, Risk Factors, and Outcomes of Preterm and Early Term Births: A Population-Based Register Study.

Preterm birth (PTB) and early term birth (ETB) are associated with high risks of perinatal mortality and morbidity. While extreme to very PTBs have been extensively studied, studies on infants born at later stages of pregnancy, particularly late PTBs and ETBs, are lacking. In this study, we aimed to assess the incidence, risk factors, and feto-maternal outcomes of PTB and ETB births in Qatar. We examined 15,865 singleton live births using 12-month retrospective registry data from the PEARL-Peristat Study. PTB and ETB incidence rates were 8.8% and 33.7%, respectively. PTB and ETB in-hospital mortality rates were 16.9% and 0.2%, respectively. Advanced maternal age, pre-gestational diabetes mellitus (PGDM), assisted pregnancies, and preterm history independently predicted both PTB and ETB, whereas chromosomal and congenital abnormalities were found to be independent predictors of PTB but not ETB. All groups of PTB and ETB were significantly associated with low birth weight (LBW), large for gestational age (LGA) births, caesarean delivery, and neonatal intensive care unit (NICU)/or death of neonate in labor room (LR)/operation theatre (OT). On the other hand, all or some groups of PTB were significantly associated with small for gestational age (SGA) births, Apgar < 7 at 1 and 5 min and in-hospital mortality. The findings of this study may serve as a basis for taking better clinical decisions with accurate assessment of risk factors, complications, and predictions of PTB and ETB.

Time interval from late preterm antenatal corticosteroid administration to delivery and the impact on neonatal outcomes.

BACKGROUND: Although administration of antenatal corticosteroids has been shown to decrease neonatal respiratory morbidity when given to women at risk for late preterm birth, the time interval from antenatal corticosteroid administration to delivery that is associated with the greatest neonatal benefit remains unknown. OBJECTIVE: This study aimed to evaluate whether the time interval from administration of late preterm antenatal corticosteroids to delivery is associated with a change in the likelihood of transient tachypnea of the newborn, respiratory distress syndrome, and hypoglycemia. STUDY DESIGN: This was a retrospective cohort study of all singleton neonates who were exposed to 1 or 2 doses of antenatal corticosteroids in the late preterm period (34+0 to 36+6 weeks' gestation) within a large healthcare system between November 2017 and March 2020. Neonates exposed to antenatal corticosteroids before 34 weeks' gestation and those with major fetal structural malformations and chromosomal disorders were excluded. Cases were stratified into the following groups based on the time interval from the first dose of antenatal corticosteroid administration to delivery: <2 days, 2 to 7 days, and >7 days. The primary outcome of transient tachypnea of the newborn was compared among the 3 groups. Secondary outcomes included respiratory distress syndrome and hypoglycemia. A multivariable logistic regression was performed to evaluate the association between the time interval and neonatal outcomes while adjusting for potential confounders. For each outcome, delivery within 2 to 7 days from the first dose of betamethasone administration was defined as the reference group. Data were presented as adjusted odds ratios with 95% confidence intervals, and statistical significance was defined as P < .05. RESULTS: The study cohort comprised 1248 neonates. Of those, 649 (52%) were exposed to 1 dose of antenatal corticosteroids. There were statistically significant differences in the maternal characteristics such as nulliparity, pregnancies complicated by hypertensive disorders and fetal growth restriction, gestational age at antenatal corticosteroid administration, gestational age at delivery, and mode of delivery among the 3 groups. There was a significantly increased risk for transient tachypnea of the newborn (adjusted odds ratio, 4.81; 95% confidence interval, 1.72-12.92) and respiratory distress syndrome (adjusted odds ratio, 9.86; 95% confidence interval, 1.15-84.24) associated with delivery <2 days of antenatal corticosteroid administration. The risk for hypoglycemia was highest in the delivery <2 days group (adjusted odds ratio, 3.44; 95% confidence interval, 2.10-5.63) and decreased as the time interval from antenatal corticosteroid administration to delivery increased (adjusted odds ratio, 0.32; 95% confidence interval, 0.20-0.51 for delivery >7 days). CONCLUSION: Adverse neonatal outcomes such as transient tachypnea of the newborn, respiratory distress syndrome, and hypoglycemia are more common when late preterm birth occurs <2 days after antenatal corticosteroid administration when compared with birth 2 to 7 days after administration. In addition, delivery >7 days after antenatal corticosteroid administration is associated with a decreased risk for hypoglycemia. Understanding the impact of antenatal corticosteroid timing on neonatal outcomes is essential in caring for patients at risk for late preterm birth.

Association between maternal country of birth and preterm birth: A population-based register study of 910,752 deliveries.

Aims: The aim of this study was to analyse associations between maternal country of birth and preterm birth among women giving birth in Norway. Methods: A population-based register study was conducted employing official national databases in Norway. All singleton births, with neonates without major anomalies, between 1999 and 2014 were included (N=910,752). We estimated odds ratios (ORs) for extremely preterm birth (<28 weeks gestation), very preterm birth (28-33 weeks gestation) and late preterm birth (34-36 weeks gestation) by maternal country of birth. We conducted multivariable regression analyses, adjusting for maternal, obstetric and socio-economic confounders. Results: For extremely preterm births (0.4% of the study population), women with an unknown country of birth (adjusted OR (aOR)=3.09; 95% confidence interval (CI) 2.26-4.22) and women born in sub-Saharan Africa (aOR=1.66; CI 1.40-1.96) had the highest ORs compared to Norwegian-born women. For very preterm births (1.2% of the study population), women with an unknown country of birth (aOR=1.72; CI 1.36-2.18) and women born in South Asia (aOR=1.48; CI 1.31-1.66) had the highest ORs. For late preterm births (3.8% of the study population), women born in East Asia Pacific/Oceania (aOR=1.33; CI 1.25-1.41) and South Asia (aOR=1.30; CI 1.21-1.39) had the highest ORs. Conclusions: After adjusting for maternal, obstetric and socio-economic risk factors, maternal country of birth remained significantly associated with preterm birth. Women with an unknown country of birth and women born in sub-Saharan Africa were found to be at increased risk of extremely preterm birth.

Practice patterns in the administration of late preterm antenatal corticosteroids.

BACKGROUND: Given the unpredictable nature of preterm birth and the short-term impact of antenatal corticosteroids on neonatal outcomes, optimal timing of antenatal corticosteroid administration (2-7 days from expected birth) remains challenging. OBJECTIVE: We set out to evaluate the likelihood of delivery between 2 and 7 days after antenatal corticosteroid administration in the late preterm period and whether this differs based on the indication for corticosteroid administration. STUDY DESIGN: Retrospective cohort of all singletons that received antenatal corticosteroids in the late preterm period (34 0/7 to 36 6/7 weeks' gestation) and delivered within a large health system between November 2017 and March 2020. Women who received antenatal corticosteroids before the late preterm period, major fetal structural malformations, and cases with missing data were excluded. Cases were stratified on the basis of the indication for antenatal corticosteroid administration, that is, anticipated spontaneous late preterm birth or medically indicated late preterm birth. The primary outcome was delivery between 2 and 7 days after the administration of the first dose of antenatal corticosteroids. Secondary outcomes included time interval from antenatal corticosteroid administration to delivery and delivery during the first 2 days or later than 7 days after antenatal corticosteroid administration. Multivariable logistic regression was performed to evaluate factors associated with optimal timing while adjusting for potential confounders. RESULTS: Of the 1238 patients included in the study, 656 (53%) delivered within the first day after antenatal corticosteroid administration and thus received only the first of 2 doses. Regardless of the indication for late preterm antenatal corticosteroid administration, the likelihood of delivery between 2 and 7 days later was 13.3% (165 of 1238). Moreover, it was more common (23.4% vs 5.0%; P≤.001) (Table 2) and more likely (adjusted odds ratio, 5.88; 95% confidence interval, 4.00-9.09) in women at risk of medically indicated preterm birth than in those with anticipated spontaneous preterm birth. Furthermore, women with anticipated spontaneous preterm birth had a shorter time interval from antenatal corticosteroid administration to delivery (10.7 vs 49.71 hour; P≤.001). CONCLUSION: Regardless of the indication for late preterm antenatal corticosteroid administration, the likelihood of delivery between 2 and 7 days later was low. Nevertheless, our data suggested that delivery within the desired time interval of antenatal corticosteroid administration is more common in women at risk of medically indicated late preterm birth compared with those at risk of spontaneous late preterm birth.

The cause of birth is associated with neonatal prognosis in late preterm singletons.

INTRODUCTION: Recent studies have shown that the cause of very preterm births may be related to neonatal morbidity and mortality. Even though these risks are lower among late preterm births, this group accounts for the vast majority of all preterm births. The objective of this study was to evaluate the relation of neonatal morbidity and mortality to the cause of late preterm birth. MATERIALS AND METHODS: This retrospective observational cohort study included all women who gave birth to liveborn singletons from 34 to 36 weeks+6 days of gestation in a French level III maternity hospital in the 5-year period 2013-2017. The causes of preterm delivery were divided into 6 mutually exclusive groups. The main outcome was a composite neonatal morbidity criterion, defined by at least one among the following criteria: neonatal respiratory distress, neurological complications, neonatal sepsis, severe necrotizing enterocolitis, and neonatal hypoglycemia. We analyzed the association between cause of preterm delivery and neonatal morbidity after adjustment for gestational age and antenatal corticosteroid therapy. The reference group was preterm labor, defined by spontaneous preterm labor with intact membranes. RESULTS: During the study period, there were a total of 27 110 births, including 1114 singleton births at 34 to 36 weeks of gestation + 6 days (4.1%). Among the 968 late preterm births included, the risk of neonatal morbidity in the group with preterm premature rupture of membranes (PPROM) was similar to that in the preterm labor (reference) group: adjusted odds ratio (aOR) 1.2 (95% CI, 0.8-1.8). All the other causes of late preterm birth were associated with a higher risk of neonatal morbidity than the reference group: aOR 2.0 [95% CI, 1.1-3.5] for hypertensive disorders without suspected fetal growth restriction (FGR) (9.1% of cases), aOR 2.4 [95% CI, 1.4-4.2] for hypertensive disorders with suspected FGR (8.9%), aOR 4.2 [95% CI, 2.2-8.0] for suspected FGR without hypertensive disorders (5.8%), and aOR 4.4 [95% CI, 2.2-8.8] for vaginal bleeding related to abnormal placental insertion (4.7%). CONCLUSION: Among infants born from 34 to 36 weeks + 6 days of gestation, PPROM and preterm labor had similar risks of neonatal morbidity, while the other causes were associated with a risk of neonatal morbidity at least twice that with preterm labor.

Stability of developmental status and risk of impairment at 24 and 36 months in late preterm infants.

BACKGROUND: Few studies investigated whether late preterm infants might have developmental delays in several domains in early life and how stable the lag in developmental status might be. AIM: We aimed to examine the stability of potential delays across developmental domains at 24 and 36 months of age in late preterm (34°-366 weeks) and term (≥37 weeks) children and whether the risk of delays remained high at 36 months. STUDY DESIGN, SUBJECTS, AND OUTCOME MEASURE: We conducted a prospective cohort analysis of the children of pregnant women participating in the Vitamin Antenatal Asthma Reduction Trial (VDAART). 652 children who were prospectively followed up and had parent-completed Ages Stages Questionnaires (ASQ-3) questionnaires at both 24 and 36 months were analyzed to assess their domain-specific developmental status. RESULTS: 6.61 % (42/635) of children had a late preterm birth. Developmental delays were stable between 24 and 36 months on all 5 domains for the children born preterm and on 4/5 domains for those born at term. The developmental domains with the status stability at 24 and 36 months in both late preterm and term children were the gross motor, communication, personal-social skills, and problem-solving. Late preterm children compared with term children remained at higher risk of delays at 36 months for gross motor, communication, and problem-solving skills (aOR = 4.54, 95 %CI: 1.81-10.79; aOR = 8.60, 95 %CI: 3.10-23.28 and aOR = 3.80, 95 %CI: 1.58-8.73, respectively). CONCLUSION: Late preterm birth is associated with suboptimal development and stability in several domains at both 24 and 36 months and compared with term birth, requiring early monitoring and assessment of the developmental lag to avoid potential long-term implications.