Singleton Neonates Research Articles

Impact of antenatal corticosteroids-to-delivery interval on very preterm neonatal outcomes: a retrospective study in two tertiary centers in Japan

BackgroundAntenatal corticosteroids (ACS) are administered to prevent neonatal complications and death in women at risk of imminent preterm birth. Internationally, the optimal interval from ACS to delivery (ACS-to-delivery interval) is within seven days; however, evidence in Asian populations specifically is limited. This study aimed to investigate the association between ACS-to-delivery interval and the incidence of neonatal complications in Japan.MethodsThis retrospective observational study enrolled singleton neonates born preterm at < 32 weeks of gestational age between 2012 and 2020 at two tertiary centers. A total of 625 neonates were divided into the following four groups according to the timing of ACS (measured in days): no ACS (n = 145), partial ACS (n = 85), ACS 1–7 (n = 307), and ACS ≥ 8 (n = 88). The following outcomes were compared between the groups: treated respiratory distress syndrome (RDS), severe intraventricular hemorrhage (IVH), treated patent ductus arteriosus (PDA), necrotizing enterocolitis, sepsis, bronchopulmonary dysplasia (BPD), treated retinopathy of prematurity (ROP), periventricular leukomalacia, and death discharge.ResultsThe ACS 1–7 group had significantly decreased adjusted odds ratios (ORs) for treated RDS (0.37 [95% confidence interval: 0.23, 0.57]), severe IVH (0.21 [0.07, 0.63]), treated PDA (0.47 [0.29, 0.75]), and treated ROP (0.50 [0.25, 0.99]) compared with the no ACS group. The ACS ≥ 8 group also showed significantly reduced adjusted ORs for RDS (0.37 [0.20, 0.66]) and treated PDA (0.48 [0.25, 0.91]) compared with the no ACS group. However, the adjusted ORs for BPD significantly increased in both the ACS 1–7 (1.86 [1.06, 3.28]) and ACS ≥ 8 groups (2.94 [1.43, 6.05]) compared to the no ACS group.ConclusionsAn ACS-to-delivery interval of 1–7 days achieved the lowest incidence of several complications in preterm neonates born at < 32 weeks of gestational age. Some of the favorable effects of ACS seem to continue even beyond ≥ 8 days from administration. In contrast, ACS might be associated with an increased incidence of BPD, which was most likely to be prominent in neonates delivered ≥ 8 days after receiving ACS. Based on these findings, the duration of the effect of ACS on neonatal complications should be studied further.

Epidural Analgesia During Labor and Neonatal Hypoxic-Ischemic Encephalopathy

Epidural analgesia is used by approximately 70% of birthing persons in the US to alleviate labor pain and is a common cause of elevated temperature in the birthing parent during labor, which, in turn, is associated with adverse neonatal outcomes such as hypoxic-ischemic encephalopathy (HIE). To determine whether epidural analgesia is associated with increased risk of HIE after adjusting for the birthing person's maximal temperature before epidural placement and for the propensity to get an epidural. This retrospective, population-based cohort study was conducted at 15 Kaiser Permanente Northern California hospitals. Participants included singleton neonates born at 35 weeks' or later gestational age between 2012 and 2019. Elective cesarean deliveries and deliveries within 2 hours of hospital admission were excluded. Data analysis was performed from November 2022 to June 2024. The primary exposure was epidural analgesia during labor. The primary outcome was HIE, defined as the presence of both neonatal acidosis (ie, pH <7 or base deficit ≥10) and encephalopathy. The presence and timing of epidural analgesia and demographic, pregnancy, and labor characteristics were extracted from electronic medical records. A propensity score for receiving epidural analgesia was created including demographic variables and comorbidities predating epidural placement. Logistic regression was used to evaluate the association between epidural analgesia and HIE, adjusting for maximal birthing parent's temperature before epidural placement and the propensity for receiving an epidural. Among 233 056 infants born at 35 weeks' or later gestational age by vaginal or unplanned cesarean delivery after at least 2 hours of in-hospital labor, 177 603 (76%) were exposed to epidural analgesia and 439 (0.19%) had HIE. On unadjusted analysis, epidural analgesia was associated with an increased risk of maximal temperature greater than 38 °C during labor (risk ratio [RR], 8.58; 95% CI, 8.06-9.14). Each degree increase in maximal temperature during labor was associated with nearly triple the odds of HIE (odds ratio [OR], 2.82; 95% CI, 2.51-3.17). However, there was no significant association between epidural analgesia and the risk of HIE either on crude (RR, 1.21; 95% CI, 0.96-1.53) or adjusted (adjusted OR, 0.93; 95% CI, 0.73-1.17) analyses. In this cohort study including more than 230 000 parent-infant dyads, epidural analgesia was associated with increased maximal temperature during labor, a known risk factor for HIE. However, epidural analgesia was not associated with increased odds of HIE.

Poor Response to Gonadotropin Stimulation and Perinatal Outcomes in Fresh In Vitro Fertilization Embryo Transfer Cycles-A Retrospective Cohort Study.

Objective: The objective was to examine the association between poor ovarian response to gonadotropin stimulation for in vitro fertilization (IVF) and adverse perinatal outcomes in singleton gestations in young patients. Methods: This was a retrospective cohort study including women aged 17-39 who underwent fresh embryo transfer and delivered a singleton neonate at a single center (pre-implantation genetic testing excluded) (2007-2022). Patients were classified as one of the following categories: poor responders-daily follicle-stimulating hormone (FSH) ≥ 150 IU yielding ≤ 3 retrieved oocytes; normal responders-4-15 oocytes; and high responders with ≥16 oocytes. The primary outcome was a composite of pre-eclampsia (mild or severe), small-for-gestational-age, gestational diabetes mellitus, and preterm birth (<37 weeks). We compared maternal and neonatal outcomes between the three groups. Multivariable logistic regression was used to control for confounders. Results: Overall, 507 women met the inclusion criteria. Of them, there were 44 (8.68%) poor responders, 342 (67.46%) normal responders, and 121 (23.87%) high responders. Poor responders, compared to normal and high responders, were characterized by a higher maternal age (34.64 ± 4.01 vs. 31.4 ± 5.04 vs. 30.01 ± 4.93, p < 0.001, respectively) and total FSH dosage (3028.41 ± 1792.05 IU vs. 2375.11 ± 1394.05 IU vs. 1869.31 ± 1089.63 IU, p < 0.001). The perinatal outcomes examined, including cesarean delivery (CD) rate and the composite outcome, were comparable between groups. Using multivariable logistic regression and adjusting for ovarian response group, maternal age, nulliparity, and estradiol level and endometrial thickness before ovulation triggering, poor response was not associated with CD rate or the composite outcome, with maternal age associated with CD (p = 0.005), and nulliparity with the composite outcome (p = 0.007). Similar results were obtained when comparing poor responders to each other group separately or to all other responders. Conclusions: Poor ovarian response is not associated with increased adverse maternal or neonatal outcomes.

Effectiveness of kangaroo mother care before clinical stabilisation versus standard care among neonates at five hospitals in Uganda (OMWaNA): a parallel-group, individually randomised controlled trial and economic evaluation

Preterm birth is the leading cause of death in children younger than 5 years worldwide. WHO recommends kangaroo mother care (KMC); however, its effects on mortality in sub-Saharan Africa and its relative costs remain unclear. We aimed to compare the effectiveness, safety, costs, and cost-effectiveness of KMC initiated before clinical stabilisation versus standard care in neonates weighing up to 2000 g. We conducted a parallel-group, individually randomised controlled trial in five hospitals across Uganda. Singleton or twin neonates aged younger than 48 h weighing 700-2000 g without life-threatening clinical instability were eligible for inclusion. We randomly assigned (1:1) neonates to either KMC initiated before stabilisation (intervention group) or standard care (control group) via a computer-generated random allocation sequence with permuted blocks of varying sizes, stratified by birthweight and recruitment site. Parents, caregivers, and health-care workers were unmasked to treatment allocation; however, the independent statistician who conducted the analyses was masked. After randomisation, neonates in the intervention group were placed prone and skin-to-skin on the caregiver's chest, secured with a KMC wrap. Neonates in the control group were cared for in an incubator or radiant heater, as per hospital practice; KMC was not initiated until stability criteria were met. The primary outcome was all-cause neonatal mortality at 7 days, analysed by intention to treat. The economic evaluation assessed incremental costs and cost-effectiveness from a disaggregated societal perspective. This trial is registered with ClinicalTrials.gov, NCT02811432. Between Oct 9, 2019, and July 31, 2022, 2221 neonates were randomly assigned: 1110 (50·0%) neonates to the intervention group and 1111 (50·0%) neonates to the control group. From randomisation to age 7 days, 81 (7·5%) of 1083 neonates in the intervention group and 83 (7·5%) of 1102 neonates in the control group died (adjusted relative risk [RR] 0·97 [95% CI 0·74-1·28]; p=0·85). From randomisation to 28 days, 119 (11·3%) of 1051 neonates in the intervention group and 134 (12·8%) of 1049 neonates in the control group died (RR 0·88 [0·71-1·09]; p=0·23). Even if policy makers place no value on averting neonatal deaths, the intervention would have 97% probability from the provider perspective and 84% probability from the societal perspective of being more cost-effective than standard care. KMC initiated before stabilisation did not reduce early neonatal mortality; however, it was cost-effective from the societal and provider perspectives compared with standard care. Additional investment in neonatal care is needed for increased impact, particularly in sub-Saharan Africa. Joint Global Health Trials scheme of the Department of Health and Social Care, Foreign, Commonwealth and Development Office, UKRI Medical Research Council, and Wellcome Trust; Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Association Between Maternal Body Mass Index and Fetal Acidosis in Term Twin Pregnancies: A Retrospective Cohort Study

ObjectivesGiven the increased risk of fetal acidosis in singleton neonates born to pregnant people with an elevated BMI, our objective was to evaluate the association between pre-pregnancy/first-trimester BMI and fetal acidosis among term twin pregnancies. MethodsRetrospective study of pregnant people with twin gestation and their term infants admitted to our centre between 2014 and 2019. Using a generalized estimating equation, the association between maternal BMI and fetal acidosis was determined using odds ratios (ORs) with 95% CIs. A two-sided P < 0.05 was considered significant. ResultsA total of 275 pregnant people and 550 infants were analyzed. The number (%) of pregnancies in each BMI class were 10 (4%) underweight, 155 (56%) normal weight, 66 (24%) overweight, 22 (8%) class I, 9 (3%) class II, and 13 (5%) class III. The prevalence of maternal diabetes and hypertension was highest in class III (31%) and class II (44%), respectively. Fetal acidosis was diagnosed in 35 (6%) infants. After adjusting for confounders (maternal age, diabetes, and hypertension), infants born to those with elevated BMI did not have increased odds of fetal acidosis compared to those born to underweight and normal weight group (OR 1.29; 95% CI 0.38–4.41 for class I, P = 0.67 and OR 2.80; 95% CI 0.62–12.62 for the combined classes II and III, P = 0.18). ConclusionsMaternal BMI was not associated with fetal acidosis in term twin pregnancies. Further research is required to corroborate study findings due to small sample size.

Reference gender-specific neonatal size at birth growth curves for singleton and twin neonates from North India.

To construct reference growth curves for the preterm population from North India and compare it with global charts. This prospective study enrolled preterm neonates (23 to 36 weeks) from July 2018 to August 2019 after excluding stillbirths and those with congenital malformations. Anthropometry was performed within 18 hours of birth. Gestation age was assessed by the best estimate of a combination of the last menstrual period, antenatal first-trimester ultrasound, and Expanded New Ballard Score (ENBS). Centile curves were constructed for both genders for twins and singleton neonates separately using the GAMLSS method using R software. During the study period, of the 14,908 births, 3253 (21.8%) were born preterm. After excluding malformations and stillbirths, 2976 preterm neonates were eligible, out of which anthropometry within 18 hours was done for 2719 neonates. Data was analyzed for 2290 singleton and 414 twin preterm neonates. Smoothed reference growth curves were constructed for all anthropometric parameters for both genders for singleton as well as twin neonates. Indian preterm infants were smaller compared to international standards. The proportion of small for gestational age (SGA) neonates was 23.1% (Fenton's charts) but only 10.9% when the data from the newly constructed chart was used. The concordance with international standards was better for very preterm neonates <32 weeks than moderate and late preterm neonates (32 to 36 weeks). The reference charts derived from the present study can be used for the North Indian preterm population. The use of western growth charts tends to overestimate the incidence of SGA.

Respiratory distress syndrome is associated with increased morbidity and mortality in late preterm births

Respiratory distress syndrome is strongly associated with prematurity, including late preterm births. Respiratory distress syndrome has been shown to be associated with certain neonatal morbidities and mortality, but these associations are not well described among late preterm births. We sought to determine the association between respiratory distress syndrome and adverse neonatal outcomes among late preterm (34-36 weeks) born singleton neonates. This is a retrospective cohort study using California's linked vital statistics and patient discharge data (2008-2019). We included singleton, nonanomalous births with a gestational age of 34-36 weeks. Outcomes of interest were interventricular hemorrhage, necrotizing enterocolitis, retinopathy of prematurity, neonatal sepsis, length of hospital stay, neonatal death, and infant death. Chi-square and multivariable Poisson regression analyses were used to examine the association of respiratory distress syndrome with outcomes at each gestational age. Adjusted risk ratio and 95% confidence interval values were estimated. A total of 242,827 births were included, of which 11,312 (4.7%) had respiratory distress syndrome. We found that among neonates with respiratory distress syndrome, necrotizing enterocolitis was higher at 35 weeks (adjusted risk ratio, 3.97 [95% confidence interval, 1.88-8.41]) and 36 weeks (adjusted risk ratio, 4.53 [95% confidence interval, 1.45-14.13]). Intraventricular hemorrhage, retinopathy of prematurity, neonatal sepsis, and length of hospital stay were significantly higher at 34-36 weeks of gestation in neonates with respiratory distress syndrome. Neonatal death was significantly higher among neonates with respiratory distress syndrome at 35 weeks (adjusted risk ratio, 3.04 [95% confidence interval, 1.58-5.85]) and 36 weeks (adjusted risk ratio, 3.25; 95% confidence interval, 1.59-6.68). In addition, infant death was significantly higher at 35 weeks (adjusted risk ratio, 2.27 [95% confidence interval, 1.43-3.61]) and 36 weeks (adjusted risk ratio, 2.60 [95% confidence interval, 1.58-4.28]). We found that respiratory distress syndrome was associated with intraventricular hemorrhage, retinopathy of prematurity, and sepsis at 34-36 weeks of gestation, whereas respiratory distress syndrome was associated with neonatal death, infant death, and necrotizing enterocolitis at 35 and 36 weeks. Clinicians should keep these outcomes in mind when making decisions about delivery timing, the potential benefits of antenatal steroids in pregnancies in the late preterm period, and the management of respiratory distress syndrome in late preterm neonates.

Health of singleton neonates in Switzerland through time and crises: a cross-sectional study at the population level, 2007-2022

BackgroundBeing exposed to crises during pregnancy can affect maternal health through stress exposure, which can in return impact neonatal health. We investigated temporal trends in neonatal outcomes in Switzerland between 2007 and 2022 and their variations depending on exposure to the economic crisis of 2008, the flu pandemic of 2009, heatwaves (2015 and 2018) and the COVID-19 pandemic.MethodsUsing individual cross-sectional data encompassing all births occurring in Switzerland at the monthly level (2007-2022), we analysed changes in birth weight and in the rates of preterm birth (PTB) and stillbirth through time with generalized additive models. We assessed whether the intensity or length of crisis exposure was associated with variations in these outcomes. Furthermore, we explored effects of exposure depending on trimesters of pregnancy.ResultsOver 1.2 million singleton births were included in our analyses. While birth weight and the rate of stillbirth have remained stable since 2007, the rate of PTB has declined by one percentage point. Exposure to the crises led to different results, but effect sizes were overall small. Exposure to COVID-19, irrespective of the pregnancy trimester, was associated with a higher birth weight (+12 grams [95% confidence interval (CI) 5.5 to 17.9 grams]). Being exposed to COVID-19 during the last trimester was associated with an increased risk of stillbirth (odds ratio 1.24 [95%CI 1.02 to 1.50]). Exposure to the 2008 economic crisis during pregnancy was not associated with any changes in neonatal health outcomes, while heatwave effect was difficult to interpret.ConclusionOverall, maternal and neonatal health demonstrated resilience to the economic crisis and to the COVID-19 pandemic in a high-income country like Switzerland. However, the effect of exposure to the COVID-19 pandemic is dual, and the negative impact of maternal infection on pregnancy is well-documented. Stress exposure and economic constraint may also have had adverse effects among the most vulnerable subgroups of Switzerland. To investigate better the impact of heatwave exposure on neonatal health, weekly or daily-level data is needed, instead of monthly-level data.

Association between Cord Blood Haematocrit and Neonatal Outcome among Neonates of Diabetic Mothers: A Cohort Study

Introduction: The perinatal mortality rate of Neonates of Diabetic Mothers (NDMs) over the years showed a reducing trend. Polycythaemia is common in NDMs, and such neonates have a risk of hyperviscosity, renal vein thrombosis, cardiac failure, metabolic abnormalities, and necrotising enterocolitis. Aim: To assess the association between cord blood haematocrit and neonatal outcomes among NDMs. Materials and Methods:The present study was a cohort study that included 130 neonates, which was conducted at Amala Institute of Medical Sciences (AIMS), Thrissur, Kerala, India, from December 2019 to June 2021. The primary inclusion criteria were singleton neonates of Gestational Diabetic Mothers (GDM) (diabetes detected after 20 weeks of gestation) and Overt Diabetes Mellitus (ODM) defined under White’s classification (known to be diabetic before the onset of pregnancy or detected in the initial visits). The parameters assessed were the frequency of distribution of hypoglycaemia, hypocalcaemia, and hyperbilirubinemia among the neonates of DM. Statistical analysis was done using Fisher’s exact test and Student’s t-test. Results: Among the 130 neonates, the majority of the mothers had GDM 111 (85.4%) than ODM 19 (14.6%). The majority were delivered by normal vaginal delivery 67 (51.5%). 10 (7.7%) of NDMs had a birth weight &gt; 4000 g. Significant associations were noted between cord Packed Cell Volume (PCV) and the presence of hypoglycaemia (p-value=0.003), hypocalcaemia (p-value=0.0001), and Neonatal Hyperbilirubinemia (NNH) (p-value=0.0001) among NDMs. Conclusion: Hypoglycaemia, hyperbilirubinemia, and hypocalcaemia were common complications noted in NDMs.

The Association Between Maternal Short Stature and Neonatal Intensive Care Unit Admission: A Longitudinal Study in Sabah.

The rising number of newborns requiring neonatal intensive care unit (NICU) care poses immediate threats to their health and places emotional and financial burdens on families and healthcare systems. This study investigates the direct effect of maternal short stature on NICU admission in Sabah, Malaysia. A longitudinal study at Hospital Wanita Dan Kanak-Kanak Sabah (HWKKS) from 2018 to 2022 included 254 Malaysian women with singleton pregnancies and neonates born after the 37th week, excluding significant disorders, smoking/alcohol use, fetal death, and malformations. Birth weight, gestational age, and neonatal condition were recorded. The association between maternal height, low birth weight(LBW), and NICU admission was analyzed. LBW prevalence was 15.35%, with an average participant height of 147.37 cm. Maternal stature was significantly associated with LBW, with the shortest quartile (Q1) having the highest risk. LBW was significantly associated with NICU admission, with LBW newborns at a sixfold higher risk. Maternal height was also significantly associated with NICU admission, with Q1having the highest risk. The receiver operating characteristic (ROC) curve suggested combining Q1 and Q2 for the best prediction of NICU admission, indicating that shorter mothers face a higher risk of neonates requiring NICU care. Maternal short stature could be a valuable predictor of LBW and NICU admission risk. It may be a screening tool to assess these risks in healthcare settings. However, further research is needed to explore this association's underlying mechanisms and potential interventions.

Predictors of the onset of neonatal sepsis at the Neonatal Intensive Care Unit of a tertiary hospital in Ghana: A cross-sectional study.

Neonatal sepsis is a systemic inflammatory response to infection during the first 4 weeks of an infant's life. It is a significant cause of neonatal morbidity and mortality in low- and middle-income countries. This study aimed to determine the predictors of the onset of sepsis at the Neonatal Intensive Care Unit of the Tamale Teaching Hospital, Ghana. A cross-sectional study was conducted among 275 mothers and their singleton neonates diagnosed clinically with sepsis. A univariate and multivariate logistic regression analysis adjusted for maternal occupational status was performed to determine the maternal and neonatal predictors of early-onset (EOS) and late-onset sepsis (LOS), respectively. Single motherhood (AOR = 1.882, 95% CI = 0.926-3.822, p = .08) and home delivery (AOR = 3.667, 95% CI = 0.584-23.026, p = .17) were predictors of EOS, with single motherhood being the predictor for LOS (AOR = 2.906, 95% CI = 0.715-11.805, p = .14) in a univariate analysis. When maternal occupation was adjusted for in a multivariate analysis, single mother (AOR = 2.167, 95% CI = 1.010-4.648, p = .04) was the main predictor of EOS, with low neonatal birth weight being the main predictor of LOS (AOR = 0.193, 95% CI = 0.038-0.971, p = .04). Maternal marital status is a significant predictor of both EOS and LOS, with predictors of EOS being lower gestational age and low birth weight, while for LOS, low birth weight is the main predictor. Findings from this study can serve as a commencement point for developing predictive models for the onset of sepsis in neonates in the study facility.

Effect of delayed cord clamping on red blood cell alloimmunization: a retrospective cohort study

Although delayed cord clamping has well-known benefits for preterm and term neonates, it has been inadequately assessed in alloimmunized neonates. This study aimed to evaluate the benefits and risks of delayed cord clamping in alloimmunized neonates. This was a retrospective comparative pre-post cohort study conducted from 2003 to 2018 in a tertiary care center in France. All living singleton neonates whose mothers were followed up for red blood cell alloimmunization during gestation and confirmed at birth (N=224) were included. Neonates were either exposed to immediate (n=125) or delayed cord clamping (n=99). Our main outcome was the time from birth to first exchange transfusions and/or transfusions. Secondary outcomes were hemoglobin level at birth, rate of exchange transfusion, number of postnatal transfusions, maximum bilirubin level, and number of phototherapy hours. Hemoglobin at birth was significantly higher in case of delayed cord clamping (mean difference, 1.7 g/dL; 95% confidence interval, 0.7-2.8). Among infants treated with exchange transfusion or transfusion, the time to initial treatment was higher in case of delayed cord clamping (median difference, 8 days; rate ratio, 1.51; 95% confidence interval, 1.09-2.10). There were no significant differences in the need for exchange transfusion, the number of transfusions, the maximum total bilirubin level, nor the number of phototherapy hours. In the subgroup analysis of neonates needing intrauterine transfusion during pregnancy (ie, severe alloimmunization), neonates had a lower rate of exchange transfusion in case of delayed cord clamping (odds ratio, 0.36; 95% confidence interval, 0.15-0.82). Our results indicate a benefit of delayed cord clamping in alloimmunization, regardless of pathology severity, without increased risk of jaundice.

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.

The Associated Factors of Low Birthweight Among Term Singletons in Japan: A Pregnancy Birth Registry Analysis.

Progress in reducing the global low birthweight (LBW) has been insufficient. Although the focus has been on preventing preterm birth, evidence regarding LBW in term births is limited. Despite its low preterm birth prevalence, Japan has a higher LBW proportion than other developed countries. This study aimed to examine the prevalence of LBW in term singleton births and its associated factors using a national database. We retrospectively analyzed the data of neonates registered in the Japan Society of Obstetrics and Gynecology Successive Pregnancy Birth Registry System who were born 2013-2017. Exclusion criteria included stillbirths, delivery after 42 gestational weeks, and missing data. Logistic regression analyses were performed to investigate the maternal and perinatal factors associated with LBW in term singletons using the data of 715,414 singleton neonates. The overall prevalence of LBW was 18.3%, and 35.7% of LBWs originated from singleton term pregnancies. Multiple logistic regression analyses indicated that both modifiable and non-modifiable factors were independently associated with LBW in term neonates. The modifiable maternal factors included pre-pregnancy underweight, inadequate gestational weight gain, and smoking during pregnancy, while the non-modifiable factors included younger maternal age, nulliparity, hypertensive disorders of pregnancy, cesarean section delivery, female offspring, and congenital anomalies. Using the Japanese pregnancy birth registry data, more than one-third of LBWs were found to originate from singleton term pregnancies. Both modifiable and non-modifiable factors were independently associated with LBW in term neonates. Prevention strategies on modifiable risk factor control will be effective in reducing LBW worldwide.

Associations between Maternal sFlt-1/PlGF Ratio and Perinatal and Neonatal Outcomes in Newborns Born to Mothers with Preeclampsia

Purpose: The ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) is considered a predictive marker of preeclampsia. However, the relationship between the sFlt-1/PlGF ratio and perinatal and neonatal outcomes remains unknown. This study aimed to determine the associations of the sFlt-1/PlGF ratio with perinatal and neonatal outcomes in newborns born to mothers with preeclampsia.Methods: This retrospective cohort study reviewed singleton neonates born to mothers with preeclampsia who underwent testing for the sFlt-1/PlGF ratio. We investigated the relationship between maternal sFlt-1/PlGF ratios and gestational age (GA), birth weight (Bwt), Bwt z-score, morbidities, and mortality of neonates born to mothers tested for the sFlt-1/PlGF ratio. Maternal sFlt-1/PlGF ratios examined within 30 days before delivery were used for analysis. Neonatal morbidities and mortality were investigated only in preterm infants born earlier than 32 weeks GA.Results: A total of 225 neonates were included, of which 163 (72.4%) were preterm infants. GA (&lt;i&gt;R&lt;/i&gt;=– 0.577, &lt;i&gt;p&lt;/i&gt;&lt;0.001), Bwt (&lt;i&gt;R&lt;/i&gt;=–0.713, &lt;i&gt;p&lt;/i&gt;&lt;0.001), and Bwt z-score (&lt;i&gt;R&lt;/i&gt;=–0.608, &lt;i&gt;p&lt;/i&gt;&lt;0.001) exhibited significant negative correlations with the sFlt-1/PlGF ratios. Among the 50 preterm infants born earlier than 32 weeks GA, neonatal morbidities were not significantly associated with the sFlt-1/PlGF ratio after adjusting for GA and Bwt.Conclusion: In mothers with preeclampsia, a higher sFlt-1/PlGF ratio was associated with the delivery of newborns with lower GA and lower Bwt. However, this ratio was not associated with increased morbidity or mortality in premature infants born earlier than 32 weeks GA.

Bacterial Colonization in the Airways and Intestines of Twin and Singleton Preterm Neonates: A Single-Center Study.

Limited studies have investigated the microbial colonization of the airways and intestines in preterm neonates. We studied the composition of intestinal and airway bacterial colonies in several preterm twin pairs and singletons to explore the dominant bacteria, assess their variability, and predict their phenotypic and metabolic functions. In this descriptive study, we collected sputum and fetal stool specimens from 10 twin pairs (20 cases) and 20 singleton preterm neonates. These specimens were analyzed using 16S rRNA deep sequencing to study the alpha and beta diversities and community structures of airway and intestinal bacteria and predict their metabolic functions. Specimens from twins and singleton neonates had distinct aggregations of intestinal and airway bacteria but showed similarities and high microbial diversities during initial colonization. The top five phyla were Proteobacteria, Firmicutes, Actinobacteriota, Bacteroidota, and Cyanobacteria. The top ten genera were Streptococcus, Acinetobacter, Ralstonia, Staphylococcus, Comamonas, Enterococcus, Stenotrophomonas, Dechlorosoma, Sphingopyxis, and Rothia. Potentially pathogenic and highly stress-tolerant Gram-negative bacteria were predominant in the intestinal flora. A considerable proportion of colonies recovered from the airway and intestines of preterm neonates were functional bacteria. The richness of the intestinal and airway flora was not significantly different between twins and singletons, and the flora clustered together. Both intestinal and airway bacteria of twins and singletons were similar. The species involved in initial colonization were similar but different in proportions; therefore, changes in microbial structure and richness may not be attributed to these species.

Maternal preconception thyroid autoimmunity is associated with neonatal birth weight conceived by PCOS women undergoing their first in vitro fertilization/intracytoplasmic sperm injection

BackgroundThyroid autoimmunity and polycystic ovary syndrome (PCOS) are the most common endocrinopathies and have close relationships based on common etiology and pathogenesis, including genetic susceptibility, metabolic disorders, hormonal dysregulation, immune response, and inflammatory activation. The co-occurrence of both diseases is associated with adverse reproductive outcomes, but its effect on neonatal outcomes remains largely unknown. We aim to explore the effect of thyroid autoimmunity on neonatal birth weight in PCOS women undergoing IVF/ICSI.MethodsThis is a retrospective analysis of 486 PCOS women who underwent the first IVF/ICSI cycles and gave birth to 361 singletons and 125 twins during 2018 – 2020 at a reproductive center. The associations between maternal preconception serum thyroid function and autoimmunity indicators and birth weights of the singleton and twin groups were evaluated using generalized linear models (GLMs) and generalized estimate equations (GEEs), respectively. Analyses were further stratified by neonatal sex, maternal age, and maternal preconception BMI to assess the possible interaction effects.ResultsMaternal preconception serum TPOAb had a significant negative association with singleton birth weight (P for trends = 0.03). Compared with women in the first tertile of TPOAb, women in the third tertile had a change in singleton birth weight of − 119.72 g (95% CI: − 222.68 g, − 16.70 g). Maternal preconception serum TPOAb had a significant positive association with twin birth weight (P for trends = 0.01). Compared with women in the first tertile of TPOAb, women in the third tertile had a change in twin birth weight of 138.62 g (95% CI: 33.96 g, 243.30 g). Besides, maternal preconception serum TPOAb had a specific association with increased twin birth weight for female neonates, a specific association with decreased singleton birth weight for PCOS women under 35 years, and a specific association with decreased twin birth weight for overweight PCOS women (all P for interactions < 0.05).ConclusionsMaternal preconception thyroid autoimmunity may affect the birth weights of both singleton and twin neonates. Further large cohorts and experimental studies are required to confirm these findings and explore the underlying mechanisms.

Association between Maternal Neuraxial Analgesia and Neonatal Outcomes in Very Preterm Infants.

Background Although the use of neuraxial analgesia has been shown to improve uteroplacental blood flow and maternal and fetal hemodynamics related to labor pain, possibly improving immediate outcomes in term neonates, the association between neuraxial analgesia use and outcomes in preterm neonates remains unclear. Objective The aim of this article was to evaluate the association between maternal use of neuraxial analgesia and neonatal outcomes in very preterm infants. Methods This is a retrospective cohort study of women delivering singleton neonates between 23 and 32 weeks' gestation at a large academic center between 2012 and 2016. Outcomes of neonates born to women who used neuraxial analgesia for labor and/or delivery were compared to those whose mothers did not. Multivariable logistic regression was utilized to assess the independent associations of neuraxial analgesia use with neonatal outcomes after controlling for potential confounders, including gestational age, mode of delivery, and existing interventions to improve neonatal outcomes of prematurity. Results Of 478 eligible women who delivered singleton very preterm neonates in this study period, 352 (73.6%) used neuraxial analgesia. Women who used neuraxial analgesia were more likely to have delivered at a later preterm gestational age, to have a higher birthweight, to have preeclampsia and/or hemolysis, elevated liver enzymes, low platelet count (HELLP), to have undergone labor induction, to have delivered by cesarean delivery, and to have received obstetric interventions such as magnesium prophylaxis for fetal neuroprotection, antenatal corticosteroids for fetal lung maturity, and antibiotics prior to delivery; they were less likely to have been diagnosed with a clinical abruption. Neuraxial analgesia was associated with decreased incidence of cord umbilical artery pH less than 7.0 (24.7 vs. 34.9%, p = 0.03), as well as decreased incidence of neonatal intensive care unit length of stay over 60 days (35.5 vs. 48.4%, p = 0.01), although these associations did not persist on multivariable analysis. On multivariable analyses, neuraxial analgesia remained independently associated with decreased odds of necrotizing enterocolitis (adjusted odds ratio [aOR]: 0.28, 95% confidence interval [CI]: 0.12-0.62) and grade III/IV intraventricular hemorrhage (aOR: 0.33, 95% CI: 0.13-0.87). These associations remained significant on sensitivity analyses, which were performed between 10 and 90% of the overall cohort in order to control for outliers, as well as between the subgroup of patients who received obstetric interventions. Conclusions Maternal neuraxial analgesia use may be associated with lower odds of adverse outcomes in very preterm infants, even after controlling for existing interventions for prematurity. Prior work has suggested such effects may be due to improved neonatal acid-base status from changes in placental perfusion and maternal pain management, but further work is required to prospectively investigate such associations.

Neonatal Mortality Rate among Twin and Singleton Births with the Gestational Age of 34-37 Weeks: A Population-Based Study

Introduction: Twin pregnancy, compared to a singleton pregnancy, is associated with a higher risk of preterm birth and other neonatal complications. This study aimed to compare neonatal mortality rates and risk factors among births with the gestational age of 34 weeks - 37 weeks in twin and singleton pregnancies. Methods: The study design was cross-sectional and population-based. We extracted the data from the birth information registry in Iran. Mothers' and neonates' information was removed from the registry systems between 2018 and 2020. We used Statistical R software to compare neonatal mortality rate, demographic variables, and risk factors between two groups of twin and singleton neonates. Results: Out of 579,873 live births with a gestational age of 34 weeks - 37 weeks, 729 (1.4/1000) singleton and 54(0.77/1000) twins (one out of two) neonates died in the delivery room in the first hour of life. Of the neonates who left the delivery room alive, 3129 (4.9 per 1000) neonates had died (5.7/1000 singleton and 3.04/1000 twin). The neonatal mortality rate in hospitalized singleton neonates (1.85%) was higher than twin group (1.06%). After adjustment of other variables, the mortality rate in twin pregnancy was significantly lower than in singletons (p value &lt; 1/1000), with an odds ratio of 0.47 (CI: 0.39 - 0.55). Antenatal corticosteroid treatment in the twin group was significantly higher than in singletons. Conclusion: Twin neonatal mortality rate was lower than singletons in the neonates with gestational age 34 weeks - 37 weeks. Clinicians could consider these results for delivery timing in uncomplicated twin pregnancies. Antenatal corticosteroid therapy can be considered to reduce the mortality rate of late preterm neonates in resource-limited countries.

Delayed versus immediate cord clamping in dichorionic twins

Objectives Strong evidence imply that delayed cord clamping (DCC) provides significant benefits for singleton neonates. However, there is little information about the safety or efficacy of DCC in twins to recommend for or against DCC in twins in guidelines. We aimed to determine the effect of DCC on dichorionic twins born at <32 weeks of gestation. Study design This is a retrospective cohort study comparing the neonatal and maternal outcomes of immediate cord clamping (ICC) [<15 second (s)] versus DCC (at 60 s). Generalized estimating equations models were performed accounting for twin correlation. Results A total of 82 pairs of twins (DCC: 41; ICC: 41) were included in analysis. The primary outcome of death before discharge occurred in 3.66% of twins in the DCC group and 7.32% in the ICC group, without a significant difference between the groups. Compared to ICC group, DCC was associated with increased hemoglobin levels [β1 coefficient 6.51; 95% confidence interval (CI) 0.69–12.32. β2 coefficient 5.80; 95% CI 0.07–11.54] at 12–24 h of life. There were no significant differences between the groups in neonatal death, neonatal major morbidities and maternal bleeding complications, although DCC was associated with higher estimated maternal blood loss in the cesarean section group (p = .005). Conclusions DCC for 60 s in dichorionic twins born at <32 weeks of gestation was associated with increased neonatal hemoglobin levels, when compared with ICC. The finding of a higher estimated maternal blood loss by cesarean section in the DCC group calls for further trials to assess maternal safety of this procedure in this patient population.