The effects of gestational age on the composition and predicted function of gut microbiota in neonates and early infants

Gut microbiota can influence cell differentiation, metabolism, and immune function and is key for the normal development and future health of early infants. Several factors have been reported to be related to the microbiota composition of neonates, such as gestational age, delivery mode, feeding method, antibiotics consumption, and ethnicity, among others. So we investigated the relationship between gestational age and the composition and predicted function of the gut microbiota of neonates and early infants by sequencing the 16S rRNA gene present in stool samples obtained from 100 prospectively enrolled full-term and preterm newborns. In the 3-day-old neonates samples, the prominent genera in the full-term group were Escherichia-Shigella, Streptococcus, Bifidobacterium, and Bacteroides, while in the preterm group, Staphylococcus, Streptococcus, Escherichia-Shigella and Clostridium were the most abundant genera identified. There were statistical difference between two groups(P<0.05). Moreover, the predominant genera in the full-term group were Bifidobacterium, Lactobacillus, Bacteroides, and Clostridium , whereas the main genera in the preterm group were Escherichia-Shigella, Clostridium, Bifidobacterium and Bacteroides, in stool samples from 30-42-day-old infants. We found the α-diversity in 3-day-old group was significantly lower than in the 30-42-day-old group whether it’s full-term or preterm (P<0.001). Functional inference analysis revealed higher levels of biodegradation and metabolism of carbohydrates, vitamins in the full-term group than in the preterm group, both in neonates and early infants, which may contribute to the stability of the microbiota in the full-term group. There were significant differences in the composition and predicted function of the gut microbiota of early infants due to gestational age. The 16S sequencing technology was an effective and reliable tool in the detection of gut microbiota in early infants.

Longitudinal associations of behavioral problems and text reading skills in school-aged children born term and preterm

We assessed the contribution of total behavioral problems at 6 years to text reading skills at 8 years in children born term and preterm. Birth group moderated associations among total behavioral problems and reading skills; total behavioral problems predicted reading skills in the term but not preterm group.

Umbilical Cord Blood Adiponectin, Leptin, Insulin, and Ghrelin in Premature Infants and Their Association With Birth Outcomes

BackgroundPremature/low-birth-weight infants are at significant risk of metabolic diseases in adulthood, which may be related to the levels of fetal adipokine. Here, we investigated the differences in the levels of umbilical cord blood adiponectin, leptin, insulin, and ghrelin in preterm and term infants and sought to elucidate the link between these hormones and fetal growth. We also evaluated the interrelationship among these metabolic hormones in both groups of newborns.MethodsA total of 149 mother–infant pairs (100 in the preterm group and 49 in the term group) were enrolled in the study. The preterm group was further subdivided according to birth weight (≤1,500, 1,501–2,000, 2,001–2,500, and &gt;2,500 g), gestational age (&lt;34 vs. ≥34 weeks), and appropriate for gestational age (AGA) vs. small for gestational age (SGA). The general condition of the mothers and the growth parameters of the newborns at birth were recorded.ResultsThe levels of adiponectin, leptin, and ghrelin were lower in the preterm group than those in the term group (p &lt; 0.05). In the preterm group, the leptin levels of infants with gestational age ≥34 weeks were significantly higher than those of infants with gestational age &lt;34 weeks (mean ln leptin = 0.63 vs. 0.36 ng/ml, p = 0.009). The levels of adiponectin were lower in the SGA group than those in the AGA group (mean ln adiponectin = 2.26 vs. 2.84 µg/ml, p = 0.001), whereas those of ghrelin displayed the opposite trend (mean ln ghrelin = 6.29 vs. 5.71 pg/ml, p &lt; 0.001). Leptin was significantly correlated with insulin both in preterm infants with birth weight (BW) &gt;2,000 g and in term infants. Umbilical cord blood leptin was positively correlated with the BW, birth length, and head circumference of newborns (r = 0.460, 0.311, and 0.310, respectively, all p &lt; 0.05), whereas ghrelin was negatively correlated with the same parameters (r = −0.372, −0.415, and −0.373, respectively, all p &gt; 0.05).ConclusionsThe lack of maturation of adipose tissue and the gastrointestinal tract by the fetus due to prematurity is associated with changes in the levels of cord blood adiponectin, leptin, and ghrelin. The dysregulation of these hormones in preterm infants may be a risk factor for fetal growth and future metabolic diseases.

Compositional differences between preterm milk of different gestational ages with the term milk: a comparative lipidomic study by LC-MS/MS

Background Studies are beginning to emerge on the important biological effects of the milk lipids exerted on the recipient infant, especially on the premature infants. The aim of this study was to comprehensively describe lipidomic differences between preterm milk of different gestational ages with the term milk over the course of lactation. Methods Breast milk samples were collected from 88 mothers giving birth prematurely and 39 mothers delivering at full-term (FT). Lipid profiles were assessed using an LC-MS/MS metabolomics strategy. Orthogonal partial least-squares discriminant analysis (OPLS-DA) and pathway analysis were subsequently performed. Results The OPLS-DA score plots significantly distinguished the lipids in preterm milk of different gestation ages from their counterparts in term milk. The concentrations of 10 out of 43 lipid subclasses were found to be persistently higher in preterm compared to term milk over the course of lactation; the diacylglycerol (DAG) and a bioactive subclass fatty acid ester of hydroxyl fatty acid (FAHFA) contributed the most to the differences. In terms of individual lipid species, the ten highest substances found in very preterm (VPT) colostrum compared to FT colostrum mainly come from the phosphatidylethanolamine class and the DAG species. Lipid species from the free fatty acid and FAHFA classes were significantly higher in either extremely preterm (EPT) or VPT mature milk (variable importance in projection > 1, P < 0.0001 for all). The differential lipids between each preterm group and its term counterpart were predicted to be mainly involved in six metabolic pathways, including glycerophospholipid metabolism, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, linoleic acid metabolism, alpha-Linolenic acid metabolism, arachidonic acid metabolism and glycerolipid metabolism. Conclusions The lipids in preterm and term milk showed substantial differences, which may be critical for postnatal growth, as well as the neural and immune development of newborns, especially EPT and VPT.

Is Preterm Birth a Risk Factor for Subsequent Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder in Children with Febrile Seizure?—A Retrospective Study

Febrile seizure (FS) is the most prevalent childhood seizure; it is significantly related to subsequent epilepsy and has possible links to childhood neurodevelopmental disorders. Separately, premature births are believed to increase the risk of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Therefore, this study investigated whether preterm birth is a risk factor for subsequent epilepsy, ASD, and ADHD in children with FS. We retrospectively collected data for children aged < 5 years with FS from 1 January 2005, to 31 December 2013. We divided these children into two groups—the premature birth group and the full-term group—and compared their incidence rates of epilepsy, ASD and ADHD. The data of 426 patients with history of febrile convulsion were retrospectively collected. The premature birth group (FS+/preterm+) had 108 patients and the full-term group (FS+/preterm−) had 318 patients. The overall epilepsy risk in the FS+/preterm+ group was higher than in the FS+/preterm− group (odds ratio [OR], 2.52; 95% confidence interval [CI], 1.14–5.58; p = 0.02). The overall risk of ADHD in the FS+/preterm+ group was higher than that in the FS+/preterm− group (OR, 6.41; 95% CI, 3.39–12.09; p = 0.0001). In addition, children with FS+/preterm+ had 16.9 times (95% CI, 4.79–59.7; p = 0.0001) higher odds of having ASD compared with those with FS+/preterm−. Preterm birth may be a risk factor for subsequent epilepsy, ASD and ADHD in children with FS

Correlation between Intrapartum Cardiotocogram findings and cord blood pH in term and preterm labors

Background: The purpose of intrapartum fetal monitoring by cardiotocograph (CTG) is to identify early signs of developing hypoxia so that appropriate action can be taken to improve the perinatal outcome. Although CTG findings are well known to monitor the progress of the labor due to the paucity of recommendations, there has always been a clinical dilemma as the term fetuses respond differently than a preterm fetus. However, umbilical cord blood pH can distinguish the infant at high risk for asphyxia and related sequel. Therefore, because of differences in fetal physiology in term and preterm fetuses, CTG findings vary, and hence the validity of CTG to determine fetal acidosis should be different. Aims and Objectives: This study aimed to correlate abnormal intrapartum CTG findings with umbilical cord blood pH in term and preterm labor and thus evaluate the success of CTG in predicting fetal acidosis during labor. Methods: The present study included 210 women in labor (70 preterm and 140 term) with abnormal intrapartum CTG that was classified as per 2015 revised International Federation of Gynecologists and Obstetrician (FIGO) guidelines. Immediately after delivery 2 ml Umbilical artery cord blood sample was taken in a pre-heparinized syringe for analysis, pH <=7.2 was taken as acidosis and pH >7.2 was taken as normal. The measured data were maternal general characteristics which included gravida status, associated comorbidities, method of induction and character of liquor, the intrapartum CTG tracings recorded the cord arterial blood pH and the neonatal characteristics such as APGAR score and neonatal outcome. Results: Data from 70 preterm labor was compared with 140 term labor. In this study, 20.9 % of the babies had acidosis. Suspicious CTG due to decreased variability were more common in the preterm group than in the term group (21.4% vs. 8.6% p<0.05). Positive predictive value (PPV) of abnormal CTG for fetal acidosis in the preterm group was found to be higher than that in term group, PPV of pathological CTG being even higher than suspicious CTG. Women with suspicious CTG had 82 % less risk of fetal acidosis as compared to pathological CTG. Women with Bradycardia had 5.9 times the risk of fetal acidosis as compared with normal and tachycardia. Conclusion: Abnormal CTG should be managed appropriately without any delay to prevent acidosis and cord blood pH should be done in all labors with abnormal CTG. However, our findings of a higher incidence of lower cord blood pH and suspicious CTG due to decreased variability alone, highlight the limitation of criteria currently used for interpretation of CTG in preterm labors.

Temporal Trends of Acute Kidney Injury and Associated Risk Exposures in Extremely Preterm Infants

Background and objectivesNeonatal AKI in the preterm population is an under-recognized morbidity. Detecting AKI in preterm infants is important for their long-term kidney health. We aimed to examine the yearly trends of incidence and the related morbidities and care practices affecting the occurrence of neonatal AKI in extremely preterm (gestational age <29 weeks) and very preterm (gestational age 29–32 weeks) infants.Design, setting, participants, & measurementsThe trends and the related risk factors and care practices of AKI were examined in the extremely preterm (n=434) and very preterm (n=257) infants who were admitted within 14 days after birth from 2005 to 2018 to the University Hospital and had at least two serum creatinine measurements during hospitalization. We defined AKI as a serum creatinine rise of 0.3 mg/dl or more within 48 hours or a 1.5-fold increase within 7 days.ResultsThe extremely preterm group had a three-fold higher incidence of AKI (30% versus 10%) than the very preterm group. Among preterm infants with AKI, 92% had one episode of AKI, and 45% experienced stage 2 or 3 AKI; the mean duration of AKI was 12±9 days. Across the 14-year period, the crude incidence of AKI declined markedly from 56% to 17% in the extremely preterm group and from 23% to 6% in the very preterm group. After adjustment, a significant decline of AKI incidence was still observed in the extremely preterm group. The declining AKI in the extremely preterm infants was related to the trends of decreasing incidences of neonatal transfer, prolonged aminoglycoside exposure, prophylactic use of nonsteroidal anti-inflammatory drugs, and sepsis.ConclusionsWe observed a declining trend in the incidence of neonatal AKI among extremely preterm infants from 2005 to 2018, which may be related to improvement of care practices.

Maternal and perinatal outcome in patients with preterm labor pains receiving tocolytic therapy

Background: The objective of this study was to assess the maternal and neonatal outcomes in patients with preterm labor pains and also to correlate threatened abortion with preterm pains.Methods: The study conducted was a prospective observational study. 100 cases of preterm labor admitted to JK hospital, Bhopal over a period of 2 years with singleton gestation between 28 to 36+6 weeks were included.Results: Maximum preterm deliveries were in the late preterm group (80%). Correlation of preterm labor with threatened abortion was not significant (OR=1.03; p>0.05). 42% cases delivered vaginally and 58% by LSCS. Prolongation of pregnancy after tocolytic therapy was upto 12 hours in 35% cases, 12-24 hours in 40% cases and >24 hours in only 15% cases. The most commonly encountered neonatal complication was RDS, 37%, out of which 9% required resuscitation at birth and 8% required ventilator support followed by jaundice in 23%, sepsis in 3% cases and NEC in 4% cases. The association between gestational age and requirement of resuscitation at birth (X2=19.9; p=0.00), need of ventilator (X2=12.6; p=0.002) and neonatal RDS (X2=6.9; p=0.031) was found to be significant.Conclusions: Preterm births are major obstetric problem that have an extensive impact on neonatal morbidity and mortality.

Pulmonary Outcomes in Children Born Extremely and Very Preterm at 11 Years of Age

Background: There is increasing evidence of prematurity being a risk factor for long-term respiratory outcomes regardless the presence of bronchopulmonary dysplasia (BPD).Aim: To assess the effect of prematurity on respiratory outcomes in children born ≤32 weeks of gestational age at 11 years of age.Materials and Methods: Fifty five ex-preterm children (≤ 32 weeks of gestational age), born in Chieti between January 1, 2006 and December 31, 2007, performed lung function and diffusing capacity test (DLCO) at 11 years of age. Furthermore, allergy evaluation by skin prick test (SPT), eosinophil blood count and assessment of eosinophilic airways inflammation by exhaled nitric oxide (FeNO) were performed. The ex-preterm group was compared to an age- and sex-matched group of term children.Results: No difference for atopic and respiratory medical history was found between ex-preterm children and term controls, except for preschool wheezing that resulted more frequent in ex-preterm children. No difference neither in school-aged asthma frequency nor in lung function assessment at 11 years of age was found between the two groups. Lower DLCO values in ex-preterm children compared to term controls regardless the presence of BPD were found; furthermore, we showed a positive association between DLCO and gestational age. Eosinophil blood count, positive SPTs and FeNO values were similar between the two groups.Conclusions: Diffusing lung capacity was decreased in ex-preterm children at 11 years of age in the absence of lung function impairment and eosinophil airway inflammation, suggesting a non-eosinophilic pattern underlying pulmonary alterations. It could be desirable to include the diffusing capacity assessment in follow-up evaluation of all ex-preterm children.

Robsons Ten Group Classification of Cesarean Section at a Tertiary Center in Nepal

Background: Increasing trend in Ceasarean birth is the issue of both demand and supply side. One of the recommended tools to characterize every pregnancy admitted for childbirth is Robson ten-group classification system that may evaluate obstetric practice. The aim of the study was to assess the cesarean section pattern based on Robson’s classification in a central referral hospital.Methods: A retrospective census of childbirths at Paropakar Maternity and Women’s Hospital in Kathmandu performed from September 2018 to February 2019 based on obstetric record. Robson ten-group classification system was the research tool to collect data and Robson Classification Report Table was used to evaluate the data.Results: There were 10500 births with 34% (32-35%) overall cesarean section rate. Excluding spontaneous and induced labor the supposedly total prelabor CS is 14.5%. Group 1+2+3 size is 81% and 21% CS; 5+10 had 11.3% and 23.3% respectively. Prelabor CS (2b+4b) is 3.54% and additional 11% from malpresentation and preterm. Group CS rate from Class 5 onwards, and ratio of 1 and 2 are as recommended by Robson; 67% of CS were not picked up by Robson class due to indications evolved as the labor progresses and the attributes not pre-classified.Conclusions: The assessed quality of data and the type of obstetric population by Robson reference values prove this study as a representative research. But the indications of cesarean sections can be predicted for only one-third of pregnancy attributes classified by Robson class. To supplement this tool to reduce rising cesarean birth requires audit of indications at decision making level.Keywords: Cesarean section; indication; prediction; robson classification