Setting and participants
This is a retrospective cohort study. The study protocol was approved by the research institute’s committee of human research in the Second Affiliated Hospital of Shantou University Medical College (NO.2018-23) and abided by the standards of the Declaration of Helsinki. The data were anonymized in this study, so we did not use the consent to participate.
We collected data of pregnant women who gave birth at 34 (0/7) to 36 (6/7) weeks gestation from January 2014 to June 2019. The data were anonymized in this study. Data were excluded from this study if the pregnant women or preterm infants met the following criteria: (1) pregnant women had serious liver, kidney, lung or heart disease before or during pregnancy, (2) pregnant women received ACS treatment before 34 gestational weeks, (3) preterm infants had a congenital malformation or needed surgery.
Variables included age of mother, gestational diabetes mellitus, pregnancy hypertension, method of delivery, premature rupture of membranes (PROM), condition of the placenta, meconium stained amniotic fluid, multiple gestation, gestational age, birth weight of preterm infants, asphyxia, pulmonary surfactant treatment for preterm infants, and mechanical ventilation for preterm infants. The short-term outcomes of preterm infants in this study included the length of neonatal hospital stay, hospitalization expenses for preterm infants, NRDS, neonatal pneumonia, neonatal hypoglycemia, neonatal sepsis, necrotizing enterocolitis of newborn, neonatal intracranial hemorrhage, and hypoxic-ischemic encephalopathy.
Assessment short-term outcomes of preterm infants
We compared nine short-term outcomes of preterm infants between the ACS group and without-ACS group. Assessment methods of these outcomes were as follows. Neonatal hypoglycemia was defined as a glucose level less than 2.2 mmol per liter at any time .
The diagnosis of NRDS is based upon the findings of respiratory difficulty (cyanosis, grunting, nasal flaring, or tachypnea) that necessitated mechanical ventilation support, and is furthermore consistent with typical radiological findings of the lung (such as frosted glass-like changes, air bronchogram, and white lung). Laboratory findings were characterized initially by hypoxemia and later by progressive hypoxemia, hypercapnia, and variable metabolic acidosis. The clinical course, chest x-ray findings, and blood gas and acid-base values helped to establish the clinical diagnosis of NRDS .
Neonatal sepsis includes early-onset or late-onset, depending on the age of onset and timing of the sepsis episode. Both early-onset and late-onset neonatal sepsis were included in this study. Diagnosis of neonatal sepsis is based on symptoms and laboratory evidence. Initial symptoms might be few, and includes apnea, tachypnoea, or tachycardia. Late complications of neonatal sepsis might include respiratory failure, pulmonary hypertension, cardiac failure, shock, renal failure, liver dysfunction, cerebral edema or thrombosis, adrenal hemorrhage or insufficiency, bone marrow dysfunction, and disseminated intravascular coagulation. Traditionally, neonatal sepsis can be diagnosed when the blood or other sterile body sites culture produces positive pathogenic bacteria or opportunistic pathogens. Other laboratory evidence that measure an inflammatory response including blood count, C-reactive protein, procalcitonin, interleukin 6, interleukin 8, and tumor necrosis factor. .
Necrotizing enterocolitis of newborn is one of the most serious complications for neonates . Necrotizing enterocolitis of newborn often occurs in the first or second week of life in the late preterm infants. It is difficulty to be identified, because of the first symptoms of this disease is not typical. Gastrointestinal signs including feeding difficulty, gastric retention, abdominal distension, bilious vomiting, and stool with blood. Diagnosis of necrotizing enterocolitis of newborn is made according to plain abdominal radiographs. The finding of pneumatosis in the intestinal wall confirms the clinical suspicion of necrotizing enterocolitis of newborn and diagnosis.
Neonatal pneumonia is inflammation of the lung caused by infection. Diagnosis of neonatal pneumonia is made according to the risk factors, such as PROM, chorioamnionitis in the mother, and low birthweight, which predispose to pneumonia. Infants with respiratory distress usually require investigation to identify infection. A chest X ray picture can help diagnosis of neonatal pneumonia, which would show increased bronchovascular shadows with small patchy and macular shadows .
Intracranial hemorrhage is suspected basis of the history, clinical manifestations, and knowledge of the birthweight-specific risks for intravascular hemolysis. Ultrasonography is the preferred imaging technique for screening. All at-risk infants should undergo cranial ultrasonography within the 3–7 days of age .
The diagnosis of hypoxic-ischemic encephalopathy were made according to the PH value of the fetal umbilical artery, the Apgar score at 5 and 10 minutes, and multi-system organ failure including combined kidney damage, liver damage, blood abnormalities, heart dysfunction, metabolic disorders, and gastrointestinal tract injury . Magnetic resonance imaging is a sensitive tool for evaluation of extensive periventricular injury. All at-risk preterm infants should undergo MRI within the first week of age.
Because this is a single center study, we compared the neonatal hospitalization expenses directly. Hospitalization expenses included the examination, drug, and nursing care costs. Length of hospital stay was counted from the day of admission to the day of discharge.
We used Shapiro-Wilk test to determine whether continuous variables are normally distributed, and the Wilcoxon-Mann-Whitney U-test was conducted for skewed distributions (presented as the median and the min-max range). Descriptive statistics for categorical variables were showed as frequency (percentage). Pearson chi-square test or Fisher's exact test were used to compare categorical variables, as appropriate. Collinearity among all covariates was assessed using the Spearman correlation test .
For binary variables, logistic regression was used to analyze the risk factors of neonatal short-term outcomes, and independent variables were chosen based on clinical knowledge. For continuous dependent variables, linear regression was used to analyze the relationship between independent variables. Regression analysis was performed by a forward stepwise method to identify the risk factors. Estimated slope and 95% confidence intervals (CI) were obtained. Statistical analyses were performed using SPSS 24.0 (SPSS, Chicago, IL). P-values of less than 0.05 were considered to be statistically significant.