Preterm labor and preterm birth

Preterm delivery is still one of the biggest problems in obstetrics, and sometimes it is not possible to differentiate pregnant patients into false or real preterm labor. Preterm delivery has remained the major contributor to neonatal morbidity and mortality globally, accounting for 70% of neonatal deaths [1]. In most cases, it occurs unexpectedly in women at low risk. Under these circumstances, it requires an elaborate clinical workup, yet it is a time-saving antenatal procedure for caregivers and patients. The identification of a single biomarker to predict spontaneous preterm delivery poses a significant challenge due to the diversity of clinical presentations. Preterm delivery is the consequence of four main mechanisms: activation of the maternal-fetal placental interaction with the hypothalamic-pituitary-adrenal axis, inflammation in the amniochorionic-decidual tissue, decidual hemorrhage and pathological distention of the myometrium [2].

The Premaquick test checks IGFBP-1 native, IGFBP-1 total and IL-6 parameters. IGFBP-1 has the advantage of not being influenced by recent sexual intercourse or urine contaminants [3], [4], [5], [6]. Eleje and coworkers [7] found that the determination of vaginal fluid IGFBP-1 (native and total) and IL-6 is a valuable method for the prediction of spontaneous delivery and preterm delivery in women at risk of preterm labor and, at present, has the best negative and positive predictive values for preterm birth. If this finding is supported by other groups and studies, it could help tremendously in the clinical practice of obstetrics.

Preterm delivery is a continuous obstetric challenge and, as such, it has many aspects that make it attractive for scientific research. One of the technical improvements in the field of ultrasound imaging is elastography. Oturina et al. [8] published another study on this matter. It is feasible and easy to make an elastographic image in the cervix at the time of transvaginal ultrasound examination of the cervix during pregnancy. Those authors found that the cervical elastography strain ratio is similarly predictive as the cervical length measurement for preterm delivery. Also, they concluded that the combination of two measurements is superior to single measurements for each parameter. Interobserver and intraobserver variability for data acquisition and measurement are low, which indicates that this is a reliable ratio.

The article by Cui et al. [9] on hepatitis in pregnancy is interesting. During recent years, many studies have explored the incidence of preterm birth (PTB) in women with hepatitis B virus (HBV) infection, but the results are inconsistent. The effect of HBV infection on PTB remains unclear. This meta-analysis indicates that individuals with chronic HBV infection seemed to be at risk for PTB as a whole.

Patients with early cervical cancer who still wish to keep their reproductivity can be treated using fertility-sparing operative approaches. Different strategies can be undertaken: conization is an appropriate therapy for patients with very small 1A1 tumors without additional risk factors. Larger tumors are treated using radical trachelectomy. Approximately 50% of the infants delivered after radical vaginal trachelectomy are born prematurely. An effective strategy to reduce this number could be the closure of the cervical os, and vaginal checks for pH can discover ascending infections. Infections should be treated adequately. Closure of the cervix can further reduce the risk of preterm deliveries after a radical vaginal trachelectomy (RVT). In Central Europe, the rate of preterm deliveries varies between 5% and 11% [10]. After conization, the rate of preterm deliveries increases to 26% [6], [10], [11]. Depending on the extent of conization, every resected millimeter increases the rate by approximately 6% [11]. In patients who are treated using radical trachelectomy, a permanent cerclage is inserted to imitate the function of the cervix and to maintain a certain uterine stabilization for a following pregnancy. According to the study of Mangler et al. [12], the possibility of becoming pregnant after radical trachelectomy does not seem to be impaired by the cervical factor, the cervix seems to be very important in maintaining the pregnancy. Almost normal rates of conception are observed, although the high preterm delivery rate still has to be reduced. However, the number of cases in this study is too small to explore more conclusively.

Use of antacid medications to treat gastroesophageal reflux in the preterm population has become more common during hospital stay and after discharge. Symptoms of gastroesophageal reflux are relatively harmless and considered normal symptoms of infants. However, gastroesophageal reflux can sometimes become severe, causing sequelae such as apnea, bradycardia and desaturation in preterm infants. Antacid medications are frequently administered to preterm infants. However, these medications can change gastric pH levels and affect regular gastrointestinal function and gut microbacterial flora. The question of whether these changes can create other problems was studied by Patil and coworkers [13]. They found that patients exposed to antacid medications may have higher rates of necrotizing enterocolitis (NEC), and that these reflux medications did not seem to be effective in reducing clinical gastroesophageal reflux-related signs. There was also a trend that antacid medications might be associated with a higher incidence of culture-proven sepsis. This information contributes to the growing literature cautioning against the use of these medications in preterm infants.

In some cases, breastfeeding might not be adequate enough to feed the preterm infant. In these circumstances, preterm infants need more nutrition and support. Some studies have proposed the fortification of breast milk. There are a few studies comparing early and late breast milk fortification. The annual rate of preterm births, defined as being born before 37 weeks of gestational age, ranges from 5% to 18% worldwide [14], [15]. Breast milk is known as the best source of nutrition for newborns. It contains antimicrobial agents, hormones, enzymes and immunoglobulins and reduces the risk of NEC and infections [16]. Breastfed infants have better feeding tolerance and neural development. As breast milk alone does not satisfy the nutritional needs of premature infants, the use of milk fortifiers is recommended, especially in premature infants less than 2000 g [11]. Alizadeh Taheri et al. [17] conducted a double-blind randomized study on this formulation. Low birth weight (LBW) infants with a gestational age of 28–34 weeks and 2000 g birth weight, who were hospitalized in the Neonatal Intensive Care Unit of Shariati Hospital (Tehran, Iran) from 2012 to 2013, were included in the study. Their findings suggest that early fortification from the first feeding with breast milk exclusively did not improve growth in the first 4 weeks in preterm neonates in comparison with late fortification.

Young maternal age is one of the main risk factors for delivery before 37 weeks of gestation and the mechanisms are unclear. The aim of the current study was to investigate the association between teenagers and the risk of preterm birth in a large and recent cohort study. Mayo et al. [18] conducted a population-based retrospective cohort study using 2007–2011 California birth certificate records linked with hospital discharge indices and United States Census data for nulliparous 13–20 year olds who gave birth to singletons. In this study, the prevalence of PTB was highest among the youngest (13 year olds, 14.5%) and lowest among the oldest (20 year olds, 6.7%). Although this study was very large and included a sizable number of potential confounding variables, it is not without limitations. First, data were derived from birth certificate records linked with hospital discharge summaries and thus are subject to bias from the patients’ self-report and improper documentation.

The use of antenatal glucocorticoids in women with preterm delivery has dramatically improved outcomes. The most commonly used antenatal glucocorticoids are betamethasone and dexamethasone. Glucocorticoids accelerate fetal lung growth by the maturation of type II pneumocytes enabling surfactant production. However, at the same time, the lipids in the lung share a similarity with those in the skin. Therefore, antenatal administration of glucocorticoids may have effects on the structure and function of the developing epidermal barrier in fetuses and neonates. August and Kandasamy [19] performed a systematic review to study these effects, and identified 11 studies (six animal and five human studies). Antenatally administered glucocorticoids accelerated skin maturation in animal studies, but studies of human fetuses found conflicting results. None of the reviewed studies compared the effects of different types of glucocorticoids. More human studies are needed to fully understand the effects of antenatal steroids.

There has always been a discussion about the objectivity of digital examination of the cervix for evaluation at the time of labor, or induction, or on the prediction of preterm delivery. Sharvit et al. [20] performed a retrospective case-control study to compare the sonographic cervical length and the Bishop score (BS) in patients with premature contractions. They found that there was a correlation between both shortened cervical length (CL) and increased BS to PTB. Neither test offered an advantage in predicting PTB. Areas under the curve for BS and CL receiving operating characteristic (ROC) were similar for PTB before 37 weeks of gestation. For nulliparous women, CL predicted PTB better than BS. For singleton and multiple pregnancies, BS and CL did not differ significantly in predicting PTB. For nulliparous women with multiple pregnancies, the BS and CL ROC curves differed nearly significantly, with better predictive ability for CL. In conclusion, in this study, CL and BS have similar value in predicting PTB in patients with PC. For nulliparous women, CL was superior over BS.