Understanding the Pathogenesis of Gestational Hypothyroidism.

Pregnancy is a complex state with many endocrinological challenges to a woman's physiology. Gestational Hypothyroidism (GHT) is an emerging condition where insufficiency of the thyroid gland has developed during pregnancy in a previously euthyroid woman. It is different to overt hypothyroidism, where marked elevation of thyroid-stimulating hormone with corresponding reduction in free thyroxine levels, is well known to cause detrimental effects to both the mother and the baby. During the past couple of decades, it has been shown that GHT is associated with multiple adverse maternal and fetal outcomes such as miscarriage, pre-eclampsia, placental abruption, fetal loss, premature delivery, neurocognitive and neurobehavioral development. However, three randomized controlled trials and a prospective cohort study performed within the last decade, show that there is no neurodevelopmental improvement in the offspring of mothers who received levothyroxine treatment for GHT. Thus, the benefit of initiating treatment for GHT is highly debated within the clinical community as there may also be risks associated with over-treatment. In addition, regulatory mechanisms that could possibly lead to GHT during pregnancy are not well elucidated. This review aims to unravel pregnancy induced physiological challenges that could provide basis for the development of GHT. During pregnancy, there is increased renal clearance of iodine leading to low iodine state. Also, an elevated estrogen level leading to an increase in circulating thyroglobulin level and a decrease in free thyroxine level. Moreover, placenta secretes compounds such as human chorionic gonadotropin (hCG), placental growth factor (PIGF) and soluble FMS-like tyrosine kinase-1 (s-Flt1) that could affect the thyroid function. In turn, the passage of thyroid hormones and iodine to the fetus is highly regulated within the placental barrier. Together, these mechanisms are hypothesized to contribute to the development of intolerance of thyroid function leading to GHT in a vulnerable individual.

Reduced mechanical function of the left atrial predicts adverse outcome in pregnant women with clustering of metabolic risk factors.

INTRODUCTION: The left atrial (LA) strain and strain rate are sensitive indicators of LA function. However, they are not widely used for the evaluation of pregnant women with metabolic diseases. The aim of this study was to assess the LA strain and strain rate of pregnant women with clustering of metabolic risk factors and to explore its prognostic effect on adverse pregnancy outcomes. MATERIALS AND METHODS: Sixty-three pregnant women with a clustering of metabolic risk factors (CMR group), fifty-seven women with pregnancy-induced hypertension (PIH group), fifty-seven women with gestational diabetes mellitus (GDM group), and fifty matched healthy pregnant women (control group) were retrospectively evaluated. LA function was evaluated with two-dimensional speckle-tracking imaging. Iatrogenic preterm delivery caused by severe preeclampsia, placental abruption, and fetal distress was regarded as the primary adverse outcome. RESULTS: The CMR group showed the lowest LA strain during reservoir phase (LASr), strain during contraction phase (LASct) and peak strain rate during conduit phase (pLASRcd) among the three groups (P < 0.05). LA strain during conduit phase (LAScd) and peak strain rate during reservoir phase (pLASRr) in the CMR group were lower than those in the control and GDM groups (P < 0.05). Multivariable Cox regression analysis demonstrated systolic blood pressure (HR = 1.03, 95% CI 1.01-1.05, p = 0.001) and LASr (HR = 0.86, 95% CI 0.80-0.92, p < 0.0001) to be independent predictors of iatrogenic preterm delivery. An LASr cutoff value ≤ 38.35% predicted the occurrence of iatrogenic preterm delivery. CONCLUSIONS: LA mechanical function in pregnant women with metabolic aggregation is deteriorated. An LASr value of 38.35% or less may indicate the occurrence of adverse pregnancy outcomes.

Factors associated with poor fetal outcome in placental abruption.

OBJECTIVES: We aimed at describing placental abruption in our county and at evaluating factors associated with poor fetal outcome. STUDY DESIGN: In this case-control study, women with placental abruption were identified from two databases of Brest University Hospital between January 2013 and December 2018. MAIN OUTCOME MEASURES: Placental histological findings, course of pregnancies, maternal and fetal characteristics were described and compared between cases (placental abruption with stillbirth or neonatal death) and controls. RESULTS: We identified 135 placental abruption, of whom 24.4% were complicated with stillbirth and 6.5% with neonatal death. Forty percent of women were smokers and 14.1% had a history of vasculoplacental disorder. Pregnancies were complicated with 42.2% of pre-eclampsia and 43% of intrauterine growth restriction. Cases were associated with more autoimmune diseases in mother (20.0% versus 3.2%, P = 0.003), more aspirin or heparin use during pregnancy (20.0% versus 6.3%, P = 0.03), less pre-eclampsia (25.0% versus 49.5%, P = 0.01) and more deliveries ≤ 34 weeks of gestation (80.0% versus 43.2%, P = 0.0001) than controls. Placentas from cases showed more placental indentation ≥ 30% (42.5% versus 5.3%, P < 0.0001) and less histological chronic inflammation, especially less chronic chorioamniotitis (2.5% versus 24.2%, P = 0.002) than controls. In multivariate analysis, factors negatively associated with poor fetal outcome were placental histological chronic inflammation (P = 0.01) and macroscopic infarcts (P = 0.01). CONCLUSIONS: Poor fetal outcome is negatively associated with certain placental histological chronic lesions, but not with pre-eclampsia, what suggests various pathophysiological processes among placental abruption.

Placental Histopathology and Pregnancy Outcomes in "Early" vs. "Late" Placental Abruption.

Placenta-associated pregnancy complications (fetal growth restriction and preeclampsia) are traditionally classified as "early" and "late" due to their different pathophysiology, histopathology, and pregnancy outcomes. As placental abruption (PA) represents another placenta-associated complication, we aimed to study if this categorization can be applied to PA as well. Pregnancy and placental reports of all pregnancies complicated by PA between November 2008 and January 2019 were reviewed. Maternal background, pregnancy outcomes, and placental histopathology were compared between cases of PA < 34 weeks (early PA group) vs. > 34 weeks (late PA group). Placental lesions were classified according to the "Amsterdam" criteria. The primary outcome was severe neonatal morbidity (≥ 1 severe neonatal complications: seizures, IVH, HIE, PVL, blood transfusion, NEC, or death). Included were 305 cases of PA, 71 (23.3%) in the early group and 234 (76.7%) in the late group. The early PA group was characterized by higher rates of vaginal bleeding upon presentation (p = 0.003), DIC (p = 0.018), and severe neonatal morbidity (p < 0.001). The late PA group was characterized by a higher rate of urgent Cesarean deliveries (p < 0.001). The early PA group was characterized by higher rates of placental maternal vascular malperfusion (MVM) lesions (p < 0.001), maternal inflammatory response (MIR) lesions (p < 0.001), placental hemorrhage (p < 0.001), and a lower feto-placental ratio (p < 0.001). Using regression analysis, we found that severe neonatal morbidity was independently associated with early abruption (aOR = 5.3, 95% CI = 3.9-7.6), placental MVM (aOR = 1.5, 95% CI = 1.2-1.9), placental MIR (aOR = 1.9, 95% CI = 1.4-2.3), and inversely associated with antenatal corticosteroids (aOR = 0.9, 95% CI = 0.6-0.98). "Early" and "late" PA significantly differ in their presentation, placental pathology, and pregnancy outcomes.

Placental Abruption as a Risk Factor for Heart Failure.

Complications of pregnancy present an opportunity to identify women at high risk of cardiovascular disease (CVD). Placental abruption is a severe and understudied pregnancy complication, and its relationship with CVD is poorly understood. The California Healthcare Cost and Utilization Project database was used to identify women with hospitalized pregnancies in California between 2005 and 2009, with follow-up through 2011. Pregnancies, exposures, covariates, and outcomes were defined by International Classification of Diseases Ninth Revision codes. Cox proportional-hazards regression was used to examine the association between placental abruption and myocardial infarction (MI), stroke, and heart failure (HF). Multivariate models controlling for age, race, medical co-morbidities, pregnancy complications, psychiatric and substance use disorders, and socioeconomic factors were employed. Among over 1.5 million pregnancies, placental abruption occurred in 14,881 women (1%). Median follow-up time from delivery to event or censoring was 4.87 (interquartile range 3.54 to 5.96) years. In unadjusted models, placental abruption was associated with risk of HF, but not MI or stroke. In fully-adjusted models, placental abruption remained significantly associated with HF (Hazard ratio 1.44; 95% confidence interval 1.09 to 1.90). Among women with placental abruptions, hypertensive disorders of pregnancy and preterm birth respectively modified and mediated the association between placental abruption and HF. In conclusion, placental abruption is a risk factor for HF, particularly in women who also experience hypertensive disorders of pregnancy and preterm birth. Placental abruption is a specific adverse pregnancy outcome associated with risk of HF.

Histologic chorioamnionitis concomitant placental abruption and its effects on pregnancy outcome.

INTRODUCTION: Two possible causative pathways have been suggested to participate in the development of placental abruption (PA), an acute inflammatory pathway and placental vascular derived, a chronic pathway. We aimed to study the impact of the inflammatory pathway on maternal and neonatal outcome. METHODS: The computerized medical files and placental reports of all pregnancies diagnosed with PA, between 11/2008-1/2019, at 24-42 weeks, were reviewed. Placental lesions were classified according to "Amsterdam" criteria into maternal and fetal vascular malperfusion lesions, acute inflammatory responses and chronic villitis. Composite neonatal morbidity included ≥1 of the following: seizures, intra-ventricular hemorrhage (IVH), hypoxic-ischemic encephalopathy, periventricular leukomalacia (PVL), blood transfusion, necrotizing enterocolitis (NEC), neonatal sepsis, respiratory distress syndrome, or neonatal death. Maternal and neonatal outcome were compared between PA with and without histologic chorioamnionitis (HC). RESULTS: As compared to the PA without HC group (n = 267), the PA with HC group (n = 77) was characterized by lower gestational age (GA) at delivery (32.9 ± 5.5 vs. 35.6 ± 4.1 weeks, p < 0.001), higher rates of oligohydramnios (p < 0.001), bloody amniotic fluid at labor (p < 0.001), maternal postpartum fever (p < 0.001), longer maternal hospitalization (<0.001), and increased composite adverse neonatal morbidity (41.6% vs. 22.8%, p = 0.002). By multivariate analysis, GA and HC were found to be independently associated with adverse neonatal outcome, aOR 0.63 95% CI 0.43-0.78, p < 0.001, and aOR1.12, 95% CI 1.02-3.87, p = 0.04, respectively. DISCUSSION: The involvement of the inflammatory causative pathway in the development of placental abruption, is associated with increased maternal and neonatal morbidity.

Thrombin-Induced Decidual Colony-Stimulating Factor-2 Promotes Abruption-Related Preterm Birth by Weakening Fetal Membranes.

Preterm premature rupture of membranes (PPROM) and thrombin generation by decidual cell-expressed tissue factor often accompany abruptions. Underlying mechanisms remain unclear. We hypothesized that thrombin-induced colony-stimulating factor-2 (CSF-2) in decidual cells triggers paracrine signaling via its receptor (CSF2R) in trophoblasts, promoting fetal membrane weakening and abruption-associated PPROM. Decidua basalis sections from term (n = 10), idiopathic preterm birth (PTB; n = 8), and abruption-complicated pregnancies (n = 8) were immunostained for CSF-2. Real-time quantitative PCR measured CSF2 and CSF2R mRNA levels. Term decidual cell (TDC) monolayers were treated with 10-8 mol/L estradiol ± 10-7 mol/L medroxyprogesterone acetate (MPA) ± 1 IU/mL thrombin pretreatment for 4 hours, washed, and then incubated in control medium with estradiol ± MPA. TDC-derived conditioned media supernatant effects on fetal membrane weakening were analyzed. Immunostaining localized CSF-2 primarily to decidual cell cytoplasm and cytotrophoblast cell membranes. CSF-2 immunoreactivity was higher in abruption-complicated or idiopathic PTB specimens versus normal term specimens (P < 0.001). CSF2 mRNA was higher in TDCs versus cytotrophoblasts (P < 0.05), whereas CSF2R mRNA was 1.3 × 104-fold higher in cytotrophoblasts versus TDCs (P < 0.001). Thrombin enhanced CSF-2 secretion in TDC cultures fourfold (P < 0.05); MPA reduced this effect. Thrombin-pretreated TDC-derived conditioned media supernatant weakened fetal membranes (P < 0.05), which MPA inhibited. TDC-derived CSF-2, acting via trophoblast-expressed CSFR2, contributes to thrombin-induced fetal membrane weakening, eliciting abruption-related PPROM and PTB.

Acute kidney injury associated with preeclampsia or hemolysis, elevated liver enzymes, and low platelets syndrome.

OBJECTIVE: To determine the prevalence of acute kidney injury (AKI), placental abruption and postpartum hemorrhage in patients with preeclampsia or HELLP syndrome. STUDY DESIGN: A retrospective study of patients with preeclampsia or HELLP syndrome treated at the University of Mississippi Medical Center from January 2000 through December 2010. MAIN OUTCOME MEASURES: Relationships among the obstetric complications of placental abruption, postpartum hemorrhage, and AKI (serum creatinine >107 µmol/L) of women with preeclampsia or HELLP syndrome. Additional analysis was undertaken to explore if there was a correlation between postpartum hemorrhage/placental abruption and the severity of HELLP syndrome according to the Mississippi classification system. RESULTS: Data from 1276 women over 11 years were included in the analysis. 67 of 466 patients (14.4%) with HELLP syndrome and 38 of 810 preeclampsia patients (4.7%) met criteria for AKI. Women with either placental abruption or postpartum hemorrhage had statistically significant increased odds of also having AKI (p < 0.01). Women with HELLP and AKI were also more likely to experience either placental abruption or postpartum hemorrhage. Women with Class 1 HELLP with placental abruption or postpartum hemorrhage were also more likely to have AKI than women with preeclampsia. CONCLUSION: HELLP syndrome, AKI and placental abruption or postpartum hemorrhage appear to be interrelated. AKI occurs more frequently in women with HELLP syndrome with or without associated postpartum hemorrhage and placental abruption.

Effects of maternal smoking on human placental vascularization: A systematic review.

The abnormal development of placental vascularization leads to placental insufficiency, which further reduces the nutrient and trace exchange between maternal circulation and fetal circulation. These changes cause maternal and fetal complications. The objective of our systematic review was to explore the effects of maternal smoking on placental vascularization. The eligibility criteria were: articles with experimental, quasi-experimental or observational design, performed on human subjects, that study the association, correlation or causation between maternal smoking and changes in placental vascular network. A total of 33 full-text papers were assessed for eligibility, resulting in 12 original articles that were included in the systematic review. Doppler studies confirm reductions in blood flow velocity waveforms and increase in RI in the uterine, umbilical and fetal middle cerebral arteries. These findings are confirmed by morphometric measurements of fetal capillaries in villi that were shown to be smaller in smoke exposure groups.

Electronic fetal monitoring characteristics of a patient with sudden onset of placental abruption and intrauterine fetal demise: A case report.

INTRODUCTION: Placental abruption (PA) is a serious complication of pregnancy, associated with significant perinatal complications, including intrauterine fetal demise (IUFD). Continuous electronic fetal monitoring (EFM) has been widely applied in China in recent decades. Exploration of potentially PA-specific patterns of EFM contributes to early detection of PA occurrence. PATIENT CONCERNS AND DIAGNOSIS: A 33-year-old woman (gravida 3, para 1) was referred to our hospital at 33 weeks gestation due to non-reassuring fetal heart rate (FHR) pattern, and suffered sudden onset of severe PA and subsequent intrauterine fetal demise. INTERVENTIONS: We analyzed the characteristics of her non-stress tests (NSTs) 1 day and 10 min before the detection of PA, aiming to explore potentially PA-specific patterns of EFM and provide reference for early detection of asymptomatic PA occurrence in obstetric practice. OUTCOMES: Unfavored characteristics of FHR patterns before PA onset are analyzed. CONCLUSION: For those who sense decreased fetal movements (DFMs), a NST and a biophysical profile (BPP) are recommended for exclusion of potential adverse maternal and fetal complications.

Analysis of 62 placental abruption cases: Risk factors and clinical outcomes.

OBJECTIVE: This study aimed to explore the clinical characteristics and outcomes of placental abruption. MATERIALS AND METHODS: A total of 62 placental abruption cases were collected from the Second Hospital of Jilin University between January 2007 and December 2012. A retrospective study was conducted to explore the risk factors for placental abruption, clinical characteristics, and maternal and fetal outcomes. RESULTS: Risk factors for placental abruption mainly include preeclampsia (39%) and premature rupture of membrane (10%). Abdominal pain (68%) and bleeding (35%) comprise the classical symptoms of placental abruption but the clinical picture varies from asymptomatic, in which the diagnosis is made by inspection of the placenta at delivery, to massive abruption leading to fetal death and severe maternal morbidity. Emergency cesarean section was performed in 45 cases (73%) of placental abruption. Sixty-two placental abruption cases were divided into 2 groups according to whether uteroplacental apoplexy occurred. The incidence of preeclampsia and the duration (time between on-set of clinical symptom and placenta delivery) in the observational group were significantly higher than that of the control group, showing statistical significance (P < 0.01). CONCLUSION: The diagnosis of placental abruption should consider risk factors, symptoms, physical signs, dynamic ultrasound monitoring, and cardiac care. Early diagnosis and treatment can improve maternal and infant prognosis.

Hepatic rupture from haematomas in patients with pre-eclampsia/eclampsia: a case series.

Hepatic rupture from haematomas is a rare complication of severe preeclampsia/eclampsia especially when complicated with the haemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome. It is associated with poor maternal and foetal outcomes as demonstrated by three cases we describe. The first case had eclampsia at 31 weeks gestation with features of abruptio placentae and at caesarean section we found haemoperitoneum of 1.5 litres, a 10cm liver rupture and a still birth. She subsequently died in ICU within 24 hours of surgery; the second case had eclampsia at 35 weeks and ended up as a table death during emergency caesarean section. She had 4 litres of haemoperitoneum, hepatic rupture, placental abruption and a stillbirth; the third case had pre-eclampsia at 33 weeks with markedly elevated liver enzymes. She had one litre haemoperitoneum, right lobe hepatic rupture and a stillbirth. She recovered after conservative management. Severe pre-eclampsia/eclampsia associated hepatic rupture calls for rapid and aggressive intervention with prompt multidisciplinary management to avert adverse outcomes.

Impact of fetal growth on pregnancy outcomes in women with severe preeclampsia.

OBJECTIVE: To estimate whether pregnancy outcomes in women with severe preeclampsia (sPE) with small for gestational age (SGA) fetuses differ from those with sPE without SGA or isolated SGA. STUDY DESIGN: We conducted a retrospective cohort study of consecutive non-anomalous, livebirths in a single tertiary care institution from 2004 to 2008. We compared pregnancy outcomes in women who had sPE with SGA (birthweight<10th percentile), and sPE without SGA to those with isolated SGA as reference. The primary outcome was a neonatal composite score including low 5-min APGAR, NICU admission and neonatal death. Secondary outcomes were components of the composite as well as placental abruption and cesarean delivery. Analysis was repeated with SGA defined as birthweight<5th percentile. Multivariable logistic regression was used to adjust for confounders. RESULTS: 1905 women met inclusion criteria: 156 sPE with SGA, 746 sPE without SGA, 1003 isolated SGA. The risk of the neonatal composite score was higher for sPE with SGA (adjusted odds ratio [aOR] 2.29; 95% confidence interval [CI] 1.39-3.79) and sPE without SGA (aOR 3.66; 95% CI 2.71-4.93) compared to isolated SGA. The risk of abruption and cesarean were similarly increased in women with sPE with SGA and sPE without SGA compared to those with isolated SGA. CONCLUSION: Similar to women with sPE without SGA fetus, women who have sPE with SGA are at a higher risk for several adverse maternal and neonatal outcomes compared to isolated SGA. These findings suggest that women with preeclampsia and SGA should be managed as sPE rather than as isolated SGA.

Cardiovascular Disease in Relation to Placental Abruption: A Population-Based Cohort Study from Denmark.

BACKGROUND: Cardiovascular (CVD) complications stemming from vascular dysfunction have been widely explored in the setting of preeclampsia. However, the impact of abruption, a strong indicator of microvascular disturbance, on the risk of CVD mortality and morbidity remains poorly characterised. METHODS: We designed a cohort analysis of 828 289 women who delivered singletons in Denmark between 1978 and 2010. We linked the National Patient Registry and the Registry of Causes of Death to the Danish Birth Registry to ascertain CVD events. We estimated CVD risks in relation to abruption from Cox proportional hazards regression following adjustments for confounders. RESULTS: With 13 231 562 person-years of follow-up of women with at least one delivery, 11 829 pregnancies were complicated by abruption. The median (interquartile range) follow-up in the non-abruption and abruption groups was 16 (8, 24) and 18 (10, 25) years, respectively. CVD mortality rates in women with and without abruption were 0.9 and 0.3 per 10 000 person-years, respectively (adjusted hazard ratio (HR) 2.7, 95% confidence interval (CI) 1.5, 5.0). The corresponding CVD morbidity complication rates were 16.7 and 10.0 per 10 000 person-years, respectively (HR 1.5, 95% CI 1.4, 1.8). The increased risks were evident for ischaemic heart disease, acute myocardial infarction, hypertensive heart disease, non-rheumatic valvular disease, and congestive heart failure. CONCLUSIONS: This study shows increased hazards of CVD morbidity and mortality in relation to abruption. A better understanding of the pathogenesis of distorted placental microvasculature is needed as this appears to be a harbinger of CVD later in life.

Fetal cerebral and umbilical Doppler in pregnancies complicated by late-onset placental abruption.

OBJECTIVE: To evaluate whether changes in the cerebroplacental Doppler and birth weight (BW) suggestive of chronic fetal hypoxemia, precede the development of late-onset placental abruption (PA) after 32 weeks. METHODS: In a multicenter retrospective study, the Doppler examinations of the fetal umbilical artery (UA) and middle cerebral artery (MCA) recorded after 32 weeks were collected in pregnancies subsequently developing PA. The BW centiles were calculated and the MCA pulsatility indices (PI), and UA PI were converted into multiples of the median (MoM). Afterwards, a comparison was made with a group of fetuses, which did not develop PA. Logistic regression was used to adjust for potential confounders and evaluate the feasibility of the prediction model. RESULTS: Pregnancies complicated by late-onset PA (n = 31) presented lower MCA PI (p = 0.015) and were smaller (p < 0.001) than those who did not (n = 1294). Logistic regression analysis indicated that cerebral vasodilation was more important than umbilical flow in the explanation of PA (MCA PI OR = 0.106, p = 0.014 and UA PI OR 1.901, p = 0.32). In addition, the influence of BW exerted was residual (BW centile OR = 0.989, p = 0.15). CONCLUSIONS: Fetuses developing late-onset PA demonstrate significant cerebral vasodilation with scarce placental dysfunction, suggesting the existence of some kind of chronic hypoxemia that follows the late-onset pattern.

The genomics of prematurity in an era of more precise clinical phenotyping: A review.

Spontaneous preterm birth is a major public health problem, with a clear genetic component. Genetic association studies have evolved substantially in recent years, moving away from the traditional candidate gene analyses to newer approaches utilizing sophisticated analysis platforms to examine sequencing data, and shifting towards functional studies including methylation analysis. It is becoming increasingly evident that careful clinical phenotyping is crucial to high quality genetic association studies regardless of the assay or platform being used. Nonetheless, genetic studies of prematurity are hampered by numerous challenges including small sample sizes, incomplete phenotying, population stratification, and multiple comparisons. As the costs of sequencing and functional analyses continue to decrease, unbiased genome-wide assays will be more widely available. Researchers have met improved success recently when critically applying clinical phenotyping knowledge to group women prior to analyzing genotyping results. Eventually, as the analytic approaches evolve, it is likely that this methodology (combining precisely clinically phenotyped subjects with genome-wide data) will provide key information regarding the pathophysiology of prematurity, and provide potential new avenues for exploring innovative therapeutic strategies.

Comparative analysis of perinatal clinical problems in early and late preterm infants.

OBJECTIVE: The aim of this study was to understand different clinical characteristics of early preterm infants (EPIs) and late preterm infants (LPIs). MATERIALS AND METHODS: The clinical and laboratory data of 561 preterm infants, admitted to this hospital from January 2013 to December 2014, were comparatively analyzed. RESULTS: EPIs accounted for 27.45% and LPIs accounted for 72.55%. The incidence rates of asphyxia at birth, placental abruption, and placenta previa in EPIs were significantly higher than those in LPIs (p < 0.01). The levels of albumin, globulin, triglycerides, serum phosphorus, serum iron, and hemoglobin in EPIs were significantly lower than those in LPIs (p <0.01). The proportion of low body temperature, low blood sugar, respiratory distress, apnea and feeding intolerance, as well as assisted ventilation therapy, in EPIs were significantly higher than those in LPIs (p < 0.01). CONCLUSIONS: LPIs accounted for the majority of preterm infants, placental abruption and placenta previa were the unique risk factors in EPIs, EPIs had lower nutritional reserves than LPIs, and would be more susceptible to the perinatal complications.