A systematic review and meta-analysis of randomized controlled trials comparing 17-alpha-hydroxyprogesterone caproate versus placebo for the prevention of recurrent preterm birth.

BACKGROUND: Preterm birth causes an increased risk for perinatal morbidity and mortality. OBJECTIVE: To determine whether mid-trimester 17-alpha-hydroxyprogesterone caproate (17-OHPC) reduces the risk of recurrent preterm birth and adverse perinatal outcomes. SEARCH STRATEGY: Systematic search to identify relevant studies published in different languages, registered after 2000, using appropriate MeSH terms. SELECTION CRITERIA: Inclusion criteria were women between 16 and 26+6  weeks of pregnancy with history of preterm delivery in any pregnancy randomized to either 17-OHPC or placebo/no treatment. DATA COLLECTION AND ANALYSIS: The number of preterm births and adverse outcomes in the 17-OHPC and placebo arms over the total number of patients in each randomized group were used to calculate the risk ratio (RR) by random-effects models using the Mantel-Haenszel method. Between-study heterogeneity was assessed using tau2 , χ2 (Cochrane Q), and I2 statistics. MAIN RESULTS: Four studies were included. There was a 29% (RR 0.71; 95% CI, 0.53-0.96; P=0.001), 26% (RR 0.74; 95% CI, 0.58-0.96; P=0.021), and 40% (RR 0.60; 95% CI, 0.42-0.85; P=0.004) reduction in recurrent preterm birth at <37, <35, and <32 weeks, respectively, in the 17-OHPC group compared with placebo. The reduction in neonatal death was 68% (RR 0.32; 95% CI, 0.15-0.66; P=0.002). CONCLUSIONS: 17-OHPC could reduce the risk of recurrent preterm birth at <37, <35, and <28 weeks and neonatal death. PROSPERO: CDR42017082190.

Tissue specific expression of human fatty acid oxidation enzyme genes in late pregnancy.

BACKGROUND: Abnormal fatty acid oxidation (FAO) is associated with maternal and fetal complications during pregnancy. The contribution of maternal and fetal tissues to FAO capacity during late pregnancy is important to understand the pathophysiology of pregnancy-associated complications. The aim of this study was to determine the expression levels of mitochondrial FAO enzymes in maternal and fetal tissues during late normal pregnancy. METHODS: We have measured by Real-time PCR the levels of long- and medium -chain acyl-CoA dehydrogenase (LCHAD and MCAD), two acyl-CoA dehydrogenases that catalyze the initial step in the mitochondrial FAO spiral. RESULTS: LCHAD and MCAD were expressed in maternal skeletal muscle, subcutaneous adipose tissue, placenta, and maternal and fetal blood cells. LCHAD gene expression was four- to 16-fold higher than MCAD gene expression in placenta, adipose tissue and skeletal muscle. In contrast, MCAD gene expression was ~5-fold higher in fetal blood than maternal blood (p = 0.02), whereas LCHAD gene expression was similar between fetal blood and maternal blood (p =0.91). CONCLUSIONS: LCHAD and MCAD are differentially expressed in maternal and fetal tissues during normal late pregnancy, which may represent a metabolic adaptation in response to physiological maternal dyslipidemia during late pregnancy.

Second-trimester amniotic fluid proinflammatory cytokine levels in normal and overweight women.

OBJECTIVE: To estimate the relationship between different adipokines and proinflammatory mediators in amniotic fluid and maternal body mass index (BMI), calculated as weight (kg)/height (m)2. METHODS: Seventy pregnant women who underwent amniocentesis for clinical reasons at 15-20 weeks of gestation were divided into two groups according to their BMI: a control group with normal weight (BMI 20-24.9, n=35) and a case group (BMI 25 or higher, n=35). The two groups were further divided into two subgroups: overweight (BMI 25-29.9, n=22) or obese (BMI 30 or more, n=13). Comparisons of amniotic fluid cytokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-8, IL-10, monocyte chemoattractant protein-1, resistin, and leptin) and C-reactive protein (CRP) levels were performed. The relationships between variables and maternal BMI were also analyzed. RESULTS: There were significant differences in amniotic fluid CRP and TNF-alpha levels among the studied groups: CRP, 0.018 (+/-0.010), 0.019 (+/-0.013), and 0.035 (+/-0.028) mg/dL (P=.007); and TNF-alpha, 3.98 (+/-1.63), 3.53 (+/-1.38), and 5.46 (+/-1.69) pg/mL (P=.003), for lean, overweight, and obese women, respectively. Both proinflammatory mediators increased in women with obesity compared with both overweight and normal women (P=.01 and P=.008 for CRP; P=.003 and P=.01 for TNF-alpha, respectively). There were significant correlations between maternal BMI and amniotic fluid CRP (r=0.396; P=.001), TNF-alpha (r=0.357; P=.003) and resistin (r=0.353; P=.003). CONCLUSION: Amniotic fluid CRP and TNF-alpha levels are increased in obese women, and both are related to maternal BMI, which suggests in utero exposure to higher proinflammatory cytokines and mediators in fetuses of these women. LEVEL OF EVIDENCE: II.

Transformed alpha-fetoprotein (t-AFP) levels in women with threatened preterm labor.

BACKGROUND/AIMS: To evaluate maternal serum transformed alpha-fetoprotein (MSt-AFP) levels, a new molecular conformation of AFP was used in cases of threatened preterm labor (TPL). METHODS: Prospective case-control study. Maternal serum levels of classical AFP and transformed AFP (t-AFP) were compared between 2 groups matched by gestational age: 25 women with TPL and 25 healthy pregnant women as controls. RESULTS: There was no significant difference in classical maternal serum AFP (MSAFP) levels between the 2 groups. In contrast, MSt-AFP levels were significantly lower in cases of TPL than in the control group [7.64 (1.78-29.06) vs. 33.38 (13.80-190.50) ng/ml; p = 0.006]. Similarly, the t-AFP:AFP ratio was also decreased in the TPL group [0.04 (0.004-0.12) vs. 0.16 (0.05-0.80); p = 0.008]. There was no significant correlation between MSAFP and MSt-AFP levels. CONCLUSIONS: MSt-AFP levels are decreased in women with TPL.

Metabolic syndrome in normal and complicated pregnancies.

OBJECTIVE: To evaluate the prevalence of metabolic syndrome and its components in normal and complicated pregnancies. SETTING: university hospital, tertiary referral centre. SUBJECTS: 90 pregnant women in four groups: 20 women with preeclampsia, 20 women with gestational hypertension, 30 women with late-onset gestational diabetes and 20 healthy pregnant women as a control group. INTERVENTION: peripheral insulin resistance was measured by using the insulin tolerance test. Glucose, triglycerides, high-density lipoprotein cholesterol, blood pressure and body mass index were analysed. Comparisons were done by Chi-squared test, one-way analysis of variance and the Bonferroni's test. Prevalence of the metabolic syndrome was calculated by adapting both the WHO and the NCEP definitions of the metabolic syndrome to pregnancy. RESULTS: There were no cases of metabolic syndrome in the control group according to any of the adapted definitions. The prevalence of this syndrome was 3.3% and 10% in the late-onset gestational diabetes group, 35% and 20% in the gestational hypertension group and 30% and 30% in the preeclampsia group for the WHO and the NCEP definitions, respectively. CONCLUSIONS: Metabolic syndrome is present in about one-third of women with pregnancy-induced hypertension but only in 10% of women with late-onset gestational diabetes.