Michel Makhlouf

Adverse pregnancy outcomes among women with prior spontaneous or induced abortions.

OBJECTIVE The aim of the article is to determine whether prior spontaneous abortion (SAB) or induced abortion (IAB), or the interpregnancy interval are associated with subsequent adverse pregnancy outcomes in nulliparous women. METHODS We performed a secondary analysis of data collected from nulliparous women enrolled in a completed trial of vitamins C and E or placebo for preeclampsia prevention. Adjusted odds ratios (ORs) for maternal and fetal outcomes were determined for nulliparous women with prior SABs and IABs as compared with primigravid participants. RESULTS Compared with primigravidas, women with one prior SAB were at increased risk for perinatal death (adj. OR, 1.5; 95% CI, 1.1-2.3) in subsequent pregnancies. Two or more SABs were associated with an increased risk for spontaneous preterm birth (PTB) (adj. OR, 2.6, 95% CI, 1.7-4.0), preterm premature rupture of membranes (PROM) (adj. OR, 2.9; 95% CI, 1.6-5.3), and perinatal death (adj. OR, 2.8; 95% CI, 1.5-5.3). Women with one previous IAB had higher rates of spontaneous PTB (adj. OR, 1.4; 95% CI, 1.0-1.9) and preterm PROM (OR, 2.0; 95% CI, 1.4-3.0). An interpregnancy interval less than 6 months after SAB was not associated with adverse outcomes. CONCLUSION Nulliparous women with a history of SAB or IAB, especially multiple SABs, are at increased risk for adverse pregnancy outcomes.

Can statins reduce the inflammatory response associated with preterm birth in an animal model

OBJECTIVE The objective of the study was to determine the effect of statins on lipopolysaccharide (LPS)-induced inflammatory response in a mouse model of preterm birth (PTB). STUDY DESIGN Day 15 CD1 mice were randomly allocated to intraperitoneal LPS injection (100 μg) or control. Mice in the LPS group were pretreated, 16 and 2 hours prior, with pravastatin (10 μg/g), simvastatin (10 μg/g), or vehicle control. Animals were sacrificed 6 hours after LPS. Cytokine messenger ribonucleic acid (mRNA) expression in the uterus and cervix, and concentrations in the maternal serum and amniotic fluid (AF) were determined. RESULTS Pravastatin reduced interleukin (IL)-1β and IL-6 mRNA expression in the uterus and cervix, respectively, and serum IL-1β and granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations. Simvastatin reduced IL-1β and IL-6 mRNA expressions in the uterus, IL-6 and tumor necrosis factor alpha (TNF-α) in the cervix, and IL-1β, IL-2, IL-12p70, IL-13, TNF-α, GM-CSF, and interferon-γ concentrations in the serum and IL-6 in AF. CONCLUSION Statins reduce the LPS-induced inflammatory responses in a mouse model of PTB.

Sex-specific effects of nicotine exposure on developmental programming of blood pressure and vascular reactivity in the C57Bl/6J mouse.

OBJECTIVE The objective of the study was to determine whether perinatal nicotine exposure adversely affects cardiovascular health in adulthood. STUDY DESIGN C57Bl/6J female mice were randomized to 200 μg/mL nicotine in 2% saccharin or 2% saccharin alone from 2 weeks before breeding until weaning. Offspring weight, vital signs, and carotid artery vascular reactivity were studied. A second cohort was subjected to shaker stress on day 4 of 7 days. Selected mediators of vascular tone were evaluated by molecular studies. Student t or Mann-Whitney U test was performed for statistical analysis (significance: P < .05). RESULTS Nicotine-exposed compared with control female offspring had significantly elevated mean blood pressure under normal and stress conditions. Nicotine females lacked heart rate elevation after stress. Nicotine males had higher mean heart rate and a blunted contractile response to phenylephrine compared with controls, without an increase in blood pressure. CONCLUSION Perinatal nicotine exposure has an impact on the developmental programming of future cardiovascular health, with adverse effects more evident in female offspring.

Should second trimester ultrasound be routine for all pregnancies

Ultrasound use has become ubiquitous in pregnancy. We review the evidence regarding the benefits of routine ultrasound use during pregnancy. Routine ultrasound use before 24 weeks improves detection of undiagnosed twins, reduces postdates inductions, and allows detection of fetal anomalies before birth. Wide variations exist in the sensitivity of ultrasound in detecting fetal anomalies. These may be related to equipment, training, and maternal characteristics, such as obesity. Standards have been developed for the performance of routine fetal ultrasonography in the second trimester. The benefits of routine first trimester ultrasound in the diagnosis of structural fetal anomalies or of routine ultrasonography after 24 weeks are not proven. As ultrasound technology improves and obstetrical care changes, new uses of routine ultrasonography may emerge.

Adipose Tissue Insulin Resistance in Gestational Diabetes

BACKGROUND Gestational diabetes mellitus (GDM) is a metabolic disorder characterized by insulin resistance (IR) and altered glucose-lipid metabolism. We propose that ectonucleotide pyrophosphate phosphodiesterase-1 (ENPP1), a protein known to induce adipocyte IR, is a determinant of GDM. Our objective was to study ENPP1 expression in adipose tissue (AT) of obese pregnant women with or without GDM, as well as glucose tolerance in pregnant transgenic (Tg) mice with AT-specific overexpression of human ENPP1. METHODS AT biopsies and blood were collected from body mass index-matched obese pregnant women non-GDM (n = 6), GDM (n = 7), and nonpregnant controls (n = 6) undergoing cesarian section or elective surgeries, respectively. We measured the following: (1) Expression of key molecules involved in insulin signaling and glucose-lipid metabolism in AT; (2) Plasma glucose and insulin levels and calculation of homeostasis model assessment of IR (HOMA-IR); (3) Intraperitoneal glucose tolerance test in AtENPP1 Tg pregnant mice. RESULTS We found that: (1) Obese GDM patients have higher AT ENPP1 expression than obese non-GDM patients, or controls (P = 0.01-ANOVA). (2) ENPP1 expression level correlated negatively with glucose transporter 4 (GLUT4) and positively with insulin receptor substrate-1 (IRS-1) serine phosphorylation, and to other adipocyte functional proteins involved in glucose and lipid metabolism (P < 0.05 each), (3) AT ENPP1 expression levels were positively correlated with HOMA-IR (P = 0.01-ANOVA). (4) Pregnant AT ENPP1 Tg mice showed higher plasma glucose than wild type animals (P = 0.046-t test on area under curve [AUC]glucose). CONCLUSIONS Our results provide evidence of a causative link between ENPP1 and alterations in insulin signaling, glucose uptake, and lipid metabolism in subcutaneous abdominal AT of GDM, which may mediate IR and hyperglycemia in GDM.